Dermatology Online Journal

Amelanotic subungual melanoma after trauma: An unusual clinical presentation
Sophia Rangwala AB, Christine Hunt MD, Gunjan Modi MD, Bhuvaneswari Krishnan MD, Ida Orengo MD
Dermatology Online Journal 17 (6): 8

Department of Dermatology, Baylor College of Medicine, Houston, Texas. srangwal@bcm.edu

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Abstract

Amelanotic subungual melanoma (SUM) is difficult to clinically diagnose owing to its rarity and variable presentation. We describe a case of a 63-year-old gentleman with an amelanotic SUM that developed after local trauma and presented as a persistent non-healing ulcer which was initially mistaken for a chronic infection. Because amelanotic SUM can mimic other lesions, the physician should have a high index of suspicion for SUM when managing atypical nail lesions to ensure prompt recognition and treatment. The prior trauma to the nail also suggests that posttraumatic inflammation may play a role in SUM development.

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Case report

A 63-year-old male was referred to the dermatology clinic for a non-healing painless wound on the nailbed of his left fifth digit (Figure 1). The patient stated that 15 months prior, his entire nail had avulsed after getting caught under a car seat, but appeared normal before the incident. Since then, the nail had not regrown. Sometimes, the exposed nailbed exuded purulent discharge. The patient had been self-treating the area with bacitracin ointment with no improvement. He was otherwise in good health and had no known family history of skin cancers.

Figure 1
Figure 1. An exposed nailbed with beefy red granulation tissue, periungual edema, and erythema extending to the proximal interphalangeal joint of the left fifth digit.

On presentation, the exposed nailbed showed beefy red granulation tissue, periungual edema, and erythema extending to the proximal interphalangeal joint. The eponychium had no visible nail growth. No purulent discharge or malodor was appreciated. There were no signs of supratrochlear or axillary lymphadenopathy.

Complete blood count and basic metabolic panel were within normal limits. Paronychia with a deep fungal or atypical mycobacterial infection was initially considered, but aerobic, anaerobic, AFB, and fungal cultures were negative. A punch biopsy of the proximal nailbed revealed a proliferation of spindle cells in the dermis accompanied by lymphocytes (Figure 2). S100 and panmelanoma (HMB 45, Melan A, and tyrosinase) immunohistochemical stains (Figure 3) were positive, whereas CD34 and cytokeratin stains were negative. These histopathology findings provided a diagnosis of amelanotic melanoma.

Figure 2	Figure 3
Figures 2 and 3. A proliferation of spindled cells in the dermis accompanied by lymphocytes.

Figure 4
Figure 4. Panmelanoma immunohistochemical stain (HMB 45, Melan A, and tyrosinase) of biopsy specimen as positive.

One month later, the patient underwent finger disarticulation at the proximal interphalangeal joint. Grossly, the sample showed a 1.6 cm x 1.2 cm ulcer of the nailbed with an underlying 1.5 x 1.0 cm dense white tumor. Microscopic examination revealed a nodular malignant melanoma with a Breslow depth of 5.0 mm and an extension down to the subcutaneous tissue (Clark level V). Also seen were a radial and vertical growth phase, a mitotic index of 5 mitotic figures per mm², perineural invasion, and tumor infiltrating lymphocytes. An in situ component was also identified adjacent to the invasive portion of the tumor. No involvement of the bone, lymphovasculature, or resection margins was noted. The cancer was pathologically staged as pT4b. After the amputation, the patient was referred to oncology for a metastatic screening. LDH was within normal range. The chest radiograph, whole body PET-CT scan, and sentinel node biopsy showed no definite evidence of metastasis. The surgical site healed well without complications. The patient remained well for 12 months, until a biopsy of an enlarged left axillary node identified metastatic melanoma. The node was dissected and a follow-up PET-CT scan 2 months ago was negative. The patient continues to have no evidence of local recurrence.

Discussion

Melanoma has the highest mortality rate of any skin cancer and the most rapidly growing incidence rate of any cancer [1]. Amelanotic melanoma, a subtype that lacks pigmentation, comprises 10 percent of melanomas and is most commonly subungual. Subungual melanoma (SUM) comprises only 1 to 3 percent of melanomas in white-skinned populations and 85 percent are initially misdiagnosed [2]. These cancers can masquerade as paronychias, pyogenic granulomas, hemangiomas, chronic infections, or squamous cell carcinomas [3]. The combination of rarity and nonspecific signs contributes to a mean diagnostic delay of 30 months. Because of the delay, SUM is usually identified at an advanced stage and associated with a poor prognosis, which may explain the 10 to 30 percent 5-year survival rate for SUM versus the 80 percent 5-year survival rate for cutaneous melanoma [4, 5]. Thus, it is crucial for physicians to have a high index of suspicion for SUM, especially if the lesion is recurrent, chronic, or resistant to treatments. A biopsy is necessary to make the diagnosis, but even microscopic findings may be insufficient. Biopsy samples should be stained for melanoma markers like S-100, HMB-45, and Melan-A in order to confirm the diagnosis.

Unlike cutaneous melanoma, SUM is not likely linked to UV exposure because the nailplate is too dense for significant light penetration. As opposed to prior assumptions, Stern et al. [6] found no UVB transmission and an average of only 1.65 percent UVA transmission though cadaver fingernails. SUM has been associated with increased nail loss [7], but it is unclear whether prior trauma to the site is a possible pathogenetic factor. In the literature, 23 to 44 percent of patients have reported local trauma preceding SUM development [8]. It remains unknown whether this association is secondary to trauma drawing attention to an area of pre-existing cancer, or to posttraumatic inflammation inducing carcinogenesis. The relationship between chronic inflammation and cancer development has already been observed in inflammatory bowel disease and colorectal carcinoma; gastroesophageal reflux disease and esophageal adenocarcinoma; and chronic skin wounds and aggressive ulcerating forms of squamous cell carcinoma. This association is likely the result of mutagenesis facilitated by increased free radicals and continuous cell proliferation in the setting of chronic inflammatory stress [9]. We believe the link established between inflammation and certain cancers might explain the onset of SUM in our patient. However, we cannot exclude the argument that the nail avulsion may have been related to a subclinical SUM weakening the nail of our patient.

Interestingly, a recent study found trauma to an already evident SUM to be a poor prognostic indicator [10]. Preliminary data suggests other prognostic indicators for SUM are similar to cutaneous melanomas [11, 12]. The most significant factors are tumor thickness (Breslow depth) and presence of ulceration, as recognized by the AJCC staging system [13, 14], followed by level of invasion (Clark level), elevated mitotic rate, and low infiltration by lymphocytes. Amelanosis also indicates poor prognosis, likely because lack of pigmentation delays diagnosis.

Conclusion

Amelanotic SUM is often difficult to diagnose because it is rare and a great masquerader. Because our case was originally mistaken for a chronic infection, it is important that the physician be suspicious for SUM when managing unusual nail lesions to ensure early recognition and prompt intervention. The prior trauma to the nail also supports the hypothesis that posttraumatic inflammation may be a significant risk factor in the carcinogenesis of SUM.

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