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Salivary duct carcinoma (SDC) is an aggressive neoplasm that resembles high-grade invasive ductal carcinoma of the breast. It can develop de novo or from the malignant transformation of pleomorphic adenoma (PA). We performed immunohistochemical stains for phosphatase and tensin homologue [PTEN androgen receptor (AR)], HER2/neu, cytokeratin 5/6, estrogen receptor-beta, high-mobility group AT-hook 2 (HMGA2), and pleomorphic adenoma gene 1 (PLAG1) on tissue microarray samples of 75 SDCs and 31 adenocarcinomas, not otherwise specified (NOS). Our data showed the following in SDC samples: loss of PTEN was found in 17 of 60 (28.3%); AR was expressed in 43 of 62 (69.4%); HER2/neu was overexpressed in 25 of 58 (43.1%); cytokeratin 5/6 was expressed in 14 of 54 (25.9%); estrogen receptor-beta was expressed in 37 of 56 (66.1%); HMGA2 was expressed in 29 of 63 (46.0%); and PLAG1 was expressed in 0 of 62 (0%). In addition, there was no statistically significant difference in the age at onset between patients with HMGA2-positive SDCs (range 32–85 years; mean: 64.3 years; median: 64.5 years) and those with HMGA2-negative SDCs (range 41–79 years; mean: 62.5 years; median: 64.5 years). There was also no statistically significant difference in overall survival between patients with HMGA2-positive and HMGA2-negative SDCs (follow-up period range 3–201 months; mean: 49.8 months; median: 30 months). Among 10 patients with a definite PA component (SDC ex-PA), 6 were positive and 4 were negative for HMGA2. Our data were consistent with previous findings that AR and estrogen receptor-beta are expressed in most SDCs, whereas HER2/neu overexpression and loss of PTEN are expressed in a subset of SDCs. In our cohort of patients, HMGA2 was expressed in approximately half of SDCs. HMGA2 and PTEN are promising therapeutic targets for salivary gland tumors.

Although the majority of conditions involving the ear and temporal bone are inflammatory or epithelial based, cartilage and osseous entities will also be encountered. The pathologic examination of these underlying cartilaginous and osseous structures and their histologic findings and associated differential diagnoses will be discussed. Correlation with clinical and imaging findings are also critical for accurate determination of the pathologic entity.

Paragangliomas (PGL) develop from the parasympathetic system in the head and neck (HN) and arise primarily in four distinct areas: Carotid body, vagal, middle ear, and larynx. Globally, the diagnosis and morphologic features are the same regardless of anatomic site, however the incidence, frequency of genetic alterations/syndromes and differential diagnosis vary. It is now recognized that nearly 40% of all HN PGLs are hereditary, including a significant subset without a known family history. Now pathologists are central to the evaluation for diagnosis and further management of patients with HNPGLs. Specifically, SDHB immunohistochemical evaluation is an excellent screening tool to detect tumors with alterations in the SDH family of genes that represent the majority of hereditary cases in HNPGL. Similarly, SDHB immunohistochemical analysis allows for screening of PGL syndrome associated tumors (gastrointestinal stromal tumor (GIST), renal cell carcinoma (RCC), and pituitary adenomas) that have now been linked by their overlapping gene alterations. Awareness of the spectrum of these syndromes, and their associated tumors, positions the pathologist to augment patient care and surveillance.

The updated edition of The World Health Organization Classification of Tumours of the Head and Neck includes discussions on mucosal melanoma of both the sinonasal and oral cavity. Since the prior edition, sinonasal origin is now recognized as the most common site of occurrence of mucosal melanoma in the head and neck (66%) with oral cavity representing 25% of cases. Histologic features of mucosal melanomas vary widely from spindled, epithelioid, and pleomorphic to rhabdoid, plasmacytoid and undifferentiated. Additionally, mucosal melanomas are commonly amelanotic (or minimal pigmentation) (~50%) leading to overlapping features and diagnostic challenges in differentiating mucosal melanomas from other small cell/undifferentiated sinonasal tumors. Since the last edition, formal staging of head and neck mucosal melanomas was added to the American Joint Committee on Cancer entities, though the traditional histologic features that have prognostic significance in cutaneous melanomas fail to stratify mucosal melanomas (i.e. tumor thickness, ulceration). Interestingly, while melanomas of all sites are a malignancy derived from melanocytes, mucosal melanomas are now recognized to have distinct molecular alterations compared to cutaneous or uveal melanomas. BRAF V600E mutations are rare (

Updated editions of The World Health Organization Classification of Tumours Pathology & Genetics for both Head and Neck Tumours and Tumours of Endocrine Organs took place in 2016 based on consensus conferences. These editions present unification of concepts in paragangliomas and highlight expanding knowledge of their etiology. There is a major emphasis in the new bluebooks on familial/syndromic paragangliomas, representing ~40% of all head and neck paragangliomas. Ancillary use of immunohistochemical evaluation, specifically of SDHB, allows the pathologist to screen for a large subset of these potentially hereditary cases. In addition, similarly to other neuroendocrine tumors, paragangliomas are now considered to represent a continuum of risk, and are assessed in terms of risk stratification. Tumors with SDHB mutations pose the highest risk for metastasis. There is currently no validated or endorsed histologic grading system. Paragangliomas remain tumors of undetermined biologic potential and should not be termed benign.

Item does not contain fulltext While high risk human papillomavirus (HPV) is well established as causative and clinically important for squamous cell carcinoma (SCC) of the oropharynx, its role in non-oropharyngeal head and neck SCC is much less clearly elucidated. In the sinonasal region, in particular, although it is a relatively uncommon site for SCC, as many as 20 % of SCC harbor transcriptionally-active high risk HPV. These tumors almost always have a nonkeratinizing morphology and may have a better prognosis. In addition, specific variants of SCC as well as other rare carcinoma types, when arising in the sinonasal tract, can harbor transcriptionally-active HPV. This article reviews the current literature on HPV in sinonasal carcinomas, attempts to more clearly demonstrate what tumors have it and how this relates to possible precursor lesions like inverted papilloma, and discusses the possible clinical ramifications of the presence of the virus.

Head and neck tumors comprise a wide spectrum of heterogeneous neoplasms for which biomarkers are needed to aid in earlier diagnosis, risk assessment and therapy response. The search for biomarkers includes evaluation of tumor tissues and surrogate materials by molecular, genomic and phenotypic means. Ideal biomarkers should be accurate and easy to perform, highly specific, objective, quantitative, and cost effective. Because of the heterogeneity of head and neck tumors, the integration of multiple selected markers in association with the histopathologic features is advocated for risk assessment. For targeted therapy, however, a single key molecule must be identified. Key molecules and pathways for targeted therapy include growth factor receptors, MAPk/ERk pathway, angiogenesis, and epithelial to mesenchymal transition. Over-expression and mutations of genes in these pathways including EGFR, VEGF, HER2, BRAF and RET, contribute to tumorigenesis in head and neck cancers from squamous carcinomas, to salivary adenocarcinomas and thyroid carcinomas, both follicular and c-cell derived. Monoclonal antibodies to the EGFR receptor and oral tyrosine kinase inhibitors are currently being studied in multiple phase II and III clinical trials to determine their efficacy in head and neck cancers and correlative studies for biomarkers are on-going.

Epithelioid hemangioendothelioma is an uncommon vascular tumor of soft tissue and bone that may rarely occur in the liver, lung and the head and neck. We present five new cases of epithelioid hemangioendothelioma of the head and neck region diagnosed and managed in one institution in order to define the phenotypic characteristics, podoplanin immunohistochemical staining and the biological outcome. Podoplanin is a transmembrane mucoprotein selectively expressed in lymphatic endothelium and recently in some vascular neoplasms. The patients were comprised of two male and three female patients ranging in age from 4 to 71 years. The lesions were found in the gingiva, submandibular region soft tissue, nasal cavity and tongue, and ranged in size from 0.7 to 2.5 cm. All tumors manifested infiltrative cords and nests of epithelioid cells with occasional spindle morphology in a myxoid stroma. Immunohistochemical analysis of vascular and epithelial markers showed strong and uniform cytoplasmic reactivity for podoplanin and variable intensity and staining of CD31 and lack of cytokeratin staining in tumor cells. Surgical treatment included simple and wide local excisions. Of the three patients with follow-up, one developed lymph node metastasis and one had no evidence of disease 10 months after surgery. The patient with multiple recurrences and LN metastases was additionally treated with chemotherapy and is under consideration for radiation therapy. Hemangioendothelioma of the head and neck is: (1) a low-grade malignancy with a tendency for local recurrence and regional lymph node metastasis, (2) complete excision with negative margins is the treatment of choice for localized disease and (3) podoplanin may be useful in differentiating epithelioid hemangioendothelioma from non-vascular tumors.