Department of Pathology, University of Chicago, Illinois, United States
Background/Case Studies: The association between follicular lymphoma and autoimmune hemolytic anemia (AIHA) is well known. We present a case of AIHA with an unusual direct antiglobulin test (DAT)/eluate result in a patient with CD10-negative follicular lymphoma with plasmacytic differentiation.
Study
Design/Methods: A 66-year-old woman presented to our institution with dyspnea and fatigue. She had been recently hospitalized for severe anemia (Hemoglobin (Hb) 5.2 g/dL; Reference range (RR): 11.5-15.5 g/dL) and received 3 units of red blood cells.
During current admission, Hb was 7.3 g/dL. Workup showed hemolysis: reticulocytes 18.6 % (RR: 0.50-1.50%), haptoglobin < 20 mg/dL (RR: 51-192 mg/dL), lactate dehydrogenase 689 U/L (RR: 116-245 U/L), and indirect bilirubin 3.2 mg/dL (RR: 0.1-1.0 mg/dL). Initial DAT was weakly positive (1+) for C3 in tube and negative for IgG in gel; plasma antibody screens were consistently negative. Cold agglutinin titer was < 2, and Donath-Landsteiner (D-L) test was negative. Peripheral blood smear showed numerous reticulocytes, polychromasia, occasional spherocytes, and rare schistocytes. Imaging revealed splenomegaly and mild lymphadenopathy (axillary and pelvic). Peripheral blood flow cytometry was negative for a clonal B-cell population or paroxysmal nocturnal hemoglobinuria clone. The patient had no reported findings of extremity rash/cyanosis, or cold sensitivity.
Results/Findings: Monospecific DAT at 4C was positive for anti-C3d and negative for anti-IgG. DAT using anti-IgA, and anti-IgM reagents was negative. Acid eluate was nonreactive in anti-human globulin (AHG) phase. Autocontrol was negative with both washed and unwashed autologous red cells in polyethylene glycol -AHG, RT-Polybrene, and Polybrene-AHG phases.
Axillary lymph node biopsy revealed a CD10-negative, kappa-restricted B-cell lymphoma with follicular architecture and plasmacytic differentiation. BCL6 and LMO2 IHC were positive (not shown). These findings were consistent with CD10-negative follicular lymphoma with plasmacytic differentiation (Figure).
Treatment with high-dose corticosteroids and rituximab was begun with improvement of Hb, reaching a maximum of 8.7 g/dL.
Conclusions: We report a case with a new diagnosis of follicular lymphoma presenting with hemolytic anemia. The patient’s DAT was positive solely for C3, but the patient did not show typical laboratory findings of cold agglutinin syndrome or paroxysmal cold hemoglobinuria.
The patient’s lack of cold sensitivity and negative cold agglutinin titer/D-L study, together with her response to corticosteroids/rituximab make this case warmer autoimmune hemolytic anemia-like. The possibility of a low avidity IgG cannot be excluded.
Advanced immunologic testing, while not revealing in this case, is critical to direct the management of immune hemolytic anemia.
