A rare case of B-cell lymphoma characteristic of persistent lactic acidosis, hypoglycemia, and dyslipidemia in the emergency department

Shuo Zhang, Bing-jie Wang, Xiao-lan Chen, Hui Xiong

1 Department of Emergency Medicine, Peking University First Hospital, Beijing 100034, China

2 Department of Hematology, Peking University First Hospital, Beijing 100034, China

Dear editor,

Lactic acidosis is a commonly encountered condition in the emergency department, and the most common causes of lactic acidosis are hypoperfusion and hypoxia induced by sepsis. A number of other diseases can also cause hyperlactatemia, such as hematological malignancies, which can sometimes be life-threatening. Treatment of hyperlactatemia is largely dependent on underlying conditions. Therefore,an accurate diagnosis is important, and prompt treatment could be lifesaving. Despite the advances in medical sciences, lactic acidosis and malignancy have been linked only in a small number of cases,[1]and hypoglycemia and dyslipidemia were rare findings. We report a case of an elderly woman who had persistent lactic acidosis and hypoglycemia with dyslipidemia and was finally diagnosed with B-cell lymphoma.The aim of this case is to highlight the importance of considering hematological malignancies when presented with persistent lactic acidosis and identify a diagnosis for appropriate and timely treatment.

CASE

A 65-year-old Chinese woman was admitted to the emergency department with nausea and edema. She also had abdominal distension but did not have fever,cough, shortness of breath, chest pain, abdominal pain,or diarrhea. The only past medical history was cerebral infarction without any lapses. No cognitive or behavioral impairments were observed in her. The vital signs were normal except for hypertension (temperature, 36.7 ℃;blood pressure, 173/97 mmHg [1 mmHg=0.133 kPa];heart rate, 73 beats/min; respiratory rate, 14 breaths/min). Physical examination was remarkable for edema in the face and lower extremity. Laboratory data showed renal insufficiency, lactic acidosis, hypoglycemia, and dyslipidemia with the main hematological parameters as follows: white blood cell (WBC), 9.5×109/L; hemoglobin count (Hb), 117 g/L; platelet count (PLT), 128×109/L, creatinine, 462.3 μmol/L; lactate dehydrogenase,1,836 U/L; uric acid, 1,538 μmol/L; albumin, 34.7 g/L; triglyceride (TG), 10.99 mmol/L; total cholesterol(TC), 7.47 mmol/L; high-density lipoprotein (HDL), 0.31 mmol/L; low-density lipoprotein (LDL), 0.27 mmol/L; glucose, 3 mmol/L. The liver and heart functions were normal, while arterial blood gas (ABG) showed: pH, 7.32;PO2, 95 mmHg; PCO2, 31.5 mmHg; HCO3-, 16.2 mmol/L; lactate, 4.6 mmol/L (FiO2, 29%), indicating lactic acidosis.

Glucose 50% 40 mL was administered immediately to treat hypoglycemia. Other treatment included fluid infusion, nutritional support, antihypertensive therapy,hepatoprotection, antiemetic treatment, and continuous renal replacement therapy (CRRT). Despite this, the patient still suffered from hypoglycemia and had persistent high levels of lactic acid (Figure 1).

A number of other examinations for kidney failure have been conducted afterward. Laboratory test results were normal, which included autoantibody profiling,Coombs, anti-neutrophilic cytoplasmic antibodies(ANCA), anti-glomerular basement membrane(GBM) antibodies, IgA, IgM, IgG, complement 4(C4), peripheral blood smear, complement factor H,von Willebrand factor cleaving protease (VWF-cp),immunofixation electrophoresis, tumor marker, and immunoglobulin free light chains. However, the C3 level was slightly decreased (0.572 g/L, normal range:0.6-1.5 g/L), and the HbAlc level was slightly increased(6.2%, normal range: 4%-6%). Superficial lymph node ultrasonography showed that the supraclavicular, axillary,and inguinal lymph nodes were normal. Abdominal computed tomography (CT) demonstrated multiple wedge-shaped low-density areas plus increasing volume in both kidneys.

A higher dose of glucose was administered, but the patient’s hypoglycemia persisted. Meanwhile, laboratory tests exhibited decreased WBC, Hb, and PLT counts,accompanied by TG and TC levels that initially increased and subsequently decreased (Table 1). On day 7, the patient lost consciousness, and CT of the head demonstrated frontoparietal epidural effusion. A neurosurgeon helped drain the bloody effusion. The blood pressure began to decrease, and vasopressors were administered. Bone marrow puncture was performed on day 8, which showed an increased level of blast cells with deeply stained cytoplasm and obvious vacuolar degeneration (Figure 2). Flow cytometric examination revealed large B cell infiltration with the phenotype of CD19+,CD20+, CD5-, CD10+, and CD38+. Both examinations showed high grade B-cell lymphoma, which should be validated by biopsy. However, the patient had severe bleeding during the bone marrow puncture and was in an extremely poor status, and the biopsy was denied by her daughter. Unfortunately, the patient died on day 9.

Figure 2. The picture of bone marrow aspirate (Wright-Giemsa staining, magnification 1,000).

Table 1. Laboratory test results of the patient

Figure 1. The variation tendency of blood glucose and lactic acid. CRRT: continuous renal replacement therapy.

DISCUSSION

We report a case of an elderly woman with nausea and edema. Her refractory hyperlactatemia could not be normalized by powerful CRRT, and even when glucose exceeding physical needs was administered, intermittent hypoglycemia was observed. She even presented with persistent hypertriglyceridemia and hypercholesterolemia when her blood sugar below normal.

Several diseases could cause hyperlactatemia, and Kraut et al[2]explicitly reported the causes, diagnosis, and management in their review. Our patient had no special medical history, nor did she use any special drugs.There were no signs of infection, sepsis, hypoxemia,or hypoperfusion. The medical examinations did not show liver diseases, diabetes, shock, or heart failure.Although she received CRRT, she still had persistent lactic acidosis, which could not be attributed to renal failure. Finally, the bone marrow aspirate confirmed large B-cell lymphoma, which might explain refractory hyperlactatemia, known as type B1 lactic acidosis.

Multiple theories were proposed to explain this phenomenon, including decreased clearance of lactate in the liver and kidney, thiamine deficiency, and increased production of lactate by tumor cells, as they prefer anaerobic glycolysis to oxidative metabolism even at normal oxygen concentrations - a phenomenon referred to as the “Warburg” effect.[3-5]However, the exact mechanisms are still unclear.

The association of malignancy with type B lactic acidosis has been largely limited to a few case reports.[1]This condition is usually refractory and difficult to treat with fluid infusions, antibiotics,or CRRT. Chemotherapy is considered the most effective treatment,[5,6]and thiamine deficiency might be helpful.[4]Often, patients with lymphoma have fever, lymphadenopathy, hepatosplenomegaly,and changes in blood cells. However, our patient showed no obvious signs of lymphoma until two days before death. Therefore, persistent lactic acidosis could be the first manifestation of lymphoma, even before the occurrence of changes in blood cells or lymphadenopathy, and we suggest performing bone marrow biopsy as soon as possible. Makino et al[7]found that the kidney was inflated with leukemia cells during autopsy, indicating that the changes in the kidney on CT might be caused by tumor invasion, and percutaneous renal biopsy may be beneficial to the patient. We did not perform renal biopsy on the patient due to a lack of awareness.

We also found the combination of hypoglycemia and dyslipidemia in our case. Dyslipidemia was characterized by hypertriglyceridemia,hypercholesterolemia, and low HDL and LDL levels. There have been several cases described hypoglycemia,[5,7]yet none of them have reported dyslipidemia. Hypoglycemia can be elucidated by the “Warburg” effect, while the relationship between cancer and dyslipidemia remains unclear. Few studies have focused on whether hematological malignancy can cause dyslipidemia and their conclusions on how blood lipids are affected are inconsistent,[8,9]which is a question deserving investigation. We suppose two theories to explain the phenomenon: (1) She had a medical history of hyperlipidemia and subsequently developed lymphoma. Tumor cells prefer sugars to lipids, leading to glucose exhaustion and excess lipids. (2) The metabolism of lipid and glucose were affected by lymphoma, leading to the presence of hypoglycemia and dyslipidemia. However, common hyperlipidemia could not explain the characteristics of dyslipidemia, especially the low LDL level,[10]and she denied having a history of hyperlipidemia. Thus,we consider that the second theory might be more reasonable. It is still unclear how cancer and blood lipids interact, so more research is needed.

CONCLUSION

We illustrate a rare case characterized by persistent lactic acidosis, hypoglycemia, and dyslipidemia,which ultimately turned out to be lymphoma. We therefore emphasize the need to consider hematological malignancy in such situations, especially without evidence of other causes. We suggest prompt biopsy of the bone marrow or other suspicious lesions, as the prognosis is poor and chemotherapy might maximize the potential for survival.

Funding:None.

Ethical approval:Not needed.

Conflicts of interest:The authors declare that they have no conflicts of interest.

Contributors:All authors are doctors in charge of this patient and contributed to the acquisition, analysis, or interpretation of data for the work. Our separate contributions are as follows: (1) SZ wrote the manuscript of this case report; (2) HX revised the article and is the corresponding author.