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

Abstract

Context The National Cancer Care Network and the combined College of American Pathologists/International Association for the Study of Lung Cancer/Association for Molecular Pathology guidelines indicate that all lung adenocarcinomas (ADCs) should be tested for epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements. As the majority of patients present at a later stage, the subclassification and molecular analysis must be done on cytologic material. Objective To evaluate the accuracy and interobserver variability among cytopathologists in subtyping non–small cell lung carcinoma using cytologic preparations. Design Nine cytopathologists from different institutions submitted cases of non–small cell lung carcinoma with surgical follow-up. Cases were independently, blindly reviewed by each cytopathologist. A diagnosis of ADC or squamous cell carcinoma was rendered based on the Diff-Quik, Papanicolaou, and hematoxylin-eosin stains. The specimen types included fine-needle aspiration from lung, lymph node, and bone; touch preparations from lung core biopsies; bronchial washings; and bronchial brushes. A major disagreement was defined as a case being misclassified 3 or more times. Results Ninety-three cases (69 ADC, 24 squamous cell carcinoma) were examined. Of 818 chances (93 cases × 9 cytopathologists) to correctly identify all the cases, 753 correct diagnoses were made (92% overall accuracy). Twenty-five of 69 cases of ADC (36%) and 7 of 24 cases of squamous cell carcinoma (29%) had disagreement (P = .16). Touch preparations were more frequently misdiagnosed compared with other specimens. Diagnostic accuracy of each cytopathologist varied from 78.4% to 98.7% (mean, 91.7%). Conclusion Lung ADC can accurately be distinguished from squamous cell carcinoma by morphology in cytologic specimens with excellent interobserver concordance across multiple institutions and levels of cytology experience.

Molecular genetic alterations in thyroid transcription factor 1–negative lung adenocarcinoma in cytology specimens: A subset with aggressive behavior and a poor prognosis

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A practical guide for ancillary studies in pulmonary cytologic specimens

“…4). [5][6][7] However, immunocytochemical tests must be ordered whenever an NSCLC is not well-differentiated or shows any equivocal cytological features and for which a cell block is available to attain a more specific subtype of NSCLC; indeed, the diagnosis "NSCLC, not otherwise specified (NOS)" should be kept to a minimum. 5,[8][9][10] Because it is important to conserve as much material as possible for subsequent molecular testing (see Cancer Cytopathology August 2018…”

Histopathologic and molecular approach to staging of multiple lung nodules

“…Precise classification into specific main types such as adenocarcinoma and squamous cell carcinoma is possible in the majority of the cases based on morphology or with the help of immunohistochemistry. Therefore, in cases of separate primary tumors of a different histologic type, small biopsy and cytology specimens can be sufficient (21)(22)(23)(24)(25). However, morphologic subclassification of lung adenocarcinoma on cytology specimen is difficult and largely depends on the procedure type and tumor cellularity of the sample (26,27).…”