Immunodeficiency-associated lymphoproliferative disorders: time for reappraisal?

Abstract

Immunodeficiency-associated lymphoproliferative disorders (IA-LPDs) are pathologically and clinically heterogeneous. In many instances, similar features are shared by a spectrum of IA-LPDs in clinically diverse settings. However, the World Health Organization (WHO) classifies IA-LPDs by their immunodeficiency setting largely according to the paradigm of posttransplant lymphoproliferative disorders but with inconsistent terminology and disease definitions. The field currently lacks standardization and would greatly benefit from thinking across immunodeficiency categories by adopting a common working vocabulary to better understand these disorders and guide clinical management. We propose a 3-part unifying nomenclature that includes the name of the lesion, associated virus, and the specific immunodeficiency setting for all IA-LPDs. B-cell lymphoproliferative disorders (LPDs) are usually Epstein-Barr virus (EBV)+ and show a spectrum of lesions, including hyperplasias, polymorphic LPDs, aggressive lymphomas, and, rarely, indolent lymphomas. Human herpes virus 8–associated LPDs also include polyclonal and monoclonal proliferations. EBV− B-cell LPDs and T- and NK-cell LPDs are rare and less well characterized. Recognition of any immunodeficiency is important because it impacts the choice of treatment options. There is an urgent need for reappraisal of IA-LPDs because a common framework will facilitate meaningful biological insights and pave the way for future work in the field.

Signaling pathways involved in the T‐cell‐mediated immunity against Epstein‐Barr virus: Lessons from genetic diseases

“…Persistence of EBV in a few B cells (and perhaps even a few epithelial cells) may cause cancer ‐ even in immunocompetent individuals . Seven forms of cancer have been linked to EBV: Hodgkin's lymphoma, diffuse large B cell lymphoma (DLBCL), Burkitt's lymphoma, T/NK lymphomas, smooth muscle carcinoma, nasopharyngeal carcinoma, and gastric carcinoma . It is estimated that worldwide, more than 2 00 000 cases of EBV‐associated cancer occur each year.…”

Novel mutation in the CD27 gene in a patient presenting with hypogammaglobulinemia, bronchiectasis and EBV-driven lymphoproliferative disease

“…In an immunocompromised individual, it may lead to chronic active EBV infection characterised by prolonged symptomatic phase of more than 6 months with fever, lymphadenopathy (LAP), hepatosplenomegaly and other atypical features like hepatitis, pneumonia or uveitis 4. Persistent EBV viremia leads to the various lymphoproliferative complications, including B-cell hyperplasia, polymorphic B-cell lymphoproliferative disorders (LPDs), indolent B-cell lymphomas, aggressive B-cell lymphomas and classic Hodgkin lymphoma (HL) like proliferations 5 6. Several other immune deficiency syndromes are known to be at high risk of developing EBV-associated LPD and these include SH2D1A/SLAM associated protein deficiency also known as X linked lymphoproliferative syndrome type 1, X linked inhibitor of apoptosis protein or X linked lymphoproliferative syndrome type 2, interleukin 2 inducible T cell kinase deficiency, magnesium transporter 1 deficiency, CD70 deficiency, cytidine triphosphate synthase deficiency and coronin 1 deficiency, all of which are genes that are involved in controlling EBV infection 4 7…”

Post-transplant indolent T cell lymphoproliferative disorder in living donor liver transplantation: a case report

“…However, persistent indolent T cell LPD over a long term (4.6-25 years) has been reported [18]. Importantly, in cases of posttransplantation and in immunodeficient states, indolent T cell LPD as a PTLD has been rarely reported [19]. To our best knowledge, our case is the second report of indolent T cell LPD of the GI tract after solid organ transplantation [20].…”