BMW57: EXTRAMEDULLARY PRESENTATION OF MIXED PHENOTYPE ACUTE LEUKEMIA
WITH T(9;22)(Q34;Q11.2); BCR-ABL1 AND BILATERAL STAGING BONE MARROW BIOPSIES
WITH T(9;22)(Q34;Q11.2) BUT NO EVIDENCE OF CHRONIC OR ACUTE LEUKEMIA
Julia T Geyer1, Susan Mathew1 and Attilio Orazi1
1.Weill Cornell Medical College, Hematopathology, New York, USA
jut9021@med.cornell.edu
Clinical history: The patient is a 59 year old male with past medical history of prostate cancer diagnosed in
2007 and treated surgically, kidney stones, coronary artery disease and coronary artery bypass graft (CABG)
surgery. Patient had been complaining of back pain for 1 year, which was attributed to kidney stones. In
September and October 2009 symptoms have worsened (pain of 10/10, worse while laying down and
walking). No alleviating factors. Patient had been taking Dilaudid and Oxycodone without improvement.
Outpatient MRI was performed demonstrating an epidural soft tissue density within the spinal canal extending
out of the neural foramen on the right at T12/L1 and an abnormal soft tissue density lateral anterior to the T12
vertebral body. There was severe spinal stenosis with epidural disease causing multilevel foraminal
compromise. An open biopsy of T12 lesion was performed. Due to spinal cord compression symptoms, a
combination chemotherapy regimen of cyclophosphamide, vincristine, prednisone, bleomycin, doxorubicin and
procarbazine (COP-BLAM) was immediately initiated. Patient had also received Neulasta due to neutropenia.
After receiving the final pathology diagnosis, a bilateral iliac bone marrow biopsy was performed. The patient
is now being treated with Hyper-CVAD and Imatinib and is doing well 3 months following diagnosis.
Hb 16.1, WBC 7.6, Plt 283. Other lab. parameters: Manual differential: 81% neutrophils, 11% lymphocytes,
6% monocytes, 1% eosinophils, 1% basophils. Calcium 10.8 (normal 8.9-10.3). All other parameters within
normal limits
Biopsy fixation: Spinal epidural biopsy was fixed in formalin. Staging bone marrow biopsies were fixed in
Bouin's solution.
Microscopy: Spinal epidural tumor: The sections show fibroadipose tissue with a diffuse and focally nested
proliferation of medium to large cells with round, oval to irregular nuclei, finely dispersed chromatin, often
prominent nucleoli and moderate amount of cytoplasm. Numerous mitoses seen. There are many admixed
eosinophils. In addition there are fragments of bone with unremarkable bony trabeculae. The bone marrow is
hypercellular for age (about 70%). The myeloid to erythroid ratio is normal. Both myeloid and erythroid series
show normal maturation. Blasts are not increased. Megakaryocytes are slightly increased, scattered and have
normal morphology. Staging right and left posterior iliac bone marrow biopsies (post Neulasta): Both biopsies
show similar findings. The marrow is hypercellular for the age of the patient (80%) with a marked myeloid
hyperplasia. The myeloid series is left shifted. Blasts are not increased in number (1% on the right side biopsy
and 3% on the left). The erythroid series is mildly left shifted. The megakaryocytes are markedly increased in
number and vary from small cells with hypolobated nuclei to large multinucleated cells. Reticulin and trichrome
stains do not show fibrosis. Atypical blasts (as seen on the spinal epidural biopsy) are not identified. Smears:
Spinal epidural tumor: not available. Staging right and left posterior iliac bone marrow biopsies: The bone
marrow aspirate is hypercellular for the patient's age. Megakaryocytes are adequate in number with some
clustered in the spicules and a few atypical forms and rare micromegakaryocytes seen. Myelopoiesis is
slightly left-shifted with increased myelocytes. Slight toxic granulation and Döhle bodies are noted in some of
the granulocytes. Full erythroid maturation is present without significant dyspoiesis. There is no eosinophilia or
basophilia.
Immunophenotype/immunohistochemistry: Spinal epidural tumor: Immunohistochemical stains show that
the tumor cells exhibit phenotypes of immature B cells and myeloid cells. They are TdT(+), PAX5(+),
CD79a(+), CD10(+), CD20(-), as well as MP0(+), CD68(+), CD117(+) and CD43(+). These cells have a very
high proliferation rate. There is no evidence of EBV based on in situ hybridization for EBER.
Right and left posterior iliac bone marrow biopsies: There is no increase in CD117(+), CD34(+) myeloid blasts
(less than 1% of all cells). In addition, these cells do not coexpress B cell markers (PAX5, CD79a) or TdT.
Cytogenetics: The FISH assay performed on a paraffin section slide from the spinal epidural tumor showed
BCR-ABL1 gene rearrangements, indicating the presence of a t(9;22) translocation. Conventional
cytogenetics analysis performed on bone marrow samples obtained from right and left posterior iliacs showed
a 46,XY,t(9;22)(q34;q11.2) karyotype. Fluorescence in situ hybridization (FISH) using the LSI BCR-ABL1 dual
color dual fusion probe (Vysis/Abbott Molecular Inc., Des Plaines, IL) showed BCR-ABL1 gene
rearrangements establishing the presence of a t(9;22) translocation in the samples.
Molecular analysis: Peripheral blood was submitted for a qualitative real time PCR for major and minor
breakpoints involving the BCR-ABL1 translocation with the following results: Positive for b3a2 major
breakpoint (p210).
Proposed diagnosis
Extramedullary mixed phenotype acute leukemia with t(9;22)(q34;q11.2); BCR-ABL1.
Interesting feature(s) of the submitted case
- Mixed phenotype acute leukemia, with t(9;22)(q34;q11.2); BCR-ABL1 is a provisional entity in the 2008
WHO classification of tumors of hematopoietic and lymphoid tissues. It accounts for <1% of acute leukemias.
This case represents an extramedullary manifestation “myeloid sarcoma like” of this rare entity.
- Evidence of BCR-ABL1 translocation in bone marrow biopsies and peripheral blood is intriguing and raises
the question of CML presenting in blastic phase. However, the patient never had a diagnosis of CML and at
the time of presentation or thereafter did not have increased peripheral blood counts, basophilia, and/or
splenomegaly. The bone marrow morphology, while obscured by recent treatment with GCSF, was not
considered as diagnostic of CML. Therefore the relationship of this subtype of t(9;22) positive extramedullary
acute leukemia with CML is, at this point, uncertain.