Morphological markers of cellular atypia
A critical step in histological diagnosis is differentiating normal, benign proliferation from true cytological atypia. Classical markers of atypical changes at the cellular level include:
- Polymorphism: cells and their nuclei lose uniformity, acquiring variable sizes and shapes.
- Hyperchromasia: variable, typically excessive staining intensity of the nuclei is observed.
- Shift in the nuclear-cytoplasmic ratio in favor of the nucleus (cytoplasmic volume becomes scant).
- Loss of polarity (disruption of the normal orientation of epithelial cells relative to the basement membrane).
- Appearance of enlarged or structurally irregular nucleoli.
Clinically significant exception: the detection of areas with pronounced cellular atypia must always be documented in the pathomorphological report, as this condition significantly increases the probability of malignant neoplasms.
Glandular epithelium hyperplasia
The leading cause of pathological proliferation of glands (taking the uterine mucosa as an example) is absolute or relative hyperestrogenism. Depending on structural and cytological changes, several forms are distinguished:
- Simple hyperplasia (glandular-cystic). Numerous proliferating glands of various shapes are unevenly distributed within a dense cytogenic stroma. Their cystic dilation is frequently observed. A key distinguishing feature is that a substantial amount of stroma remains between the glands. The stroma itself is rich in fibroblasts and lymphoid elements; hematoxylin and eosin staining may reveal vascular congestion and thrombi.
- Complex hyperplasia (adenomatous). The glands acquire a tortuous, "corkscrew" configuration. The volume of the stroma drops sharply, and the glandular structures are located closely together ("back-to-back"). The epithelium becomes pseudostratified (multilayered), but without cytological atypia — the cells retain their regular shape and orientation.
- Atypical hyperplasia. A classic histological marker of progression toward malignancy. True cellular atypia of the epithelium appears against the background of convoluted, branching glands and papillary outgrowths (often in a restricted area of tissue).
Lentiginous melanocytic hyperplasia
A specific variant of cellular hyperplasia is the proliferation of melanocytes characteristic of dysplastic nevi (greater than 4 mm in size). This pathology is typically characterized by symmetry, well-defined borders, and a complex, uneven microarchitecture.
Features of the histological picture:
- Uneven clustering of melanocyte nests along the dermo-epidermal junction and in the area of epidermal ridges.
- Fusion of adjacent nests forming bridging structures.
- «Shoulder» sign: the extent of the epidermal component exceeds the dermal component (extending beyond it peripherally by at least 3 epidermal ridges).
- Additional features of dysplasia: presence of perivascular lymphocytic infiltrates and fibrotic changes in the papillary dermis (in the form of concentric eosinophilic fibroplasia).
The presence of multiple dysplastic or giant nevi (more than 50) is a major risk factor for developing malignant melanoma, a highly aggressive tumor of significant social importance due to its frequent occurrence in relatively young patients.
To memorize the classic signs of cellular atypia, use the «Plus-Minus» mnemonic rule: Plus (increased nuclear polymorphism, hyperchromasia, nuclear-cytoplasmic ratio, nucleolar size) and Minus (decreased cytoplasmic volume, loss of cellular polarity).
Class and exam questions
How to distinguish simple hyperplasia from complex hyperplasia?
The main criterion is the glandular-stromal ratio. In simple hyperplasia, sufficient stromal volume is preserved between glands. In complex hyperplasia, the amount of stroma is sharply reduced, and convoluted glands lie tightly, «back-to-back».
Is the degree of dysplasia indicated in the diagnosis of a dysplastic nevus?
No. According to the WHO classification (2006), the degree of dysplasia in such nevi is not specified. However, if pronounced cellular atypia is present in the tumor, the pathologist is obligated to document it in the report due to the high risk of melanoma.
What risk factors lead to the development of endometrial hyperplasia?
These include reproductive factors (anovulation, late onset of menopause, polycystic ovary syndrome), iatrogenic factors (estrogen monotherapy, tamoxifen intake), and comorbid conditions (obesity, type 2 diabetes mellitus, Lynch syndrome).
What else to study on this topic
- Mechanisms of genetic predisposition to the development of malignant melanoma.
- Features of stromal reactions in dysplastic processes (eosinophilic fibroplasia).
- Differential diagnosis of rare nevi (plexiform spindled cell, combined).
- Clinical significance of estrogen-secreting tumors (granulosa cell) in the pathogenesis of hyperplastic processes.
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