Abstract
Introduction/Objective
Papillary squamous cell carcinoma (PSCC) is a rare cervical neoplasm composed of papillae lined by atypical squamous/transitional cells without koilocytosis. It is unclear whether PSCC is related to human papillomavirus (HPV) infection, though rare cases were reportedly associated with HPV type 16. PSCC is thought to be more common in postmenopausal women. Some authors have suggested that PSCC may be understaged due to the prominent exophytic nature of the superficial aspect and relatively deep location of underlying infiltrative nests. It has also been suggested that PSCC has a tendency to recur and/or metastasize late.
Methods
The surgical pathology database of a single large academic institution was searched for squamous cell carcinoma (or squamous cell carcinoma in situ) with papillary features from the cervix, sampled between 1996 and 2018. PCR for human papillomavirus (HPV) L1 protein was run, with sequencing of positive samples.
Results
5 cases diagnosed as “papillary squamous cell carcinoma” were identified. Patient age ranged from 21–63 years (mean 46 years). All tumors showed papillary architecture, often with complex branching and/or fusion. The neoplastic cells had a squamous/transitional appearance with moderate to marked cytologic atypia and at most focal keratinization. Stage ranged from pT1b1 to pT3b (clinical stage IB1 to IVB). HPV L1 PCR was positive in only one case; sequencing confirmed HPV type 16. Upon closer review, the HPV-positive case was from the youngest patient and showed adjacent low-grade squamous intraepithelial lesion (LSIL) as well as focal koilocytic change within the papillary tumor.
Conclusion
Our findings suggest that even in patients with HPV infection, PSCC may be an HPV-independent malignancy. In multiple cases, it was difficult to obtain definitive histologic evidence of invasion prior to resection.
Methylation of p16 ink4a promoter is independent of human papillomavirus DNA physical state: a comparison between cervical pre-neoplastic and neoplastic samples
