Reevaluation of the Diagnostic Utility of Villin and Mammaglobin in the Differential Diagnosis between Metastatic Breast Ductal Carcinoma and Intrahepatic Cholangiocarcinoma in the Liver
Zhaohai Yang. Penn State Milton S. Hershey Medical Center, Hershey, PA
Background: Liver is a common metastatic site for breast cancer; differentiation of metastasis from intrahepatic cholangiocarcinoma (ICC) is crucial for patient management. We recently encountered a patient with a history of ER-negative microinvasive breast cancer who presented with a liver mass; a definite diagnosis cannot be made due to similar morphology and lack of specific markers. Villin and mammaglobin are markers of gastrointestinal and breast tissue, respectively; however, they were considered not useful in cholangiocarcinoma for various reasons. We decided to reevaluate these two markers in the differential diagnosis between metastatic breast ductal carcinoma and ICC.
Design: Fifty-two cases of breast ductal carcinoma (26 ER-positive, 26 ER-negative), 27 cases of ICC, and 19 cases of extrahepatic bile duct adenocarcinoma (EBC) were retrieved from the pathology archive. Available lymph node metastases (LNM) were included in all breast cases. Immunohistochemical staining for villin was performed on all cases; mammaglobin was performed on the breast and ICC cases. Villin was interpreted as positive with any luminal staining, mammaglobin was interpreted as positive with at least 1% of the cells showing cytoplasmic staining. Fisher's exact test was used for statistical analysis.
Results: Villin was negative in all ER-positive (23 invasive ductal carcinomas [IDC], 18 ductal carcinoma in situ [DCIS], 24 LNM) and ER-negative (23 IDC, 12 DCIS, 11 LNM) cases of breast carcinoma. It was positive in all 27 cases of ICC (6 surgical resections, 9 resections with matched prior biopsies, 12 biopsies) and 12 of 19 cases of EBC (63%). Mammaglobin was positive in 6 of 46 IDC (13%), 7 of 30 DCIS (23%), and 12 of 35 LNM (34%), with no significant difference between ER-positive and negative cases. Notably, discrepancy of mammaglobin staining in matched IDC, DCIS and LNM was common. All ICCs were negative for mammaglobin staining, when caution was taken not to misinterpret nonspecific staining in the interspersed hepatocytes as positive.
Conclusions: Contrary to earlier belief, villin expression is highly accurate in the differential diagnosis between ICC and metastatic breast ductal carcinoma, which is particularly useful for ER-negative cases. Mammaglobin is useful when it is positive (in about a third of breast cancer cases). The same conclusion is expected to apply to microinvasive carcinoma based on staining in DCIS and IDC.
Wednesday, March 6, 2013 1:00 PM
Poster Session VI # 117, Wednesday Afternoon