Pediatr Nephrol (2005) 20:679–682
DOI 10.1007/s00467-004-1740-5
BRIEF REPORT
Anelia Boueva · Raymonde Bouvier
Precursor B-cell lymphoblastic leukemia as a cause
of a bilateral nephromegaly
Received: 24 March 2004 / Revised: 30 September 2004 / Accepted: 1 October 2004 / Published online: 16 February 2005

IPNA 2005
Abstract Nephromegaly and non-oliguric acute renal
failure is an unusual manifestation of lymphoblastic in-
filtration of the kidneys. We report the clinical history of
a female child where a precursor B-cell lymphoblastic
proliferation was diagnosed at the age of 21 months by a
surgical renal biopsy for an unexplained bilateral neph-
romegaly. Lymphoblastic infiltration should be suspected
in any patient presenting with unexplained renal failure
and enlarged kidneys. The importance of renal biopsy to
identify the etiology of renal failure and nephromegaly is
emphasized.
Keywords Nephromegaly · Precursor B-cell
lymphoblastic leukemia
Introduction
Precursor B-cell acute lymphoblastic leukemia (B-ALL)/
lymphoblastic lymphoma (B-LBL) is defined as a neo-
plasm of lymphoblasts committed to the B-cell lineage,
typically composed of small- to medium-sized blast cells
with scant cytoplasm, moderately condensed to dispersed
chromatin, and inconspicuous nucleoli [1]. The disease
involves bone marrow and blood (B-cell lymphoblastic
leukemia, LBL) and occasionally presents with primary
involvement of nodal or extranodal sites (LBL). Com-
monly used criteria to distinguish LBL from ALL are: (1)
manifestation as a bulky mass in solid organs; (2) focal
A. Boueva ())
Department of Pediatric Nephrology,
Faculty of Medicine,
11 Ivan Geshov Boulevard, 1606 Sofia, Bulgaria
e-mail: boueva@yahoo.com
Tel.: +359-2-373432
Fax: +359-2-9521650
R. Bouvier
Central Laboratory of Pathological Anatomy and Cytology,
Edouard Herriot Hospital,
Place d’Arsonval, 69437 Lyon cedex 03, France
(25%) or absent bone marrow involvement; and (3)
absence of peripheral blood involvement [2].
The most-frequent sites of B-LBL involvement are
skin, bone, soft tissue, lymph nodes, ovaries, retroperi-
toneum, tonsillar primary tumor, and mediastinum [3] and
biopsy is important for the diagnosis [4, 5,6]. Tumor in-
filtration of the kidney may occur, but accounts for renal
insufficiency in only 1% of patients [7]. We report an
unusual case of a female child with precursor B-ALL/B-
LBL presenting with nephromegaly and acute renal fail-
ure (ARF).
Case study
The child’s history was eventful (Table 1). Pharyngitis was noted at
the age of 8 months and successive tonsillitis accompanied by
pneumonia at the age of 11 months. Due to asthenia and pallor at
the age of 12 months, leukopenia (1,100/mm3), low ðlatelet count
69,000/mm3, and anemia (hemoglobin 50 g/l) justified a blood
transfusion. Urine investigation was normal.
Bone marrow examination at the age of 12 months revealed
normal to hyperplastic bone marrow with significant proliferation
of a myeloid series dominated by younger representatives (up to
promyelocyte) due to a blockage in the maturation. A markedly
reduced number of erythrocytic precursors and a lack of patho-
logical blasts were also observed.
À secondary aplastic syndrome was diagnosed and the child
was treated with cortisone, intravenous immunoglobulin, to support
passive immunity, and fligrastime, due to a greatly decreased
number of neutrophils.
At the age of 16 months, painful edema of the right ankle re-
sulted in treatment for rheumatoid arthritis with cortisone for
4 months. At 20 months of age, the child was febrile (up to 40C),
with high levels of C-reactive protein and leukocytosis with non-
oliguric ARF with a plasma creatinine of 148 mmol/l. For the first
time in the course of treatment significant bacteriuria, nitrites (+),
and mass leukocytes were recorded by urinalysis. Successive
treatment with ceftriaxone was carried out.
Her abdomen and navel were swollen but there was no ascites.
Bilaterally, the kidneys were palpated as two solid tumor masses
with uneven surface engaging the whole abdomen. Pain in both
ankle joints interfered with walking.
Since we diagnosed acute pyelonephritis and tumor formations
by palpation of the child’s abdomen, the first ultrasound exami-
nation of the abdomen was performed. Bilateral non-obstructive
nephromegaly (>2 SD for age, 140 mm long and 50 mm wide) with
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Table 1 Disease history—clinical and laboratory data (Hb hemoglobin, IVIG intravenous immunoglobulin)
Age (months) 8 12 14 16 20
Clinical Fever Fever Painful edema Pyelonephritis
manifestations of right ankle
Tonsillitis Otitis Non-obstructive
bilateral nephromegaly
Otitis Asthenia
Pneumonia Pallor
Pharyngitis Infected dermoid cyst
Hb (g/l) 50 79 97 114
Leukocytes/mm3 1,100 3,900 11,300
Platelets/mm3 69,000 273,000 448,000
Bone marrow Normal normal
Treatment Antibiotics Methylprednisolone Methylprednisolone Methylprednisolone Ceftriaxone
IVIG IVIG
Blood transfusions Fligrastime

Fig. 1 Renal magnetic reso-

nance imaging

a hyperechogenic parenchyma was revealed. Magnetic resonance Discussion

imaging (Fig. 1) showed no additional abdominal or retroperitoneal
anomaly. A repeated bone marrow examination showed neither
blast cells nor maturation disorder. A surgical renal biopsy was
performed.
The specimen revealed extensive infiltration of interstitial tissue
by small round cells surrounding relatively well-preserved renal
structures. The nuclei showed fine chromatin pattern with incon-
spicuous nucleoli. Mitotic figures were numerous (Fig. 2). Immu-
noperoxidase studies demonstrated negative staining of the neo-
plastic cells for CD45. CD20 was detected on only a few cells, but
CD79a was diffusely positive, demonstrating B-cell lineage. In
addition, CD10 and CD 99 were strongly expressed as usually
observed in pre-B proliferation. MIB1 was positive in all the nuclei.
Barely 2 weeks after the start of treatment according to the ALL
protocol, plasma creatinine values and kidney dimensions were
significantly reduced. At the end of the 1st month of therapy,
plasma creatinine values, kidney dimensions, and parenchymal
features became normal (Table 2).
As in most B-ALL patients, the clinical features of our
patient were anemia, neutropenia, bone pain, and
arthralgias. The initially suspected acute leukemia (be-
cause of the severe anemia) was rejected due to several
normal bone marrow biopsies and the absence of suspi-
cious cells in multiple peripheral blood count. The cor-
ticoid treatment of the secondary aplastic anemia and of
the “rheumatoid arthritis” later masked the hematological
disease.
ARF and nephromegaly [8] is an unusual manifesta-
tion of lymphomatous infiltration of the kidneys. Such an
infiltration was reported in patients with a diffuse lym-
phoma [7]. Although renal involvement is not uncommon,
only a few cases of renal failure secondary to a diffuse
bilateral parenchymal infiltration have been reported in
the literature and in only a few is renal failure the initial
manifestation of lymphoma [9, 10, 11,12]. The recogni-
tion of this cause of ARF is important because it often

Fig. 2 Renal biopsy showing
dense infiltration of interstitial
tissue by small blue round cells
encasing a glomerulus and tu-
bules (H and E, x20)
Table 2 Dynamics of basic renal parameters (plasma creatinine and kidney length) monitored before and during treatment according to
acute lymphoblastic leukemia (ALL) protocol
Parameter Before
treatment
Plasma creatinine (mmol/l) 148
Kidney length, left/right (mm) 140/138
responds to chemotherapy as it was the case in our pa-
tient.
Bilateral cellular infiltration of the renal interstitium
may be seen both in hematological malignancies and
nephroblastomatosis. In most cases, the ultrasound find-
ings in leukemia or lymphoma include renal enlargement
and diffuse or focal areas of homogenous hypoe-
chogenicity [13, 14,15]. In our patient, the ultrasound
image of both kidneys impressed by their dimensions and
by the thickness of parenchyma, which significantly ex-
ceeded the age reference values [16]. They were also the
main parameters suggesting the search for any cellular
infiltration within the renal parenchyma. Renal dimen-
sions shown by the ultrasound examination strikingly
reduced after the onset of therapy, as noted by other au-
thors [17], following the initial 14 days of treatment
(Table 2), plasma creatinine values and renal dimensions
were reduced, and on the 30th day they were within ref-
erence ranges.
When a pediatrician is faced with a hematopoietic
malignancy presenting with renal insufficiency, a renal
biopsy is not indicated. However, since morphologically
evident bone marrow and peripheral blood involvement
681
On day 7 On day 14 On day 30
of ALL protocol of ALL protocol of ALL protocol
117 45 35
110/110 86/83 73/72
was absent in our patient, the diagnosis of the hemato-
logical disease was possible on the basis of the results of
the renal biopsy.
A literature survey [4] showed that in 103 lympho-
blastic lymphoma patients the skin was involved in 34,
the lymph nodes in 23, the bones in 20, the mediastinum
in 5, and in 21 patients miscellaneous sites were involved
(parotid gland, tonsils, breast, ovary, brain, retroperito-
neum, soft tissues). Lin et al. [18] also reported cases with
colon and stomach involvement, and Kahwash and
Qualman [19] reported a lymphoblastic lymphoma lo-
cated in the scalp, face, and orbital subcutaneous tissue.
Bilateral nephroblastomatosis was ruled out by the
monotonous mononuclear population of round cells,
without tubular differentiation. Although rare, B-LBL
should be considered in the differential diagnosis of small
round cell tumors of the kidney. A limited panel of an-
tibodies can lead to an erroneous diagnosis. Precursor B-
LBL may be negative for CD45 and CD20 but positive for
CD99, mimicking a primitive neuroectodermal tumor
[20].
This observation may correspond to a precursor B-
LBL lymphoma with a bilateral renal localization. How-
682
ever, the clinical history of this patient suggests rather the
diagnosis of an acute precursor B-ALL manifested by an
aplastic syndrome, which is common, although masked
by the steroid therapy (multiple normal bone marrow
examination). This type of leukemia is very sensitive to
steroid therapy. Bone marrow involvement may be dis-
crete, with less than 25% of lymphoblasts. Arthralgia is
sometimes a predominant clinical symptom. Extramed-
ullary involvement is frequent, sometimes at presentation.
In conclusion, we report an unusual presentation of
precursor B-cell ALL in a child with a non-oliguric ARF
due to precursor B-cell ALL infiltration of the renal pa-
renchyma. In a clinical presentation such as this one,
when other procedures (peripheral smear examination,
bone marrow analysis) do not show the cause of ARF and
nephromegaly, a renal biopsy is mandatory for rapid di-
agnosis and therapy.
This observation emphasizes the crucial role of renal
biopsy combined with immunohistochemical examination
using a panel of antibodies to identify the origin of a
bilateral nephromegaly, as well as the diagnostic diffi-
culties of a precursor B-cell lymphoblastic proliferation
without bone marrow involvement. The negative result
for CD45 may easily lead to an erroneous diagnosis of
other small round cell tumors of children. The correct
diagnosis is extremely important because B-ALL is usu-
ally curable in the pediatric age group.
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