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 regularly present at conferences sponsored by clinical branches in the NCI 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. Our work has led to improvement in the diagnosis and classification of several rare diseases including multicentric Castleman disease, Erdheim-Chester disease, autoimmune lymphoproliferative syndrome, KSHV- and EBV-associated proliferations, and rare histiocytic disorders, such as Rosai-Dorfman disease. The studies of Castleman disease involve large multi-center collaborative efforts, in which we play a major role, both in the design and conduct of the studies. As a member of an expert review panel, I review all cases submitted to a registry, to validate the diagnosis, and correlate with biological and translational 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. We published a Perspective article in Blood, discussing key issues related to the classification of lymphoproliferative disorders associated with immune deficiencies. I also serve on an expert review panel to validate the diagnosis of Burkitt lymphoma for a comprehensive TCGA analysis of this tumor. I was a key contributor to the WHO Bluebook on the classification of cutaneous neoplasms, and a review article summarizing updates to the classification of cutaneous lymphomas was published in Blood. Several reports published in the literature highlighted diagnostic problems related to atypical dendritic cell proliferations, intravascular large B-cell lymphoma, and histological progression of follicular lymphoma.
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