a proton-pump inhitor + bismuth subcitrate + tetracycline + metronidazole). Much lower detection rates are reported in the United Kingdom and Southern China while there has been little or no evidence of this organism in cases from the United States and Japan. [14] Indications that gastric Helicobactor pylori is the causes for gastric EMZL include: a positive urea breath test; a positive stool test that detects an antigen of the pathogen in the patient's feces; a positive urease test in a biopsied tissue specimen; a positive serum or whole blood test using specific antibodies directed against the pathogen; and growth of the pathogen in tissue cultures of a biopsied tissue. The diagnosis of Helicobacter heilmannii sensu lato therefore depends upon detecting the organism in tissues or fecal material histologically using special silver staining methods and then sequencing certain genes (i.e. No trial with novel agents was specifically dedicated to SMZL, although some data about activity in MZL of different histology can be derived from published studies conducted in indolent NHL (Table 5).101-104. Bronchoalveolar lavage fluid may contain >10% of cells which bear these markers. Epithelioid-like histiocytes may be found in the red pulp. [34] Patients with conjunctiva disease may be asymptomatic. The first description of SMZL by Schmid et al16  relied on the recognition of a histologic pattern recapitulating the marginal zone (MZ), as observed in the splenic white pulp. Bruton tyrosine kinase inhibitor ibrutinib (PCI-32765) has significant activity in patients with relapsed/refractory B-cell malignancies. Survival of patients with marginal zone lymphoma: analysis of the Surveillance, Epidemiology, and End Results database. 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. The clinical scores are neither 100% sensitive nor 100% specific in identifying high-risk patients. 1999 ; 17 (12) : 3835-3849. eyelid drooping) (6%) and/or, less commonly, diplopia (i.e. [7][9] These EMZLs are classified into subtypes based on the organ(s) involved. Approximately 20% of patients show an autoimmune manifestation,1  including autoimmune hemolytic anemia, immune thrombocytopenia, cold agglutinin disease, circulating anticoagulants, acquired von Willebrand disease, or angioedema as a result of acquired C1-esterase inhibitor deficiency.2,3. [40] While the disease almost always has a highly indolent course, it is subject to repeated relapses that are usually limited to the skin. CD5 expression identifies a subset of splenic marginal zone lymphomas with higher lymphocytosis: a clinico-pathological, cytogenetic and molecular study of 24 cases. Patients refractory to antibiotic therapy have been treated with chemotherapy (i.e. The notion that the most frequently mutated genes in SMZL (ie, nuclear factor κB [NF-κB] signaling genes, NOTCH2 and other NOTCH pathway genes, and KLF2) are physiologically involved in proliferation and commitment of mature B cells to the MZ points to homing to the spleen compartment and MZ differentiation as the major programs deregulated in this lymphoma. Search for other works by this author on: Treatment of splenic marginal zone B-cell lymphoma: an analysis of 81 patients. The combination of rituximab with bendamustine (BR) is effective in indolent NHL, although it has never been tested in a dedicated trial of SMZL.97,98  In the Bright study,97  the overall response rate to BR was 92% in 25 patients with MZL. Molecular aspects of SMZL (ie, Ig gene mutation status, NOTCH2 and KLF2 mutations, TP53 abnormalities, and aberrant promoter methylation) represent promising prognostic biomarkers associated with inferior outcome,32,38,43,45  and their incorporation into the currently available clinical prognostic models might improve risk stratification of patients. A watch-and-wait approach is advisable for asymptomatic patients. [7], Primary pulmonary EMZL (or primary pulmonary MALT lymphoma) is a rare disorder but nonetheless represents up to 80% of all lymphomas originating in the lung. [63][67][65] The genomic abnormalities thought to contribute to this malignant transformation include: Overall, mutations in the NOTCH, NF-κB, and KLF2 signaling pathways appear particularly important in the pathogenesis of SMZL. This course is recommended for the ~33% of SMZL patients who present with asymptomatic, non-progressive, or slowly progressive disease. Lymphoma cells may involve the red pulp in patchy or diffuse fashion, with subsequent spread to the sinuses. Marginal zone B-cell lymphomas, also known as marginal zone lymphomas (MZLs), are a heterogeneous group of lymphomas that derive from the malignant transformation of marginal zone B-cells. [61], Splenic marginal zone lymphoma (SMZL) is a low grade lymphoma in which malignant B-cells accumulate in the spleen, bone marrow, and, less commonly, the circulation. Splenic lymphoma with villous lymphocytes: clinical presentation, biology and prognostic factors in a series of 100 patients. [73] Of the >60 published cases, 95% of Pediatric NMZL cases occurred in adolescent boys with >90% of cases presenting as an asymptomatic, localized (Stage I/II) disease involving enlargement of the lymph nodes of the head and neck regions. A case report. Proliferation index (Mib-1/Ki-67) is low (usually <5%) and depicts a distinctive targetoid picture (Figure 1). While both terms are used here for these subtypes, the primary (organ involved) EMZL is preferred to indicate that the EMZL subtype initially developed in and may remain limited to the indicated tissue. However, approximately 30% of cases disseminate to other sites, predominantly lymph nodes and in rare cases the bone marrow. Some 20% of cases present with or progress to involve local lymph nodes or the spleen to cause lymphadenopathy or splenomegaly while ~10% of cases present with or progress to a high-grade lymphoma, primarily diffuse large B-cell lymphoma. While usually a component of Sjorgen syndrome, these histological finding can also occur in patients without evidence of this syndrome. Immunoglobulin heavy- and light-chain repertoire in splenic marginal zone lymphoma. This treatment regimen has achieved 5 year overall survival rates of 70%. Splenic lymphoma with villous lymphocytes, associated with type II cryoglobulinemia and HCV infection: a new entity? Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. The American journal of pathology. Long-term maintenance therapy with rituximab appears to improve these results and patients who relapse after rituximab therapy commonly respond to a second course of the drug. Medium-size monocytoid B cells are organized into a pale ring around the follicle with a MZ pattern, whereas small centrocyte-like cells efface the mantle zone and colonize the germinal centers (Figure 1). weight loss, malnutrition, and anemia), small bowel obstruction, ascites (i.e. All of these findings contrast with those seen in extranodal marginal zone lymphomas occurring in children. Cytogenetic aberrations and their prognostic value in a series of 330 splenic marginal zone B-cell lymphomas: a multicenter study of the Splenic B-Cell Lymphoma Group. Systematic antibiotic-based eradication therapy to treat Helicobactor pylori-associated EMZL of the esophagus had not been reported[31] until a recent case with the disease was treated with vonoprazan + amoxicillin + clarithromycin for 1 week. [44] Patients with extensive disease or disease that has progressed to a higher grade lymphoma (principally diffuse B-cell lymphoma) have been treated with chemotherapy (usually CHOP[44][45]) and/or immunotherapy (i.e. Groupe Francais d’Hématologie Cellulaire (GFHC). It runs an indolent course. Hilar lymph nodes are frequently involved, displaying a nodular proliferation with obliteration of the reactive germinal centers and engulfment of the sinuses. High-throughput sequencing analysis of the chromosome 7q32 deletion reveals IRF5 as a potential tumour suppressor in splenic marginal-zone lymphoma. Numerous factors appear involved in the development of EMZL. Cancer research. Less commonly, patients presented with paresthesias (i.e. The most common presenting symptoms were headache (30 cases); seizures (22 cases); and visual changes (19 cases). [71], Recommended treatments for NMZL depend on the diseases state. Accordingly, in a large series from Italy,4  HCV serology was positive in 19% of the patients with more frequent presence of nodal disease, cryoglobulinemia, and serum monoclonal component. 1997 ; 57 (18) : 3944-3948. [22] These lesions localizes to the duodenum, jejunum, or ilium in about 63, 17, and 8% of cases, respectively, or involve more than one small intestinal site in ~17% of cases. The lack of these abnormalities may help distinguish SMZL from pathologically mimicking tumors. In other words, it slows the growth of B-cells. [66] Patients with SMZL may also present with signs and symptoms of acquired von Willebrand disease, angioedema due to C1-esterase inhibitor deficiency,[64] or hepatitis C virus infection (e.g. abnormal skin sensations), motor deficits, and ataxias, memory failures, and dizziness. [73] It therefore appears that the postulated role of chronic immune stimulation in promoting extranodal and splenic marginal zone lymphomas has not been clearly demonstrated in and may not apply to NMZL: the underlying initiating cause for developing this disease is currently unclear. Endoscopic examination reveals a rectal polyp, rectal mass, or, less commonly, a rectal ulcer. PET/CT), Magnetic resonance imaging (i.e. Rather, its diagnosis has rested exclusively on examination of surgically-removed gallbladders.