Nail unit squamous cell carcinoma (NSCC) is a malignant neoplasm that can arise from any part of the nail unit. Diagnosis often is delayed due to its clinical presentation mimicking benign conditions such as onychomycosis, warts, and paronychia. Nail unit SCC has a low rate of metastasis; however, a delayed diagnosis often can result in local destruction and bone invasion. It is imperative for dermatologists who are early in their training to recognize this entity and refer for treatment. Many approaches have been used to treat NSCC, including wide local excision, digital amputation, cryotherapy, topical modalities, and recently Mohs micrographic surgery (MMS). This article provides an overview of the clinical presentation and diagnosis of NSCC, the role of human papillomavirus (HPV) in NSCC pathogenesis, and the evidence supporting surgical management.
NSCC Clinical Presentation and Diagnosis
Nail unit squamous cell carcinoma is a malignant neoplasm that can arise from any part of the nail unit including the nail bed, matrix, groove, and nail fold.1 Although NSCC is the most common malignant nail neoplasm, its diagnosis often is delayed partly due to the clinical presentation of NSCC mimicking benign conditions such as onychomycosis, warts, and paronychia.2,3 Nail unit SCC most commonly is mistaken for verruca vulgaris, and thus it is important to exclude malignancy in nonresolving verrucae of the fingernails or toenails. Another reason for a delay in the diagnosis is the painless and often asymptomatic presentation of this tumor, which keeps patients from seeking care.4 While evaluating a subungual lesion, dermatologists should keep in mind red flags that would prompt a biopsy to rule out NSCC (Table 1), including chronic nonhealing lesions, nail plate nodularity, known history of infection with HPV types 16 and 18, history of radiation or arsenic exposure, and immunosuppression. Table 2 lists the differential diagnosis of a persisting or nonhealing subungual tumor.
Nail unit SCC has a low rate of metastasis; however, a delayed diagnosis often can result in local destruction and bone invasion.5 Based on several reports, NSCC more commonly is found in middle-aged and older individuals, has a male predilection, and more often is seen on fingernails than toenails.1,2,6 Figure A shows an example of the clinical presentation of NSCC affecting the right thumb.
A, Nail unit squamous cell carcinoma (NSCC) tumor prior to performing a biopsy. B and C, Histopathology of NSCC biopsied from the tumor showed atypical keratinocytes in the epidermis extending to the dermis (H&E, original magnifications ×30 and ×80). Images courtesy of Adam I. Rubin, MD (Philadelphia, Pennsylvania).
Although there often is a delay in the presentation and biopsy of NSCC, no correlation has been observed between time to biopsy and rate of disease invasion and recurrence.7 Nevertheless, Starace et al7 noted that a low threshold for biopsy of nail unit lesions is necessary. It is recommended to perform a deep shave or a nail matrix biopsy, especially if matrical involvement is suspected.8 Patients should be closely followed after a diagnosis of NSCC is made, especially if they are immunocompromised or have genetic skin cancer syndromes, as multiple NSCCs can occur in the same individual.9 For instance, one report discussed a patient with xeroderma pigmentosum who developed 3 separate NSCCs. Interestingly, in this patient, the authors suspected HPV as a cause for the field cancerization, as 2 of 3 NSCCs were noted on initial histopathology to have arisen from verrucae.10