Subtyping of nonsmall cell lung cancer on cytology specimens: Reproducibility of cytopathologic diagnoses on sparse material

Abstract

Cytologic examination of fine-needle aspiration (material is increasingly used in diagnosing lung cancer. High interobserver agreement in distinguishing small-cell lung cancer from nonsmall-cell lung cancer (NSCLC) on cytologic material has been demonstrated. Because of new treatment-modalities, subclassification of NSCLC into squamous cell carcinoma (SQC) and non-SQC has clinical impact. Subclassification based on morphology alone may be difficult, but applying immunohistochemistry (IHC) to clot-material has proved helpful. When insufficient material is available to make a clot from the aspirate, cytoscrape (CS) can convert cytologic material into tissue fragments useful for IHC. The purpose of this study was to test the reproducibility of pulmonary malignant diagnoses, in particular distinction between subgroups of NSCLC, based on smeared material and IHC on CS. A consecutive series of May-Grunwald-Giemsa (MGG) stained smears and CS with IHC on material from 79 patients suspected of having lung cancer was included. The material was circulated twice to four pathologists. The diagnoses were categorized in five groups: SQC, adenocarcinoma of the lung, non-SQC, benign lesion and other forms of malignancy, including metastases. Reproducibility was analyzed using Kappa statistics. Interobserver reproducibility of the diagnoses in round 1 was good to very good (kappa 0.57-0.71) and very good in round 2 (0.63-0.80). Reproducibility of subclassification of NSCLC based on MGG stained smear and IHC on CS, was very good among experienced pathologists. With only sparse material available, CS should be used to achieve reproducible diagnoses, including subtyping of NSCLC.

Morphologic Accuracy in Differentiating Primary Lung Adenocarcinoma From Squamous Cell Carcinoma in Cytology Specimens

“…The accuracy of such subtyping in cytologic material is not well established, 11 particularly in reference to newer IHC stains such as p40, TTF-1, and napsin A. A few studies are available in the literature, 4,10–15 but most are reports from single institutions with relatively small numbers of cases. One large series of 1182 transbronchial and transthoracic aspirates demonstrated that the positive predictive value of FNA in subtyping NSCLC was 92% for ADC and 82% for SqCC.…”

“…The greatest accuracy was achieved after the introduction of targeted therapy and with the use of IHC stains, 4,10,13–15 suggesting that the criteria necessary to separate ADC from SqCC may not have been carefully applied prior to the recognition of the increased need for subtyping.…”

“…The majority of ADC and SqCC cases can be diagnosed by cytomorphology alone, 9 but there remain difficult cases that defy this approach. High interobserver agreement in distinguishing small cell lung cancer from NSCLC in cytologic material is well established, 10 but less information is available on interobserver variability in subtyping NSCLC.…”

Subclassification of pulmonary non-small cell lung carcinoma in fine needle aspirates using a limited immunohistochemistry panel

“…Also, the recognition of squamous cell carcinoma (SCC) is important because if this subset of lung carcinoma patients is given bevacizumab, then it may lead to serious pulmonary bleeding. [2]…”

“…[234] It is well documented that cytomorphology and immunohistochemistry (IHC) are useful in further categorization of NSCLC. [5] In centers where IHC is not readily accessible, a limited panel of antibodies can be used to categorize the tumor.…”