Cytologic Criteria of Malignancy

Any slide showing one or a combination of the following cellular changes should be carefully reviewed for potential malignancy. A cytology laboratory should be consulted for clarification if needed.

Cytologic Characteristics / Tumor Cell Types / Image
Nuclear
• Anisokaryosis
• Macrokaryosis
• Variation in nuclear/cytoplasmic ratio
• Coarse chromatin pattern that clumps
• Irregular nuclear pattern
• Abnormal size, shape, and appearance of nucleoli
• Irregular nuclear membrane / Epithelial
• Round nucleus that is usually centrally located with a smooth to slightly coarse chromatin pattern
• One or more nucleoli
Mesenchymal
• Oval, centrally located nucleus
Round Cell
• Centrally or eccentrically located /
Cytoplasmic
• Vascuolization
• Variable amount of cytoplasm from cell to cell
• Basophilia with Wright’s stain
• Abnormal cytoplasmic boundaries / Epithelial
•  Cytoplasm with secretory products or vacuolates
Mesenchymal
• Abnormal cytoplasmic boundaries and extensions
• Moderate amount
Round Cell
• Well-defined cytoplasmic boundaries
• Variable amount, granularity, and vacuolization /
Structural
• Anisocytosis
• Macrocytosis
• Pleomorphic / Epithelial
• Large to very large cells
• Round to oval to caudate cells, easily exfoliating into sheets, clusters, or clumps
Mesenchymal
• Small to medium cells
• Spindle-shaped cells hard to exfoliate
• Individual cells or in disorganized clusters
Round Cell
• Small to medium cells
• Round to oval cells; easy to exfoliate individual cells /

Table 1 / Cytologic Criteria of Malignancy

Normal/Hyperplasia / Malignant Neoplasia
General or Population Criteria
Cellularity / Low to moderate
/ Moderate to high

Location / Normal tissue present for tissue sample / Abnormal tissue present for tissue location
Pleomorphism anisocytosis macrocytosis / None to minimal
/ Moderate to marked

Nuclear Criteria of Malignancy
Size (anisokaryosis) / Uniform
/ Variable

Nuclear/cytoplasmic ratios / Uniform
/ Variable

Nucleoli / Generally small and round; single to few in number
/ Large, multiple, prominent, and irregular in shape

Nuclear chromatin / Uniform patterns
/ Abnormally clumped (around nucleoli, along nuclear envelopes)

Mitosis / Few and normal
/ Increased in normal and abnormal configurations

Nuclear shape / Uniform, round to oval
/ Potentially irregular, deeply indented, possible support for abnormal division

Nuclei number / Usually one or even numbers present
/ Potentially multiple with odd or even number of nuclei and variably sized nuclei in individual cells

Table 2 / Cytoplasmic Criteria of Malignancy

Normal/Hyperplasia / Malignant Neoplasia
Basophilia / Minimal unless actively producing proteins / Potentially increased or deep blue
Vacuolization / Normal in phagocytic, secretory or degenerating cells / Potential large and abnormal “signet ring” morphology
Cannibalism / None / Potentially present