Development of Non-Hodgkin’s Lymphoma As Second Primary Cancer in Hepatitis C Virus-Infected Patients with a Different Primary Malignancy – a Case Series

Background:Hepatitis C virus (HCV) is carcinogenic and infected patients are at increased risk of developing hepatocellular carcinoma (HCC) and non-Hodgkin’s lymphoma (NHL). HCC can develop as a as a second primary cancer (SPC) in HCV-infected cancer patients with a nonliver first primary cancer. However, reports on HCV-infected patients who develop NHL as SPC are lacking.

Methods:Records of patients with chronic HCV infection who were seen at MD Anderson Cancer Center, Houston, TX, between 01/2008 - 5/2014 were reviewed. Patients who developed NHL in the setting of a different primary malignancy were described in this case series. HCV therapy did not include newly approved antivirals.

Results:Eighty four patients with HCV-associated NHL were seen during the study period. Among, them, six (7%) developed NHL as SPC; most were men (n=4; 67%), Caucasians (n=5; 83%), and had genotype 1 infection (two patients had genotype known; both had genotype 1b infection). All patients had solid first primary cancers, mostly prostate cancer (n=3; 50%), followed by choriocarcinoma (n=1; 17%), chondrosarcoma (n=1; 17%), and squamous cell carcinoma of larynx (n=1; 17%). Most patients (n=5; 83%) had their first primary cancers in complete remission, and only 1 had cirrhosis at lymphoma diagnosis. Surgery (n=3; 50%) and chemotherapy (n=2; 34%) were the main treatment modalities for first primary malignancies, with leuprolide acetate and carboplatin as the only chemotherapeutic agents administered. The types of NHL developed as SPC were diffuse large B cell lymphoma (n=3; 50%), marginal zone B cell lymphoma (n=2; 33%), and mantle cell lymphoma (n=1; 17%). None of the patients had a family history of lymphoma. NHL was not suspected and was found incidentally in all patients at a median of 34 months (range, 2 – 410 months) after the diagnosis of the first primary malignancy. Hepatitis B core antibodies were detected in 4 (67%) patients. A majority of patients had persistent HCV viremia (n=4; 67%) when NHL was diagnosed. Two of the 3 patients who were treated for HCV infection had attained sustained virological response (regarded as virological cure).

Conclusions:NHL may develop as SPC in HCV-infected patients with a different primary malignancy, especially in patients who have primary solid tumors or unresolved infection. Therefore, surveillance not only for the development of HCC but also NHL as SPCs should be continued in HCV-infected patients with different primary malignancy. Eradication of this carcinogenic virus with better tolerated and more efficacious antivirals may potentially reduce the risk of NHL development as SPC.