Abstract

Introduction: Digital papillary adenocarcinoma (DPA) is a rare cutaneous neoplasm. Recently, Human papillomavirus (HPV) 42 has been reported in association with DPA. We investigated this association in a multi-institution cohort and characterized the molecular profile of these tumors.

Methods: DPA cases were searched in the archives of three tertiary hospitals. RNA in situ hybridization (HPV-ISH) was used to identify the presence of high- and low-risk HPV, which includes HPV42. For molecular testing, cases were submitted for Next-generation sequencing using the Oncomine Comprehensive Assay Plus and a custom assay, Iowa Cancer Mutation Profiling.

Results: A total of seven patients with DPA were included in the study. This tumor was predominantly seen in males, and the median age was 45 years. All cases presented with painful skin lesions arising on fingers or toes. The median duration of follow-up was 36 months. Local recurrence was seen in two patients while distant recurrence was noted in one. Microscopically, tumor cells formed deep dermal solid, tightly packed papillary structures lined by atypical epithelioid cells. Expression of low-risk HPV, which includes HPV42, was confirmed in 6/7 cases by HPV-ISH. POLE sequence variants were identified in 50% of cases (3/6), while NF1 and TP53 variants were present in two (33%) and one case (17%), respectively.

Conclusions: This study confirms the association between DPA and low-risk HPV. POLE mutations frequently occurred in DPA and their clinical significance and association with low-risk HPV in DPA warrants further investigation.