Refractory cold autoimmune hemolytic anemia as initial presentation of gastric B cell lymphoma: a case report

Cold agglutinin disease is one of main two types of cold-antibody autoimmune hemolytic anemias, which can be either primary or, commonly, secondary to an infection or underlying lymphoproliferative disease [1]. We report a rare case of refractory cold autoimmune hemolytic anemia as an initial presentation of gastric B cell lymphoma.

A 53-year-old Sri Lankan woman with diabetes mellitus, dyslipidemia, and hyperthyroidism presented with increased fatigue and shortness of breath on mild exertion for 1 month. She reported yellowing of eyes and passage of dark urine. Examination findings revealed pallor, icterus, and moderate splenomegaly with no hepatomegaly or lymphadenopathy. She was found to have hemoglobin of 8.3 g/dl with mean corpuscular volume 90.8 fL and mean corpuscular hemoglobin 30.4 pg. Elevated reticulocyte count (8%), lactate dehydrogenase (357 U/L), and indirect hyperbilirubinemia (total bilirubin 1.2 mg/dl and indirect bilirubin 0.6 mg/dl) was suggestive of hemolysis. The presence of red cell autoagglutination in the peripheral blood smear with direct antibody testing positivity for C3d (3+) specificity confirmed cold autoimmune hemolytic anemia. Her initial contrast enhanced computed tomography of the chest, abdomen and pelvis failed to show any enlarged lymph nodes or underlying malignancy, and a bone marrow biopsy only showed moderate erythroid hyperplasia. She had poor response to intravenous methylprednisolone pulses, mycophenolate mofetil, and intravenous rituximab. In view of refractory hemolysis, she underwent a repeat imaging, which showed a heterogeneous mass lesion arising from the greater curvature of the stomach with regional lymph node involvement. Gastroscopy revealed a submucosal mass arising from the gastric fundus with a smooth surface. Endoscopic ultrasound guided biopsy confirmed the diagnosis of high-grade B cell gastric lymphoma, which was identified as the culprit for refractory cold autoimmune hemolytic anemia.

This case report highlights that refractory cold autoimmune hemolytic anemia can be an initial presentation of gastric B cell lymphoma. This also emphasizes the importance of reassessments and reimaging to exclude underlying secondary causes in cases of refractory cold autoimmune hemolytic anemias.