This 10-month-old boy was admitted to the hospital for evaluation of jaundice and abdominal pain. He was in his usual state of good health until three weeks prior to admission when his mother noted the development of bilateral cervical adenopathy. Over the ensuing two weeks, he developed increasing irritability and vague abdominal pain. One week prior to admission, his mother noted that his eyes turned yellow. On review of systems, he had decreased appetite for the past two weeks and had been constipated. He had been drinking only cow's milk recently, and his solid food intake had decreased. There was no history of vomiting, diarrhea, or other symptoms; there were no recent sick contacts. The past medical history, birth history, and family history were unremarkable.
On exam, he was a fussy, consolable infant who was crying during the examination. Temperature was 38° C, pulse 136, respiratory rate 53, and blood pressure 113/66. Weight was in the 10th percentile, length in the 25th percentile, and head circumference in the 25th percentile. There was scleral icterus. There were multiple 0.5 cm mobile, tender, left posterior cervical lymph nodes. There was no other significant adenopathy. Lungs were clear. Sl and S2 were normal with a UNI vibratory systolic murmur heard best at the left upper sternal border. The abdomen was diffusely tender to palpation but was not distended. The liver was palpable 2 cm below the right costal margin. The spleen was not palpable. Genitalia were normal. Both testes were descended. Neurologic examination was unremarkable.
Laboratory evaluation: hemoglobin 11.4 g/dL, white blood count 9.1 with 20% neutrophils, 75% lymphocytes, platelet count was 493,000/mmp 3; SGOT 101 IU/mL, SGOT 173 IU/mL, total bilirubin 7.5 mg/dL, direct bilirubin 5.1 mg/dL, total protein 6.8 g/dL, albumin 2.9 g/dL, alkaline phosphatase 883 IU/L, GGT 813 IU/L, amylase 21 IU/L, and lipase 6 IU/L.
Robert Listernick, MD, moderator: First impressions?
Peter Whitington, MD, pediatric hepatologist: He appears to have an obstructive cholestatic jaundice because the alkaline phosphatase is elevated. The albumin is mildly depressed, but it is a very poor liver function test because the liver has a fair reserve for synthesis of albumin and albumin has a half life of 17 days. I'd rather use the prothrombin time as a measure of synthetic function. He really doesn't have any signs of either acute liver failure, usually with markedly elevated serum transaminases and encephalopathy, or chronic liver failure with splenomegaly. This is not the picture of acute hepatitis, such as hepatitis A.
Stanford T. Shulman, MD, pediatric infectious disease physician: Often, in a subacute inflammatory process such as Kawasaki disease, we see a mildly depressed albumin. The mechanism is obscure but may include the results of a vasculitis and mild capillary leak as well as decreased synthesis.
David Steinhorn, MD, pediatric intensive care physician: There's evidence that an inflammatory state will turn off albumin gene transcription and synthesis.
Because plasma albumin is approximately four times the concentration of interstitial albumin, it doesn't take much change in permeability to allow translocation of albumin to the extravascular space, even without associated edema.
Dr. Listernick: Speaking about hepatitis A, why do most young children who have this infection have a mild gastroenteritis with anicteric hepatitis, as opposed to adults who often develop severe transaminase elevation, jaundice, and occasionally liver failure?
Dr. Whitington: It's not known, but even in endemic areas of hepatitis A such as South America, children rarely develop liver failure or require transplantation.
Dr. Listernick: No one believed that this child had infectious hepatitis, but hepatitis serologies were sent and were negative. What next?
Valeria Cohran, MD, pediatric gastroenterologist: The markedly elevated GGT and alkaline phosphatase suggest an obstructive process, perhaps a structural problem, such as a choledochal cyst. Although these days most choledochal cysts are diagnosed in utero by prenatal ultrasound, older children may become symptomatic if the cyst was previously undetected. Fever, jaundice, abdominal pain, and a right upper quadrant mass are highly suggestive of a choledochal cyst. Another possibility in this child is that he has gallstones secondary to an undiagnosed congenital hemolytic anemia. There are other very rare diagnoses that we don't need to consider initially. The first diagnostic test I would want would be an abdominal ultrasound.
Daniel Schwartz, MD, pediatric radiologist: The ultrasound shows significant dilatation of the common hepatic duct and common bile duct. There's no significant intrahepatic biliary ductal dilatation. There were no obstructing stones or masses. The cystic duct looks a little dilated, which is a bit unusual because we generally don't see cystic duct or intrahepatic dilatation with choledochal cysts. Nonetheless, the overall findings were consistent with a choledochal cyst. The pancreas was noted to be somewhat enlarged, which is also unusual but not much was made of it at the time.
Dr. Listernick: What is a choledochal cyst?
Marieta Reynolds, MD, pediatric surgeon: A choledochal cyst is a congenital focal or diffuse dilatation of the biliary tract more commonly seen in girls (4:1 female-male ratio). Although they generally present in neonates or infants, often as an initially asymptomatic finding on prenatal ultrasound, they also may become evident in later childhood or adulthood. They have been divided into five types based on anatomy. The most common type, type I, is a focal extrahepatic dilatation that may be cystic, fusiform, or saccular. The pathogenesis of the cysts is unknown; speculation has included the possibility of reflux of pancreatic juices into the biliary tree leading to an inflammatory response or an in utero traumatic event. The older these children present, the larger the inflammatory reaction we find at surgery.
Dr. Listernick: How do they present?
Dr. Reynolds: As previously stated, the classic triad of symptoms is jaundice, right upper quadrant pain, and an abdominal mass. However, this triad occurs in the minority of patients. More commonly, patients have just abdominal pain variably associated with vomiting or fever. Occasionally, an infant presents with an asymptomatic abdominal mass.
Dr. Listernick: How do you approach the patient with a suspected choledochal cyst?
Dr. Reynolds: Following the ultrasound, we surgically explore the patient and perform an intraoperative cholangiogram to better define the anatomy.
Dr. Listernick: Are there longterm complications from choledochal cysts?
Dr. Reynolds: It has been reported that as many as 25% of cases of choledochal cysts can be associated with malignancy, specifically cholangiocarcinoma.
Dr. Listernick: What happened with this patient?
Deiadra Garrett, MD, pediatric surgeon: We didn't see an inflammatory mass arising from the common bile duct as we had expected. Rather, we saw a large, dilated common bile duct, a distended gallbladder, and a dilated left intrahepatic duct. The latter two findings were distinctly unusual for a routine choledochal cyst. The intraoperative cholangiogram confirmed these findings. The pancreas also felt fibrotic and hard, which we couldn't explain.
Dr. Schwartz: Without getting into the nuances of the cholangiogram, the other unusual finding is that the common and intrahepatic ducts had a tapered narrowing, suggestive of a process that is surrounding and compressing them rather than the more typical dilated inflammatory picture we generally see with choledochal cysts.
Dr. Listernick: How did you proceed?
Dr. Garrett: Whatever we were dealing with, it wasn't a choledochal cyst. We inserted a T-tube into the common bile duct to provide adequate external biliary drainage and performed a liver biopsy.
Dr. Listernick: Why didn't you biopsy the pancreas as well?
Dr. Reynolds: That's an extremely risky procedure, which carries a significant risk of causing a leak of pancreatic juices and serious peritonitis.
Dr. Garrett: The surgical mantra is "Eat when you can, sleep when you can, but don't mess with the pancreas."
Dr. Reynolds: If this had been a choledochal cyst, they would have performed a formal biliary diversion, excised the cyst, and reconnected it with the duodenum.
Dr. Listernick: Immediately after the surgery, he underwent a computed tomography (CT) scan of the abdomen.
Dr. Schwartz: The most significant finding is that the pancreas is diffusely enlarged. There is no focal mass. This is an extremely unusual finding and suggests either an inflammatory or infiltrative process.
Dr. Listernick: So as not to hold anyone in more suspense, the postoperative blood count had 10% blasts on the peripheral smear, a finding clearly not present on the preoperative CBC. A bone marrow biopsy was performed, which revealed acute myeloblastic leukemia (AML). In case anyone was wondering, because we never mentioned the lymphadenopathy after the initial presentation, they were small, rubbery, non-pathologic-appearing nodes. Should this diagnosis have been suspected or been made preoperatively?
Dr. Reynolds: If an infant has a prenatal diagnosis of a choledochal cyst with a cystic mass in the right upper quadrant on ultrasound, I would operate without hesitation. However, in an older infant who has fusiform dilatation of the duct, I would question the diagnosis and perform either a preoperative magnetic resonance cholangiogram or CT scan. If necessary, one could drain the gallbladder percutaneously, if it is distended.
Dr. Schwartz: The MR cholangiogram can be very difficult to perform in young children. In order to get the best pictures, breath-holding is preferred, often necessitating general anesthesia in infants.
Dr. Listernick: Could the child have been treated medically if the diagnosis had been known?
Elaine Morgan, MD, pediatric oncologist: This was an extremely difficult diagnosis to make preoperatively. Even with the CT findings of an enlarged pancreas, I don't believe that a bone marrow biopsy would have been performed without blasts present on the peripheral smear. In addition, it's difficult to treat a child who has a total bilirubin of 7.5 mg/dL with daunomycin, which is part of the chemotherapy regimen for AML. Percutaneous drainage of the gall bladder might still have been necessary.
Dr. Listernick: How rare of a presentation of AML is this?
Dr. Morgan: AML might present as a granulocytic sarcoma or a paraspinal mass. This isn't a typical presentation, but it's probably not an unprecedented one.
Dr. Listernick: How do you approach the treatment of a child with AML?
Dr. Morgan: AML is subtyped histologically into multiple different forms, which are all treated the same way, save for the M3 type of promyelocytic leukemia. There may be a predilection for the M4 and M5 subtypes, which have monocytic components, to present in extramedullary sites. Specific cytogenetics can be performed to identify prognostic factors. Currently, approximately 50% of children with AML are cured with chemotherapy alone. If the child has unfavorable cytogenetic predictors or doesn't have a good response to chemotherapy, then the next step is bone marrow transplantation. The overall cure rate for the children in the poor prognostic group is approximately 30%. This child had an 1 lq23 translocation, which would convey an unfavorable prognosis in acute lymphocytic leukemia but is not prognostic in AML.
Dr. Listernick: Thank you, everybody.