Isolated bone marrow Hodgkin lymphoma in a human immunodeficiency virus-negative patient: a second case.

Hodgkin lymphoma (HL) is considered one of the most curable forms of cancer, with a 5-year survival rate of up to 90% [1]. Extranodal HL represents only 15% of HL, and is mainly observed in advanced stages, i.e. stage IV [2]. Isolated bone marrow involvement without nodal or other extranodal manifestation is rare, and has been reported previously in six human immunodefi ciency virus (HIV)positive patients [3], and in only one HIV-negative patient [4]. Herein, we report a second HIV-negative patient with isolated bone marrow HL. A 50-year-old male patient of African origin with a previous history of malaria was hospitalized for general physical deterioration, weight loss and fever without chills, lasting for 1 month. Initial clinical examination showed an Eastern Cooperative Oncology Group (ECOG) performance status scale of 2, no lymphadenopathy, no liver or spleen involvement and no hemorrhage or thrombosis. Th ere were also no cardiac or pulmonary abnormalities, and arterial blood pressure was in the normal range. Th e initial blood tests revealed a pancytopenia, with leukopenia of 2.1  10 9 /L, neutropenia of 1.1 10 9 /L, a profound lymphopenia of 0.3  10 9 /L, thrombocytopenia of 40 10 9 /L and a non-regenerative normocytic anemia with a hemoglobin level of 7.4 g/dL. Clotting tests were all normal. Renal and liver functions were not initially altered, but serum lactic dehydrogenase levels were increased. Serum protein electrophoresis showed hypoalbuminemia of 29 g/L with elevated α 2 globulins secondary to an infl ammatory syndrome confi rmed by elevated C-reactive protein and serum ferritin levels. Serum lipids were within the normal range. Bacterial blood cultures were negative as well as tests for malaria. Viral serology tests were negative for cytomegalovirus (CMV), hepatitis C virus (HCV), hepatitis B virus (HBV) and B19 parvovirus, as well as for HIV-1/2 and p24 antigen. Epstein – Barr virus (EBV) serology refl ected a past infection, with detection of immunoglobulin G (IgG) for viral capsid antigen (VCA) and Epstein – Barr virus-encoded nuclear antigen 1 (EBNA-1) without IgM VCA. Because of pancytopenia, bone marrow aspiration was performed, and revealed a hypocellular marrow without leukemic or lymphoma cells, and no features of myelodysplasia. Th us, a formalin-fi xed paraffi n-embedded bone marrow biopsy was performed which showed typical scattered, large Reed – Sternberg cells (RSCs) [Figures 1(a) and 1(b)] with diff use anti-CD3 reactive T-cells, without Hodgkin granuloma, epithelioid cells or eosinophilia. Th e hematopoietic tissues were preserved but showed hypoplasia with a grade III reticulin fi brosis. RSCs were positive for CD30 (Figure 2), CD15, EBV-latent membrane protein 1 (LMP1) and PAX 5, and negative for CD3, CD20, CD45 and ALK1. Th ese results were indicative of a bone marrow manifestation of classical HL. Both a thorax – abdominal computed tomography (CT) scan and positron emission tomography did not show pathologic lymph nodes, spleen or additional sites of malignancy besides the bone marrow. Th us, a diagnosis of isolated bone marrow HL in an HIV-negative patient was made. Indeed, adverse prognostic factors for HL were identifi ed: male gender, over 45 years old, low blood albumin and hemoglobin levels and low lymphocyte count. While chemotherapy combining adriamycin, bleomycin, vinblastine and dacarbazine (ABVD) was started, the patient developed an Enterobacter cloacae -positive septicemia and, secondarily, an encephalopathy with respiratory distress that necessitated mechanical respiration in the intensive care unit. Viral encephalitis was also suspected because of a positive polymerase chain reaction (PCR) for herpes simplex virus-1 in the cerebrospinal fl uid. Despite chemotherapy, antibiotic therapy and antiviral therapy, the patient developed multiple organ failure and died 21 days after admission to hospital. L eu k L ym ph om a D ow nl oa de d fr om in fo rm ah ea lth ca re .c om b y IN SE R M T es t I D o n 04 /1 4/ 14