ZIA BC 011070 (ZIA) | |||
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Title | Hematopathology Diagnosis | ||
Institution | NCI, Bethesda, MD | ||
Principal Investigator | Jaffe, Elaine | NCI Program Director | N/A |
Cancer Activity | N/A | Division | CCR |
Funded Amount | $427,025 | Project Dates | 10/01/2007 - 00/00/0000 |
Fiscal Year | 2014 | Project Type | Intramural |
Research Topics w/ Percent Relevance | Cancer Types w/ Percent Relevance | ||
Autoimmune Diseases (20.0%) Cancer (100.0%) Childhood Cancers (10.0%) Herpes - Other (10.0%) |
Childhood Leukemia (5.0%) Hodgkins disease (30.0%) Leukemia (5.0%) Non Hodgkins Lymphoma (65.0%) |
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Research Type | |||
Technology and/or Marker Testing in a Clinical Setting Resources and Infrastructure Related to Detection, Diagnosis, or Prognosis |
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Abstract | |||
The Hematopathology Section of the Laboratory of Pathology, NCI, offers expert diagnostic services in the field of hematopathology. Dr. Stefania Pittaluga, Staff Clinician, and I handle diagnostic service responsibilities equally, each rotating as the staff on service 50% of the time. Dr. Pittaluga oversees triage of clinical protocol samples received by the laboratory, and the Section also provides in situ hybridization services for detection of Epstein Barr viral (EBV) sequences, and other diagnostic and experimental targets. NIH protocols frequently mandate specialized testing to characterize the biological markers relevant to the particular study. We often perform the laboratory development for new hematopathology tests that are later introduced into the routine test library. Dr. Pittaluga is supported in her diagnostic efforts by a laboratory technician, and a Post-Baccalaureate fellow. Dr. Pittaluga is also Program Director of the Hematology Fellowship program. The Section provides assistance in the diagnosis and classification of reactive and neoplastic lymphoproliferative disorders, immunodeficiency states, and diverse hematological malignancies. We provide consultative and collaborative services to physicians in the NCI, as well as to physicians studying patients with hematolymphoid disorders in other institutes, in particular NIAID, NHLBI, NHGRI, and NIAMSD. Studies from the Hematopathology Section have helped to characterize the pathological findings associated with many rare diseases, including the autoimmune lymphoproliferative syndrome (ALPS), (1) GATA2 deficiency (2), PI3Kinase deficiency, (3, 4), multicentric Castleman's disease and related HHV-8/KSHV-associated conditions,(5) and mediastinal grey zone lymphomas.(6) We receive more than 2000 cases in consultation each year. Recent studies have highlighted the importance of secondary review for the diagnosis and proper treatment of patients with lymphoma. (7) Many cases are submitted by other academic institutions, based on diagnostic uncertainty, or because of differences of opinion among several institutions. We frequently make novel observations based on this unique clinical practice, and a number of publications have emanated from case material originally reviewed in consultation. Thus, I believe our clinical work enhances, rather than detracts, from our academic productivity. For example, through our consultation practice we contributed to the recognition of a high grade B-cell lymphoma resembling Burkitt lymphoma, but lacking involvement of the MYC translocation, and instead having other recurrent genetic alterations.(8) We also provided evidence that EBV can be associated with nodular lymphocyte predominant Hodgkin's lymphoma, albeit an infrequent but important diagnostic finding.(9) New insights were provided to enhance diagnostic accuracy for several other conditions: hyaline vascular Castleman's disease(10), Rosai-Dorfman disease(11), and cutaneous T-cell lymphoma(12). 1. Price S, Shaw PA, Seitz A, et al. Natural history of autoimmune lymphoproliferative syndrome associated with FAS gene mutations. Blood. 2014. 2. Hsu AP, Sampaio EP, Khan J, et al. Mutations in GATA2 are associated with the autosomal dominant and sporadic monocytopenia and mycobacterial infection (MonoMAC) syndrome. Blood. 2011;118:2653-2655. 3. Lucas CL, Kuehn HS, Zhao F, et al. Dominant-activating germline mutations in the gene encoding the PI(3)K catalytic subunit p110delta result in T cell senescence and human immunodeficiency. Nature immunology. 2014;15:88-97. 4. Crank MC, Grossman JK, Moir S, et al. Mutations in PIK3CD can cause hyper IgM syndrome (HIGM) associated with increased cancer susceptibility. Journal of clinical immunology. 2014;34:272-276. 5. Polizzotto MN, Uldrick TS, Wang V, et al. Human and viral interleukin-6 and other cytokines in Kaposi sarcoma herpesvirus-associated multicentric Castleman disease. Blood. 2013;122:4189-4198. 6. Wilson WH, Pittaluga S, Nicolae A, " |