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B-cell lymphoma, thiamine deficiency, and lactic acidosis Umair Masood, MD, Anuj Sharma, MD, Sonny Nijjar, MD, and Karthikeyan Sitaraman, MD Type B lactic acidosis is found in the absence of tissue hypoperfusion, can be associated with malignancies, and can be caused by thiamine deficiency. We present a patient who presented with an abdominal mass that biopsy disclosed to be a diffuse large B-cell lymphoma. Because thiamine deficiency is a rare cause of lactic acidosis in cancer, the patient was treated with intravenous thiamine with rapid normalization of the lactic acid level. The level prior to treatment was low. The case emphasizes a rare cause of lactic acidosis. T ype A lactic acidosis is commonly due to marked tissue hypoperfusion, whereas type B lactic acidosis is found without tissue hypoperfusion (1). Rarely, lactic acidosis is associated with aggressive solid tumors such as lymphomas. It can be due to various causes including thiamine deficiency. We present a patient with type B lactic acidosis due to deficiency of thiamine in the setting of a B-cell lymphoma. CASE DESCRIPTION A healthy 72-year-old man presented to the emergency department with vague abdominal discomfort and swelling of his left lower extremity. He had a left lower quadrant palpable mass with mild diffuse tenderness and 2+ edema of the entire left leg. His bicarbonate level was 18 mmol/L (reference range, 24 mmol/L). Other laboratory findings revealed a lactic acid level of 6.7 mmol/L (reference range, 0.5–2 mmol/L) and hemoglobin of 10.2 g/dL (reference range, 13.5–17.5 g/dL). His anion gap was calculated to be 21 (reference range, 12–14). Liver function tests, including albumin and total protein levels, were normal (Table 1). A computed tomographic scan of the abdomen showed a 9.8 × 8.4 × 12.0 cm retroperitoneal mass that appeared contiguous with the left kidney, with moderate left-sided hydronephrosis (Figure 1). A left nephrostomy tube was placed. Biopsy of the retroperitoneal mass confirmed it to be a diffuse large B-cell lymphoma (Figure 2). Despite adequate resuscitation and hydration, the patient’s lactic acid level remained elevated. At that point, his thiamine level was obtained, and the patient was treated with intravenous thiamine (500 mg every 8 hours). By the morning, the lactic acid level was 1.5 mmol/L. His thiamine level was found to be 0.9 μg/dL (reference range, 2.5–7.5 μg/dL). He was then started Proc (Bayl Univ Med Cent) 2017;30(1):69–70 Table 1. Laboratory findings Test Value Sodium (mEq/L) 136 Potassium (mEq/L) 4.3 Chloride (mEq/L) 97 Bicarbonate (mmol/L) 18 Blood urea nitrogen (mg/dL) 18 Creatinine (mg/dL) 0.9 Glucose (mg/dL) 135 Anion gap 21 Alanine aminotransferase (U/L) 45 Aspartate aminotransferase (U/L) 38 Alkaline phosphatase (U/L) 98 Albumin (g/dL) 3.6 Total protein (g/dL) 6.5 Total bilirubin (mg/dL) 0.5 Lactic acid (mmol/L) 6.7 Hemoglobin (g/dL) 10.2 Hematocrit 30.5% White blood cell count (cell/mcL) 7400 Platelets (/mcL) 210,000 on chemotherapy for his malignancy. He had a prolonged hospital course with a chemotherapy-related complication of bone marrow suppression but eventually responded well and was transferred back to his hometown for physical rehabilitation and follow-up with oncology. DISCUSSION Type A lactic acidosis is commonly found in patients with marked tissue hypoperfusion that can be caused by sepsis, From the Department of Internal Medicine, State University of New York Upstate Medical University, Syracuse, New York. Corresponding author: Umair Masood, MD, Department of Internal Medicine, State University of New York Upstate Medical University, 750 East Adams Street, Syracuse, NY 13204 (e-mail: [email protected]). 69 Figure 1. CT of the abdomen showing a left retroperitoneal mass contiguous with the left kidney with some associated hydronephrosis. cardiac failure, or hypovolemia. On the contrary, type B lactic acidosis is found in the absence of tissue hypoperfusion (1). It is a rare occurrence in patients with lymphomas, leukemias, and solid neoplasms. While the mechanism is not entirely understood, there are many proposed theories, which include intrinsic lactate production by the tumor cells, impaired clearance of lactate in kidney or liver dysfunction, and riboflavin or thiamine deficiency (2). Tumor cells have been found to have increased lactate production, as they primarily utilize aerobic glycolysis, which is also known as Warburg effect (3). Thiamine acts as a cofactor for various enzymes involved in aerobic metabolism, such as pyruvate dehydrogenase. Therefore, its deficiency promotes anaerobic metabolism, which results in the production of lactate (3). Only a few reported cases illustrate this phenomenon in patients with lymphomas (4, 5). The cases have generally been reported in pediatric patients receiving parenteral nutrition without vitamin supplementation. Friedenberg et al examined this phenomenon in hematological malignancies and found type B lactic acidosis due to thiamine deficiency in patients with leukemia rather than lymphoma (6). Seligmann et al reported subclinical thiamine deficiency in 35% of 14 untreated CLL patients (7). Lactate levels were not reported in either of the studies. 70 Figure 2. Hematoxylin and eosin stain, 20×, showing lymphoid cells with fine nuclear chromatin, scant pale cytoplasm, and round nuclei consistent with diffuse large B cell lymphoma. Acknowledgments The authors thank Dr. Daniel Zaccarini for providing the histological image. 1. 2. 3. 4. 5. 6. 7. Adeva-Andany M, Lopez Ojen M, Fungasta-Calderon R, AmeneirosRodriguez E, Donapetry-Garcia C, Vila-Altesor M, Rodriguez-Seijas J. Compressive review on lactate metabolism in human health. Mitochondrion 2014;17:76–100. Sillos EM, Shenep JL, Burghen GA, Pui CH, Behm FG, Sandlund JT. Lactic acidosis: a metabolic complication of hematologic malignancies: a case report and review of the literature. Cancer 2001;92(9):2237–2246. Dhup S, Dadhich RK, Porporato PE, Sonveaux P. Multiple biological activities of lactic acid in cancer: influences on tumor growth, angiogenesis and metastasis. Curr Pharm Des 2012;18(10):1319–1330. Shah S, Wald E. Type B lactic acidosis secondary to thiamine deficiency in a child with malignancy. Pediatrics 2015;135(1):e221–e224. Svahn J, Schiaffino MC, Caruso U, Calvillo M, Minniti G, Dufour C. Severe lactic acidosis due to thiamine deficiency in a patient with B-cell leukemia/lymphoma on total parenteral nutrition during high-dose methotrexate therapy. J Pediatr Hematol Oncol 2003;25(12):965–968. Friedenberg AS, Brandoff DE, Schiffman FJ. Type B lactic acidosis as a severe metabolic complication in lymphoma and leukemia: a case series from a single institution and literature review. Medicine (Baltimore) 2007;86(4):225–232. Seligmann H, Levi R, Konijn AM, Prokocimer M. Thiamine deficiency in patients with B-chronic lymphocytic leukaemia: a pilot study. Postgrad Med J 2001;77(911):582–585. Baylor University Medical Center Proceedings Volume 30, Number 1