A 78-year-old woman presented to the Montreal General Hospital in April 2010 with a 1-week history of fever, productive cough, worsening fatigue, bilateral leg swelling, and jaundice. Three years prior to admission (pta), she had been diagnosed with stage 0 B-cell chronic lymphocytic leukemia (cll). Initial lymphocyte count was 10.2×109/L, and flow cytometry demonstrated a population of cells that were positive for CD5, CD19, CD23, and CD38. One year pta, she developed cervical and axillary lymphadenopathy indicative of progression to stage 1 cll. She continued to be followed without treatment. Three months pta, she was diagnosed with deep-vein thrombosis complicated by pulmonary embolism, for which she received low molecular weight heparin. The patient was a non-smoker and non-drinker, and had no family history of cancer or gastrointestinal diseases.
Physical examination on final admission revealed dullness on percussion and fine crackles on auscultation in the lower lung fields, and also cervical, axillary, and inguinal lymphadenopathy, scleral and sublingual jaundice, and bilateral pitting leg edema. Abdominal examination revealed no masses, no hepatosplenomegaly, and no evidence of ascites.
Admission laboratory tests showed white blood cells 18.10×109/L (normal: 4.80–10.80×109/L), hemoglobin 100 g/L (normal: 120–160 g/L), platelets 325×109/L (normal: 140–440×109/L), sodium 135 mmol/L (normal: 136–147 mmol/L), and potassium 3.4 mmol/L (normal: 3.5–5.0 mmol/L). Liver function tests revealed total bilirubin 103.7 μmol/L (normal: 1.7–18.9 μmol/L), direct bilirubin 69 μmol/L (normal: 1.7–8.6 μmol/L), aspartate aminotransferase 225 U/L (normal: 10–31 U/L), alanine aminotransferase 217 U/L (normal: 10–31 U/L), alkaline phosphatase 615 U/L (normal: 53–141 U/L), gamma glutamyl transferase 478 U/L (normal: 7–50 U/L), and lactate dehydrogenase 434 U/L (normal: 110–210 U/L). Serology was negative for Epstein–Barr virus, cytomegalovirus, and hepatitis A, B, and C viruses. Screening for alcohol and acetaminophen in the blood was negative. Testing for Wilson disease, hemochromatosis, and α1-antitrypsin deficiency was unrevealing.
Imaging of the abdomen by computed tomography (ct) and ultrasonography revealed massive retroperitoneal lymphadenopathy, a normal liver and spleen, and no evidence of hepatic vascular obstruction. There was also no evidence of gallstones nor of biliary obstruction, the latter confirmed by magnetic resonance cholangiopancreatography. Doppler ultrasound of the legs showed no deep-vein thrombosis. Imaging of the chest by ct revealed areas of consolidation consistent with pneumonia, and a course of broad-spectrum antibiotics was started, with resolution of the patient’s respiratory symptoms.
Liver biopsy revealed cholestasis, moderate steatosis, and in the portal spaces, prominent small lymphocytic infiltrates that co-expressed CD20, Bcl2, CD5, CD43, and faintly CD23, consistent with a diagnosis of cll (). There was no evidence of progression to a large B-cell lymphoma, thus ruling out a Richter transformation. A diagnosis of liver failure because of leukemic infiltration was made, and the patient was started on fludarabine, cyclophosphamide, and rituximab on hospital day 13.
FIGURE 1 Representative light photomicrographs of the liver biopsy, showing prominent infiltration by lymphocytes. (A) Low-power view of liver core, showing moderate steatosis and prominent portal infiltration by lymphoid cells. Hematoxylin and eosin stain, 40× (more ...)
Liver function tests were closely monitored and remained unchanged during chemotherapy. Several septic episodes associated with urinary tract and upper respiratory tract infections supervened. These, combined with progressive hepatic encephalopathy, resulted in deterioration of the patient’s mental status, with a decreased level of consciousness and irreversible delirium. The patient died 48 days after admission. No post-mortem examination was done.