DOI:10.2214/AJR.06.0245
AJR 2007; 188:1589-1595
© American Roentgen Ray Society
Imaging Findings of Leukemic Involvement of the Pancreaticobiliary System in Adults
Eugene K. Choi1,2,
Jae Ho Byun1,
Soon Jin Lee3,
Seung Eun Jung4,
Mi-Suk Park5,
Seong Ho Park1 and
Moon-Gyu Lee1
1 Department of Radiology and Research Institute of Radiology, University of
Ulsan College of Medicine, Asan Medical Center, 388-1 Pungnap-2dong,
Songpa-gu, Seoul 138-736, Korea.
2 Weill Medical College of Cornell University, New York, NY.
3 Department of Radiology and Center for Imaging Science, Samsung Medical
Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
4 Department of Radiology, St. Mary's Hospital, College of Medicine, The
Catholic University of Korea, Seoul, Korea.
5 Department of Radiology, Severance Hospital, Yonsei University College of
Medicine, Seoul, Korea.
Received February 16, 2006;
accepted after revision July 31, 2006.
Address correspondence to J. H. Byun
(jhbyun{at}amc.seoul.kr).
Abstract
OBJECTIVE. Our objective was to review the imaging findings of
patients with leukemic involvement of the pancreaticobiliary system in
adults.
CONCLUSION. Pancreatic myeloid and lymphoid leukemia show single or
multiple mass lesions of homogeneous low attenuation and poor contrast
enhancement on CT that is radiographically indistinguishable from that of
pancreatic lymphoma. Although more cases are needed for confirmation, leukemic
infiltration of the biliary tract is characterized by wall thickening of the
bile duct with minimal contrast enhancement—a feature that may be
helpful in differentiating it from infiltrating hilar or extrahepatic
cholangiocarcinoma.
Keywords: biliary system • CT • pancreas • pancreatic neoplasms • pancreaticobiliary imaging
Introduction
Leukemia-associated extramedullary disease can occur as lymphoid or myeloid
masses in leukemic patients. It occurs most commonly in patients with myeloid
leukemias and in such a setting is called granulocytic sarcoma (GS), which is
an extramedullary mass of immature cells of the myeloid series. GS has been
described in virtually every organ system but has a particular predilection
for soft tissue, bone, skin, lymph nodes, and the periosteum
[1]. To our knowledge, GS of
the pancreas and biliary tract is extremely rare, with only nine
[2–5]
and three cases [4,
6,
7], respectively, reported in
the English-language literature.
Of the total 12 patients with GS of the pancreas and biliary tree for whom
clinical data are available, obstructive jaundice was reported in 10 patients,
and GS was the presenting sign of a hematologic malignancy in nine.
Infiltration of the pancreaticobiliary system with lymphoid leukemic cells is
even rarer in adult patients with lymphocytic leukemia. Mizumoto et al.
[8] described a pancreatic
tumor formed by infiltration of adult T-cell leukemia cells, and Malpica et
al. [9] reported a case of
plasma cell leukemia presenting as a pancreatic mass with symptoms of
obstructive jaundice.
Although imaging characteristics of lymphoma of the pancreaticobiliary
system have been analyzed in several series
[10,
11], description of the
imaging findings of leukemia has been limited to isolated case reports. To our
knowledge, there has been no evaluation of the radiologic characteristics in a
single series. The purpose of the present study was to retrospectively
evaluate the imaging findings of leukemia of the pancreaticobiliary
system.
Materials and Methods
We retrospectively identified patients with leukemic involvement of the
pancreas or biliary tract at four university-based tertiary institutions
during an 8-year period (January 1997 to September 2005). A computer search of
the pathologic, radiologic, and medical records of the four institutions
identified a total of six patients with leukemic involvement of the pancreas
(n = 4) or biliary tract (n = 2) in patients with
myelogenous (n = 3) or lymphoblastic (n = 2) leukemia or
without any history of acute leukemia (n =1). The study group
consisted of four men and two women. The mean age was 35.8 years (age range,
23–57 years). The institutional review boards of all four institutions
required neither their approval nor informed patient consent for this type of
retrospective study.
The medical records were reviewed to determine each patient's clinical
presentation and examine the surgical and pathology reports. Four of the six
collected patients initially presented without any known history of leukemia.
The remaining two patients carried a diagnosis of acute lymphoblastic leukemia
(ALL) at presentation. Three patients received the diagnosis of acute myeloid
leukemia (AML) and two patients received the diagnosis of ALL on bone marrow
aspiration and examination. The remaining patient with GS of the biliary tract
did not have any evidence of systemic disease on repeated bone marrow
examinations. Because the diagnosis of AML is, by definition, based on
bone-marrow evidence of excess leukemic cells, this final patient was given a
diagnosis of isolated GS. Therefore, the total number of patients with GS was
four, including two patients with pancreatic GS and two with biliary GS.
The two patients with leukemic involvement of the biliary tract underwent
surgery for suspected hilar cholangiocarcinoma. Direct histologic confirmation
of leukemic involvement of the pancreas was confirmed with sonography-guided
needle core biopsy in one patient. In one other patient, a sonography-guided
needle biopsy of a retroperitoneal mass infiltrating the pancreas confirmed
the diagnosis of a leukemic mass. In the remaining two patients, the
pancreatic mass was presumed to represent GS after resolution of both the
pancreatic mass and a pathologically proven GS in another intrabdominal organ
with antileukemic treatment. In all patients, histopathologic examination of
the surgical or biopsy specimens revealed leukemic cells, with
immunohistochemical staining showing myeloid lineage in four patients and
lymphoid non-T-cell type in two.
Contrast-enhanced abdominal CT was available in all six patients. All CT
scans were obtained with one of the following commercially available MDCT or
single-detector CT scanners (Somatom Plus 4, Siemens Medical Solutions
[n = 1]; LightSpeed Plus or QX/i, GE Healthcare [n = 5]).
Each patient received 120–150 mL of iopromide (Ultravist 300 or
Ultravist 370, Schering) at a rate of 3 mL/s. In two patients, single-phase
examinations were performed 70–75 seconds after IV administration of
contrast material with a 5-mm section thickness and 5 mm reconstruction
interval. In the remaining four patients, CT scans were obtained during the
arterial phase (using a bolus-tracking technique or a 25–35 second
delay) and portal venous phase (using a 70–75 second delay) after IV
administration of contrast material with a 3–5 mm section thickness and
3–5 mm reconstruction interval. In one patient, MR
cholangiopancreatography (MRCP) was performed on a 1.5-T unit (Magnetom
Vision, Siemens Medical Solutions) with a phased-array body coil. An MRCP
sequence using thick-slab single-shot RARE with TR/TE, infinite/1,080 and flip
angle, 150° was applied. In two patients, sonography was performed using
an Acuson Sequoia 512 scanner (Siemens Medical Solutions) with 3.5–5.0
MHz convex transducers.
All images were retrospectively reviewed by two experienced
gastrointestinal radiologists in consensus. We evaluated the involved sites of
the pancreas and biliary tree, lesion morphology, and attenuation and degree
of contrast enhancement of the lesion. The presence of pancreatic duct and
biliary duct dilatation and lymphadenopathy were also assessed. Images were
also reviewed for other sites of leukemic involvement.
Results
The principal clinical and imaging findings are summarized in Tables
1 and
2. Four of six patients
presented with symptoms of obstructive jaundice with corresponding CT findings
of biliary duct dilatation and concomitant cholestatic laboratory values. In
the other two patients without jaundice, the lesion was exclusively localized
to the body and tail of the pancreas. Symptoms associated with leukemic
involvement of the pancreaticobiliary system were the presenting signs of
hematologic disease in four of six patients. One patient carried a diagnosis
of isolated biliary GS after repeated bone marrow examination showed no
evidence of systemic disease.
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Fig. 1A —32-year-old woman with history of acute lymphoblastic
leukemia who presented with jaundice and abdominal pain with total bilirubin
of 3.5 mg/dL. Contrast-enhanced axial CT scan shows dilatation of intrahepatic
biliary ducts (arrow).
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Fig. 1B —32-year-old woman with history of acute lymphoblastic
leukemia who presented with jaundice and abdominal pain with total bilirubin
of 3.5 mg/dL. Contrast-enhanced axial CT scan shows low attenuating, diffuse
lesion with poorly defined borders in pancreatic body (white arrow)
and nodular lesion in tail (black arrow) of pancreas. There is
evidence of extrahepatic biliary duct (black arrowhead) and
pancreatic duct (white arrowhead) dilatation.
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Fig. 1C —32-year-old woman with history of acute lymphoblastic
leukemia who presented with jaundice and abdominal pain with total bilirubin
of 3.5 mg/dL. Contrast-enhanced axial CT scan shows dilatation of pancreatic
duct (white arrowhead) upstream in relation to diffuse mass
(white arrow) infiltrating body of pancreas and encasing celiac axis.
Accompanying dilatation of extrahepatic biliary duct (black
arrowhead) is also noted.
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Fig. 1D —32-year-old woman with history of acute lymphoblastic
leukemia who presented with jaundice and abdominal pain with total bilirubin
of 3.5 mg/dL. Contrast-enhanced axial CT scan shows large infiltrative mass
(white arrow) replacing pancreatic head and body. Dilatation of
extrahepatic biliary duct is noted (black arrowhead).
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On CT, the leukemic lesion in all four patients with pancreatic involvement
was characterized as homogeneous and low attenuating relative to the normal
pancreatic parenchyma. The attenuation of the mass was isodense with that of
the erector spinae muscles. In this study, three morphologic types were noted:
well- or ill-circumscribed nodular lesions (n = 1; number of nodules,
3; size, 8, 14, and 20 mm), an infiltrative lesion with well- or ill-defined
margins and diffuse or localized pancreatic enlargement (n = 2), and
a combination of the nodular and infiltrative lesion (n = 1) (Figs.
1A,
1B,
1C,
1D and
2A,
2B,
2C,
2D).
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Fig. 2A —30-year-old woman with no history of leukemia who presented
with abdominal mass. Contrast-enhanced axial CT scan at level of celiac axis
shows two ill-circumscribed nodules in tail of pancreas
(arrowheads).
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Fig. 2B —30-year-old woman with no history of leukemia who presented
with abdominal mass. Contrast-enhanced axial CT scan at level of root of
superior mesenteric artery shows large retroperitoneal mass (arrow)
that has infiltrated left kidney. Needle biopsy of mass confirmed diagnosis of
granulocytic sarcoma. Well-margined, nodular lesion (arrowhead) is
present in tail of pancreas. Mass shows low contrast enhancement with respect
to normal pancreas parenchyma.
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Fig. 2C —30-year-old woman with no history of leukemia who presented
with abdominal mass. Contrast-enhanced axial CT scan obtained 2 months after
chemotherapy at level of A shows absence of any nodular lesions
throughout length of pancreas.
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Fig. 2D —30-year-old woman with no history of leukemia who presented
with abdominal mass. Contrast-enhanced axial CT scan obtained 2 months after
chemotherapy at the level of B shows marked resolution of
retroperitoneal and pancreatic masses. Despite absence of direct pathologic
proof, pancreatic lesions most likely represented granulocytic sarcoma of
pancreas that resolved with therapy.
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In all three cases of infiltrative involvement, there was significant
extension into the retropancreatic and retroperitoneal space and encasement of
the celiac axis. In the two cases of leukemic infiltration of the pancreatic
head, the biliary duct was dilated. In contrast, the case of nodular
involvement did not exhibit any dilatation of the biliary ducts. Of the four
patients with pancreatic leukemia, mild pancreatic duct dilatation was noted
in the patient with the combined morphologic pattern of leukemic involvement.
In the two cases of biliary involvement of leukemia, the CT findings included
dilatation of the intrahepatic biliary ducts and slightly thickened proximal
extrahepatic bile duct wall with mild contrast enhancement relative to the
normal bile duct wall (Fig. 3A,
3B,
3C,
3D,
3E,
3F).
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Fig. 3A —44-year-old man with no history of leukemia who presented
with jaundice and fever with total bilirubin of 9.5 mg/dL. Contrast-enhanced
axial CT scan shows dilatation of intrahepatic biliary ducts
(arrow).
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Fig. 3B —44-year-old man with no history of leukemia who presented
with jaundice and fever with total bilirubin of 9.5 mg/dL. Contrast-enhanced
axial CT scan shows mild ductal wall thickening of hilum of intrahepatic bile
ducts (arrow).
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Fig. 3C —44-year-old man with no history of leukemia who presented
with jaundice and fever with total bilirubin of 9.5 mg/dL. Contrast-enhanced
axial CT scan shows extrahepatic biliary ductal wall thickening with complete
obliteration of lumen and mild periductal infiltration (arrow).
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Fig. 3D —44-year-old man with no history of leukemia who presented
with jaundice and fever with total bilirubin of 9.5 mg/dL. MR
cholangiopancreatography shows presence of luminal narrowing and obstruction
from confluence (arrow) of intrahepatic bile duct to proximal
extrahepatic bile duct and central portion of right posterior intrahepatic
bile duct (arrowhead). Drainage of right posterior bile duct into the
common duct represents anatomic variant.
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Fig. 3E —44-year-old man with no history of leukemia who presented
with jaundice and fever with total bilirubin of 9.5 mg/dL. Photograph of gross
pathologic specimen shows ill-defined, diffusely fibrotic, and thickened
extrahepatic bile duct (arrows). Intrahepatic bile duct wall is
mildly thickened due to inflammatory and fibrotic change.
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Fig. 3F —44-year-old man with no history of leukemia who presented
with jaundice and fever with total bilirubin of 9.5 mg/dL. Photomicrograph of
specimen shows infiltration of biliary ductal epithelial and subepithelial
space with immature and mature myeloid cells confirmed by immunohistochemistry
staining. (H and E, x100)
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Localized lymphadenopathy was noted in three of six patients. The affected
sites include the mesenteric (n = 1), celiac axis (n = 1),
and portacaval (n = 1) nodes. Multiorgan involvement was noted in all
four patients with leukemic involvement of the pancreas, whereas the biliary
tract was the sole site of involvement in the two patients with biliary
GS.
MRCP images were available for one patient with biliary GS (Fig.
3A,
3B,
3C,
3D,
3E,
3F) and showed ductal
narrowing of the hilum of the intrahepatic bile ducts, the central portion of
the right posterior intrahepatic bile duct (most likely draining into the
common duct), and the proximal extrahepatic bile duct, resulting in diffuse
dilatation of the intrahepatic bile ducts. The presumed diagnosis was a
Klatskin's tumor.
Sonography results were available in one patient each with pancreatic and
biliary involvement of leukemia. The case of pancreatic leukemia showed
diffuse pancreatic enlargement with diffuse dilatation of the biliary ducts
and narrowing of the intrapancreatic common bile duct. Sonography of the
patient with biliary involvement showed mild thickening of the ductal wall at
the hilum of both the intrahepatic bile ducts and the proximal extrahepatic
bile duct with diffuse dilatation of the intrahepatic bile ducts.
Discussion
Leukemic involvement of the pancreas and biliary tree is a rare but
clinically important entity that commonly presents with obstructive jaundice.
Our series is consistent with previous reports of the association between
obstructive jaundice and leukemic involvement of the biliary tract and the
pancreas [4], particularly when
the mass involves the head of the pancreas. Although a preexisting history of
hematologic disease may suggest the diagnosis, patients may commonly present
with symptoms associated with leukemic infiltration of the pancreaticobiliary
tract as their initial sign of systemic leukemia
[4]. Because extramedullary
involvement of leukemia is known to be highly responsive to systemic
antileukemic therapy, consideration of this rare diagnosis in the differential
diagnosis of obstructive jaundice is critical in subsequent management,
including the avoidance of unnecessary surgery.
Our study shows that leukemic involvement of the pancreas is
indistinguishable radiographically from pancreatic lymphoma. Leukemia of the
pancreas is characterized by homogeneous, hypodense lesions with poor
enhancement after administration of IV contrast material on CT. Similarly,
pancreatic lymphoma has been described as being homogeneous, less dense than
muscle, and poorly enhancing with IV contrast administration on CT
[11]. In this study,
pancreatic leukemia, as seen in cases of pancreatic lymphoma, shows three
different morphologic types: a well- or ill-circumscribed nodular form; a
diffuse, infiltrative form; and a combination of the nodular and diffuse
infiltrative forms. Despite the aggressive infiltration of the pancreas, the
pancreatic duct is not commensurately dilated—a feature that is also
observed in pancreatic lymphoma
[10]. Pancreatic duct
dilatation secondary to leukemic infiltration of the pancreas was seen in one
case in which the degree of dilatation was small in relation to the gland
width. Although jaundice is reported to be an infrequent finding even in large
lymphomatous involvement of the pancreatic head
[11], our results, in
conjunction with previously reported cases of pancreatic leukemia, suggests
that jaundice is a common clinical feature, especially in the setting of
lymphoid and myeloid leukemic infiltration of the pancreatic head.
Lymphadenopathy may or may not be present with pancreatic leukemia because it
was seen in two of our four patients with pancreatic leukemia. Although
surrounding extensive lymphadenopathy has been associated with pancreatic
lymphoma, this feature is not reliable
[10]. Our results show that a
majority of patients with leukemia may have widespread extramedullary
multiorgan involvement. All four patients with pancreatic leukemia in our
series had at least two other sites of involvement. Although two patients
appeared to have primary pancreatic leukemic involvement with concurrent
involvement of distant organs, there was secondary pancreatic involvement in
two cases with invasion by a primary leukemic mass from the
retroperitoneum.
Leukemic infiltration of the biliary tree may mimic the presentation of
hilar cholangiocarcinoma. In the five previously reported cases of leukemic
involvement of the biliary tract (including our two cases), imaging findings
show a focally thickened ductal wall with lumen obliteration and concomitant
dilatation of the extra- or intrahepatic biliary ducts
[4,
7]. To further complicate the
diagnosis, all five cases did not have any history of peripheral blood
evidence of leukemia at the time of presentation. Of the five patients, four
were subsequently given a diagnosis of AML on bone marrow examination, whereas
one patient in our series has not yet developed any evidence of acute leukemia
during 3 years of follow-up. Our results indicate that one key distinguishing
CT feature of biliary GS from hilar cholangiocarcinoma may be the degree of
enhancement of the affected biliary ductal wall. Our two cases of biliary GS
showed minimal contrast enhancement of the biliary ductal wall in contrast to
the hyperenhancement generally observed in cases of infiltrating hilar or
extrahepatic cholangiocarcinoma
[12,
13].
Apart from the intrinsic limitations of any retrospective study, two other
limitations should be emphasized. The predominantly limiting factor, the small
sample size, was due to the rarity of the tumor. Also, two lesions of the
pancreas in our series were not confirmed by histopathology, and the diagnosis
was established by noting its response to chemotherapy along with another mass
that was pathologically confirmed. Although this does not represent a standard
of reference, we believe that the combination of these criteria represents a
compelling confirmation of diagnosis.
In conclusion, leukemic involvement of the pancreaticobiliary system is an
extremely rare but clinically important cause of obstructive jaundice in
patients with a history of leukemia or, more rarely, in nonleukemic patients
who subsequently develop systemic disease. Leukemia of the pancreas cannot be
distinguished from pancreatic lymphoma on imaging findings alone. Leukemic
involvement of the biliary tract, however, may be distinguished from a closely
mimicking infiltrating hilar or extrahepatic cholangiocarcinoma by noting the
relatively minimal degree of ductal wall enhancement, although more cases are
needed to confirm this. In nonleukemic patients, a histopathologic
confirmation is mandatory for further patient management.
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Abstract
Introduction
