Clinical Forms and Growth Phases
Melanoma development typically progresses through two distinct phases: the radial growth phase (horizontal spread of atypical cells within the epidermis) and the vertical growth phase (invasion downward into the dermis along nerves and blood vessels). There are four primary clinical forms:
- Superspreading Melanoma (Superficial Spreading Melanoma): The most common form, characterized by a prolonged radial growth phase. Macroscopically, it appears as an irregularly shaped macule/patch greater than 6 mm in diameter with variegated pigmentation.
- Nodular Melanoma: Accounts for approximately 10–15% of cases. Its defining feature is the complete absence of a radial phase; the tumor initiates invasive vertical growth immediately. It presents as a well-circumscribed, dark, raised nodule on a broad base (sometimes resembling a papilloma). The surface is initially smooth, later becoming verrucous and prone to ulceration.
- Lentigo Maligna Melanoma: Typically occurs in elderly individuals (peak incidence around age 70). It develops from precancerous melanosis (melanosis circumscripta praeblastomatosa Dubreuilh), most frequently on the face. It begins as a flat brown patch that gradually changes color and develops elevated nodules.
- Acral Lentiginous Melanoma: The most prevalent variant in dark-skinned populations. It is localized on the palms and soles and exhibits both growth phases.
Pathomorphology and Cellular Polymorphism
The histological presentation of melanoma exhibits marked cellular diversity. The epidermis shows proliferation of atypical melanocytes arranged in nests throughout the epithelial layer.
- Cytology: Tumor cells may be large and polygonal (epithelioid), elongated and spindle-shaped, or small with a scant cytoplasm. The cytoplasm is typically pale and abundant, containing fine, dust-like melanin granules. Nuclei are atypical with irregular chromatin distribution, and pathological mitoses are frequent. Morphologically, cells may occasionally mimic Paget cells.
- Stroma and Inflammation: A lymphocytic infiltrate typically surrounds the tumor. A patchy or completely absent inflammatory response is an additional indicator of a malignant phenotype.
- Signs of Regression: Areas of partial or complete regression may be present, characterized by fields of fibrosis, prominent vascularity, and macrophage-lymphocytic infiltrates containing melanophages. Notably, regression zones can mask the onset of dangerous invasive growth.
- Adnexal Structures: Hair follicles and eccrine sweat glands may become involved. The surrounding dermis frequently shows signs of solar elastosis or residual nevus remnants.
Prognostic Criteria: Clark and Breslow Systems
Pathologists use two primary grading systems to assess disease severity and survival prognosis.
Clark Levels of Invasion: Evaluates the depth of tumor penetration into the anatomical layers of the skin.
- Level I: Cells are confined to the epidermis (melanoma in situ). 5-year survival is 100%.
- Level II: Invasion into the papillary dermis without completely filling it (survival is 90%).
- Level III: The tumor fills the papillary dermis up to the junction with the reticular dermis (survival is 70%).
- Level IV: Invasion into the reticular dermis (survival is 40%).
- Level V: Penetration into the subcutaneous adipose tissue (survival drops to 25%).
Breslow Tumor Thickness: Measurement of the absolute thickness of the neoplasm in millimeters using an ocular micrometer. This method is considered more precise and reproducible.
- < 0.76 mm — Prognosis approaches 100%.
- 0.76–1.5 mm — 90–95%.
- 1.5–4.0 mm — 60–75%.
- > 4.0 mm — Survival is less than 50%.
The clinical TNM staging system is also applied, where Stage I carries a 95% survival rate, whereas Stage IV drops to roughly 20%.