[1603] Hepatocellular Carcinomas Occasionally Express Neuroendocrine Markers While Neuroendocrine Tumors Metastatic to the Liver Do Not Show Hepatocellular Expression.

Xiaoping Zhou, Martha M Yearsley, Kimberley S Jones, Wendy L Frankel. The Ohio State University, Columbus

Background: Neuroendocrine tumors (NETs) of gastrointestinal tract are generally slow growing but frequently metastasize to the liver, ranking second to colorectal carcinoma as a source of liver metastases. Distinction between NET and hepatocellular carcinoma (HCC) can be challenging on a small biopsy because both can show nested and trabecular patterns. In addition, immunostaining for neuroendocrine markers has been observed occasionally in HCCs. Utilizing immunohistochemistry for hepatocyte, glypican-3, CD56, synaptophysin (Syn) and chromogranin A (Chr), we analyzed the staining profile in HCCs and NETs to determine how often the tumors show an overlapping pattern of expression.
Design: Tissue microarrays were constructed from formalin-fixed, paraffin-embedded blocks of 48 NETs metastatic to the liver and 114 HCCs from our archives and stained for hepatocyte, glypican-3, CD56, Syn and Chr. Immunostaining was evaluated by two pathologists; > 5% immunoreactivity was considered positive and intensity was scored for each (1+, weak; 2+, strong).
Results: Of the 114 HCCs, 107 (94%) were positive for hepatocyte or glypican-3, 92 (81%) for hepatocyte, 67 (59%) for glypican-3, and 52 (46%) for both. Seven HCCs (6%) showed positivity for CD56 (4 focal, 3 diffuse, 2 weak and 5 strong), of which 3 (3%) were also positive for Syn (all focal, 1 weak and 2 strong). All 7 HCCs positive for CD56 or Syn expressed hepatocyte or glypican-3 and none were fibrolamellar type. None of the HCCs expressed Chr. All 48 NET liver metastases expressed at least one neuroendocrine marker. All but one (98%) NETs were positive for Syn, 40 (83%) for Chr and 39 (81%) for CD56. Thirty-four NETs (71%) expressed all neuroendocrine markers. No hepatocyte or glypican-3 expression was present in the NET liver metastases.

Positive immunostaining in HCCs and NETs metastatic to the liver

	Hepatocyte	Glypican-3	Synaptophysin	Chromogranin A	CD56
HCC (n = 114)	92	67	3	0	7
NET (n = 48)	0	0	47	40	39

HCC, hepatocellular carcinoma; NET, neuroendocrine tumor.


Conclusions: Occasional HCCs express CD56 and Syn, while all express either hepatocyte or glypican-3. NETs metastatic to the liver do not express hepatocyte or glypican-3 and almost always express Syn, while Chr and CD 56 are seen in most cases. Utilizing a limited immunohistochemistry panel, including hepatocyte, glypican-3, Syn and Chr, can efficiently distinguish HCC from NET liver metastases and help avoid diagnostic pitfalls on small biopsies.
Category: Liver & Pancreas

Tuesday, March 1, 2011 9:30 AM

Poster Session III # 255, Tuesday Morning