B Lymphoblastic Leukemia With a Novel t(11;15) (q23;q15) and Unique Burkittoid Morphologic and Immunophenotypic Findings in a 9-Year-Old Boy.

B lymphoblastic leukemia is a B progenitor cell neoplasm with a range of immature immunophenotypes and several associated cytogenetic lesions. In contrast, Burkitt leukemia/lymphoma is a mature B lymphocyte neoplasm with a characteristic germinal center immunophenotype and MYC rearrangement. With modern immunophenotyping and cytogenetic methods, the distinction between these 2 entities is seldom ambiguous. Herein, we report a case of a 9-year-old white boy with circulating leukemic cells that demonstrate morphologic overlap between Burkitt leukemia and B lymphoblastic leukemia. Flow cytometry and immunohistochemical stains demonstrated expression of sets of markers with overlap between immature and mature immunophenotypes. While the leukemic cells tested positive for terminal deoxynucleotidyl transferase (TdT), they expressed CD20, BCL6 (in a subset), and lambda-restricted surface light chain. Molecular studies confirmed a true clonal light chain rearrangement, whereas fluorescent in situ hybridization (FISH) results were negative for MYC rearrangement. Metaphase cytogenetics identified a novel gene rearrangement, t(11;15)(q23;q15), that does not involve the MLL gene. This unique cytogenetic abnormality involves the loss of INO80, an adenosine triphosphatase (ATPase) with DNA binding ability. This cytogenetic abnormality may represent a unique feature of this overlap entity of B lymphoblastic lymphoma that expresses markers of maturity and demonstrates Burkitt-like morphology.

Limited utility of fluorescence in situ hybridization for common abnormalities of myelodysplastic syndrome at first presentation and follow-up of myeloid neoplasms.

Fluorescence in situ hybridization for abnormalities common to myelodysplastic syndrome (MDS FISH) is often used with traditional karyotype in the diagnosis and monitoring of myeloid neoplasms. However, its value in these roles has been questioned. To evaluate its utility, we compared MDS FISH results with karyotype in 544 bone marrow specimens obtained for diagnosis (180 cases) or follow-up (364 cases) of myeloid neoplasia. We found excellent concordance between FISH and karyotype, such that FISH is rarely abnormal (1.7% at diagnosis and 3.0% at follow-up) in cases with normal karyotype. Even in the rare discordant cases, the abnormal FISH has little or no clinical value. Thus, we propose that this test should be limited to cases with inadequate karyotype only. Such guidelines could result in significant cost savings with no impact on patient diagnosis.

Optimizing personalized bone marrow testing using an evidence-based, interdisciplinary team approach.

OBJECTIVES: To address the overuse of testing that complicates patient care, diminishes quality, and increases costs by implementing the diagnostic management team, a multidisciplinary system for the development and deployment of diagnostic testing guidelines for hematologic malignancies. METHODS: The team created evidence-based standard ordering protocols (SOPs) for cytogenetic and molecular testing that were applied by pathologists to bone marrow biopsy specimens on adult patients. Testing on 780 biopsy specimens performed during the six months before SOP implementation was compared with 1,806 biopsy specimens performed during the subsequent 12 months. RESULTS: After implementation, there were significant decreases in tests discordant with SOPs, omitted tests, and the estimated cost of testing to payers. The fraction of positive tests increased. Clinicians reported acceptance of the new procedures and perceived time savings. CONCLUSIONS: This process is a model for optimizing complex and personalized diagnostic testing.