Cytologic Features Useful for Distinguishing Small Cell From Non–Small Cell Carcinoma in Bronchial Brush and Wash Specimens

Abstract

One blinded observer (C.D.S.) retrospectively reviewed 76 previously diagnosed and biopsy-confirmed malignant bronchial brush and wash specimens, 46 non-small cell and 30 small cell carcinomas, obtained from 55 patients. Each case was scored for the presence or absence of 36 standard criteria (architectural, cytoplasmic, and nuclear). Logistic regression analysis was used to determine which criteria were most useful for separating small cell from non-small cell lesions. Although no single criterion displayed 100% sensitivity and specificity for small cell cancer, univariate statistical analysis indicated that 3 individual criteria (nuclear molding, finely granular or "salt and pepper" chromatin, and scant delicate cytoplasm) were more than 90% sensitive and specific in cases of small cell carcinoma. The presence of nuclear molding alone provided the best fit for the logistic regression model. When nuclear molding was present, the odds of a small cell diagnosis increased more than 300-fold. Nuclear molding, finely granular or salt and pepper chromatin, and scant, delicate cytoplasm are the 3 most sensitive and specific cytomorphologic features traditionally used to separate small cell from non-small cell carcinoma. Nuclear molding alone represents the most significant cytomorphologic feature for distinguishing between these malignant lesions.

Utility of the Quantitative Ki-67 Proliferation Index and CD56 Together in the Cytologic Diagnosis of Small Cell Lung Carcinoma and Other Lung Neuroendocrine Tumors

“…Cytomorphologic features of SCLC are well defined, and an accurate diagnosis can be made based on cytomorphology in the majority of cases [5,27]. However, there are instances in which these features may overlap with those of other neuroendocrine neoplasms including atypical carcinoid tumor and LCNEC, NSCLC including basaloid squamous cell carcinoma, lymphoma, Markel cell carcinoma, and rarely, sarcomas such as synovial sarcoma [5,27,28,29]. Distinguishing SCLC from NSCLC and other neuroendocrine neoplasms is essential for the treatment and prognosis of lung neoplasms.…”

“…Twenty-five percent of primary lung neoplasms are neuroendocrine tumors, and the 75% remaining are composed of non-small cell lung carcinoma (NSCLC) [4]. Being considered highly accurate, fine needle aspiration (FNA) is a first-line diagnostic approach in the workup of pulmonary masses [5,6]. In cytological classification, distinction of small cell lung carcinoma (SCLC) from NSCLC and from low-grade and intermediate-grade neuroendocrine neoplasms and large cell neuroendocrine carcinoma (LCNEC) is essential because of differences in prognosis and management.…”

Molecular pathology via IR and Raman spectral imaging

“…Gross morphological changes that occur with the transition from healthy to diseased tissue include abnormal tissue architecture, the appearance of cells at locations where they are normally not found (metaplasia), the presence of inflammatory cells, abnormal cell morphology including changed nucleus to cytoplasm (N/C) ratio, abnormal nuclear membrane morphology, abnormal chromatin distribution, the number of nucleoli in the nucleus, the presence of unusually large number of mitotic figures indicating rapid cell division, and a plethora of other, often ill-defined features such as foaminess of the cytoplasm, etc. [3] To arrive at these diagnostic descriptors, tissue sections, generally about 5 mm thick, are obtained by cutting, via a microtome, either formalinfixed, paraffin embedded tissue blocks, or unfixed, flash-frozen tissue sections. However, in either case, the tissue sections present themselves as white or grayish deposits on microscope slides, and show very little contrast under the microscope.…”

Significance of Cytologic Criteria in Distinguishing Small Cell from Non–Small Cell Carcinoma of the Lung

“…4,13 Pulmonary pathologists disagree over the distinction between SCC and NSCC in 5-7% of the cases. 15 Recently cytologic features were statistically analyzed 13 to determine the significance of each in separating SCC from NSCC. In this study, univariate analysis was performed for each of the nine cytologic features of SCC.…”