Combined Primary Neuroendocrine Carcinoma and Hepatocellular Carcinoma of the Liver

Abstract

We report a unique case of combined primary neuroendocrine carcinoma (NEC) and hepatocellular carcinoma (HCC) of the liver in a 65-year-old male patient. The patient underwent segmental resection of the liver and regional lymph node dissection for a tumor mass that measured 7.5 cm in diameter in the right lobe, with regional lymphadenopathy. Histologically, the hepatic tumor was composed of predominantly small-cell NEC, but admixed with a small island of moderately differentiated HCC. We speculate that the NEC originated from a poorly differentiated tumor clone of an HCC that underwent neuroendocrine differentiation, and that this tumor was now at the end stage of the transitional period from HCC to NEC, based on the small amount of disappearing HCC. Ki-67 and p53 expression were higher in the NEC than in the HCC, and the lymph nodes showed only metastatic NEC. Therefore, this kind of tumor had a more aggressive clinical course in accordance with being an NEC rather than a conventional HCC. Three months after operation, the patient had multiple recurrent tumor nodules within the liver, spreading the metastasis to the adrenal glands and para-aortic lymph nodes. The patient died 1 year after operation.

Hepatocellular Carcinoma

“…The neuroendocrine component can be admixed with the hepatocellular carcinoma, where it is often found growing between trabeculae, or the neuroendocrine component can be distinct and form an adjacent tumor nodule. Focal transitional areas can be sometimes found [ 73 ], especially in well-sectioned tumors. In most cases, the hepatocellular component makes up the majority of the tumor, but less commonly, the hepatocellular carcinoma can be a minor component [ 73 ].…”

Caso Clínico: Hepatocarcinoma Combinado con Carcinoma Nueroendocrino Primario de Higado. Hospital de Especialidades José Carrasco Arteaga

“…Se han postulado dos hipótesis: la transformación maligna de las células madre hepáticas; y la diferenciación neuroendocrina de las células HCC bajo ciertas circunstancias; además se ha hablado de que el NEC tiene mayor actividad proliferativa y mayor potencial maligno que un simple HCC por lo que se cree que, a largo plazo, pudiera existir una transformación completa a NEC [4].…”

“…Tres meses después de la operación los exámenes de imagen mostraron nuevas masas a nivel de ambos lóbulos hepáticos, trombosis de la vena porta y metástasis que alcanzaban las glándulas suprarrenales bilaterales y los ganglios linfáticos paraaórticos. El paciente falleció un año después de la operación [4].…”

“…Una mezcla de Hepatocarcinoma (HCC) y NEC primario de hígado es aún más raro; existiendo así dos tipos, el combinado en el cual el HCC y el NEC primario se entre mezclan entre sí; y por colisión en el cual existen dos tipos histológicos de tumor bien separados por una banda fibrosa sin zonas de transición [4][5]. El de tipo combinado es más frecuente y representa el 2.0 -3.6 % de las neoplasias primarias del hígado, en comparación al 0.1 -1 % del tipo por colisión.…”

Diagnosis and Therapy of Primary Hepatic Neuroendocrine Carcinoma: Clinical Analysis of 10 Cases

“…However, the majority of these tumors showed no pancreas specific endocrine function (Balta et al, 2008). It is even speculate that the PHNEC originated from a poorly differentiated tumor clone of an HCC that underwent neuroendocrine differentiation, and that this tumor was the end stage of the transitional period from HCC to NEC (Yang et al, 2009).…”