B Lymphoproliferative Neoplasms of Uncertain Biological Significance: Report from the IV Workshop of the Italian Group of Hematopathology and Review of the Literature
Gioia Di Stefano,
Francesca Magnoli,
Massimo Granai,
Federico Vittone,
Raffaella Santi,
Domenico Ferrara,
Emanuela Boveri,
Ada M. Florena,
Falko Fend,
Elena Sabattini,
Marco Paulli,
Maurilio Ponzoni,
Stefano Lazzi,
Stefano A. Pileri,
Lorenzo Leoncini,
the Italian Group of Hematopathology
Affiliations
Gioia Di Stefano
Pathology Section, Department of Health Sciences, University of Florence, 50100 Florence, Italy
Francesca Magnoli
Department of Pathology, University Hospital, 21100 Varese, Italy
Massimo Granai
Institute of Pathology and Neuropathology, Tübingen University Hospital and Comprehensive Cancer Center Tübingen-Stuttgart, 72070 Tübingen, Germany
Federico Vittone
Department of Pathology, Ivrea Hospital ASLTO4, Piazza Credenza 2, 10015 Ivrea, Italy
Raffaella Santi
Pathology Section, Department of Health Sciences, University of Florence, 50100 Florence, Italy
Domenico Ferrara
Section of Pathology, Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy
Emanuela Boveri
Department of Pathology, IRCCS Fondazione Policlinico San Matteo, 27100 Pavia, Italy
Ada M. Florena
Anatomic Pathology, Department of Sciences for the Promotion of Health and Mother and Child Care, University of Palermo, 90127 Palermo, Italy
Falko Fend
Institute of Pathology and Neuropathology, Tübingen University Hospital and Comprehensive Cancer Center Tübingen-Stuttgart, 72070 Tübingen, Germany
Elena Sabattini
Haematopathology Unit, Department of Experimental Diagnostic and Specialty Medicine, S. Orsola-Malpighi Hospital, University of Bologna, 40138 Bologna, Italy
Marco Paulli
Unit of Anatomic Pathology, Department of Molecular Medicine, Fondazione IRCCS Policlinico San Matteo and Università degli Studi di Pavia, 27100 Pavia, Italy
Maurilio Ponzoni
Faculty of Medicine, Vita-Salute San Raffaele University, 20100 Milan, Italy
Stefano Lazzi
Section of Pathology, Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy
Stefano A. Pileri
Division of Hematopathology, European Institute of Oncology, IRCCS, 20100 Milan, Italy
Lorenzo Leoncini
Section of Pathology, Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy
Lymphoproliferative neoplasms of uncertain biological significance are increasingly encountered due to widespread usage of immunophenotypic and molecular techniques. Considering that clearer biological criteria and patient management have been established for B-cell lymphoproliferative diseases of undetermined significance occurring in the peripheral blood, many issues are still obscure for early lesions detected in lymphoid tissues. Regardless that some categories of lymphoproliferative neoplasms of uncertain biological significance have been recognized by the 4th edition of the WHO, other anecdotal early lymphoproliferative lesions still remain fully undefined. Some early lesions frequently originate from the germinal center, including atypical germinal centers BCL2-negative, an early pattern of large B-cell lymphoma with IRF4 rearrangement, and “in situ” high-grade B lymphomas. Moreover, other early lymphoproliferative lesions arise outside the germinal center and include those developing within the setting of monocytoid B-cell hyperplasia, but they also can be directly or indirectly associated with chronic inflammations. This review aims to summarize the concepts discussed during the IV Workshop organized by the Italian Group of Hematopathology, focus on the state-of-the-art on B-cell lymphoproliferative neoplasms of uncertain biological significance, and offer operative insights to pathologists and clinicians in routine diagnostics.
