Browsing by Author "Dave, Sandeep S."

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    Enteropathy-associated T cell lymphoma subtypes are characterized by loss of function of SETD2
    (Rockefeller University Press, 2017-05-01) Moffitt, Andrea B.; Ondrejka, Sarah L.; McKinney, Matthew; Rempel, Rachel E.; Goodlad, John R.; Teh, Chun Huat; Leppa, Sirpa; Mannisto, Susanna; Kovanen, Panu E.; Tse, Eric; Au-Yeung, Rex K.H.; Kwong, Yok-Lam; Srivastava, Gopesh; Iqbal, Javeed; Yu, Jiayu; Naresh, Kikkeri; Villa, Diego; Gascoyne, Randy D.; Said, Jonathan; Czader, Magdalena B.; Chadburn, Amy; Richards, Kristy L.; Rajagopalan, Deepthi; Davis, Nicholas S.; Smith, Eileen C.; Palus, Brooke C.; Tzeng, Tiffany J.; Healy, Jane A.; Lugar, Patricia L.; Datta, Jyotishka; Love, Cassandra; Levy, Shawn; Dunson, David B.; Zhuang, Yuan; Hsi, Eric D.; Dave, Sandeep S.; Pathology and Laboratory Medicine, School of Medicine
    Enteropathy-associated T cell lymphoma (EATL) is the most common oncologic complication of celiac disease. Moffitt and colleagues identify novel EATL-defining mutations in SETD2, as well as clinically relevant mutations in the JAK-STAT pathway., Enteropathy-associated T cell lymphoma (EATL) is a lethal, and the most common, neoplastic complication of celiac disease. Here, we defined the genetic landscape of EATL through whole-exome sequencing of 69 EATL tumors. SETD2 was the most frequently silenced gene in EATL (32% of cases). The JAK-STAT pathway was the most frequently mutated pathway, with frequent mutations in STAT5B as well as JAK1, JAK3, STAT3, and SOCS1. We also identified mutations in KRAS, TP53, and TERT. Type I EATL and type II EATL (monomorphic epitheliotropic intestinal T cell lymphoma) had highly overlapping genetic alterations indicating shared mechanisms underlying their pathogenesis. We modeled the effects of SETD2 loss in vivo by developing a T cell–specific knockout mouse. These mice manifested an expansion of γδ T cells, indicating novel roles for SETD2 in T cell development and lymphomagenesis. Our data render the most comprehensive genetic portrait yet of this uncommon but lethal disease and may inform future classification schemes.
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    Progression and transformation of chronic lymphocytic leukemia/small lymphocytic lymphoma and B-cell prolymphocytic leukemia: Report from the 2021 SH/EAHP Workshop
    (Oxford University Press, 2023) Czader, Magdalena; Amador, Catalina; Cook, James R.; Thakkar, Devang; Parker, Clay; Dave, Sandeep S.; Dogan, Ahmet; Duffield, Amy S.; Nejati, Reza; Ott, German; Xiao, Wenbin; Wasik, Mariusz; Goodlad, John R.; Pathology and Laboratory Medicine, School of Medicine
    Objectives: Session 3 of the 2021 Workshop of the Society for Hematopathology/European Association for Haematopathology examined progression and transformation of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and B-cell prolymphocytic leukemia (B-PLL). Methods: Thirty-one cases were reviewed by the panel. Additional studies such as immunohistochemistry and molecular genetic testing, including whole-exome sequencing and expression profiling, were performed in select cases. Results: Session 3 included 27 CLL/SLL cases and miscellaneous associated proliferations, 3 cases of B-PLL, and 1 case of small B-cell lymphoma. The criteria for -accelerated CLL/SLL are established for lymph nodes, but extranodal disease can be diagnostically challenging. Richter transformation (RT) is a broad term and includes true transformation from original CLL/SLL clone(s) and clonally unrelated neoplasms. The morphologic, immunophenotypic, and genetic spectrum is diverse with classical and highly unusual examples. T-cell proliferations can also be encountered in CLL/SLL. B-cell prolymphocytic leukemia is a rare, diagnostically challenging disease due to its overlaps with other lymphoid neoplasms. Conclusions: The workshop highlighted complexity of progression and transformation in CLL/SLL and B-PLL, as well as diagnostic caveats accompanying heterogeneous presentations of RT and other manifestations of disease progression. Molecular genetic studies are pivotal for diagnosis and determination of clonal relationship, and to predict response to treatment and identify resistance to targeted therapy.
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    Progression of follicular lymphoma and related entities: Report from the 2021 SH/EAHP Workshop
    (Oxford University Press, 2023-05-11) Duffield, Amy S.; Dogan, Ahmet; Amador, Catalina; Cook, James R.; Czader, Magdalena; Goodlad, John R.; Nejati, Reza; Xiao, Wenbin; Happ, Lanie; Parker, Clay; Thacker, Elizabeth; Thakkar, Devang; Dave, Sandeep S.; Wasik, Mariusz A.; Ott, German; Pathology and Laboratory Medicine, School of Medicine
    Objectives: The 2021 Society for Hematopathology and European Association for Haematopathology Workshop addressed the molecular and cytogenetic underpinnings of transformation and transdifferentiation in lymphoid neoplasms. Methods: Session 4, "Transformations of Follicular Lymphoma," and session 5, "Transformations of Other B-Cell Lymphomas," included 45 cases. Gene alteration analysis and expression profiling were performed on cases with submitted formalin-fixed, paraffin embedded tissue. Results: The findings from session 4 suggest that "diffuse large B-cell lymphoma/high-grade B-cell lymphoma with rearrangements of MYC and BCL2" is a distinct category arising from the constraints of a preexisting BCL2 translocation. TdT expression in aggressive B-cell lymphomas is associated with MYC rearrangements, immunophenotypic immaturity, and a dismal prognosis but must be differentiated from lymphoblastic -lymphoma. Cases in session 5 illustrated unusual morphologic and immunophenotypic patterns of transformation. Additionally, the findings support the role of cytogenetic abnormalities-specifically, MYC and NOTCH1 rearrangements-as well as single gene alterations, including TP53, in transformation. Conclusions: Together, these unique cases and their accompanying molecular and cytogenetic data suggest potential mechanisms for and unusual patterns of transformation in B-cell lymphomas and indicate numerous opportunities for further study.
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    The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Lymphoid Neoplasms
    (Springer Nature, 2022) Alaggio, Rita; Amador, Catalina; Anagnostopoulos, Ioannis; Attygalle, Ayoma D.; Araujo, Iguaracyra Barreto de Oliveira; Berti, Emilio; Bhagat, Govind; Borges, Anita Maria; Boyer, Daniel; Calaminici, Mariarita; Chadburn, Amy; Chan, John K. C.; Cheuk, Wah; Chng, Wee-Joo; Choi, John K.; Chuang, Shih-Sung; Coupland, Sarah E.; Czader, Magdalena; Dave, Sandeep S.; de Jong, Daphne; Du, Ming-Qing; Elenitoba-Johnson, Kojo S.; Ferry, Judith; Geyer, Julia; Gratzinger, Dita; Guitart, Joan; Gujral, Sumeet; Harris, Marian; Harrison, Christine J.; Hartmann, Sylvia; Hochhaus, Andreas; Jansen, Patty M.; Karube, Kennosuke; Kempf, Werner; Khoury, Joseph; Kimura, Hiroshi; Klapper, Wolfram; Kovach, Alexandra E.; Kumar, Shaji; Lazar, Alexander J.; Lazzi, Stefano; Leoncini, Lorenzo; Leung, Nelson; Leventaki, Vasiliki; Li, Xiao-Qiu; Lim, Megan S.; Liu, Wei-Ping; Louissai, Abnerm, Jr.; Marcogliese, Andrea; Medeiros, L. Jeffrey; Michal, Michael; Miranda, Roberto N.; Mitteldorf, Christina; Montes-Moreno, Santiago; Morice, William; Nardi, Valentina; Naresh, Kikkeri N.; Natkunam, Yasodha; Ng, Siok-Bian; Oschlies, Ilske; Ott, German; Parrens, Marie; Pulitzer, Melissa; Rajkumar, S. Vincent; Rawstron, Andrew C.; Rech, Karen; Rosenwald, Andreas; Said, Jonathan; Sarkozy, Clémentine; Sayed, Shahin; Saygin, Caner; Schuh, Anna; Sewell, William; Siebert, Reiner; Sohani, Aliyah R.; Tooze, Reuben; Traverse-Glehen, Alexandra; Vega, Francisco; Vergier, Beatrice; Wechalekar, Ashutosh D.; Wood, Brent; Xerri, Luc; Xiao, Wenbin; Pathology and Laboratory Medicine, School of Medicine
    We herein present an overview of the upcoming 5th edition of the World Health Organization Classification of Haematolymphoid Tumours focussing on lymphoid neoplasms. Myeloid and histiocytic neoplasms will be presented in a separate accompanying article. Besides listing the entities of the classification, we highlight and explain changes from the revised 4th edition. These include reorganization of entities by a hierarchical system as is adopted throughout the 5th edition of the WHO classification of tumours of all organ systems, modification of nomenclature for some entities, revision of diagnostic criteria or subtypes, deletion of certain entities, and introduction of new entities, as well as inclusion of tumour-like lesions, mesenchymal lesions specific to lymph node and spleen, and germline predisposition syndromes associated with the lymphoid neoplasms.