Intravascular large B-cell lymphoma presenting with fever and refractory acidosis

Intravascular large B-cell lymphoma (IVLBCL) is a rare form of diffuse large B-cell lymphoma, characterized by malignant B-cells primarily localized to the lumina of small- and medium-sized blood vessels without lymphadenopathy. Two patients initially presented with fever of unknown origin and persistent lactic acidosis without evidence of tissue hypoxia. Neither patient had an identifiable source of infection and both underwent peripheral blood smear demonstrating leukocytosis with a neutrophilic predominance and thrombocytopenia without evidence of hematologic malignancy. One had previously had a bone marrow biopsy which was unremarkable. Both patients' condition deteriorated rapidly, progressing to multiorgan failure requiring pressors and mechanical ventilation, which ultimately resulted in cardiopulmonary arrest. At autopsy, each patient demonstrated malignant lymphocytoid cells, staining positive for CD20, localized to the lumina of small- and medium-sized vessels in multiple organs, including the lungs, liver, spleen, and kidneys, among others, allowing for the diagnosis of IVLBCL. IVLBCL is exceedingly rare, which in combination with significant variability in presentation, can make identification and diagnosis challenging. Diagnosis requires biopsy, therefore a high index of suspicion is needed to obtain an adequate tissue sample, whether pre- or postmortem. In the presented cases, both patients exhibited type B lactic acidosis with an unknown etiology that was ultimately determined at autopsy.

[Type B lactic acidosis associated with marginal lymphoma of the spleen: report of one case]. / Linfoma marginal del bazo asociado a acidosis láctica tipo B: caso clínico.

Lactic acidosis in the absence of hypoxia or tissue hypoperfusion (type B) is very rare and is associated with the use of some drugs or malignancy. We report a 79-year-old woman, with a marginal non-Hodgkin's lymphoma of the spleen that was subjected to a splenectomy one year ago. She presented with unexplained tachypnea associated with pancytopenia and elevation of IgM to 10 times over the higher normal limit. Laboratory tests showed the presence of metabolic acidosis and high lactic acid levels in the absence of infection, tissue hypoxia or hypoperfusion. She was treated with sodium bicarbonate and steroids without obtaining a reduction in lactate levels. Twelve days after admission, a single dose of Rituximab quickly normalized lactate concentrations and platelet count. After the fourth dose of Rituximab, pancytopenia disappeared and IgM fell to 25% of its baseline concentration.

Linfoma marginal del bazo asociado a acidosis láctica tipo B: Caso clínico / Type B lactic acidosis associated with marginal lymphoma of the spleen: Report of one case

Lactic acidosis in the absence of hypoxia or tissue hypoperfusion (type B) is very rare and is associated with the use of some drugs or malignancy. We report a 79-year-old woman, with a marginal non-Hodgkin's lymphoma of the spleen that was subjected to a splenectomy one year ago. She presented with unexplained tachypnea associated with pancytopenia and elevation of IgM to 10 times over the higher normal limit. Laboratory tests showed the presence of metabolic acidosis and high lactic acid levels in the absence of infection, tissue hypoxia or hypoperfusion. She was treated with sodium bicarbonate and steroids without obtaining a reduction in lactate levels. Twelve days after admission, a single dose of Rituximab quickly normalized lactate concentrations and platelet count. After the fourth dose of Rituximab, pancytopenia disappeared and IgM fell to 25% of its baseline concentration.

Fatal infantile liver failure associated with mitochondrial DNA depletion.

A 3-month-old girl was admitted to the hospital because of hypotonia and frequent vomiting. She had severe metabolic acidosis and her liver function was abnormal. Hepatomegaly and rapidly progressive liver failure developed, and she died at 4 months of age. Two half-siblings from a different mother had died in infancy of an undiagnosed myopathy. The liver was fatty and hepatocytes were filled with large and small lipid droplets. Other tissues were morphologically normal. The respiratory chain enzymes containing subunits encoded by mitochondrial DNA were markedly decreased in liver, partially decreased in muscle, but normal in other tissues. Southern blot analysis showed 90% depletion of mitochondrial DNA in liver, 53% depletion in muscle, and normal amounts in other tissues. This is the second case of fatal infantile liver failure associated with mitochondrial DNA depletion. This pathogenetic mechanism should be considered in infants with multiple respiratory chain defects and variable tissue expression.

Mitochondrial encephalomyopathies with the mutation of the mitochondrial tRNA(Leu(UUR)) gene.

Four families with mitochondrial encephalomyopathy are described. Probands of three families had typical clinical presentations of mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes (MELAS), but the proband of family 4 lacked strokelike episodes. The mitochondrial DNA mutation of tRNA(Leu(UUR)) (transfer ribonucleic acid specific to leucine (UUR codon)) found in MELAS was examined in muscle DNA obtained from biopsy samples of the probands of four families and the maternal relatives of family 2. The mutation was detected in all muscle samples, and the degree of the mutated DNA was 68% to 84% by Southern blot analysis. However, the clinical patterns of the maternal relatives of family 2 were mild and distinctly different from MELAS. The same mutation was also detected in blood-derived DNA samples of all family members examined, including healthy mothers but not fathers, although the degree of mutation did not correlate with the clinical severity. These results confirmed the maternal inheritance of this disease and suggested that the mitochondrial DNA mutation (tRNA(Leu(UUR))) may cause clinical symptoms other than MELAS. The clinical findings of mitochondrial encephalomyopathy should be reinvestigated in terms of the mitochondrial gene mutation; the polymerase chain reaction method will be useful for screening for this mutation of mitochondrial DNA in blood samples.