Melanoma is a type of skin cancer that arises in the melanocytes or cells that produce melanin and determines the color of your skin, or pigment. Melanoma can form in the eyes, and on rare occasions inside the body such as the nose or throat. Its exact causes are not always clear, but evidence does support exposure to ultraviolet (UV) radiation from sunlight or tanning beds as increasing a person’s risk of developing the disease.

Invasive melanoma accounts for about 1% of all skin cancer cases in the United States according to the American Cancer Society Cancer Facts and Figures 2022. In 2022 about 99,780 new invasive melanoma cases will be diagnosed and 97,920 cases of in situ melanoma, and over 7,000 people will die from this disease. Rates are higher in women than in men who are under the age of 50 years but increases in men over the age of fifty, due to occupational, recreational, or environmental exposure.

There are four major subtypes of melanoma, including:

• Superficial Spreading Melanoma: the most common subtype.
• Nodular Melanoma: which is always vertical growth phase present melanomas and commonly found on the chest, back, head or neck.
• Acral Lentiginous: most common type of melanoma found in dark-skinned and Asian individuals. These lesions most frequently appear on the soles of the feet, palms of hands or under nails.
• Lentigo Maligna Melanoma typically occurs on sun-exposed areas of skin on older people. They are often found on the face or neck.
• Rare subtypes of melanoma include mucosal melanoma, desmoplastic melanoma and nevoid melanoma.

Understanding how melanoma is diagnosed, staged and treated is important. For our use in this post we will focus on identifying and describing most clinical and pathologic terms used to describe melanoma.

Breslow Depth: is a measurement of the thickness of a melanoma, at its thickest point, in millimeters. This measurement is important to determining prognosis. For example, the thicker the melanoma the poorer the prognosis. Breslow thickness is a more important factor than Clark’s Level for determining prognosis or staging. Breslow’s Depth Classification is made as follows:

• Melanoma in situ or thin invasive tumors: less than 1.0mm in depth.
• Intermediate risk melanoma: 1mm – 4mm in thickness.
• High risk, or thick, melanoma: greater than 4.0mm in depth.

Clark’s Level: also called anatomic level, is another measure of depth of invasion identifying the layer of skin the melanoma extends into (or penetrates) as opposed to a measurement in millimeters. The higher the Clark’s Level the deeper into the tissue it penetrates. Depending on the patient’s skin, the millimeter depth for each Clark’s Level can vary. For example, one person’s Clark’s Level III may be 1 mm while another’s 2mm’s. Clark’s Level is not an indicator of stage. Here is how Level is assigned:

• Clark’s Level I: lesion involves the dermis.
• Clark’s Level II: lesion involves the papillary dermis.
• Clark’s Level III: lesion invades into and fills the papillary dermis.
• Clark’s Level IV: lesion invades the reticular dermis.
• Clark’s Level V: lesion invades sub-cutaneous tissue.

Radial Growth Phase (RGP): Pathologists describe RGP as either being present or absent. If present, RGP indicates that the melanoma is growing horizontally (radially) within a single plan of the skin layer, meaning it is growing outward (horizontally) across the skin. RGP melanomas are typically thin and considered cured with surgical resection.

Vertical Growth Phase (VGP): This term is also described as either present or absent. If present VGP means the melanoma is growing vertically or deeper into the tissue. VGP melanomas are invasive and have potential to metastasize to other areas of the body.

Tumor-Infiltrating Lymphocytes (TILs): TILs describe the patient’s immune response to the melanoma. When examining the specimen, the pathologist looks for the number of lymphocytes, or white blood cells, in the lesion. This response, or TILs, are usually noted as “brisk,” “non-brisk,” or “absent.” Occasionally the Registrar may see it documented as “mild” or “moderate.” TILs tell us that the immune system has recognized the melanoma as abnormal.

Ulceration: is the sloughing of dead tissue that may occur in the center of the melanoma lesion. The presence of ulceration is used in AJCC staging. It is thought to reflect rapid tumor growth, which leads to cell death in the center of the melanoma.

Regression: Regression is either present or absent. If present the extent of regression is identified as an area where it appears there had been active melanoma cells in the past. But these may have been destroyed by the immune system or replaced with inflammation or scar tissue. When regression is present the total size of the melanoma is hard to measure because it is difficult to determine how extensive it was before regression occurred.

Of note: regressing melanoma is a reportable cancer in the United States. You can read about this more on the SEER SINQ website, Question ID 20210009 at: SEER Inquiry System – Search (cancer.gov).

Mitotic Rate: is a term used to describe the frequency of cell division within the melanoma lesion. The higher the rate the more rapidly the cells are dividing. Larger lesions, with greater potential for metastasis and a poorer prognosis will have a higher mitotic rate. It is the second most important factor, behind Breslow’s thickness, to determine prognosis. Mitotic rate is also used to stage very thin melanomas (see Breslow thickness above). Mitotic rate is reported by the pathologist as a value per mm2 or may be given within a range, such as 1-4/mm2.

Satellites: satellite lesions may also be called micro-satellites and are areas of tumor located more than 0.05 mm, but less than 2cm, away from the primary lesions. Satellites are described as either present or absent and are used for staging of melanomas.

In-Transit Metastases: this term is like satellite lesions, however in-transit metastases are areas that are more than 2cm from the primary lesion but do not go beyond the local lymphatic drainage, or the lymph node basin. Again, in-transit metastases are also used for staging of melanoma.

Blood Vessel/Lymphatic Invasion: is described as either present or absent. Its presence means the tumor cells have invaded the blood or lymphatic system.

Lactate Dehydrogenase (LDH): is a blood test for the LDH enzyme normally found in the body in low levels. High levels of LDH may be an indicator of metastasis. LDH is also used for cancer staging.

BRAF Mutation Analysis: BRAF is a protein kinase that impacts the regulating genes responsible for cell replication and survival. An estimated 50% or more of melanomas contain an abnormal BRAF mutation. BRAF is also used to identify medications or treatments that the melanoma will respond to in a favorable manner.

For further reading see: AJCC Cancer Staging Manual, Eighth Edition, Chapter 47, the Commission on Cancer (CoC) Standards for Oncology Registry Entry (STORE) Manual, SEER Program Coding and Staging Manual 2022, or other cancer program coding or abstracting guidelines published by the standard setting agencies, state or federal cancer registries.