Melanoma
Understanding Your Diagnosis
Melanoma can only be confirmed with a biopsy. However, every melanoma diagnosis is not the same. Because of that, it is extremely important for you and your medical team to learn as much as possible about your type of melanoma. To do that, you will undergo other tests in addition to a biopsy. The results will be crucial in helping your doctors determine the most appropriate treatment plan for you. Understanding your diagnosis begins with being aware of the tests you may have and know why they are important.
Biopsy
The biopsy you have will depend on the size and location of the melanoma. An excisional biopsy removes an entire lump or suspicious area. An incisional biopsy removes a portion of a lump or suspicious area. A punch biopsy removes a small round piece of tissue about the size of a pencil eraser. A shave biopsy removes a skin abnormality and a thin layer of surrounding skin.
After the biopsy sample is removed, a pathologist, a doctor who has special training in identifying diseases by studying cells and tissues under a microscope, examines it for these and other characteristics:
- The type and subtype of melanoma
- The thickness of the melanoma
- Whether the top skin layer is intact or broken (ulcerated)
- How fast the melanoma cells are growing (mitotic rate)
- Whether the melanoma has spread to lymph vessels, blood vessels, lymph nodes or other organs.
The information obtained from your biopsy will be noted in a pathology report, which is the description of cells and tissues made by a pathologist based on microscopic evidence. It will be used to diagnose and stage your melanoma, and it will guide your doctor in selecting treatment options. You may request a copy of your pathology report at any time.
Sentinel Lymph Node Mapping
In cases where there is an increased risk that the primary melanoma may have spread to nearby lymph nodes, sentinel lymph node (SLN) mapping is recommended (see Figure 1). This procedure tracks the exact path of the bodily fluid (lymph) that carries white blood cells as it drains from the skin surrounding the melanoma to the nearest lymph node.
The draining lymph node closest to the melanoma is called the sentinel lymph node.
Accurately identifying which lymph node is the SLN is important for many reasons. The decision to remove lymph nodes often depends on whether melanoma has spread to an SLN. It also helps determine the stage as well as the need for genomic testing, which in turn, guides treatment.
SLN mapping uses lymphoscintigraphy, a special type of imaging technique done in a hospital’s nuclear medicine department. Ideally, it is performed on the same day as surgery to remove the melanoma. A radioactive tracer is injected into the skin around the site of the melanoma, and an imaging device that detects radioactivity makes a series of images that show the path of the radioactive material as it travels to the nearest group of lymph nodes. The surgeon injects a special dye into the skin around the site of the melanoma to visually identify the SLN. The surgeon then makes a small incision in the area of the lymph nodes and removes the SLN. The node(s) are carefully examined by a pathologist for the presence of melanoma cells. Because the SLN is the first place to which lymph drains from the site of the melanoma, it is highly unlikely the melanoma will have spread to any other lymph nodes if no cancer cells are found in the SLN.
Genomic Testing
Many cancers are caused by genetic mutations, which are changes that occur in DNA. While examining your biopsy sample under a microscope, the pathologist may perform genomic, or molecular, testing to check certain genes, proteins or other molecules for mutations. This information could indicate the cancer’s behavior, how aggressive it might be and whether it will metastasize (spread). With that knowledge, doctors can choose more personalized treatment options. In certain cancers, for example, mutations have been discovered that can be treated with targeted therapy, a type of treatment specifically designed for certain mutations or determine whether you may qualify for immunotherapy.
Mutations
These and other mutations enable melanoma to be classified into distinct subtypes:
- BRAF (pronounced BEE-raff, roughly half of all melanomas contain these mutations)
- NRAS (pronounced EN-rass)
- NF-1
- KIT
- MEK 1 and MEK2 (pronounced meck, these mutations increase the growth of cancer cells)
- NTRK (pronounced EN-track)
Several targeted therapies, such as BRAF inhibitors, MEK inhibitors, KIT inhibitors and tumor-agnostic therapies, are approved by the U.S. Food and Drug Administration to treat some of these mutations. Clinical trials are testing treatments that target other mutations. It is important to understand that not all melanomas have actionable mutations. However, in that case, other treatment options are available.
Biomarkers
Biomarkers, also called tumor markers, biological markers or molecular biomarkers, are produced by cancer cells or other cells in the body in response to cancer. Genomic testing may be used to detect biomarkers such as genes or molecules that can be measured in the blood, plasma, urine, cerebrospinal fluid or other body fluids or tissues. Multiple types of biomarkers offer different information. For example, predictive biomarkers indicate whether an approved drug is appropriate for treating a person’s melanoma. Companion diagnostic tests for molecular biomarkers, such as BRAF or KIT, may indicate that the person may be eligible for future clinical trials.
Certain cancers are routinely tested for some biomarkers. Your doctor may test for the following.
- Lactate dehydrogenase (LDH) is the accepted serum (blood test) biomarker for melanoma. It is a prognostic biomarker that is measured to determine whether a person has an elevated risk for metastasis. Elevated LDH may indicate the cancer has progressed. A decrease in LDH has been associated with response to immunotherapy because it is released when melanoma cells are damaged or die.
- PD-L1 expression (also called the combined positive score or CPS) may be measured to determine whether the tumor cells or immune cells in the tumor’s microenvironment contain a higher level of PD-L1, which may mean that a patient could be a good candidate for immune checkpoint inhibitors. However, testing for this biomarker alone is not sufficient to determine a therapeutic response to immunotherapy in patients with melanoma or other skin cancers.
- Tumor mutational burden (TMB) is an assessment of the number of genetic mutations in a tumor. It can help doctors determine whether a patient may respond to immunotherapy. It is believed that the higher the TMB level, the more likely the patient may be to respond.
- Tumor-infiltrating lymphocytes (TILs) are a type of immune cell that has moved from the blood into a tumor. TILS can recognize and kill cancer cells. Melanomas with higher numbers of TILs and those with TILs inside the tumor have been shown to have a better prognosis and may respond better to therapy. In addition, some treatments result in higher TILs, and they may be a biomarker for response with these therapies.
