Pathological, genetic, immunological and molecular diagnostics of tumors

1. Concept

Tumor diagnosis combines morphological, immunological, genetic, and molecular methods to confirm malignancy, classify the tumor, and guide therapy/prognosis.

2. Morphological & cytological methods

Method	Use
Excision / biopsy	Tissue diagnosis (beware necrotic center of large masses)
Frozen section	Rapid intraoperative evaluation
Fine-needle aspiration (FNA)	Cytology of palpable lesions (breast, thyroid, nodes) or deep organs
Cytological smear	Shed/less-cohesive neoplastic cells (e.g. Pap smear)

3. Immunological methods

• Immunohistochemistry (IHC) — labeled monoclonal antibodies: PSA (prostate origin), estrogen receptor (breast prognosis/therapy), cytokeratin (carcinoma vs lymphoma).
• Flow cytometry — classifies leukemia/lymphoma by surface markers/differentiation antigens.

4. Tumor markers

Not diagnostic alone — used for screening, monitoring therapy response, detecting recurrence:

• PSA → prostate (also ↑ in BPH).
• CEA → colon, pancreas, stomach, breast.
• AFP → hepatocellular carcinoma, yolk-sac/embryonal tumors.

5. Molecular diagnostics

• Diagnosis by translocations — FISH/PCR detect e.g. BCR-ABL (CML).
• Prognosis — oncogene amplification: HER2/neu (breast), N-MYC (neuroblastoma).
• Minimal residual disease — PCR for BCR-ABL after CML therapy.
• Hereditary predisposition — germline TSG mutations (e.g. BRCA1) → screening/prophylaxis.
• DNA microarray — simultaneous expression profiling of thousands of genes (normal vs tumor cDNA hybridization).

💡 High-yield: Morphology (biopsy, frozen section, FNA, smear) + IHC (PSA, ER, cytokeratin) + flow cytometry (leukemia/lymphoma). Markers (PSA, CEA, AFP) = monitor, not diagnose. Molecular: FISH/PCR for translocations (BCR-ABL/CML), amplifications (HER2, N-MYC), MRD, BRCA1 germline, microarray profiling.