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Low-grade oncocytic tumor (LOT) has been recently proposed as a unique renal tumor. However, we have encountered tumors with more oncocytoma-like morphology that show diffuse keratin 7 reactivity, which we sought to characterize molecularly. Eighteen tumors with a diffuse keratin 7 positive and KIT negative pattern were identified from 184 with predominantly oncocytoma-like histology. These tumors were subjected to detailed immunohistochemical evaluation and 14 were evaluated using the Illumina® HiSeq 4000 platform for 324 cancer-associated genes. Patients' ages ranged from 39 to 80 (median = 59.5 years) with a male to female ratio of 1.25:1. Morphology was predominantly oncocytoma-like with discrete nests, compared to the solid and edematous patterns described in LOT. Other than positive keratin 7 and negative KIT, the tumor cells were positive for PAX8, E-cadherin, AE1/AE3, Ber-EP4, AMACR, CD10, and MOC31, and were negative for other studied markers. FH and INI1 were normal. Eleven of 14 harbored genomic abnormalities, likely sporadic, primarily involving the MTOR pathway (73%). Overall, the alterations included MTOR activating mutation (n = 1), TSC1 inactivating mutation (n = 1), TSC2 mutation (p.X534 splice site, n = 1), STK11 (a negative regulator of the MTOR pathway) mutation (n = 1), both STK11 and TSC1 mutations (n = 1), biallelic loss of PTEN and TSC1 deletion (n = 1), and MET amplification and TSC1 inactivating mutation (n = 1). Amplification of FGFR3 was identified in one additional tumor. Other alterations included FOXP1 loss (n = 1), NF2 E427 homozygous loss (n = 1), and PI3KCA activating mutation (n = 1). At a median follow-up of 68 months (2-147 months) for 15 patients, all were alive without disease. Oncocytic renal tumors with diffuse keratin 7 labeling show frequent alterations in the TSC/MTOR pathway, despite more oncocytoma-like morphology than initially described in LOT, likely expanding the morphologic spectrum of the latter.

Renal oncocytoma is the most common benign epithelial renal neoplasm. Several adverse features that would typically increase the stage of renal cell carcinomas are not uncommon in renal oncocytoma, including perinephric, sinus fat, or renal vein invasion. Herein, we report the largest single institutional series of renal oncocytoma with adverse pathologic features. The cohort comprised 50 patients, 38 were men (76%) and 12 were women (24%), with a mean age of 68 years (range, 50-87 years). All cases were diagnosed on nephrectomy specimens. No laterality predilection was noted. The tumors ranged in size from 1.5-15.7 cm (mean, 5.3 cm). Adverse pathologic features included perinephric fat invasion (n = 25; 50%), renal sinus fat invasion (n = 9; 18%), and renal vein invasion (n = 5; 10%). More than one adverse feature was seen in 11 tumors (22%). All tumors showed diffuse reactions to KIT (n = 40; 100%) and cyclin D1 (n = 27; 100%). Keratin 7 highlighted rare (

We evaluated keratin 7 (K7) hepatocellular expression in 92 patients with common types of acute and chronic cholestatic diseases caused by bile duct obstruction/destruction or parenchymal lesions [acute hepatitis (n=20), mixed/pure cholestasis (n=16), primary biliary cholangitis-PBC (n=35), primary sclerosing cholangitis-PSC (n=10), vanishing bile duct syndrome (n=3), complete large bile duct obstruction due to space-occupying lesions (n=8)]. K7 immunohistochemical hepatocellular expression and ductular reaction (DR) were semi-quantitatively assessed. Results were correlated with liver enzyme serum levels, cholestasis type, histological features, hepatocellular Ki67 labelling index (LI) and HepPar1 expression. Hepatocellular K7 expression was detected in 87% (81/92) cases and in all cholestatic disease types with lowest incidence in pure/mixed cholestasis and highest in incomplete bile duct obstruction (iBDO), reaching 100% in PSC. K7-positive hepatocytes had low Ki67 LI (0-5%) retaining HepPar1 expression, irrespective of disease type. PSC cases had high K7 hepatocellular expression even with intact bile ducts, a feature that may aid differential diagnosis of cholestatic syndromes. K7 hepatocellular expression significantly correlated with cholestasis type, bile duct loss and fibrosis stage. It was higher in milder acute cholestatic hepatitis showing inverse correlation with hepatocyte proliferation and serum transaminase levels. In iBDO, younger age independently correlated with high K7 expression, while serum GGT levels showed a nearly significant correlation. Correlation with DR findings implied that K7-positive hepatocytes may result through metaplasia. In conclusion, K7 hepatocellular expression is a sensitive though non-specific marker of cholestasis. It may represent a cytoprotective reaction of resting hepatocytes in cholestasis of longer duration especially in younger patients.

Yuexian Li, Zhou Su, Biwei Wei, Zhihai Liang Department of Gastroenterology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of ChinaCorrespondence: Zhihai LiangDepartment of Gastroenterology, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning, Guangxi, 530021, People’s Republic of ChinaTel +86-771-5356501Fax +86-771-5350031Email ahhai@163.comBackground: Pancreatic adenocarcinoma (PAAD) is a deadly tumor with a high recurrence rate and poor prognosis. Keratin 7 (KRT7) is a member of the keratin gene family that is involved in the regulation of cell growth, migration and apoptosis in many cancers. However, the role of KRT7 and its biological functions in PAAD remain unclear. We systemically analyzed the expression and clinical values of KRT7 in PAAD.Methods: The Gene Expression Profiling Interactive Analysis (GEPIA), Oncomine and Human Protein Atlas (HPA) databases were used to analyze the mRNA and protein expression of KRT7 in PAAD. The prognosis and subgroup analysis of KRT7 in PAAD patients was performed using the GEPIA, PROGgeneV2 and UALCAN databases. Later, the correlation between KRT7 expression and tumor immune molecules in PAAD was evaluated using the Immune Cell Abundance Identifier (ImmuCellAI) and TISIDB databases. Finally, the functional enrichment pathway of KRT7 and its coexpressed genes were analyzed by the Database for Annotation, Visualization, and Integrated Discovery (DAVID) and Metascape databases and Gene Set Enrichment Analysis (GSEA).Results: The mRNA and protein expression of KRT7 was increased in PAAD tissues compared with normal tissues. High KRT7 expression was closely associated with tumor grade, TP53 mutations and poor prognosis in PAAD patients. Cox regression analysis proved that overexpressed KRT7 was an important and independent risk factor for poor overall survival (P = 0.006, HR =1.87) and disease-free survival (P = 0.019, HR =1.793) in PAAD. Additionally, KRT7 expression was significantly associated with immune infiltration of tumor immune cells and immunomodulators. Functional enrichment analyses and GSEA indicated that KRT7 might be involved in the regulation of the p53 pathway in PAAD.Conclusion: Overexpressed KRT7 could be a promising prognostic and therapeutic target biomarker for PAAD by bioinformatics analysis.Keywords: pancreatic adenocarcinoma, KRT7, prognosis, biomarker, bioinformatics analysis

The aim of the research was to study the expression of marker genes for the epithelial-mesenchymal transition in the ductal adenocarcinoma of the pancreas.Material and methods. Surgical material from 44 patients with ductal adenocarcinoma of the pancreas was subjected to morphological analysis with molecular genetic research. Total RNA was detected in the detected sections of the anaplastic component using the RNeasy Mini Kit (Qiagen, Germany). 5 marker genes were used for molecular genetic studies of the epithelial-mesenchymal transition (EMT): ZEB1, ZEB2, CDH1, VIM, SNAIL1 (SLUG). Gene expression was measured in triplicate using an EvaGreen intercalating dye. On serial paraffin sections using tissue microarrays technology, immunohistochemical detection of p63, smooth muscle actin, total cytokeratin, cytokeratin 7, vimentin, E-cadherin (Ventana) was performed.Results. As a result of the study, a positive reaction with mesenchymal markers (vimentin, p63, smooth muscle actin) was detected in the cells of the anaplastic component, in contrast to the glandular component. In a molecular study of the anaplastic component, changes in gene expression were characterized as EMT-positive.Conclusion. The heterogeneity of ductal cancer is manifested in the appearance of an anaplastic (sarcomalike) component, in which the ability of epithelial tumor cells to acquire the property of mesenchymal cells that do not require stroma and have aggressive malignant potential that affects the survival of patients is traced.

During tubo-ovarian high-grade serous carcinoma (HGSC) progression, tumoral cells undergo phenotypic changes in their epithelial marker profiles, which are essential for dissemination processes. Here, we set out to determine whether standard epithelial markers can predict HGSC patient prognosis. Levels of E-CADH, KRT7, KRT18, KRT19 were quantified in 18 HGSC cell lines by Western blot and in a Discovery cohort tissue microarray (TMA) (n = 101 patients) using immunofluorescence. E-CADH and KRT7 levels were subsequently analyzed in the TMA of the Canadian Ovarian Experimental Unified Resource cohort (COEUR, n = 1158 patients) and in public datasets. Epithelial marker expression was highly variable in HGSC cell lines and tissues. In the Discovery cohort, high levels of KRT7 and KRT19 were associated with an unfavorable prognosis, whereas high E-CADH expression indicated a better outcome. Expression of KRT7 and E-CADH gave a robust combination to predict overall survival (OS, p = 0.004) and progression free survival (PFS, p = 5.5 × 10−4) by Kaplan–Meier analysis. In the COEUR cohort, the E-CADH-KRT7 signature was a strong independent prognostic biomarker (OS, HR = 1.6, p = 2.9 × 10−4, PFS, HR = 1.3, p = 0.008) and predicted a poor patient response to chemotherapy (p = 1.3 × 10−4). Our results identify a combination of two epithelial markers as highly significant indicators of HGSC patient prognosis and treatment response.

Introduction/Objective Pancreatic metastases are rare, and the most common neoplasms are carcinomas from the kidney, lung, and breast. Methods/Case Report We present four cases of breast ductal carcinoma in patients with metastases to the pancreas diagnosed by endoscopic ultrasound guided fine needle aspiration (EUS-FNA). The four female patients ranged from 37 to 64 years in age. Three patients had breast cancer histories, ranging from 1 to 21 years. The patient without cancer history was found to have breast mass also. Two patients had triple negative breast ductal carcinoma. The breast cancer biomarkers on the other two patients showed ER+, PR-, Her2 3+, and ER-, PR-, Her2 3+, respectively. Two patients had histories of metastatic breast cancer involving bone, liver and brain. All patients presented with symptoms associated with pancreatic mass. By imaging, solitary pancreatic head masses were found in three patients, ranging from 2.4 to 3.7 cm. One patient had two pancreatic masses (head, 2.6 cm; body, 2.9 cm). EUS-FNAs targeting the pancreatic head masses were performed on the four patients. Cell blocks were available for all except one (due to limited cells), which had subsequent histology diagnosis. Results (if a Case Study enter NA) FNAs demonstrated loosely cohesive tumor cells with enlarged, hyperchromatic nuclei, occasional prominent nucleoli, and occasional intracytoplasmic vacuoles, morphologically and immunohistochemically (CK7 +, GCDFP-15 focally +, CA19.9 -, biomarkers similar to primary tumors) consistent with breast primary. Follow-up revealed three patients expired one month, 2.5 years, and 5 years post-diagnosis, respectively. One patient without prior cancer history has been stable for 7 years. Conclusion Our study demonstrates the clinicopathological features of four cases of breast ductal carcinoma metastasized to the pancreas. We emphasize the important role of EUS-FNA for diagnoses of pancreas metastases. The finding of two of four cases with triple negative biomarkers may raise the importance of close follow-up in these patients for pancreatic metastasis.

Background and Aims Differentiating biliary atresia (BA) from idiopathic neonatal hepatitis (INH) is vital in routine pediatric practice. However, on liver biopsy, few cases offer a diagnostic challenge to discriminate these entities with certainty. Bile ductular reaction (DR), intermediate hepatobiliary cells (IHBC) and extra-portal ductules (EPD) indicate progenitor cell activation, as a response to various hepatic insults. The present study aims to quantify DR, IHBC and EPD by Keratin 7 (CK7) immunohistochemistry (IHC) in BA and INH and to devise a mathematical approach to better differentiate the two, especially in histologically equivocal cases. Methods A total of 98 cases were categorized on biopsy as BA, INH or equivocal histology, favoring BA or INH. CK7 DR mean, IHBC mean and EPD mean values were compared between BA and INH. A formula was derived to help distinguish these two entities, the cut-off value, sensitivity and specificity of which were determined by receiver operating characteristic (ROC) curve. This formula was applied and validated on histologically equivocal cases. Results Univariate logistic regression revealed significant difference between BA and INH with respect to CK7 DR and CK7 EPD mean (p 2 + (CK7 EPD)/(CK7 IHBC) was derived to help distinguish BA from INH. Cut off value of 10.5 and above, determined by ROC curve, favored a diagnosis of BA (sensitivity= 93.4%, specificity= 94.6%). Histologically equivocal and discrepant cases could be correctly categorized using this formula. Conclusions Formula using CK7 IHC parameters may aid pathologists better distinguish BA from INH, especially in histologically equivocal cases.

We evaluated keratin 7 (K7) hepatocellular expression in 92 patients with common types of acute and chronic cholestatic diseases caused by bile duct obstruction/destruction or parenchymal lesions [acute hepatitis (n=20), mixed/pure cholestasis (n=16), primary biliary cholangitis-PBC (n=35), primary sclerosing cholangitis-PSC (n=10), vanishing bile duct syndrome (n=3), complete large bile duct obstruction due to space-occupying lesions (n=8)]. K7 immunohistochemical hepatocellular expression and ductular reaction (DR) were semi-quantitatively assessed. Results were correlated with liver enzyme serum levels, cholestasis type, histological features, hepatocellular Ki67 labelling index (LI) and HepPar1 expression. Hepatocellular K7 expression was detected in 87% (81/92) cases and in all cholestatic disease types with lowest incidence in pure/mixed cholestasis and highest in incomplete bile duct obstruction (iBDO), reaching 100% in PSC. K7-positive hepatocytes had low Ki67 LI (0-5%) retaining HepPar1 expression, irrespective of disease type. PSC cases had high K7 hepatocellular expression even with intact bile ducts, a feature that may aid differential diagnosis of cholestatic syndromes. K7 hepatocellular expression significantly correlated with cholestasis type, bile duct loss and fibrosis stage. It was higher in milder acute cholestatic hepatitis showing inverse correlation with hepatocyte proliferation and serum transaminase levels. In iBDO, younger age independently correlated with high K7 expression, while serum GGT levels showed a nearly significant correlation. Correlation with DR findings implied that K7-positive hepatocytes may result through metaplasia. In conclusion, K7 hepatocellular expression is a sensitive though non-specific marker of cholestasis. It may represent a cytoprotective reaction of resting hepatocytes in cholestasis of longer duration especially in younger patients.

Apocrine adenocarcinoma is a rare primary cutaneous malignancy that arises from areas with high apocrine gland density, most frequently described in the axilla. There have only been three previously reported cases of apocrine adenocarcinoma in the anal/perianal region. A 72-year-old female presented for evaluation of a perianal lesion with persistent drainage that she had noticed for over a year. The patient proceeded with surgical excision of the perianal nodule. Diagnosis was made based on pathology demonstrating areas of mixed solid and trabecular areas with large nuclei and many prominent mitotic figures, which stained positive for periodic acid–Schiff–diastase, cytokeratin 7 and gross cystic disease fluid protein 15. We are reporting just the fourth such case of apocrine adenocarcinoma in the anal/perianal region. It is important to consider apocrine adenocarcinoma in our differential, because though apocrine adenocarcinoma has a benign clinical presentation, it can have a high incidence of lymph invasion on presentation.

Circular RNAs (CircRNAs) are a type of non-coding RNAs, which contain a covalently closed loop structure without 5&prime, to 3&prime, free ends. CircRNAs play essential roles in the regeneration of secondary hair follicle (SHF) and cashmere growth in goats. CircRNA-1926 was previously identified in SHF of cashmere goats, but its potential roles are unclear. In this study, we confirmed the expression of circRNA-1926 in SHF bulge of nine cashmere goats with a significantly higher level at anagen than that of telogen. Through the use of both overexpression and siRNA interference, we showed that circRNA-1926 promoted the differentiation of SHF stem cell into hair follicle lineage in cashmere goats which was evaluated via indictor genes Keratin 7 and Keratin 17. Using RNA pull-down, we found that circRNA-1926 bound with miR-148a/b-3p. Additionally, our data indicated that circRNA-1926 promoted the expression of the CDK19 gene. Using dual-luciferase reporter assays, it was revealed that circRNA-1926 positively regulated the CDK19 expression through miR-148a/b-3p. The results from this study demonstrated that circRNA-1926 contributes the differentiation of SHF stem cells into hair follicle lineages in cashmere goats via sponging miR-148a/b-3p to enhance CDK19 expression.

SUMMARY: Nine tumor and various potential biomarkers were measured and combined the information to diagnose disease, all patients accepted fiber bronchoscopy brush liquid based cytologyand histopathology examination in order to reliably detect lung cancer. The samples from 314 Chinese lung cancer patients were obtained and CK5/6, P63, P40, CK7, TTF-1, NapsinA CD56, Syn and CgA were measured with the immunohistochemical SP method and analyzed correlation of the expression of these markers with pathological and clinical features of squamous cell carcinoma, adenocarcinoma, and small cell lung carcinoma. Squamous cell carcinoma, adenocarcinoma and small cell carcinoma were 61 cases, 114 cases and 139 cases,CK5/6 and P63 expression were more frequent in squamous cell carcinoma, with sensitivity and specificity of 77.05 % and 96.44 %, 83.61 % and 88.93 %,and compared with adenocarcinoma and small cell carcinoma difference was statistically significant (P

Background: Clear cell papillary renal cell carcinoma (CCPRCC) is a new but rare tumor entity as listed in the World Health Organization 2016 renal tumor classification. Around 360 cases have been reported in the English literature to date, and only one tumor with sarcomatoid change was reported to develop distant metastasis. In the present study, we aim to review the clinical course and analyze the treatment outcome of CCPRCC in our institution. Methods: We retrospectively collected patients diagnosed with CCPRCC between January 2008 and September 2016 in our institute. The clinical features, pathology slides, and clinical outcomes were reviewed. Results: Twenty-five patients were collected during the study period, with a mean age at diagnosis of 62.8 years (range 35–85 years). Three patients developed the tumor in their native kidney following a kidney transplant, and three patients were diagnosed by needle biopsy before cryoablation therapy due to high surgical risk. The mean follow-up time was 49.7 months (range 12–119 months). During the follow-up period, all patients were alive without local recurrence or distant metastasis. All tumor specimens in our series expressed cytokeratin 7 (CK7) diffusely in immunohistochemistry staining. One patient was diagnosed with pT3a cN0M1, Fuhrman grade 3 CCPRCC with renal vein invasion and lung metastasis in 2010 on the basis of the histologic pattern and immunoreactivity for CK7. The clinical course was not compatible with any of the reported cases in the literature, so the kidney specimen was re-examined using whole-exome sequencing. The diagnosis was then revised to clear cell renal cell carcinoma. Conclusion: Our series confirmed that CCPRCC has an indolent clinical behavior. When the diagnosis is made in a high-grade renal tumor, it should be carefully re-confirmed using cytogenetic or genomic methods. Keywords: Clear cell papillary renal cell carcinoma, Cytokeratin 7 immunoreactivity, Whole-exome sequencing

Mixed neuroendocrine nonneuroendocrine neoplasms (MiNEN) are tumors composed of adenocarcinoma and neuroendocrine neoplasm and include collision, combined, and amphicrine. Within the hepatobiliary tree, tumors of this histologic type are extremely rare, particularly the amphicrine type. In this case study, we describe a 63-year-old man with a hepatic hilar amphicrine tumor. An initial diagnosis of neuroendocrine tumor was made based on biopsy (chromogranin and synaptophysin positivity). On resection, the tumor contained histologic features of both adenocarcinoma and neuroendocrine carcinoma. Immunohistochemically, all tumor cells expressed both chromogranin and synaptophysin, keratin 7, and Cam5.2. Mucin production was evident in both components demonstrated by mucicarmine stain. Albumin RNA in situ hybridization (ISH) was positive, supporting hepatic source. The tumor is classified as an amphicrine carcinoma given the dual expression of both adenocarcinoma and neuroendocrine markers in both components. This is the first amphicrine carcinoma of the hepatic hilum reported in the literature. Keywords: Cholangiocarcinoma, Mixed neuroendocrine-nonneuroendocrine carcinoma, Neuroendocrine tumor, Liver, Immunohistochemistry, Hepatobiliary

Background Extramammary Paget's disease (EMPD) is a rare intraepithelial malignancy with high recurrence rates following standard surgical treatments, ranging from 22% to 60% in large retrospective reviews. Objective To evaluate the local recurrence rate of Mohs micrographic surgery (MMS) supplemented with intraoperative immunohistochemistry for cytokeratin-7 (MMS + CK-7) for primary and recurrent EMPD. Materials and methods Retrospective, multi-center, cross-sectional study of patients treated using MMS + CK-7. Demographic, clinicopathologic, treatment, and follow-up data were obtained by chart review. Results The observed local recurrence rate for MMS + CK-7 is 3.3% (2/61 tumors) with a mean follow-up of 43.5 months (1-120 months). Local recurrence occurred in 2.3% (1/43) of primary tumors and 5.6% (1/18) of recurrent tumors. Kaplan-Meier 5-year tumor-free rates are 94.6% overall, 97.1% for primary tumors, and 80.0% for recurrent tumors. The Kaplan-Meier 5-year tumor-free rates for all EMPD tumors treated with MMS + CK-7 versus a historical cohort of MMS alone are 94.6% versus 72.0% (p = .012). Conclusion MMS + CK-7 is an effective treatment for EMPD, demonstrating improved outcomes compared with historical controls.

Aims Hepatic progenitor cells (HPCs) are activated in various liver diseases, but their role in the carcinomatous environment remains unknown. We aimed to identify the possible presence and topography of HPCs in liver metastases. Methods and results We examined 14 liver resection specimens for colorectal adenocarcinoma (n = 13) and anal squamous cell carcinoma (n = 1) metastases. Immunohistochemical markers of colonic origin (keratin 20 and CDX2) and squamous cell origin (p63), HPC [keratin 19 (K19) and CD56] and stem cell (CD44) markers, and the biliary marker keratin 7 (K7), which may also highlight HPCs, were applied on routinely processed tissue sections. Double immunohistochemistry/immunofluorescence (K7/CDX2) and confocal microscopy were used on selected sections. K7-positive, Κ19-positive and CD56-positive ductular structures were encountered within the metastatic tumour (tumour interior and periphery), and in the immediate peritumoral area. Hybrid structures composed of HPCs and metastatic adenocarcinoma cells were recognised and confirmed by double immunostaining (K7/CDX2). Carcinoma cells were also observed singly or in groups within the epithelium of interlobular bile ducts and/or ductules in portal tracts without evidence of carcinomatous infiltration and at a distance from the metastatic foci. Conclusions HPCs are observed at the periphery and in the interior of liver metastatic carcinomas. Bile ductules and small interlobular bile ducts may attract carcinoma cells serving as a potential 'metastatic niche', in line with their recognised role as HPC niches in non-neoplastic liver.

The favorable features of high-risk human papillomavirus (HPV) in the head and neck are limited to those harboring transcriptionally-active HPV, which occur predominantly in the oropharynx (OP). Factors rendering the OP susceptible to HPV oncogenesis are largely unexplored. The role of cytokeratin 7 (CK7) in predisposition to HPV and cancer in the cervix has been evaluated. However, its significance in the H&N is unknown. CK7 immunohistochemistry was performed on a tissue microarray cohort of OP and non-oropharyngeal (NOP) squamous cell carcinomas (SCC) with known clinical follow-up and HPV E6/7 mRNA status. Expression was graded based on the distribution (1 ≤ 33%, 2 = 33–66%, 3 ≥ 66%) and intensity (1 = weak, 2 = strong) with combined score of ≥ 2 considered positive. Survival analysis was performed. Seventy-four NOPSCCs and 204 OPSCCs were studied. HPV was positive in 2.7% of NOPSCCs and 70.9% of OPSCCs. CK7 was positive in 23.0% of OPSCCs and 14.8% of NOPSCCs (p = 0.2), and in 24.1% of HPV positive versus 17.2% of negative patients (p = 0.2). There was no correlation with age, race, gender, HPV status, histologic type, tumor subsite, treatment, stage, or co-morbidities, and CK7 expression was not significantly associated with overall or disease specific survival. In our series, CK7 is positive in ~ 25% of H&N SCCs, although usually only focally. While CK7 has been suspected to be overexpressed selectively in HPV-related OPSCCs due to their origination from tonsillar crypt epithelium, we did not find any significant difference by anatomic H&N subsite, nor by HPV status, for its expression and found no association with patient survival.

Combined hepatocellular-cholangiocarcinoma (CHC) is a mixed tumor containing elements of both hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC). Its remarkable histological heterogeneity has been linked to putative hepatic progenitor cell (HPC) origin. However, detailed histological or phenotypic description is rarely documented. In the present study, we reassessed 68 cases previously diagnosed as hepatitis B-related CHCs by immunohistochemistry and double-fluorescence immunostaining, focusing on HPC associated phenotypic observation of intermediate area of the tumor. It was found that tumor cells showed remarkable heterogeneity in intermediate area. Tumor cells with intermediate morphology between hepatocytes and cholangiocytes were oval-shaped and small with scant cytoplasm and hyperchromatic nuclei, arranging in solid nests mostly. By Keratin 7 (K7) staining, it appeared that the nests of tumor cells represented a maturation process from the undifferentiated small cells to mature hepatocytes through the "transitional" cells. Then, these small cells were further confirmed with intermediate phenotype as HPC by exploring immature hepatocellular marker and HPC/biliary markers co-localization. In conclusion, the HPC associated trait in CHC can be interpreted by HPC origin or gain of "stemness" by dedifferentiation. It is still too soon to give a final word that it is innate or acquired signature of HPC associated trait in CHC.

Three cases of primary pulmonary adenocarcinoma with prominent lymphoid stroma and papillary features mimicking Warthin's tumor are presented. The patients are two women and one man ages 52, 62, and 74 years respectively. Clinically, the patients presented with non-specific symptoms of cough, dyspnea, and chest pain. Imaging showed the presence of an intrapulmonary mass in the right lower, right upper and left lower lobe. All patients underwent lobectomy. Histologically, the tumors were characterized by the presence of and oncocytic papillary growth pattern embedded in a lymphoid rich background. Immunohistochemical stains for TTF-1, keratin 7, and beta-catenin were positive in the epithelial component, while CD20 showed strong positive staining in the lymphoid component. In addition, CD4 and CD8 also showed positive staining in a ratio of 3-4:1, EBER was negative. Kras mutations with wild type EGFR were identified in one case. Clinical follow-up ranging from 8 to 24 months was obtained showing that all patients are alive without recurrence. The cases herein presented represent an unusual histological variant of primary lung adenocarcinoma, which closely mimics Warthin's tumor.

Introduction/Objective Papillary Renal Cell Carcinoma (PRCC), the 2nd most common RCC, accounts for 10-15% of cases and is usually composed of tubules and papillae with foamy histiocytes in papillary cores. Mucinous tubular and spindle cell carcinoma (MTSC) is composed of tightly packed, elongated, curvilinear tubules with smooth luminal surfaces, separated by mucinous stroma. MTSC is associated with a more favorable prognosis than PRCC. PRCC and MTSC have significant histologic and histochemical overlap including elongated tubules and stromal Alcian blue positive mucin deposits. Methods/Case Report We report a case of a 75 year old female who underwent a robotic assisted partial nephrectomy for resection of a 5.7 x 5.2 x 5.0 cm left upper pole solid renal mass. Spindle cell change with elongated tubules reminiscent of MTSC was present in several blocks; however, the luminal surface was shaggy favoring PRCC. Patchy prominent extracellular Alcian blue positive mucin deposits were also present. PRCC and MTSC both express CK7, AMACR, and EMA. However, absent expression of E-cadherin and strong CD10 expression favored PRCC. Multiple foci of solid spindle cells in a whorled pattern with clear cell change, necrosis, and high grade nuclei bordering on sarcomatoid RCC were present in other blocks. Multiple papillations and psammoma bodies also supported PRCC. A spectrum of spindle cell change was present, ranging from elongated tubules reminiscent of MTSC to whorled foci with high grade nuclei approaching sarcomatoid RCC. Results (if a Case Study enter NA) NA Conclusion Submission of multiple sections and awareness of the protean morphologic features of PRCC are essential in making the correct diagnosis.

Introduction/Objective SMARCA4-deficient thoracic sarcoma/carcinoma is a highly aggressive neoplasm characterized by SMARCA4 (chromatin remodeling complex) deficiency. It affects mostly smokers (85%) with a broad age range of presentation (mean age: 50 years). Most patients present with advanced disease and extensive involvement of thoracic structures. The cytomorphologic features of this entity have not been fully described. Methods/Case Report A 59-year-old female, former smoker, with a prior history of lung adenocarcinoma, presented with a new 2.8 cm right infrahilar nodule concerning for recurrence. The second patient, a 54-year-old male who is a smoker, presented with an 8.0 cm right perihilar mass extending into the right lung and mediastinum with encasement of the right main pulmonary artery. Cytologically, the smears from both aspirates were comprised of single cells and loosely cohesive clusters of ovoid to spindle cells with scant to moderate cytoplasm, stippled chromatin, and focally prominent nucleoli. Numerous mitotic figures were appreciated. Necrosis was present within the smear background. The cell block sections showed tumor cells arranged in glandular and focal papillary architecture with a myxoid background. In one case, intermediate to large-sized cells with focal cytoplasmic clearing and patchy extracellular metachromatic material were also noted. Rhabdoid morphology was not appreciated. Immunohistochemically, the tumor cells were at least focally positive for vimentin, TLE-1, SALL4, CK AE1/AE3 and TTF-1, while being negative for CK7, CK20, Napsin-A, SOX-10, p40 and neuroendocrine markers. Both tumors showed SMARCA4 (BRG1) loss of expression. Results (if a Case Study enter NA) N/A Conclusion While the cytomorphologic findings of SMARCA4-deficient thoracic sarcomas/carcinomas are not specific, the FNA diagnosis should be considered for any poorly differentiated neoplasm involving the lungs or mediastinum which should prompt an appropriate immunocytochemical work-up that includes SMARCA4/BRG1 assessment

Introduction/Objective Endobronchial metastasis (EBM) is uncommon, with a reported prevalence of 2% in cases of non-lung primary malignancies. The most frequently observed carcinomas in EBM are from breast, colon, and renal origins. We present a rare case of endobronchial metastasis from a primary tumor of the appendix without lung masses by computed tomography (CT). Methods/Case Report An 83-year-old woman with signet-ring cell carcinoma of the appendix underwent right hemicolectomy and chemotherapy. Two years later, she returned with intractable nausea and vomiting, and respiratory distress. CT of the chest demonstrated diffuse bilateral pulmonary opacities without lung masses. CT of the abdomen showed peritoneal carcinomatosis. Cytology of ascitic fluid displayed metastasis of the patient’s known appendiceal tumor. Bronchoscopy found significant friable debris appearing to be tumor tissue and occluding multiple bronchioles in the right lung. A bronchoalveolar lavage (BAL) specimen from the right lung was sent for liquid-based cytology, which revealed a few atypical cells with eccentric nuclei and intracytoplasmic vacuoles, abundant macrophages, degenerated mixed inflammatory cells, and scattered bronchial epithelial cells. Cell block demonstrated signet-ring cells mimicking macrophages and infiltrating into small fragments of bronchiolar wall. The signet-ring cells were morphologically similar to those found in the ascitic fluid and the patient’s primary tumor, and were highlighted by mucicarmine stain and immunohistochemical stains for CDX-2 and CK20, but not CK7. Results (if a Case Study enter NA) N/A Conclusion Collectively, the findings supported the diagnosis of endobronchial metastasis of signet-ring cell carcinoma from the lower gastrointestinal tract, i.e. the patient’s known appendiceal primary. Our case demonstrates a rare endobronchial metastasis of a primary neoplasm of the appendix, an important diagnostic consideration when evaluating respiratory distress in patients with such cancer histories. We have described the significant role of BAL cytology to uncover endobronchial metastases without lung masses by CT, and illustrated the finding of signet-ring cells mimicking macrophages in a BAL cytology specimen.

Introduction/Objective Extramammary Paget disease (EMPD) is a rare neoplasm commonly affects postmenopausal women. It usually presents in the anogenital area where apocrine sweat glands are abundant, most commonly in the vulva. The disease is characterized by slow grow and high local recurrence rates. Clinically, EMPD present as well demarcated erythematous lesion or plaques that may ulcerated. Microscopically, it shows a group of atypical cells with abundant clear cytoplasm and nuclear pleomorphism. Methods/Case Report Here in we present a 58-year-old female with history of vulvar intraepithelial neoplasia III (VIN III) status post wide local excision, and poorly differentiated squamous cell carcinoma status post radical hysterectomy and bilateral salpingo-oopherectomy and chemoradiation who presented for perineal pain, itching and discomfort. She also noticed skin changes on her left labia without bleeding or discharge. Punch biopsies of the vulva and periurethral areas revealed acanthosis of the epidermis with intraepidermal scattering of single or clusters of large cells with round/ovoid nuclei and abundant clear cytoplasm. The cells are positive for p16, CK19, CK7, PAX8 supporting the diagnosis of EMPD without evidence of dysplasia. The concurrent PAP smear shows hypercellular specimen composed of hyperchromatic fragments of tissue with high nuclear-to-cytoplasmic rations, and apoptotic bodies. The presence of intracytoplasmic mucin and the tridimensionality of the fragments supported the diagnosis of adenocarcinoma. The HPV testing was positive for HPV-16. Results (if a Case Study enter NA) N/A Conclusion This study compares the histological and cytomorphological features of EMPD with high-grade squamous intraepithelial lesion (HSIL), since the molecular pathways, precursor lesions, etiologic associations, staging, clinical treatment, and prognosis differ substantially and may have a significant clinical impact for the patient’s treatment.

Introduction/Objective Although squamous cell carcinoma of the esophagus rarely metastasizes to the uncommon sites, colonic metastasis from squamous cell carcinoma of the esophagus is extremely rare. There has been no case report of colonic metastasis from squamous cell carcinoma of the esophagus to an anastomotic site of the colon. Methods/Case Report A 73-year-old female with a history of right hemicolectomy for advanced ascending colon cancer in 2006 was referred to our facility for a two-month history of solid food dysphagia. The patient has been followed up in the survivorship clinic for surveillance with no evidence of recurrence for 13 years to date. An esophagogastroduodenoscopy revealed a 7 cm fungating and ulcerated mass in the middle to lower esophagus. The biopsy from the esophageal mass showed a moderately to poorly differentiated squamous cell carcinoma. A colonoscopy showed an end-to-end ileocolonic anastomosis with a 7 mm ulceration in the transverse colon. The biopsy from the ulceration at the anastomotic site showed a moderately to poorly differentiated squamous cell carcinoma. Immunostains performed on both esophageal and colonic biopsies demonstrate that the tumor cells in both esophageal and colonic biopsies are positive for p40, p63, p16, and negative for CK7, CK20, and CDX2. The diagnosis of metastatic esophageal squamous cell carcinoma to the colonic anastomotic site of previous right hemicolectomy was rendered based on the morphology and immunoprofile. A subsequent computed tomography (CT) and positron emission tomography (PET) demonstrated no other distant metastases. Chemotherapy with 5-FU and oxaliplatin has been started. A metastasis to the anastomotic site is extremely rare. Although the anastomotic site might be a good niche for cancer cells to metastasize to, the pathogenesis of a metastasis to the anastomotic site remains unknown. Our case is very intriguing because a metastasis occurred at the anastomosis site, and no other metastasis was found. Results (if a Case Study enter NA) N/A Conclusion We have reported the first case of metastatic esophageal squamous cell carcinoma to the colonic anastomotic site of previous right hemicolectomy in a 73-year-old female. Although the pathogenesis of a metastasis to the anastomotic site remains unknown, the possibility of contribution of surgical trauma to metastasis formation at the ileocolonic anastomosis cannot be completely ruled out.

Introduction/Objective Rectal adenocarcinoma metastatic to the brain occurs in 0.6%-3% of cases and is associated with advanced-stage disease.TTF-1 expression in rectal adenocarcinoma is an uncommon finding and less than five cases of TTF-1 positive rectal adenocarcinomas have been reported in the literature. Herein, we report a primary rectal adenocarcinoma with biopsy-proven brain metastasis, radiographic evidence of hepatic and pulmonary involvement and unique expression of TTF-1, a marker with high sensitivity for primary pulmonary and thyroid lesions. Furthermore, we discuss the importance of distinguishing this entity from Pulmonary Enteric Adenocarcinoma (PEA). Methods/Case Report A 68-year-old male with hypertension presented with a two-day history of left facial drooping and dysarthria. Brain MRI revealed a 2.9 cm, contrast-enhancing, solitary, right insular mass. A pterional craniotomy and gross total resection of the lesion was performed. Microscopic examination revealed metastatic adenocarcinoma with immunohistochemical expression of CAM 5.2, CDX2, CK20, focal immunoreactivity with Napsin A and TTF-1, and lack of expression of CK7 and Synaptophysin. Radiographic investigation revealed a right posterior rectal lesion and multiple hepatic and bilateral pulmonary nodules. Sigmoidoscopy a fungating, partially circumferential, ulcerated, and friable rectal mass extending 6 cm proximally from the anal verge. Biopsy demonstrated invasive well- differentiated rectal adenocarcinoma with microsatellite stable phenotype, expression of CDX2, CD20, TTF-1 in the lesional cells, and lack of immunostaining with CK7. Given these findings, we favored a diagnosis of invasive well- differentiated rectal adenocarcinoma. Results (if a Case Study enter NA) N/A Conclusion TTF-1 positive rectal adenocarcinoma is an important differential diagnosis for PEA. As the two primary lesions share histomorphological features, clinical history, radiological findings and immunohistochemical staining with CK7 can aid in distinguishing between the two entities. Recent literature suggests a possible role for CDH17 and SATB2 immunostaining to increase the sensitivity and specificity of distinction between the two entities. Lack of expression of CK7 in both the rectal and brain lesion biopsies, radiological finding of numerous bilateral pulmonary infiltrates and one large, solitary rectal mass supports the diagnosis of advanced stage primary rectal adenocarcinoma with distal metastasis in our patient.

Background Intraductal tubulopapillary neoplasm (ITPN) depicts a distinct entity in the subgroup of premalignant epithelial tumors of the pancreas. Although the histomorphological and immunophenotypical characterization of ITPN has been described by several authors in terms of report of case series in the past, the rarity of that tumor subtype and similarity to other entities still makes identification of ITPN a challenge for radiologists and pathologists. To date, little is known about tubulopapillary carcinoma that can evolve from ITPN. Case presentation In the present work, we analyze one case of ITPN associated with an invasive component and discuss the results involving the current literature. Collected patient data included medical history, clinical symptoms, laboratory tests, radiological imaging, reports of interventions and operation, and histopathological and immunohistochemical examinations. The patient initially presented with acute pancreatitis. A solid tumor obstructing the main pancreatic duct and sticking out of the papilla of Vater was detected and caught via endoscopic intervention. Histopathological examination of the specimen revealed mainly tubular growth pattern with back to back tubular glands. Immunohistochemically, the tumor was strongly positive for keratin 7 (CK7) and pankeratin AE1/AE3, and alpha 1 antichymotrypsin; negative for synaptophysin and chromogranin A, CDx2, CK20, S100, carcinoembryonic antigen (CEA), MUC 2, MUC5AC, and somatostatin; and in part positive for CA19-9. Extended pancreatoduodenectomy was performed, the final diagnosis was tubulopapillary carcinoma grown in an ITPN. Conclusion The identification of an ITPN of the pancreas can be a challenging task. Endoscopic retrograde cholangiopancreaticography is an excellent tool to directly see and indirectly visualize the intraductal solid tumor and to take a biopsy for histopathological evaluation at the same time. Together with a thorough immunohistochemical workup, differential diagnoses can be ruled out quickly. To date, reports of ITPN are rare and little is known about the potential for malignant transformation and the prognosis of tubulopapillary carcinoma grown from an ITPN. Radical surgical resection following oncologic criteria is recommended; however, more data will be needed to assess an adequate treatment and follow-up standard.

Clear cell papillary renal cell carcinoma (CCPRCC) is a low-grade, indolent neoplasm with no reported cases of death from disease or metastasis. These lesions can show clinical, morphologic, and immunophenotypic overlap with several aggressive forms of renal cell carcinoma (RCC), including clear cell RCC, translocation RCC, and papillary RCC with cytoplasmic clearing. Given the difference in behavior, it is important to reliably separate these entities. We retrospectively reviewed 47 tumors from 45 patients with morphologic features of CCPRCC. All cases were stained against cytokeratin 7 (CK7), carbonic anhydrase IX (CAIX), and GATA3. Cases inconsistent with CCPRCC were reclassified. In addition, we stained tissue microarrays with 103 typical clear cell RCCs and 62 papillary RCCs, each in triplicate. Twenty-five cases were morphologically and immunophenotypically consistent with CCPRCC; all of them showed diffuse CK7 expression and cup-like reactivity with CAIX. Of these, 19 (76%) showed strong nuclear reactivity for GATA3. Although some non-CCPRCC neoplasms showed at least partial CK7/CAIX coexpression, none were immunopositive for GATA3. All background normal kidneys studied showed GATA3 expression in the distal tubules, collecting ducts, and retention cysts of the distal nephron. On follow-up, none of the patients with CCPRCC had recurrences or metastasis. Sensitivity and specificity for GATA3 staining in the diagnosis of CCPRCC were 76% and 100%, with positive and negative predictive values of 100% and 74%. In conclusion, GATA3 is specific and sensitive for CCPRCC and can be used for accurate distinction from its main mimickers. Coexpression of GATA3 and CK7 in most CCPRCC provides evidence of their origin from distal nephron.

Objectives Hyalinizing clear cell carcinoma (HCCC) is common in head and neck sites but extremely rare in the lung. This case report describes an HCCC in the lung of a 54-year-old female patient. Methods We summarize the histomorphologic, immunophenotypic, and molecular features for our and three previously reported HCCCs of the lung with emphasis on potential diagnostic pitfalls. Results Sections of a well-circumscribed 3.5-cm lung mass were characterized by a bronchocentric tumor growing in sheets, nests, and cords in a background of hyalinized stroma. Tumor cell appearance was clear to eosinophilic, lacking significant pleomorphism or mitotic activity. By immunohistochemistry, the tumor cells were strongly positive with antibodies to pan-keratin, p63, and CK5/6 while negative for CK7, CK20, thyroid transcription factor 1, napsin A, chromogranin, and synaptophysin. Next-generation sequencing demonstrated an EWSR1-ATF1 fusion transcript. Conclusions Awareness of key morphologic features of pulmonary HCCC is crucial for the recognition of this rare entity in the lung. Ancillary studies, including immunohistochemistry and molecular testing, are essential for the distinction from its mimics.

Aims The scirrhous variant of hepatocellular carcinoma (S-HCC) and fibrolamellar HCC (FL-HCC) are less common subtypes of HCC that are characterized by abundant fibrous stroma. Here, we aimed to investigate differences in the tumour microenvironment and the tumour epithelial cell characteristics of S-HCC and FL-HCC. Methods and results Whole tissue sections of 17 S-HCCs and 9 FL-HCCs were subjected to immunohistochemical stains for keratin 7 (K7), K19, EpCAM, CD56/NCAM, CD163, CD68, pSTAT3, FAP, CCN2 and Ki-67. FL-HCC patients were younger than S-HCC patients (P < 0.001), and chronic liver disease was seen in the background of 88.2% of S-HCC and in none of the FL-HCC. CD68 and CD163-positive tumour-infiltrating macrophages, and FAP-positive cancer-associated fibroblasts (CAFs) were more abundant in the stroma of S-HCCs compared to FL-HCCs (all P < 0.05). Tumour epithelial K19 expression was more frequent in S-HCCs compared to FL-HCCs (P = 0.023). Significant positive correlations were seen between pSTAT3 expression status in tumour epithelial cells and CAFs, the extent of stromal CAF and macrophage infiltration and K19 expression status. No significant differences were seen for K7, EpCAM, CD56/NCAM, CCN2 expression and Ki-67 labelling index between S-HCCs and FL-HCCs. Conclusion S-HCC and FL-HCC are subtypes of HCC with extensive fibrosis, and the nature of the fibrous stroma differs between them. While the stroma of FL-HCC is composed of dense lamellated collagenous bands with sparse cellular components, S-HCC demonstrates more abundant CAF and tumour-infiltrating macrophages and stemness-related marker expression, suggesting the presence of a complex tumour microenvironment that may influence the aggressive behaviour of S-HCCs.

Whether invasive mucinous adenocarcinoma (IMA) and colloid adenocarcinoma (ICA) of the lung represent separate tumour entities, or simply lie within a spectrum of phenotypic variability, is worth investigating. Fifteen ICA, 12 IMA, 9 ALK-rearranged adenocarcinomas (ALKA), 8 non-mucinous KRAS-mutated adenocarcinomas (KRASA) and 9 mucinous breast adenocarcinomas (MBA) were assessed by immunohistochemistry for alveolar (TTF1, cytoplasmic MUC1), intestinal (CDX-2, MUC2), gastric (membrane MUC1, MUC6), bronchial (MUC5AC), mesenchymal (vimentin), neuroendocrine (chromogranin A, synaptophysin), sex steroid hormone-related (oestrogen and progesterone receptors), pan-mucinous (HNF4A) and pan-epithelial (keratin 7) lineage biomarkers and by targeted next generation sequencing (TNGS) for 50 recurrently altered cancer genes. Unsupervised clustering analysis using molecular features identified cluster 1 (IMA and ICA), cluster 2 (ALKA and KRASA) and cluster 3 (MBA) (p

PAX6, a paired box transcription factor, is necessary for eye development. However, how it regulates the cell identity of human corneal epithelial cells (CECs) is not well understood. We aimed to clarify the function of PAX6 in human CECs using gene knockout via the clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR associated protein 9 (Cas9) system. We designed guide RNAs for different targets in PAX6. PAX6-depleted CECs maintained the epithelial morphology, but became larger. Global analyses using microarray revealed that down-regulated genes were primarily CEC-specific and included keratin 12, keratin 3, clusterin (CLU), aldehyde dehydrogenase 3 family member A1 (ALDH3A1), angiopoietin-like 7 (ANGPTL7) and transketolase (TKT), while up-regulated genes were primarily epidermis-related and included keratin 10, keratin 1, involucrin (IVL), filaggrin (FLG). These findings suggest that PAX6 maintains CEC identity by regulating differentiation.

Introduction/Objective High-grade endometrial neoplasms frequently pose a diagnostic challenge on purely histologic evaluation due to their ambiguous morphologic features. High grade endometrioid adenocarcinoma, serous carcinoma, undifferentiated carcinoma, and a minority of sarcoma cases can present with a solid growth pattern. Methods We present a 59-year-old patient who underwent a hysterectomy and bilateral salpingo-oophorectomy for a biopsy proven FIGO grade 2 endometrial carcinoma. Results Grossly, the entire endometrial cavity was involved by a hemorrhagic tumor. Microscopic examination showed the entire specimen to be replaced by predominantly non-cohesive diffuse sheets of mitotically active, pleomorphic cells without any glandular, papillary, serous or clear cell features.The differential diagnosis included undifferentiated carcinoma, serous carcinoma, carcinosarcoma, stromal sarcoma and other tumors including high- grade lymphoma. By immunohistochemistry, the tumor cells showed variable positivity for CK7, EMA, CK19, CK18, CK8, AE1/AE3, pan-keratin, CAM5.2, CD56, synaptophysin, p53, cyclinD1 and with a high Ki-67 proliferation index of 80%. The tumor was diffusely/intensely positive for CD10 and P16 while being negative for ER, PR, PAX8, HPV, mesenchymal and lymphoid markers. While diffuse/intense CD10 positivity and ER/PR negativity raised a concern for stromal sarcoma component, the above phenotype confirmed an aggressive/high grade carcinoma. Diffuse/intense p53 and p16 expression raised a consideration of serous carcinoma, but morphology and absence of PAX-8 failed to support this diagnosis. Undifferentiated carcinoma of the endometrium is a high-grade carcinoma which has been recognized as a distinct entity with diffuse p16 and p53 positivity in the absence of PAX-8 and hormone receptors. Positive vimentin, along with a negative HPV, confirmed the endometrial rather than cervical origin of this neoplasm. Conclusion By reporting this case, we draw attention to the previously unreported diffuse intense CD10 expression in undifferentiated carcinoma of endometrium to avoid misdiagnosis with considerations that include stromal sarcoma.

Casestudy: Chordoma is an uncommon primary malignant tumor of the bone showing notochordal differentiation. The current World Health Organization classifies chordoma into three subtypes: conventional, chondroid, and dedifferentiated. Poorly differentiated chordoma (PDC) is a newly described variant of chordoma, with its own distinct features in terms of age distribution (common in pediatric and young adults), histopathology (lack of physaliphorous cells and chondromyxoid matrix), immunohistochemical and molecular characteristics (loss of SMARCB1/INI1 expression) and clinical outcome (poor prognosis with rapid onset of local recurrence and metastasis). Herein, we report the case of a 43 year old man with history of fall and injury of tailbone 2 years prior, who presented with pain and swelling at the sacrcoccygeal region and intermittent numbness in the legs. MRI of the pelvis showed a 9.8 cm lobulated mass centered on the sacrum with osseous destruction of S5 through coccyx, with intralesional hemorrhage, and mild heterogeneous enhancement. Biopsy of the sacrococcygeal mass demonstrated a malignant neoplasm composed of lobules of epithelioid cells with abundant eosinophilic cytoplasm showing focal vacuolization, and mild to moderate nuclear pleomorphism with an average 3 mitoses per high power field (400x). Immunohistochemically, the neoplastic cells were positive for pancytokeratin, CAM 5.2, vimentin and brachyury. They had loss of SMARCB1 (INI1) and were negative for S100, CK7, CK20, desmin and actin. The location, imaging studies, morphologic features and immunohistochemical profile were consistent with poorly differentiated chordoma with rhabdoid features. With its specific clinical, morphologic, immunophenotypical, and molecular features, PDC may be recognized as a chordoma subtype in a future WHO classification. According to current knowledge, the diagnosis of PDC should be restricted to cases with brachyury expression (specific for notochord tumors) and INI1 protein loss, especially in tumors of pediatric and young patients, regardless of cellular characteristics.