BackgroundThe molecular classification of gastric cancer recognises two subtypes prone to immune checkpoint blockade: the microsatellite unstable and the Epstein-Barr virus (EBV)-related tumours. We aim to assess the concordance between immunohistochemistry and PCR for microsatellite status evaluation, and explore the value of microsatellite instability (MSI) and EBV as predictive survival factors.Material and methodsWe collected 246 consecutively diagnosed gastric cancer cases in all stages and evaluated the microsatellite status using immunohistochemistry for mismatched repair (MMR) proteins and PCR. EBV expression was studied through in situ hybridisation.ResultsForty-five (18%) cases presented MSI and 13 (6%) were positive for EBV. MSI was associated with female sex, older age, distal location and distal non-diffuse type of the modified Lauren classification. EBV expression was most frequent in proximal location and proximal non-diffuse type. The sensitivity, specificity, positive predictive value and negative predictive value of immunohistochemistry for the microsatellite study were 91%, 98%, 91% and 98%, respectively. In the multivariate analysis, MSI was an independent predictor of favourable tumour-specific survival (TSS) in stages I–III (MSI: HR: 0.37, 95% CI 0.12 to 0.95, p=0.04).ConclusionsThe MSI status and the EBV expression should be incorporated in routine pathological report for two reasons. First, MSI defines a different pathological entity with a better outcome. Second, MSI and EBV may be useful biomarkers to identify patients who will respond to immune checkpoint blockade inhibitors. For this purpose, immunohistochemical study for MMR proteins and in situ hybridisation study for EBV evaluation are feasible and cost-effective methods.

The term “cutaneous lymphadenoma” was coined in this journal for an unusual lymphoepithelial cutaneous adnexal neoplasm, possibly with immature pilosebaceous differentiation. Some authors further proposed that cutaneous lymphadenoma was an adamantinoid trichoblastoma. However, although a hair follicle differentiation is widely accepted, the fact that this is a lymphoepithelial tumor is not appropriately explained by the trichoblastoma hypothesis. Our goal was to further clarify the phenotypic and genotypic features of cutaneous lymphadenoma in a series of 11 cases. Histologically, a lobular architecture surrounded by a dense fibrous stroma was present in all cases. The lobules were composed of epithelial cells admixtured with small lymphocytes and isolated or clustered large Reed-Sternberg–like (RS-L) cells. The epithelial cells were diffusely positive for the hair follicle stem cell markers CK15, PHLDA1, and for androgen receptor. No immunostaining for markers of sebaceous differentiation was found. Intraepithelial lymphocytes were predominantly CD3 + , CD4 + , FoxP3 + T cells. RS-L cells showed both strong Jagged-1 and Notch1 cytoplasmic immunostaining. Androgen-regulated NKX3.1 nuclear immunostaining was present in a subset of large intralobular cells in all cases. Double immunostaining showed coexpression of NKX3.1 and CD30 in a subset of RS-L cells. No immunostaining for lymphocytic or epithelial markers was present in RS-L cells. EGFR, PIK3CA, and FGFR3 somatic mutations were found by next-generation sequencing in 56% of the cases. We consider that cutaneous lymphadenoma is a distinct benign lymphoepithelial tumor with androgen receptor and hair follicle bulge stem cell marker expression, RS-L cell-derived Notch1 ligand, and common EGFR gene mutations.

Isolated cases of basal cell carcinoma (BCC) with partial myoepithelial component have been described. However, myoepithelial differentiation has not been described in sarcomatoid basal cell carcinomas, which usually show features resembling osteosarcoma, chondrosarcoma, or leiomyosarcoma. We report a case of an 87‐year‐old man with a forehead lesion that histologically showed a minor component of conventional nodular BCC in transition with a major biphasic sarcomatoid growth composed of invasive spindle‐cell and epithelial‐like components, the latter with a reticular pattern and scattered ductal structures. Both components showed cytological atypia and high mitotic rate (26/10HPF), with atypical mitotic figures. BER‐EP4 immunostaining was exclusively found in the nodular BCC component whereas the sarcomatoid component revealed immunostaining for α‐smooth muscle actin (SMA), muscle‐specific actin (MSA), calponin, and p63 in both epithelial‐like and spindle‐cell populations. Focal immunoreactivity was observed in the epithelial component for S100 and glial fibrillary acidic protein (GFAP). Furthermore, EWSR1‐PBX1 gene fusion was also detected. This is to our knowledge, the first fully documented case of biphasic sarcomatoid BCC with myoepithelial carcinoma differentiation.

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