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 9-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 several rare diseases including multcentric Castleman disease, Erdheim-Chester disease, autoimmune lymphoproliferative syndrome, and KSHV- and EBV-associated germinotropic lymphoproliferative disorder. The studies of Erdheim-Chester disease and Castleman disease involved large multi-center collaborative efforts, in which we played a major role, both in the design and conduct of the studies. Another controversial and difficult area is the diagnosis and classification of lymphoproliferative disorders and lymphomas associated with diverse forms of immunodeficiency, including congenital, post-transplant, other iatrogenic causes, and acquired secondary to HIV, or advanced age with associated immune senescence. As one of eight members of an expert panel, I particpated in an international workshop to evaluate the spectrum of disease and provide enhanced criteria for diagnosis and patient management. 415 cases were received from 21 countries. The conclusions of the workshop were published in a series of 6 papers. The Workshop Review Panel proposed a unifying nomenclature to enable study of all immunodeficiency-related lymphoproliferative disorders within a single conceptual framework. This effort should improve the accurate diagnosis and management of patients with lymphoproliferative disorders resulting from diverse forms of immune deficiency.
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