Telocytes have recently emerged as unique interstitial cells defined by their extremely long, thin and moniliform prolongations termed telopodes. Despite growing evidence that these cells consistently reside in the stromal compartment of various organs from human beings, studies dealing with telocytes in structures of the oral cavity are scarce. Hence, the present morphologic study was undertaken to explore for the first time the presence and specific localization of telocytes within tissues of the normal human tongue, a complex muscular organ whose main functions include taste, speech, and food manipulation in the oral cavity. Telocytes were initially identified by CD34 immunostaining and confirmed by CD34/PDGFRα double immunofluorescence and transmission electron microscopy. CD34+/PDGFRα+ telocytes were organized in interstitial meshworks either in the tongue lamina propria or in the underlying striated muscle. Lingual telocytes were immunonegative for CD31, c-kit and α-SMA. Telopodes were finely distributed throughout the stromal space and concentrated beneath the lingual epithelium and around CD31+ vessels, skeletal muscle bundles/fibers, and intramuscular nerves and ganglia. They also enveloped salivary gland units outside the α-SMA+ myoepithelial cells and delimited lymphoid aggregates. These findings establish telocytes as a previously overlooked interstitial cell population worth investigating further in the setting of human tongue pathophysiology.

Background: Secretory carcinoma (SC; synonym: mammary analogue SC= MASC) is a lowgrade salivary gland tumor which occurs both in major and in minor salivary glands. SC is known for its wide morphological, architectural and immunohistochemical spectrum, that overlaps with several salivary gland neoplasms, including acinic cell carcinoma (AciCC) and intraductal carcinoma (IDC) of intercalated type in major, and polymorphous adenocarcinoma (PAC) in minor salivary glands. These tumors share with SC some morphological features, SOX10 immunoreactivity, and, with the exception of AciCC, they all coexpress S100 and mammaglobin. Methods: We compare MUC4 and mammaglobin Accepted Article This article is protected by copyright. All rights reserved expression in 125 salivary gland carcinomas (54 genetically confirmed SCs, 20 AciCCs, 21 PACs, and 30 IDCs) to evaluate its potential in differentiating these entities. Results: Moderate to strong diffuse MUC4 positivity was detected in 49 SCs (90.7%) compared to none of IDCs and PACs. On the contrary, mammaglobin is frequently expressed in SC (30 of 36 cases; 83.3%), IDC (24/28; 85.7%) and PAC (7/19; 36.8%). Two of 3 high grade SCs lost MUC4 expression in the high-grade tumor component. No significant correlation was found between MUC4 expression and the fusion variant in SC (ETV6-NTRK vs. non-ETV6-NTRK). Conclusion: The results of our study identify MUC4 as a sensitive (90.7%) and specific (100%) marker for SC, with high positive (100%) and negative (93.4%) predictive values. Thus, MUC4 may be used as a surrogate for SC in limited biopsy material and in cases with equivocal morphology.

Sinonasal carcinomas are a heterogeneous group of rare tumors, often with high-grade and/or undifferentiated morphology and aggressive clinical course. In recent years, with increasing molecular testing, unique sinonasal tumor subsets have been identified based on specific genetic alterations, including protein expression, chromosomal translocations, specific gene mutations, or infection by oncogenic viruses. These include, among others, the identification of a subset of sinonasal carcinomas associated with HPV infection, the identification of a subset of squamous cell carcinomas with EGFR alterations, and of rare variants with chromosomal translocations (DEK::AFF2, ETV6::NTRK and others). The group of sinonasal adenocarcinomas remains very heterogeneous at the molecular level, but some recurrent and potentially targetable genetic alterations have been identified. Finally, poorly differentiated and undifferentiated sinonasal carcinomas have undergone a significant refinement of their subtyping, with the identification of several new novel molecular subgroups, such as NUT carcinoma, IDH mutated sinonasal undifferentiated carcinoma and SWI/SNF deficient sinonasal malignancies. Thus, molecular profiling is progressively integrated in the histopathologic classification of sinonasal carcinomas, and it is likely to influence the management of these tumors in the near future. In this review, we summarize the recent developments in the molecular characterization of sinonasal carcinomas and we discuss how these findings are likely to contribute to the classification of this group of rare tumors, with a focus on the potential new opportunities for treatment.