Brown-Gray Longitudinal Melanonychia in a Young Adult: What Lies Beneath?

Clinical Findings A 27-year-old man presented with a 2-month history of onycholysis and longitudinal melanonychia affecting the right second finger. He denied any history of trauma or similar changes in other nails. His medical history was notable for an in situ squamous cell carcinoma on the proximal nail fold of the same finger, which had been treated with topical 5-fluorouracil (applied twice daily) for 3 months, concluding 2 months before presentation. Clinical examination revealed a 2 mm homogeneous brown-gray longitudinal melanonychia associated with distal V-shaped onycholysis Figure 1A. Dermoscopic evaluation demonstrated irregular blue-gray bands, small distal splinter hemorrhages, and, on frontal view, pigmentation involving the lower two-thirds of the nail plate, with an irregular border of the ventral plate Figure 1B.Figure 1: A. Clinical view: 2 mm homogeneous brown-gray longitudinal melanonychia associated with distal V-shaped onycholysis. B. Dermoscopic view: irregular blue-gray bands, small distal splinter hemorrhages. C. Intraoperative dermoscopic view: 2 mm whitish structureless area on the distal nail bed, along with a longitudinal light brown band of the nail bed, without involvement of the nail matrixA nail biopsy was performed, and following nail avulsion, a 2 mm whitish papule was observed on the distal nail bed, along with longitudinal light brown pigmentation of the nail bed, without involvement of the nail matrix. Intraoperative dermoscopy showed a whitish, structureless area and longitudinal brown bands Figure 1C. Histological Findings An excisional biopsy was performed, and histopathological examination revealed parakeratosis, marked papillomatosis, and full-thickness dysplastic squamous epithelium characterized by nucleomegaly, anisokaryosis, loss of polarity, and the presence of mitotic figures Figures 2 and 3.Figure 2: H&E stain (20× magnification) keratinocytes with abundant cytoplasm and visible desmosomes. Nuclei are markedly hyperchromatic with evidence of anisokaryosisFigure 3: H&E stain (40× magnification) keratinocytes with abundant eosinophilic cytoplasm, multinucleation, nuclear hyperchromasia, and anisokaryosis—features consistent with nuclear atypiaWhat Is Your Diagnosis? Recurrent squamous cell carcinoma in situ of the nail manifesting as longitudinal melanonychia. Diagnosis Squamous cell carcinoma of the nail apparatus (SCCU) is a rare, slow-growing malignant tumor, usually originating under the nail plate and with potential for bone invasion.1,2 It accounts for approximately 14 cases per 50,000 dermatological consultations and constitutes 90% of malignant neoplasms of the hand and nail, with few cases of metastasis described (2%–3%).1,3 The peak incidence occurs between 50 and 69 years of age with a male predominance (2:1 ratio).3 The main risk factor is chronic infection by high-risk human papillomavirus (HPV), implicated in 60% of cases, especially serotype 16 (75%).3 Up to one-third of patients with SCCU have a history of genital HPV infection, suggesting possible genital–digital transmission as a pathogenic pathway, since serotype 16 is also common in genital warts.2,3 Other risk factors include chronic trauma, sun exposure, carcinogens such as arsenic, and immunosuppression.1 SCCU is characterized by an insidious evolution, which leads to misdiagnosis and late presentations, which is why it has been called “the great imitating nail tumor.”1,4 It can involve any part of the nail unit, including periungual tissues, nail plate, and nail bed.1 It is usually located in the lateral folds, with hyperkeratotic or papillary growth.1 In advanced stages, it may present with onycholysis, ulceration, and erosion of the nail bed.4 Its evolution varies from benign lesions to aggressive forms, which highlights the importance of follow-up in persistent or recurrent nail lesions.2 Subungual SCCU poses a diagnostic challenge, as it simulates multiple clinical entities, such as infections, inflammations, or benign tumors.1 Among the most relevant differential diagnoses are HPV warts, which manifest as hyperkeratotic exophytic papules or nodules, even affecting the nail bed.1 Subungual melanoma is crucial to rule out, especially in cases of longitudinal melanonychia or onychodystrophy, due to its overlapping clinical presentation.1,4 Other benign lesions that may be mistaken for SCCU include onychopapilloma, which may show erythronychia or longitudinal pigmentation, and onychomatricoma, characterized by subungual hyperkeratosis, lamina pigmentation, and striations that mimic SCCU or melanoma.5 Histopathological diagnosis is crucial.1 Histologically, squamous cell carcinoma is characterized by a variable degree of irregular and incomplete keratinization and superficial ulceration.1 A high degree of atypia is observed with large, hyperchromatic nuclei of basal and spinous cells, unicellular necrosis, and pathological mitosis with frequent keratin pearls.1 The epidermis shows vacuolated superficial keratinocytes with pyknotic raisin-shaped nuclei. In the late stage, deep bone invasion is observed.1 Invasive SCCU demonstrates marked cytological atypia and infiltration, contrasting with the confined, noninvasive nature of SCCU in situ.1 Conclusion SCCU, the great imitator, must always be kept in mind when faced with any chronic, pigmented nail alteration, since its ability to simulate benign entities such as warts, onychopapilloma, or even subungual melanoma, makes its diagnosis challenging. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.