Ciliated Adenosquamous Carcinoma: Expanding the Phenotypic Diversity of Human Papillomavirus-Associated Tumors

Abstract

This study describes a unique subset of ciliated, human papillomavirus (HPV) related, adenosquamous carcinomas (AsqCA) of the head and neck that in contrast to most AsqCA, often show areas with lower grade cytonuclear features. They are comprised of largely nonkeratinizing squamous cell carcinoma components with cystic change, gland formation, mucin production, and cilia in tumor cells. Seven cases of ciliated AsqCA were retrieved. Site distribution was as follows: palatine tonsil-3/7, base of tongue-1/7, and neck (unknown primary site)-3/7. Despite the occasional resemblance to mucoepidermoid carcinoma (MEC), the tumors showed focal keratinizing morphology and atypia, and all tumors were negative for MAML2 rearrangements. Oropharyngeal and neck tumors were uniformly p16 positive and showed punctate staining by in situ hybridization for high risk HPV DNA. There were two distant metastases (lung), and one tumor related death. Thus, ciliated AsqCA are HPV-associated lesions that pose unique pitfalls, closely mimicking MEC and other salivary gland tumors. These tumors add to the list of those which defy the dogma that ciliated epithelium always equates to a benign process.

Intra-Cystic (In Situ) Mucoepidermoid Carcinoma: A Clinico-Pathological Study of 14 Cases

“…Despite its high specificity, MAML2 testing is no longer considered a useful prognostic indicator for already diagnosed MECs, and may be avoided when the diagnosis of MEC is reached straightforwardly, based on typical morphologic features [34,35,37]. Consequently, MAML2 testing as an ancillary diagnostic tool should be reserved for MECs showing unusual histological appearances [38,39], such as the oncocytic variant of MEC, to rule out oncocytoma and oncocytic carcinoma; and the Whartin-like variant and the recently described ciliated MEC variant, to rule out benign developmental cysts and ciliated, HPV-related squamous cell carcinomas [40,41].…”

Morphologic diversity in human papillomavirus-related oropharyngeal squamous cell carcinoma: Catch Me If You Can!

“…HPV-related cystic nodal metastases have also recently been shown to occasionally have true gland formation with mucin, to have columnar are lining cells, and to have, on rare occasions, apical cilia ( Figure 6). In two recently published series, 48,49 determining these tumors as either 'ciliated adenosquamous carcinoma' or just 'ciliated HPV-related carcinoma,' 10 patients were reported in whom all had cystic neck lymph node metastases. Five of these patients had identifiable primary lesions in the oropharynx, most of these also showing ciliated cells and gland formation.…”

Update from the 4th Edition of the World Health Organization Classification of Head and Neck Tumours: Oropharynx

“…It also includes, as recently described in small patient series, the presence of ciliated tumor cells "ciliated adenosquamous carcinoma". Although the number of reported cases of these variant forms is limited, the best available data suggests that patients with transcriptionally-active HPV have clinical outcomes that are similar to HPV-positive OPSCC with typical morphology [11][12][13][14][15][16][17][18][19][20][21].…”