HMB-45 (Human Melanoma Black-45) is an antibody used by pathologists to detect a protein called gp100. This protein is normally found in melanocytes—cells that produce melanin, the pigment responsible for skin, hair, and eye color. Melanocytes are mostly located in the skin but can also appear in mucosal areas (like the mouth) and eyes. Because HMB-45 identifies gp100, it helps pathologists recognize melanocytes and related cells in both healthy tissue and tumors.
In normal tissue, the gp100 protein detected by HMB-45 is primarily expressed in melanocytes, cells that produce melanin pigment, found in the skin, mucosal surfaces, and eyes.
Pathologists test for HMB-45 using a method called immunohistochemistry (IHC). In this technique, specialized antibodies (HMB-45 antibodies) are applied to tissue samples obtained from a biopsy. These antibodies specifically bind to gp100 protein if it is present in the tissue. If the protein is detected, the antibody binding causes a visible color change under the microscope. Pathologists interpret this staining by reporting if it is positive (protein detected) or negative (protein not detected), and they also note the percentage of positive cells and the strength of staining.
HMB-45 can be expressed by tumors made up of melanocytes and other types of cells. The presence and pattern of HMB-45 staining help pathologists accurately diagnose and distinguish between various benign and malignant tumors.
Common melanocytic nevi (moles): Typically express HMB-45 near the skin surface, but staining fades as the lesion gets deeper.
Spitz nevi and atypical Spitz nevi: Often show variable HMB-45 staining.
Blue nevi: Usually express HMB-45 throughout the lesion.
Halo nevi: May aberrantly express HMB-45 in about half of cases.
Deep penetrating nevus (plexiform melanocytoma): Typically positive for HMB-45.
Melanoma: A common type of skin cancer that is typically positive for HMB-45, aiding in the diagnosis of primary and metastatic melanoma.
Spitz melanoma: Often strongly expresses HMB-45 deep within the lesion.
Clear cell sarcoma: Frequently expresses HMB-45, which helps distinguish it from similar-looking tumors.
Primary diffuse leptomeningeal melanomatosis (PDLM): A rare tumor involving the brain and spinal cord membranes; typically expresses HMB-45.
Meningeal melanocytoma and melanoma: Tumors involving membranes covering the brain and spinal cord, commonly express HMB-45.
Renal cell carcinomas with TFE3 and TFEB rearrangements: Occasionally express HMB-45.
Angiomyolipoma: Kidney tumors strongly positive for HMB-45, helpful in distinguishing them from similar tumors (e.g., leiomyomas or angiolipomas).
Perivascular epithelioid cell tumor (PEComa): Consistently expresses HMB-45, important for diagnosis.
Lymphangioleiomyomatosis (LAM): A lung disease that frequently expresses HMB-45.
Malignant melanotic nerve sheath tumor and melanotic schwannoma: Rare tumors strongly expressing HMB-45.
Pigmented (melanotic) neurofibroma: Typically expresses HMB-45, aiding in diagnosis.
Melanotic neuroectodermal tumor of infancy: A pediatric tumor commonly positive for HMB-45.
Testing for HMB-45 helps pathologists accurately identify and classify tumors, particularly those that start from melanocytes. It is commonly used to distinguish melanoma from other skin cancers or benign skin conditions. Because HMB-45 can also be expressed by other tumor types, pathologists combine it with additional markers (such as SOX10, MelanA/MART1, S100, MITF, and tyrosinase) to increase diagnostic accuracy.
Specific situations where HMB-45 testing is particularly useful include:
Distinguishing melanoma (HMB-45 positive) from benign moles or other tumors.
Differentiating melanoma from Paget disease, carcinomas, and other epithelioid tumors, which are typically HMB-45 negative.
Evaluating lymph nodes (sentinel nodes) for metastatic melanoma, although care is needed because certain benign cells (melanophages, nodal nevi) may also stain positively.
Differentiating between angiomyolipoma and other kidney tumors with similar appearance.
Diagnosing rare tumors like PEComas and lymphangioleiomyomatosis by distinguishing them from other similar-looking cancers.
Because staining patterns can vary, pathologists interpret HMB-45 results carefully, always in combination with other tests, microscopic appearance, and clinical details to ensure an accurate diagnosis and effective treatment planning.