Non-MALT marginal zone lymphoma

Abstract

SMZL and NMZL often present with disseminated disease at diagnosis, with specific clinical presentation, SMZL with predominant enlarged splenomegaly and NMZL with disseminated nodal involvement. Diagnosis may be difficult among the small B-cell lymphomas and criteria for diagnosis have been recently improved. The therapeutic approaches comprise splenectomy for SMZL, and immunochemotherapy for both of SMZL and NMZL, but with no consensus about the best treatment, except when associated with hepatitis C virus. This review addresses the current knowledge on the biological findings, clinical features and therapeutic approaches for the individual SMZLs and NMZLs.

Pathology of nodal marginal zone lymphomas

“…It is clear that this distinction, which almost completely relies on clinical/instrumental findings, may have several limitations, because it basically represents a diagnosis of exclusion [2]. Notwithstanding this bias, forms of marginal zone lymphomas limited to lymph node(s) do definitely exist.…”

The Genetics of Nodal Marginal Zone Lymphoma

“…Indeed, though NMZL is generally characterized by an indolent course, its prognosis is heterogeneous and considered less favorable than that of SMZL and EMZL. 4 The notion that NMZL share with SMZL mutations of NOTCH2 and KLF2, which are physiologically involved in the commitment of mature B cells to the marginal zone (MZ), 64,65 points to MZ differentiation as one of the major programs deregulated in MZL arising outside MALT. Although the genetic signatures of NMZL and SMZL largely overlap, the association of PTPRD mutations with NMZL, alongside the lack of 7q deletion in this lymphoma, 66 support the distinction of NMZL and SMZL as different entities rather than different clinical presentations of the same disease, and is consistent with their separation in the WHO Classification of hematopoietic tumors.…”

“…Conversely, the lack of typical markers, with the exception of IRTA1 expression in a fraction of NMZL, 2,3 and the absence of clear consensus criteria for diagnosis, make the pathologic classification of NMZL and SMZL difficult, laborious, and not easily reproducible. 4 NMZL and SMZL share similar morphology and phenotype and are distinguished solely by the different pattern of dissemination. SMZL involves the spleen without concomitant lymphoadenopathy, whereas NMZL is primarily a nodal B-cell tumor without clinical evidence of extranodal or splenic disease.…”

“…SMZL involves the spleen without concomitant lymphoadenopathy, whereas NMZL is primarily a nodal B-cell tumor without clinical evidence of extranodal or splenic disease. 1,4 In this context, understanding the biological bases of NMZL and SMZL may be helpful to: (1) generate disease-specific markers for differential diagnosis and for their correct identification, and (2) understand whether they represent a continuum of the same disease entity that home in different anatomical sites, or, alternatively, they should be kept as separate disorders. The genetics of SMZL has been clarified to a certain detail and is characterized by mutations of genes involved in the physiologic differentiation and homeostasis of MZ B cells.…”

Splenectomy prior to allogeneic hematopoietic SCT increases the risk of post-transplant lymphoproliferative disease

“…1,2 However, much is still unknown regarding the impact of splenectomy on the outcome of allo-SCT. Previous work has suggested an association between acute and chronic GVHD and splenectomy prior to allo-SCT.…”