Malignant Melanoma: Complications

The following are the most important diseases or complications that may be contributed to by malignant melanoma (MM):

Neoplasms – Tumor diseases (C00-D48).

• Paraneoplastic syndrome (concomitant symptoms of cancer not primarily due to the neoplasm (solid tumors or leukemias)): Degeneration of the cerebellum, Guillain-Barré syndrome, limbic encephalitis (meningitis), and chronic inflammatory demyelinating polyneuropathy (diseases of the peripheral nervous system associated with chronic disorders of peripheral nerves or portions of nerves).
• Squamous cell carcinoma (PEK) of the skin as a secondary tumor after malignant melanoma.
• Recurrence (recurrence) of a melanoma
• Melanoma as a second tumor (4-8% of melanoma patients).
  • Risk is two to three times higher than compared with normal population; high risk of recurrence of primary melanoma, especially if first disease is under 40 years of age, especially in familial patients (19 times more common than normal population); probable cause is sun exposure rather than a genetic cause
  • Second melanomas were thinner, averaging 0.65 mm, than first tumors, 0.90 mm; subsequent melanomas occurred during the first five years of follow-up, 36.8% in the first year. 27.3% were detected only after five or more years.
• Age-adjusted, sex-specific standardized incidence ratios (SIRs) for melanoma as a second tumor and other neoplasms (neoplasms) after a first melanoma.
  • Men: a second melanoma after a first melanoma (SIR 28.2); a pancreatic cancer (cancer of the pancreas) after a melanoma (SIR 10.61),
  • Women: a second melanoma after a first melanoma (SIR 38.9); an ovarian cancer (ovarian cancer) after a melanoma (SIR 14.73).
• Other neoplasms after melanoma (numbers: standardized incidence ratio (SIR) as the ratio of observed to expected tumor frequencies):
  • Non-Hodgkin’s lymphoma 3.12-fold.
  • Mammary carcinoma (breast cancer) 4.10-fold
  • Thyroid carcinoma 4.67-fold
  • Brain tumors 6.13-fold

Metastasis

• Surrounding skin (locoregional lesion), including soft tissues.
• Lymph nodes (most commonly in regional lymph nodes, but also in lymph nodes distant from the primary tumor)
• Lungs
• Central nervous system (CNS)
• Liver
• Bones

Psyche – nervous system (F00-F99; G00-G99)

• Parkinson’s disease (4-fold higher risk).

Prognostic factors

• The location of the melanoma influences the prognosis: patients with melanoma of the scalp have a worse prognosis than patients with melanoma of other body sites.
• De novo melanomas have a worse prognosis, i.e., shorter survival than forms arising from melanocytic nevi.
• Melanomas of the skin that have an NRAS mutation have a more aggressive course than melanomas with a BRAF mutation status:
  • Duration to progression in the NRAS group median 1.5 years; locoregional recurrence median 3, 3 years; metastases after 2.9 years
  • Duration to progression in BRAF group median 2.4 years; locoregional recurrence was not seen during the observation period; metastases after 4.1 years
  • Duration to progression in the group of patients without mutation 1.7 years; metastases after 2.6 years
• In patients with thin melanoma, the risk of positive sentinel lymph nodes is significantly increased by:
  • Male gender
  • Age < 60 years
  • Breslow thickness between 0.8 and 1.0 mm
  • Clark level IV or V
  • Dermal mitotic rate; this has a particularly strong prognostic value for melanomas up to 1 mm tumor thickness
  • Ulcerations (ulcerations)
• Calculated melanoma area in histological section: calculation based on the invasive cancer cells of a cross-sectional area of melanoma, starting from the section of the sample with the deepest melanoma cell. Melanoma area was found to be the most weighty prognostic factor. The calculated area captured the prognosis of melanoma better than Breslow thickness with stages I (≤ 1.0 mm) to IV (≥ 4 mm).
• Thin melanoma (thickness of 1 mm), with poor prognosis: the subdivision of the depth of infiltration of the tumor is seminal:
  • T1a (< 0.8 mm without ulceration) and
  • T1b (< 0.8 mm with ulceration; 0.8-1.0 mm with or without ulceration) [quoad vitam (“in terms of life/survival”) prognostically particularly unfavorable]

  Furthermore, prognostically particularly unfavorable is a location of the tumor on the scalp (compared to a localization on the back) [here already an increase from a thickness of 0.6 mm]

• Vitamin D: 20 ng/ml as a cut-off value: overall survival hazard ratio (HR) of 1.44 and melanoma-specific survival a HR of 1.37, i.e. the probability of dying or dying from the consequences of melanoma was increased by 44% and 37%, respectively
• Pregnancy-associated malignant melanoma (SAMM); regarding this, from a study, the following facts:
  • Diagnosis made during or within one year after the end of pregnancy.
  • Women were slightly younger than non-SAMM at 32.6 vs. 34.7 years of age
  • Localization: legs (40%) versus trunk (37%) in non-SAMM.
  • Recurrence rate was significantly increased in SAMM (12.5 vs. 1.4%)
  • Metastases occurred more frequently (25 versus 12.7%).
  • Mortality rate/sterility rate (20% versus 10.3%), with no significant difference.
• Obese men (≥ BMI 30; but not women) with metastatic melanoma who received the BRAF inhibitor dabrafenib or the MEK inhibitor trametinib lived longer:
  • 33.0 months, including 15.7 without tumor progression versus normal-weight men (BMI 18.5 to 24.9): 19.8 months, including 9.6 months without tumor progression
  • Women (regardless of BMI): median overall survival at least 33 months.