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 other clinical branches in the NCI (Pediatric Oncology, Medical Oncology, Dermatology, Experimental Transplantation & Immunology), and other Institutes (NIAID, NHLBI, and NHGRI.) We receive more than 2000 cases in consultation each year. We try to restrict consultations to difficult or challenging cases, and do not accept cases for routine second opinions. A significant proportion (approximately 20%) of the cases are submitted by other academic institutions based on diagnostic uncertainty, or because of differences of opinion among several institutions. We are often the final arbiter on challenging diagnostic problems. Additionally, we have made novel observations based on our clinical practice, and a number of publications have emanated from case material originally reviewed in consultation. Our clinical consultation practice also synergizes with other NIH clinical groups, enhancing referral to NIH clinical protocols. With our international collaborators, a revision of the nearly 8-year-old World Health Organization classification of the lymphoid neoplasms and the accompanying monograph is being published. It reflects a consensus among hematopathologists, geneticists, and clinicians regarding both updates to current entities as well as the addition of a limited number of new provisional entities. The revision clarifies the diagnosis and management of lesions at the very early stages of lymphomagenesis, refines the diagnostic criteria for some entities, details the expanding genetic/molecular landscape of numerous lymphoid neoplasms and their clinical correlates, and refers to investigations leading to more targeted therapeutic strategies. The revised classification reflects the most important advances in our understanding that impact our diagnostic approach, clinical expectations, and therapeutic strategies for the lymphoid neoplasms. A summary of the revised classification was published in 2016 in Blood, and is being adopted on a worldwide basis. In other work, our studies have led to improvement in the diagnosis and classification of a rare form of T-cell lymphoma is systemic anaplastic large cell lymphomas lacking the ALK-tyrosine kinase. We recently reported that ALK-negative ALCLs are genetically heterogeneous. The largest subset, representing 30% of cases, had rearrangements of the DUSP22 locus. These cases had favorable outcomes similar to ALK-positive ALCL, and superior to other ALK-negative ALCLs. In a recent study we examined the morphologic features of these cases in more detail. First, we conducted blinded review of hematoxylin and eosin slides of 108 ALCLs from our previous study, scoring cases for the presence of 3 histologic patterns and 5 cell types. Cases then were unblinded and re-reviewed to understand these features further. DUSP22-rearranged ALCLs were more likely than other ALK-negative ALCLs to have so-called doughnut cells (23% vs. 5%; P=0.039), less likely to have pleomorphic cells (23% vs. 49%; P=0.042), and nearly always (95%) had areas with sheet-like growth (common pattern). To examine the reproducibility of these findings, we conducted blinded review of hematoxylin and eosin slides of 46 additional ALK-negative ALCLs using a 0 to 3 scoring system to predict likelihood of DUSP22 rearrangement, the results of which correlated strongly with subsequent findings by fluorescence in situ hybridization (P0.0001). Although all ALCLs share certain morphologic features, ALCLs with DUSP22 rearrangements show significant differences from other ALK-negative ALCLs, typically showing sheets of hallmark cells with doughnut cells and few large pleomorphic cells. These morphologic findings and our previous outcome data suggest that ALK-positive ALCLs and DUSP22-rearranged ALCLs represent prototypical ALCLs, whereas ALCLs lacking rearrangements of both DUSP22 and ALK require further study. Accurate recognition of this subtype is important because these patients can be managed successfully with chemotherapy, and do not require more aggressive approaches such as stem cell transplantation.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIABC011070-09
Application #
9343789
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
9
Fiscal Year
2016
Total Cost
Indirect Cost
Name
Basic Sciences
Department
Type
DUNS #
City
State
Country
Zip Code
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
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
Gratzinger, Dita; Jaffe, Elaine S; Chadburn, Amy et al. (2017) Primary/Congenital Immunodeficiency: 2015 SH/EAHP Workshop Report-Part 5. Am J Clin Pathol 147:204-216
Jaffe, Elaine S; Barr, Paul M; Smith, Sonali M (2017) Understanding the New WHO Classification of Lymphoid Malignancies: Why It's Important and How It Will Affect Practice. Am Soc Clin Oncol Educ Book 37:535-546
Jaffe, Elaine S (2017) The Microscope as a Tool for Disease Discovery-A Personal Voyage. Annu Rev Pathol 12:1-24

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