August 2020 Case

Male in his mid-sixties, with past medical history of coronary artery disease status post stent (2001) on aspirin, HIV on HAART, hypertension, hyperlipidemia and anal intraepithelial neoplasia (AIN) III presented with several months of epistaxis and a progressively enlarging left nasal cavity mass. CT sinus with contrast revealed an ill-defined polypoid mass measuring approximately 4 centimeters in its greatest dimension. The patient underwent an elective endoscopic surgery in a piecemeal manner.

HPV-related multiphenotypic sinonasal carcinoma (HMSC) 

Here we present a case of HMSC (previously known as HPV-related carcinoma with adenoid cystic carcinoma-like features), a rare entity associated with high-risk HPV, most commonly subtype 33. The majority of HPV-positive head and neck cancers arise from the oropharynx, while another anatomical hotspot for HPV-related neoplasm is in the sinonasal cavity. HMSC is associated with 1) HPV, most commonly subtype 33; 2) overlying dysplastic squamous epithelium, which may be present; 3) negative for MYB gene rearrangements; and 4) appearing, generally, to have indolent clinical behaviors.

HMSC occurs in a broad age group, ranging from 20s to 90s, with female preponderance. Patients may present with epistaxis, nasal congestions, obstruction and sinus pressure. HMSC most commonly arises in the sinonasal cavity but has also been reported in the lacrimal duct, orbit and cranial fossa. The term "multiphenotypic" captures the histologic diversity of this entity. The architecture can vary widely, being solid, inverted, cribriform and/or tubular growth. The predominant basaloid myoepithelial cells can exhibit clear cell changes, cell spindling and plasmacytoid appearance as well as extracellular hyaline matrix deposition. The morphologic spectrum includes, but is not limited to, anaplastic giant cells, squamous cell component and the rarer sarcomatoid differentiation with heterologous cartilaginous formation. The cell of origin and the HPV mechanism infection in the nasal cavity remain unknown. However, the overlying dysplastic squamous epithelium is suggestive of the origin to be at the surface and not of a minor salivary gland origin. The morphology and immunohistochemistry profile are reminiscent of a salivary gland tumor, particularly adenoid cystic carcinoma, with biphasic ductal and myoepithelial cell differentiation. In contrast to adenoid cystic carcinoma, HMSC is diffusely positive for P16 and negative for MYB gene rearrangements.

Due to the limited number of cases, the prognostic factor is unknown. However, they generally appear to have indolent clinical behaviors. The clue to diagnosis is recognizing a high-grade "salivary-gland tumor" within the sinonasal cavity. Pulmonary and hand have been reported as metastasis sites for HMSC, but there are no tumor-associated deaths to date. There is currently no consensus treatment guideline for HMSC. The standard of care is surgical resection, but chemoradiation may be warranted if the margin status is unknown or positive. Since cervical lymph nodes metastasis have not been recorded, neck dissection or treatment is not necessary. Lifelong clinical surveillance may be warranted since local recurrence occurring 30 years after disease-free survival has been reported.