Liver Metastases of Neuroendocrine Tumors Rarely Show Overlapping Immunoprofile with Hepatocellular Carcinomas

Abstract

The distinction of hepatocellular carcinoma (HCC), neuroendocrine tumor (NET) metastatic to the liver, and cholangiocarcinoma (CC) can sometimes be challenging on small biopsies. Tissue microarrays were constructed from HCCs, NETs, and CCs. The immunoprofile was evaluated using HepPar1, glypican-3 (GPC3), synaptophysin (SYN), chromogranin A (CHR), CD56, MOC-31, and pCEA. One hundred thirteen HCCs, 48 NETs, and 44 CCs were included. Of HCCs, 107 (95 %) expressed HepPar1 and/or GPC3, 52 (46 %) both, and 97 (88 %) marked with pCEA (canalicular pattern). Seven (6 %) expressed CD56, of which 3 (3 %) expressed SYN. All 7 HCCs that expressed CD56 and/or SYN also expressed HepPar1 and/or GPC3, and none of the HCCs expressed CHR. Fourteen (13 %) expressed MOC-31. All 48 NETs expressed at least one neuroendocrine marker: 47 (98 %) positive for SYN, 40 (83 %) for CHR, 39 (81 %) for CD56, and 34 (71 %) for all three markers. None expressed HepPar1 or GPC3. All 44 CCs showed at least focal reactivity with MOC-31 and pCEA (membranous/cytoplasmic). One (2 %) was positive for HepPar1, 4 (9 %) for GPC3, 1 (2 %) for SYN and CHR, and 7 (16 %) for CD56. HCCs rarely express CD56 and SYN, while all express either HepPar1 or GPC3. NETs do not express HepPar1 or GPC3 and almost always express SYN, while CHR and CD56 are seen in most cases. Rare CCs focally express HepPar1 and GPC3. Utilizing a limited staining panel can efficiently distinguish HCCs, NETs, and CCs and help avoid diagnostic pitfalls on small biopsies.

Can glypican‐3 be a disease‐specific biomarker?

“…Increasing evidence suggests soluble GPC3 as a novel diagnostic candidate marker in hepatocellular carcinoma [ 13 ]. GPC3 is expressed in 95% of hepatocellular carcinomas, but not in neuroendocrine tumor metastatic to the liver, and cholangiocarcinoma, measured by liver cancer tissue microarrays which were constructed from hepatocellular carcinoma, neuroendocrine tumor, and cholangiocarcinoma samples [ 23 ]. The high positive rate of GPC3 in hepatocellular carcinoma indicates the specificity of GPC3 in hepatocyte-origin carcinogenesis.…”

Thyroid-like intrahepatic cholangiocarcinoma: An easily misdiagnosed case and molecular features analysis

“…Though the expression pattern of CD34 (not shown) mimicked the hepatocellular carcinoma, the lack reactivity of hepar1, Glypican-3, AFP and CD10 while high expression of CK7 and CK19 ruled out the diagnosis of hepatocellular carcinoma [10] and supported the diagnosis of ICCA. The neuroendocrine markers, including CgA, Syn and CD56 were negative that excluded the possibility of neuroendocrine tumor/carcinoma [11][12][13]. Likewise, negative expression of germ cell marker (Sall4) also excluded the diagnosis of germ cell tumor.…”

Neuroendocrine tumors in Panama: A nationwide database analysis

“…SYN is considered as the most sensitive biomarker, whereas CgA is the most specific for NETs (21,22). In addition, the percentage of Ki-67 staining is often used as a proliferation marker (23,24). Test yields were calculated for each of the immunohistology markers detected; the results revealed that, on average, SYN had the highest yield (67.0%), followed by CgA (54.8%) and CD56 (19.1%).…”