Contents lists available at ScienceDirect Annals of Diagnostic Pathology journal homepage: www.elsevier.com/locate/anndiagpath Primary breast carcinomas with neuroendocrine features: Clinicopathological features and analysis of tumor growth patterns in 36 cases Canan Kelten Talu a, ⁎ , Cem Leblebici a , Tulin Kilicaslan Ozturk b , Ezgi Hacihasanoglu a , Sevim Baykal Koca a , Zuhal Gucin c a University of Health Sciences, Istanbul SUAM, Department of Pathology, Turkey b Istanbul University, Cerrahpasa Faculty of Medicine, Department of Pathology, Turkey c Bezmialem University, Faculty of Medicine, Department of Pathology, Turkey ARTICLE INFO Keywords: Breast Neuroendocrine carcinoma ABSTRACT Primary breast carcinoma with neuroendocrine features (NEBC) is an uncommon tumor. In the classification of WHO 2012, these tumors were categorized as: 1- neuroendocrine tumor, well-differentiated; 2- neuroendocrine carcinoma, poorly differentiated/small cell carcinoma; and 3- invasive breast carcinoma with neuroendocrine differentiation. In this study, we reviewed NEBC except poorly differentiated/small cell carcinoma variant in order to define the morphological growth patterns and cytonuclear details of these tumors. All breast surgical excision materials between 2007 and 2016 were re-evaluated in terms of neuroendocrine differentiation. Thirty- six cases showing positive staining for synaptophysin and/or chromogranin A in ≥50% of tumor cells were included in the study. All cases were female with a mean age of 67.4. Mean tumor diameter was 26 mm. Multifocality was noted in 5 cases. Grossly, they were mostly infiltrative mass lesions. T stages, identified in 34 cases, were as follows: 13 cases with pT1; 19 pT2 and 2 pT3. We described schematically 4 types of patterns depending on predominant growth pattern, except one case: 1) Large-sized solid cohesive groups (6 cases), 2) Small- to medium-sized solid cohesive groups with trabeculae/ribbons and glandular structures (6 cases), 3) Mixed growth patterns (20 cases), 4) Invasive tumor with prominent extracellular and/or intracellular mucin (3 cases). The tumor cells were mostly polygonal-oval with eosinophilic/eosinophilic-granular cytoplasm. The nuclei of tumor cells were mostly round to oval with evenly distributed chromatin. Only 5 cases showed high grade nuclear and histological features. Molecular subtypes of the cases were as follows: 33 luminal A, 2 luminal B, and 1 triple negative. NEBC should come to mind when a tumor display one of the morphological patterns described above, composed of monotonous cells with mild to moderate nuclear pleomorphism and abundant eosinophilic/eosinophilic granular or clear cytoplasm, especially in elderly patients. 1. Introduction Primary breast carcinoma with neuroendocrine features is an un- common tumor that was first recognized in 1963 by Feyrter and Hartmann as carcinoid growth pattern in two cases with invasive breast carcinoma [1]. Later, in 1977, Cubilla and Woodruff described eight cases of breast carcinoma also as carcinoid tumor [2]. Initially, the presence of neurosecretory granules within these tumors was revealed by modified silver stain and/or electron microscopy. However, after immunohistochemistry became routine practice in the 1980s, many markers such as NSE (neuron-specific enolase), synaptophysin, chro- mogranin, PGP9.5 and CD56 (N-cellular adhesion molecule) have been used to show neuroendocrine differentiation in these tumors. Initially, the reported incidence of these tumors changed from < 1% to 20%, mostly due to lack of clear diagnostic criteria [3-9]. In 2003, the World Health Organization (WHO) classification of tumors of the breast and female genital organs defined neuroendocrine carcinoma (NEC) of the breast as a specific histological type of invasive breast carcinoma in which > 50% of the tumor cells express at least one of neuroendocrine markers [10]. According to the 2003 WHO classifica- tion, the reported incidence of these tumors was limited between % 2 and 5% [10]. In 2012, however, the WHO classification was revised and the minimum percentage of cells exhibiting positive immunostaining for neuroendocrine markers was removed. It has been defined that ‘all https://doi.org/10.1016/j.anndiagpath.2018.03.010 ⁎ Corresponding author. E-mail addresses: esracanankelten.talu@sbu.edu.tr, ecanankelten@gmail.com (C. Kelten Talu), ezgihaci@yahoo.com (E. Hacihasanoglu). Annals of Diagnostic Pathology 34 (2018) 122–130 1092-9134/ © 2018 Elsevier Inc. All rights reserved. T