Renal involvement is a known complication of leukemia in children. This study reviewed the CT imaging findings of renal involvement in 12 children with various forms of leukemia. The most common CT finding was multiple bilateral low-attenuation renal masses, seen in 5 patients. Nephromegaly (enlarged kidneys) was present in most patients. While renal involvement was seen, most patients did not have impaired renal function based on creatinine levels. This study demonstrated that renal involvement in pediatric leukemia can present with diverse CT imaging appearances.

1. Pediatr Radiol (2008) 38:424–430
DOI 10.1007/s00247-007-0741-5
ORIGINAL ARTICLE
Pediatric renal leukemia: spectrum of CT imaging findings
Melissa A. Hilmes & Jonathan R. Dillman &
Rajen J. Mody & Peter J. Strouse
Received: 8 October 2007 / Revised: 4 December 2007 / Accepted: 18 December 2007 / Published online: 1 February 2008
# Springer-Verlag 2008
Abstract while three patients demonstrated large areas of wedge-
Background The kidneys are a site of extramedullary shaped and geographic low attenuation. Four other
leukemic disease that can be readily detected by CT. patients presented with unique imaging findings, includ-
Objective To demonstrate the spectrum of CT findings in ing a solitary unilateral low-attenuation mass, solitary
children with renal leukemic involvement. bilateral low-attenuation masses, multiple bilateral low-
Materials and methods Twelve children were identified attenuation masses including unilateral large conglomer-
retrospectively as having renal leukemic involvement by ate masses, and bilateral areas of ill-defined parenchymal
contrast-enhanced CT of the abdomen. Contrast-enhanced low attenuation. Two patients showed unilateral nephro-
CT images through the kidneys of each patient were megaly, while eight other patients showed bilateral
reviewed by two pediatric radiologists. Pertinent imaging nephromegaly. Two patients had normal size kidneys.
findings and renal lengths were documented. The electronic Two patients had elevated serum creatinine concentrations
medical record was accessed to obtain relevant clinical and at the time of imaging.
pathologic information. Conclusion Renal leukemic involvement in children can
Results Five patients with renal leukemic involvement present with a variety of CT imaging findings. Focal renal
presented with multiple bilateral low-attenuation masses, abnormalities as well as nephromegaly are frequently
observed. Most commonly, renal leukemic involvement
M. A. Hilmes : J. R. Dillman : P. J. Strouse
does not appear to impair renal function.
Section of Pediatric Radiology,
University of Michigan Health System, Keywords Leukemia . Kidneys . Children . CT
C.S. Mott Children’s Hospital,
Ann Arbor, MI, USA
R. J. Mody Introduction
Division of Pediatric Hematology-Oncology and Bone Marrow
Transplantation, University of Michigan Health System, Acute lymphoblastic leukemia (ALL), acute myelogenous
C.S. Mott Children’s Hospital,
leukemia (AML), and juvenile myelomonocytic leukemia
Ann Arbor, MI, USA
(JMML) are forms of leukemia that commonly affect
J. R. Dillman (*) children. Unlike patients with lymphoma, children with
Department of Radiology, University of Michigan Health System, leukemia do not generally require routine CT imaging for
1500 E. Medical Center Drive,
staging or follow-up. Children with leukemia usually
Ann Arbor, MI 48109, USA
e-mail: jonadill@med.umich.edu instead are monitored with bone marrow aspiration, lumbar
puncture with cytology, and complete blood count with
Present address: smear and differential. When children with leukemia are
M. A. Hilmes
imaged with CT, a variety of renal abnormalities might
Section of Pediatric Radiology,
Vanderbilt University Children’s Hospital, suggest the possibility of extramedullary leukemic involve-
Nashville, TN, USA ment. Leukemic patients who are at a higher risk for

2. Pediatr Radiol (2008) 38:424–430 425
extramedullary disease, including renal parenchymal in- of the clinical situation, biopsy of the renal mass was
volvement, include those with T-cell ALL as well as those pursued in order to guide appropriate therapy.
with the M4 and M5 subtypes of AML [1–3]. Available contrast-enhanced CT scans of the abdomen of
CT imaging of the abdomen in children with leukemia is each child were reviewed retrospectively by two pediatric
typically utilized in the assessment of possible disease- radiologists in consensus, and imaging findings pertaining
related complications or in the evaluation of some other to the kidneys and adjacent perinephric/paranephric spaces
clinical problem. Consequently, renal leukemic involve- were documented. Bilateral craniocaudad renal lengths
ment might be a completely unexpected incidental imaging were measured on sagittal reformatted images and recorded
finding. Based on a review of the literature, renal for all patients. The number of standard deviations above or
parenchymal leukemic deposits are sometimes associated below mean renal length for patient age was also
with impaired renal function. There are a few case reports determined. Images were loaded on a picture archiving
of new-onset renal failure that were directly attributable to and communication system (PACS) workstation and
renal leukemic involvement [4–6]. reviewed utilizing both standard soft-tissue and narrow
The purpose of this study was to describe the CT CT level/window settings.
imaging findings of renal leukemic involvement in children Our institutional electronic medical record system was
with a variety of forms of leukemia, including ALL, AML, accessed for each child in order to elicit the specific form of
and JMML. In addition, we sought to correlate the presence leukemia, the indication for CT imaging, laboratory values
of renal leukemic involvement with renal function. pertaining to renal function, and additional extramedullary
extrarenal sites of disease. Serum creatinine concentration
analysis was performed by our institutional Department of
Materials and methods Pathology. Abnormal serum creatinine levels were institu-
tionally defined as follows: greater than 0.8 mg/dl for a
Institutional review board (IRB) approval was obtained child younger than 5 years and greater than 0.9 mg/dl for a
prior to the initiation of this retrospective investigation. child older than 5 years.
Using our Department of Radiology information system The initial age at diagnosis of leukemia in our patient
(RIS), all contrast-enhanced abdominal CT imaging reports cohort ranged from 5 months to 18 years (mean 5.8 years).
were identified for children with leukemia during a 10-year The age at presentation with renal leukemic involvement
period from 1 January 1996 to 31 December 2005. Imaging ranged from 7 months to 21 years (mean 7.1 years). Ten
reports were then reviewed by a single author (P.J.S.) for children were boys and two were girls. During the study
possible leukemic renal involvement. The review of the time period, a total of 423 children with leukemia were
imaging reports identified 12 children with leukemic renal diagnosed and/or treated at our institution (300 children
involvement demonstrated by CT imaging. with ALL, 120 with AML, and 3 with JMML).
In 11 of the 12 children, the diagnosis of leukemia as the All children included in this investigation were diag-
etiology for the child’s renal parenchymal abnormality was nosed according to World Health Organization (WHO)
presumed based upon a combination of CT imaging criteria [7, 8]. All ALL patients had ≥25% bone morrow
findings (including follow-up studies after chemotherapy involvement with lymphoblasts, while all AML patients
and bone marrow transplantation, BMT) and clinical had >20% bone marrow involvement with myeloblasts.
information documented in the medical record. The renal Children with <25% lymphoblasts were diagnosed as having
lesions observed in three children had markedly decreased lymphoblastic lymphoma, while children with <20% myelo-
in size/extent upon follow-up CT imaging after chemother- blasts were diagnosed as having myelodysplastic syndrome
apy and/or BMT. All 12 children had additional sites of (MDS). Children with lymphoma and MDS were excluded
concomitant extramedullary disease. Care was taken to from this investigation. JMML is associated with <20%
exclude children in whom infectious disease was a possible blasts (including promonocytes) in the blood and bone
cause of the renal parenchymal abnormality. Specifically, marrow (with an average blast count of less than 2%).
two children (in addition to the 12 described above) with Eight children (66%) included in this investigation had
leukemia and bilateral renal masses with signs and some form of ALL: four (33%) had precursor T-cell ALL,
symptoms of an infectious process (i.e. positive blood/ two (17%) had mature T-cell ALL, and two (17%) had
urine cultures and fever) were excluded from this study. A relapsed precursor B-cell ALL. Three children (25%) had
single child underwent biopsy of a renal mass that proved AML, including one child (8%) with relapsed M4 subtype
the diagnosis of renal leukemia. Biopsy was indicated as and two (17%) with M5 subtype. A single child (8%) had
this child had Li-Fraumeni syndrome and a history of both JMML. Prior BMT had been performed in five children
recurrent fibrosarcoma and relapsed precursor B-cell ALL (42%). Five (42%) of the 12 children had died by the time
(for which he had received BMT). Based on the complexity of this image review.

3. 426 Pediatr Radiol (2008) 38:424–430
A review of electronic medical records revealed that the multiple bilateral renal low-attenuation masses (5 of 12
most common indication for contrast-enhanced CT exam- patients, 42%; Figs. 1, 2, 3, and 4). Three children (25%)
ination of the abdomen in children included in this study presented with large areas of bilateral wedge-shaped and
was to “evaluate for extramedullary leukemic involvement” geographic low attenuation (Fig. 5). A single child (8%)
(five children with known mediastinal masses and one child presented with multiple large conglomerate low-attenuation
with an orbital mass). Indications for examinations per- masses in a single kidney with additional small discrete
formed in other children included: “lactic acidosis, concern low-attenuation masses within the contralateral kidney.
for a leukemic relapse,” “acute abdominal pain,” “back and Other individual children presented with a unilateral
abdominal pain,” “fever, rule out infection,” “persistent solitary low-attenuation mass (8%), bilateral solitary low-
emesis,” and “pre-bone marrow transplant evaluation.” attenuation masses (8%; Fig. 6), and bilateral ill-defined
Nine of the 12 children’s CT scans evaluated in this areas of abnormal low attenuation (8%).
study were performed at our institution. Three scans were Abnormally increased renal length (nephromegaly, or a
performed at other institutions, for which the exact imaging renal length more than two standard deviations greater than
technique was unknown. Scans included in this study that the expected size for patient age) was present in the
were performed at our institution were obtained using majority of children with renal leukemic involvement
routine pediatric CT abdomen and pelvis examination (Table 1). Bilateral nephromegaly was observed in eight
techniques. Scans were performed from the lung bases children (66%), while unilateral nephromegaly was ob-
through the ischia using either a 2.5-mm or 5-mm section served in two children (16.5%). Only two children (16.5%)
thickness with no section overlap. Imaging was performed had normal bilateral renal length.
approximately 65 s following the initiation of intravenous All 12 children with renal involvement, whether at
contrast material administration. The mAs was selected per primary leukemia presentation or relapse, had additional
the standard departmental protocol based on patient weight, evidence of extramedullary leukemic involvement. These
and ranged from 50 to >170 (but never exceeding the additional areas of disease were identified by imaging and
patient’s weight in pounds if the patient weighed greater physical examination. Areas of extramedullary leukemic
than 150 pounds). A kVp of 120 was used for all children. involvement, other than the kidneys, included the medias-
Both oral (either diatrizoate sodium for hospital inpa- tinum, pericardium, peritoneum, spleen, liver, pancreas,
tients or dilute iohexol for outpatients) and intravenous lymph nodes, spinal canal, brain, skin, orbit, testes, and
contrast materials were administered to all children includ- gingivae.
ed in this investigation who were imaged at our institution. Two children had abnormally elevated serum creatinine
Two different intravenous low-osmolality nonionic iodinat- concentrations at the time of CT imaging. A single child
ed contrast agents were used in pediatric patients during the who was found to have an elevated creatinine was
study period: iohexol 300 mg I/ml (Omnipaque 300; GE discovered to have partial obstruction of the right renal
Healthcare, Princeton, NJ) and iopromide 300 mg I/ml
(Ultravist 300; Bayer HealthCare, Wayne, NJ). The volume
of intravenous contrast material administered was based on
the standard departmental protocol related to patient weight.
In general, we administer an intravenous contrast material
dose of 2 ml per kilogram in children weighing 15 kg or
greater (up to 75 kg). Slightly more contrast material per
kilogram is used in children weighing less than 15 kg, and a
maximum dose of 150 ml of contrast material is adminis-
tered to patients weighing 75 kg or greater. Intravenous
injections of contrast medium greater than 20 ml are
administered utilizing a power injector unless specifically
contraindicated, while intravenous injections less than or
equal to 20 ml are typically hand-injected.
Results
Fig. 1 T-cell ALL and a mediastinal mass in a 9-year-old boy.
Contrast-enhanced CT examination was performed to evaluate for
Renal leukemic involvement presented with a wide variety additional sites of extramedullary disease. Axial image shows
of contrast-enhanced CT imaging findings. The most scattered small bilateral low-attenuation renal masses (arrows) and
common focal parenchymal abnormality was that of an enlarged spleen (S)

4. Pediatr Radiol (2008) 38:424–430 427
Fig. 2 A 3-year-old boy with T-cell ALL and a mediastinal mass. Fig. 4 A 5-month-old girl with emesis found to have AML. Axial
Axial contrast-enhanced CT image demonstrates numerous bilateral contrast-enhanced CT image shows numerous bilateral low-attenuation
low-attenuation renal masses (arrows). Abnormally enlarged retroper- renal masses as well as frank bilateral nephromegaly
itoneal lymph nodes are also seen (arrowheads)
creatinine level that coincided with the date of imaging
collecting system and globally decreased ipsilateral renal was not available for two children.
perfusion (Fig. 7). This patient presented with back and
abdominal pain as well as evidence of impaired renal
function (creatinine 1.6 mg/dl, baseline creatinine 0.8 mg/dl). Discussion
Another child who was undergoing chemotherapy at the
time of imaging had a minimally elevated serum creatinine Multiple reports suggest that nephromegaly is the most
level for age (creatinine 0.9 mg/dl, baseline creatinine common imaging manifestation observed in the setting of
0.6 mg/dl). This child had multiple bilateral renal masses renal leukemic involvement. This finding has been reported
that completely regressed with chemotherapy and BMT. following the use of sonography, excretory urography, and
Follow-up creatinine upon resolution of the renal masses CT [9–13]. Ten of 12 patients in our study had either
was normal (Fig. 8). Eight children had normal serum unilateral or bilateral renal enlargement, confirming that
creatinine levels at the time of the CT scan that
demonstrated renal leukemic involvement. A serum
Fig. 5 A 12-year-old boy with relapsed T-cell ALL. The boy
presented with lactic acidosis, similar to his initial presentation with
Fig. 3 A 9-month-old boy with AML and a biopsy-proven leukemic leukemia. Axial contrast-enhanced CT image shows bilateral renal
orbital mass. Axial contrast-enhanced CT image shows numerous geographic areas of low attenuation (arrows). There is also frank
bilateral low-attenuation renal masses. The masses decreased in size bilateral (left greater than right) nephromegaly. A conglomerate
following chemotherapy retroperitoneal lymph node mass is also present (arrowheads)

5. 428 Pediatr Radiol (2008) 38:424–430
Fig. 6 A 5-year-old boy with relapsed JMML. Axial contrast- Fig. 7 A 20-year-old man with history of Li-Fraumeni syndrome,
enhanced CT image shows a solitary mass in the right kidney with relapsed B-cell ALL, and recurrent fibrosarcoma. The man presented
measured attenuation greater than that of water (arrow). A large with back and abdominal pain and elevated serum creatinine level.
conglomerate upper abdominal lymph node mass is also identified Axial contrast-enhanced CT image shows asymmetric renal parenchy-
(arrowheads). A solitary mass was present in the left kidney (not mal perfusion, concerning for right kidney malperfusion. Enlarged
shown) right renal hilar and retroperitoneal nodes (arrowheads) are seen
adjacent to the right renal artery and vein. Mild right renal collecting
system dilation (asterisks) as well as multiple bilateral renal masses
(arrows) are also present
nephromegaly is a common imaging finding in the setting
of renal leukemic involvement in children. It should be
noted, however, that focal renal parenchymal abnormalities
were even more common than nephromegaly. Such focal appearances, including small and large round low-attenuation
abnormalities were most commonly bilateral and multifo- masses, wedge-shaped and geographic low-attenuation
cal, although unilateral and solitary abnormalities were masses, and ill-defined areas of low attenuation. No
noted in a few children. Such focal renal parenchymal perinephric leukemic involvement was identified in our
lesions were noted to take on a variety of imaging patients.
The presence of renal leukemic involvement itself does
Table 1 Maximum renal size in 12 children with renal leukemic not appear to commonly cause significant renal dysfunc-
involvement tion. Only two patients had abnormally elevated serum
creatinine concentrations at the time that CT imaging
Age at Craniocaudad renal length (cm)
revealed renal leukemic involvement. One patient’s abnor-
diagnosisa
Right kidney Left kidney mally elevated creatinine likely was not the result of renal
parenchymal leukemic involvement but was instead caused
Maximum Standard Maximum Standard by retroperitoneal lymphadenopathy. The abnormal lymph
deviations deviations
nodes in this patient caused upper urinary tract obstruction
above or above or
belowb belowb
as well as compression of the main renal artery and vein,
near the renal hilum, resulting in ipsilateral renal malperfu-
7 months 10.0 >+4.0 8.5 >+4.0 sion (Fig. 7).
9 months 7.6 +2.5 7.5 +2.5 Another child with minimally elevated creatinine at the
3 years 9.5 +3.5 9.4 +3.5 time of imaging had normal renal size and multiple bilateral
4 years 8.2 +1.0 9.4 +3.0
renal low-attenuation masses. The elevated creatinine
5 years 9.1 +2.0 8.4 +1.0
6 years 9.0 +1.5 9.5 +2.5
obtained in this child might have been the result of recently
6 years 10.5 +4.0 10.8 >+4.0 initiated chemotherapy and tumor lysis syndrome [14, 15].
8 years 9.7 +2.5 10.0 +3 This condition can occur after the initiation of chemother-
9 years 10.2 +2.5 10.8 +3.5 apy, frequently is associated with T-cell ALL, and can result
10 years 9.0 ±0.0 8.0 −1.0 in acute renal failure secondary to urate nephropathy.
12 years 12.3 +4.0 12.9 >+4.0 Chemotherapy induces rapid tumor cell necrosis or apo-
21 years 15.1 >+4.0 14.2 +4.0 ptosis that can induce numerous metabolic abnormalities,
a
Diagnosis of renal leukemic involvement. including hyperkalemia, hyperuricemia, hyperphosphate-
b
For patient age based on reference [20]. mia, and hypocalcemia. A follow-up creatinine level

6. Pediatr Radiol (2008) 38:424–430 429
or bilateral. In these patients, the clinical presentation
(fever, dysuria, flank pain, etc.) and urine gram stain and
culture will help to establish the correct diagnosis.
Renal lymphomatous involvement can appear quite
similar to renal leukemic involvement [18, 19]. Renal
lymphoma can present with unilateral or bilateral low-
attenuation masses or as a relatively diffuse infiltrative
process. Lymphoma also has a propensity to involve the
perinephric spaces. Imaging alone unfortunately cannot
distinguish leukemic from lymphomatous renal involve-
ment. Nephroblastomatosis can also be difficult to distin-
guish from renal leukemic involvement based solely on CT
imaging features; however, the lack of other sites of
extramedullary disease is a clue. These patients might also
have a known syndrome such as Beckwith-Wiedemann
syndrome.
Angiomyolipomas can usually be correctly diagnosed by
CT imaging with or without intravenous contrast material
when they contain demonstrable macroscopic fat, and,
therefore, are associated with negative Hounsfield unit
measurements. Angiomyolipomas are benign neoplasms
composed of vascular, smooth muscle, and fatty elements.
While approximately 80% of such lesions are sporadic,
20% can be found in the setting of tuberous sclerosis (and
are often bilateral and multiple). The diagnosis of tuberous
sclerosis is usually well-established before the renal lesions
are manifest because of central nervous system abnormal-
ities that often lead to mental retardation and seizures as
well as specific skin findings. Benign renal simple cysts can
Fig. 8 A 9-year-old boy with relapsed AML and abdominal pain. a also mimic renal leukemic involvement, although the
Axial contrast-enhanced CT image demonstrates numerous small presence of multiple bilateral renal cysts is rare in children.
bilateral low-attenuation renal lesions. In addition, there are multiple
Unless they are too small to be characterized by CT, renal
peritoneal, mesenteric, and greater omental soft-tissue attenuation
masses, best seen along the liver and lateral conal fascia (arrowheads). cysts usually can be differentiated from neoplasm by their
b Follow-up CT image 1 month later after chemotherapy and BMT lower (water) attenuation, sharp margins, and lack of
shows resolution of the masses enhancement. Syndromes such as tuberous sclerosis and
von Hippel-Lindau should be considered when multiple
bilateral renal cysts are observed in pediatric patients.
obtained from this child following chemotherapy and upon Our study had a few limitations. First, this investiga-
resolution of the renal masses was normal (Fig. 8). tion was a retrospective review of a relatively small
The differential diagnosis for low-attenuation renal number of patients. Although we treat many children
masses in children includes, but is not limited to, infection, with leukemia at our institution, these children do not
lymphoma, nephroblastomatosis, simple cysts, angiomyoli- routinely undergo abdominal CT imaging. When abdom-
pomas, and metastases (in addition to renal leukemic inal CT imaging is performed in children with leukemia,
involvement). All of these conditions can be unilateral or renal leukemic involvement is more often than not an
bilateral as well as solitary or multifocal. Infection, unexpected finding. A second limitation is that direct
frequently atypical (fungal) in leukemic patients, presents pathologic correlation was available for only a single
with microabscesses that can involve the liver, spleen, and patient, and diagnosis of renal leukemic involvement was
kidneys. These infectious lesions typically appear as focal made by correlating clinical and CT imaging features in
small nonenhancing areas of parenchymal abnormality on the remaining patients. Although the CT imaging findings
CT images [16, 17]. The diagnosis of renal parenchymal described here in children with presumed renal leukemic
infection can typically be confirmed with urine gram stain involvement are clearly abnormal, it is still possible
and culture. Focal acute bacterial pyelonephritis can also (although thought to be unlikely) that another unrecog-
produce low-attenuation renal masses that can be unilateral nized etiology was responsible for the visualized renal

7. 430 Pediatr Radiol (2008) 38:424–430
parenchymal lesions. Third, the true incidence of renal 5. Hayek M, Srinivasan A (2003) Acute lymphoblastic leukemia
presenting with lactic acidosis and renal tubular dysfunction. J
leukemic involvement in children cannot be calculated
Pediatr Hematol Oncol 25:488–490
from this study, as only a fraction of children with 6. Gilboa N, Lum GM, Urizar RE (1983) Early renal involvement in
leukemia at our institution undergo CT imaging of the acute lymphoblastic leukemia and non-Hodgkin’s lymphoma in
abdomen. A final limitation is that some children with children. J Urol 129:364–367
7. Jaffe ES, Harris NL, Stein H et al (eds) (2001) Pathology and
renal leukemic involvement could have been excluded
genetics of tumours of haematopoietic and lymphoid tissues.
from this study because of a lack of overt CT imaging IARC, Lyon, pp 45–115
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Blood 100:2292–2302
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10. Araki T (1982) Leukemic involvement of the kidney in children:
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11. Ali AA, Flombaum CD, Brochstein JA et al (1994) Lactic acidosis
and renal enlargement at diagnosis and relapse of acute lympho-
Renal leukemic involvement in children can present with a blastic leukemia. J Pediatr 125:584–586
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focal renal parenchymal abnormalities might be observed. leukemia as a cause of bilateral nephromegaly. Pediatr Nephrol
20:679–682
When detected on CT imaging, renal leukemic involvement
13. Gore RM, Shkolnik A (1982) Abdominal manifestations of
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