Nail squamous cell carcinoma: what separates in situ from invasive

Design

multicentre, multinational retrospective cohort with multinomial logistic regression comparing in situ and invasive disease

Population

269 nail squamous cell carcinomas in 261 patients; 72.4% men, typically in the sixth decade

Primary outcome

clinical and morphological features distinguishing in situ from invasive disease, and treatment outcomes

Effect

subungual ooze predicted invasive disease, odds ratio 3.98 (95% CI 1.19 to 13.2, P=0.025); overall recurrence 9.7% with no difference between treatments

Nail squamous cell carcinoma is the commonest nail malignancy and is routinely mistaken for warts, onychomycosis or chronic paronychia. This multicentre retrospective review characterised 269 tumours in 261 patients, comparing in situ with invasive disease.

The distribution is worth memorising: mostly the right index and middle fingers and both thumbs, accounting for 62%, predominantly in men (72.4%), typically in the sixth decade. Koilocytosis, used here as a histological proxy for human papillomavirus with 15 cases confirmed by PCR, appeared in 32.2% of tumours and was commoner in in situ disease. On multinomial regression, subungual ooze independently predicted invasive disease, odds ratio 3.98 (95% CI 1.19 to 13.2, P=0.025). Pain (P=0.022) and nail plate loss (P=0.004) were associated with invasion on univariate analysis. Mohs micrographic surgery was the commonest treatment at 39.5%, overall recurrence was 9.7%, and no treatment modality outperformed another.

Two clinical shapes emerge. A periungual warty papule or plaque growing horizontally is the in situ, HPV-associated presentation - the one most often treated as a viral wart for years. An oozing, ulcerating subungual tumour with pain and plate loss is the invasive one. The reassuring part is that digit-sparing surgery works: recurrence was under 10% and equivalent across modalities, so amputation is not the default it once was.

• Treat a persistent periungual 'wart' that has not responded to standard therapy as a biopsy candidate, not a treatment failure.
• Ask specifically about subungual ooze, pain and nail plate loss - these mark invasive disease.
• Remember the digits: right index and middle fingers and both thumbs account for most cases.
• Offer digit-sparing surgery first; recurrence was 9.7% overall with no difference between modalities.
• Where HPV is implicated in periungual disease, examine the genital area and take a sexual history - transmission is often sexual.

The statistics, in plain English

An odds ratio of 3.98 with a confidence interval running from 1.19 to 13.2 is a wide interval - the finding is statistically significant but the size of the effect is poorly pinned down, which is what happens when a predictor is examined in a few hundred retrospective cases. It is still the only feature that survived multivariable adjustment, which is why pain and nail plate loss are reported as univariate associations only: they may simply track with ooze rather than adding information. HPV status came from koilocytosis on histology in most cases rather than PCR, so the 32.2% figure is a proxy measurement and probably imprecise in both directions.

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