Anatomic pathology selected abstracts

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Protein expression and morphologic factors in lung carcinoid tumors

World Health Organization classification of thoracic tumors defines lung carcinoid tumors as well-differentiated neuroendocrine neoplasms that comprise low-grade typical (TC) and intermediate-grade atypical carcinoids (AC). Limited data are available regarding protein expression and morphologic factors for predicting disease aggressiveness. Ki-67 has proven to be a powerful diagnostic and prognostic factor for gastroenteropancreatic neuroendocrine neoplasms (NENs), but its role in lung NENs is still being debated. The authors conducted a study to evaluate the role of the Ki-67 proliferation index and examine its correlation with disease evolution and recently proposed IHC markers for patients with lung carcinoid tumors. A retrospective series of 370 lung carcinoid tumors from two oncology centers was centrally reviewed. Morphology and IHC markers, including Ki-67, TTF-1, CD44, OTP, SSTR-2A, Ascl1, and p53, were studied and correlated with overall survival, cancer-specific survival, and disease-free survival. Carcinoid histology was confirmed in 355 patients: 297 (83.7 percent) TC and 58 (16.3 percent) AC. A Ki-67 of three percent was the best value for predicting disease-free survival. A Ki-67 of three percent or more was significantly associated with AC histology; stage III–IV; smoking; vascular invasion; tumor spread through air spaces OTP negativity; and TTF-1, Ascl1, and p53 positivity. After adjusting for center and period of diagnosis, AC histology and high Ki-67 (three percent or more versus less than three percent) were the strongest predictors of cancer-specific survival, together with age (10-year increase), stage (III–IV versus I–II), and OTP (present versus absent). In terms of disease-free survival, AC histology and high Ki-67 were again the strongest prognostic factors, together with age (10-year increase), lymph node involvement (N1/2/3 versus zero), residual tumor (R1/2 versus R0), and OTP (present versus absent). The authors concluded that Ki-67 of three percent or more plays a potentially pivotal role in lung carcinoid tumor prognosis, irrespective of histological grade.

Centonze G, Maisonneuve P, Simbolo M, et al. Lung carcinoid tumours: histology and Ki-67, the eternal rivalry. Histopathology. 2023;82(2):324–339.

Correspondence: Dr. Massimo Milione at massimo.milione@istitutotumori.mi.it

Cytomorphologic and molecular features of intraductal papillary neoplasm of the bile duct

Intraductal papillary neoplasm of the bile duct is a rare premalignant neoplasm that can progress to invasive adenocarcinoma. The authors conducted a retrospective study in which they reviewed cases of intraductal papillary neoplasm of the bile duct (IPNB) to examine cytomorphologic and molecular features. IPNB cytology cases with histopathologic confirmation were retrieved from participating institutions’ pathology archives. The authors analyzed such cytomorphologic features as cellularity, architecture, cell type, and cellular details. The study cohort included 13 cases (six brushings, six fine-needle aspirations [FNA], and one combined brushing and FNA). The lesions involved the common bile duct in nine (69 percent) cases and hepatic duct in four (31 percent) cases. Original cytological diagnoses included adenocarcinoma (five, 38 percent), suspicious for adenocarcinoma (one, eight percent), neoplasm (three, 23 percent), atypical (three, 23 percent), and reactive (one, eight percent). The cytomorphologic features included moderate/high cellularity (12, 92 percent); papillary or complex papillary architecture, or both (10, 77 percent); columnar cells (11, 85 percent); vacuolated cytoplasm (12, 92 percent); enlarged nuclei (13, 100 percent); and fine granular chromatin (12, 92 percent). Background mucin, necrosis, and acute inflammation were seen in four (31 percent), four (31 percent), and two (15 percent) cases, respectively. KRAS mutation testing was performed in nine cases, with mutant KRAS found in five (56 percent). The study demonstrated that IPNB cytology specimens were relatively cellular, with a wide spectrum of cytomorphology. However, most cases harbored adenocarcinoma or high-grade dysplasia. The characteristic cytomorphologic features included papillary/complex papillary clusters of columnar cells with vacuolated cytoplasm, enlarged nuclei, and fine granular chromatin in relatively cellular specimens. The KRAS mutations identified may have potential diagnostic and therapeutic implications.

Stendahl K, Gilani SM, Basturk O, et al. Intraductal papillary neoplasm of the bile duct: Cytomorphologic and molecular features. Cancer Cytopathol. 2023;131:37–49.

Correspondence: Dr. Carlie Sigel at sigelc@mskcc.org