Specialty Guide · Path-iQ Global Pathology Review
Cytopathology is the examination of individual cells and small cell clusters for diagnostic purposes. Its greatest strength is speed and minimally invasive sampling — a fine needle can aspirate a deep-seated lesion under ultrasound guidance in minutes, yielding a diagnosis that would otherwise require major surgery. Cytopathology underpins cervical cancer screening programmes that have reduced cervical cancer mortality by over 70% in countries with high uptake.
| Sample Type | Collection Method | Common Applications | Processing |
|---|---|---|---|
| Fine needle aspiration (FNA) | 22–25G needle, US-guided or palpation-guided | Thyroid, lymph node, breast, salivary gland, pancreas, liver, lung | Direct smears + cell block or LBC |
| Cervical cytology (Pap smear) | Cervical brush → LBC vial or direct smear | Cervical cancer screening; HPV triage | LBC (ThinPrep/SurePath) or conventional |
| Urine cytology | Voided midstream urine | Urothelial carcinoma detection/surveillance | LBC + Paris System reporting |
| Sputum cytology | 3 early-morning deep-cough specimens | Suspected central lung carcinoma (squamous, SCLC) | Saccomanno fixative; Papanicolaou stain |
| Bronchial wash/BAL | Bronchoscope flush of airways | Lung carcinoma, Pneumocystis jirovecii, MAC | Centrifugation; Diff-Quik + Pap stain |
| EBUS-FNA | Endobronchial ultrasound-guided FNA | Mediastinal staging; sarcoidosis; lymphoma | Rapid on-site evaluation (ROSE) + cell block |
| EUS-FNA | Endoscopic ultrasound-guided FNA | Pancreatic lesions, submucosal GI tumours | ROSE + cell block; molecular ancillary |
| Pleural/peritoneal fluid | Thoracocentesis or paracentesis | Malignant effusion detection; mesothelioma | Cytocentrifuge; cell block for IHC |
| CSF cytology | Lumbar puncture | Leptomeningeal carcinomatosis; CNS lymphoma; medulloblastoma | Cytocentrifuge within 1 hour of collection |
The Bethesda System (last revised 2014) standardised cervical cytology reporting into six categories that link directly to clinical management algorithms. The system uses a single terminology for both conventional smears and liquid-based cytology (LBC).
| TBS Category | Definition | Approximate CIN2+ Risk | Recommended Management |
|---|---|---|---|
| Negative for intraepithelial lesion or malignancy (NILM) | No abnormal squamous or glandular cells | <1% | Routine screening interval |
| ASC-US | Atypical squamous cells of undetermined significance | 5–10% | HPV co-test; colposcopy if HPV positive |
| ASC-H | Atypical squamous cells — cannot exclude HSIL | 25–40% | Colposcopy |
| LSIL | Low-grade squamous intraepithelial lesion (HPV/CIN1) | 15–25% | Colposcopy |
| HSIL | High-grade squamous intraepithelial lesion (CIN2/3) | 70–80% | Colposcopy + biopsy; LEEP/cone if CIN2+ |
| AGC / AIS | Atypical glandular cells; adenocarcinoma in situ | Variable; AIS 48–72% CIN2+ risk | Colposcopy + ECC + endometrial sampling |
| Squamous cell carcinoma | Malignant squamous cells | — | Urgent colposcopy + biopsy; oncology referral |
| Adenocarcinoma | Malignant glandular cells (endocervical, endometrial, extrauterine) | — | Urgent colposcopy + biopsy; oncology referral |
The Bethesda System for Reporting Thyroid Cytology (3rd edition, 2023) classifies thyroid FNA into six categories with associated malignancy risks and management recommendations.
| Category | Bethesda Category | Malignancy Risk (ROM) | Usual Management |
|---|---|---|---|
| I | Non-diagnostic / unsatisfactory | 5–10% | Repeat FNA with ultrasound guidance |
| II | Benign | 0–3% | Clinical follow-up; repeat ultrasound |
| III | Atypia of undetermined significance (AUS/FLUS) | 10–30% | Repeat FNA; molecular testing (ThyroSeq, Afirma) |
| IV | Follicular neoplasm / Hürthle cell neoplasm | 25–40% | Lobectomy or molecular testing |
| V | Suspicious for malignancy | 60–75% | Lobectomy or total thyroidectomy |
| VI | Malignant | 97–99% | Total thyroidectomy |
| System | Organ/Sample | Edition | Published By |
|---|---|---|---|
| The Paris System (TPS) | Urine cytology | 2nd ed. 2022 | International urine cytology working group |
| Papanicolaou Society of Cytopathology (PSC) Pancreaticobiliary | Pancreas, bile duct, ampulla | 2nd ed. 2020 | PSC working group |
| Milan System (MSRSGC) | Salivary gland FNA | 2nd ed. 2022 | International salivary gland cytology group |
| International System for Serous Fluid Cytopathology (ISfSFC) | Pleural, peritoneal, pericardial fluid | 1st ed. 2020 | IAC-ISFC working group |
| Yokohama System | Pancreatic cyst fluid | Revised 2024 | IAP working group |
| RCPath/IAC Urinary Cytology | Urine, bladder wash | Updated 2023 | RCPath / IAC joint committee |
Liquid-based cytology (LBC) transfers the cervical sample into a preservative vial (ThinPrep/Hologic or SurePath/BD). A thin layer of cells is prepared from the vial for microscopic examination. LBC offers several advantages: fewer unsatisfactory samples (1–2% vs 5–8% for conventional smears), the ability to test the residual sample for HPV and other molecular assays, better cell preservation, and a cleaner preparation. Most European and Australasian national screening programmes have transitioned entirely to LBC; the United States uses both LBC and conventional smears.
ROSE is the practice of having a cytotechnologist or cytopathologist immediately evaluate a preliminary stained smear during an FNA procedure to confirm specimen adequacy and preliminary diagnosis. ROSE has been shown to reduce non-diagnostic rates in EBUS-FNA and EUS-FNA of pancreatic lesions from 15–20% to under 5%, and improves overall diagnostic yield. It is standard of care for EBUS-guided mediastinal staging in many high-volume centres.
One of the architects of the Bethesda System for Reporting Thyroid Cytology. Editor of multiple editions of the TBSRTC atlas and an authority on thyroid FNA adequacy criteria.
Former Secretary General of the International Academy of Cytology (IAC). Expert in breast FNA, liquid-based cytology standardisation, and molecular ancillary testing in cytopathology.
Lead editor of The Bethesda System for Reporting Cervical Cytology (4th edition). Expert in HPV-related cervical disease and the evolution of cervical cancer screening algorithms.
Lead author of the Papanicolaou Society of Cytopathology System for Reporting Pancreaticobiliary Cytology. Expert in EUS-guided FNA of pancreatic lesions and cyst fluid cytology.
Expert in urinary tract cytology, pulmonary FNA, and the Paris System for urine cytology. Editor of the RCPath cytology curriculum and a leading figure in UK cytopathology education.
Authority on thyroid cytology, salivary gland FNA, and the application of molecular testing to Bethesda III and IV thyroid nodules. A contributor to the Milan System for Salivary Gland Cytology.