HMB-45

Synonyms: Melanosome specific antigen, gp100

by Assia Bassarova

Background

Melanosome specific antigen (MSA) has been identified as an 10 kDa oncofetal oligosaccharide side chain of a 10 kDa glycoprotein. The antigen is detected by the monoclonal antibody HMB-45 (Human Melanoma, Black). The antigen is localized mainly on stages II and III melanosomes in the melanocytes from fetuses and infants. HMB-45 appears mainly on the immature melanosomes during melanogenesis in both neoplastic and non-neoplastic melanocytes regardless of their tyrosinase activity.
The monoclonal antibody HMB-45 has been known as a highly specific marker for malignant melanoma.

Staining in normal tissues

MSA is present in immature and activated melanocytes (due to, e.g., inflammation, increased vascularity or underlying tumour), but not in mature, resting melanocytes. Melanocytes in the normal skin show strong cytoplasmic staining both cell body and the dendrites.

Staining in tumors

HMB-45 shows a positive immunoreactivity in 60-90 % of malignant melanomas. It is important to remember that spindle cell and desmoplastic malignant melanoma are MSA negative or only focally positive. MSA is found in varying proportions of benign melanocytic tumours like junction naevus and compound naevus. In these lesions, the intraepidermal part is usually strongly positive, while the dermal component is weakly stained or mostly negative. MSA is uniformly and strongly positive in most cases of blue naevus, cellular blue naevus, dysplastic nevi and Spitz nevi.
MSA is also demonstrated in some melanosome producing tumours such as:

  • clear cell sarcoma
  • proximal type epitheloid sarcoma
  • pulmonary blastoma and hepatoblastoma
  • phaeochromocytoma
  • melanotic neurofibroma and schwannoma and other neural crest derived tumours
  • PEComas (perivascular epitheloid cell) derived from modified smooth muscle cells: angiomyolipoma, lymphangioleiomyoma, and pulmonary sugar tumour, and cardiac rhabdomyoma

Carcinomas are MSA negative.

Staining pattern

Strong cytoplasmic staining of both cell body and the dendritic extensions is observed especially in the epidermal portion of the compound nevi and melanomas.

Control tissue

A multi-tissue block combining junction/compound nevus and malignant melanomas with varying expression of MSA is recommended.

Application

  •  MSA is a highly specific marker, widely used for the identification of melanocytic differentiation. In general, MSA is less sensitive marker than Melan-A and microphthalmia transcription factor (Mitf) in compound benign melanocytic nevi and in desmoplastic / spindle cell melanoma.
  • Uniform and strong staining or heterogeneous expression in the dermal component of a compound melanocytic tumor is usually aberrant. Strong and uniform expression in the dermal portion is observed in blue nevi.
  • MSA is also a useful marker in combination with either S-100 or SOX-10 and Melan-A in the sentinel lymph node diagnosis of malignant melanoma.
  • MSA is useful for the identification of PEComa (together with alpha smooth muscle actin), but also here Melan-A may give a stronger staining.

Selected references

  1. Kikuchi A, Shimizu H, Nishikawa T. Expression and ultrastructural localization of HMB-45 antigen. Br J Dermatol. 1996 Sep;135(3):400-5. PMID: 8949433.
  2. Holbrook KA, Underwood RA, Vogel AM, et al.. The appearance, density and distribution of melanocytes in human embryonic and fetal skin revealed by the anti-melanoma monoclonal antibody, HMB-45. Anat Embryol (Berl). 1989;180( 5): 443-55. doi: 10.1007/BF00305119. PMID: 2619087.
  3. Gown AM, Vogel AM, Hoak D, et al. Monoclonal antibodies specific for melanocytic tumors distinguish subpopulations of melanocytes. Am J Pathol. 1986 May;123(2):195-203. PMID: 3518473; PMCID: PMC1888307.
  4. Kapur RP, Bigler SA, Skelly M, Gown AM. Anti-melanoma monoclonal antibody HMB45 identifies an oncofetal glycoconjugate associated with immature melanosomes. J Histochem Cytochem. 1992 Feb;40(2):207-12. doi: 10.1177/40.2.1552165. PMID: 1552165.
  5. Hornick JL, Fletcher CD. PEComa: what do we know so far? Histopathology. 2006 Jan;48(1):75-82. doi: 10.1111/j.1365-2559.2005.02316.x. PMID: 16359539.
  6. Pižem J, Nicholson KM, Mraz J, Prieto VG. Melanocytic differentiation is present in a significant proportion of nonpigmented diffuse neurofibromas: a potential diagnostic pitfall. Am J Surg Pathol. 2013 Aug;37(8):1182-91. doi: 10.1097/PAS.0b013e31828950a3. PMID: 23715161.
  7. Goto Y, Ferrone S, Arigami T, et al. Human high molecular weight-melanoma-associated antigen: utility for detection of metastatic melanoma in sentinel lymph nodes. Clin Cancer Res. 2008 Jun 1;14(11):3401-7. doi: 10.1158/1078-0432.CCR-07-1842. PMID: 18519770; PMCID: PMC2686117.
  8. Prieto VG. Sentinel lymph nodes in cutaneous melanoma: handling, examination, and clinical repercussion. Arch Pathol Lab Med. 2010 Dec;134(12):1764-9. doi: 10.5858/2009-0502-RAR.1. PMID: 21128773.