CD20-negative diffuse large B-cell lymphoma presenting with lactic acidosis
Authors: Megha Garg, Brian E. Lee, Kelly McGarry, Shamlal Mangray, Jorge J. Castillo
Journal: American Journal of Hematology (2014)

To the Editor: A 61-year-old man presented with acute onset confusion and one month of persistent fevers. Review of systems revealed abdominal distension and anasarca, weight loss, diarrhea, and poor oral intake. Laboratory workup showed acute kidney injury (creatinine 1.48 mg/dL) and pancytopenia (WBC 2.6 × 109/L, hemoglobin 11.5 g/dL, platelets 109 × 109/L). He also had transaminitis (AST 105 IU/L, ALT 56 IU/L, alkaline phosphatase 131 IU/L), normal bilirubin level, profound hypoalbuminemia (albumin 1.4 g/dL), and elevated lactate of 4.9 mEq/L. HIV and viral hepatitis serologies were negative. Extensive workup including paracentesis and stool cultures was unrevealing. Computed tomography (CT) scans showed no lymphadenopathy, hepatosplenomegaly, or discrete masses. On day 4 of admission the patient experienced diarrhea with blood clots, developed ventricular tachycardia, and died. Histopathology revealed large malignant cells diffusely involving extranodal sites: heart, epicardium, peripancreatic tissue, liver, subserosa of the digestive tract, and pituitary gland (Fig. 1). Immunohistochemical staining was negative for CD20 but positive for CD45 and CD79a providing evidence of B-cell lineage. T-cell markers CD3, CD4, and CD8 were negative. The malignant cells did not express CD5, CD10, CD138, CD30, CD15, IRF4/MUM1, EBV LMP1, HHV8 LANA, cyclin D1, MYC, or anaplastic lymphoma kinase (ALK). Ki-67 expression was 50%. These findings were consistent with stage IV CD20− diffuse large B-cell lymphoma (DLBCL). Pancreas is outlined by dots while the arrow shows tumor in the peripancreatic fat. Section of the pituitary shows similar morphology of cells intermixed with cells of the pituitary and surrounding fibrous tissue. Submucosa of the stomach shows infiltration around a vessel. Liver section shows an infiltrate (arrow) with non-neoplastic liver to the right. Tumor cells range in size from medium size to large lymphocytes including multinucleated forms. Heart with tumor infiltrating the right atrium and tumor cells infiltrating a vessel wall (arrow). Immunohistochemical profile shows lack of CD20 expression, positivity for CD79a, and Ki-67 expression in 50% of cells. As the spectrum of CD20− DLBCL continues to evolve, specific entities have been described. Plasmablastic lymphoma (PBL) is associated with HIV and Epstein-Barr virus (EBV) co-infection with median survival of 12 months 1. Based on a recent study, PBL is the most common CD20− DLBCL subtype, accounting for 75% of the cases 2. PBL cells usually express plasma cell markers CD138 or IRF4/MUM1 with Ki67 >90%. Primary effusion lymphoma (PEL) is associated with co-infection by HIV, EBV, and HHV8, and presents as pleural, peritoneal and/or pericardial effusion without mass or lymphadenopathy. Survival is poor at 9 months 3. HHV8-positive DLBCL arising from multicentric Castleman disease (MCD) presents in the setting of HIV infection and is associated with poor survival 4. ALK+ DLBCL presents with nodal and extranodal involvement, malignant cells express ALK and patients have median survival of 20 months 5. ALK+ DLBCL is not associated with viral infections 6. Our patient did not meet criteria for PBL, PEL, HHV8+ DLBCL arising from MCD or ALK+ DLBCL. Our patient also presented with type B1 lactic acidosis since there was no evidence of hypoperfusion in the setting of malignancy. Type B lactic acidosis is rare in hematologic malignancies and often goes unrecognized, and is a marker of poor prognosis 7, 8. A report showed that with appropriate chemotherapy, a portion of patients could obtain a survival benefit 9. We present a patient with CD20− DLBCL with diffuse extranodal disease but no discrete masses who presented with type B1 lactic acidosis. Such association is rare and we have not found similar reports in the literature. Our patient did not meet criteria for well-described CD20− DLBCL subtypes, and suggests that the spectrum of CD20− DLBCL continues evolving. Given the poor prognosis of these lymphomas and lack of benefit from anti-CD20 therapy, the development of new therapies is warranted. Megha Garg,1* Brian E. Lee,1 Kelly McGarry,1Shamlal Mangray,2 and Jorge J. Castillo3 1Department of Medicine, Rhode Island Hospital, The Warren Alpert Medical School of Brown University, Providence, Rhode Island; 2Department of Pathology, Rhode Island Hospital, The Warren Alpert Medical School of Brown University, Providence, Rhode Island; 3Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts