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.

A cholesteroloma or cholesterol granuloma of the breast is an uncommon lesion representing an inflammatory/reactive process with unclear etiology. In this study, we reviewed our 10‐year experience with cholesteroloma of the breast with clinical, radiologic, and histopathological correlation. Seventy‐nine cases were selected. The mean patient age was 57.7 (range 25‐90) years old. Patients had hypercholesterolemia with mean blood cholesterol level of 201 mg/dL (P < 0.001). The mean body mass index (BMI) was 26.7 kg/m2 (P = 0.1976). The indications for the breast biopsies were mass lesion on radiology (85.5%, n = 65) and microcalcifications (10.5%, n = 8). Of the 65 cases of the mass lesions, 52 presented as solid masses and 13 were cystic. On the diagnostic mammogram or ultrasound, 81.9% were BI‐RADS 4% and 6.9% were BI‐RADS 5. Macrocysts were the most common pathological finding associated with cholesteroloma suggesting the etiology of cholesteroloma may be the result of repair process from obstruction and rupture of the macrocysts. Six cases (9.2%) of cholesterolomas had persistent masses during follow‐up. The recognition of this lesion and radio‐pathological correlation can help us better understand this entity and distinguish it from its mimickers.