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 (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. Recent examples include the recognition of EBV-positive diffuse large B-cell lymphomas in young patients,1 the description of a novel intestinal T-cell lymphoproliferative disease,2 and a comprehensive analysis of the diverse forms of follicular lymphoma that occur in the pediatric age group.3 We have recently reported on the pathology of entities that were the subject of NCI clinical trials, lymphomatoid granulomatosis4 and mediastinal grey zone lymphomas.5 Our clinical consultation practice also synergizes with other NIH clinical groups. Because of our longstanding interest in EBV-driven lymphoproliferative disorders, we often receive challenging cases in consultation. Our review frequently leads to patient referral and entry on protocols under the direction of Dr. Jeffrey Cohen, NIAID, who has a basic and clinical interest in EBV. Dr. Pittaluga has played a major role in characterizing the pathological features of novel immunodeficiency syndromes being studies by Drs. Holland and Lenardo.6-8 Efforts on behalf of clinical colleagues at the NIH or extramurally, have led to publications on a variety of topics including common variable immunodeficiency syndrome, 9 autoimmune lymphoproliferative syndrome,10 breast implant associated anaplastic large cell lymphoma,11 and T-cell lymphomas associated with acquired generalized lipodystrophy.12 1. Nicolae A, Pittaluga S, Abdullah S, et al. EBV positive large B cell lymphomas in young patients: a nodal lymphoma with evidence for a tolerogenic immune environment. Blood. 2015. 2. Perry AM, Warnke RA, Hu Q, et al. Indolent T-cell lymphoproliferative disease of the gastrointestinal tract. Blood. 2013;122:3599-3606. 3. Liu Q, Salaverria I, Pittaluga S, et al. Follicular lymphomas in children and young adults: a comparison of the pediatric variant with usual follicular lymphoma. Am J Surg Pathol. 2013;37:333-343. 4. Song JY, Pittaluga S, Dunleavy K, et al. Lymphomatoid granulomatosis--a single institute experience: pathologic findings and clinical correlations. Am J Surg Pathol. 2015;39:141-156. 5. Wilson WH, Pittaluga S, Nicolae A, et al. A prospective study of mediastinal gray-zone lymphoma. Blood. 2014;124:1563-1569. 6. Betts K, Abusleme L, Freeman AF, et al. A 17-year old patient with DOCK8 deficiency, severe oral HSV-1 and aggressive periodontitis - a case of virally induced periodontitis? J Clin Virol. 2015;63:46-50. 7. 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. Nat Immunol. 2014;15:88-97. 8. Kuehn HS, Ouyang W, Lo B, et al. Immune dysregulation in human subjects with heterozygous germline mutations in CTLA4. Science. 2014;345:1623-1627. 9. da Silva SP, Resnick E, Lucas M, et al. Lymphoid proliferations of indeterminate malignant potential arising in adults with common variable immunodeficiency disorders: unusual case studies and immunohistological review in the light of possible causative events. J Clin Immunol. 2011;31:784-791. 10. Price S, Shaw PA, Seitz A, et al. Natural history of autoimmune lymphoproliferative syndrome associated with FAS gene mutations. Blood. 2014;123:1989-1999. 11. Lee YS, Filie A, Arthur D, et al. Breast implant-associated anaplastic large cell lymphoma in a patient with Li-Fraumeni syndrome. Histopathology. 2015. 12. Brown RJ, Chan JL, Jaffe ES, et al. Lymphoma in acquired generalized lipodystrophy. Leuk Lymphoma. 2015:1-6.
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