Invasive Melanoma of the Skin: Understanding Your Pathology Report

By Jason Wasserman MD PhD FRCPC
April 23, 2026

Invasive melanoma is a type of skin cancer that starts from melanocytes, the cells that produce the pigment melanin. Melanocytes are normally found in the deepest part of the epidermis (the outer layer of the skin). When melanoma first develops, the abnormal melanocytes remain confined to the epidermis — a stage called melanoma in situ. In invasive melanoma, the cancer cells have grown downward into the deeper layers of the skin, beginning with the dermis. This matters because the dermis contains blood vessels and lymphatic channels that can act as pathways for the cancer to spread to lymph nodes or distant organs.

Melanoma is the most serious of the common skin cancers, but when detected and treated early, outcomes are very good. This article will help you understand the findings in your pathology report for invasive melanoma of the skin — what each term means and why it matters for your care.

What causes invasive melanoma?

Most invasive melanomas of the skin are caused by DNA damage in melanocytes from ultraviolet (UV) radiation. Most of this damage comes from the sun, but artificial sources such as tanning beds cause similar injury. Unlike many skin cancers, melanoma can be linked to both intense intermittent UV exposure (severe sunburns, particularly in childhood) and chronic long-term sun exposure, depending on the subtype. A smaller number of melanomas — particularly those that start on the palms, soles, under the nails, or in the mouth or genital area — arise without any clear connection to sun exposure.

Other risk factors include:

• Fair skin — People with lighter skin, light-colored eyes, freckles, and red or blond hair are at higher risk because their skin contains less protective melanin.
• Many or unusual moles — People with a large number of moles, or with atypical (dysplastic) moles, have a higher lifetime risk of developing melanoma.
• Personal or family history — A previous melanoma or a close relative with melanoma substantially increases the risk.
• Inherited conditions — Inherited mutations in genes such as CDKN2A and CDK4 are responsible for a small percentage of melanomas, sometimes occurring in families with multiple affected members at a young age.
• Weakened immune system — People taking anti-rejection medications after an organ transplant, or living with other forms of immune suppression, have a higher risk.
• Older age — The risk of melanoma increases with age, although melanoma is also one of the more common cancers in younger adults.

What are the symptoms of invasive melanoma?

Invasive melanoma often starts as an unusual spot on the skin that changes in size, shape, or color over time. It is usually painless in the early stages, although it can eventually itch, ooze, crust, or bleed. Common features include:

• Irregular shape and border — Melanomas often have an uneven or poorly defined edge, in contrast to most benign moles, which are round and symmetrical.
• Mixed colors — Melanomas commonly contain several shades of brown, black, or even red, white, or blue within a single lesion. Pale or white areas may indicate tumor regression (see below).
• Growth and change — A new spot that grows quickly, or an existing mole that begins to change, is a warning sign.
• Surface changes — As the tumor progresses, the surface may become raised, dome-shaped (as in nodular melanoma), or develop an ulcer.
• Amelanotic melanoma — A smaller number of melanomas produce little or no pigment and appear as pink or skin-colored bumps. These can resemble non-cancerous growths, making them harder to recognize.

Any new spot, a changing mole, or a lesion that looks different from the others on your body (“the ugly duckling sign”) should be assessed by a healthcare professional.

How is the diagnosis made?

The diagnosis of invasive melanoma is made after a tissue sample is examined under the microscope by a pathologist. The sample is obtained by a skin biopsy. For a lesion suspected of being melanoma, an excisional biopsy — in which the entire lesion is removed with a narrow margin of surrounding skin — is preferred whenever possible because it allows the pathologist to accurately measure the tumor’s full thickness. Punch or shave biopsies may be used when an excisional biopsy is not practical because of lesion size or location.

Under the microscope, the pathologist identifies abnormal melanocytes that have grown in an irregular pattern across the epidermis and into the dermis. Features that help confirm invasive melanoma include large, irregularly shaped cells, prominent nucleoli, atypical mitotic figures (dividing cells), and a disordered growth pattern that differs from that of a benign mole.

In difficult cases, immunohistochemistry (a special test that uses antibodies to detect specific proteins) is used to confirm that the tumor cells are melanocytes. Markers commonly used to identify melanoma include SOX10, MITF, HMB-45, and Melan-A (also called MART1). PRAME is another marker that is often positive in melanoma and can help distinguish it from benign mimics. A dual stain combining Ki-67 (a marker of cell growth) with Melan-A can help highlight areas of active tumor cell division. These tests confirm the diagnosis but are different from the biomarker tests used to guide treatment, which are discussed in the biomarker section below.

Once invasive melanoma is confirmed, imaging — such as ultrasound, CT, MRI, or PET — may be performed to check for spread to lymph nodes or distant organs, particularly for thicker tumors. A sentinel lymph node biopsy is often recommended for melanomas with specific high-risk features to check for microscopic spread.

Histologic subtypes of invasive melanoma

Invasive melanoma of the skin is divided into subtypes based on how the cancer cells are arranged and the pattern of growth. The subtype is reported to help describe the tumor but has less impact on treatment than features such as tumor thickness and ulceration.

• Superficial spreading melanoma — The most common subtype in fair-skinned populations. The cancer cells spread horizontally along the epidermis and into the superficial dermis. The surrounding skin typically shows changes of moderate sun damage, including solar elastosis. Superficial spreading melanoma usually arises from a preceding area of melanoma in situ.
• Nodular melanoma — The cancer cells form large clusters or sheets in the dermis with little or no horizontal growth along the epidermis. Nodular melanoma tends to grow more rapidly and is more likely to be thick at the time of diagnosis.
• Lentigo maligna melanoma — Develops from a preceding area of lentigo maligna (a form of melanoma in situ) on chronically sun-damaged skin, typically on the face of older adults. The background skin shows extensive solar elastosis.
• Acral lentiginous melanoma — Arises on the palms, soles, or under the nails (subungual). It is not linked to sun exposure and is the most common subtype in people with darker skin. Because of its location, it is often not recognized until it is thick.
• Desmoplastic melanoma — An uncommon subtype in which the cancer cells are spindle-shaped and embedded in dense scar-like tissue. Desmoplastic melanoma has a high rate of perineural invasion and local recurrence, but it is less likely to spread to lymph nodes than other melanoma subtypes.

Tumor thickness (Breslow thickness)

Tumor thickness, also called Breslow thickness, is the single most important feature in a melanoma pathology report. It is measured in millimeters from the top of the granular layer of the epidermis down to the deepest invasive tumor cell. Tumor thickness determines the pathologic tumor stage (pT) and is strongly linked to the risk of spread and survival. In general:

• Melanomas no more than 1 mm thick are considered thin and have the best prognosis.
• Melanomas between 1 and 4 mm thick carry an intermediate risk of spread.
• Melanomas thicker than 4 mm are at the highest risk of spread.

Ulceration

Ulceration refers to the loss of the normal epidermis over the surface of the tumor, usually replaced by an inflammatory layer of dead cells. The pathologist identifies ulceration under the microscope. Ulceration is an important finding because melanomas with ulceration behave more aggressively than melanomas of the same thickness without ulceration. Ulceration is used together with tumor thickness to determine the pathologic tumor stage.

Mitotic rate

A mitotic figure is a cell that is in the process of dividing to form two new cells. The mitotic rate is the number of mitotic figures counted in a set area of tumor tissue (usually 1 square millimeter). A higher mitotic rate indicates that the tumor is growing more quickly and is associated with a higher risk of spread. Mitotic rate is particularly important in thin melanomas, where it helps identify tumors that may behave more aggressively than expected from thickness alone.

Microsatellites, satellites, and in-transit metastases

Melanoma can spread locally through the skin and lymphatic channels close to the primary tumor before reaching the lymph nodes. Three related findings describe this type of local spread:

• Microsatellites — Small clusters of tumor cells, visible only under the microscope, that are separate from the main tumor and found in the surrounding skin.
• Satellites — Clinically visible tumor nodules within 2 cm of the primary tumor.
• In-transit metastases — Tumor nodules in the skin or soft tissue between the primary tumor and the nearest regional lymph node basin, more than 2 cm from the primary.

All three findings indicate that the melanoma has begun to spread through local lymphatic channels, thereby changing the pathologic nodal stage.

Tumor-infiltrating lymphocytes (TILs)

Tumor-infiltrating lymphocytes (TILs) are immune cells called lymphocytes that have moved into or around the tumor. TILs represent the body’s immune response against cancer, and in melanoma, higher TIL counts are generally associated with a better prognosis. Pathologists usually describe TILs in one of three categories:

• Absent — No TILs are identified.
• Non-brisk — TILs are present but scattered.
• Brisk — TILs are present throughout the tumor in large numbers.

Tumor regression

Tumor regression describes an area where tumor cells appear to have been destroyed by the immune system and replaced by inflammation and scar tissue (fibrosis). Regression may be partial (some tumor cells remain) or complete (no viable tumor cells are left). Regression can make it harder to measure the true thickness of the tumor, since the deepest part of the original melanoma may have disappeared.

Lymphovascular invasion

Lymphovascular invasion (LVI) means cancer cells have entered a small blood vessel or lymphatic channel. Lymphatic channels connect to lymph nodes, providing a direct route for melanoma cells to spread. Lymphovascular invasion is associated with a higher risk of nodal and distant spread.

Neurotropism (perineural invasion)

Neurotropism, also called perineural invasion, means cancer cells are growing along or into a nerve. Nerves can act as a highway that allows the cancer to extend beyond the visible edge of the tumor. Neurotropism is particularly common in desmoplastic melanoma and increases the risk of local recurrence, sometimes leading to recommendations for additional surgery or radiation therapy.

Margins

A margin is the edge of the tissue removed during surgery. Pathologists examine margins under the microscope to see whether any cancer cells are present at the cut edge. For melanoma, both the peripheral margin (the sides of the removed skin) and the deep margin (the base of the removed tissue) are evaluated. Margins are usually reported separately for invasive melanoma and melanoma in situ, because adequate margins around in situ disease are also important for preventing recurrence.

• Negative margin — No cancer cells are seen at the cut edge. The tumor is considered completely excised, with a lower risk of local recurrence.
• Close margin — Cancer cells are near the cut edge but do not reach it. Many pathologists report the exact distance (in millimeters) from the tumor to the margin. Close margins may warrant recommendations for additional surgery, depending on tumor features.
• Positive margin — Cancer cells are present at the cut edge. Additional surgery — known as a wide local excision — is usually recommended.

After an initial diagnostic biopsy shows invasive melanoma, a wide local excision is almost always performed to obtain a clear margin around the original tumor site. The size of the margin taken depends on the tumor thickness.

Lymph nodes

Melanoma often spreads first to nearby lymph nodes through the lymphatic channels. For this reason, lymph node evaluation is an important part of the pathologic staging of invasive melanoma.

Sentinel lymph node biopsy

A sentinel lymph node is the first lymph node (or nodes) that receives lymphatic drainage from the area of the tumor. Because it is the first place melanoma cells are likely to spread, a sentinel lymph node biopsy is a way to check for microscopic spread without removing many nodes. Sentinel lymph node biopsy is usually recommended for melanomas thicker than 0.8 mm, or for thinner tumors with high-risk features such as ulceration.

What the report describes

If lymph nodes are removed and examined, the pathology report will usually include:

• The total number of lymph nodes examined and the number that contain cancer.
• The location of the examined lymph nodes.
• The size of the largest deposit of melanoma within a lymph node.
• Whether extranodal extension is present. Extranodal extension means cancer cells have broken through the outer capsule of a lymph node into surrounding tissue and is associated with a higher risk of recurrence.
• Whether the lymph node involvement was detected only under the microscope (clinically occult) or was clinically suspected before surgery.

Finding melanoma in a lymph node changes the pathologic stage and usually influences decisions about systemic treatment, such as immunotherapy.

Biomarker and molecular testing

Biomarker testing is an important part of the pathology workup for many patients with invasive melanoma, particularly when the tumor is thick, has spread to lymph nodes, or has spread to distant organs. The goal of biomarker testing is to identify patients who can benefit from specific targeted drugs or immunotherapy. The tests described here are different from the immunohistochemistry markers used to confirm the diagnosis (see the diagnosis section above).

BRAF

BRAF is a gene that makes a protein involved in cell growth signaling. A specific mutation, BRAF V600E, is found in roughly half of all cutaneous melanomas. When this mutation is present, the BRAF protein is permanently switched on, driving uncontrolled tumor growth. BRAF mutations make the tumor eligible for targeted therapy with a BRAF inhibitor (such as dabrafenib, vemurafenib, or encorafenib), usually combined with a MEK inhibitor (such as trametinib, cobimetinib, or binimetinib). BRAF testing is typically performed using polymerase chain reaction (PCR), next-generation sequencing (NGS), or immunohistochemistry to detect the V600E mutation. Results are reported as positive (a mutation is detected, and the specific mutation is named) or negative.

NRAS

NRAS is another gene in the same signaling pathway as BRAF. NRAS mutations are found in about 20% of cutaneous melanomas and almost never occur together with BRAF mutations. There are no approved targeted therapies specifically for NRAS-mutant melanoma, but identifying an NRAS mutation helps explain the tumor’s biology and may influence clinical trial eligibility.

KIT

KIT is a gene involved in cell growth and survival. KIT mutations are uncommon overall (found in less than 5% of melanomas) but are enriched in acral, mucosal, and chronically sun-damaged melanomas. When a specific KIT mutation is present, the tumor may respond to targeted therapy with drugs such as imatinib.

PD-L1

PD-L1 is a protein that cancer cells can use to evade the immune system. Immunotherapy drugs called immune checkpoint inhibitors — including pembrolizumab (Keytruda), nivolumab (Opdivo), and ipilimumab (Yervoy) — block this pathway, allowing the immune system to attack the cancer. Immunotherapy is approved for advanced melanoma regardless of PD-L1 status, so PD-L1 testing is not required before treatment. In practice, PD-L1 is tested less often in melanoma than in other cancer types.

Tumor mutational burden

Tumor mutational burden (TMB) is a measure of the number of mutations present in cancer cells. Melanoma has one of the highest TMB of any cancer type because UV radiation causes a large number of DNA mutations. A high TMB helps explain why melanoma responds particularly well to immunotherapy — more mutations create more abnormal proteins that the immune system can recognize. TMB is not routinely measured in every melanoma but may be reported when broad molecular profiling is performed.

p16

p16 is a tumor suppressor protein that helps control cell division. Loss of p16 expression is common in invasive melanoma, particularly in more advanced or aggressive tumors. Loss of p16 is not typically used to guide treatment but may support the diagnosis in difficult cases and provide additional prognostic information.

For more information about biomarkers and molecular testing in cancer, visit the Biomarkers and Genetic Testing section.

Pathologic stage (pTNM)

The pathologic stage for invasive melanoma is based on the TNM system created by the American Joint Committee on Cancer (AJCC). This system uses information about the primary tumor (T), regional lymph nodes (N), and distant metastatic disease (M) to determine the overall stage. The M category is usually determined by imaging rather than by pathology. The stage helps predict the likely outcome and guides treatment decisions.

Tumor stage (pT)

• pTis — Melanoma in situ (cancer cells confined to the epidermis).
• pT1 — Tumor 1 mm thick or less.
  • pT1a — Less than 0.8 mm thick and no ulceration.
  • pT1b — Less than 0.8 mm thick with ulceration, OR 0.8 to 1.0 mm thick with or without ulceration.
• pT2 — Tumor more than 1 mm but no more than 2 mm thick.
  • pT2a — No ulceration.
  • pT2b — Ulceration present.
• pT3 — Tumor more than 2 mm but no more than 4 mm thick.
  • pT3a — No ulceration.
  • pT3b — Ulceration present.
• pT4 — Tumor more than 4 mm thick.
  • pT4a — No ulceration.
  • pT4b — Ulceration present.

Nodal stage (pN)

• pN0 — No cancer in regional lymph nodes and no microsatellites, satellites, or in-transit metastases.
• pN1 — Cancer in one regional lymph node, OR microsatellites, satellites, or in-transit metastases without lymph node involvement.
• pN2 — Cancer in two or three regional lymph nodes, OR microsatellites, satellites, or in-transit metastases with one positive lymph node.
• pN3 — Cancer in four or more regional lymph nodes, matted lymph nodes, OR microsatellites, satellites, or in-transit metastases with two or more positive lymph nodes.

The AJCC system further divides each nodal stage (pN1, pN2, pN3) into “a,” “b,” and “c” categories based on whether the involved nodes were clinically occult (found only on microscopic examination of a sentinel lymph node biopsy) or clinically detected (suspected before surgery), and whether microsatellites, satellites, or in-transit metastases are present.

What is the prognosis?

The prognosis for invasive melanoma depends most strongly on the pathologic stage, but several individual features contribute to the overall outlook. Five-year survival rates remain excellent for thin, node-negative melanomas and have improved substantially for advanced melanoma in recent years because of targeted therapy and immunotherapy.

General five-year survival estimates by stage:

• Stage I (thin, node-negative) — Greater than 95%.
• Stage II (thicker, node-negative) — Approximately 70 to 90%, depending on thickness and ulceration.
• Stage III (regional lymph node involvement) — Approximately 40 to 90%, varying widely by the number of nodes involved, ulceration, and tumor thickness.
• Stage IV (distant metastasis) — Historically below 25%, but substantially improved with modern immunotherapy and targeted therapy; many patients now achieve long-term disease control.

Pathologic features associated with a higher risk of recurrence or spread include:

• Increased tumor thickness — Thicker tumors are more likely to spread to lymph nodes and distant organs.
• Ulceration — Tumors with ulceration behave more aggressively than tumors of the same thickness without ulceration.
• Higher mitotic rate — More dividing cells indicate faster growth and higher risk.
• Lymphovascular invasion — Cancer cells within blood or lymphatic channels increase the risk of spread.
• Microsatellites, satellites, or in-transit metastases — Indicate local spread and a higher pathologic stage.
• Positive lymph nodes — Particularly when multiple nodes are involved, or extranodal extension is present.
• Positive or close surgical margins — Increase the risk of local recurrence.
• Absent tumor-infiltrating lymphocytes — Suggest a weaker immune response to the tumor.

What happens after the diagnosis?

Treatment of invasive melanoma is coordinated by a team that may include a dermatologist, a surgical oncologist, a medical oncologist, and a radiation oncologist. The approach depends on the tumor’s stage and molecular features.

For most primary invasive melanomas, the first step after diagnosis is a wide local excision to remove the tumor site with a clear margin of healthy tissue. The size of the margin is based on the original tumor thickness. For tumors above a certain thickness — generally 0.8 mm — or for thinner tumors with high-risk features such as ulceration, a sentinel lymph node biopsy is usually performed at the same time to check for microscopic spread.

When melanoma is found in lymph nodes, further imaging is performed to assess for distant spread. In the past, all remaining lymph nodes in the affected basin were removed, but current practice usually favors close imaging surveillance instead of complete lymph node dissection, except in specific situations.

Adjuvant therapy — treatment given after surgery to reduce the risk of recurrence — is often recommended for Stage IIB, IIC, and III melanoma. Options include:

• Immunotherapy — PD-1 inhibitors such as pembrolizumab (Keytruda) or nivolumab (Opdivo).
• BRAF-targeted therapy — The combination of dabrafenib and trametinib for patients with BRAF V600E or V600K mutant melanoma.

For locally advanced or metastatic melanoma that cannot be cured by surgery alone, systemic therapy is the main treatment. Options include:

• Immunotherapy — PD-1 inhibitors alone, or the combination of a PD-1 inhibitor (nivolumab) with an anti-CTLA-4 drug (ipilimumab) or with the anti-LAG-3 drug relatlimab.
• Targeted therapy — Combination of a BRAF inhibitor and a MEK inhibitor for BRAF-mutant melanoma.
• Radiation therapy — Often used to treat symptomatic sites of metastasis, particularly in the brain and bones.

After treatment, regular clinical follow-up and skin examinations are essential. People who have had one melanoma are at increased risk of developing additional melanomas and other skin cancers, and ongoing sun protection is an important part of prevention.

Questions to ask your doctor

• Where on my body did the melanoma develop, and what subtype was diagnosed?
• What was the tumor thickness (Breslow thickness), and what does that mean for my prognosis?
• Was ulceration present?
• What was the mitotic rate?
• Were microsatellites, satellites, or in-transit metastases found?
• Was lymphovascular invasion or neurotropism (perineural invasion) found?
• Were the surgical margins negative, close, or positive? Do I need a wide local excision?
• Do I need a sentinel lymph node biopsy? Was one performed, and what were the results?
• What is the pathologic stage of my melanoma?
• Was my tumor tested for BRAF, NRAS, or KIT mutations? What were the results?
• Do I need additional treatment, such as immunotherapy, targeted therapy, or radiation?
• How often should I be seen for follow-up, and what imaging or tests will be performed?
• Am I at higher risk of developing additional melanomas or other skin cancers? How often should I have full skin examinations?
• Should my family members be screened or evaluated for inherited melanoma risk?
• What steps can I take to reduce my risk of future skin cancers?