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Stains

HMB45

Reviewer: Nat Pernick, M.D. (see Reviewers page)
Revised: 15 October 2012, last major update October 2012
Copyright: (c) 2002-2012, PathologyOutlines.com, Inc.

General
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● Human Melanoma Black, discovered in 1986 (Am J Pathol 1986;123:195)
● Monoclonal antibody originally identified from melanoma abstract, recognizes melanosomal glycoprotein gp100 ( Pmel17)
● Membrane protein required to form melanosomal fibrils, facilitates maturation of stage I pre-melanosomes to stage II
● Identifies oncofetal glycoconjugate associated with immature melanosomes and probably related to the tyrosinase enzymatic system (J Histochem Cytochem 1992;40:207)

Uses by pathologists
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● Common marker to confirm melanoma (invasive melanomas with paradoxical maturation show at least focal deep HMB45 reactivity, in contrast to nevi, which are negative in deep dermis)
● Evaluating sentinel lymph nodes for melanoma (Am J Surg Pathol 2001;25:1039)
● Diagnosis (or ruling out diagnosis) of perivascular epithelioid cell tumors (angiomyolipoma, lymphangioleiomyomatoisis, PEComa, clear cell "sugar" tumor)

Micro images
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Bladder: metastatic melanoma is HMB45+, paraganglioma is HMB45-


Colon: leiomyomatosis-like lymphangioleiomyomatosis

   
Esophagus: melanoma

       
Kidney: angiomyolipoma (right: smooth muscle cells are HMB45+)

   
Kidney: atypical epithelioid angiomyolipoma (figure 3A)

   
Lung: left-clear cell "sugar" tumor, right-lymphangioleiomyomatosis (figure D)


Lymph nodes: isolated positive cells


Mediastinum: melanoma

   
Perivascular epithelioid cell tumors: left-cervix, right-colon


Skin: melanoma

   
Skin: nevi and melanomas


Uterus: melanoma

   
Uterus: perivascular epithelioid cell tumors

Cytology images
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Thyroid: metastatic melanoma

Positive staining - normal
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● Lymph nodes: scattered mononuclear cells
● Skin: junctional melanocytes, activated melanocytes

Positive staining - disease
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● Skin and other sites: melanoma (85-90%, see exceptions under Negative staining); also blue nevus, Spitz nevus (Spitz nevi may be HMB45- at other sites)
● Nevus cells may be HMB45+ in intraepidermal and superficial dermal component; nevus cells may also have weak nuclear staining that is overwhelmed by hematoxylin and usually not seen (Mod Pathol 2008;21:1121)
● Angiomyolipoma (various sites, usually negative in nasal cavity)
● Clear cell sarcoma of soft tissue (Am J Surg Pathol 2008;32:452)
● Clear cell "sugar" tumor (Am J Surg Pathol 2002;26:670)
● Epithelioid sarcoma (occasional)
● Kidney: t(6;11)(p21;q12) renal cell carcinoma (Hum Pathol 2012;43:726)
● Lymphangioleiomyomatosis (also stains nonproliferative cells)
● Melanocytosis
● PEComa (Am J Surg Pathol 2005;29:1558)
● Pheochromocytoma (30%, Arch Pathol Lab Med 1992;116:151 )
● Pigmented neural tumors (some), including some nerve sheath tumors, some neurofibromas (Hum Pathol 2005;36:871), pigmented neuroectodermal tumor of infancy
● Tuberous sclerosis complex components

Negative staining
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● Adult/resting melanocytes
● Some melanomas: desmoplastic, oral mucosal, spindle cell (but 50% of HMB45 negative melanoma cells have premelanosomes on EM)
● Atypical fibroxanthoma
● Epithelioid malignant peripheral nerve sheath tumors
● Leiomyosarcoma, liposarcoma
● Paget's disease of breast, scrotum, vulva
● Pigmented dermatofibrosarcoma protuberans, pigmented epithelioid melanocytoma
● Uterine tumors resembling ovarian sex cord tumors (Am J Surg Pathol 2010;34:1749)

End of Stains > HMB45

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