Background. Nasopharyngeal carcinoma (NPC) is highly associated with Epstein-Barr virus (EBV), particularly the undifferentiated nonkeratinizing subtype. Prevalence of EBV in NPC in countries such as Guatemala and Brazil has not been studied. Methods. We analyzed 19 cases of NPC, 11 from Guatemala and 8 from Brazil, for the presence of EBV by in situ hybridization and immunohistochemistry. Additionally, 19 hyperplastic adenoids from children were analyzed for EBV by in situ hybridization, 12 from Guatemala and 7 from Brazil. Results. All the NPC cases from Guatemala and 5 from Brazil were of the undifferentiated nonkeratinizing type. EBV-negative cases comprised 2 keratinizing NPC and 1 differentiated nonkeratinizing NPC. All undifferentiated nonkeratinizing NPC from both samples showed intense positivity for EBER, while LMP-1 only focally and scarcely expressed. EBER was positive in 75% and 43% of the adenoids from Guatemala and Brazil, respectively. Conclusions. All undifferentiated nonkeratinizing NPC irrespective of origin from Guatemala or Brazil were highly associated with EBV.
We report the presence of epididymis-like tubules in unilateral renal hypodysplasia in 3 adult men. Microscopy showed dilated tubules lined by ciliated columnar epithelium and smaller basal cells, morphologically resembling epididymal tubules. Small tubules lined by cuboidal epithelium were also present in all cases, with glomeruli in 2 cases. The epididymis-like tubules expressed CD10, CK7, PAX8, and AR in the luminal epithelium, while the basal cells were positive for p63, CK7, and focally for CD10. The smooth muscle bundles around the epididymis-like tubules were focally AR and WT1 (cytoplasmic) positive. The epididymis-like tubules were negative for ER, PR, and WT1. CK7 and PAX8 stained all the collecting ducts, with AR staining some. Bowman’s capsule, parietal and visceral epithelial cells expressed CD10; WT1 stained the visceral and parietal epithelial cells. Glomerular parietal cells expressed PAX8 and focally, CK7. Proximal tubules were positive for CD10 (luminal membranous and weak cytoplasmic). Distal tubules expressed CK7, PAX8 and AR. An occasional small tubule was ER positive. Scattered stromal cells expressed ER, PR, and AR. The urothelium of the renal pelvis/upper ureter expressed CK7 in all layers, CD10 in the superficial layers, PAX8 in the basal layers and p63 in all layers except the umbrella layer. The epididymis-like tubules replicate the pattern of the mesonephros-derived normal epididymis in expressing CK7, PAX8, CD10, and AR. This supports a mesonephric rather than metanephric origin for these tubules. The aberrant expression of some markers may be a manifestation of the dysplastic nature of the kidneys.
Patients with multifocal breast cancers (MBCs) have a poorer prognosis than patients with unifocal breast cancers. Studies have attributed this to tumor size underestimation in MBC. An alternative hypothesis is that some MBCs behave in a fashion analogous to the "satellite" and "in-transit metastasis" observed in melanoma and, thereby, are more clinically aggressive. We identified 79 cases of MBC, which we classified into 2 groups: study cases defined as ≥2 morphologically similar tumor foci with ≥1 focus without in situ carcinoma (n = 21); and a control group defined as ≥2 morphologically similar or dissimilar foci with associated in situ carcinoma in all foci (n = 58). The odds of being a study case is 1.86 (95% confidence interval [CI] 1.26-2.74) times greater per unit increase in number of tumor foci (median of 4 tumor foci; P = .002). Study cases were 73.33 (95% CI = 8.91-603.16) times more likely to have lymphovascular invasion (LVI) and 14.72 (95% CI = 4.37-49.61) times more likely to have nodal metastases. Grade I/II tumors were 0.20 (95% CI = 0.07-0.59) times less likely to be study cases. There was a significant positive interaction (P < 0.001) indicated by the relationship of LVI status and nodal status with the study case and control group. We conclude that there is a subset of MBC that presents with more numerous tumor foci and a higher rate of nodal metastasis. The aggressive behavior of these cases may be attributed to their proclivity for LVI.
Aims. Pseudoangiomatous stromal hyperplasia (PASH) diagnosed on core needle biopsy is generally excised. As a consequence, PASH as an incidental finding, may lead to unnecessary excisions. This study categorized PASH in biopsies as diffuse versus focal to determine if this correlates with the presence of a mass. Methods. In a 10-year period, 253 biopsies were identified and 159 met inclusion criteria. Of these, 47 biopsies had excisions. Biopsies and excisions were classified as diffuse, involving 2 adjacent lobules, or focal PASH in a single lobule or noncontiguous lobules. The diffuse or focal category on biopsy was correlated to the category on excision. Fibroadenomas with PASH were defined as concordant with diffuse PASH on biopsy. The category was correlated to the presence/absence of a mass determined from radiographic/clinical data for the 159 biopsies. Results. The biopsies were classified as diffuse (105, 66%) and focal (54, 34%). A total of 67% of biopsies with focal PASH showed either focal or no PASH on excision. Diffuse PASH on biopsy, had diffuse PASH in 93% of excisions. Concordance of this classification between biopsy and excision, using a Fisher’s exact test (2-tailed P value is <.0001), is statistically significant. A mass was present in 102/105 (97%) of biopsies with diffuse PASH. In biopsies with focal PASH, 78% had a mass lesion. Conclusions. Classification of diffuse versus focal PASH on biopsy was concordant with findings on excision. We found that diffuse PASH on biopsy showed strong correlation with a mass lesion. Quantifying PASH may assist with clinical-pathologic correlation and reduce unnecessary excisions.
Hirschsprung disease (HSCR) is a congenital disorder characterized by intestinal aganglionosis leading to pseudoobstruction. The majority of cases are limited to the rectum or rectosigmoid (S-HSCR). A variably longer segment can be affected (L-HSCR), which may show many deviations from S-HSCR. We retrospectively reviewed 48 clinicopathologically confirmed total cases of HSCR at a single institution in a 21-year period to identify L-HSCR cases and determine their deviations from known features of S-HSCR. Eight L-HSCR cases were found where aganglionosis extended to the terminal ileum (7/8) or to the splenic flexure (1/8). L-HSCR lacked male preponderance and was in contrast more common in females (6/8). Associated anomalies included congenital heart disease (2) and neonatal hypothyroidism (1), previously underreported associations. The clinical diagnosis of L-HSCR was often delayed (average age at diagnosis 13 days) and the diagnosis was more often made operatively (5/8) rather than on rectal suction biopsy (3/8). Histologically, apart from aganglionosis, neural hyperplasia was either absent or focal, compounding the diagnostic difficulty. Although the number of cases in our study was limited due to the rarity of L-HSCR, this study still highlights the spectrum of deviations of L-HSCR from known clinicopathological features of S-HSCR.
This article reports differences between the properties of extravascular carcinoma, which generally forms the vast bulk of a tumor, and those of intravascular carcinoma, at both primary and metastatic lymph node sites. In a morphological and immunohistochemical study of 19 diffuse gastric adenocarcinomas, we report that in comparison to extravascular carcinoma, the intravascular tumor compartment showed frequent and profound phenotypic change, including increased tumor cell cohesion, differentiation and cadherin/catenin expression. For example, greatest cohesion was seen at the intravascular site in 78% (P = .00006) of primary cancers and in 84% (P = .000015) of their lymph node metastases. Pan cadherin showed a statistically significant increase at the intravascular metastatic site (P = .031). We suggest that this change from an extravascular isolated cell phenotype to an intravascular cohesive phenotype represents reversal of the epithelial to mesenchymal transition. Since this proposed reversal of epithelial to mesenchymal transition in intravascular carcinoma is frequently conspicuous in routine histological sections of many types of cancer, as our previous publications have indicated, this process is likely to have widespread significance for the biology of metastasis.
Background. We investigated the reliability of combined DOG1 and mammaglobin immunohistochemistry compared with ETV6 fluorescence in situ hybridization (FISH) in the assessment of salivary tumors previously diagnosed as acinic cell carcinoma (ACC). Ultrastructural features of cases reclassified as mammary analogue secretory carcinoma (MASC) were assessed by transmission electron microscopy (TEM). Methods. Immunohistochemical (IHC) reactivity to DOG1 and mammaglobin was validated against FISH targeting the ETV6 gene in all 14 cases. Results. Three cases with papillary cystic histomorphology previously diagnosed as ACC were revised to MASC. TEM features of the ETV6 rearrangement-positive MASC cases showed large numbers of secretory granules with extrusion into the intercellular spaces, well-developed endoplasmic reticulum, lipid-laden vacuoles, well-formed microvilli, and large lining cystic spaces. Conclusions. Combined DOG1 and mammaglobin immunohistochemistry is comparable to ETV6-breakapart analysis for differentiating between papillary cystic variants of ACC and MASC.
Triple-negative breast cancers (TNBCs) are characterized by negative expression for estrogen (ER), progesterone (PR), and human epidermal growth factor 2 (HER2) receptors. Although the majority of basal-like breast cancers (BLBCs) diagnosed based on gene expression profiling belong to the TNBC group, both entities are not synonymous. Core BLBCs are TNBCs, which are positive for basal cytokeratin (CK) and/or epidermal growth factor receptor (EGFR). We aimed to study and correlate a TNBC cohort for various histomorphological features and immunohistochemical (IHC) profile in Indian patients. We studied 205 naïve TNBCs for histopathological features, which were further evaluated for basal CKs—namely, CK5/6, CK14, CK17—and EGFR expression to classify them as core BLBCs, using criteria of any basal CK and/or EGFR positivity and 7-negative phenotype (7NP). Among 205 TNBCs, 91% of cases were core BLBCs, and absence of ductal carcinoma in situ (DCIS) was significantly associated (P = .014) with core BLBC. Geographic necrosis was correlated with expression of CK17 (P = .002) and EGFR (P = .038). A ribbon-like trabecular pattern and absence of DCIS were associated with CK17 (P = .0002 and P = .043, respectively) and CK14 (P = .04 and P = .0008, respectively). TNBC is a heterogeneous subgroup with adverse clinicopathological features, and many of them show significant correlation with basal CKs. TNBCs cannot be classified as core BLBC or 7NP based on morphological features, except absence of DCIS. However, this study illustrates the heterogeneity in TNBCs on the basis of IHC markers.
Peritoneal metastasis in colorectal carcinoma is associated with a dismal prognosis; however, features that correlate with patterns of metastatic spread are not well characterized. We analyzed the clinicopathologic and molecular features of 166 patients with colorectal carcinomas stratified by metastases to the peritoneum or liver. Mucinous and signet ring cell differentiation were more frequently observed in colorectal carcinoma with peritoneal dissemination compared to colorectal carcinoma with liver metastasis (mucinous differentiation: 62% vs 23%, P < .001; signet ring cell differentiation: 21% vs 0%, P < .0001). The significant association of mucinous differentiation with peritoneal dissemination compared with liver metastasis was identified in patients with both synchronous and metachronous development of metastasis (P < .01). In contrast, colorectal carcinomas with liver metastasis were more frequently low-grade (90% vs 72%, P = .005) and associated with dirty necrosis (81% vs 56%, P = .001) compared with colorectal carcinomas with peritoneal dissemination. No significant differences were identified between colorectal carcinoma with peritoneal metastasis versus liver metastasis with respect to KRAS mutations, BRAF mutation, or high levels of microsatellite instability. Patients with tumors involving the peritoneum had a significantly worse overall survival in comparison to patients with liver metastasis lacking peritoneal involvement (P = .02). When including only those patients with peritoneal metastasis, the presence of any mucinous or signet ring cell differentiation was associated with a significantly worse overall survival (P = .006). Our findings indicate that mucinous and signet ring cell differentiation may be histologic features that are associated with an increased risk of peritoneal dissemination and poor overall survival in patients with peritoneal metastasis.
Intravascular large B-cell lymphoma (IVLBCL) is a rare subtype of diffuse large B-cell lymphoma. Thirteen cases of IVLBCL with a median age of 56 years were analyzed retrospectively. Nonspecific symptoms such as fever and hepatosplenomegaly were the most common manifestations, and the bone marrow was usually involved in 8/13 (61.5%) cases. All tumors expressed CD20, and 12/13 (92.3%) of the tumors exhibited a nongerminal center phenotype by Hans algorithm. CD5 was expressed in 3/12 (25%) of the tumors. MYC was negative in all cases, and BCL2 was positive in 10/12 (83.3%) cases. Cytogenetic analysis revealed 5 cases that did not have rearrangements in either the MYC or the BCL2 gene. No association with Epstein-Barr virus was found. Seven of 11 patients received chemotherapy. The median survival time was 6 months. Patients with hemophagocytic syndrome had poor prognoses. Our study demonstrates that IVLBCL has a poor clinical outcome with a high frequency of bone marrow involvement and that the MYC gene may not play an important role in the poor prognosis of IVLBCL.
Introduction: The purpose of this study was to associate immunohistochemical expression of β-catenin, EGFR, CK7, CK20, MUC1, MUC2, and CDX2 in ampullary adenocarcinomas with the type of differentiation and prognosis. Methods: Forty-seven patients with ampullary adenocarcinoma who underwent pancreatoduodenectomy with curative intent from 1997 to 2014 were included in this study. Nine patients with perioperative death were included in the association analysis but excluded from survival analysis. All tumors were classified as intestinal or pancreatobiliary type, according to histologic criteria, and immunohistochemically stained against the aforementioned markers. Results: Eighteen carcinomas were classified as intestinal type and 29 carcinomas as pancreatobiliary type. Univariate analysis revealed that CK20 and CDX2 expression correlates with intestinal type, whereas MUC1 positivity indicates pancreatobiliary type. A marginally significant trend was shown for intestinal-type tumors toward larger size and more frequent MUC2 expression. Using multivariate analysis CK20 (P = .003) and MUC1 (P = .004) were identified as independent predictors of the intestinal and pancreatobiliary types, respectively. Mean and median survival was 90.3 and 55 months, respectively. Overall 5-year survival rate was 48%. On univariate survival analysis, overall survival was adversely influenced by the number of infiltrated lymph nodes, elevated Ca19-9 serum levels, jaundice, poor differentiation, T4 stage, N1 stage, TNM stage III, and CDX2 immunonegativity. Multivariate analysis identified TNM stage as the only independent prognostic factor in ampullary adenocarcinoma (P = .048). Conclusions: Immunoreactivity against CK20 and MUC1 in ampullary carcinomas is a useful adjunct to histologic examination in determining histotype. None of the immunohistochemical markers studied had prognostic significance.
Discrepancies between intraoperative consultations with frozen section diagnosis and the final pathology report have the potential to alter treatment decisions and affect patient care. Monitoring these correlations is a key component of laboratory quality assurance, however identifying specific areas for improvement can be difficult to attain. Our goal is to develop a standardized method utilizing root cause analysis and a modified Eindhoven classification schematic to identify the source of discrepancies and deferrals and subsequently to guide performance improvement initiatives. A retrospective review of intraoperative consultations performed at a tertiary level hospital and cancer center over a 6-month period identified deferrals and discrepancies between the intraoperative consult report and the final pathology report. We developed and applied a classification tool to identify the process errors and cognitive errors leading to discrepant results. A total of 48 (4.6%) discrepancies and 24 (2.3%) deferrals were identified from the 1042 frozen sections. Within the entire data set of frozen sections, the process errors (n = 26, 54.2%) were due to gross sampling (n = 16, 33.3%), histologic sampling (n = 8, 16.7%), and surgical sampling (n = 2, 4.2%). Interpretation errors (n = 22, 45.8%) included undercalls/false negatives (n=8, 16.7%), overcalls/false positives (n = 10, 20.8%), and misclassification errors (n = 4, 8.3%). Application of our classification tool demonstrated that the root cause of discrepancies and deferrals varied both between organ systems and by specific organs and that classification models may be utilized as a standardized method to identify focused areas for improvement.
Background. The clinical implications of the diagnosis of atypical ductal hyperplasia (ADH) and ductal carcinoma in situ (DCIS) are very different. Yet there are "borderline" breast lesions that have characteristics of both ADH and DCIS. We examined interobserver diagnostic variability for such lesions and correlated pathologic features of the lesions with clinical outcomes. Methods. We identified all cases of borderline ADH/DCIS lesions treated at our center from 1997 to 2010. Five specialized breast pathologists blinded to clinical outcomes independently reviewed all available slides from each case and were instructed to classify each as benign, ADH, or DCIS. A majority diagnosis (MajDx) was defined as a diagnosis agreed upon by ≥3 pathologists. Results. A total of 105 women with borderline ADH/DCIS and slides available for review were identified. The MajDx was ADH in 84 (80%), and DCIS in 18 (17%). There were split diagnoses in 3 (3%). MajDx of DCIS correlated significantly with lesion size and nuclear grade. There was diagnostic agreement by all 5 pathologists in 30% of cases, 4 pathologists in 42%, and 3 pathologists in 25%. At a median follow-up of 37 months, 4 (3.8%) patients developed subsequent ipsilateral breast carcinoma (2 invasive, 2 DCIS); all 4 cases had MajDx of ADH. Conclusions. Borderline ADH/DCIS represents an entity for which reproducible categorization as ADH or DCIS cannot be achieved. Furthermore, histologic features of borderline lesions resulting in MajDx of ADH vs. DCIS are not prognostic for risk of subsequent breast carcinoma.
Background: Pseudoangiomatous stromal hyperplasia (PASH) is a benign lesion of myofibroblasts that is composed of a network of slit-like channels that resemble vascular spaces. The aims of this study were to document the frequency of PASH in core needle biopsy specimens (CNBS) of the breast, to describe which histopathologic findings coexist with PASH and to examine any endothelial cell differentiation. Materials and Methods: We reevaluated hematoxylin and eosin–stained sections of all CNBS that were obtained during a 1-year period. First, we performed CD34 and CD31 immunostainings to highlight the areas of PASH, then performed D2-40/podoplanin (lymphatic endothelial marker) and Fli-1 (vascular endothelial cell marker) immunostains. Results: The total number of CNBS was 412. Areas of PASH were noted in 37 of the 412 cases (9%), with a mean age of 38.5 years. The lesions that were described in association with PASH were "benign breast parenchyma with stromal fibrosis" (17/37; 46%), "fibroepithelial tumors" (17/37; 46%), "columnar cell changes (CCC)" (2/37; 5%), and "invasive carcinoma" (1/37; 3%). There were 2 cases of CCC within the foci of PASH (direct contact with PASH), and 8 additional cases of CCC that coexisted in the same specimen but were not in direct contact. There was no staining for D2-40 or Fli-1 within PASH foci. Conclusion: PASH lesions occurred with a frequency of 9% in CNBS and were mostly in association with benign breast lesions in premenopausal women. CCC was determined as an accompanying epithelial lesion within or near PASH areas. No obvious immunopositivity compatible with endothelial cell differentiation was revealed.
Clear cell urothelial carcinoma (CCUC) is a rare variant of urothelial carcinoma (UC) and its clinical significance has not been well elucidated. Consecutive cases of UC over a period of 5 years were reviewed. Histopathological tumor parameters, including the proportion of tumor cells with clear cell change, and patient outcomes were recorded. Expression of the following immunohistochemical markers was investigated: CK7, CK20, CK5, CD44, and PAX8. We also conducted a review of the literature for case reports/series of CCUC. Ten CCUCs were identified out of a total of 872 cases of UC. The clear cell component was characterized by prominent cytoplasmic membranes and voluminous clear cytoplasm, and accounted for 30% to 90% of the invasive tumor component. Of all the non-CCUC cases reviewed, at least 50% (noninvasive or invasive UC) showed focal areas of clear cell change that accounted for less than 5% of the neoplastic cells. Immunohistochemically, CCUC exhibited positive reactivity for CK5/CD44 (n = 9); CK20 (n = 5), PAX8 (very focal to extensive) (n = 6), and GATA3/CK7 (n = 10). Eight of 10 CCUC were of advanced clinical stage (pT3/pT4) and 6 of 10 experienced tumor recurrence and/or death due to disease. In conclusion, CCUC can be distinguished from non-CCUC by the extensive clear cell change in more than 30% of cells. This variant is associated with rapid progression to muscle invasion and metastasis, with an aggressive clinical course. Expression of CK5/CD44 may represent basal cell features in most CCUC cases, while PAX8 expression is suggestive of mesonephric derivation.
Autoimmune liver disease (AILD) is a type of chronic liver disease with autoimmune etiology. The diagnosis of the disease is multipronged and detection of autoantibodies in AILDs is an important diagnostic tool and it also helps in the classification of the disease. There are multiple autoantibodies that are detected in AILDs but none is diagnostic. Moreover, these autoantibodies are detected in many other pathological and nonpathological conditions. So the significance of seropositivity for these autoantibodies should be known by both the pathologists as well as the clinicians. In addition, there is prognostic significance associated with some of the antibodies and they also sometimes help in the disease monitoring. The whole array of antibodies detected in AILDs is discussed in detail in this review along with their clinical significance and interpretation.
Background. Pelvic lymphadenectomy has prognostic and therapeutic implications in both bladder and prostate cancer. Pelvic lymphadenectomy specimens are fatty and identification of lymph nodes (LNs) can be difficult during the grossing process. We investigated the benefit of a new grossing method requiring entire LN packet submission. Materials/Methods. We introduced a new grossing protocol requiring total submission of LN packets for patients undergoing radical prostatectomy (RP) or radical cystectomy (RC). A retrospective review was performed to evaluate clinical and pathologic data for RP (n = 59) and RC (n = 56) cases performed 18 months prior to and 18 months following implementation of the new lymphadenectomy grossing protocol. Results. For RP and RC cases, significantly more LNs were found when total LN packets were submitted with the new technique: mean 14.1 versus 8.7, and mean 25.2 versus 15.9, respectively (P = .007, P = .011). For RP cases, there was no significant change in the number of LN packets submitted for evaluation from the operating room (P = .76). For RC cases, more LNs were found with the new technique despite a significantly fewer number of LN packets sent from the operating room in the cohort that were processed with the new technique: mean 2.2 versus 4.0 LN packets (P < .001). Significantly more paraffin blocks were required using the new grossing method for both RP and RC: mean 13.53 versus 6.9 and mean 19.0 versus 12.4, respectively (P < .001, P = .018). Conclusions. Submitting all additional fatty tissue after palpable identification of LNs can significantly increase the detection of LNs in RP and RC cases.
Triple hit lymphomas are a subset of so-called double hit non-Hodgkin lymphomas exhibiting simultaneous gene translocations/disruption of MYC, BCL2, and BCL6; however, their overlapping morphologic features and complex genetic rearrangements can render classification and prognostication vexing. Clinically triple hit lymphomas are thought to demonstrate aggressive behavior, similar to or worse than that of double hit lymphomas. Only rare reports of long term survivors exist and raise the possibility that unidentified morphologic, immunologic, or cytogenetic differences may impart a less adverse prognosis than current literature and opinion may suggest. Here we report 3 such cases with less aggressive behavior. Cases such as these may prove useful in comparing outcomes, and underlying mechanisms of tumor progression, in aggressive non-Hodgkin lymphomas.
Aims. Epithelial mesenchymal transition (EMT) is a crucial process for acquisition of malignant phenotype, aggressiveness, and metastatic capacity in neoplasms. It is characterized by loss of epithelial markers and gain of mesenchymal markers. Studies on EMT and its potential association with the histological grading are sparse in oral squamous cell carcinoma (OSCC). This study aims to evaluate the expression of EMT-associated proteins—E-cadherin, β-catenin, and N-cadherin—in different grades of OSCC. Methodology. In all, 60 cases of OSCC further subdivided into 20 cases each of well-, moderately, and poorly differentiated OSCCs were stained immunohistochemically with E-cadherin, β-catenin, and N-cadherin antibodies. The differences in the expression were evaluated using 2 and Fisher exact tests, whereas Spearman’s correlation was used to analyze the correlation between the markers. Results. A reduced E-cadherin expression noted in 40% of the OSCCs was associated with reduced β-catenin expression in 66.6% of the cases and increase in the expression of mesenchymal N-cadherin seen in 80% of cases. This expression pattern demonstrated a significant association with histological grades. A membrane to cytoplasmic shift of E-cadherin (73.3%) and β-catenin (78.3%) increased with histological grade. A negative correlation was observed with the E-cadherin and N-cadherin localization, though it did not reach statistical significance. Conclusion. OSCC tissues had high levels of EMT phenotype as compared with the normal oral mucosa. This phenotype was characterized by reduced E-cadherin and β-catenin expression and overexpression of N-cadherin. Aberrant localization of the studied proteins was a hallmark for depicting EMT.
CD138 (syndecan-1) immunoexpression has been reported to be specific for the plasmacytoid variant of urothelial carcinomas (UCs). The aim of this study was to examine the utility of CD138 immunohistochemistry for diagnosing the plasmacytoid variant of UCs. The extent and intensity of CD138 immunostaining were evaluated in 22 infiltrating UCs, 2 other infiltrating carcinomas, 15 noninvasive urothelial lesions, 3 other benign lesions, and perilesional normal tissues. CD138 immunostaining of the normal urothelial epithelium was universally diffuse and strong. In addition, all 42 cases of urinary tract lesions exhibited positive CD138 immunostaining; however, 1 of 3 plasmacytoid variants exhibited focal CD138 expression. The frequency of CD138 positivity in plasmacytoid variants may be relatively low, compared with that observed in the conventional types and other variants; thus, it is not appropriate to assume that CD138 expression in UCs is specific for plasmacytoid variants.
Introduction. Breast lesions might be missed by the traditional method of inspection, palpation, and sectioning of the specimen. Lymph node revealing solution (LNRS) was first introduced by us as a fixative that enhances the retrieval of lymph nodes in breast carcinoma and other malignancies. This is a preliminary report of our experience with the use of LNRS in order to visualize malignant breast tumors that were not detected by the traditional method. Material and Methods. Eight post–chemoradiation-treated tumors, 6 relumpectomy specimens, and 1 post mammotome lumpectomy with no grossly detectable residual tumor and 2 mastectomy specimens with multifocal tumors which were missed by the first inspection were postfixed in LNRS for 24 hours and sectioned. Results. In some of the cases, small tumors up to 0.5 cm were visualized as white gray lesions. Carcinoma has been confirmed by histopathologic examination and the final diagnosis had to be changed. Conclusion. Postfixation in LNRS enhances the visualization of grossly undetectable breast lesions and it is worthwhile to use it in problematic cases in order to arrive at a more accurate diagnosis.
Objectives. The aims of this study are to evaluate expressions of Ki67, RacGAP1 (MgcRacGAP) and topoisomerase 2 alpha (TOP2a), the markers related with cell proliferation that have been proposed to affect the prognosis in the literature and correlate the results with clinicopathological parameters of breast cancer patients. Methods. Ki67, RacGAP1, and TOP2a antibodies were applied immunohistochemically to the tissue micrarray blocks of 457 female breast cancer patients. The results were correlated with clinical, prognostic, histopathological features, and other immunohistochemical findings (estrogen receptor [ER], progesterone receptor [PR], HER2, cytokeratin [CK]5/6, CK14, epidermal growth factor receptor [EGFR] and vimentin), statistically. Results. Ki67 expression demonstrated direct correlation with TOP2a expression, mitotic count, tumor grade, geographic necrosis, basal-like phenotype. RacGAP1 expression was directly correlated with TOP2a expression, nipple invasion, and number of metastatic lymph nodes, and it was inversely correlated with PR expression. TOP2a expression was directly correlated with vimentin and Ki67 expressions, mitotic count, tumor grade, and geographic necrosis, and nipple invasion, and negatively correlated with ER and PR expressions. Higher TOP2a and Ki67 expressions were correlated with shorter overall survival. Higher TOP2a expression and RacGAP1 positivity were directly correlated with shorter disease-free survival. Conclusion. This study showed that the overexpressions of Ki67, RacGAP1, and TOP2a affect the prognosis adversely, thus to develop target therapies against RacGAP1 and TOP2a as well as using Ki67 as a part of routine pathology practice might be beneficial in breast cancer therapy and prediction of prognosis.
Ectomesenchymal chondromyxoid tumor (ECT) is a rare benign tumor of uncertain lineage, which almost exclusively affects the anterior tongue. Herein, we report 2 cases of ECT occurring in 58- and 56-year-old males on the right and on the left side of the dorsum of the anterior tongue, measuring 18 mm and 10 mm, respectively. Despite positive resection margin in one case, none of the tumors recurred during follow-up of 6 and 5 years. Microscopically, both tumors had lobular architecture with a mixture of solid, microcystic, and chondromyxoid areas. The tumor cells were polygonal or elongated and showed mild atypia in one case. Immunohistochemically, both tumors showed diffuse expression of vimentin and focal positivity of CD10 and of smooth muscle actin. Regarding neural tissue-related markers, there was nearly diffuse expression of CD56 and neuron-specific enolase and focal positivity of PGP 9.5 in both cases and variable expression of CD57, synaptophysin, glial fibrillary acidic protein, and S-100 protein. Interestingly, we observed diffuse expression of SOX10 in one case. In both tumors, diffuse strong nuclear expression of cyclin D1 was present, without CCND1/IGH translocation or CCND1 amplification. The EWSR1 gene rearrangement was not detected. To the best of our knowledge, expression of SOX10, which may support neural crest origin of this peculiar lesion, has not been reported in ECT. The significance of strong cyclin D1 expression remains to be further investigated.
Chronic lip discoid lupus erythematosus (DLE) is a potentially malignant disorder that can develop into lip squamous cell carcinoma (LSCC). Podoplanin is a specific marker for lymphatic endothelial cells and plays a role in cancer progression. The objective of this study was to determine the immunoexpression of podoplanin in samples of patients with DLE and its correlation with the risk of progression to LSCC. In a retrospective study, podoplanin expression was determined using immunohistochemistry in samples from 52 patients with DLE, including 44 patients with untransformed DLE and 8 patients with malignant transformed DLE. Ten samples of normal oral mucosa and 10 samples of LSCC were used as normal and cancer controls, respectively. The results showed that podoplanin expression was observed in 12 of 44 (27.3%) patients with untransformed DLE and in 7 of 8 (87.5%) patients with transformed DLE (P = .002). Podoplanin was not expressed in normal oral mucosa, but it was overexpressed in all of the 10 patients with LSCC. Regression analysis revealed that podoplanin expression was significantly associated with an 18.67-fold increase in the risk of malignant progression (95% confidence interval = 2.07-168.10; P = .009). In summary, podoplanin expression is significantly associated with malignant transformation of DLE into LSCC. Thus, podoplanin expression may identify a subgroup with a high risk of malignant progression of DLE.
Background. Malignant melanoma of the nail apparatus is exceedingly rare. Increasingly, genetic studies have been employed to aid in distinguishing between malignant melanoma and benign melanocytic nevi. Methods. Archived nail apparatus melanomas were analyzed by fluorescence in situ hybridization (FISH) using probes targeting the genes at 6p25 (RREB1), 11q13 (CCND1), 8q24.1 (MYC), 6q23 (MYB), 9p21 (CDKN2A) and the centromeres of chromosomes 8 (D8Z2) and 6 (D6Z1). The results were correlated with clinical and demographic information. Results. Mean patient age was 57.8 years (range 23-92 years). In all, 5 of 7 (71%) cases involved the upper extremity digits. RREB1 gain was seen in all cases. CCND1 gain was seen in 6 of 7 (86%) cases, 3 of which were amplified. MYB loss and MYC gain were both seen in 5 of 7 (71%) cases. Homozygous loss of CDKN2A was not observed in any case. Two of 7 (28.6%) patients had lymph node metastasis and died of widely metastatic disease. These 2 patients harbored the most genetic aberrations: gains of RREB1, CCND1, and MYC, and MYB loss. Both benign melanocytic nevi controls showed normal FISH results. Conclusions. RREB1 and CCND1 gains are common in nail apparatus melanoma as in most melanomas, and an increased number of genetic aberrations may be associated with a poorer prognosis, though the limited number of cases precludes definitive correlation. FISH appears to be a useful adjunct in the diagnosis of nail apparatus melanomas and improves diagnostic confidence even in the setting of unambiguous histomorphology.
Sclerosing pneumocytoma (SP) is a rare benign neoplasm of the lung. Conservative surgical excision is curative with an excellent prognosis. Preoperative diagnosis of SP can be difficult. Thus, intraoperative frozen sections play a crucial role in guiding surgical management. However, the interpretation of frozen section can be challenging due to freezing artifact. Intraoperative cytology provides a complementary and better morphological detail. In this study, we review and compare the intraoperative cytology and frozen section of 14 cases of SP. SP is characterized by containing 2 cell types: round stromal cells and cuboidal surface cells. The round stromal cells were small with uniform nuclei and inconspicuous nucleoli. The cuboidal surface cells were more differentiated into type II pneumocytes and showed slightly larger in size with intranuclear inclusions. The immunocytochemical double-labeling staining could display 2 distinct population of vimentin-positive round stromal cells and cytokeratin 7–positive cuboidal surface cells. Recognition of the cytological features of SP circumvents the frozen section artifact and is a useful adjunct to the frozen section in leading to the correct diagnosis of SP.
Hyperplastic polyps of the stomach are routinely encountered during upper endoscopy and often arise in the setting of abnormal surrounding mucosa, particularly Helicobacter pylori, autoimmune gastritis, and reactive gastropathy. Not infrequently gastroenterologists fail to biopsy the surrounding mucosa, thus determining the underlying etiology of the gastric hyperplastic polyp can be difficult. Recently, the Rodger C. Haggitt Gastrointestinal Pathology Society published guidelines on the use of special stains. The society guidelines indicate that H pylori are not usually present in hyperplastic polyps and special stains in this setting may have limited utility. We analyzed the histologic features of 32 gastric hyperplastic polyps in which the nonpolypoid mucosa demonstrated H pylori gastritis. A consecutive series of 50 hyperplastic polyps in which no surrounding mucosa was sampled was also analyzed. When H pylori are identified in biopsies of the nonpolypoid mucosa, it is also commonly present within the polyp tissue (22/32, 69%). The majority of H pylori organisms were identified on routine hematoxylin and eosin stain (16/22, 72%). In contrast, H pylori were only seen in 2/50 consecutive hyperplastic polyps in which the surrounding mucosa was not sampled. Compared with the hyperplastic polyps that lack the organisms, H pylori associated hyperplastic polyps more commonly had dense lymphoplasmacytic inflammation (P = .0001) and neutrophils within gastric epithelium (P = .036). Polyp location, number, size, and presence of intestinal metaplasia was not associated with H pylori. These results provide empirical data to guide evaluation of hyperplastic polyps for H pylori.
Introduction. The term intracholecystic papillary-tubular neoplasm (ICPN) is suggested by some authors for a group of exophytic lesions of the gallbladder. In our study, demographic, pathological, and immunohistochemical features of 45 ICPN cases and their relationship with invasive carcinoma were analyzed. Material and methods. A total of 45 ICPN cases were retrieved out of 7334 cholecystectomies performed between1996 and 2014. Cases were evaluated with regard to demographic, pathological, and immunohistochemical features. Correlation between the clinical and histopathological data and occurrence of invasion was sought. Results. The incidence of ICPN was 0.61% in our series. Invasive carcinoma was observed in 56% of cases. Factors associated with invasion were diffuse high-grade dysplasia (P = .002), papillary growth pattern (P = .001), greatest diameter of the lesion, and high Ki67 proliferation index (P < .0001). Discussion. Some authors have reported that small intracholecystic exophytic lesions without high-grade dysplasia are considered to be inconsequential. However, there are not enough data concerning the features of large lesions with high-grade dysplasia and their prognoses. Our data suggest that cases with diffuse high-grade dysplasia and tubulopapillary/papillary growth pattern, large tumor size, and high Ki67 proliferation index should be studied for the presence of invasion.
While endometriosis, defined as the presence of endometrial tissue in extrauterine sites, is most frequently encountered within the peritoneal cavity, a small but significant proportion of cases occur at extra-abdominal soft tissue sites, particularly in relation to previous abdominal surgery. We reviewed the cases of endometriosis of soft tissue sites seen at a tertiary soft tissue center. All cases of extra-abdominal soft tissue endometriosis diagnosed at this institution over a 13-year period were reviewed, and clinical and pathologic findings were recorded. Forty-five patients had diagnoses of soft tissue endometriosis and there were 34 diagnostic biopsies and 26 surgical excision specimens. All but 1 case were abdominal wall lesions, with 1 located in the upper arm. A total of 33 patients presented with lesions in scars of previous operations (31 in Pfannenstiel incisions for Caesarean sections, presenting with a median interval of 6 years (range 1-16 years) following surgery). The lesions ranged in size from 1 to 8 cm (median 3.5 cm). One case showed decidualized stroma with trophoblast cells, while 2 had secondary adenocarcinoma arising from endometriosis. Eighteen cases were tested for β-catenin expression immunohistochemically, of which 5 showed at least focal nuclear positivity in the surrounding fibrous tissue (although not within glands or stroma). Soft tissue endometriosis is seen most commonly in surgical scars, particularly following Caesarean sections. Spontaneous endometriosis also most commonly occurs in the abdominal wall, although can occur exceptionally at unusual sites, such as extremities. Secondary changes, including carcinomas, can arise from endometriosis. The differential diagnosis of these lesions includes fibromatosis, which may be erroneously diagnosed on small, nonrepresentative core biopsy specimens.
Introduction. Neuroendocrine carcinoma (NEC) of the cervix is associated with a poor prognosis despite multimodal treatment. The correct diagnosis of this tumor type is imperative to provide clinicians and patients with prognostic information and ensure that appropriate treatment is provided. Methods. A clinicopathological study was undertaken on all cervical tumors registered as NEC with the West Midlands Cancer Intelligence Unit between January 1, 1998 and December 31, 2009. Of the 45 cases diagnosed during the study period, the tumor samples of 41 cases were traced, anonymized, and then independently reviewed by 2 gynecological pathologists. Results. The review confirmed 31/41 (78%) cases to be NEC, which overall, represented 1.3% of all the cervical cancers registered in the West Midlands over the period of the study. In the correct histological context, synaptophysin was the most sensitive and specific positive immunohistochemical marker of NEC differentiation. The cases that on review were confirmed as NEC had a significantly worse outcome than the non-NEC cases: median survival for NEC cases was 33.3 months versus 315.0 months for the non-NEC cases, P = .013. Conclusions. Histological review of a series of NECs has shown significantly reduced survival in those patients with confirmed NEC in comparison with those patients where a diagnosis of NEC was not confirmed. We propose morphological and immunohistochemical criteria for the diagnosis of cervical NEC; and discourage unqualified use of the term "small cell carcinoma" as this does not accurately convey the diagnosis of SCNEC. We urge pathologists to use the 2014 World Health Organization classification when reporting these tumors.
This study attempted to review the impact of extent of squamous differentiation in 56 infiltrating duct carcinomas (IDC) with squamous differentiation (metaplastic squamous carcinomas [MSC]). Tumors showing 100% squamous elements were labeled as primary squamous carcinomas (PSC; n = 28) and compared with 28 MSC showing lesser squamous components. A clinicopathological comparison revealed that lymphovascular emboli were never seen in any PSC but were noted in 7/28 of other MSC, while perineural invasion was seen only in PSC and not in MSC. Nodal metastasis was significantly more in other MSC as opposed to PSC. Most MSC presented with 2- to 5-cm sized tumors while PSC were 5 to 10 cm in size. PSC showed cystic change while MSC did not. Disease free survival (DFS) for MSC versus PSC was 64% versus 39.8%, while overall survival (OAS) was 72.7% in MSC versus 66.7% in PSC. Tumor stage affected DFS in MSC while none of the factors affected DFS/OAS in PSC. The extent of squamous differentiation affected DFS with best behavior for metaplastic carcinomas showing <40% squamous elements and worse for those with >90% squamous component (P = .024). PSC of breast is an aggressive disease and show distinct clinicopathological features from other MSC, and though the current definition of MSC does not advocate quantifying the squamous element, clearly this affects prognosis.
Hypoxia-inducible factor-1α (HIF-1α) promotes proteins that enable cell survival during hypoxia, such as glucose transporter 1 (GLUT-1). Their coexpression has been associated with aggressiveness in malignancies and has not been studied in odontogenic tumors. Immunohistochemical expression of HIF-1α and GLUT-1 was analyzed in 13 tooth germs (TGs), 55 ameloblastomas (AMs), and 3 ameloblastic carcinomas (ACs). HIF-1α was negative in all TGs, and just 1 case of AM and 1 of AC had nuclear positivity. GLUT-1 expressed in ameloblastic cells of all TGs, AMs, and ACs, with an increasing intensity, respectively, and was significantly higher in solid AM than in unicystic AM (P = .041). Absence of nuclear HIF-1α in TGs and most AMs suggest that GLUT-1 may be induced by alternative pathways to hypoxia. However, in ACs, HIF-1α may be activated; however, to confirm this, additional cases are needed. GLUT-1 overexpression could be related to aggressiveness in AMs and ACs and must represent a normal metabolite in TGs.
Pseudohyperplastic adenocarcinoma (PHA) with foamy changes is composed of neoplastic glands that show a cytoarchitectural combination of both neoplasms. However, none of the previously reported cases have shown typical areas of foamy or PHA. We report on the clinicopathological characteristics of 5 cases consisting predominantly of pseudohyperplastic and foamy adenocarcinomas. In several histological fields, this neoplasm mimicked hyperplastic nodules or prostatic adenosis because they showed the nodular pattern of the PHA and the inconspicuous cytological atypia of foamy gland carcinoma. Four cases had a Gleason score of 6. In the prostatectomies, the neoplasm was limited to the prostatic gland. The evolution has been favorable in all patients after 3 years of follow-up, on average. The cases reported herein demonstrate that PHA and foamy adenocarcinoma may be associated and occasionally show overlapping histological criteria. The PHA with foamy changes must be distinguished from conventional foamy adenocarcinoma and PHA because it can closely resemble hyperplastic glands mainly in needle prostatic biopsy.
Background. Turnaround time (TAT) is the benchmark to assess the performance of a laboratory, pathologists, and pathology services, but there are few articles on TAT of surgical pathology, particularly in relation to oral or head and neck specimens. This study investigates the TAT for oral histopathology reporting in an academic institution’s training laboratory and offers recommendations to achieve better overall quality of diagnostic services. Methods. This study examined data obtained from biopsy request forms for specimens received from the Oro-Maxillofacial Surgery Department of Hospital Tengku Ampuan Rahimah Klang in the Oral Pathology Diagnostic Laboratory of the Faculty of Dentistry, University of Malaya, over a period of 3 years between January 2012 and October 2014. Results. TAT for surgical and decalcified specimens were increased significantly compared to biopsies. Additional special handling did not influence TAT, but increased specimen volume resulted in greater TAT. Slide interpretation was the most time-consuming stage during histopathology reporting. Overall, mean TAT was acceptable for most specimens, but the TAT goals were less than satisfactory. Conclusion. A TAT goal appropriate for this laboratory may hence be established based on this study. Collective efforts to improve the TAT for various specimens are essential for better laboratory performance in the future.
Aim. To identify aggressively behaving classical Hodgkin lymphoma (CHL) of mediastinum and primary mediastinal B-cell lymphoma (PMBCL) and to classify them as mediastinal gray zone lymphoma(MGZL) and to define a minimum immunopanel for the diagnosis of MGZL. Materials and Methods. Ninety-two mediastinal B-cell lymphomas were reviewed with a wide immunopanel and were classified as CHL, PMBCL, or MGZL. CHL with an expression of 3 or 4 transcription factors performed worse, and hence the CHL with ≥3 transcription factors were classified as MGZL-CHL. In PMBCL, the cases with a weak or negative CD20 and positive CD15 as well as those cases showing cyclin E positivity with a negative or focal LCA and any one of the transcription factors were classified as MGZL-PMBCL. Results. The MGZL cases expanded from 9 to 28 cases after using an extended immunopanel. CHL and PMBCL had a disease-free survival rate of 86.8% and 69.2% and an overall survival rate of 97.4% and 80.8%, respectively. MGZL-CHL and MGZL-PMBCL had a disease-free survival rate of 33% and 40% and an overall survival rate of 66.7% and 60%, respectively. Conclusion. Thus, the MGZL may be a wider category than we think and hence the use of a wide immunopanel is recommended to identify the aggressively behaving mediastinal B-cell lymphomas.
A 3.0 x 2.5 cm rhabdoid myomelanocytic tumor was incidentally found in the left ovary of a 43-year-old black woman. The tumor cells were cytologically bland with minimal proliferation rate, multifocally weakly or moderately expressed TFE3, strongly expressed smooth muscle markers and SMARCB1/INI1, and focally expressed HMB45. They contained numerous paranuclear whorls of intermediate filaments that were verified by ultrastructure. No other lines of differentiation were detected within the tumor. Neither translocation nor increased number of copies of the TFE3 gene at Xp11.22 was detected by fluorescence in situ hybridization. The patient remains well, free of tumor, 7 years after surgery. A rhabdoid variant of myomelanocytic tumor is a rarity, with only a single case described previously.
The cytokine interleukin-33 (IL-33) is abundantly expressed in epithelial barrier tissues such as salivary glands. Here, we characterized nuclear IL-33 protein expression by immunohistochemistry in benign and malignant salivary gland tumors and associated it with disease outcome. Most benign salivary gland tumors expressed IL-33, and all Warthin’s tumors showed strong and consistent IL-33 expression in the basally oriented cells of their bilayered epithelium. In the malignant group of neoplasms, nuclear IL-33 expression was limited to specific tumor entities—for example, to epithelial-myopepithelial carcinomas (n = 9/11), acinic cell carcinomas (n = 13/27), and oncocytic carcinomas (n = 2/2). IL-33 expression in the combined group of malignant salivary gland neoplasms was significantly associated with favorable histological parameters, lack of metastasis, and longer overall survival, compared with IL-33–negative tumors. We conclude that IL-33 expression is a novel prognostic marker for malignant salivary gland tumors with potential use in clinical diagnostics.
An incidental finding of napsin A–positive breast carcinoma with apocrine features during workup for metastatic cancer in an axillary lymph node led to our investigation of the incidence of napsin A expression in breast carcinomas, focusing on those with apocrine features. We included 97 cases of breast carcinomas and performed immunohistochemistry with napsin A, GATA-3, thyroid transcription factor-1, and GCDFP-15. There was a statistically significant difference between apocrine and nonapocrine cases with respect to polyclonal napsin A H-scores (P < .00152), monoclonal napsin A H-scores (P < .00631), GATA-3 H-scores (P < .00029), and GCDFP-15 H-scores (P < .00251). Of the 49 cases of apocrine carcinoma, monoclonal napsin A antibody was positive in 66.7% of cases, including in 7 (14.6%) that showed 3+ staining. The majority of nonapocrine cases were negative (62.5%) or weakly (1+) positive (29.2%), with none exhibiting 3+ strength. It is important for pathologists to be aware that breast carcinomas with apocrine features can express napsin A.
Background. Cytomegalovirus (CMV) infection of the gastrointestinal (GI) tract is associated with high mortality in immunosuppressed patients. However, few studies have correlated blood CMV load with GI histopathological findings. Furthermore, there have been few studies determining the clinical significance of isolated CMV infection. Design. Cases were selected for the diagnosis of GI CMV infection by searching the information system of a tertiary hospital. The electronic medical record was reviewed for each case to determine blood viral load, clinicopathological features at the time of diagnosis and clinical outcomes after discharge. Results. In all, 30 patients with CMV-positive intestinal biopsies confirmed by immunohistochemistry (IHC) were identified. All were immunosuppressed. CMV inclusions were also recognized by hematoxylin and eosin stain in 27% of the cases, and the remaining cases were identified by IHC alone. CMV blood load was only positive in 17% of the cases; 8 cases had only isolated CMV-infected cells (0.1-0.5 IHC count/high-power field), with the following outcomes: worsening symptoms that responded to antiviral therapy (n = 5); clinical improvement without treatment (n = 1); death without treatment (n = 2). Conclusions. CMV infection of the intestines is clinically significant but will not always present with classic viral cytopathic changes. IHC should be considered in any case where there is a clinical suspicion for CMV infection. Identification of isolated CMV infection by IHC should be considered clinically significant. Current blood viral load tests have poor sensitivity in detecting CMV intestinal infection. Future studies will investigate the predictive value of positive peripheral blood viral load in patients with intestinal symptoms.
Giant cell tumors of bone (GCTs) are generally benign, locally aggressive neoplasms that rarely metastasize. The beta subunit of human chorionic gonadotropin (beta-hCG) is expressed in syncytiotrophoblasts and several nongynecologic neoplasms but has not been described in GCT. At our institution, we observed cases of elevated beta-hCG in patients with GCT leading to diagnostic difficulty and in one case, concern for metastatic choriocarcinoma. This study aims to determine the frequency of beta-hCG expression in GCT and any relationship to clinical aggressiveness. We evaluated tissue expression of beta-hCG by immunohistochemistry with 58% of cases staining for beta-hCG. Additionally, 2 of 11 patients with available serum and/or urine beta-hCG measurements demonstrated elevated beta-hCG due to tumor. It is important to be aware of beta-hCG expression by GCT and the potential for elevated urine and serum beta-hCG levels in patients with GCT so as to avoid misdiagnosis of pregnancy or gestational trophoblastic disease.
We assessed the contribution of histopathological features to systemic recurrence (SR) in patients with colorectal cancer, using a case-control design: 71 cases and 184 controls were included, with a mean time until SR of 1.4 ± 0.1 years and a mean follow-up of controls of 1.6 ± 0.06 years. Cases had significantly greater odds of rectal site (odds ratio [OR] = 1.82), stage ≥pT3 (OR = 2.11), suboptimal (<12) lymph node yield (OR = 4.6), stage ≥pN1 (OR = 2.46), KRAS mutation (OR = 2.76), and extramural venous invasion (OR = 1.97). By multiple regression analysis, rectal site, stage ≥pT3, suboptimal lymph node yield, and lymph node positivity independently predicted SR. Rectal cancers were more likely to have a suboptimal node yield than nonrectal cancers (relative risk = 1.6) among the entire cohort. We conclude that rectal cancers have greater risk of SR than colon cancers. A lower yield of lymph nodes in rectal cancer specimens may contribute to this.
Common variable immunodeficiency (CVID) is associated with an increased risk of gastric cancer. The aim of the study was to determine the morphological features of CVID-associated gastric adenocarcinoma (CAGA) and of the background gastritis. The population of gastric cancer patients with CVID of Mayo Clinic in the period 2000-2010 was studied; 6 cases of CVID (2 males, 4 females, average age 47 years, age range 26-71 years) were found in 5793 patients with gastric cancer in the study period. Each patient underwent gastric resection for which histology slides were reviewed. Chronic gastritis variables, CVID-related findings, and features of the adenocarcinoma were recorded. CAGA was of intestinal type, with high number of intratumoral lymphocytes (ITLs). Cancer was diagnosed in younger patients than in the overall population of gastric cancer. Severe atrophic metaplastic pangastritis with extensive dysplasia was present in the background in 4 cases, with features of lymphocytic gastritis in 2 cases. Features of CVID (plasma cells paucity in 4 of 6 cases, lymphoid nodules prominent in four cases) could be detected. In summary, gastric adenocarcinoma at young age with ITLs, accompanied by atrophic metaplastic pangastritis, should alert the pathologist of the possibility of CAGA. It follows that, in presence of those characteristics, the search of CVID-associated abnormalities should be undertaken in the nonneoplastic tissues.
The role and diagnostic efficacy of gene and protein products RB1, CDK4, CHMP2B, HSP90, and cPLA2G4A, all previously shown to be involved in tumor genesis and cell proliferation, were examined by immunohistochemical techniques in 32 cases of myxofibrosarcomas and 29 myxoid liposarcomas (all diagnosis had been confirmed by fluorescence in situ hybridization). HSP90 demonstrated strong nuclear and cytoplasmic positivity in all myxoid liposarcoma cases, while only 4 myxofibrosarcomas showed scattered HSP90 positivity. All but 4 cases of myxofibrosarcoma displayed strong positivity for cPLA2G4A, while only 2 myxoid liposarcoma cases were cPLA2G4A positive and both were CHMP2B negative. Overexpression of both cPLA2G4A and CHMP2B also suggested higher tumor grade. In conclusion, HSP90 and cPLA2G4A immunohistochemical stains are useful markers to distinguish myxofibrosarcoma from myxoid liposarcoma.
We describe 2 new cases of malignant melanoma with divergent rhabdomyoblastic differentiation occurring in adult patients. The patients were women aged 67 and 51 years with primary cutaneous and uterine cervical melanoma, respectively. Rhabdomyoblastic differentiation in melanoma is very rare in adult patients, and to our knowledge, only 7 such cases have been described in the world literature, of which only 4 have conclusive documentation of the presence of rhabdomyoblastic differentiation. We present the fifth and sixth cases of adult melanomas with conclusive divergent rhabdomyoblastic differentiation, including the first noncutaneous (cervical) case; we also review the literature and highlight the potential for underrecognition of this phenomenon.
We report a case of an encapsulated, noninvasive, follicular thyroid neoplasia with high-grade features in a 59-year-old man who developed multiple metastases. The 5-cm lesion was originally categorized by thyroid fine-needle aspiration as "suspicious for a follicular lesion" and as a "follicular adenoma" on the subsequent hemithyroidectomy specimen. The high-grade features were represented by foci of solid, trabecular, and insular pattern (10% of the tumor), necrosis (< 5% of the tumor), and up to 14 mitoses per 10 high-power fields in the solid areas. No immunohistochemical and molecular markers associated to thyroid malignancy were observed. Although encapsulated noninvasive follicular tumors are usually regarded as benign lesions that never metastasize or recur, our case was characterized mainly by an elevated number of mitoses, and the patient progressed to widespread metastatic disease. This uncommon lesion should most likely be considered as an early form of poorly differentiated thyroid carcinoma with a dismal prognosis.
Plasmablastic lymphoma (PBL) is reported rarely in children. To date, 10 cases are documented in the English-language literature. This study, based on 13 biopsies from 11 HIV-positive children (9 males, 2 females), documents the clinicopathologic features of PBL. The CD4 count ranged from 9 to 800 cells/mm3. All biopsies demonstrated exclusive plasmablastic morphology; CD20 immunonegativity; and VS38c, EMA, CD31, MUM-1, CD45, and CD79a immunopositivity. B-cell monoclonality was confirmed in all biopsies. Of 3 biopsies subjected to FISH investigation, 2 had a t(8,14) translocation. Nine patients with follow-up details were treated exclusively with HAART (highly active antiretroviral therapy) or with combinations of HAART, chemotherapy, and radiotherapy. Seven patients died. PBL histomorphology, disease stage, and treatment modalities employed were not predictive of outcome. The survival of 2 stage 4 patients for 3 and 8 years each, managed on HAART, chemotherapy, and radiotherapy, however, may justify a role for combined therapeutic modalities for PBL.
Gestational cancer is a dramatic situation, with a deep impact on the patient and family, with an overall incidence of 1 per 100 pregnancies. Lung cancers are extremely rare during pregnancy but have become more frequent in past years, as the mean age of pregnancy has increased. The purpose of this case report is to present a gestational lung adenocarcinoma, with metastasis in the liver and ovaries, diagnosed in the third trimester, with a fatal outcome in days after birth through cesarean section.
Pulmonary mucin-producing adenocarcinomas may be indistinguishable on conventional histology from a metastasis, as thyroid transcription factor-1 (TTF-1) expression often is lacking and KRAS mutations are widely present even in extrapulmonary sites. Few data have been reported on the diagnostic role of napsin-A and epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) gene alterations in this challenging differential diagnosis. Seventy-seven surgically resected cases, including 53 primary and 24 metastatic tumors from different sites, were evaluated for napsin-A, TTF-1, and ALK by immunohistochemistry and for EGFR mutations by direct sequencing. Overall, napsin-A expression in primary lung mucin-producing adenocarcinomas was 36% (8% mucinous, 17% colloid, 87.5% solid, and 100% signet ring cell) and TTF-1 expression reached an overall figure of 42% (12.5% mucinous, 33% colloid, 87.5% solid, and 100% signet ring cell). Metastatic mucinous adenocarcinomas did not react with napsin-A or with TTF-1. All primary and metastatic tumors lacked EGFR mutations, while a single case of signet ring cell lung adenocarcinoma showed ALK expression and rearrangement at fluorescent in situ hybridization analysis. Napsin-A has a lower sensitivity compared with TTF-1 in primary mucin-producing adenocarcinomas of the lung. However, both antibodies have an absolute specificity, being always negative in metastatic mucinous adenocarcinomas. EGFR mutations and ALK translocation or expression are exceedingly rare in mucin-producing adenocarcinomas of the lung, resulting unnecessary as diagnostic tool in this setting.
Twelve cases of urothelial cell papillary carcinoma with a whorled pattern of growth are described. This variant is reported with clinicopathological correlations and immunohistochemical findings. All cases showed this peculiar and distinctive curlicue histological pattern, ranging from 50% to 100% of the neoplastic population. Despite the disordered/turbulent growth pattern, the cytological grade was uniformly low. All the lesions were Ta staged and no patient experienced progression after transurethral resection, while 2 showed clinical recurrences. The immunophenotype (low p53, high p27, low Ki67, and high GATA3) of the cases contributes to define this rare variant as a low-grade tumor.
Male endometriosis and endomyometriosis (also termed "uterus-like mass") are 2 unusual manifestations of endometriosis. We report a case of male endomyometriosis with immunohistochemical and molecular confirmation. A 52-year-old man presented with stabbing pelvic pain. Computed tomography scan showed a mass in the right inguinal area, at the site of prior hernia repair. The lesion was tubular in shape, with a thick muscular wall and a central blood-filled lumen. Microscopically, the tissue showed layers of concentric smooth muscle, with endometrial glands and stroma lining the lumen. Many theories have been proposed regarding the etiology of both endomyometriosis and male endometriosis, including remnant rests of Müllerian tissue and metaplasia. Cases of male endometriosis typically have been linked to estrogen therapy for prostate cancer. Our patient had a history of cirrhosis and took spironolactone, possibly leading to an altered hormonal state that interacted with a reactive/metaplastic process at a site of prior surgery.
Wagner-Meissner corpuscles are touch receptors that are located in dermal papillae and are usually absent in gastrointestinal mucosa. Wagner-Meissner–like corpuscles have been reported in association with benign neural neoplasm. A case of Wagner-Meissner–like corpuscles in endoscopically normal gastric mucosa biopsy of a 48-year-old woman is presented here. The corpuscles were positive for S-100 and clinical evidence of neurofibromatosis was negative. From a review of the literature, only 2 cases of tactile corpuscle-like structures in gastric mucosa are available.
Although Paget disease of the nipple (PDN) is a well-established clinical and pathological neoplastic process, invasive PDN (IPDN) is a relatively newly described disease. The latter entity is characterized by invasive carcinoma that is localized to the nipple and is associated with PDN as well as with either intraductal and/or invasive carcinoma in the underlying breast. To our knowledge, only 17 cases of IPDN, all node negative, have been reported. Here, we report the case of a 68-year-old woman with invasive Paget disease of the left nipple. The patient had a history of intraductal carcinoma, treated by lumpectomy alone. She presented 6 years later with "eczematous" lesion of the ipsilateral nipple, a punch biopsy of which showed a superficially IPDN as well as conventional PDN. The subsequently performed wide excision of the nipple, areola, and underlying breast tissue showed the invasive carcinoma to span 0.6 cm. Then, 3 months later, the patient presented with ipsilateral palpable axillary lymphadenopathy. Axillary dissection revealed metastatic carcinoma in 7 of 19 lymph nodes. This case of IPDN not only represents the deepest extent of invasion reported thus far but also the only one known to be node positive.
Inflammatory myofibroblastic tumor (IMT) is a locally aggressive neoplasm, most frequently occurring in the abdominal cavity as multiple recurrent nodules. We report a case of IMT in a 24-year-old male presenting as multiple nodules involving the omentum, the liver, and the colon. Spindle tumor cells expressed ALK with a cytoplasmic granular distribution, the CLTC-ALK fusion gene was demonstrated by reverse-transcriptase polymerase chain reaction analysis, and break-apart fluorescence in situ hybridization (FISH) probes for the ALK gene showed a pathological pattern (single red signal associated with 1/2 normal fused signals) highly suggestive for combined gene fusion and deletion. To reduce the surgically unresectable liver mass, the patient was treated with crizotinib, and after 4 months of treatment the disease was defined stable according to RECIST criteria. Interestingly, ALK and FISH/FICTION analysis revealed that tumor cells were widely dispersed as multiple microscopic foci or as single cells beneath the omental mesothelium. These findings indicate that IMT multifocality might result either from dissemination from the main tumor mass or development of multiple independent neoplastic foci; furthermore, they underline the need of omentectomy in abdominal IMT to obtain surgical radicality.
A 52-year-old otherwise healthy woman presented with a solitary firm mass in the right breast. Histopathological evaluation of the 1.5-cm mass showed a mammary myofibroblastoma of the conventional spindle-cell type. High-power examination of hematoxylin–eosin-stained sections showed round, eosinophilic, intracytoplasmic, as well as extracellular, hyaline globules. These 5- to 20-µm globules appeared gray with a pinkish rim on Masson’s trichrome stain. Immunohistochemically, the hyaline globules were strongly reactive with smooth muscle myosin heavy chain, desmin, and caldesmon. Histologically similar inclusion bodies have been reported in phylloides tumors—including those with myoid differentiation. To our knowledge, this is the first description of hyaline globules, a peculiar histological curiosity with no known clinical significance, in mammary myofibroblastoma.
Adequate management of phyllodes tumors of the breast (PTB) remains a challenge because of the difficulty in correctly establishing preoperative diagnosis. The aim of this study was to evaluate the usefulness of Ki-67, CD10, CD34, p53, CD117, and of the number of mast cells in the differential diagnosis of benign PTB and cellular fibroadenomas (CFs) as well as in the grading of PTB. Fifty-one primary PTB and 14 CFs were examined by immunohistochemistry.When evaluating CD117 expression, higher epithelial expression was present in CF as well as an increased number of mast cells in benign PTB. Stromal expression of Ki-67, CD10, CD34, and p53 were relevant to PTB grading, of which the first 3 showed significance in the distinction of benign and borderline PTB, as well as between benign and malignant PTB. P53 was relevant only for the discrimination between benign and malign PTB. None of the markers showed significance in distinguishing between borderline and malign PTB.
Myelolipomas are rare benign tumors of poorly understood tumorigenesis composed of mature hematopoietic tissue and fat. They mostly occur in the adrenal glands, but extra-adrenal myelolipomas have been reported in other locations such as the presacral region or retroperitoneum. It is not unusual that they are incidental findings revealed in the study of different diseases. We report 3 unusual examples of myelolipomas. The first is a multiple, unusually large, extra-adrenal myelolipoma, presented as an autopsy finding in an individual who had died suddenly from a central nervous system hemorrhage. The remaining 2 were incidental findings in patients studied for different reasons. Both were located within another neoplasm, namely an adrenal adenoma and a liver focal nodular hyperplasia. Moreover, the first showed infiltration by a non-Hodgkin lymphoma.
An adult man underwent arm amputation for a sarcoma. Pain and three masses observed radiologically prompted surgical exploration five years later. Microscopically, the masses represented amputation neuromas. One of them was located in the lumen of an artery, in a remote organized thrombus. Intravascular growth of an amputation neuroma has not been described previously.
Distinguishing between malignant mesothelioma and reactive mesothelial hyperplasia is often inestimable, but may be a challenging gauntlet for pathologists. A 62-year-old man underwent appendectomy after the identification of a peritoneal mass and the histological examination showed mesothelial proliferation along the appendix surface with no clear images of infiltration. After a few months the patient developed mediastinal and supraclavicular lymphadenopathies, and a nodal biopsy showed mesothelial cell proliferation invading lymphatic sinuses, consistent with the cells seen in the abdominal cavity. Since overt morphologic criteria for malignancy were lacking and reactive mesothelial cell deposits have been documented in lymph nodes, a molecular investigation of the CDKN2A (henceforth simply p16) gene status via fluorescence in situ hybridization was performed, which showed homozygous deletion in 100% tumor cells. These data ruled out the hypothesis of reactive mesothelial cells inclusion in lymph nodes, thus confirming the diagnosis of epithelioid malignant mesothelioma.
Castleman’s disease in the pelvic cavity is rare. We present a 72-year-old woman with hyaline vascular type of Castleman’s disease of the right ovary. Right ovarian enlargement was detected in the medical examination. Computed tomography revealed a solid mass, measured 2.5 cm in size, in the right ovary. A bilateral salpingo-oophorectomy was performed. Morphologically, lymphoid follicles with regressed germinal centers (GCs) were surrounded by a broad mantle zone composed of concentric rings of small lymphocytes, and the hyalinized blood vessels with plump endothelial cells penetrated radially into GCs. Proliferation of follicular dendritic cells, which were positive for CD21 and epidermal growth factor receptor, were detected in GCs and mantle zone. No other lesions were found. To the best of our knowledge, this is the first case of hyaline vascular type of Castleman’s disease of ovarian primary.
Primary salivary gland–type lung cancers are a rare group of tumors. When they do occur, the most common type is adenoid cystic carcinoma, followed by mucoepidermoid carcinoma. Primary high-grade salivary-type duct carcinoma (HGSDC) arising in the lung has not been described. We report a case of primary pulmonary HGSDC in a 55-year-old woman who was referred to our hospital for a suspicious lung tumor. The chest computed tomography revealed a solid mass in the left upper lobe. A lobectomy was performed afterward, and the mass was a primary lung HGSDC. To the best of our knowledge, HGSDC arising in the lung has not been reported previously.
Membranous fat necrosis is an unusual type of fat necrosis occurring in the breast and normally involves the parenchyma. This report describes an apparently unique intraductal focus in a fibroadenoma following prior needling. Displacement of fatty tissue in the form of membranous fat necrosis within ducts could be added to the list of histological features following core biopsy.
Introduction. Prior studies have revealed that the concordance between biopsy and surgical specimens has been improving over time. However, to date, this has not been analyzed in an African American population, for whom data have often shown more aggressive prostate cancer than for other races. Methods. We analyzed 250 patients who were operated on at the NY Harbor Department of Veterans Affairs for localized prostate cancer between 2003 and 2010. The clinical biopsy scores were compared with the pathological biopsy scores. We compared the concordance using the coefficient. Univariate and multivariate logistic regressions were used to identify predictors for poor concordance. Results. This population consisted of 59.6% African Americans, 32% Caucasians, and 8.4% Hispanics. Overall, there was a 50% exact concordance between the biopsy and surgical specimens. The was 0.33, indicating fair agreement. Patients with a Gleason score of 6 were found to have an exact concordance 66% of the time, and those with a score of Gleason 7 (3 + 4) had an exact concordance 50% of the time. On univariate and multivariate analyses, only an increasing prostate-specific antigen was associated with reduced concordance. Race was not a significant predictor. Conclusions. These data are in line with prior studies of concordance. Despite being a population with more aggressive prostate cancer, there does not appear to be an increase in the risk of discordance in African American men.
Schwannoma is a benign peripheral nerve sheath neoplasm of soft tissue that consistently demonstrates immunohistochemical staining for S100 protein. Intraosseous location of schwannoma is very uncommon. We report the first case of an intraosseous schwannoma located in the epiphysis of tibia in an adult patient. Radiologically, it mimicked a primary bone tumor and despite benign histological appearance, the tumor eroded cortical bone. Morphologically on routine stains and electron microscopy it has features of a schwannoma. But by immunohistochemistry, the tumor was positive for both desmin and S100 protein in the same region.
We report an extremely rare case in which cilia were identifiable on light microscopic examination in cells of a moderately differentiated peripheral adenocarcinoma in the lung. The cells were positive for cytokeratin 7, and the cilia were highlighted by epithelial membrane antigen staining. The prognostic significance of these extremely well-differentiated ciliated tumor cells will be known only with long-term follow-up of the patient and analysis of more such tumors.
A case of melanoma with rhabdomyoblastic differentiation is presented in the context of the previously reported cases. The emerging literature seeking to identify the molecular basis of rhabdoid and rhabdomyoblastic differentiation, as well as their poor prognosis, is reviewed. The combination of a diverse range of morphology and the potential for spontaneous primary tumor regression, despite metastasis, makes the accurate diagnosis of melanoma challenging. Histopathology review is often recommended in these cases, as is referral to a specialized cancer center for discussion in a multidisciplinary meeting. Improved recognition of this rare pattern of melanoma morphology may provide the means for omics-based techniques to identify novel therapeutic targets to improve the prognostic outlook for these patients.
Histologic mimics of poorly cohesive gastric carcinoma are uncommon but are important for pathologists to recognize. Here we report 2 cases of a novel histologic pattern mimicking poorly cohesive gastric carcinoma. In both cases, light microscopy revealed sheets of discohesive epithelial cells with prominent mitoses that have high proliferative activity, with a Ki67 proliferation index greater than 70%. One case was diagnosed as poorly cohesive carcinoma at an outside hospital and the other was referred in consultation as atypia of undetermined significance. Reexamination of the hematoxylin–eosin slides revealed morphologic clues that these sheets of discohesive cells represent artifactual extrusion of the highly proliferative neck zone from the surrounding benign mucosa. In contrast to poorly cohesive cancer, this artifact lacks all of the following diagnostic features: nuclear atypia, signet ring cell morphology, and intercellular stroma with infiltrating single cells between glands. Eight and 14 months later, both patients remain cancer free.
Follicular colonization is occasionally observed in marginal zone lymphoma. In rare cases, it has also been associated with mantle cell lymphoma. Chronic lymphocytic leukemia typically involves nodal or extranodal tissues as diffuse proliferation by complete effacement of the normal architecture. The involvement of chronic lymphocytic leukemia may be less frequently limited to the interfollicular areas. Here, we report a case of Richter syndrome of the small intestine that was initially diagnosed as follicular lymphoma of the gastrointestinal tract because of a partial follicular growth pattern in addition to a mainly diffuse proliferation pattern. The follicular pattern mimicking follicular lymphoma was shown to be composed of reactive follicles with follicular colonization of the original chronic lymphocytic leukemia cells. As the prognoses of Richter syndrome and follicular lymphoma of gastrointestinal tract are quite different, clinicians must carefully diagnose these conditions to avoid a misdiagnosis.
Primitive myxoid mesenchymal tumor of infancy (PMMTI) is a relatively recently described tumor arising in infants and demonstrating a unique histomorphology. We present an unusual case of PMMTI with rosettes, a hitherto undescribed finding in the reported cases. We also present the cytogenetic and ultrastructural findings of this tumor and review the literature. As awareness of PMMTI increases, additional clinical data and histopathologic findings will aid in the morphologic and behavioral characterization of this neoplasm.
Fibroblastic reticulum cells (FBRCs) belong to a major subtype of stromal support cells in the lymphoid system and rarely give rise to tumors. We report a case of fibroblastic reticulum cell tumor arising in the spleen. The tumor was clinically and radiologically mistaken for a metastatic deposit in the spleen. Microscopically the tumor was composed of spindle cells arranged in fascicles and storiform pattern. The cells had oval to elongated vesicular nuclei and pale eosinophilic cytoplasm with indistinct cell borders. There were admixed inflammatory cells, including large numbers of plasma cells. The tumor cells were positive for smooth muscle actin, desmin, AE1/AE3, and MNF116. They were negative for S100, CD1a, CD21, CD23, CD34, CD31, and CD35 among other markers. The morphological features and immunoprofile of this rare tumor in comparison to the few cases reported in the literature are discussed along with the positive reaction with cytokeratins and their relationship to the smaller subset of FBRCs, the cytokeratin-positive interstitial reticulum cells in the spleen.
Intra-abdominal cysts have a variety of origins, of which lymphatic and mesothelial types are the most commonly encountered. Here we describe a combined mesothelial cyst and lymphangioma arising within the small bowel subserosa of an 80-year-old woman. This was found incidentally at laparotomy performed for an unrelated condition. To date, such a hybrid lesion has not been previously reported. The ways by which this lesion might have arisen are discussed.
Combined blue nevus and benign nevus cells were identified in the same sentinel lymph node. Blue nevus alone was also present in an additional sentinel lymph node in the same axilla in a patient who underwent needle localization, wide local excision, and sentinel lymph node biopsy for her pT1cN1mi(sn)M(na) invasive duct carcinoma of the breast. Of the 4 sentinel lymph nodes, 1 showed micrometastasis and 2 other lymph nodes showed blue nevus involving the capsule and trabeculae of the nodes. The patient had no significant previous clinical history of any skin tumors and had a negative clinical examination for malignant melanoma or pigmented skin lesions after the diagnosis of nodal blue nevus. To our knowledge, this is the first case report of combined blue nevi involving multiple sentinel lymph nodes in the same axilla. An equally interesting finding is the presence of benign nonpigmented nevus cells in continuation with the blue nevus in the same node.
Multicentric Castleman’s disease is a rare condition of systemic nonclonal lymph node hyperplasia. Because of its strong association with human herpes virus 8 (HHV8), the multicentric, more aggressive, form may progress to Kaposi sarcoma or non-Hodgkin lymphoma. While surgery is curative in the treatment of localized Castleman’s disease, operative treatment of the diffuse form has as yet been unsatisfactory. We report the case of a patient presenting with postprandial vomiting of 1 month duration consistent with partial small bowel obstruction secondary to terminal ileum intussusception. Resection of the small bowel showed a stenosing tumor triggering the intussusception. On pathological examination, the tumor was found to be composed of HHV8-positive plasmablastic lymphoma cells. To our knowledge, this represents the first case of a complication due to the progression of multicentric Castleman’s disease requiring surgical intervention for intussusception.
Kayexalate (sodium polystyrene sulfonate), a cation exchange resin often used to treat hyperkalemia, is known to produce gastrointestinal complications in a minority of patients. These complications range from mild gastrointestinal bleeding to perforation with acute abdomen. The typical histopathologic findings include mucosal ulceration, necrosis, and the presence of polygonal basophilic refractile crystals with a "fish scale" appearance. We present a unique case of Kayexalate crystals embedded in a perihepatic inflammatory pseudotumor, developing adjacent to a colostomy site in a 62-year-old woman following Kayexalate treatment. Microscopically, the lesion demonstrated a myofibroblastic proliferation rich in histiocytes and inflammation (lymphocytes, plasma cells, and eosinophils) as well as the presence of scattered typical Kayexalate crystals. This is the first report of extraintestinal Kayexalate identification in association with an inflammatory pseudotumor.
Endometrial stromal tumors (ESTs) with limited infiltration were first proposed by Dionigi et al.1 However, the prognostic significance of these tumors is unclear. We report a case of a 60-year-old woman who presented with a prolapsed uterine corpus and then underwent laparoscopic-assisted vaginal hysterectomy. A very small EST was incidentally found. The tumor manifested focal irregularity and finger-like permeation into the adjacent myometrium not exceeding 3 mm but exceeding 3 in number, features intermediate between a low-grade endometrial stromal sarcoma and an endometrial stromal nodule. By definition, we rendered a descriptive diagnosis of "endometrial stromal tumor with limited infiltration." A subsequent staging operation confirmed metastasis and, hence, a malignant potential.
Hydatidiform mole (HM) is rare in postmenopause, with only 7 cases reported. The occurrence of ectopic HM is also rare, with 26 fully documented tubal cases. We are not aware of any reported cases of ectopic HM in a postmenopausal patient. In a 51-year-old patient with 3 years amenorrhea, surgery revealed a necrotic, hemorrhagic mass involving the right peritubal space. Microscopically, chorionic villi were seen within the hemorrhagic mass accompanied by circumferential trophoblast hyperplasia. Immunohistochemically, p57kip2 positive nuclei were prominent in the extravillous (intermediate) trophoblast. The HER2 FISH expression was diploid, consistent with the diagnosis of an early complete HM.
Ewing’s sarcoma/primitive neuroectodermal tumor (PNET) has been the subject of recent reports describing morphologic variants (adamantinoma-like, large cell, spindle cell, sclerosing, clear cell, and vascular-like) of the most classic form, as well as cases displaying unusual morphologic differentiation and atypical immunohistochemical features. We report a case of an uncommon lung tumor in a 20-year-old female, morphologically and molecularly consistent with an Ewing’s sarcoma/PNET tumor with foci of squamous differentiation, and peculiar expression of vimentin, high-molecular-weight keratins, p63, synaptophysin, and chromogranin. This case raises a challenging differential diagnostic problem with therapeutic implications: Should the patient be treated following the protocols for Ewing’s sarcoma/PNET tumors or as for lung carcinoma with neuroendocrine features? The patient we report here was treated with neoadjuvant chemotherapy for Ewing’s sarcoma/PNET according to Euro Ewing 99 study protocol followed by surgery and has no evidence of disease 15 months after the initial diagnosis. This highlights the importance of achieving the correct diagnosis of these atypical tumors using all clinical, morphological, and ancillary methods available to allow for their correct and timely treatment.
Malignant mesothelioma is a primary neoplasm of the serosal membranes that usually presents with a diffuse pattern of growth. However, cases of localized mesotheliomas have been described. The predominant localization is the pleura; peritoneum and pericardium being rarer localizations. Only few cases of true intraparenchymal mesothelioma arising in organs such as liver, gonads, lung, and pancreas have been described. We report a case of an otherwise healthy 48-year-old man without asbestos exposure with a nodule of 3 cm in diameter, localized in the spleen, discovered incidentally at the ultrasonographic examination, for which histopathological and immunohistochemical findings were consistent with epithelioid mesothelioma: large round cells with eosinophil dense cytoplasm and macronucleoli and with immunohistochemical positivity for pancytokeratins, calretinin, Wilms tumor-1, and others markers of mesothelial differentiation. The diagnosis of localized intrasplenic epithelioid malignant mesothelioma was carried out. To the best of our knowledge, this is the first case of a localized intrasplenic mesothelioma published in the indexed literature.
Undifferentiated embryonal sarcoma of the liver (UESL) is an uncommon hepatic tumor usually found in children, with rare cases reported in adults. We present a case of a 53-year-old woman with an undifferentiated sarcoma of the liver (USL), which resembles UESL, who initially presented with a markedly elevated hematocrit (61.2%). Cytogenetic studies for polycythemia vera were negative, but the patient’s erythropoietin (EPO) was elevated. A computed tomography scan and subsequent partial hepatectomy revealed a well-circumscribed, partially cystic mass in the right lobe of the liver measuring 34 cm. Following surgery, the patient’s EPO level and hematocrit dropped to within normal range and remained so for 1 year, at which point it rose again. A subsequent magnetic resonance imaging scan showed a liver mass at the previous resection margin, consistent with a recurrence. In this case study, we describe the first reported USL resembling an UESL that secretes EPO, which was a useful marker of tumor recurrence.
Adult rhabdomyoma is a rare benign tumor. It mainly occurs in the head and neck region and rarely occurs outside the head and neck region. We present an extremely rare case of the adult rhabdomyoma arising in the left foot in a 46-year-old male. Microscopically, large polygonal cells and large strap-shaped cells were observed. This is the third case of adult rhabdomyoma arising in an extremity.
Langerhans cell sarcoma (LCS) is a rare malignancy requiring differential diagnosis from other high-grade nonhematologic and hematologic tumors. The pathogenesis of LCS remains unknown. Notably, LCS and its benign counterpart, Langerhans cell histiocytosis (LCH), are frequently associated with other malignancies. To the best of our knowledge, we describe the first case of LCS in a chronic myelogenous leukemia (CML) patient undergoing imatinib mesylate therapy. We performed molecular cytogenetic analyses for investigating the association between LCS and CML. In our case, molecular cytogenetic analysis did not reveal BCR-ABL1 fusion and BRAF V600E mutation, suggesting that LCS may be coincident in this patient. However, recurrent BRAF V600E mutation has been found in LCH. Published reports have revealed the clonal relationship between LCH/LCS and other hematologic malignancies, especially lymphoid neoplasms. However, there are only 2 reports demonstrating the clonal relationship between LCH and myeloid neoplasms. The association of LCH/LCS with myeloid neoplasms and the role of BRAF V600E mutation in LCS are discussed.
Although vertical banded gastroplasty is rarely performed at present, most bariatric surgery departments continue to follow up patients who underwent this procedure in the past few decades. In view of this, it is advisable for bariatric and general surgeons to know how to diagnose the very rare event of the development of a gastric cancer after this restrictive procedure. In this report, 2 cases of gastric cancer occurring years after vertical banded gastroplasty are presented, and clinical presentation and diagnostic difficulties are discussed.
Background. Mesenchymal colorectal polyps are uncommon lesions, particularly those of neurogenic origin. We describe a mucosal Schwann cell hamartoma of the colon with tactoid features, so far reported in peripheral nerve sheath tumours, and address its differential diagnosis and clinical implications. Case presentation. A 72-year-old man underwent screening colonoscopy that presented a 5-mm polyp on distal sigmoid. Histologically, it displayed a lesion in the lamina propria comprising oval structures with tactoid features and bland spindle cells, entrapping adjacent crypts. No ganglion cells were seen. Spindle cells expressed only S-100 protein and vimentin. Discussion. Mucosal Schwann cell hamartoma was recently recognized as distinct from common (submucosal) colorectal Schwannomas and so far not associated to inherited syndromes. Thus, it should be considered in the differential diagnosis of look-alike lesions (eg, ganglioneuroma, neuroma, and neurofibroma) that may occur in the setting of inherited syndromes such as Cowden syndrome, multiple endocrine neoplasia-2B, and type 1 neurofibromatosis.
A minor component of smooth muscle may be present in the stroma of benign endometrial polyps and 2 distinctive endometrial polypoid lesions, atypical polypoid adenomyoma and adenomyoma, are characterized by stroma with a predominant smooth muscle component. In this report, we describe 2 unusual endometrial polyps in 43- and 60-year-old women in which the stromal component was predominantly composed of smooth muscle with an epithelioid appearance, a phenomenon which, as far as we are aware, has not been previously reported.
Introduction. Paget’s disease of the vulva is a rare malignancy primarily affecting Caucasian women in their seventh to eighth decades. Most patients experience an indolent disease course and undergo surgical excision for disease control. Although progression to invasive adenocarcinoma is rare, recurrence is common because of the difficulty of achieving negative surgical margins. Case presentation. We report a case of a 73-year-old woman with a long-standing history of recurrent vulvar Paget’s disease who presented with postmenopausal bleeding. Workup revealed extensive endocervical involvement by Paget’s disease, resulting in Paget cells on endocervical curettage, as well as endometrial curettage (because of cervical contamination). Conclusion. Extensive endocervical involvement by vulvar Paget’s disease can occur despite multiple reexcisions and topical therapy. The presence of Paget cells on endometrial and endocervical curettings, particularly in patients without visible vulvar or cervical lesions, should raise suspicion of endocervical involvement and prompt further evaluation of disease extension.
The expression level of Notch1 has been studied in many primary tumor types, but has not been widely investigated in metastatic lesions from human malignancies. Using immunohistochemistry (IHC), the expression level of Notch1 was evaluated and compared between primary and metastatic tumors in 12 different cancers. The mean IHC score of Notch1 was significantly increased in metastatic hepatocellular carcinoma (HCC; 5.4 ± 0.7) and in metastatic renal cell carcinoma (RCC; 5.0 ± 2.3) compared with primary HCC (3.1 ± 0.7, P = .035) and RCC (1.3 ± 0.6, P = .049), respectively. Similarly, the expression level of Notch1 showed an increasing trend in the metastatic malignancies in the larynx, prostate, and stomach compared with corresponding primary malignancies (P values are .055, .072, and .074, respectively). The results demonstrate elevated expression of Notch1 in some metastatic tumors, suggesting that Notch1 may play an important role in the development or maintenance of metastatic lesions, and targeting of Notch1 might be a therapeutic approach against tumor metastasis.
Background. Diagnosis of cervical intraepithelial neoplasia (CIN), the precursor forms of cervical cancer, can be tricky and it has led to discrepancy between pathologists in distinguishing them from its mimics such as atypical immature metaplasia (AIM), immature squamous metaplasia (ISM), reactive atypia (RA), atrophy, and basal cell hyperplasia (BCH). To overcome this problem this study aims at using immunohistochemical (IHC) markers p16, p63, CK17, and human papillomavirus (HPV) to differentiate CIN from its mimics. Materials and methods. This study analyzed 350 cervical samples with histomorphological diagnosis of CIN and its mimics and the utility of IHC markers p16, p63, CK17, and HPV in distinction was analyzed. Results. p16 showed 67.76% sensitivity and 99.4% specificity whereas HPV showed 57.9% sensitivity and 91.6% specificity in detecting CIN. CK17 and p63 did not show any significance in distinguishing CIN from its mimics. After IHC of AIM cases, 66.7% were reclassified as CIN III, 27.8% as ISM with reactive atypia (ISMRA), and 5.5% case as immature condyloma. In total, 3.7% of diagnosis was upgraded to CIN and 0.6% of pre-IHC diagnosis was downgraded from CIN to reactive lesions. Conclusion. IHC panel comprising p16, p63, CK17, and HPV are useful adjuncts in distinguishing CIN from its mimics particularly when histomorphology has overlapping morphological features.
Changes in breast tissue in female-to-male transsexuals following gender reassignment and androgen therapy can cause difficulties in interpreting breast core biopsies. Clinical history and awareness of histological changes in breast tissue associated with androgen treatment are important in such cases. Specimen mislabeling is a potential pitfall to be borne in mind while evaluating unusual presentations in breast core biopsies. We report a case of a 58-year-old male with a well-defined supra areolar lesion clinically thought to be a fibroadenoma.
Mucinous cystadenoma of the salivary gland is a very rare disease, and only a few cases have been reported. We report here 2 cases of mucinous cystadenoma in the upper lip. The first case was a 57-year-old man and the second was a 42-year-old woman. The tumors were painless nodules with a smooth-surfaced mucosa, and surgical excisions were performed. Histologically, the tumors were surrounded by a fibrous capsule and were composed of multiple cysts lined with columnar epithelial cells. The tumor cells contain mucous substances that reacted with periodic acid-Schiff base and Alcian blue. Immunohistochemical staining revealed that the tumor cells expressed cytokeratin (AE1/3 and CK7), but their immunoreactivity with MIB-1 (Ki-67) was less than 3%. They had negative immunoreactivity for neuroectoderm markers, S-100 protein, and myoepithelial markers, p63, α-smooth muscle actin, and calponin, except for the accompanying myoepithelial-like cells. No recurrences were noted after surgery at 7 years and 1 year, respectively.
Epstein–Barr virus–associated smooth muscle tumors (EBV-SMTs) are rare lesions that occur in immunocompromised patients. Dural involvement appears to be less common in organ transplant recipients than in HIV patients. Due to the paucity of reported cases following organ transplantation, the natural history of these lesions is unclear. We describe an 8-year-old female who presented with adrenal, small bowel, and intracranial tumors 6 years following renal transplantation. Histopathological analysis revealed a highly cellular, mitotically active, smooth muscle neoplasm without necrosis. The tumor stained diffusely for smooth muscle actin and myosin. In situ hybridization for EBV-encoded RNA was diffusely positive. Following gross total resection, antiviral therapy, and a reduction in immunosuppression, the patient is tumor-free at 3 years follow-up. In patients with compromised immune systems, it is important to recognize this unique form of SMT because, even when there are multiple lesions, the prognosis may be excellent.
Micropapillary pattern of growth (MPG) of carcinoma is a unique morphologic pattern. It is uncommon but predicative of poor outcome. MPG has not been described in any germ cell tumor, most notably embryonal carcinoma, which may have papillary configuration. In this study, we reviewed 25 primary testicular germ cell tumors (pure or mixed) containing embryonal carcinoma and 2 lymph node metastases with embroynal carcinoma. Five of the 25 primary cases demonstrated MPG. With available clinical information, 3/3 (100%) cases with MPG and 5/12 (42%) cases without MPG showed evidence of metastases. The 2 lymph node metastases contained predominantly MPG. At metastasis, the median tumor size in primary tumors with MPG was significantly smaller than in those without MPG. Reticulum staining was negative in the regions of MPG and positive for other coexisting non-micropapillary growth patterns in all the 6 embryonal carcinomas. In conclusion, we described MPG in embryonal carcinoma. Although limited by the number of cases, our clinicopathological correlation results raised the possible association of the presence of MPG to the high-rate metastasis of embryonal carcinoma, similar to that seen in other carcinomas with MPG. It is therefore of importance to document this variant growth pattern if present in embryonal carcinoma. We also demonstrated that reticulum is a useful negative marker for identification of MPG.
Recognition of an appendiceal diverticulum is important because of its association with an appendiceal neoplasm. The incidence of mucosal Schwann cell proliferation in 24 cases of appendiceal diverticular disease, 17 serrated polyps, 4 cases of mucosal hyperplasia, and 45 normal appendices was determined. Ten (42%) of 24 cases with diverticula, 2 (50%) of 4 cases of mucosal hyperplasia with concurrent surface low-grade dysplasia, and 9 (20%) of 45 cases of normal appendices showed mucosal Schwann cell proliferation. It was not seen within the 17 cases of serrated polyps. Mucosal Schwann cell proliferation is common in appendiceal diverticular disease and may serve as a histologic marker for the presence of an appendiceal diverticulum. Thus, when routine histologic sections of a removed appendix demonstrate Schwann cell proliferation, further examination of the specimen may detect possible coexisting diverticular disease, which in turn may be associated with appendiceal neoplasms and epithelial dysplasia.
C-erbB2/HER2 serves as an important prognostic and predictive biomarker in various human tumors, especially in breast cancer, whereas its role in human intracranial tumors is more uncertain. We therefore performed a search in PubMed to get an update. This literature review comprises immunohistochemical studies on the clinical significance of c-erbB2/HER2 overexpression in gliomas, medulloblastomas, and meningiomas. In general, the findings were discrepant with regard to correlations between overexpression, tumor grade, and prognosis. Use of various antibodies may be a contributing factor to these discrepancies. Standardization of the immunohistochemical procedures is a relevant topic for discussion.
Solitary fibrous tumors (SFTs) are unusual spindle cell neoplasms initially described in the pleura but have since been discovered in many extrapleural locations. SFT of the kidney is extremely rare, the majority occurring in middle-aged adults. To date, only two pediatric cases of renal SFT have been reported. We report a case of large SFT in the kidney of a 3-year-old boy that was clinically and radiologically thought to be a nephroblastoma. This case is the first pediatric renal SFT to be reported with detailed histopathologic and cytogenetic analyses. SFT should be included in the differential diagnosis of pediatric renal tumors.
Benign vascular lesions have a diverse appearance and can be extremely difficult to classify. We present renal anastomosing hemangiomas from 2 patients that exemplify the potential diverse range of appearances that can occur in this recently described, rare variant of capillary hemangioma. The lesion from one patient was an intravenous hemangioma with closely packed, fenestrated vascular channels that were reminiscent of the splenic red pulp. Also, the endothelial cells contained hyaline globules. On the other hand, the second patient had multifocal tumor. The lesions showed more extensive hyalinization and vascular ectasia reminiscent of cavernous hemangioma. Extramedullary hematopoiesis was a feature in all the tumors, particularly in the second patient where numerous immature blasts were present within vascular spaces.
Nitrofurantoin-induced lung toxicity is relatively common, but rare histologic patterns sometimes occur that may make diagnosis difficult. We present the case of a 69-year-old woman taking prophylactic nitrofurantoin for urinary tract infections, who developed granulomatous interstitial pneumonia. She improved with cessation of nitrofurantoin, without other therapy. To our knowledge, this is the fourth reported case of granulomatous interstitial pneumonia associated with nitrofurantoin, and the first to show complete resolution with cessation of the drug alone, without steroids. It is important to recognize that idiosyncratic reactions to nitrofurantoin can produce a wide spectrum of histologic patterns. Of these patterns, granulomatous interstitial pneumonia is a rarely evidenced manifestation (possibly because few cases undergo a confirmatory lung biopsy). Recognition of granulomatous interstitial pneumonia as a manifestation of nitrofurantoin toxicity can aid in early identification of the reaction and prompt withdrawal of the drug, both of which are essential to prevent long-term complications.
Introduction. Clusterin (CLU) has been noted to mark synovium adjacent to tenosynovial tumors, and studies suggest that podoplanin (PP) is upregulated in inflammatory arthritis. Characterization of synovial staining with CLU and PP in various nonneoplastic disease states has not been described. Methods. A microarray was created from paraffin-embedded human synovium, including 19 normal/noninflammatory (10 weight-bearing joints, 8 non-weight-bearing joints), 9 rheumatoid arthritis, 10 synovial cysts, and 3 osteoarthritis and stained with PP (D2-40) and CLU. Staining intensity was graded semiquantitatively (0-3+). Results. PP and CLU stained synovium in 88% and 95% cases, respectively. PP and CLU showed moderate to strong (3+) staining in 26% and 19% of noninflammatory and 44% and 0% of inflammatory synovia, respectively (P < .01). Conclusions. PP and CLU are reliable markers of human synovium and can confirm its presence in limited specimens. Although CLU was more sensitive, PP may be more useful in the setting of chronic inflammation.
Tailgut cysts, also known as retrorectal cystic hamartomas, are congenital lesions derived by an abnormal remnant of the postanal primitive hindgut, consisting of unilocular or multilocular cysts usually lined by squamous, transitional, or glandular epithelium. Malignant transformation is an uncommon event, and it mainly involves the neuroendocrine or glandular epithelium; other histotypes are sporadic. Here, we report, for the first time, the clinicopathological features of a transitional cell carcinoma that arose in a tailgut cyst.
We present a case of a 61-year-old female presenting with a bladder tumor that occurred 7 years after her previous diagnosis of Clark’s level III mid-back melanoma. The bladder tumor was submitted to histopathology without accompanying clinical history, and an initial diagnosis of high-grade urothelial carcinoma was rendered based on epithelioid and sarcomatoid appearing pleomorphic histopathology. We present this case to highlight the diagnostic challenge presented by the rare occurrence of metastatic melanoma to the urinary bladder and the potential pitfall of this lesion being diagnosed as high-grade urothelial carcinoma in the presence of limited clinical history.
Our aim was to determine whether or not non-small-cell lung cancer is squamous cell carcinoma (SQCC); even in small samples, it is essential in view of the side effects attendant on new therapeutics. Lung adenocarcinoma (ADC) with the EML4-ALK fusion gene has been described as demonstrating mucinous cribriform/acinar growth and signet-ring cells, sometimes partially simulating SQCC. We investigated the relation among morphology, anaplastic lymphoma kinase (ALK) rearrangement, and immunophenotype in 321 ADCs by tissue microarray using SQCC markers cytokeratin (CK)5/6, CK14, desmocollin-3, desmoglein-3, p40, p63 versus ADC markers thyroid transcription factor (TTF)-1 and napsin A. Unlike 312 ALK-negative ADCs, 9 ALK-positive cases were negative for 4 SQCC markers. Only 1 ALK-positive ADC showing assertive morphology was positive for CK5/6 and p63 as well as for TTF-1 and napsin A. Coexpression of TTF-1/p40 was not observed, unlike that of TTF-1/p63 reported previously. There was no statistically significant difference between ALK-negative and ALK-positive ADC by immunohistochemical profiling.
Renal oncocytoma is a renal neoplasm considered to be benign. A small cell variant comprising predominantly of oncoblasts is rare. Metastases from a renal oncocytoma are extremely rare. A case of small cell variant of renal oncocytoma with liver metastases is described.
Plexiform fibromyxoma (plexiform angiomyxoid myofibroblastic tumor) is a rare benign mesenchymal tumor of stomach. The plexiform growth of bland-looking spindly cells in a richly vascularized fibromyxoid stroma is distinctive. The described cases are solid tumors associated with ulceration, with the patients presenting with symptoms related to the ulcer or mass effect of the tumor. We report an unusual case presenting as a fistulating abscess. A 42-year-old woman presented with abdominal pain, fever, and elevated white cell count. Computed tomography scan revealed a 12-cm cavitating mass in the gastric antrum, with fistulation to the gastric lumen through an ulcer. Histologic examination showed transmural involvement of the stomach by plexiform islands of fibromyxoid tumor with interspersed delicate capillaries. There was a pseudocyst-like component. The unusual presentation therefore broadens the clinical and pathologic spectrum of this rare tumor type.
Thirteen melanocytic skin neoplasms with a consultation diagnosis by A. Bernard Ackerman were submitted to immunohistochemistry for HMB-45, Ki67, cyclin D1, e-cadherin, and p16; 9/13 cases underwent fluorescence in situ hybridization (FISH) test targeting 6p25 (RREB1), 6q23 (MYB), centromere 6 (Cep6), and 11q13 (CCND1), as well as the centromere 7 (Cep7). A "consensus diagnosis" among 3 experts was also advocated both before and after morphomolecular information. Three neoplasms with a consultation diagnosis of Spitz nevus showed at least 3 abnormal immunohistochemical patterns; 2 of these cases were also FISH-positive for CCND1 gain, but none of them had a final consensus diagnosis of melanoma. Two neoplasms with a consultation diagnosis of congenital nevus received a consensus diagnosis of melanoma. Molecular morphology techniques can highlight the atypical features of melanocytic neoplasms and support existence of a morphobiologic "spectrum": This should be mirrored in the final report by abandoning the dichotomic (benign vs malignant) diagnostic approach.
Ameloblastoma is a locally aggressive, epithelial odontogenic tumor involving mandibles and maxillas. Distant metastasis is a very rare condition and is designated as metastasizing (malignant) ameloblastoma despite its benign histological appearance. Up to now, only 27 well-documented cases of metastasizing ameloblastomas are reported in the literature, and lung is the most commonly involved organ. In previous reports of pulmonary metastasizing ameloblastomas, there was little description of the histopathologic finding. Here, the authors report 2 cases of pulmonary metastasizing ameloblastomas with special emphasis on their interesting, interstitial spread along alveolar septa, resulting in a unique 2-cell pattern under microscopic examination. Pulmonary metastasizing ameloblastoma may pose difficulty in diagnosis if the pathologist is not aware of patient’s clinical history of ameloblastoma.
We compared claudin-4 with Ber-EP4 and carcinoembryonic antigen as markers to distinguish mesothelioma from lung adenocarcinoma, poorly differentiated lung squamous cell carcinoma, and serous adenocarcinoma of the uterus or ovary. All mesothelioma specimens were negative for claudin-4, but 3 of 18 specimens were focally positive for Ber-EP4. In contrast, lung adenocarcinoma including poorly differentiated adenocarcinoma was highly positive for claudin-4, but expression of Ber-EP4 and carcinoembryonic antigen varied widely. Claudin-4 in poorly differentiated squamous cell carcinoma had a lower positive expression rate than in adenocarcinoma. Granular claudin-4 immunoreactivity was conspicuous in poorly differentiated squamous cell carcinoma; this immunoreactive pattern was also observed in mesothelioma. Claudin-4 was thus considered very useful marker for distinguishing mesothelioma and adenocarcinoma, even if histological specimens are small, as in biopsies that contain limited numbers of tumor cells. However, it should be mentioned that claudin-4 has a limit in discrimination between squamous cell carcinoma from mesothelioma.
Colorectal liver metastases with intrabiliary growth are uncommon and difficult to characterize by radiology alone. We present the case of a 61-year-old woman previously operated on for a left colon cancer who developed a metacronous lesion at liver segment II-III. Radiologic workup was indicative for cholangiocarcinoma. Thus, the patient underwent an anatomical left lateral hepatectomy. Pathology showed instead a colorectal metastases with intrabiliary growth. We suggest that in cases of radiological uncertainty between an intrabiliary growth metastasis and a cholangiocarcinoma, the correct surgical strategy should always be an anatomical liver resection without preoperative biopsy because it would not change the operative planning and instead it may increase the risk of dissemination.
Primary pulmonary lymphoma is an uncommon neoplastic disorder representing approximately 0.5% to 1% of primary pulmonary malignancies. The vast majority are of low-grade, mucosa-associated lymphoid tissue type. Primary diffuse large B-cell lymphoma of the lung is rare, though cases of the centroblastic and immunoblastic variants have been described. We present herein an interesting case of an 80-year-old man who presented with both respiratory and constitutional symptoms and was found to have a 4.5 cm left hilar mass with bilateral hilar and mediastinal lymphadenopathy on imaging. Endobronchial biopsy revealed an aggressive large cell lymphoma, with scattered large, bizarre-shaped nuclei resembling Reed–Sternberg cells, positive for CD20, PAX5, CD30, and MUM-1, consistent with an anaplastic variant of diffuse large B-cell lymphoma. Imaging showed no evidence of extrathoracic disease. Standard treatment with cyclophosphamide/vincristine/prednisone and rituximab resulted in significant clinical and radiological response and the patient remains in remission 21 months later. To the best of our knowledge, this modified Ann Arbor stage II2E primary pulmonary lymphoma, is the first description in the English literature of anaplastic variant of diffuse large B-cell lymphoma presenting as a lung primary.
Metastases of non-thyroid malignancies to the thyroid gland have been reported in 1.4% to 3% of patients undergoing thyroid surgery for thyroid malignancy. We report a case of thyroid metastases from renal cell carcinoma in a 57-year-old man, who underwent a left nephrectomy 11 years earlier for a renal cell carcinoma. The histological examination demonstrated a CD-10 positive and thyroglobulin and thyroid transcription factor-1 negative tissue, with numerous noncaseating gigantocellular granulomas. These findings are interesting for the possible role of the immune response in metastatic localizations.
Mixed epithelial and stromal tumor (MEST) is a distinctive adult biphasic neoplasm of the kidney characterized by the presence of solid and cystic areas composed of spindled stroma and epithelium lining tubules and cystic spaces respectively. Most MESTs are benign although sarcomatous transformation has rarely been reported. It has not been clearly established whether the epithelial component represents entrapped tubules or constitutes a true neoplastic component. We report an unusual case of a biphasic tumor of the kidney with a benign stroma and a focal component of papillary carcinoma arising in one of the cysts and discuss its pathogenesis.
We present here the first report of an adult patient with simultaneous LCH and AML with t(9;11).5
How pathologists communicate an error is complicated by the absence of a direct physician–patient relationship. Using 2 examples, we elaborate on how other physician colleagues routinely play an intermediary role in our day-to-day transactions and in the communication of a pathologist error to the patient. The concept of a "dual-hybrid" mind-set in the intermediary physician and its role in representing the pathologists’ viewpoint adequately is considered. In a dual-hybrid mind-set, the intermediary physician can align with the patients’ philosophy and like the patient, consider the smallest deviation from norm to be an error. Alternatively, they might embrace the traditional physician philosophy and communicate only those errors that resulted in a clinically inappropriate outcome. Neither may effectively reflect the pathologists’ interests. We propose that pathologists develop strategies to communicate errors that include considerations of meeting with the patients directly. Such interactions promote healing for the patient and are relieving to the well-intentioned pathologist.
Craniopharyngioma is an epithelial tumor of the sellar region with a high survival rate but a high rate of recurrence, especially in children. Hypothalamic involvement, tumor recurrence, and multiple treatments result in clinical deterioration and impaired quality of life. Using immunohistochemistry, we investigated the expression pattern of osteonectin, a marker of tumor invasion and aggressive behavior, in 43 cases of craniopharyngioma. We observed a positive correlation of osteonectin expression in connective-type stromal tissue surrounding the epithelial tumor cells of craniopharyngioma with the extent of central nervous system infiltration and recurrence rate (P < .001). Given the previous success of chemotherapeutic agents that target the tumor microenvironment, our findings on osteonectin expression in stroma of craniopharyngiomas might, hopefully, be a guide to find newer prognostic markers capable of estimating the risk of progression or recurrence. They may also aid in the development of therapeutics that target tumor microenvironment to improve patient outcome.
The rare reports of primary, nonneuroendocrine small cell carcinomas of the thyroid have not provided enough evidence to support the recognition of these tumors as an entity or to understand their etiopathogenesis. We report the second case of a primary, nonneuroendocrine small cell carcinoma of the thyroid displaying diffuse expression of cytokeratins, CD99, and p63, in the absence of vimentin expression, in a 24-year-old male who is alive without any signs of disease 13 years after total thyroidectomy and radioactive iodine. The tumor disclosed the EWSR1-FLI1 rearrangement, and we propose to designate it as a carcinoma of the thyroid with Ewing family tumor elements.
An unusual granular variant of ameloblastoma presenting as a mandibular mass in a 43-year-old woman is described. These visually striking tumors display unusual and inconsistent immunohistochemical staining patterns although differential diagnosis from other granular cell lesions of the head and neck is usually not problematic.
Primary hepatic and hepatosplenic diffuse large B-cell lymphomas (DLBCLs) are rare cancers and form nodules in most instances. However, very rare cases can diffusely infiltrate the whole liver without nodules. The general clinicopathological features of these lymphomas have not been reported to date. In our current study, we attempted to elucidate the features of these lesions through our direct observations and by reviewing the current literature. We describe the characteristics of 2 patients with hepatic and hepatosplenic DLBCL by autopsy. The lymphoma cells showed diffuse infiltration of the liver, red pulp of the spleen, and bone marrow with intrasinusoidal and interstitial lymphomatous infiltration of the organs. We discuss our observations in relation to previously reported DLBCLs with a similar pathology.
Selective internal radiation therapy is a relatively new technique that irradiates primary and metastatic liver cancer using yttrium 90 microspheres. Increasing reports have shown this to be a useful treatment for unresectable primary hepatocellular carcinoma and others metastases from colon, lung, breast, sarcoma, and ocular melanoma. On the other hand, more and more therapy-related complications have been described. Since the morphologic description of injured organs are relatively uncommon, we report 2 cases of selective internal radiation therapy–related gastric injury, which represent basophilic round bodies in gastritic biopsies little known by pathologists. The appearances in esophagogastroduodenoscopy include gastrointestinal ulcer, edema, or bleeding. Histological findings show mucosal atrophy, mild to moderate cytologic atypia, edema of the stroma, and inflammatory infiltration. The most characteristic feature is round blue and dark microspheres in the stromal blood vessels.
A placental site nodule is a benign proliferation of intermediate trophoblasts from a previous gestation that failed to completely involute. It is a rare entity that is often asymptomatic and is usually found incidentally weeks or even years after the pregnancy. The most common location for placental site nodules is in the uterus within the endometrium and occasionally in the cervix, diagnosed by uterine curettings or hysterectomy. However, rare extrauterine cases have been documented and should be considered as a differential diagnosis when encountered in locations such as the fallopian tube. Here, we present a case of a 28-year-old woman with a history of spontaneous abortions who was found to have a placental site nodule of the fallopian tube after postpartum tubal ligation.
Acinic cell carcinoma (ACC) of the breast is a rare tumor that is listed in the 2003 World Health Organization (WHO) classification of tumors of the breast. Pure form ACC of the breast is even rarer. To date, only 12 cases have been reported in the English-language literature. A case of primary ACC of the breast in a 38-year-old woman is presented in this report. Histologically, the neoplastic cells are characterized by widespread acinci cell-like differentiation with a eosinophilic granular or clear cytoplasm, resembling acinic cells of the parotid gland. In addition, the neoplastic cells are positive for lysozyme, EMA, S-100, CD68 and GCDFP-15 and negative for α-anti-chymotrypsin, synaptophysin, ER, PR and Her-2/neu. This primary breast tumor was confirmed by clinical, morphological, and immunohistochemical studies. Characteristic features and differential diagnosis of this tumor were discussed in the light of pertinent literature.
Thanatosomes, a form of degenerative intracellular hyaline globules, have been described in various neoplastic and nonneoplastic disease processes in several organs. These structures are indicative of apoptotic cell death. Herein, we report 2 cases of malignant phylloides tumor, both of which showed numerous thanatosomes—to the point of dominating the histological appearance and masking the stromal element. Our subsequently conducted study showed that thanatosomes were present in 14 of 86 (16.3%) high-grade malignant breast tumors. The structures were identified in 5/25 (20%) malignant phylloides tumors, 4/19 (21.1%) metaplastic spindle cell carcinomas, 3/21 (14.3%) invasive carcinomas s/p neoadjuvant chemotherapy, and 2/21 (9.5%) poorly differentiated invasive ductal carcinomas. When present, thanatosomes were typically a rare and focal finding in most types of cases. In malignant phylloides tumors, the structures were relatively more numerous when present. Our study shows that although thanatosomes can be present in several types of malignant breast tumors, they are more common in malignant phylloides tumor. Only rarely, as evident from our 2 index cases, do thanatosomes cause diagnostic difficulty.
We present 2 cases of blastic plasmacytoid dendritic cell neoplasm (BPDCN) showing unusual histological features. One patient, a 73-year-old male, presented with a nonpruritic macular erythema of the skin on the anterior and posterior chest wall, the biopsy of which was originally diagnosed as malignant melanoma. The neoplastic cells were negative for S100 and HMB45 and strongly positive for CD45, CD4, CD56, and CD123. The final diagnosis was a BPDCN associated with abundant melanin pigment and numerous melanophages. The second patient was a 73-year-old male with a 5-month history of small, slowly enlarging, bruise-like plaques on his limbs and chest. Histologic examination of the skin biopsy revealed an atypical cellular/myxoid infiltrate with numerous macrophages, which was originally diagnosed as consistent with lepromatous leprosy. The atypical cells were immersed in an alcian blue–positive myxoid matrix at pH 2.5. The Fite-Faraco stain was negative. Positive immunoreactivity was demonstrated for CD4, CD56, and CD123. Based on the histopathology and immunohistochemistry findings, a diagnosis of BPDCN with prominent myxoid matrix was rendered.
Solitary fibrous tumor (SFT) is a rare mesenchymal neoplasm, most commonly arising from the pleura. It has also been recently described to occur in extrapleural sites. To our knowledge, only 16 cases of SFT have been reported in the urinary bladder to date. We report the clinicopathological features of a vesical SFT occurring in a 60-year-old man who presented a concomitant invasive high-grade urothelial cell carcinoma. No similar association has been found in the accessible literature. The morphologic and immunohistochemical clues leading to the correct diagnosis of SFT have been correlated with the data of the literature, and the differential diagnosis is briefly discussed.
A 66-year-old male patient presented with nausea, abdominal pain, occasional rectal bleeding, progressive dysgeusia, onicodystrophy, and alopecia. Endoscopic exam and biopsies revealed severe atrophy and diffuse marked edema of mucosa of stomach and duodenum. No evidence of polyps was found in any portion of the gastrointestinal tract. The diagnosis of Cronkhite–Canada syndrome (CCS) was rendered. The patient symptoms resolved completely after initiation of steroid treatment. This additional case of CCS illustrates how the diagnosis of CCS does not require the presence of polyps but is defined by the appreciation of the diffuse marked edema and atrophy of the gastrointestinal mucosa.
We report 2 rare cases of nonsebaceous lymphadenoma (NSL) in the parotid gland. In both cases, microscopic examination revealed central dilated duct-like structure and its surrounding many cysts in the background of the lymphoid stroma. The cysts were lined with luminal cells and abluminal cells, with the latter being predominant. Occasionally, foci of abluminal epithelial islands were observed. Immunohistochemical findings showed that these tumors had basal cell phenotypes and could support the diagnosis of NSL. The microscopic architectural pattern indicated a cystic dilated duct–glands unit and metaplasia or hyperplasia of abluminal cells. We wondered whether these NSLs were true neoplasia or an indication of a nonneoplastic reactive process. Further investigation of molecular studies of large series in, for example, the clonal or chromosomal state, would be necessary to clarify this point.
Perineal nodular induration (PNI) is a fibroblastic pseudotumor that presents almost exclusively in male cyclists. It develops in the soft tissues of the perineum immediately posterior to the scrotum, as a bilateral or single, central or lateralized mass. Although well known to sport medicine specialists, it is a scarcely documented entity in the pathology literature. We present 2 cases of PNI with fine-needle aspiration cytology and immunohistochemistry. They consisted of a paucicellular fibroblastic proliferation containing CD34-reactive spindle and epithelioid cells, small foci of fibrinoid degeneration, numerous blood vessels, and entrapped groups of mature fat cells. Our cases show that the histopathological features of PNI are more varied than those previously described and its immunohistochemical profile is wider. A central cystic focus and a zonal pattern are not consistent features of this entity. The lesional cells can express CD34, a hitherto unreported immunohistochemical finding.
Collision tumors within the retroperitoneum are rare. We present the case of a 54-year-old man with an incidental finding of a well-defined iliopsoas mass. He underwent marginal resection via an anterior superior ilio-inguinal approach. Histological examination revealed typical features of a schwannoma surrounded by a notable plasma cell infiltrate. On immunohistochemistry stains, the spindled cells displayed diffuse, strong nuclear and cytoplasmic positivity for S100, whereas epithelial membrane antigen, glial fibrillary acidic protein, and neurofilament stains were uniformly negative. The plasma cell infiltrate was diffusely positive for CD 138, with a majority of them demonstrating positive staining for lambda light chain and negative for kappa light chain. Hematological review found no evidence of marrow plasmacytosis and multiple myeloma was ruled out. At 12 month follow-up, the patient remains free of any recurrence. To our knowledge this is the second case of a schwannoma coexisting with a monoclonal plasma cell infiltrate and the first in the retroperitoneum.
KRAS is one of the most common genes mutated in pancreatic adenocarcinoma. Multiple KRAS mutations may be detected within the same pancreatic adenocarcinoma, but it is usually unclear whether the different mutations represent biologically irrelevant molecular events or whether they indicate the coexistence of distinct sizable neoplastic clones within a given tumor. We identified a case of pancreatic adenocarcinoma with 5 different mutations in the KRAS gene and have been able to characterize the allelic distribution of the KRAS mutations and the size of the neoplastic clones using allele-specific locked nucleic acid polymerase chain reaction and next-generation sequencing (454 GS-Junior). The results indicate that the tumor is composed of 5 distinct cell populations: one is KRAS G12V mutated (~38% of neoplastic cells), the second is KRAS G12V in one allele and KRAS G12D in the other (~32%), the third is KRAS G12V in one allele and KRAS G12R in the other (~24%), and the fourth is KRAS G12V in one allele and KRAS G12C in the other (~6%). The fifth clone, representing a minority of neoplastic cells, has a KRAS Q61H mutation in addition to one of the above alterations. Microsatellite analysis identified mutation of the NR21 marker out of the 13 tested, indicating that the tumor has a defect in maintaining DNA integrity different from loss of conventional DNA mismatch repair. These results are consistent with the successive selection of divergent populations of tumor cells and underscore the relevance of nucleotide instability in pancreatic adenocarcinoma.
The behavior of littoral cell neoplasms ranges from benign (littoral cell angioma, LCA) to highly malignant (angiosarcoma). Two unusual cases of low-grade metastatic littoral cell angiosarcoma (LCAS) have been reported with late recurrence and bulky metastases. We present the third case of this rare neoplasm in a 38-year-old man with cirrhosis and a large splenic artery aneurysm, without extrasplenic masses. The spleen showed nodules resembling LCA, immunoreactive for CD31, factor VIII, CD68, and CD163 but not CD8 or CD34. Also present were solid areas of immunophenotypically identical bland spindle cells, although lighter CD31 immunostaining distinguished them from LCA-like angiomatous channels. Similar cells diffusely infiltrated the cirrhotic liver. After splenectomy, pancytopenia resolved, and he is asymptomatic 19 months later. Low-grade LCAS is a previously unreported cause of cirrhosis and may metastasize without forming masses. In cases of LCA, CD31 immunohistochemistry may facilitate detection of LCAS and indicate metastatic potential.
Thymolipoma is a very rare anterior mediastinal mass of thymic origin, accounting for only 2% to 10% of all thymic neoplasm. Histologically, the tumor is usually composed of adipose tissue interspersed with thymic tissues. We report a case of a 58-year-old man who presented with a few weeks history of shortness of breath, cough, and chest pain, found to have a retrocardiac infiltrate on chest X-ray. Computed tomography scan of the chest showed a large anterior mediastinal mass. Surgical excision revealed an ovoid fatty mass, which on histological examination displayed thymic tissue intermixed with lipomatous tissue consistent with a thymolipoma. Of note was the presence of a microscopic nodule of thymic epithelial proliferation with sebaceous differentiation and focal cylindroma-like architecture. Although sebaceous tissue has been rarely reported in thymic tissue, to the best of our knowledge, this is the first case report of sebaceous differentiation in a thymolipoma.
Dyskeratosis congenita (DC) is a rare inherited disorder characterized by bone marrow failure and cancer predisposition. We present a case of a 28-year-old woman with DC who was admitted for hematopoietic stem cell transplantation (HSCT) for aplastic anemia and who developed acute myeloid leukemia with complex genetic karyotype abnormalities including the MLL (11q23) gene, 1q25, and chromosome 8. After transplantation, a monomorphic Epstein–Barr virus (EBV) negative posttransplant-associated lymphoproliferative disorder (PTLD) diffuse large B-cell lymphoma was discovered involving the liver, omental tissue, and peritoneal fluid samples showing additional MLL (11q23) gene abnormalities by fluorescence in situ hybridization. Despite treatment, the patient died of complications associated with transplantation and invasive fungal infection. This case represents the first bona fide documented case of EBV-negative monomorphic PTLD host derived, with MLL gene abnormalities in a patient with DC, and shows another possible mechanism for the development of a therapy-related lymphoid neoplasm after transplantation.
Dedifferentiated epithelial–myoepithelial carcinoma (DEMC) is very rare salivary gland neoplasm with only anecdotal reports. We present an analysis of DEMC, based on a case and review of literature. Our patient, an 85-year-old woman, presented with a submandibular mass of 5 years duration that was increasing in size over a 5-week period. Histologically, there were areas of typical epithelial–myoepithelial carcinoma, with dedifferentiation of both components, manifesting morphologically as salivary duct carcinoma and areas of myoepithelial carcinoma. A review of literature revealed 21 previously reported cases of DEMC. DEMC occurs at an average age of 72 years, most often in the parotid gland (72%) followed by submandibular gland (17%). Dedifferentiation more often involves the epithelial component (13/15 cases) than the myoepithelial component (5/15 cases). Although typical epithelial–myoepithelial carcinomas are fairly indolent (average disease-free survival of 11.34 years), dedifferentiation confers a poor prognosis (survival reported from 1 to 72 months).
We report the case of a 33-year-old male with multiple intrascrotal neurofibromas not associated with neurofibromatosis, treated by surgical excision.
This article reports the clinical and the histological features in a 7-year-old girl affected by common variable immunodeficiency (CVID) who developed multiple Epstein–Barr virus–associated tumors, represented by bilateral adrenal smooth muscle tumors (EBV-SMT) and multifocal diffuse large B-cell lymphoma. The EBV-SMTs showed features compatible with a benign or at least a low-malignant potential neoplasm. A peculiar feature observed in both EBV-SMTs was the occurrence of numerous lymphocytes intermingled with the spindle cells, which consisted of CD3+ CD5+ T-cells, with a predominant cytotoxic CD8+ component. Interestingly, EBV status differed in the neoplasms, since the EBV-SMTs were negative for LMP1 and positive for EBER, whereas the B-cell lymphoma expressed both EBV markers. Furthermore, EBV-LMP1 deletion was positive only in the EBV-SMTs, thus indicating that these tumors were the consequence of 2 distinct, EBV-dependent transformations. Similarly, lymphocyte clonality assay also showed different clonal bands in different sites (skin and nasal cavity), suggesting the development of intratumoral mutations. Finally, the authors review all 127 previously reported EBV-SMT, with discussion of their clinical and pathological features.