Comprehensive Cytomorphologic Analysis of Pulmonary Adenoid Cystic Carcinoma: Comparison to Small Cell Carcinoma and Non-pulmonary Adenoid Cystic Carcinoma

Abstract

Background: Cytologic diagnosis of pulmonary adenoid cystic carcinoma (AdCC) is frequently challenging and differential diagnosis with small cell carcinoma is often difficult.

Methods: Eleven cytologically diagnosed cases of pulmonary AdCC were collected and reviewed according to fifteen cytomorphologic characteristics: small cell size, cellular uniformity, coarse chromatin, hyperchromasia, distinct nucleolus, frequent nuclear molding, granular cytoplasm, organoid cluster, sheet formation, irregular border of cluster, hyaline globule, hyaline basement membrane material, individual cell necrosis or apoptotic body, and necrotic background. Twenty cases of small cell carcinoma and fifteen cases of non-pulmonary AdCC were also reviewed for the comparison.

Results: Statistically significant differences were identified between pulmonary AdCC and small cell carcinoma in fourteen of the fifteen cytomorphologic criteria (differences in sheet formation were not statistically significant). Cellular uniformity, distinct nucleolus, granular cytoplasm, distinct cell border, organoid cluster, hyaline globule, and hyaline basement membrane material were characteristic features of AdCC. Frequent nuclear molding, individual cell necrosis, and necrotic background were almost exclusively identified in small cell carcinoma. Although coarse chromatin and irregular cluster border were observed in both, they favored the diagnosis of small cell carcinoma. Hyaline globules were more frequently seen in non-pulmonary AdCC cases.

Conclusions: Using the fifteen cytomorphologic criteria described by this study, pulmonary AdCC could be successfully distinguished from small cell carcinoma. Such a comprehensive approach to an individual case is recommended for the cytologic diagnosis of pulmonary AdCC.

Keywords: Carcinoma, adenoid cystic; Carcinoma, small cell; Cytology; Lung.

Fig. 1.

Cytomorphology of pulmonary adenoid cystic carcinoma. (A) Small cell size, cellular uniformity and hyperchromasia (case 1). (B) Infrequently identified nuclear molding (case 7). (C) Granular cytoplasm and well-defined cell borders (case 7). (D) Distinct nucleoli and sheet formation (case 2). (E) Organoid tumor clusters with smooth border (case 9). (F) Hyaline globules (case 3). (G) Hyaline basement membrane materials (case 3). (H) Necrotic background (case 6).

Fig. 2.

Cytologic comparison between pulmonary adenoid cystic carcinoma (AdCC) and small cell carcinoma with histologic confirmation. (A) Lack of cellular uniformity in small cell carcinoma. (B) Uniform tumor cells of pulmonary AdCC with occasional nuclear molding (case 1). (C)Biopsy specimen of pulmonary AdCC case 1, which mimicked small cell carcinoma morphology. (D) Coarse chromatin pattern with frequent nuclear molding in small cell carcinoma. (E) Size variation of the tumor cells with fine-stippled to coarse chromatin in pulmonary AdCC (case3). (F) Biopsy specimen showing typical histology of AdCC (case 3). (G) Extensively necrotic background with frequent single cell necrosis and apoptotic bodies in the small cell carcinoma aspirate. (H) Necrotic background without individual tumor cell necrosis or apoptotic body in pulmonary AdCC (case 6). (I) Surface ulceration identified in the resection specimen of pulmonary AdCC (case 6).