Case 2: 53-year-old female with sinonasal mass

HMSC is a rare sinonasal malignancy primarily observed in adults, with a mean age in the 50s (range 20–90 years) and a slight female predominance. It predominantly involves the nasal cavity (89%), particularly the turbinate, with or without concurrent paranasal sinus involvement. Rare cases exclusively affect the sinuses. Patients typically present with symptoms such as nasal congestion or epistaxis.

Histologically, HMSC demonstrates multiple lines of cellular differentiation. Tumor cells often form solid sheets, cribriform patterns, or ductal structures, closely resembling adenoid cystic carcinoma HMSC exhibits both ductal and myoepithelial differentiation, which can be identified through immunostaining. Myoepithelial differentiation is highlighted by markers such as p40, p63, SMA, and calponin, while ductal differentiation is marked by KIT (CD117). Both cell types express S100 and SOX10. MYB immunohistochemistry and MYB RNA in situ hybridization are typically positive, however, no MYB rearrangements is detected by FISH. HMSC is positive for p16 and high-risk HPV by direct HPV assays such as RNA in situ hybridization. It harbors high-risk HPV, most commonly type 33 (about 80%), and occasionally types 35, 16, 52, 56, or 82. Local recurrences are common in about one third of cases, but distant metastases are rare (5%).

Adenoid cystic carcinoma (AdCC)
Approximately 60% of adenoid cystic carcinomas (AdCCs) occur in the major salivary glands, while 30% are found in the minor salivary glands. AdCC is composed of two primary cell types: ductal and myoepithelial cells. The tumor exhibits three characteristic growth patterns: tubular, cribriform, and solid. Perineural invasion is a common feature of this malignancy. The diagnosis of AdCC can be supported by demonstrating MYB/MYBL1 rearrangements or gene fusions through FISH or other molecular techniques. While approximately 6% of AdCCs show p16 positivity, they are negative for high-risk HPV by RNA in situ hybridization or genotyping.

Basaloid squamous cell carcinoma (BSCC)
BSCC is characterized by its basaloid morphology and aggressive clinical behavior, most commonly occurring in the larynx. The tumor often contains a myxoid to hyaline stromal matrix deposited between tumor nests, creating a pseudocribriform appearance. Tumor cells are diffusely positive for squamous markers, such as p40 and p63. BSCC frequently expresses SOX10, KIT (CD117), and MYB, which can pose a diagnostic challenge due to overlapping with other entities. High-risk HPV is not typically associated with BSCC

Neuroendocrine carcinoma (small cell or large cell NEC)
NECs are composed of a single cell population. Small cell NECs are characterized by large hyperchromatic nuclei, finely granular to stippled chromatin, and nuclear molding. In contrast, large cell NECs typically exhibit abundant eosinophilic cytoplasm and prominent nucleoli. NECs are positive for neuroendocrine markers, including synaptophysin, chromogranin, and INSM1. A subset of NECs has been associated with high-risk HPV.

1. HPV-related Multiphenotypic Sinonasal Carcinoma: An Expanded Series of 49 Cases of the Tumor Formerly Known as HPV-related Carcinoma With Adenoid Cystic Carcinoma-like Features. Justin A Bishop, Simon Andreasen, Jen-Fan Hang, et al. Am J Surg Pathol. 2017 Dec;41(12):1690-1701.

2. p16 Immunoexpression in sinonasal and nasopharyngeal adenoid cystic carcinomas: a potential pitfall in ruling out HPV-related multiphenotypic sinonasal carcinoma. Vijay M Antony, Aanchal Kakkar, Kapil Sikka, et al. Histopathology. 2020 Dec;77(6):989-993