IMAGES IN HEMATOLOGY

Multiple intracranial tumors in Philadelphiachromosome-positive acute lymphoblastic leukemia

Naoki Hatakeyama • Tsukasa Hori • Masaki Yamamoto •

Natsuko Inazawa • Keita Igarashi • Hiroyuki Tsutsumi •

Nobuhiro Suzuki

Received: 1 October 2012 / Revised: 22 January 2013 / Accepted: 22 January 2013 / Published online: 24 March 2013

� The Japanese Society of Hematology 2013

Keywords Acute lymphoblastic leukemia � Intracranial

tumors � Philadelphia chromosome

A three-year-old female presented with prolonged fever

and petechiae. Her initial complete blood workup showed a

white blood cell (WBC) count of 159 9 109/L with 92 %

lymphoblasts, hemoglobin of 9.3 g/dL, and a platelet count

of 22 9 109/L. Marked elevations of C-reactive protein

(CRP) and lactate dehydrogenase were identified.

The immunophenotype of the blast cells was CD101,

CD191, HLA-DR?, smIg-, and smIg j=k�, which is

compatible with a diagnosis of precursor B cell lympho-

blastic leukemia (pre-B ALL). CD66c expression was also

detected, so we confirmed the bcr/abl rearrangement by

fluorescence in situ hybridization analysis, and used

transcriptase-polymerase chain reaction analysis to detect

the minor bcr/abl fusion gene transcript. Given these

results, the patient was diagnosed with Philadelphia chro-

mosome-positive acute lymphoblastic leukemia (Ph?

ALL). By conventional cytogenetic analysis of bone mar-

row and peripheral blood cells at the onset, abnormalities

of 9p-q? and 22q- were suggested, but the complete

karyotype of this case could not be confirmed at the time;

however, the karyotype was later revealed at her first relapse to

be 46, XX, dup(1)(q25q32), add(1)(q32), del(3)(q2?),

der(9)t(9;22)(q34;q11)del(9)(p13), del(14)(13).

As she presented with severe hyperleukocytosis, she

received intravenous hyperhydration and prednisone at low

doses for the purpose of cytoreduction until the beginning

of remission induction therapy. A broad-spectrum anti-

bacterial agent and fluconazole were also administered

intravenously against her suspected systemic infection.

However, her blood culture was negative, and her serum

b-D glucan was not elevated.

Whole-body computed tomography (CT) imaging was

performed and high-density multiple intracranial tumors

were detected (Fig. 1a–c) despite the absence of focal

neurological symptoms or meningeal irritation. However,

an analysis of her cerebrospinal fluid (CSF) showed no

nucleated cells, and normal protein (18 mg/dL) and glu-

cose (69 mg/dL) levels. The CRP level became negative at

3 days before starting induction chemotherapy, so both the

antibacterial agent and fluconazole were stopped. During

the period of myelosuppression after starting induction

therapy, she remained afebrile with no elevation of CRP.

Head CT scans at 16 days and 30 days after induction

therapy, showed the intracranial masses to be markedly

reduced compared with those on her head CT scans before

induction therapy (Fig. 2a–c). Her intracranial tumors

completely disappeared after two cycles of chemotherapy

and never recurred. Unfortunately, she died from refractory

leukemia, although she received allogeneic cord blood

transplantation twice.

At first, the intracranial lesions were suspected to be

multiple brain abscesses or cerebral hemorrhage. If either

were the case, rapid regression of intracranial lesions such

as those observed in the present case would not be expected

to occur. Moreover, several patients with acute leukemia

who developed multiple intracranial hemorrhages associ-

ated with hyperleukocytosis have been reported. In such

patients, severe neurological symptoms are commonly

N. Hatakeyama (&) � T. Hori � M. Yamamoto � N. Inazawa �K. Igarashi � H. Tsutsumi � N. Suzuki

Department of Pediatrics,

Sapporo Medical University School of Medicine,

South-1, West-16 Chuo-ku, Sapporo,

Hokkaido 060-8543, Japan

e-mail: nhatake@sapmed.ac.jp

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Int J Hematol (2013) 97:441–442

DOI 10.1007/s12185-013-1285-0

observed and fatal outcomes are not uncommon if adequate

and aggressive therapies, including neurosurgery treat-

ments, are not received as rapidly as possible. For these

reasons, the multiple intracranial tumors in our case were

regarded as originating from Ph? ALL cells.

Extramedullary tumors occur less commonly in pre-B

ALL, and those in intracranial sites are extremely rare. To

our knowledge, other than the present case, there has only

been one reported case of multiple intracranial tumors at

diagnosis of pre-B ALL [1]. Interestingly, both of these

two cases were diagnosed with Ph? ALL. We suggest that

due to certain biological properties, Ph? ALL cells may

tend to invade into the brain parenchyma and develop

multiple intracranial tumors.

Reference

1. Cuvelier GD, Vitali AM, Ford JC, et al. Multiple intracranial

tumors in Philadelphia chromosome positive acute lymphoblastic

leukemia: successful treatment following aggressive supportive

care, early cranial radiation, high dose chemotherapy and imatinib.

Pediatr Blood Cancer. 2008;51:135–7.

Fig. 1 Non-contrast computed tomography of head. Multiple intracranial tumors were demonstrated (a–c)

Fig. 2 Computed tomography images at the same lesion before

induction therapy (a), at day 16 (b) and at day 30 (c) after the

beginning of induction therapy. The intracranial tumor was markedly

and rapidly reduced

442 N. Hatakeyama et al.

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