IMP3, NESP55, TTF-1 and CDX2 Serve as an Immunohistochemical Panel in the Distinction Among Small-cell Carcinoma, Gastrointestinal Carcinoid, and Pancreatic Endocrine Tumor Metastasized to the Liver

Abstract

Histopathologic distinction among small-cell carcinoma (SCC), pancreatic endocrine tumor (PET), and gastrointestinal carcinoids metastasized to the liver in needle core biopsies can be extremely challenging because of limited material, crush artifact, and lack of detailed clinical history. In this study, a total of 61 surgically resected or biopsied specimens, including 27 SCCs (lung, 17; colon, 1; gallbladder, 2; stomach, 1; and unknown primary, 6), 18 gastrointestinal carcinoid tumors (GICTs) (stomach, 2; small intestine, 14; colon, 2), and 16 PETs were immunohistochemically examined for the expression of IMP3, TTF-1, CDX2, and NESP55 to evaluate their diagnostic value. The results showed that 24 (89%) of 27 SCCs exhibited strong cytoplasmic staining for IMP3 in 60% to 100% of the tumor cells. Eighteen (67%) SCCs were strongly and diffusely positive for TTF-1. In the remaining 9 TTF-1-negative SCCs (including 4 extrapulmonary cases), 7 showed strong and diffuse IMP3 expression. All SCCs were negative for CDX2 except for 1 case of colonic origin that showed strong CDX2 immunoreactivity. All 16 metastatic PETs were positively stained for IMP3 with 12 cases (75%) showing a diffuse and moderate-to-strong staining pattern while they were negative for TTF-1. Six PETs exhibited moderate-to-strong positivity for CDX2 with nuclear staining in 5% to 40% of tumor cells, and 5 showed a varying degree of positivity for NESP55. Three (17%) of 18 metastatic GICTs showed moderate IMP3 staining in 50% to 90% of the tumor cells, whereas CDX2 was expressed in 17 (94%) cases with moderate-to-strong staining in 50% to 100% of tumor cells. No NESP55 immunoreactivity was detected in metastatic SCCs and GICTs. In conclusion, a panel of these 4 markers is useful in segregating among SCC, PET, and GICT to help determine the primary site of hepatic metastasis.

Original paper Morphological and immunohistochemical profile of pancreatic neuroendocrine neoplasms

“…The labelling in pancreatic tissues is usually lighter and more variegated than in colorectal carcinoma [56]. Although expression of CDX2 has been reported in a small fraction of PNENs [97,98], it was absent both from PNENs and islets in the present study.…”

SATB2 protein expression by immunohistochemistry is a sensitive and specific marker of appendiceal and rectosigmoid well differentiated neuroendocrine tumours

“…1 Neuroendocrine secretory protein-55 (NESP-55), a member of the chromogranin family, is expressed in 37-56% of pancreatic neuroendocrine tumours. [29][30][31] In summary, current markers are only moderately useful, lacking sensitivity and specificity for site of origin. SATB2 has been validated as a marker of lower GI epithelium in several studies.…”

“…This marker is expressed in most pancreatic and duodenal NNs, but is found uncommonly in lung and has never been detected in jejunal primaries . Neuroendocrine secretory protein‐55 (NESP‐55), a member of the chromogranin family, is expressed in 37–56% of pancreatic neuroendocrine tumours . In summary, current markers are only moderately useful, lacking sensitivity and specificity for site of origin.…”

Histopathological, immunohistochemical, genetic and molecular markers of neuroendocrine neoplasms

“…Isl-1 positivity is also typical of duodenal and rectal WD-NENs (39,40). Twelve percent (12%) of 94 pulmonary and 17% of 42 primaries ANENs have also shown positivity (41,42), and it is also expressed in MTC (43).…”