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. However, because of the challenging nature of the material we receive for review, and obligations related to specific clinical protocols and teaching conferences, our clinical obligations extend well beyond the designated on-service time. In the past year we were responsible for more than 2700 cases (36% of all department-wide surgical pathology cases), and a 12-15% increase in service load over the past four years. Dr. Pittaluga spends at least 75% of her time on clinical service or educational activities. She oversees triage of clinical samples received by the laboratory, a time consuming activity due to the complicated and sometimes competing demands of clinical protocols. In addition to serving as a Staff Hematopathologist, she assists in supervising the Immunohistochemistry service, and does the laboratory development for new hematopathology tests that are later introduced into the routine test library. She also directs the In Situ Hybridization service. She is supported in these activities by a laboratory technician, and a Post-Baccalaureate fellow. As will be discussed below, Dr. Pittaluga is also Program Director of the Hematology Fellowship program. Her contributions to the clinical, research, and educational programs of the NIH were recognized in 2010, when she was one of a select group to receive an NIH Individual Merit Award from the NCI Director, Dr. Varmus, and the only member of the Laboratory of Pathology to be so honored. Dr. Pittaluga and I provide 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. We cosponsor a monthly multidisciplinary case review conference discussing diagnostic or management problems in lymphoma, and in addition regularly present at conferences sponsored by NCI clinical branches (Pediatric Oncology, Medical Oncology, Dermatology, Experimental Transplantation &Immunology), and by NIAID, NHLBI, and NHGRI. We serve as Associate Investigators on more than 40 clinical protocols being conducted in the NCI and other NIH institutes. These protocols frequently mandate specialized testing to characterize the biological markers relevant to the particular study. In collaboration with other service units (Specialized Diagnostics, Cytogenetics, Flow Cytometry), we utilize a variety of diagnostic tools. The Section also provides in situ hybridization services for detection of Epstein Barr viral (EBV) sequences, and other diagnostic and experimental targets. We receive more than 2200 cases in consultation each year. Recent studies have highlighted the importance of secondary review for the diagnosis and proper treatment of patients with lymphoma.1, 2 Because of the demands that the consultation service places on our time, we try to restrict consultations to difficult or challenging cases. Many cases are submitted by other academic institutions, based on diagnostic uncertainty, or because of differences of opinion among several institutions. We regularly refuse to accept consultations that we regard to be of a routine nature, and recommend that such cases be sent to routine reference laboratories. 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. In many instances consultation cases are submitted to us based on prior publications from our laboratory. These cases contribute to our research mission, as they help us to expand our knowledge of rare entities, and characterize these disorders. Specific examples and the relevant publications are discussed under other projects. However, among them they include in situ follicular lymphoma,3 pediatric marginal zone lymphomas, 4, 5 NK-cell enteropathy,6 histiocytic sarcomas arising in B-cell or T-cell malignancies,7-9 and plasmacytomas with production of IgA.10 1. Proctor IE, McNamara C, Rodriguez-Justo M, Isaacson PG, Ramsay A. Importance of Expert Central Review in the Diagnosis of Lymphoid Malignancies in a Regional Cancer Network. J Clin Oncol 2011. 2. Jaffe ES. Centralized Review Offers Promise for the Clinician, the Pathologist, and the Patient With Newly Diagnosed Lymphoma. J Clin Oncol 2011. 3. Cong P, Raffeld M, Teruya-Feldstein J, Sorbara L, Pittaluga S, Jaffe ES. In situ localization of follicular lymphoma: description and analysis by laser capture microdissection. Blood 2002;99:3376-82. 4. Taddesse-Heath L, Pittaluga S, Sorbara L, Bussey M, Raffeld M, Jaffe ES. Marginal zone B-cell lymphoma in children and young adults. The American journal of surgical pathology 2003;27:522-31. 5. Rizzo KA, Streubel B, Pittaluga S, et al. Marginal zone lymphomas in children and the young adult population;characterization of genetic aberrations by FISH and RT-PCR. Mod Pathol 2010;23:866-73. 6. Mansoor A, Pittaluga S, Beck PL, Wilson WH, Ferry JA, Jaffe ES. NK-cell enteropathy: a benign NK-cell lymphoproliferative disease mimicking intestinal lymphoma: clinicopathologic features and follow-up in a unique case series. Blood 2011;117:1447-52. 7. Feldman AL, Minniti C, Santi M, Downing JR, Raffeld M, Jaffe ES. Histiocytic sarcoma after acute lymphoblastic leukaemia: a common clonal origin. The lancet oncology 2004;5:248-50. 8. Feldman AL, Berthold F, Arceci R, et al. Clonal relationship between precursor T-lymphoblastic leukaemia/lymphoma and Langerhans-cell histiocytosis. Lancet Oncology 2005;6:435-7. 9. Feldman AL, Arber DA, Pittaluga S, et al. Clonally related follicular lymphomas and histiocytic/dendritic cell sarcomas: evidence for transdifferentiation of the follicular lymphoma clone. Blood 2008;111:5433-9. 10. Shao H, Xi L, Raffeld M, et al. Nodal and extranodal plasmacytomas expressing immunoglobulin a: an indolent lymphoproliferative disorder with a low risk of clinical progression. The American journal of surgical pathology 2010;34:1425-35.

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Roswarski, Joseph; Roschewski, Mark; Lucas, Andrea et al. (2018) Phase I dose escalation study of the anti-CD2 monoclonal antibody, siplizumab, with DA-EPOCH-R in aggressive peripheral T-cell lymphomas. Leuk Lymphoma 59:1466-1469
Wu, David; Lim, Megan S; Jaffe, Elaine S (2018) Pathology of Castleman Disease. Hematol Oncol Clin North Am 32:37-52
Egan, Caoimhe; Jaffe, Elaine S (2018) Non-neoplastic histiocytic and dendritic cell disorders in lymph nodes. Semin Diagn Pathol 35:20-33
Chen, Jing; Zhang, Yong; Petrus, Michael N et al. (2017) Cytokine receptor signaling is required for the survival of ALK- anaplastic large cell lymphoma, even in the presence of JAK1/STAT3 mutations. Proc Natl Acad Sci U S A 114:3975-3980
Bhavsar, Tapan; Lee, John C; Perner, Yvonne et al. (2017) KSHV-associated and EBV-associated Germinotropic Lymphoproliferative Disorder: New Findings and Review of the Literature. Am J Surg Pathol 41:795-800
Gru, Alejandro A; Jaffe, Elaine S (2017) Cutaneous EBV-related lymphoproliferative disorders. Semin Diagn Pathol 34:60-75
Lionakis, Michail S; Dunleavy, Kieron; Roschewski, Mark et al. (2017) Inhibition of B Cell Receptor Signaling by Ibrutinib in Primary CNS Lymphoma. Cancer Cell 31:833-843.e5
Natkunam, Yasodha; Gratzinger, Dita; de Jong, Daphne et al. (2017) Immunodeficiency and Dysregulation: Report of the 2015 Workshop of the Society for Hematopathology/European Association for Haematopathology. Am J Clin Pathol 147:124-128
Fajgenbaum, David C; Uldrick, Thomas S; Bagg, Adam et al. (2017) International, evidence-based consensus diagnostic criteria for HHV-8-negative/idiopathic multicentric Castleman disease. Blood 129:1646-1657
Gru, Alejandro A; Jaffe, Elaine S (2017) The Landscape of Cutaneous Lymphomas in 2016, An Introduction. Semin Diagn Pathol 34:1-2

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