Background The management of high‐risk human papillomavirus (HR‐HPV)–related oropharyngeal head and neck squamous cell carcinomas (HNSCCs) are distinct from HNSCC linked to smoking and alcohol use. HR‐HPV–positive HNSCC frequently presents as a cervical lymph node metastasis. Because fine‐needle aspiration (FNA) is often the initial diagnostic procedure, evaluating HR‐HPV status in cytology specimens is important. The overexpression of p16 is a surrogate for HR‐HPV; however, the evaluation of p16 in FNAs remains controversial. Methods From September 2015 to December 2016, cytopathologists performed 25 FNAs of neck lymph nodes that were suspicious for HR‐HPV–positive HNSCC. Initial passes produced smears for on‐site evaluation and CytoLyt material. Additional passes were formalin‐fixed. A CytoLyt cell block (CCB) and a formalin‐fixed cell block (FFCB) were prepared, and p16 immunocytochemistry was performed. Results In 24 of 25 cases, the FFCB had diffuse (≥70% of cells), strong nuclear/cytoplasmic p16 staining. In all 24 of these cases, HR‐HPV was detected by in situ hybridization. The corresponding CCB had weak‐to‐moderate p16 staining in <70% of cells (range, 5%‐60% of cells) in 17 cases, 4 had weak‐to‐moderate diffuse staining, and 4 were acellular. The percentage of p16‐positive cells was significantly higher with FFCB than with CCB (formalin: 94% ± 2%; CytoLyt, 38% ± 7%; 2‐tailed, paired Student t test; P < .001; Fisher exact test, P < .001). Conclusions The fixative used had a drastic impact on p16 staining, which explained the staining variability reported in the literature. FFCBs show a diffuse staining pattern, which correlates with HR‐HPV status, whereas CCBs show a weaker and inconsistent staining pattern, which is more difficult to interpret.
Primary hepatic "lymphoepithelioma-like" carcinomas are very rare. The majority are cholangiocarcinomas, most of which are also associated with Epstein-Barr virus (EBV) infection by staining for viral proteins and/or RNA. Here we report a "lymphoepithelioma-like" biliary lesion with EBV infection with uncertain or low malignant potential. A 72-year-old Asian woman with chronic hepatitis B and prior bladder cancer was incidentally found to have a 3.7 cm liver mass on CT scan. Right partial hepatectomy was performed. Histology shows the usual prominent inflammation, though epithelial components are unusual. These are cystic spaces surrounded by a mature collagenous stroma with elongated, inter-anastomosing tubular stellate projections. The epithelial cells are cuboidal, fairly monomorphic, though with high nuclear:cytoplasmic ratios and prominent nucleoli. Tissue invasion is absent. Immunohistochemically, the tumor epithelial cells are strongly positive for keratins 7 and 19. Carcinoembryonic antigen (CEA) mostly shows distinctly apical staining (similar to normal bile ducts). Hepatocyte markers (HepPar1, arginase 1, alpha-fetoprotein [AFP], glutamine synthetase, canalicular pCEA, and CD10) are absent. The surrounding infiltrating inflammatory cells are positive for CD3, CD7, CD1a, and CD68, which confirm a mixed inflammatory cell population. Ki-67 labeling is ~5% in the inflammatory cells and <1% in the biliary component. Fluorescence in situ hybridization (FISH) for EBV is positive throughout the epithelial component. A diagnosis of lymphoepithelioma-like biliary lesion is considered. However, though all previously reported biliary "lymphoepithelioma-like" lesions have been cholangiocarcinomas, this lesion -with monotonous epithelia, hamartomatous-like epithelial structures, low Ki-67 index, lack of invasion, absence of recurrence or metastasis in 3 years follow-up -indicates, at most, low malignant potential or even a "lymphoepithelioma-like" bile duct adenoma.
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