Low-risk HPV CISH identifies digital papillary adenocarcinoma: look for punctate nuclear dots

Design

Retrospective single-institution diagnostic study

Population

12 digital papillary adenocarcinomas and 8 tubular adenomas

Primary outcome

Low-risk HPV CISH positivity and staining pattern

Effect

CISH positive 12/12 vs 0/8; BRAF V600E negative 9/9 vs positive 8/8

Digital papillary adenocarcinoma is a rare, aggressive adnexal tumour of the fingers and toes, and most cases carry HPV42. HPV42-specific testing is not routine, so this study tested a commercially available low-risk HPV chromogenic in situ hybridisation (CISH) probe set that includes HPV42.

All 12 digital papillary adenocarcinomas were CISH-positive and all 8 tubular adenomas negative. BRAF V600E immunohistochemistry showed the reverse: positive in all tubular adenomas and negative in the 9 adenocarcinomas tested. All adenocarcinomas were on the fingers of men (median age 62). The signal was consistently punctate and nuclear rather than diffuse, and in some cases visible only at high magnification.

This gives laboratories a routine, available test for a tumour that is easily undercalled as benign and can metastasise. The staining pattern is the practical trap: pathologists used to diffuse nuclear low-risk HPV signal in condylomas may read these dots as negative. The series is small and single-institution.

• Order low-risk HPV CISH for papillary or tubular adnexal tumours of the digits where digital papillary adenocarcinoma is in the differential.
• Examine the CISH at high power for punctate nuclear dots; diffuse staining is not the expected pattern.
• Add BRAF V600E immunohistochemistry; positivity favours tubular adenoma.
• Do not accept a benign adnexal diagnosis on a digital tumour without considering this test.

Why it matters

An aggressive tumour that is often called benign now has a routine confirmatory test.

Don't overread it

Twelve cases from one institution; sensitivity and specificity need testing in larger, multicentre series.

The statistics, in plain English

12 of 12 positive and 8 of 8 negative gives perfect separation in this series, but with 20 tumours in total the true sensitivity and specificity could each be noticeably lower.

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