Anomalous dilatations of the biliary tree may be primary (choledochal cysts) or secondary (1). An extramedullary tumor (EMT) is a gross mass of leukemic tissue at a site other than the bone marrow. In acute myeloid leukemia (AML), obstructive jaundice associated with dilatation of the biliary tree has been rarely reported as being caused by an EMT. To our knowledge, this is the first reported pediatric case of AML presenting with extrahepatic obstruction of the biliary tract.
A 4-year-old boy presented with a 7-day history of jaundice and constant dull pain in his right upper abdominal quadrant. There was no history of blunt abdominal injury or stigmata of chronic liver disease. On examination he was pale and icteric. The liver was palpable 5 cm below the costal margin, and the span was 6 cm at the right midclavicular line.
Laboratory studies on admission in April 2000 revealed the following: leukocyte count, 52.1 x 10 9 /L; blasts, 10.5%; promyelocytes, 3.5%; polymorphonuclear neutrophils, 2.5%; basophils, 0.5%; monocytes, 11%; lymphocytes, 57.5%; atypical lymphocytes, 1%; abnormal monocytes, 13.5%; hemoglobin, 76 g/L; platelets, 34 x 10 9 /L; lactate dehydrogenase 3.52 μkat/L (reference range, 0.82–2.66 μkat/L); amylase, 4.40 μkat/L (reference range, 0–2.17 μkat/L); lipase, 18.44 μkat/L (reference range, 0–2.66 μkat/L); and creatinine, 40 μmol/L (reference range, 10–40 μmol/L). The ratio of amylase clearance to creatinine clearance was 2%. A hepatic function test gave abnormal results, with levels of total bilirubin at 154 μmol/L (reference range, 2–18 μmol/L), direct bilirubin at 92 μmol/L (reference range, 0–4 μmol/L), alanine aminotransferase at 2.70 μkat/L (reference range, 0–0.58 μkat/L), aspartate aminotransferase at 4.48 μkat/L (reference range, 0–0.58 μkat/L), alkaline phosphatase at 6.3 μkat/L (reference range, 0.5–2.0 μkat/L), and prothrombin time of 13.6 seconds (control, 12.3 seconds).
Virologic tests including those for hepatitis A, B, and C; cytomegalovirus; and Epstein-Barr virus were negative. A bone marrow aspirate showed 90% leukemic cells. These were cells of medium-to-large size, some of which contained prominent nucleoli, folded or cleft nuclei, and granular cytoplasm with rare Auer rods. Most of the blasts cells stained with myeloperoxidase, and about 20% to 30% were positive for nonspecific esterase. The periodic acid Schiff stain was negative. Flow cytometry for the cell surface markers was positive for CD34, 13, 14, 33, and HLA-DR, suggesting an immature myeloid lineage. The diagnosis of AML (M4) was made.
A transabdominal ultrasound showed a dilated gallbladder, suggestive of a Todani type IV-A choledochal cyst, with dilatation of the left and right intrahepatic ducts and the common bile duct. These measured about 34 mm, 8 mm, and 6 mm, respectively (Fig. 1A). A computed tomographic scan of the abdomen showed a mass lesion at the pancreatic head associated with dilatation of the intrahepatic ducts and the common hepatic duct as well as a diffuse enlargement of the pancreatic body and tail (Fig. 1B). Together the computed tomography and bone marrow findings enabled us to make the presumptive diagnosis of EMT causing obstructive jaundice.
On April 11, 2000, antileukemic chemotherapy was initiated with a 7-day infusion of cytarabine. Elevated amylase/lipase levels and cholestasis resolved within 14 days after diagnosis. The follow-up transabdominal ultrasound demonstrated resolution of the biliary tree dilatation. A second course of induction chemotherapy with cytarabine, idarubicin, and etoposide was given later, and hematologic remission was achieved in June 2000. Consolidation chemotherapy was instituted at regular intervals, followed by an allogeneic bone marrow transplantation from his younger brother in October 2000. By the fifteenth day after transplantation, rising blood counts indicated engraftment. One month after bone marrow transplant, a follow-up computed tomographic scan demonstrated disappearance of the EMT. Molecular analysis using short tandem repeat sequences proved the patient's and donor's blood had identical alleles. The patient is now disease-free 15 months after diagnosis.
The most common causes of bile duct obstruction include choledocholithiasis, malignancy, choledochal cysts, and strictures. In this patient, it was important that the presence of leukemia was recognized at the time that the child had signs of obstructive jaundice. The clinical status initially created a therapeutic dilemma; however, pretreatment with cytarabine made it possible to resolve obstructive jaundice successfully and to begin a more aggressive protocol of chemotherapy for the malignancy.
Although an inaccurate diagnosis may be made before surgical exploration, the role of transabdominal ultrasound in the evaluation of biliary diseases is well established and it is usually the first line of imaging investigation (2,3). Transabdominal ultrasound has the disadvantage of restricted spatial resolution when visualizing deeper tissue structures (4), such as the pancreaticobiliary junction. In biliary neoplasms, dilatation of the bile duct is always found proximal to the responsible tumor. Patients with sonographically suspected choledochal cysts should be further investigated using more sensitive methods such as magnetic resonance cholangiopancreatography before surgery (4,5). However, there has been little experience with magnetic resonance cholangiopancreatography in pediatric patients.
Biliary tract dilatation caused by the EMT and in which the duct was returned to its normal caliber after resolution of the underlying disease should be defined as a “secondary biliary dilatation.” Hence, underlying hematologic diseases should be looked for when cholestasis is encountered. In this case, the obstruction of drainage from the pancreas may have increased cellular enzyme leakage into the blood or the lymphatics.
Jenkin et al. (6) reported children with AML and EMT were younger than those with AML but without EMT. Furthermore, EMT was reported to occur more frequently in AML with M4 or M5 morphology. Extramedullary tumor occurs most commonly in the skull and surrounding tissues, lymph nodes, skin, and soft tissues (7–9). It may precede the diagnosis of AML, may present coincidentally with the hematologic diagnosis, or may herald a relapse after therapy. This case of EMT is rare in view of its initial presentation at the pancreaticobiliary location.
Biliary tree dilatation caused by an EMT as the first symptom of AML is extremely rare, although Lillicrap et al. (10) noted extrahepatic obstruction of the biliary tract in an adult with relapsed AML. In the deep tissue regions around the distal bile duct, computed tomography provides better imaging than transabdominal ultrasound in terms of spatial resolution. This case should alert clinicians to yet another cause of obstructive jaundice. We emphasize that image studies including computed tomography should be initially performed in cases of leukemia with obstructive jaundice.
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