Distinguishing Metastatic Neuroendocrine Tumors to the Breast from Primary Invasive Mammary Carcinomas with Neuroendocrine Differentiation
Stacey Kim, Sambit K Mohanty, Richard B Mertens, Shikha Bose, Lily J Jih, Deepti Dhall. Cedars-Sinai Medicine, Los Angeles, CA
Background: Metastatic neuroendocrine tumors (MNETs) to the breast can show histologic overlap with invasive mammary carcinoma (IMC) and may be misdiagnosed as such, with undesirable consequences, since the management of the two conditions is completely different. This study was undertaken to characterize the histologic features and immunohistochemical (IHC) profile of MNETs to the breast and primary IMC with neuroendocrine differentiation (NED) and to determine whether IHC is helpful in distinguishing these two diagnostic entities.
Design: The anatomic pathology database of our institution was searched from January 2005 to July 2011 for MNETs to the breast and primary IMCs with NED. The histopathologic features, IHC profile (ER, PR, Her-2/neu, and Ki-67), and Her-2/neu overexpression by FISH were studied.
Results: Ten cases of MNET to the breast (median age=64 years; 10 females) and 14 cases of IMC with NED (median age=64 years; female:male=13:1) were identified. The metastatic tumors originated in the lung (n=4), gastrointestinal tract (n=4), ovary (n=1) and pancreas (n=1). With the exception of one case, all MNETs were unilateral. They were comprised of uniform tumor cells exhibiting predominantly nested and trabecular architecture, with characteristic salt and pepper- like nuclear chromatin. Most MNETs were intermediate grade. Cases of IMC with NED exhibited Modified Bloom-Richardson grade of II or III, with grade 2 nuclei and a tubule score of 3 in most cases. Coexistent DCIS was identified in more than half (8/14) of IMC with NED, whereas DCIS was not identified in any cases of MNET. A comparison of the demographic and IHC characteristics of the two groups is illustrated in Table1.
|Tumor type (n)||ER positive||PR positive||Her-2/neu amplification (FISH + & IHC 3+)||Synaptophysin positive||Chromogranin positive||Ki-67 proliferative index (mean & range)|
|MNET (10)||2/9 (22%) (weak to moderate)||1/9 (11%) (weak)||0/3 (0%)||9/9 (100%) (strong & diffuse)||10/10 (100%) (strong & diffuse)||9 (2-19%)|
|IMC with NED (14)||12/14 (86%)||9/14 (64%)||2/12 (17%)||11/14 (79%) (variable staining)||14/14 (100%) (variable staing)||33 (11-86%)|