Erythrocytosis caused by an erythropoietin-producing hepatocellular carcinoma

Abstract

A case of erythrocytosis caused by a hepatocellular carcinoma (HCC) that produced erythropoietin (Epo) is described. A 64-year-old man, with a huge HCC tumor in the right lobe of the liver, showed a high concentration of hemoglobin and increased levels of serum Epo, alpha-fetoprotein (AFP), and protein induced by vitamin K absence II (PIVKA-II). Right lobectomy of the liver was performed. Histological findings of the specimen showed a moderately differentiated HCC. The existence of Epo was confirmed immunohistochemically only in the tumor tissue and not in the normal liver tissue. Erythrocytosis disappeared and the serum levels of Epo, AFP, and PIVKA-II returned to the normal range after the operation. Within 2 months after the operation, recurrent tumors appeared in the remnant liver, and the patient died 13 months after the operation.

Secondary Erythrocytosis Associated with Schwannoma in a Dog

“…Secondary inappropriate polycythemia refers to renal diseases or neoplasia without systemic hypoxia [9,14]. A variety of neoplasms, including renal cell carcinoma [13], hepatocellular carcinoma [11], Wilms' tumors [3], cerebellar hemangioblastomas [17], and uterine leiomyomas [18] have been associated with erythrocytosis in humans. In dogs, there have been several reports on secondary erythrocytosis associated with renal neoplasm, including carcinoma [15], lymphosarcoma [12], fibrosarcoma [7], and adenocarcinoma [5], as well as with nasal fibrosarcoma [4] and cecal leiomyosarcoma [16].…”

“…Although EPO is normally produced by the kidney and fetal liver, apparently increased levels of EPO polypeptide and messenger ribonucleic acid (mRNA) have been found in neoplastic cells from renal cell carcinoma [6]. In addition, immunohistochemical staining revealed the presence of EPO in the tumor tissue of hepatocellular carcinoma, but not in normal liver tissues [11]. Erythropoietin was also detected in a cerebellar hemangioblastoma at the protein and mRNA levels [17], and ectopic EPO protein was identified in a uterine leiomyoma by immunohistochemistry [18].…”

Paraneoplastic Phenomena in Patients with Hepatocellular Carcinoma

“…Of southern African Blacks with HCC living on the Highveld of South Africa (altitude 1,750 meters above sealevel), 3.9% have a hemoglobin level of greater than 19.2 grams % (the upper limit of normal at that altitude) at the time of admission to hospital [2,4,5,8,10,11,13]. In two early studies in countries not in Africa, the incidence of the syndrome was 3% and 12%, respectively [14,15]. A possible reason for the lower incidence of the phenomenon in the sub-Saharan Black African population is the late recognition of the tumor in these patients, by which time any erythrocytosis present earlier may already have been counteracted by the anaemia of the advanced malignant disease.…”

“…A possible reason for the lower incidence of the phenomenon in the sub-Saharan Black African population is the late recognition of the tumor in these patients, by which time any erythrocytosis present earlier may already have been counteracted by the anaemia of the advanced malignant disease. Prevalences in Chinese patients range from 2.0 to 5.0% [12] and patients in the U.S.A. [6,7,14,15] have similar prevalences to those in sub-Saharan Africa.…”

Paraneoplastic erythrocytosis as a primary presentation of hepatocellular carcinoma

“…Thirdly, certain HCC cells are capable of producing "ectopic erythropoietin" even in the absence of tissue hypoxia. [3] Direct evidence of erythropoietin production by HCC cells was demonstrated by electron microscopy and immunohistochemistry of HCC tissue from patients with paraneoplastic erythrocytosis. [4] HCC-related paraneoplastic erythrocytosis is signiÞ cantly associated with large tumor volume, markedly elevated AFP levels, advanced disease and reduced survival.…”