Differentiation and anaplasia: how a tumour cell looks under the microscope !
- Lesion
The more a tumour looks like its normal tissue, the better differentiated it is. Anaplasia means the cells have lost that likeness.
Updated 2026-11-01
What it is
Differentiation is how closely neoplastic cells resemble their normal counterparts in shape and function; anaplasia is the lack of it and is the hallmark of malignant cells. The degree of differentiation is the basis of tumour grade, and well differentiated tumours often keep functions such as making keratin, mucin or hormones. Undifferentiated tumours tend to grow fast and behave aggressively, as anaplastic thyroid carcinoma shows.
Structure
- Pleomorphism: cells and nuclei vary widely in size and shape; bizarre tumour giant cells may appear.
- Nuclei are large and hyperchromatic (dark), with coarse chromatin and one or more prominent nucleoli.
- The nucleus takes up a much larger share of the cell than normal.
- Mitoses are numerous and may be abnormal (tripolar or multipolar spindles).
- Loss of polarity: cells no longer line up in their normal orientation and grow in disorganised sheets.
- Areas of ischaemic necrosis appear where growth outruns the blood supply.
Markers
- Cytokeratins (epithelial)
- Vimentin (mesenchymal)
- CD45 (leukocytes)
- S-100, SOX10, HMB-45 (melanocytic)
- Desmin (muscle)
- Chromogranin, synaptophysin (neuroendocrine)
- Ki-67 (proliferation index)
Clinical notes
- Tumour grade is usually reported from well differentiated (low grade) to poorly differentiated or undifferentiated (high grade).
- A carcinoma of unknown primary is worked up largely through its differentiation pattern and immunoprofile.
In the lab
- Routine haematoxylin and eosin (H&E) shows nuclear and architectural atypia; grade is assigned on that slide.
- When a tumour is too undifferentiated to recognise, immunohistochemistry identifies its lineage with markers such as those above.
- The Ki-67 index estimates the fraction of cycling cells and helps grade some tumours (for example neuroendocrine tumours).
Test yourself
Think of the answer, then tap the question to see it.
What is anaplasia?
Lack of differentiation of neoplastic cells; it is a hallmark of malignant transformation.
What are three nuclear features of anaplasia?
Hyperchromasia, pleomorphism with a high nuclear-to-cytoplasmic ratio, and large prominent nucleoli (also atypical mitoses).
What is the difference between grade and stage?
Grade describes how differentiated the cells look under the microscope; stage describes size and spread (nodes, metastases) and usually carries more prognostic weight.
What immunohistochemical marker suggests an epithelial origin for an undifferentiated tumour?
Cytokeratin positivity suggests a carcinoma; vimentin suggests mesenchymal, CD45 lymphoid and S-100 or SOX10 melanocytic origin.
Related
- Benign vs malignant tumours: the comparison table
- Dysplasia and carcinoma in situ
- Grading and staging: what TNM means
- Immunohistochemistry: the principle and the markers to know
- Naming tumours: -oma, carcinoma, sarcoma, and the misleading names
Related conditions
- Follicular, oncocytic (Hürthle cell) and anaplastic thyroid carcinoma
- Thyroid cancer (papillary)
- Cutaneous squamous cell carcinoma
- Carcinoma of unknown primary
- Soft tissue sarcomas (liposarcoma, leiomyosarcoma, rhabdomyosarcoma)
- Glioblastoma
- Head and neck squamous cell carcinoma (oral cavity and oropharynx, HPV)
Elsewhere in DurgiPedia
- Microscopy and stains: H&E, PAS, trichrome, silver, immunohistochemistry
- Cell cycle, mitosis and meiosis
- Stem cells and tissue renewal: labile, stable and permanent tissues
Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.
Sources: Tumor Grade (National Cancer Institute (NCI), 2026); What Is Cancer? (National Cancer Institute (NCI), 2026); Cancer Classification (SEER Training Modules, National Cancer Institute, 2026).
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Representative model, for educational purposes only.