What is the role of immunochemistry in the workup of oral malignant melanoma?

Updated: Jan 31, 2020
  • Author: Elizabeth Ann Bilodeau, DMD, MD, MSEd; Chief Editor: Jeff Burgess, DDS, MSD  more...
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Answer

Melanomas have a number of histopathologic mimics, including poorly differentiated carcinomas, PEComas (perivascular epithelioid cell tumors), and anaplastic large-cell lymphomas. Balloon cell, small cell, and desmoplastic variants of melanoma may be primary or metastatic in the oral mucosa. Differentiation requires the use of immunohistochemical (IHC) techniques to highlight intermediate filaments or antigens specific for a particular cell line. Proliferative markers such as Ki-67, p53, and bcl-2 are useful in separating benign from malignant melanocytic lesions, with Ki-67 being the most useful.

Amelanotic melanomas can resemble many different mesenchymal neoplasms, and immunohistochemical stains must be used for diagnosis. The astute pathologist will look for evidence of a lymphocytic reaction within the connective tissue and an increased number of melanocytes in the basal cell layer as an indication to request immunohistochemical staining.

Leukocyte common antigen and Ki-1 are used to identify the lymphocytic lesions. Cytokeratin markers, often cocktails of high– and low–molecular-weight cytokeratins, can be used to help in the identification of epithelial malignancies.

S-100 protein and homatropine methylbromide (HMB-45) antigen positivity are characteristic of, although not specific for, melanoma. S-100 protein is frequently used to highlight the spindled, more neural-appearing melanocytes, whereas HMB-45 is used to identify the round cells (see the image below). Melanomas, unlike epithelial lesions, are identified by using vimentin, a marker of mesenchymal cells. 

This image depicts tumor cell cytoplasmic homatrop This image depicts tumor cell cytoplasmic homatropine methylbromide (HMB-45) immunohistochemical staining (original magnification, ×40). The diagnosis is oral melanoma.

Microphthalmic-associated transcription factor (MITF), tyrosinase, and melanoma antigen recognized by T-cells 1 (MART-1)/Melan-A immunostains have been used to highlight melanocytes. See the image below. The inclusion of these stains in a panel of stains for melanoma may be beneficial. The use of at least two different immunostains is recommended for diagnosis.

MITF has value in decorating amelanotic melanomas and desmoplastic melanomas when other immunohistochemical stains have failed. S-100 protein and tyrosinase show the highest percentage of positivity. MART-1/Melan-A is reported to be much more useful than HMB-45 for highlighting melanocytic tumors, but because it is a marker of melanocyte lineage, benign lesions such as melanocytic nevi also stain.

This image depicts both nuclear and cytoplasmic MI This image depicts both nuclear and cytoplasmic MITF (melanocyte-inducing transcription factor) immunohistochemical staining (original magnification 20x). The diagnosis is oral melanoma.

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