Clinical Forms and Growth Phases
The development of melanoma typically goes through two stages: radial (horizontal spread of atypical cells within the epidermis) and vertical (growth deep into the dermis along nerves and vessels). Four main forms are distinguished:
- Superficially spreading melanoma: the most common form. It is characterized by prolonged radial growth. Macroscopically, it appears as an irregularly shaped patch more than 6 mm in diameter, combining areas of varying pigmentation.
- Nodular melanoma: accounts for approximately 10–15% of cases. Its key feature is the complete absence of a radial phase. The tumor immediately exhibits invasive vertical growth. It appears as a well-circumscribed dark nodule on a broad base (sometimes resembling a papilloma). The surface is initially smooth, then becomes warty (verrucous) and ulcerates.
- Lentigo maligna melanoma (lentigo maligna): typical for elderly individuals (peak incidence around 70 years). It develops on the background of precancerous Dubreuilh's melanosis, most often on the face. It begins as a flat brown patch that eventually changes color and forms elevated nodules.
- Acral lentiginous melanoma: the most common variant among Black populations. It is localized on the soles of the feet and palms of the hands and exhibits both growth phases.
Pathomorphology and Cellular Polymorphism
The histological picture of melanoma features marked diversity. In the epidermis, proliferation of atypical melanocytes is observed in the form of nests throughout the entire thickness of the layer.
- Cytology: Tumor cells may be large polygonal (epithelioid), elongated spindle-shaped, or small with a narrow rim of cytoplasm. The cytoplasm is typically pale and abundant, containing finely dispersed (dust-like) melanin. Nuclei are atypical with uneven chromatin distribution, and pathological mitoses are frequent. Morphologically, cells may resemble Paget cells.
- Stroma and Inflammation: A lymphocytic infiltrate forms around the tumor. If it is unevenly distributed or completely absent, this further supports the malignancy of the process.
- Signs of Regression: Areas of partial or complete regression may appear within the tissue. They are represented by fields of fibrosis, abundant vasculature, and macrophagic-lymphocytic infiltrates with melanophages. It is important to remember that the appearance of regression zones often masks the onset of dangerous invasive growth.
- Surrounding Tissues: Hair follicles and eccrine sweat glands may be involved in the process. Signs of solar elastosis or remnants of a nevus are frequently found in the surrounding dermis.
Prognostic Criteria: Clark and Breslow Systems
To assess disease severity and survival prognosis, pathologists use two main grading systems.
Clark Levels of Invasion (Clark): evaluate the depth of tumor penetration into anatomical skin layers.
- Level I: cells do not extend beyond the epidermis (melanoma in situ). Five-year survival is 100%.
- Level II: penetration into the papillary dermis without completely filling it (survival is 90%).
- Level III: the tumor fills the papillary dermis up to the lower boundary of the interpapillary pegs (survival is 70%).
- Level IV: invasion into the reticular dermis (survival is 40%).
- Level V: extension into the subcutaneous adipose tissue (survival drops to 25%).
Breslow Tumor Thickness (Breslow): measurement of the absolute thickness of the neoplasm in millimeters. This method is considered more accurate and reproducible.
- Up to 0.76 mm — prognosis is close to 100%.
- 0.76–1.5 mm — 90–95%.
- 1.5–4 mm — 60–75%.
- More than 4 mm — survival is less than 50%.
The clinical TNM staging system is also applied, where stage I yields a 95% survival rate, while stage IV yields only 20%.
Briefly: answers to topical questions
Which precancerous conditions and background processes precede the development of melanoma?
- Melanocytic dysplasia (dysplastic/atypical nevus) — a pathological process in which melanoma develops in approximately one-third of cases.
- Dubreuilh's melanosis (circumscribed precancerous melanosis of Dubreuilh) — a skin pathology on the background of which lentigo maligna develops, predominantly in elderly individuals.
- Pigmented nevomelanocytic nevus (melanocytic nevus) — a benign lesion on the background of which the tumor may also develop.
What metastasis pathways are characteristic of melanoma?
- Lymphogenous pathway — spread of tumor cells via lymphatic vessels with involvement of regional lymph nodes.
- Hematogenous pathway — spread of tumor cells via blood vessels with the development of distant metastases.
What immunohistochemical markers are used to verify melanoma?
- Melan A — a marker for immunohistochemical staining.
- Tyrosinase — an immunohistochemical marker.
- HMB45 — an immunohistochemical marker.
- SOX-10 — a marker for immunohistochemical staining.
What clinical signs are included in the ABCDE diagnostic rule for melanoma?
- A (Asymmetry) — asymmetry of the tumor.
- B (Border irregularity) — irregular borders of the lesion.
- C (Color variation) — uneven pigmentation or color change.
- D (Diameter) — diameter greater than 6 mm.
- E (Evolution) — evolution of the lesion, a key sign of change over time.
For quick memorization of Clark levels, imagine the skin layers from top to bottom: Epidermis (I) → Papillary dermis partially (II) and fully (III) → Reticular dermis (IV) → Adipose tissue (V).
Class and exam questions
What is the main difference between nodular melanoma and superficial spreading melanoma?
Nodular melanoma lacks a radial (horizontal) growth phase. It grows vertically from the start, invading the dermis, which makes it extremely aggressive.
From which lesions does melanoma most frequently develop?
About 40% of melanomas arise de novo from normal melanocytes. Approximately one-third of cases develop on the background of dysplastic (atypical) nevi.
What does the regression phenomenon in melanoma signify?
This is the replacement of part of the tumor with fields of fibrosis and macrophages. Despite the apparent "improvement," the appearance of regression areas requires a thorough rule-out of the onset of deep invasive growth.
What else to study on this topic
- Benign pigmented lesions (freckles, simple and senile lentigo)
- Nevomelanocytic and Blue Nevi: Histology and Classification
- Melanocytic Dysplasia and Lamellar Fibroplasia
- Dubreuilh's Melanosis as a Precancerous Condition
- Clinical TNM Staging System for Melanoma
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