A 43-year-old woman presented with malaise and fatigue that had developed one month prior. She was mentally retarded but was in good health until the symptoms developed. A CBC performed in a private clinic showed a hemoglobin level of 4.2 g/dL, a white blood cell count of 3,000/µL, and a platelet count of 234,000/µL. After a packed red cell transfusion, she was transferred to our hospital for further evaluation and treatment.
She had no signs of fever, weight loss, or night sweats. Laboratory finding at admission showed a hemoglobin level of 6.9 g/dL (MCV 84.9 fL), a white blood cell count of 3,900/µL, a platelet count of 197,000/µL, a reticulocyte count of 0.2%, serum ferritin of 814.8 µg/L, LDH of 664 U/L, total protein of 6.1 g/dL, albumin of 3.9 g/dL, and normal liver and kidney function tests. A peripheral blood smear revealed normocytic normochromic anemia. Direct and indirect Coombs' tests were indicative of strong positivity (4+). ANA was skeleton level 3, and C4 was decreased. A serologic test for EBV revealed that the patient was negative for EBV IgM and positive for EBV IgG. PCR for parvovirus B19 was negative. A CT scan of the abdomen revealed marked hepatosplenomegaly and small multiple lymphadenopathies in the aortocaval, para-aortic, and retrocaval areas. A PET-CT showed mild FDG uptake in the bilateral axillary, aortocaval, para-aortic, and retrocaval lymph nodes with hepatosplenomegaly and diffuse bone marrow involvement. A bone marrow biopsy revealed one lymphoid follicle, focal infiltration of abnormal lymphoid cells and the absence of red cell precursors (). The infiltrated lymphoid cells were mostly positive for CD3. A chromosomal study showed 46, XX. These finding are consistent with a pure red cell aplasia with lymphoma involvement. A splenic biopsy showed diffuse infiltration of lymphoplasma cells admixed with congested vascular spaces. There were multifocal and perivascular aggregations of atypical lymphoid cells with clear cytoplasm, which were positive for CD3 (). Despite the fact that there was not enough tissue biopsied to achieve a diagnosis, it was considered to be AITL. In accordance with the clinical manifestations, results of laboratory tests, and bone marrow and splenic biopsies, we finally diagnosed the patient as having a pure red cell aplasia associated with AITL (stage IVA).
Fig. 1 (A) Bone marrow biopsy shows focal infiltration of abnormal lymphoid cells and the absence of red cell precursors (H&E, ×400). (B) Splenic biopsy shows diffuse infiltration of atypical lymphoid cells which are positive for CD3 (CD3, ×400). (more ...)
During diagnostic work-up, she developed fever, jaundice, hematuria, and skin rash on her whole body. Her hemoglobin rapidly decreased from 6.1 to 3.7 g/dL. Laboratory tests at that time were consistent with hemolytic anemia. She was treated with a washed RBC transfusion and prednisone but there was no response. The patient was started on CHOP (cyclophosphamide, adriamycin, vincristine, prednisone) chemotherapy. After one cycle, hemoglobin levels increased to 9.7 g/dL and all of the above noted symptoms disappeared. A bone marrow biopsy after one cycle of CHOP showed hypercellular marrow with erythroid hyperplasia. describes change in hemoglobin levels during treatment. After 6 cycles of CHOP therapy, she achieved complete remission and a normal hemoglobin level and remained so out to 20 months.
Change of hemoglobin levels during treatment.