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

Abstract

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.

Diagnostic utility of the combined use of HNF4A and GATA3 in distinction between primary and metastatic breast and gastric carcinomas

“…In this work, GATA3 exhibited the strongest qualities to differentiate between the groups with high sensitivity varying from 88 to 92% and specificity varying from 95.8–100%. These results are in agreement with findings from prior studies on primary breast tumors [5, 19, 20].…”

“…Another study by Hui et al [20], demonstrated that all PDGC were negative for GATA3 and recommended the utility of this marker for the distinction from lobular breast carcinoma.…”

SATB2 Versus CDX2: A Battle Royale for Diagnostic Supremacy in Mucinous Tumors

“…[23][24][25][26][27][28][29][30][31] In a study with 40 breast adenocarcinomas of exclusively mucinous phenotype undertaken by de Andrade Natal et al, 29 all cases were negative for CDX2 expression. Additionally, in a cohort of 33 breast and 50 gastrointestinal (upper and lower) signet ring cell adenocarcinomas reported by Hui et al, 30 CDX2 staining was 100% specific for tumors of gastrointestinal origin. Keeping in line with these data, our CDX2 false-positive rate was 0% in our purely mucinous cohort of breast adenocarcinomas regardless of H-score (Table 2) although any SATB2 expression was observed in 16.1% of cases.…”

Gastric metastases from invasive lobular carcinoma of the breast: Case report

“…It has 100% positivity in lobular breast carcinoma and 96% positivity in ductal carcinoma of the breast [3] . In primary gastric carcinoma it is positive in only 5% (in well-differentiated adenocarcinomas, with no reported cases in carcinomas with poorly cohesive cells, such as signet ring carcinomas) [13] .…”