Immunophenotyping of amelanotic
melanoma. A case report
V. Lazarevic, J. Tiodorovic, D. Tiodorovic-Zivkovic, M. Stanojevic,
D. Popovic and A. Jankovic
- S U M M A R Y
Amelanotic malignant melanoma (AMM) is a subtype of cutaneous melanoma with little or no pigment upon visual inspection. The lack of pigmentation is the reason for late diagnosis of lesions and a poor prognosis. We report a case of a 55-year-old female with an AMM diagnosed by immunophenotyping. Monoclonal antibodies S-100, HMB-45, and antibodies to cytokeratin were used. Our patient underwent a wide local excision (a 2 cm wide margin) 2 years ago. So far there are no signs of a recurrence. In doubtful cases, immunophenotyping with monoclonal antibodies HMB-45 and S-100 is important for confirming the correct diagnosis of AMM.
Introduction
KEY WORDS
melanoma, amelanotic, immunophenotyping
Amelanotic malignant melanoma (AMM) is a subtype of cutaneous melanoma with little or no pigment. True AMMs are rare: there may be some pigmentation at the periphery of the lesion. AMMs represent 2-8% of all malignant melanomas (1). The clinical diagnosis can be difficult because AMM may mimic different benign and malignant melanotic and nonmelanotic lesions. Because of the lack of pigmentation, amelanotic melanomas are often diagnosed in an advanced stage and have a poor prognosis.
Case report
We report the case of a 55-year-old female with a lightly erythematous, slightly infiltrated macula on
her right shoulder. The patient was not able to state how long the lesion had been present or whether it had undergone any changes. She denied itching or bleeding, as well as a personal or family history of melanoma. There were no enlarged lymph nodes on examination, and routine laboratory investigations did not reveal abnormalities. The lactate dehydro-genase level was normal, and either Bowen's disease or basal cell carcinoma were suggested diagnoses.
A biopsy was taken, embedded in paraffin, and stained with hematoxylin-eosin. Immunophenot-yping was done with immunoalkaline phosphatase, using the APAAP method. Monoclonal antibodies S-100, HMB-45, and antibodies to cytokeratin (DAKO) were used. The melanocyte cytoplasm was stained
Figure 1. Tumor cells express HMB-45, (APAAP, 80x).
red with S-100 and HMB-45. Cytokeratin antibodies were used to exclude possible carcinoma.
Discussion
Due to the lack of pigment, AMM is often misdiagnosed as dermatitis, Spitz nevus, Bowen's disease, su-
Figure 2. Tumor cells express S-100 (APAAP, 80x).
perficial basal cell carcinoma, squamous cell carcinoma, or a secondary inclusion in the skin (2).
Clinical symptoms such as peripheral pigmentation, ulceration, and asymmetry are usually not helpful in diagnosis of AMM (l).
Any clinical subtype of cutaneous melanoma may be amelanotic, although it is more common in subungual tumors and desmoplastic melanoma (3). In our case, biopsy revealed superficial spreading melanoma invading the dermis (tumor thickness measured 1.2 mm).
HMB-45 can be important in the evaluation of neo-plastic lesions suspected to be melanomas (4). Immuno-phenotyping in our case showed red deposits in the melanocyte cytoplasm when stained with HMB-45 (Figure 1) and S-100 (Figure 2). Negative staining for cytokeratin excluded the diagnosis of basal cell carcinoma. These findings supported the diagnosis of an amelanotic melanoma.
The lack of pigmentation in AMM is due to the rapid growth of the tumor and to the dedifferentiation of malignant melanocytes (2). The melanoma cells contain inactive tyrosinase, and thus the melanin synthesis is suppressed and the cells are amelanotic (5).
AMM has a similar natural history to pigmented malignant melanoma; the diagnosis is delayed and it is usually recognized in a more advanced stage (2). In our case, the localization of the lesion and the absence of symptoms prevented the patient from seeking medical advice sooner.
The prognosis of primary cutaneous AMM is similar to that of the pigmented lesion and is determined by tumor thickness, location, and patient age, as well as sex (6).
Metastatic melanoma not uncommonly presents as one or more amelanotic lesions even when the primary tumor was pigmented (4). Metastases may include both pigmented and non-pigmented lesions in a zosteriform pattern (7).
In doubtful cases, immunophenotyping with monoclonal antibodies HMB-45 and S-100 is important for revealing the diagnosis.
R E F E R E N C E S
1.	Pizzichetta MA, Talamini R, Stanganelli I, Puddu P, Bono R, Argenziano G, et al. Amelanotic/ hypomelanotic melanoma: clinical and dermoscopic features. Br J Dermatol, 2004; 150: 1117-24.
2.	Colver G, editor. Skin cancer: a practical guide to management. 1st ed. London: Martin Dunitz Ltd, 2002.
3.	Koch SE, Lange JR. Amelanotic melanoma: the great masquerader. J Am Acad Dermatol, 2000; 42: 731-4.
4.	Perniciaro C. Dermatopathologic variants of malignant melanoma. Mayo Clin Proc, 1997; 72: 2739.
5.	Ancans J, Thody AJ. Activation of melanogenesis by vacuolar type H+-ATP-ase inhibitors in amelanotic, tyrosinase positive human and mouse melanoma cells. FEBS Letters, 2000; 478: 57-60.
6.	Schuchter L, Schultz DJ, Synnestvedt M, Trock BJ, Guerry D, Elder ED, et al. A prognostic model for predicting 10-year survival in patients with primary melanoma. Ann Intern Med, 1996; 125: 369-75.
7.	North S, Mackey JR, Jensen J. Recurrent malignant melanoma with zosteriform metastases. Cutis, 1998; 62: 143-6.
AUTHORS' Viktor Lazarevic, MD, Clinic for Dermatovenerology, Niš Clinical Center, ADDRESSES Bul. Zorana Djindjica 48,18 000 Niš, Serbia
Jelica Tiodorovic, MD, Professor Danica Tiodorovic-Živkovic, MD, same address
Milenko Stanojevic, MD, Professor of dermatovenereology, same address Danijela Popovic, MD, same address Aleksandar Jankovic, MD, same address