Journal of Cytology
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Year : 2014  |  Volume : 31  |  Issue : 4  |  Page : 207-209
Cytodiagnosis of epithelioid malignant melanoma (amelanotic) and diagnostic dilemmas

Department of Pathology, Medical College, Kolkata, West Bengal, India

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Date of Web Publication10-Feb-2015


Melanoma is an aggressive neoplasm, and early diagnosis can reduce mortality in such patients. Diagnosis may be delayed in amelanotic tumors. We present one such case, a 35-year-old lady with a rapidly growing mass over the right angle of mandible. Fine-needle aspiration cytology was done, and smears showed discretely arranged large epithelioid cells with high N:C ratio, prominent single to multiple nucleoli. Occasional binucleated and multinucleated tumor giant cells were also noted. Poorly differentiated carcinoma, high-grade non-Hodgkin lymphoma, amelanotic melanoma, and pleomorphic sarcoma were included as differential diagnoses. Immunocytochemistry (ICC) revealed Melan-A/MART-1 positivity in some cells and S-100 positivity in most tumor cells. Desmin, pancytokeratin, and leukocyte common antigen were negative. Based on cytomorphological features and ICC findings, a diagnosis of epithelioid variant of amelanotic melanoma was rendered. Later on, true cut biopsy and histologic examination of excised specimen and adjunct immunohistochemistry with positive Melan-A and S-100 confirmed the diagnosis.

Keywords: Amelanotic epithelioid melanoma; differential diagnoses; fine-needle aspiration cytology; immunocytochemistry

How to cite this article:
Mondal SK, Mondal PK, Dutta SK. Cytodiagnosis of epithelioid malignant melanoma (amelanotic) and diagnostic dilemmas. J Cytol 2014;31:207-9

How to cite this URL:
Mondal SK, Mondal PK, Dutta SK. Cytodiagnosis of epithelioid malignant melanoma (amelanotic) and diagnostic dilemmas. J Cytol [serial online] 2014 [cited 2022 Sep 27];31:207-9. Available from:

   Introduction Top

Melanoma is a malignant neoplasm of melanocytes and is uncommon in India. Although it comprises only 3-5% of all skin cancers, it is responsible for approximately 75% of all deaths from skin cancers. [1] Though the common age of the tumor is 50 years and above, it can occur in all ages and is 20 times more common in whites than blacks. [2]

Malignant melanoma is diagnosed clinically by ABCDE mnemonic that is asymmetry, irregular border, uneven color, diameter over 6 mm, and evolving over time. [3] An early diagnosis may be done by fine-needle aspiration cytology (FNAC). Cytomorphology shows mixture of epithelioid, spindle, plasmacytoid, and bizarre cells. The cells show malignant features along with melanin pigment either in cells or background. However, biopsy remains the gold standard for both diagnosis and prognosis by measuring the depth of lesion-Breslow thickness. [4]

The cytodiagnosis becomes challenging when only one type of cells is found and is devoid of melanin pigment, that is amelanotic type. It may mimic small cell anaplastic carcinoma, non-Hodgkin lymphoma (NHL), undifferentiated carcinoma, epithelioid sarcoma, or even neuroendocrine carcinoma. This is an important reason for the delay in diagnosis and treatment in these tumors. We present one such case of primary cutaneous melanoma (amelanotic) which cytologically showed only bizarre malignant epithelioid cells without melanin pigment, thus creating a diagnostic dilemma.

   Case Report Top

A 35-year-old lady presented with a rapidly growing mass (6 cm × 5 cm) near right angle of mandible. Clinically, the mass was firm, angry-looking, with surface ulcerations. There was no fixity to deeper structures or any lymphadenopathy. Clinically, it appeared as malignant parotid tumor [[Figure 1]a]. Routine investigations were within normal limits.
Figure 1: Ulcerated globular mass (6 cm × 5 cm) over angle of right mandible (b) Smear shows pleomorphic cells with bi and multi nucleated cells (MGG ×400) (c) Smear shows pleomorphic cells with eccentric nuclei, prominent nucleoli, and pseudoinclusion in inset (Pap ×400) (d) Some tumor cells are positive for Melan-A/Mart-1 (IHC, ×400)

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Fine-needle aspiration cytology smears showed epithelioid cells arranged discretely with high N:C ratio, prominent single to multiple eosinophilic nucleoli and pseudoinclusions. Occasional binucleated and multinucleated tumor giant cells were seen. Few cells had eccentric nuclei [[Figure 1]b and c]. Features were suggestive of an undifferentiated malignant neoplasm. Epithelioid melanoma (amelanotic), poorly differentiated carcinoma, high grade NHL, epithelioid sarcoma were kept in differential diagnoses. Immunocytochemistry (ICC) was advised.

On ICC, some tumor cells were positive for Melan-A/MART-1 [[Figure 1]d] while most were positive for S-100; but pancytokeratin, leukocyte common antigen, and desmin were negative. Based on these findings, cytodiagnosis of epithelioid variant of malignant melanoma (amelanotic) was rendered.

Subsequently, surgical resection of the mass was done and sent for histopathology. Grossly, the mass was globular, measuring 5.3 cm × 4.4 cm and attached to the skin. Adjoining parotid gland was free. Cut surface was whitish solid, with spotty areas of hemorrhage. Microscopic examination showed a tumor arising from the epidermis and was composed of the epithelioid type of malignant cells devoid of melanin pigment in sheets and alveolar pattern at some places. These cells had high N:C ratio and large single or more eosinophilic nucleoli. A few binucleated and occasional multinucleated cells were also noted [[Figure 2]a and b]. The mitotic count was high. The tumor exhibited junctional activity. Focal areas of necrosis and chronic inflammatory cell infiltrate were seen. Immunohistochemistry (IHC) revealed Melan-A and S-100 positivity in tumor cells. A final diagnosis of amelanotic melanoma (epithelioid), Clark's level V was established [[Figure 2]c and d]. This corroborated with previous ICC findings.
Figure 2: (a) Pleomorphic epithelioid cells with high N:C ratio (H and E, ×100) (b) Prominent nucleoli and occasional binucleated cells (H and E, ×400) (c) Tumor cells showing strong immunoreactivity with Melan-A (IHC, ×400), (d) Tumor cells showing strong nuclear and cytoplasmic reactivity with S-100 (IHC, ×400)

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   Discussion Top

Malignant melanoma is an aggressive neoplasm with early metastasis to lymph nodes. Several cytologic patterns have been identified in materials obtained by FNAC of metastatic melanomas such as pleomorphic, carcinomatous, spindle cell, myxoid, lymphomatous, anaplastic, and clear cell patterns. Due to its varied morphological types, a diagnosis may be delayed which is more for amelanotic types. [5] Amelanotic melanoma is used for both true amelanotic lesions with no pigmentation and lesions with minimal residual pigment. The amelanotic lesions are usually of the nodular type and are highly undifferentiated. [6],[7] For the above-mentioned reasons, most cases of amelanotic melanomas present at a later stage, though early lesions have also been described. [8] In men, these are commonly found in the trunk while in women these are found commonly in lower limbs. The lady in this case presented with a lesion in the head-neck region at an advanced stage.

In the present case while reporting FNAC, the diagnosis of epithelioid melanoma (amelanotic) was favored over other differential diagnoses (NHL, anaplastic small cell carcinoma, and epithelioid sarcoma) because the tumor cells were large, showed discrete arrangements, eccentric nuclei in some cells, occasional multinucleation, single to multiple eosinophilic nucleoli, nuclear pseudoinclusions/apitz bodies (considered characteristic for melanoma), and basophilic cytoplasm. Neuroendocrine carcinoma comes as a differential diagnosis in some melanoma cases, but the morphology of this case was different and hence neuroendocrine marker was not put in the ICC panel. Confirmed opinion could only be given with the help of ICC panel of markers. Early diagnosis remains a cornerstone of management of melanomas and ancillary tests like cytochemistry (Masson Fontana stain), ICC, electron microscopy (EM) etc., can clinch the diagnosis. [8]

In present day practice, ICC is favored due to its specificity, easy availability, and lower cost compared to EM. Of the various ICC/IHC markers used to diagnose melanomas, S-100 is most sensitive (100%) but least specific. Both Melan-A and HMB-45 are equally specific, but Melan-A is more sensitive than HMB-45. [9],[10] In the present case, Melan-A was preferred because of these reasons and it is also cheaper. Cytodiagnosis with the help of ICC can rapidly diagnose problematic cases like amelanotic melanoma and reduce the morbidity and mortality in these patients.

   References Top

Sharma K, Mohanti BK, Rath GK. Malignant melanoma: A retrospective series from a regional cancer center in India. J Cancer Res Ther 2009;5:173-80.  Back to cited text no. 1
Shenenberger DW. Cutaneous malignant melanoma: A primary care perspective. Am Fam Physician 2012;85:161-8.  Back to cited text no. 2
Rigel DS, Friedman RJ, Kopf AW, Polsky D. ABCDE - An evolving concept in the early detection of melanoma. Arch Dermatol 2005;141:1032-4.  Back to cited text no. 3
Balch CM, Gershenwald JE, Soong SJ, Thompson JF, Atkins MB, Byrd DR, et al. Final version of 2009 AJCC melanoma staging and classification. J Clin Oncol 2009;27:6199-206.  Back to cited text no. 4
Gualandri L, Betti R, Crosti C. Clinical features of 36 cases of amelanotic melanomas and considerations about the relationship between histologic subtypes and diagnostic delay. J Eur Acad Dermatol Venereol 2009;23:283-7.  Back to cited text no. 5
Cheung WL, Patel RR, Leonard A, Firoz B, Meehan SA. Amelanotic melanoma: A detailed morphologic analysis with clinicopathologic correlation of 75 cases. J Cutan Pathol 2012;39:33-9.  Back to cited text no. 6
Wain EM, Stefanato CM, Barlow RJ. A clinicopathological surprise: Amelanotic malignant melanoma. Clin Exp Dermatol 2008;33: 365-6.  Back to cited text no. 7
Oiso N, Yoshida M, Kawara S, Kawada A. Amelanotic vulvar melanoma with intratumor histological heterogeneity. J Dermatol 2010;37:537-41.  Back to cited text no. 8
Blessing K, Sanders DS, Grant JJ. Comparison of immunohistochemical staining of the novel antibody melan-A with S100 protein and HMB-45 in malignant melanoma and melanoma variants. Histopathology 1998;32:139-46.  Back to cited text no. 9
Sheffield MV, Yee H, Dorvault CC, Weilbaecher KN, Eltoum IA, Siegal GP, et al. Comparison of five antibodies as markers in the diagnosis of melanoma in cytologic preparations. Am J Clin Pathol 2002;118:930-6.  Back to cited text no. 10

Correspondence Address:
Santosh Kumar Mondal
"Teenkanya Complex", Flat 1B, Block, 204 RN Guha Road, Dumdum, Kolkata - 700 028, West Bengal
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0970-9371.151134

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