Subclassification of Poorly Differentiated Non Small Cell Carcinoma on Small Biopsy Specimens: Utility of a Panel of Immunohistochemical Stains
S Mukhopadhyay, A Katzenstein. State University of New York Upstate Medical University, Syracuse, NY
Background: The availability of targeted therapies has created a need for precise subtyping of non small cell lung carcinomas. The most difficult cases to classify are poorly differentiated or extensively necrotic carcinomas in small biopsy specimens. The aim of this study was to assess the utility of immunohistochemical markers in subtyping such tumors. The study is unique in that it includes only those non-small cell carcinomas that could not be precisely classified on biopsy and in which subsequent resection specimens were available for determination of the final gold standard diagnosis.
Design: Cases of poorly differentiated non small cell lung carcinomas diagnosed on small lung biopsies (bronchial biopsies and core biopsies) were included in the study if: (1) they could not be further subtyped on the biopsy specimen on the basis of H&E morphology alone, and (2) a subsequent resection specimen was available. The resected tumor was classified on the basis of H&E morphology alone according to WHO criteria by two pulmonary pathologists blinded to immunohistochemical findings. Each biopsy was stained with CK7, TTF-1, napsin, p63, CK5/6 and 34βE12. For all markers, any expression of the marker within tumor cells was considered positive. The utility of the various stains in classifying the tumors was assessed.
Results: On resection, there were 15 squamous cell carcinomas (SQCCA), 7 adenocarcinomas (ADCA), 3 adenosquamous carcinomas, 1 large cell carcinoma, 1 sarcomatoid carcinoma and 1 small cell carcinoma. Positivity for 2 squamous markers occurred in 8/15 SQCCAs (34βE12 and p63 in 5, 34βE12 and CK5/6 in 2, CK5/6 and p63 in one) but in none of the 7 ADCAs. Positivity for both TTF-1 and napsin was seen in 3/7 ADCAs but none of the 15 SQCCAs. p63 staining was seen in 2 ADCAs that were also TTF-1-positive, while TTF-1 staining occurred in 2 SQCCAs that were also 34βE12-positive. Staining for CK7 was not helpful, since it was present in all 7 ADCAs and 11/15 SQCCAs.
Conclusions: Poorly differentiated non small cell lung carcinomas can be accurately subtyped on small biopsy specimens in about half of all cases using a panel of immunohistochemical stains. The combination of TTF-1, napsin, p63, CK5/6 and 34βE12 is most informative.
Wednesday, March 24, 2010 9:30 AM
Poster Session V # 243, Wednesday Morning