Splenic marginal zone lymphoma: from genetics to management

Abstract

Splenic marginal zone lymphoma (SMZL) is a rare B-cell malignancy involving the spleen, bone marrow, and frequently the blood. SMZL lymphomagenesis involves antigen and/or superantigen stimulation and molecular deregulation of genes (NOTCH2 and KLF2) involved in the physiological differentiation of spleen marginal zone B cells. Diagnosis requires either spleen histology or, alternatively, the documentation of a typical cell morphology and immunophenotype on blood cells coupled with the detection of intrasinusoidal infiltration by CD20+ cells in the bone marrow. Among B-cell tumors, deletion of 7q and NOTCH2 mutations are almost specific lesions of SMZL, thus representing promising diagnostic biomarkers of this lymphoma. Although the majority of SMZLs show an indolent course with a median survival of approximately 10 years, nearly 30% of patients experience a poor outcome. No randomized trials are reported for SMZL, and few prospective trials are available. A watch-and-wait approach is advisable for asymptomatic patients. Treatment options for symptomatic patients ranges from splenectomy to rituximab alone or combined with chemotherapy. In some geographic areas, a subset of patients with SMZL associates with hepatitis C virus infection, prompting virus eradication as an effective lymphoma treatment. It would be worthwhile to explore deregulated cellular programs of SMZL as therapeutic targets in the future; improved clinical and biological prognostication will be essential for identifying patients who may benefit from novel approaches.

Splenic marginal zone lymphoma: a literature review of diagnostic and therapeutic challenges

“…The overall age-adjusted incidence is 0.13/100,000 habitants per year. The percentage change in age-adjusted incidence is 4.81%, with most of the patients being White 8 . Gender prevalence is controversial,6, 7 but there is an increasing trend to male predominance 8, 10, 11…”

“…There are some clinical features associated with a worse outcome such as the development of lymphadenopathy, increase in β2-microglobulin, non-hematopoietic site involvement, leukocyte count >20 × 10 9 /L, lymphocytosis >9 × 10 9 /L, lymphopenia, anemia, thrombocytopenia, use of chemotherapy, monoclonal component, performance status ≥2, incomplete response, advanced age, diffuse pattern of bone marrow infiltration and histologic transformation 8, 10, 35, 36, 37, 38…”

“…As a rare disease with an indolent course, determining the standard treatment and management is a challenge as there have been no randomized trials and most reports are of single-center series of retrospective cases; few prospective trials have been completed or are ongoing 8 . Therefore, nowadays there is no standard care for SMZL.…”

“…Hyperviscosity syndromes are not usual, 3 but 20% of patients present autoimmune hemolytic anemia and other autoimmune disorders, such as thrombocytopenia, cold agglutinin disease, circulating anticoagulants and even angioedema because of acquired C1-esterase inhibitor deficiency 5, 7, 8…”

A 80-Year-Old Woman with B-Cell Prolymphocytic Leukemia

“…11 Peripheral blood atypical lymphocyte morphology consists of villous lymphocytes with basophilic cytoplasm. 11,12 Franco et al reported that bone marrow (BM) infiltration of the SMZL was mostly of the intrasinusoidal type and BM infiltration tended to become frankly nodular after splenoctomy. 13 On the other side, atypical neoplastic lymphocytes of our patient did not have villous projections.…”