Recognition of malignant melanoma by monoclonal antibody HMB‐45. An immunohistochemical study of 200 paraffin‐embedded cutaneous tumors

Abstract

Antibodies to S-100 protein have been used widely as markers of malignant melanoma, despite abundant evidence that they are non-specific for this neoplasm. Hence, alternatives to these reagents are desirable in diagnostic dermatopathology. We evaluated the characteristics of a new monoclonal antibody (HMB-45) which does have putative specificity for melanoma, and compared it with a polyclonal anti-S-100 reagent in immunohistochemical staining of 67 melanomas of the skin and 133 non-melanomatous cutaneous neoplasms. All specimens were formalin-fixed and paraffin-embedded, and were studied with the avidin-biotin-peroxidase complex technique. HMB-45 labelled 62 of 67 melanomas, while anti-S-100 recognized all tumors of this type. On the other hand, S-100 also was expressed by 15 of the non-melanocytic neoplasms, all 133 of which were HMB-45-negative. The only cases of melanoma that were missed by the latter reagent were of the spindle-cell type. Hence, HMB-45 was 100% specific and 93% sensitive, relative to a diagnosis of malignant melanoma in paraffin sections. Epithelioid and small-cell neoplasms are reliably recognized by this antibody, but it would appear that spindle-cell melanomas must be detected by other immunohistochemical means.

Unusual variants of malignant melanoma

“…27,28 The tumor cells of desmoplastic melanoma decorate with antibodies to S100 protein in an almost ubiquitous fashion, 6 with antibodies to neuron-specific enolase in 40-96% of cases, 6,17 and with HMB-45 in roughly 20% of cases 6 ( Figure 7). Typically, HMB-45 either gives negative results 29 or shows differential staining patterns in which tumor cells are weakly positive superficially, with negative results in the deep portions of the tumor. 30 As previously mentioned, this staining pattern is different from that observed in the blue nevus with atypia seen in elderly patients.…”

Immunohistochemical characteristics of melanoma

“…5,11 The reported sensitivity of HMB45 for melanoma ranges from 69% to 93%, 5,6,[11][12][13][14][15][16][17] and expression is maximal in primary melanoma specimens (77-100%) and less in metastases (58-83%). 6,[11][12][13][14][15][16][17] Staining may be patchy, and melanoma cells are less diffusely positive than with other markers. 11,14,15,17 There may be strong staining with HMB45 in the epidermal component of a primary melanomas with gradually weaker staining in the deeper vertical growth phase.…”

“…5,6,14 ( Figure 1) There is some dispute as to whether HMB45 is less sensitive in amelanotic melanomas. 5,11 HMB45 is very specific for melanomas and has been reported to be absent from nonmelanocytic tumors by Wick et 7,11,12,13 However, HMB45 is expressed in PEComas (i.e. angiomyolipomas, lymphangiomyomatosis and pulmonary Ôsugar' tumors), sweat gland tumors, meningeal melanocytomas, clear cell sarcoma of the tendons and aponeuroses, some ovarian steroid cell tumors and some breast cancers as well as renal cell carcinomas with a t(6,11)(p21;q12) translocation.…”

Atypical fibroxanthoma

“…HMB45 and MART-1 are melanocyte-specifi c markers, and these antibodies recognize gp100 and PMel17, respectively (SmithZagone MJ et al 2004). However, it should be remembered that some poorly differentiated squamous cell carcinomas may not express cytokeratin, and S100 and HMB45 are not detectable in all malignant melanoma cases (Lodding P et al 1990;Wick MR et al 1988). Furthermore, dendritic cells within AFX may express S100 (Longacre TA et al 1993;Ricci A Jr et al 1988;Winkelmann RK and Peters MS, 1985).…”