Differentiating Breast Carcinoma with Signet-Ring Features from Gastrointestinal Signet-Ring Carcinoma: Assessment of Immunohistochemical Markers

Publication date: Available online 6 January 2018
Source:Human Pathology
Author(s): Yiang Hui, Yihong Wang, Gahie Nam, Jacqueline Fanion, Ashlee Sturtevant, Kara A. Lombardo, Murray B. Resnick
Signet-ring morphology is recognized throughout the gastrointestinal tract. However, this pattern may be observed in other primary sites giving rise to diagnostic challenges in the work-up of metastases. Relatively newer immunohistochemical markers have not been evaluated in this context. We assessed expression patterns of several common immunohistochemical markers in tumors with signet-ring morphology to delineate a pragmatic approach to this differential diagnosis. Primary breast and gastrointestinal carcinomas showing signet-ring features were reviewed. Non-mammary and non-gastrointestinal tumors with this morphology were included for comparison. Estrogen receptor (ER), progesterone receptor (PR), e-cadherin, CK7, CK20, GCDFP-15, mammaglobin, CDX2, GATA-3, and HepPar-1 immunohistochemistry was performed. Expression patterns were compared between breast and gastrointestinal tumors as well as lobular breast and gastric tumors. Ninety-three cases were identified: 33 breast carcinomas including 13 lobular, 50 gastrointestinal tumors including 23 gastric, and 10 from other sites. ER (Sensitivity=81.8%, Specificity=100%, Positive predictive value (PPV)=100%, Negative predictive value (NPV)=89.3%) and GATA-3 (Sensitivity=100%, Specificity=98%, PPV=96.8%, NPV=100%) expression were associated with breast origin. CK20 (Sensitivity=66.7%, Specificity=93.3%, PPV=94.1%, NPV=63.6%) and CDX2 (Sensitivity=72%, Specificity=100%, PPV=100%, NPV=68.9%) demonstrated the strongest discriminatory value for gastrointestinal origin. These markers exhibited similar discriminatory characteristics when comparing lobular and gastric signet ring carcinomas. In a limited trial on metastatic breast and gastric cases, these markers successfully discriminated between breast and gastric primary sites in 15 of 16 cases. ER and GATA-3 are most supportive of mammary origin and constitute an effective panel for distinguishing primary breast from primary gastrointestinal signet-ring tumors when combined with CK20 and CDX2 immunohistochemistry.



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