Hepatoid carcinoma of the pancreas with lymphoid stroma: first description of the clinical, morphological, immunohistochemical, and molecular characteristics of an unusual pancreatic carcinoma

Abstract

We report a case of tumour in the head of the pancreas observed in a 57-year-old man with a history of worsening jaundice and elevated alpha-fetoprotein (AFP) serum level, who underwent Whipple pancreatoduodenectomy. Histologically, the tumour was predominantly composed of solid sheets of large eosinophilic cells with a prominent lymphoid infiltration without association neither with DNA microsatellite instability nor Epstein-Barr virus infection. The tumour was diffusely and strongly positive for hepatocyte paraffin-1 (Hep Par-1) and glypican-3 leading to the diagnosis of hepatoid carcinoma. Strong cytoplasmic staining for AFP was focally observed. Moreover, tumour cells showed countless cytoplasmic eosinophilic globules immunoreactive for the stress protein p62. A primary hepatocellular carcinoma of the liver was ruled out by careful clinical analysis. Hepatoid carcinoma is an extremely rare pancreatic neoplasm, and here, we describe the first case of such variant associated with lymphoid stroma. The characteristic histologic features and the immunophenotypic profile help in distinguishing this carcinoma from other pancreatic tumours, notably from medullary carcinoma.

Primary Hepatoid Carcinoma of the Pancreas: A Clinicopathological Study of 3 Cases With Review of Additional 31 Cases in the Literature

“…Although more hepatoid carcinomas of the pancreas need to be tested, arginase-1 seems to be a promising marker to distinguish PHC from ACC. Hepatoid carcinomas without acinar cell differentiation were negative for trypsin and other acinar cell markers, 10,15,25,31 though the neuroendocrine component in one hepatoid carcinoma with neuroendocrine differentiation showed focal trypsin staining. 20 Pancreatoblastoma may be associated with elevated serum AFP level and show positive AFP staining.…”

“…Hepatoid carcinoma with pure HCC-like morphology is the most common histological subtype, including 22 of 34 (65%) reported cases * (Table 1). Serum AFP level was elevated in 6 (mean = 179.7 ng/mL; range = 11-623 ng/mL), 10,15,23,26,30,31 normal in 9, † and not measured in 7 patients. 12,18,24,33,36 This subtype shows similar morphological features to orthotopic HCC.…”

“…Hepatoid carcinomas of the pancreas are often positive for hepatocellular immunohistochemical markers (Table 4) such as AFP (18/27 or 67%), Hep Par1 (25/26 or 96%), glypican-3 (7/9 or 78%), and arginase-1 (3/4 or 75%). 9-38 Hepatoid carcinomas with pure HCC-like morphology are less likely to be immunohistochemically positive for AFP (9/17 or 53%) than those with other differentiation (9/9 or 100%; P = .007). Among the hepatoid carcinomas with neuroendocrine differentiation, those with homogeneous tumor cells show AFP 22,38 and Hep Par1 22,34 in the same group of cells, whereas those with 2 different populations of cells show positive AFP and Hep Par1 in the hepatoid component but not in the neuroendocrine component.…”

“…3-8 The first primary pancreatic hepatoid carcinoma (PHC) was reported by Hruban et al in 1987. 9 So far, only 31 primary PHCs have been reported in the English literature, 9-38 and the vast majority of them are single case reports except 1 study with 2 cases. 12 In addition, the vast majority of these reports were in nonpathology journals, * and therefore, the pathological features of these tumors and their correlation with prognosis have not been analyzed.…”

Pure pancreatic hepatoid carcinoma: a surgical case report and literature review

“…In the present case, preoperative immunohistochemistry precluded correct diagnosis because of the small amount of the tissue and the under-recognition of this tumor. In patients with an accurate preoperative diagnosis of pure pancreatic HC, laparoscopic distal pancreatectomy might be a better choice of treatment, because some reports described regional lymph node metastasis on pathological review of resected specimens [12, 33].…”