The thumb that wouldn’t heal: A diagnostic pitfall in subungual squamous cell carcinoma

INTRODUCTION

Subungual squamous cell carcinoma (SSCC) is rare, yet the most common malignant subungual tumour, arising from the nail bed. It generally presents as a slow-growing, low-grade malignancy with a much better outlook than squamous cell carcinoma (SCC) occurring elsewhere on the skin. Delayed diagnosis often occurs due to physicians’ lack of awareness, varied clinical presentation, slow progression and the frequent presence of various benign nail conditions that mask its symptoms, often leading to misdiagnosis and delayed treatment. Very few cases have been reported in the literature. The cause of SSCC is unclear, though it is often linked to high-risk human papillomavirus (HPV), chronic trauma, inflammation or radiation. It frequently mimics benign nail conditions, but malignancy should be suspected when standard antifungal or antibiotic treatments fail. Treatment is stratified by tumour extent. Limited lesions are best managed with a tissue-sparing approach, whereas bone invasion typically necessitates digital amputation, with radiotherapy reserved for unresectable or adjuvant cases.

CASE REPORT

A 52-year-old male, farmer by occupation, presented to our outpatient department with a painful non-healing wound on the left thumb, with pus discharge, for 5 years. Pain was throbbing in nature, aggravated at night, leading to sleep disturbance. The patient had recurrent pus discharge from the left thumb, aggravating pain that was relieved with medications or drainage. He underwent multiple incision and drainage procedures, and nail avulsion on six different occasions, suspecting an ingrown nail. This was done at various medical facilities, but no biopsy or histopathology was ever performed. His medical history was unremarkable. There was no history of trauma, warts, psoriasis, immunosuppression, exposure to radiation or chemicals.

Physical examination showed onychodystrophy with yellowish discolouration of the nail plate, and subungual hyperkeratosis of the left thumb [Figure 1]. There was marked tenderness of the distal phalanx, more so on the lateral nail fold. Left axillary lymph nodes were palpable and non-tender. Onychoscopy was not done due to non-availability of the dermoscope at that time.

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Figure 1:

Onychodystrophy with yellowish discolouration of nail plate with subungual hyperkeratosis of the left thumb.

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Nail clippings for potassium hydroxide examination and fungal culture were negative. X-ray of the left hand revealed no abnormality. Ultrasonography of the axilla revealed left axillary lymphadenopathy. Magnetic resonance imaging (MRI) showed altered signal intensity in subungual soft tissue of the distal phalanx of the left thumb with cortical erosion of the lateral aspect of the distal phalanx. Thus, subungual glomus tumour, subungual wart, subungual foreign body impaction, and subungual SCC were considered as differential diagnoses. Nail bed biopsy was performed from the friable tissue after avulsion of the dystrophic nail [Figure 2]. Histopathology revealed infiltration by malignant epithelial cells arranged in nests and aggregates in the epidermis, extending into the underlying dermis. The neoplastic cells exhibited rounded nuclei with moderate amounts of basophilic cytoplasm and mild-to-moderate nuclear pleomorphism [Figure 3] depicts infiltration of malignant squamous cells into the underlying dermis (red arrow), thus confirming the diagnosis of SCC. ¹⁸F-fludeoxyglucose positron emission tomography scan showed low-grade metabolism involving the distal phalanx of the left thumb with a metabolically inactive left axillary lymph node (reactive lymphadenopathy). The patient was subsequently referred to a higher oncologic centre where he underwent distal interphalangeal joint disarticulation combined with local flap reconstruction [Figure 4]. Post-surgical management included antibiotics and routine wound care, which led to the resolution of reactive lymphadenopathy. The patient remains under regular follow-up and reports no active symptoms or signs of recurrence until now.

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Figure 2:

Friable subungual tissue and nail bed biopsy (Blue arrow).

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Figure 3:

Section showing infiltration of malignant squamous cells into the underlying dermis, with neoplastic cells showing round nuclei, basophilic cytoplasm, and mild to moderate nuclear polymorphism (red arrows) (H&E, ×100). H&E: Hematoxylin and eosin.

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Figure 4:

Distal interphalangeal joint disarticulation of the left thumb with flap reconstruction shown immediately post-surgery (left) and after 6 weeks (right).

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DISCUSSION

SSCC primarily occurs in men between 50 and 69 years of age, most commonly involving the thumb and index fingers.^[1-3] Delayed diagnosis is common due to a low index of clinical suspicion, and depends on whether the possibility is considered at all. Its initial presentation often resembles a wide range of conditions, including paronychia, onychomycosis, verruca, pyogenic granuloma, glomus tumour, chronic osteomyelitis, malignant melanoma, fibroma and herpetic whitlow.^[4] Definitive diagnosis requires histopathological confirmation through biopsy. In our case, the MRI imaging gave a presumptive diagnosis of glomus tumour, which may be misleading.

Most reported cases of SSCC involve the thumb or fingers, though toenail involvement has also been described.^[5] Trauma is therefore considered a probable etiologic factor. Other proposed factors include chronic infections, repeated chemical or mechanical microtrauma, congenital ectodermal dysplasia, prior exposure to radiation, tar, arsenic, immunosuppression and HPV infection.^[6,7] A strong association with HPV, particularly types 16, 26 and 56, has been documented, with HPV DNA being detected in 60–90% of cases and over 60% being HPV 16. However, as hand warts are common and SSCC rare, additional cofactors are likely contributory.^[3] In the present case, no history or clinical evidence of genital warts or other known risk factors was noted.

SSCC is a low-grade malignancy with low metastatic potential, but it is often difficult to diagnose. Palpable axillary nodes, as in our patient, usually regress after tumour removal. Bone invasion typically results from delayed diagnosis. Histopathology typically shows dysplastic stratified squamous epithelium with focal malignant infiltration into subepithelial tissue, showing nuclear pleomorphism, atypia, abnormal mitoses and keratin formation.^[3]

As SSCC is rare, there are no standard treatment guidelines; however, surgical excision with or without digital amputation is required in most cases. Wide local excision is preferred due to the low incidence of recurrence. Other treatment modalities that have been tried are simple excision, wide local excision with flap coverage, Mohs microscopic surgery,^[1] or radiation therapy ^[8]. Therapies commonly used for in situ cutaneous SCC (including electrodessication, cryotherapy, CO₂ laser and topical 5-fluorouracil) are generally avoided in subungual SCC due to its typically invasive nature at presentation and the physical barrier posed by the nail plate, which hinders effective therapeutic delivery.^[1] In our case, amputation of the distal phalanx with flap coverage was performed.

Sentinel lymph node biopsy (SLNB) is a procedure widely used in breast cancer and melanoma management, for an early detection of lymphatic spread.^[9] It is generally not considered part of the surgical algorithm for management of subungual disease as the nail bed is a low-risk location for SCC. Our patient presented with superficially invasive SCC of the nail bed; thus was not considered for SLNB.

CONCLUSION

Maintaining a high index of suspicion, ensuring early diagnosis, and initiating prompt treatment are key to improving outcomes and minimising disease progression in cases with subungual SCC.