Theories of carcinogenesis and relationship of neoplasms
In pathological anatomy, the exact mechanism of malignant transformation of melanocytes is explained by two fundamental theories describing the relationship between benign nevi and malignant melanomas:
- Direct relationship. This is the most common perspective among specialists. According to it, malignant melanoma forms directly from the cells of a pre-existing benign nevus.
- Independent development. This concept suggests that a nevus and a melanoma represent two completely different, parallel pathways of tumor transformation of the original melanocyte. In other words, a malignant tumor can arise independently, bypassing the benign precursor stage.
Epidemiological features
The epidemiology of malignant tumors of melanin-producing tissue shows an alarming trend: incidence rates are rapidly rising. Statistical estimates indicate a high degree of risk: every hundredth person born in 2000 will develop melanoma during their lifetime.
The age distribution of patients has specific characteristic features:
- Main group: the pathology is most frequently diagnosed in individuals aged 40–60 years, with the absolute peak incidence occurring in the 50s.
- Young age: the disease poses a tremendous threat to young women. In the 25–29 age cohort, it is the most frequent malignant tumor.
Mortality rates also remain significant, with approximately 6,000 deaths registered from this pathology.
Tumor dynamics and growth patterns
The morphological picture and clinical behavior of melanoma directly depend on the direction of its spread. The initial stage may present as a preinvasive tumor—melanoma in situ. Subsequently, the neoplasm exhibits two fundamentally different growth directions:
- Horizontal (radial) growth. Atypical cells spread exclusively within the epidermis. This pattern of spread is typical of superficial spreading melanoma and lentigo maligna melanoma.
- Vertical growth. Characterized by aggressive invasion of tumor masses deep into the dermis. This growth pattern is characteristic of nodular melanoma.
It is extremely critical to understand the dynamics of the pathological process: if a radially growing tumor is left untreated, it will eventually progress to vertical growth.
Clinical and morphological classification
Depending on the growth pattern and depth of tissue invasion, 4 clinical and morphological types of melanoma are distinguished. Their prevalence statistics (using US data) are as follows:
- Superficial spreading: the most frequent form, accounting for 75% of cases.
- Nodular: less common, accounting for 15%.
- Lentigo maligna melanoma: diagnosed in 5% of cases.
- Acral lentiginous: the rarest variant, accounting for only 2–3%.
Prognostic factors and staging
Patient prognosis is largely determined by the depth of invasion of the melanoma into underlying tissues. Special invasion-level systems are used for the most accurate histological staging (microstaging), allowing for an objective assessment of lesion severity at the microscopic level.
Briefly: answers to topical questions
What classifications are used in pathological anatomy to assess the depth of melanoma invasion?
Two systems are used to assess the depth of melanoma invasion: Clark levels and Breslow thickness.
- Clark levels of invasion (Clark) — evaluate the penetration of cells into anatomical layers of the skin: from Level I — melanoma in situ, when cells are confined to the epidermis, to Level V — invasion into the subcutaneous adipose tissue.
- Breslow thickness (Breslow) — based on measuring tumor thickness in millimeters. The following gradations are distinguished: up to 0.76 mm; 0.76–1.5 mm; 1.5–4 mm; more than 4 mm. This system is considered more objective and reproducible; prognosis directly depends on tumor thickness and level of invasion.
What microscopic signs of cellular and tissue atypia are characteristic of malignant melanoma?
Malignant melanoma is characterized by cellular polymorphism and alterations in tissue architecture.
- Tissue features — proliferation of individual melanocytes or their nests throughout the entire thickness of the epidermis, asymmetric arrangement of tumor cell clusters during the transition to the vertical growth phase, and invasion with destruction of the basement membrane.
- Cellular features — variation in cell size and shape: round, elongated, spindle-shaped, dendritic, epithelioid; cytoplasm may be scanty or abundant, clear or dark, vacuolated. Cells may contain melanin or be amelanotic; dark atypical nuclei are characteristic. Mitotic figures, including atypical ones, may also be observed.
What are the main pathways of metastasis of malignant melanoma?
Malignant melanoma spreads via two main pathways: lymphatic and hematogenous.
- Lymphatic pathway — leads to the formation of regional lymph node metastases.
- Hematogenous pathway — results in distant metastasis. Melanoma exhibits a pronounced tendency for early hematogenous spread even with a small primary tumor thickness. Metastases most frequently affect the lungs, liver, brain, and bones.
The appearance of satellites—daughter tumor foci around the primary lesion—is also characteristic.
What prognostic factors are considered in melanoma staging according to the international TNM system?
The following parameters are considered when staging melanoma according to the AJCC/UICC TNM system:
- Breslow tumor thickness.
- Presence of ulceration.
- Mitotic rate.
- Status of lymph nodes, including the presence of regional metastases.
- Extent of metastatic disease, including the presence of distant metastases.
Additionally, Clark level of invasion, presence of satellites, and signs of tumor regression may be evaluated.
To memorize the 4 melanoma types by frequency (from most common to rare), use the mnemonic: Superficial Nodule Lightly Attacks (Superficial spreading — 75%, Nodular — 15%, Lentigo maligna melanoma — 5%, Acral lentiginous — 2-3%).
Class and exam questions
What is the origin of the cells from which these tumors develop?
The source of all neoplasms in this group is melanocytes. During development, these cells originate from the neural crest.
Does malignant melanoma always develop from a preexisting nevus?
No. Although the theory of direct relationship (development from a nevus) is the most common, the theory of independent development also exists, according to which a nevus and a melanoma represent two different pathways of melanocyte transformation.
Which type of tumor growth is considered more prognostically dangerous?
Vertical growth poses the greatest danger, as cells invade deep into the dermis. If left untreated, a radially growing tumor will eventually transition into the vertical growth phase.
Which clinical and morphological form of melanoma is the most common?
According to statistics, the most frequent form is superficial spreading melanoma, accounting for approximately 75% of all cases.
What else to study on this topic
- Invasion-level systems for determining histological microstaging
- Histological criteria for preinvasive melanoma in situ
- Morphological differences between superficial spreading and nodular melanoma
- Localization and growth features of acral lentiginous melanoma
- Cellular mechanisms of transition from radial to vertical growth
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