General approach to melanocytic lesions: evaluation of clinical and pathological features
| Histopathological feature | Favours benign | Favours malignant |
| Clinical | ||
| Age | Children/young adult (<30 years) | Adults/elderly (≥30 years) |
| Gender/location | M=F; any location | M, trunk; F, trunk/lower extremities |
| Colour | Uniform brown | Variegated, black |
| Borders/circumscription | Irregular | Regular |
| Size/diameter | <10 mm | >10 mm |
| Symmetry | Symmetrical | Asymmetrical |
| Evolution | Stable lesion | New, changing or ulcerated lesion; symptomatic lesion (pain/pruritus) |
| Architectural | ||
| Size | <10 mm | >10 mm |
| Symmetry | Symmetrical | Asymmetrical |
| Circumscription | Well circumscribed | Poor circumscription |
| Regularity† | Regular | Irregular |
| Density of growth | Uniform, non-dense | Dense, sheet-like or confluent growth |
| Pagetoid ascent of cells | Absent | *Present |
| Architectural maturation‡ | Present | Absent |
| Epidermal reaction | Characteristic of certain lesions | Ulceration or ‘consumption of epidermis’ |
| Cytological | ||
| Nuclear size | Small (less than keratinocyte) | Large (larger than keratinocyte) |
| Nuclear/cytoplasmic ratio | Low | High |
| Chromasia | Hypo/normochromatic | Hyperchromatic |
| Pleomorphism | Absent | Present |
| Nuclear membranes§ | Regular: thin and uniform | Irregular: non-uniform thickenings, abnormal nuclear shapes |
| Nucleoli | Absent—variable/small | Present—macronucleoli, multiple nucleoli |
| Chromatin | Fine/dispersed | Coarse |
| Cellular cohesion | Cohesive | Dyscohesive |
| Pigmentation | Coarse melanin granules | Fine dusty melanin, amelanotic |
| Cytological maturation‡ | Present | Absent¶ |
| Stromal | ||
| Lymphocytic infiltrate | Absent—Mild | Present (often ‘brisk’) |
| Plasma cells** | Absent | May be present |
| Regressive features†† | Absent | May be present (partial or complete) |
| Solar elastosis | Absent or incidental | Supportive in certain lesions (desmoplastic melanoma, lentigo maligna, lentigo maligna melanoma) |
| Immunohistochemical‡‡ | ||
| Proliferative index (Ki67, MIB-1) | Negligible (<5%) | Increased (>15%) |
| Immunophenotypic maturation (HMB-45, proliferative index)‡ | Stratified staining pattern with loss of dermal expression with descent | Diffuse positivity |
| Other | ||
| Mitotic activity | Negligible; none in deep dermis | Increased numbers, deep dermal forms, clustering atypical forms, mitoses in pagetoid cells |
| Perineural invasion | Absent | May be present |
| Angiolymphatic invasion | Absent | May be present |
| Necrosis | Absent | May be present |
↵* Benign exceptions exist—please see text.
↵† Regularity of growth refers to a nested (or occasionally diffuse) pattern that shows uniformity in size and shape of nests, and which does not reveal destructive growth or large expansile nodules.
↵‡ Maturation may be evident in three ways: architectural—diminishment of nesting pattern with decrease in nest size; cytological—decrease in size of melanocytes with loss of cytoplasm and nucleoli; immunophenotypic—loss of activated melanocytic markers (HMB-45, decreased proliferative index).
↵§ Intranuclear cytoplasmic inclusions are a common feature of melanocytes both benign and malignant and offer no discriminating value in terms of biological potential; however, other nuclear membrane irregularities are suggestive of an atypical/malignant lesion (eg, nuclear membrane thickenings, nuclear snouts/indentations/grooves).
↵¶ Do not mistake a residual dermal naevic component as evidence of maturation.
↵** Plasma cells may accompany foci of scarring or concurrent inflammatory conditions.
↵†† Regressive features include: fibrosis, mononuclear inflammatory infiltrate, vascular proliferation, presence of melanophages, and a scattered distribution of any remaining dermal component (ie, in partial regression).
↵‡‡ See also table 2.