Differentiating breast carcinoma with signet ring features from gastrointestinal signet ring carcinoma: assessment of immunohistochemical markers

作者：Hui Yiang; Wang Yihong; Nam Gahie; Fanion Jacqueline; Sturtevant Ashlee; Lombardo Kara A; Resnick Murray B^*

来源：Human Pathology, 2018, 77: 11-19.

DOI：10.1016/j.humpath.2018.01.002

• Signet ring carcinoma
• Lobular carcinoma
• Estrogen receptor
• GATA-3
• CDX2
• Immunohistochemistry

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.

• 出版日期2018-7