Lung cytology — pattern-based approach to small samples
Author: Faruk Skenderi, MD, PhDReviewed by: Semir Vranić, MD, PhDLast reviewed:
- Schmitt FC, et al. The World Health Organization Reporting System for Lung Cytopathology. Acta Cytol. 2023;67(1):80-91. https://doi.org/10.1159/000527580 (opens in new tab)
- Canberk S, et al. A brief review of the WHO reporting system for lung cytopathology. J Am Soc Cytopathol. 2023;12(4):251-257. https://doi.org/10.1016/j.jasc.2023.04.002 (opens in new tab)
- Lindeman NI, et al. Updated molecular testing guideline for the selection of lung cancer patients for treatment with targeted tyrosine kinase inhibitors: guideline from the CAP, IASLC and AMP. Arch Pathol Lab Med. 2018;142(3):321-346. https://doi.org/10.5858/arpa.2017-0388-CP (opens in new tab)
- Hendriks LE, et al. Oncogene-addicted metastatic non-small-cell lung cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2023;34(4):339-357. https://doi.org/10.1016/j.annonc.2022.12.009 (opens in new tab)
EBUS-TBNA and CT-guided FNA samples are limited. A pattern-first approach helps preserve material for ancillary testing.
- Adenocarcinoma: glandular/acinar groups, vacuolated cytoplasm, prominent nucleoli — confirm with TTF-1 and napsin A.
- Squamous cell carcinoma: keratinisation, dense cytoplasm, hyperchromatic nuclei — p40 is the preferred marker.
- Small cell carcinoma: nuclear moulding, scant cytoplasm, salt-and-pepper chromatin, high mitotic/apoptotic rate.
- Always preserve a cell block for immunohistochemistry and molecular studies: EGFR, ALK, ROS1, BRAF V600E, MET exon 14 skipping, RET, NTRK1–3, KRAS G12C and ERBB2, plus PD-L1 immunohistochemistry (ESMO 2023 guideline, Hendriks et al., Ann Oncol 2023; CAP/IASLC/AMP 2018 guideline).
- ROSE (rapid on-site evaluation) improves diagnostic yield and triages material for ancillary tests.
- Mesothelioma vs adenocarcinoma: calretinin, WT1, D2-40 vs claudin-4, MOC-31, BerEP4, TTF-1.