Amelanotic subungual melanoma presenting as a non-healing post-operative nail bed wound - A case report

INTRODUCTION

Subungual melanoma (SUM) is an uncommon subtype of cutaneous melanoma arising from the nail apparatus, accounting for approximately 2–3% of all melanoma cases.^[1,2] Despite its relatively low incidence, it is associated with a poorer prognosis compared to other cutaneous melanomas. This is largely due to delays in diagnosis and more advanced stage at presentation.^[2,3] Unlike more typical melanomas, SUM frequently presents with increased tumor thickness and a higher likelihood of regional or distant metastasis at the time of diagnosis.^[3,4]

The amelanotic variant presents a particular diagnostic challenge because it lacks the characteristic pigmentation that typically prompts suspicion. Instead, it may present as a vascular, ulcerated, or granulating lesion and is often mistaken for benign conditions such as localized infection, pyogenic granuloma, or post-operative complications.^[5-7]Consequently, misdiagnosis rates remain high, particularly outside specialist dermatological settings. This often leads to delays in appropriate management.^[2,5]

Prognosis in melanoma is strongly determined by tumor thickness (Breslow depth), ulceration, and stage at diagnosis. Increasing tumor thickness is directly associated with a higher risk of metastasis and reduced survival. This emphasizes the importance of early detection and intervention. Early biopsy of suspicious lesions remains critical in improving outcomes.^[8]

This case describes an amelanotic SUM presenting as a non-healing wound following toenail surgery (left hallux total nail avulsion [TNA]). The diagnostic challenges and clinical consequences of delayed histological assessment are highlighted.

CASE REPORT

A 61-year-old female patient was referred to the podiatric foot and ankle surgery unit with a persistent, painful lesion affecting the left hallux. The referral described a non-healing surgical site following left hallux TNA with nail matrix phenolization.

The patient reported that the initial symptoms began following trauma to the left hallux, after which the TNA was performed [Figure 1]. Despite this intervention, the wound failed to heal over a 3-month period and progressively became more painful, significantly affecting her daily activities.

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Figure 1: Clinical photograph demonstrating dystrophic changes of the distal nail unit, including partial nail plate destruction, subungual hyperkeratotic debris, and irregular nail bed granulation tissue. The nail plate appears thickened and opaque with partial onycholysis. There is focal erythema and friability of the exposed tissue. These non-specific findings may mimic benign conditions such as onychocryptosis or traumatic nail dystrophy, contributing to delayed diagnosis.

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Her past medical history was notable for treated throat cancer approximately 9 years earlier as well as diverticular disease, hiatus hernia, hypertension, and hypothyroidism. There is a family history of malignancy. She was a non-smoker and did not consume alcohol.

On clinical examination, the left hallux revealed a non-healing nail bed wound with granulation tissue, mild serous exudate, and associated malodor [Figure 2]. There were no systemic features of infection. Baseline blood investigations including inflammatory markers were within normal limits. Plain radiographs of the left foot did not demonstrate any evidence of osteomyelitis or bony abnormality [Figure 3]. A wound swab cultured Staphylococcus aureus and Corynebacterium striatum, and the patient was commenced on oral flucloxacillin 500 mg four times a day (QDS), for 7 days.

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Figure 2: Clinical photograph demonstrating a persistent non-healing nail bed lesion following total nail avulsion with phenol matricectomy. The nail plate is absent, revealing an erythematous, friable nail bed with areas of granulation tissue, focal hemorrhage, and serous exudate. Surrounding periungual tissue shows mild inflammation, and a wound swab grew Staphylococcus aureus and Corynebacterium striatum, which were treated with appropriate oral antimicrobial therapy. The chronicity and atypical appearance of the lesion initially attributed to delayed healing after chemical matricectomy, prompted further evaluation. Histopathologic analysis confirmed the diagnosis of amelanotic malignant subungual melanoma.

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Figure 3: Anteroposterior weight-bearing radiograph of the left foot obtained during evaluation of the persistent, non-healing nail bed lesion. No radiographic evidence of cortical erosion, periosteal reaction, or osteolysis is identified to suggest underlying osteomyelitis. Joint spaces are preserved, and there is no acute fracture or dislocation. These findings supported a nonosseous etiology for the chronic wound, prompting further diagnostic investigation.

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Within 4 days of initial presentation, a tissue sample was obtained under local anesthesia and sent for histopathological analysis. Over the following weeks, the patient was reviewed on multiple occasions. Although signs of acute infection improved, the wound failed to demonstrate meaningful healing. It remained persistently granulomatous with areas of slough and ongoing pain. Repeat courses of antibiotics were prescribed based on microbiology results; there was minimal clinical improvement. At 4 weeks, the lesion remained unchanged, prompting further multidisciplinary discussion [Figure 4].

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Figure 4: Clinical photograph demonstrating interval progression of a previously identified nail bed lesion with increased size and prominence of friable, erythematous tissue following total nail avulsion with phenol. The lesion exhibits irregular surface architecture, focal hemorrhage, and persistent granulation-like appearance extending across the distal nail unit. Despite prior conservative management, the rapid growth and failure to epithelialize raised concern for an underlying malignant process.

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At the multidisciplinary team review, the lesion was considered suspicious due to its atypical appearance and lack of response to standard treatment. An urgent referral to dermatology and a sarcoma center was initiated.

Histopathological examination confirmed malignant melanoma. Microscopy demonstrated dermal infiltration by atypical melanocytes with marked pleomorphism, prominent nucleoli, and a high mitotic rate (up to 6–7 mitoses/mm²).

This was in keeping with malignant melanoma in the vertical growth phase. There was extensive ulceration and necrosis. The Breslow thickness was reported as at least 2.1 mm although this was likely to be an underestimate due to involvement of the deep margin. Tumor cells were present at both deep and peripheral margins.

Immunohistochemical analysis showed strong positivity for melanocytic markers including SRY-box transcription factor 10 (SOX-10), Melan-A, and Human Melanoma Black-45 (HMB-45), confirming the diagnosis. Histopathological images were not available for inclusion; however, the diagnosis was confirmed by formal histopathological assessment and multidisciplinary team review. There was no evidence of lymphovascular or perineural invasion. The tumor was classified as malignant melanoma in the vertical growth phase with staging of at least pT3b.

The patient was subsequently referred for further staging investigations including ultrasound-guided lymph node biopsy, magnetic resonance imaging of the brain, and whole-body fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) scanning which were all clear for metastatic disease [Figure 5]. The patient remains under specialist care for ongoing oncological management and has been counseled about possible hallux amputation.

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Figure 5: Maximum intensity projection 18^F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET-CT) image of the lower extremities demonstrating focal intense tracer uptake in the left hallux (arrow), corresponding to the primary melanoma. No additional abnormal FDG-avid lesions are identified to suggest regional or distant metastatic disease.

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DISCUSSION

This case illustrates the diagnostic complexity of amelanotic SUM, particularly when it presents in the context of a plausible alternative diagnosis such as post-operative wound complications. The absence of pigmentation combined with features such as granulation tissue, exudate, and delayed healing can lead clinicians to attribute the lesion to infection or benign inflammatory processes.

SUM is recognized to present at a more advanced stage compared to other melanoma subtypes. It typically demonstrates increased tumor thickness and has poorer outcomes.^[3,4] This is largely due to delays in diagnosis which may arise from both patient-related and clinician-related factors.^[2] In the present case, the lesion was initially managed conservatively with repeated courses of antibiotics and wound care while waiting for histopathological analysis, reflecting a common clinical pathway for presumed postoperative infection.

Amelanotic melanoma further complicates diagnosis as it lacks the visual cues typically associated with melanoma. Previous studies have demonstrated that these lesions are frequently misdiagnosed as benign entities, including pyogenic granuloma, chronic paronychia, or non-healing wounds.^[5-7] As a result, diagnosis is often delayed until histopathological evaluation is performed.

A key clinical lesson from this case is that failure of a lesion to respond to appropriate treatment should prompt reconsideration of the diagnosis. Chronic non-healing wounds of the nail unit should raise suspicion for malignancy, particularly when associated with persistent granulation tissue, ulceration, or unexplained pain.

Breslow thickness remains the most important prognostic indicator in melanoma with increasing depth strongly associated with reduced survival.^[8] Tumors measuring >2 mm in thickness are associated with significantly worse outcomes, especially when ulceration and high mitotic activity are present. Unfortunately, both were identified in this case.^[8,9]

Malignant melanoma is classified into several subtypes, including superficial spreading melanoma, nodular melanoma, lentigo maligna melanoma, and acral lentiginous melanoma. Tumor progression is characterized by an initial radial growth phase followed by a vertical growth phase, the latter being associated with increased metastatic potential. The depth of invasion may also be described using Clark levels (I–V), ranging from confinement to the epidermis to invasion into subcutaneous tissue.^[6,8]

Staging of melanoma is based on the American Joint Committee on Cancer tumour–node–metastasis (TNM) classification which incorporates tumor thickness, ulceration, nodal involvement, and metastatic spread.^[8] The presence of ulceration as observed in this patient is associated with more aggressive disease and poorer prognosis. Whole-body FDG PET/CT imaging has been shown to have clinical value in staging and detecting metastatic disease in melanoma patients.^[10]

Management of SUM is primarily surgical and typically involves wide local excision or digital amputation, depending on tumor extent.^[11] Sentinel lymph node biopsy is recommended in patients with intermediate- and high-risk disease and provides important prognostic information.^[12] Systemic therapy may be indicated in advanced disease. It is suggested that acral and SUMs are less likely to harbor targetable mutations compared to other melanoma subtypes, limiting therapeutic options.^[4]

Overall survival in melanoma varies widely depending on stage at diagnosis with early-stage disease associated with favorable outcomes and advanced disease associated with significantly reduced survival.^[8] SUM continues to demonstrate poorer survival rates compared to other cutaneous melanomas largely due to delayed diagnosis and advanced disease at presentation.^[2,3]

CONCLUSION

Amelanotic SUM is an uncommon but important diagnosis that can closely resemble benign or post-operative conditions. This case highlights the need to reconsider the diagnosis in any nail bed lesion that fails to heal as expected, particularly where there is ongoing pain or persistent granulation despite appropriate treatment. Early biopsy is crucial in such cases to avoid delay and allow timely management.

Although there is no established link between SUM and a history of non-cutaneous malignancy, the presence of previous cancer and a family history of malignancy may reasonably lower the threshold for further investigation. Further work is needed to determine whether these factors influence diagnostic pathways or contribute to delays in atypical presentations.