Submitting Author: Wang, Wei, MD, PhD
Institution: Wake Forest Baptist Health
Additional authors:Mark Pettenati, Ph.D and Changlee Pang, MD
Session: B Lymphoblastic Leukemia/Lymphoma

An 8-year-old male presented in July 2009 with one month history of fever, fatigue and night sweats. On physical examination, scrotal edema was noted but no skin rash, lymphadenopathy, hepatosplenomegaly or cardiorespiratory symptoms were observed. CBC at admission revealed leukocytosis (29.3 x10^3/µL) with marked eosinophilia (66%, 19.3 x10^3/µL). There was a mild maturational left shift of granulocytes with 1% myelocytes and 4% bands without circulating blasts. The hemoglobin was 10.1g/dL and the platelet count was 289,000/µL. The bone marrow biopsy revealed involvement by B lymphoblastic leukemia with extensive areas of necrosis and numerous eosinophilic elements. The following cytogenetics of the bone marrow showed 47, XY, t(5;14)(q31;q32),+22. Bilateral testicular involvement was diagnosed clinically. The patient underwent induction chemotherapy (Cytarabine, Decadron, VCR, Daunomycin and PEG Asparaginase), consolidation chemotherapy (cyclophosphamide, ARA-C and 6MP) and maintenance therapy. Currently the patient is in complete remission.

The bone marrow core biopsy was B+ fixed, paraffin embedded, and stained with hematoxylin-eosin. Bone marrow aspirate smears were stained with Wright-Giemsa.

The bone marrow core biopsy (B09-1005) was remarkable for large areas of necrosis with aggregates of monomorphic blasts as well as numerous eosinophilic elements.

The bone marrow aspirate smears revealed 31% blasts. Most blasts appeared lymphoid with scant cytoplasm and variably conspicuous nucleoli. The eosinophilic elements displayed atypical morphology including hypolobated nuclei, vacuolated cytoplasm and unevenly distributed cytoplasmic granules. The peripheral blood smears showed numerous eosinophils with similar morphology. No circulating blasts were identified.

Additionally the second bone marrow core biopsy and aspirate sample (B09-1016) were received in two days. In this sample, the marrow space was extensively replaced by blasts with decreased numbers of eosinophilic elements. The blast fraction had increased to 46% on the aspirate smears and nearly 90% in the core biopsy. On the other hand, the peripheral eosinophil count had decreased from 19.3 x10^3/µL to 12.9 x10^3/µL.

By immunohistochemistry, the blasts were positive for CD10, CD79a, and CD34. TdT was technically unsatisfactory due to extensive necrosis. Myeloperoxidase highlighted the numerous eosinophilic precursors.

By flow cytometric analysis, the blasts expressed CD10 (bright), CD19 (moderate), nTdT, CD34, CD38, HLA-DR and CD33 (dim). They did not express CD3, CD5, CD13, CD14, CD15, CD20 and CD56.

Karyotype showed 47, XY, t(5;14)(q31;q32),+22[15]/46,XY[1].

FISH analysis revealed break-apart of 14q32. However, the DNA probes specific for PDGFRB (5q32) showed no break-apart. There were no abnormalities involving chromosomes 4, 10, and 17. ABL(9q34) and BCR(22q11) genes revealed lack of fusion signals.

B lymphoblastic leukemia with t(5;14) is a rare disease and comprise <1% of cases of acute lymphoblastic leukemia. The increased eosinophils in this entity is believed to be reactive and caused by IL-3 overproduction by neoplastic blast cells due to the activation of IL-3 gene on chromosome 5 after its translocation.

In our case, the patient initially presented with fever, night sweats, eosinophilia, and scrotal edema without skin rash or cardiorespiratory symptoms. Of note, cardiorespiratory problems were present at diagnosis or had developed during the clinical course in the majority of the reported patients, which is similar to idiopathic hypereosinophilic syndrome.

The difference in the morphologic findings of the subsequent bone marrow was striking in this case (compare B09-1016 to B09-1005). It showed a more pronounced proliferation of the blasts with decreased numbers of eosinophilic elements. This likely resulted in decreased peripheral blood eosinophil counts. There was also persistent lack of circulating blasts noted, which is typically observed in this disease.

In addition, the karyotype revealed t(5;14)(q31;q32) as well as a break-apart of 14q32 by FISH. However, PDGFRB probe did not show break-apart by FISH analysis. This excludes a possibility of being a lymphoid neoplasm with eosinophilia and abnormalities of PDGFRB (2008 WHO classification).

B lymphoblastic leukemia with t(5;14)(q31;q32)

B-acute lymphoblastic leukemia with t(5;14)(q31;q32)

Case 104