Malignant melanoma stage III – Diagnostics

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Stage III melanoma represents a critical point where cancer has spread beyond the original skin site to nearby lymph nodes, lymph vessels, or surrounding skin areas. Understanding how doctors identify and confirm this stage through various diagnostic methods is essential for anyone facing this diagnosis, as accurate testing guides treatment decisions and helps predict outcomes.

Introduction: Who Should Undergo Diagnostics

If you have been told that melanoma might have spread beyond the skin where it first appeared, your doctor will likely recommend diagnostic testing to determine whether you have stage III melanoma. This stage means that cancer cells have moved to nearby areas but have not yet reached distant parts of your body. Knowing exactly where the cancer is and how far it has spread is crucial for choosing the right treatment approach.[1]

People who should consider diagnostic testing for stage III melanoma include those who have had a melanoma removed from their skin and show signs that cancer may have spread to nearby lymph nodes. Sometimes, you might notice swollen lymph nodes near where the melanoma was found. In other cases, your doctor might recommend testing even if you don’t notice any obvious changes, especially if the original melanoma was thick or had certain features that suggest a higher risk of spreading.[3]

Understanding when to seek diagnostics is important because melanoma at stage III requires different treatment than earlier stages. The lymph nodes are part of your body’s lymphatic system, which is a network of tissues and organs that helps remove waste and supports your immune system by transporting infection-fighting white blood cells. When melanoma reaches the lymph nodes, it indicates that cancer cells have started traveling through this system.[1]

If you had melanoma removed previously and notice any new lumps, bumps, or areas of concern near the original site or along the path to nearby lymph nodes, it’s advisable to contact your doctor promptly. Early detection through proper diagnostic testing at this stage can significantly impact treatment options and outcomes. You don’t need to wait for symptoms to become severe before seeking evaluation.

⚠️ Important
Stage III melanoma is divided into four subgroups (IIIA, IIIB, IIIC, and IIID) based on the thickness of the original tumor, whether the skin was broken when examined under a microscope, and how extensively cancer has spread to lymph nodes or nearby skin. Your exact subtype affects your treatment plan and prognosis, so accurate diagnostic testing is essential to classify your melanoma correctly.[1]

Diagnostic Methods for Stage III Melanoma

Initial Biopsy and Pathology Examination

The diagnostic process for melanoma begins with an excision biopsy, where your doctor removes the abnormal area along with a small amount of surrounding healthy skin. This removed tissue is sent to a specialist doctor called a pathologist, who examines it under a microscope to look for cancer cells. If melanoma cells are present, the pathologist determines important characteristics such as how thick the tumor is and whether the top layer of skin appears broken, which is called ulceration.[3]

The thickness of the melanoma is measured in millimeters and plays a major role in staging. For example, stage IIIA melanoma might involve a tumor up to 1.0 millimeter thick (about the size of a sharpened pencil point) or one between 1.0 and 2.0 millimeters (roughly the size of a new crayon point). These measurements might seem very small, but they make a significant difference in how doctors classify and treat the disease.[1]

Sentinel Lymph Node Biopsy

One of the most important tests for diagnosing stage III melanoma is the sentinel lymph node biopsy, often abbreviated as SLNB. This procedure identifies whether cancer cells have spread to the nearest lymph nodes. The sentinel lymph node is the first lymph node that fluid from the area around the melanoma would drain into, making it the most likely place for cancer cells to appear first if they have started spreading.[3]

During this procedure, your doctor removes one or more of these sentinel lymph nodes and examines them for cancer cells. The SLNB is typically performed at the same time as a wide local excision, which is a surgery to remove the melanoma site with a larger margin of healthy tissue around it. By combining these procedures, doctors can both treat the original melanoma and check for spread to lymph nodes in one operation.[3]

The results of the sentinel lymph node biopsy are critical for staging. If cancer cells are found in one to three nearby lymph nodes detected through this biopsy, and the disease has not spread to distant sites in your body, you may be diagnosed with stage III melanoma. The specific subtype depends on factors like tumor thickness, ulceration, and the number of lymph nodes involved.[1]

Evaluation of Swollen Lymph Nodes

Sometimes, lymph nodes near the melanoma become noticeably swollen or enlarged. If your doctor can feel swollen lymph nodes during a physical examination, you usually won’t need a sentinel lymph node biopsy. Instead, you will typically have an ultrasound scan of the area. Ultrasound uses sound waves to create pictures of the inside of your body and can show whether lymph nodes appear abnormal.[3]

If the ultrasound reveals concerning findings, your doctor may take a sample of tissue from the lymph node through a procedure called a biopsy. This sample is examined under a microscope to check for cancer cells. This approach provides a less invasive way to confirm whether melanoma has spread when lymph nodes are already visibly affected.[3]

Identifying Metastases Between Melanoma and Lymph Nodes

Stage III melanoma is also diagnosed when cancer cells are found in the area between the original melanoma and the nearby lymph nodes. These deposits of cancer cells have specific names depending on their location and size. Microsatellite metastases are tiny amounts of cancer cells found right next to the melanoma that can only be seen through a microscope. Satellite metastases are cancer cells found within 2 centimeters of the melanoma. In-transit metastases are cancer cells that have spread more than 2 centimeters away from the melanoma but haven’t reached the nearest lymph node yet.[3]

Detecting these different types of metastases requires careful examination by the pathologist during biopsy analysis. Sometimes these deposits are visible to the naked eye, appearing as small bumps or nodules on the skin between the original melanoma site and the lymph node region. Other times, they are only discovered during microscopic examination of tissue samples.

Additional Imaging and Scanning Tests

Beyond biopsies and physical examination, your doctor will normally recommend additional tests and scans to complete the staging process. These help ensure that cancer has not spread to distant parts of your body, which would indicate a different stage. The specific tests ordered depend on your individual situation and the characteristics of your melanoma.[3]

Common imaging tests might include computed tomography (CT) scans, which use X-rays and computer technology to create detailed pictures of the inside of your body, or other scanning methods that can detect cancer in organs or distant lymph nodes. These tests help doctors confirm that the melanoma is truly stage III (regional spread) rather than stage IV (distant spread).

Understanding the TNM Staging System

Doctors also use a detailed classification called the TNM staging system alongside the numbered staging system. TNM stands for Tumor, Node, and Metastasis. The “T” describes the size and characteristics of the tumor, including its thickness and whether ulceration is present. The “N” describes whether cancer cells are in the lymph nodes and how many nodes are affected. The “M” describes whether the cancer has spread to different parts of the body.[3]

In the TNM system, stage III melanoma is classified as “Any T, N1 to N3, M0.” This means the tumor can be any thickness (Any T), there is involvement of nearby lymph nodes at various levels (N1 to N3), but there is no spread to distant body parts (M0). While the TNM system provides very detailed information that specialists use, the numbered staging system (stage III with subtypes A, B, C, and D) groups these details together in a way that’s easier to understand and communicate.[3]

Diagnostics for Clinical Trial Qualification

If you are considering participating in a clinical trial for stage III melanoma, you will need to undergo specific diagnostic tests to determine whether you qualify. Clinical trials have strict eligibility criteria to ensure that the research results are reliable and that participants are appropriate candidates for the experimental treatments being studied.[10]

For many clinical trials involving stage III melanoma, especially those testing treatments after surgical removal of the cancer, qualification typically requires confirmation that the melanoma and affected lymph nodes have been completely removed by surgery. This is often described as “resectable” melanoma, meaning the cancer can be surgically removed. Diagnostic imaging such as CT scans or other scanning methods may be required before enrollment to confirm that there is no evidence of cancer remaining after surgery or spreading to distant sites.[10]

Pathology reports from your biopsy and surgery are essential documents for clinical trial qualification. These reports must clearly show the stage and subtype of your melanoma. For instance, trials might specify enrollment only for certain subtypes like stage IIIB or IIIC, or they might accept all stage III patients. The pathology report provides the detailed information about tumor thickness, ulceration, and lymph node involvement that trial coordinators need to verify your eligibility.

Some clinical trials also require biomarker testing as part of the qualification process. Biomarkers are biological indicators that can be measured in tissue or blood samples. For melanoma, one important biomarker is the BRAF gene. Approximately half of melanomas have mutations in the BRAF gene, and some clinical trials specifically recruit patients based on whether their melanoma has this mutation or not. Testing for BRAF and other genetic markers is typically done using tissue from your biopsy or surgery.[9]

Blood tests are commonly required before entering a clinical trial to assess your overall health and ensure you don’t have conditions that might interfere with the study treatment or put you at risk. These might include tests of your liver function, kidney function, blood cell counts, and other measures. You may also need baseline imaging scans before starting treatment in a trial so that researchers can later compare these to scans taken during and after treatment to measure how well the therapy is working.

⚠️ Important
Clinical trials for stage III melanoma often test treatments given after surgery to prevent the cancer from coming back or spreading. Even after complete surgical removal, there remains a risk of recurrence, which is why post-surgery (adjuvant) treatments are being actively studied. Participating in a clinical trial may give you access to newer therapies that are not yet widely available.[10]

The diagnostic tests required for clinical trial enrollment serve multiple purposes. They help researchers ensure that all participants truly have stage III disease, they establish baseline measurements to track treatment effects, and they identify any health concerns that might make certain treatments unsafe for specific individuals. While the testing process for trial qualification can seem extensive, each test serves an important purpose in protecting participants and advancing medical knowledge.

If you are interested in clinical trials, discuss with your oncologist or dermatologist whether any trials might be appropriate for you. They can explain what diagnostic tests would be needed for qualification and help you understand whether the potential benefits of trial participation align with your treatment goals. Keep in mind that even if initial screening tests show you might qualify, additional evaluations may be required before final enrollment.

Prognosis and Survival Rate

Prognosis

The outlook for people with stage III melanoma depends on several factors that doctors consider when estimating how the disease might progress. These factors include the thickness of the original melanoma tumor, whether the top layer of the melanoma appeared broken (ulcerated) under microscopic examination, how many lymph nodes contain cancer cells, and whether there are satellite or in-transit metastases between the original melanoma and the lymph nodes.[1]

Patients with stage III resectable melanoma face a significant risk of the cancer returning after surgical treatment alone. Historically, the risk of melanoma recurrence has ranged from approximately 40% to 90% at five years following surgery without additional treatment. This wide range reflects the different subtypes within stage III, with some subtypes having better outcomes than others.[10]

Even after surgery to remove stage III melanoma and the affected lymph nodes, there remains a possibility that the cancer can return or spread to other parts of the body. When melanoma comes back after treatment, this is called recurrence. Research examining medical records of patients with stage III melanoma who chose to “watch and wait” after surgery showed that 50% of people (125 out of 251) experienced cancer recurrence, and among those who had recurrence, 53% (66 out of 125) saw their cancer spread to other body parts.[9]

The same research also looked at patients who received treatment after surgery, showing that 33% (43 out of 129) had their cancer return, and of those, 47% (20 out of 43) experienced spread to other parts of their body. These statistics demonstrate that while treatment after surgery can reduce recurrence risk, careful monitoring remains important for all stage III melanoma patients.[9]

Survival rate

Survival rates for stage III melanoma vary considerably based on the specific subtype and individual patient factors. While precise survival statistics depend on which subgroup of stage III melanoma you have been diagnosed with (IIIA, IIIB, IIIC, or IIID), understanding your prognosis requires discussing your specific situation with your healthcare team, who can provide information relevant to your individual case.

It’s important to remember that survival statistics are based on groups of people and cannot predict exactly what will happen in any individual case. Many factors influence outcomes, including how quickly treatment begins, the specific treatments used, your overall health, and how your body responds to therapy. Advances in melanoma treatment in recent years have improved outcomes for many patients with stage III disease compared to historical data.[10]

Your doctor or specialist nurse can provide the most accurate information about your expected prognosis based on your exact stage of melanoma and personal health factors. They can explain what your stage means for your treatment options and long-term outlook. Don’t hesitate to ask questions about what the statistics mean for your specific situation and what steps you can take to improve your chances of a favorable outcome.[3]

Ongoing Clinical Trials on Malignant melanoma stage III

  • Study Comparing Ipilimumab and Nivolumab to Nivolumab Alone for Patients with Resectable Stage III Melanoma

    Recruiting

    1 1 1 1
    Investigated diseases:
    Investigated drugs:
    Sweden
  • Study of Regorafenib with BRAF/MEK-Inhibitor Combination for Patients with Advanced Melanoma After Previous Treatment

    Recruiting

    1 1 1
    Investigated drugs:
    Belgium
  • Study of LTX-315 and Pembrolizumab for Patients with Resectable Stage III-IV Melanoma

    Recruiting

    1 1
    Investigated diseases:
    Investigated drugs:
    Norway
  • A study of ipilimumab and nivolumab to observe immune system changes in patients with unresectable stage III or IV melanoma

    Not yet recruiting

    1 1 1
    Investigated drugs:
    The Netherlands
  • Study of BNT111 and cemiplimab in patients with advanced melanoma who have not responded to other therapies

    Not recruiting

    1 1 1
    Investigated drugs:
    Germany Italy Poland Spain
  • Study of local treatment options for large metastases in patients with BRAF V600 mutated melanoma receiving Encorafenib and Binimetinib combination therapy

    Not recruiting

    1 1 1 1
    Investigated drugs:
    Germany
  • Study on L19IL2 and L19TNF Treatment Before Surgery for Patients with Advanced Melanoma

    Not recruiting

    1 1 1
    Investigated diseases:
    France Germany Italy Poland
  • Study on the Safety of Continued Treatment with GME751 (Pembrolizumab Biosimilar) for Patients with Melanoma or Non-Small Cell Lung Cancer

    Not recruiting

    1 1 1 1
    Lithuania Romania Spain
  • Study of Nivolumab and Relatlimab for Patients with Stage III-IV Melanoma After Surgery

    Not recruiting

    1 1 1 1
    Investigated drugs:
    Austria Belgium Czechia Denmark Finland France +7
  • Study on the Safety and Effects of ATL001 and Nivolumab for Adults with Metastatic or Recurrent Melanoma

    Not recruiting

    1 1 1
    Investigated drugs:
    Spain

References

https://www.curemelanoma.org/about-melanoma/melanoma-staging/stage-3

https://www.aimatmelanoma.org/stages-of-melanoma/stage-iii/

https://www.cancerresearchuk.org/about-cancer/melanoma/stages-types/stage-3

https://www.mskcc.org/cancer-care/types/melanoma/diagnosis/melanoma-stages

https://my.clevelandclinic.org/health/diseases/14391-melanoma

https://www.aimatmelanoma.org/stages-of-melanoma/stage-iii/

https://www.curemelanoma.org/about-melanoma/melanoma-staging/stage-3

https://www.cancerresearchuk.org/about-cancer/melanoma/stages-types/stage-3

https://www.keytruda.com/melanoma/stage-3/

https://pubmed.ncbi.nlm.nih.gov/38527258/

https://www.cancer.gov/types/skin/patient/melanoma-treatment-pdq

https://www.curemelanoma.org/about-melanoma/melanoma-staging/stage-3

https://www.curemelanoma.org/blog/practical-recommendations-for-surviving-and-thriving-despite-melanoma

https://www.aimatmelanoma.org/stages-of-melanoma/stage-iii/

https://www.cancer.org/cancer/types/melanoma-skin-cancer/after-treatment/follow-up.html

https://conquer-magazine.com/issues/special-issues/the-journey-through-stage-iii-melanoma-a-guide-for-patients

https://medlineplus.gov/diagnostictests.html

https://www.questdiagnostics.com/

https://www.healthdirect.gov.au/diagnostic-tests

https://www.who.int/health-topics/diagnostics

https://www.yalemedicine.org/clinical-keywords/diagnostic-testsprocedures

https://www.nibib.nih.gov/science-education/science-topics/rapid-diagnostics

https://www.health.harvard.edu/diagnostic-tests-and-medical-procedures

https://www.roche.com/stories/terminology-in-diagnostics

FAQ

How long does it take to get results from a sentinel lymph node biopsy?

The timing for sentinel lymph node biopsy results typically depends on your healthcare facility, but results usually become available within several days to about a week after the procedure. The lymph nodes removed during surgery must be carefully examined by a pathologist under a microscope to look for cancer cells, which requires time for proper tissue processing and analysis. Your doctor will schedule a follow-up appointment to discuss the results and explain what they mean for your treatment plan.

What’s the difference between a sentinel lymph node biopsy and removing all the lymph nodes?

A sentinel lymph node biopsy removes only the first one or two lymph nodes that drain the area where the melanoma was located, while complete lymph node removal (called lymph node dissection) takes out many more nodes from that region. The sentinel node biopsy is done first to see if cancer has spread to the lymph nodes. If cancer is found in the sentinel nodes, your doctor may recommend removing additional lymph nodes, though this decision depends on various factors including the extent of cancer involvement and current treatment guidelines.

Can stage III melanoma be detected through blood tests alone?

No, stage III melanoma cannot be diagnosed through blood tests alone. While blood tests may be part of your overall evaluation, diagnosing stage III melanoma requires tissue examination through biopsies of the melanoma and lymph nodes. Blood tests can assess your general health and may detect certain tumor markers in some cases, but tissue analysis under a microscope remains the gold standard for confirming melanoma and determining its stage.

Do I need imaging scans if my sentinel lymph node biopsy is positive?

Yes, if your sentinel lymph node biopsy shows cancer cells, your doctor will typically recommend imaging scans such as CT scans or other tests to check whether melanoma has spread beyond the regional lymph nodes to distant parts of your body. These scans help confirm that you have stage III disease (regional spread only) rather than stage IV disease (distant spread), which would change your treatment approach. The specific scans recommended depend on your individual situation and your doctor’s assessment.

What happens if my pathology report shows ulceration?

If your pathology report indicates that the melanoma had ulceration (broken skin when examined under a microscope), this information affects how your melanoma is classified within stage III. Ulceration is one of the factors used to determine your specific subtype (IIIA, IIIB, IIIC, or IIID) and can influence your prognosis and treatment recommendations. Melanomas with ulceration are generally considered higher risk than those without ulceration at the same thickness, so your doctor may recommend more aggressive monitoring or treatment approaches.

🎯 Key takeaways

  • Stage III melanoma diagnosis requires tissue examination through biopsies, with the sentinel lymph node biopsy being a critical test for detecting cancer spread to nearby lymph nodes.
  • The lymphatic system serves as a pathway for melanoma to spread, making lymph node evaluation essential for accurate staging.
  • Stage III melanoma has four subtypes (IIIA, IIIB, IIIC, IIID) determined by tumor thickness, ulceration, lymph node involvement, and presence of satellite or in-transit metastases.
  • If lymph nodes near the melanoma are visibly swollen, ultrasound examination with possible biopsy often replaces the sentinel lymph node biopsy procedure.
  • Clinical trial qualification requires specific diagnostic tests including pathology confirmation, imaging scans, blood work, and sometimes biomarker testing like BRAF gene analysis.
  • Cancer can appear between the original melanoma and lymph nodes as microsatellite, satellite, or in-transit metastases, each defined by their distance from the primary tumor.
  • Even after complete surgical removal of stage III melanoma, significant recurrence risk remains, ranging from 40% to 90% at five years without additional treatment.
  • Modern diagnostic methods using the TNM classification system provide detailed information that helps doctors precisely categorize melanoma and plan appropriate treatment strategies.