Lymphoma is 20 times more common in the HIV-infected population [1–4]. In this setting, common subtypes are diffuse large B-cell lymphoma and, to a lesser extent, Burkitt's lymphoma, primary effusion, plasmablastic, Hodgkin's disease, and primary central nervous system lymphoma [3,4]. Indolent lymphomas are not well described in the setting of HIV, and it is not known whether the course is different from those without retroviral infection. We describe a rare case of splenic marginal zone lymphoma (SMZL) in a patient with known HIV presenting with malaise, increasing abdominal girth, and pancytopenia. Years of follow-up demonstrate that he has done extremely well with only a splenectomy.
A 50-year-old man presented with 10 days of severe fatigue and increasing abdominal girth. He denied fever, early satiety, weight loss, or any other symptoms. He had been diagnosed with HIV infection 10 years earlier when he presented with a hemolytic anemia treated successfully with high-dose corticosteroids, but complicated by permanent left optic nerve damage. Over the next 10 years, he had no opportunistic infections. His CD4 cell count ranged between 150 and 250 cells/μl, and his HIV viral load remained less than 400 copies/μl maintained on stavudine, lamivudine and indinavir. Other medications were as follows: atovaquone, acyclovir, fluoxetine, dextroamphetamine, trazodone, alprazolam, zolpidem, lansoprazole, allopurinol, folic acid, ferrous sulfate, albuterol, and prednisone. Concurrent illnesses included asthma and chronic, severe depression.
Ten days before admission he presented with marked splenomegaly. He had new onset pancytopenia with a white blood cell count of 1.4 × 103/μl, an absolute neutrophil count of 0.8 × 103/μl, hemoglobin level of 8.1 g/dl, and platelet count of 91 × 103/μl. The CD4 cell count was 153 cells/μl, with a viral load of less than 400 copies/μl. Further studies consisted of a total bilirubin level of 2.6 mg/dl, a conjugated bilirubin of 0.6 mg/dl, and lactate dehydrogenase (LDH) of 276 U/l. Six days later, repeat laboratory tests showed a white cell count of 1.0 × 103/μl, an absolute neutrophil count of 0.6 × 103, a hemoglobin level of 6.6 g/dl, and an elevated reticulocyte count of 4.4%. Direct Coomb's test was positive and LDH was 918 U/l.
A computed tomography scan of the chest, abdomen, and pelvis demonstrated a 33 cm homogeneously enlarged spleen in the absence of any adenopathy.
A bone marrow biopsy was markedly hypercellular with increased M: E ratio, megakaryocytes and mild plasmacytosis. Lymphoid cells were also increased and predominantly small in morphology. Although immunohistochemistry analysis showed a mixture of CD20 and CD3 positive lymphocytes consistent with a mixture of B and T cells, a small population of cells with kappa light chain restriction was reported on flow cytometry. The constellation of the marrow findings and the clinical presentation were most consistent with an indolent B-cell lymphoma.
As the bone marrow findings did not account for the pancytopenia, splenic sequestration was considered the most probable mechanism. In addition, anemia appeared to be multifactorial. First, an autoimmune hemolytic anemia was demonstrated by an elevated reticulocyte count, a positive direct Coomb's test, and an increased indirect bilirubin and LDH. In addition, vitamin B12 was low [156 pg/ml (199–732 pg/ml), but iron stores were adequate (ferritin 124 ng/ml)]. Finally, HIV infection may also have had a direct suppressive effect on the marrow as well as inhibiting the production of erythropoietin to a decreased level of 161 mIU/ml.
Preoperative steroids resulted in a clinical improvement to a hemoglobin level of 8 g/dl, a white blood cell count of 2.8 × 103/μl, a platelet count of 120 × 103/μl, and a decrease in LDH to 253 U/l.
Splenectomy revealed a 1750 g specimen demonstrating SMZL. A del (7q) abnormality on cytogenetic study further supported the diagnosis of SMZL. Steroids were discontinued immediately postoperatively. The blood counts and chemistries promptly normalized.
Since splenectomy, the patient has been stable with no progression of lymphoma for 5 years by physical examination, hematological and radiographic criteria.
SMZL is a very indolent small B-cell lymphoma. The incidence has been estimated at less than 1% of non-Hodgkin lymphomas . Patients typically present as this patient did with marked splenomegaly, absent lymphadenopathy, pancytopenia, and variably an autoimmune condition such as hemolytic anemia .
Although aggressive lymphomas are associated with HIV infection, indolent ones are not. Moreover, it is not known whether HIV exacerbates the course of the indolent lymphoma. Levine et al.  retrospectively compared 10 cases of indolent non-Hodgkin lymphoma with 336 intermediate/high grade cases from the AIDS Lymphoma Registry at the University of Southern California, with marginal zone lymphoma representing one of the indolent cases. Patients with indolent lymphoma were more likely to have bone marrow involvement, higher CD4 cell counts, and longer survival . Despite HIV infection, our patient has enjoyed an excellent outcome after splenectomy alone, an often used surgical approach to SMZL. If confirmed in larger studies, it seems possible that HIV infection may not alter the prognosis of indolent lymphomas. Demonstrating this is important to the approach of non-AIDS-defining cancer in the HIV-infected population, an area in which little research and no guidelines exist.
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