Dermatology Online Journal
Amelanotic subungual melanoma after trauma: An unusual clinical presentation
- Author(s): Rangwala, Sophia
- Hunt, Christine
- Modi, Gunjan
- Krishnan, Bhuvaneswari
- Orengo, Ida
- et al.
Amelanotic subungual melanoma after trauma: An unusual clinical presentationDepartment of Dermatology, Baylor College of Medicine, Houston, Texas. firstname.lastname@example.org
Sophia Rangwala AB, Christine Hunt MD, Gunjan Modi MD, Bhuvaneswari Krishnan MD, Ida Orengo MD
Dermatology Online Journal 17 (6): 8
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.
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. 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. 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.
Melanoma has the highest mortality rate of any skin cancer and the most rapidly growing incidence rate of any cancer . 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 . These cancers can masquerade as paronychias, pyogenic granulomas, hemangiomas, chronic infections, or squamous cell carcinomas . 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.  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 , 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 . 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 . 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 . 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.
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.
References1. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer statistics, 2009. CA Cancer J Clin. 2009 Jul-Aug;59(4):225-49. [PubMed]
2. Gosselink CP, Sindone JL, Meadows BJ, Mohammadi A, Rosa M. Amelanotic subungual melanoma: a case report. J Foot Ankle Surg. 2009 Mar-Apr;48(2):220-4. [PubMed]
3. Shukla VK, Hughes LE. Differential diagnosis of subungual melanoma from a surgical point of view. Br J Surg. 1989 Nov;76(11):1156-60. [PubMed]
4. Rigby HS, Briggs JC. Subungual melanoma: a clinico-pathological study of 24 cases. Br J Plast Surg. 1992 May-Jun;45(4):275-8. [PubMed]
5. Metzger S, Ellwanger U, Stroebel W, Schiebel U, Rassner G, Fierlbeck G. Extent and consequences of physician delay in the diagnosis of acral melanoma. Melanoma Res. 1998 Apr;8(2):181-6. [PubMed]
6. Stern DK, Creasey AA, Quijije J, Lebwohl MG. UV-A and UV-B penetration of normal human cadaveric fingernail plate. Arch Dermatol. 2011 Apr;147(4):439-41. Epub 2010 Dec 20. http://www.ncbi.nlm.nih.gov/pubmed/21173303 [PubMed]
7. Harrington P, O'Kelly A, Trail IA, Freemont AJ. Amelanotic subungual melanoma mimicking pyogenic granuloma in the hand. J R Coll Surg Edinb. 2002 Aug;47(4):638. [PubMed]
8. Mohrle M, Hafner HM. Is subungual melanoma related to trauma? Dermatology. 2002;204(4):259-61. [PubMed]
9. Mantovani A, Allavena P, Sica A, Balkwill F. Cancer-related inflammation. Nature. 2008 Jul 24;454(7203):436-44. [PubMed]
10. Bormann G, Marsch WC, Haerting J, Helmbold P. Concomitant traumas influence prognosis in melanomas of the nail apparatus. Br J Dermatol. 2006 Jul;155(1):76-80. [PubMed.]
11. O'Leary JA, Berend KR, Johnson JL, Levin LS, Seigler HF. Subungual melanoma. A review of 93 cases with identification of prognostic variables. Clin Orthop Relat Res. 2000 Sep;(378):206-12. [PubMed]
12. Heaton KM, el-Naggar A, Ensign LG, Ross MI, Balch CM. Surgical management and prognostic factors in patients with subungual melanoma. Ann Surg. 1994 Feb;219(2):197-204. [PubMed]
13. Balch CM, Soong SJ, Gershenwald JE, Thompson JF, Reintgen DS, Cascinelli N, Urist M, McMasters KM, Ross MI, Kirkwood JM, Atkins MB, Thompson JA, Coit DG, Byrd D, Desmond R, Zhang Y, Liu PY, Lyman GH, Morabito A. Prognostic factors analysis of 17,600 melanoma patients: validation of the American Joint Committee on Cancer melanoma staging system. J Clin Oncol. 2001;19:3622-34. [PubMed]
14. Tan KB, Moncrieff M, Thompson JF, McCarthy SW, Shaw HM, Quinn MJ, Li LX, Crotty KA, Stretch JR, Scolyer RA. Subungual melanoma: a study of 124 cases highlighting features of early lesions, potential pitfalls in diagnosis, and guidelines for histologic reporting. Am J Surg Pathol. 2007;31:1902-12. [PubMed]
© 2011 Dermatology Online Journal