A Rare Paraneoplastic Manifestation of Hepatocellular Cancer

Abstract

Introduction: Neutrophilic leukocytosis has been seen in many solid non-hematological tumors producing G-CSF(granulocyte-colony secreting factor). However, few cases have been reported worldwide of hepatocellular cancer (HCC) with neutrophilic leukocytosis. (1)(2) Case: 84 year old male patient presented with failure to thrive and loss of weight. No alcohol abuse. On examination there was tenderness in right upper quadrant of abdomen and splenomegaly. Labs: Hb- 8.6gm/dl, RBC- 2.9 M/mcl,Hct-26.5%, WBC-17.2 K/mcL(Granulocyte- 86.7%, Lymphocyte-8.2%,Monocyte-4%,Eosinophil-1.1% and Basophil 0%). Hepatitis panel was negative. CA 19-9:100.7 U/ml. Pan cultures revealed no growth. JAK2 V617F- Negative. BCR-ABL, t(9,22)- Negative. Bone marrow biopsy: hyper-cellular with cellularity ranging from 60-70% with myeloid hyperplasia and neutrophilia. CT abdomen: Spleen- 16 cm and liver mass- 10cm. Biopsy of the liver mass was done as shown in figure 1.Figure 1Histopathology: Biopsy of liver mass-positive for pan-cytokeratin, weakly positive for HepPar-1 and negative for CK7 and CK20, favoring poorly differentiated adenocarcinoma of liver. Discussion: HCC is 5th leading cancer in men and 8th leading cancer in women worldwide.3 In US annual incidence of hepatocellular cancer is 6 per 100,000 with men at three times higher risk than women 4. The common paraneoplastic syndrome manifestations include hypercalcemia, hypocholesteremia, hypoglycemia and erythrocytosis. On reviewing literature, there were 8 reported cases of HCC with increased G-CSF and interleukin-6 levels that caused neutrophilic leukocytosis. (1) (2) It is known to induce rapid growth of tumors and poorly differentiated carcinoma. Among the cases reported it was noted that these tumors were large in size and the size of the tumor was 10 cm in our patient. Neutrophils produce hydrogen peroxide (H2O2) which causes aggressive tumor growth.1 Increased neutrophil count is a sign of poor prognosis in most of the cancer. The diagnosis of neutrophilic leukocytosis as paraneoplastic manifestation can be supported by elevated G-CSF levels, elevated interleukin-6 levels,decrease in leukocyte count after tumor resection and immunohistochemical analysis of the specimen for G-CSF secreting tumor cells but since our patients opted for palliative therapy none of the mentioned tests was done. All the other causes for neutrophilic leukocytosis was ruled out in our patient and HCC was the only attributable cause.