Genetic Characterization and Clinical Features of Helicobacter pylori Negative Gastric Mucosa-Associated Lymphoid Tissue Lymphoma

Background: In Western countries, the prevalence of gastric mucosa-associated lymphoid tissue (MALT) lymphoma has declined over the last three decades. Contemporaneously, H. pylori negative gastric MALT lymphoma is increasingly encountered, and their genetic basis and clinical features remain elusive. Methods: A total of 57 cases of H. pylori negative gastric MALT lymphoma were reviewed and investigated for chromosome translocation by fluorescence in-situ hybridization and for somatic mutations by the targeted sequencing of 93 genes. Results: MALT1 translocation, most likely t(11;18)(q21;q21)/BIRC3-MALT1, was detected in 39% (22/57) cases, and IGH translocation was further seen in 12 MALT1-negative cases, together accounting for 60% of the cohort. Targeted sequencing was successful in 35 cases, and showed frequent mutations in NF-κB signaling pathways (TNFAIP3 = 23%, CARD11 = 9%, MAP3K14 = 9%), together affecting 14 cases (40%). The NF-κB pathway mutations were mutually exclusive from MALT1, albeit not IGH translocation, altogether occurring in 86% of cases. There was no significant correlation between the genetic changes and clinicopathological parameters. The patients showed a median of progression-free survival (PFS) of 66.3 months, and a significant superior PFS when treated with systemic versus antibiotic therapy (p = 0.004). Conclusion: H. pylori negative gastric MALT lymphoma is characterized by highly frequent genetic changes in the NF-κB signaling pathways

Primary Large B-Cell Lymphoma of Immune-Privileged Sites of the Cerebellum: A Case Series and Review of the Literature

Primary large B-cell lymphoma of immune-privileged sites (IP-LBCL) is a rare malignant hematological neoplasm. Involvement of the cerebellum is even rarer and its diagnosis is often difficult to make due to its non-specific clinical and radiological presentation. Methods: We reported 3 cases of cerebellar IP-LBCL followed at our hospital and reviewed the medical literature to unravel the peculiarities of this poorly studied entity. Outcomes: Analyzing our cases and reviewing the literature, we could collect and study 26 cases of cerebellar IP-LBCL. To the best of our knowledge, this is the largest cohort of such patients currently published. Conclusion: Cerebellar IP-LBCL presents more often in adult females with cerebellum-related focal neurological signs such as ataxia, headache, and nausea. Histological confirmation is mandatory for a correct diagnosis and treatment and all cases feature diffuse large B-cell lymphoma histopathology. Compared to other encephalic IP-LBCL, cerebellar cases seem to include a higher number of cases with germinal center B-cell phenotype and better survival. These differences may be related to a different immune microenvironment and especially immunoregulation that distinguishes the cerebellum from other areas of the CNS

Small Bowel Carcinomas Associated with Immune-Mediated Intestinal Disorders: The Current Knowledge

Small bowel carcinomas (SBC) are uncommon neoplasms, whose predisposing conditions include hereditary syndromes and immune-mediated intestinal disorders including coeliac disease (CD) and Crohn’s disease (CrD). Although both CD-associated SBC (CD-SBC) and CrD-associated SBC (CrD-SBC) arise from an inflammatory background, they differ substantially in tumour cell phenotype, frequency of microsatellite instability and nuclear β-catenin expression, as well as in prognosis. For these patients, high tumour-infiltrating lymphocyte density and glandular/medullary histotype represent independent positive prognostic factors. Dysplasia adjacent to SBC is rare and characterized by intestinal phenotype and nuclear β-catenin in CD, while it is frequent and typified by gastro-pancreatobiliary marker expression and preserved membranous β-catenin in CrD. Recent evidence suggests that Epstein-Barr virus-positive dysplasia and SBC, albeit exceptional, do exist and are associated with CrD. In this review, we summarize the novel pathological and molecular insights of clinical and therapeutic interest to guide the care of CD-SBC and CrD-SBC

Case Report: A rare case of small bowel obstruction secondary to plasma cell myeloma

Gastrointestinal (GI) involvement of plasma cell neoplasms is extremely rare. Herein, we describe the case of a 74-year-old Caucasian woman who came to our attention with abdominal pain, food vomiting, and weight loss of 10 kg over 1 year. A computed tomography scan of the abdomen revealed circumferential thickening of terminal ileum, for which the patient underwent an urgent 20-cm-long ileal resection. Histopathological and immunophenotypic analysis revealed a plasma cell neoplasm of the ileum. Subsequent investigations found a serum monoclonal immunoglobulin A component, an osteolytic lesion of the left jaw, and a clonal bone marrow plasma cell infiltrate carrying 1q21 amplification. Given the final diagnosis of plasma cell myeloma (PCM), the patient underwent a VMD (bortezomib, melphalan, and dexamethasone) chemotherapy regimen, achieving a complete remission after a 12-month treatment. For disease relapse, two further chemotherapy regimens were later attempted. At the last follow-up 4 years after the diagnosis, the patient is still alive. This case draws attention to the extramedullary presentation of plasma cell neoplasms, even if rare, as a prompt diagnosis seems to result in a better prognosis. In addition, it highlights the relevance of a multidisciplinary approach, involving gastroenterologists, hematologists, and pathologists, to the diagnosis and management of these neoplasms

Double expressor and double/triple hit status among primary cutaneous diffuse large B cell lymphoma: A comparison between leg type and NOS Subtypes

none13Primary cutaneous diffuse large B-cell lymphomas (pcDLBCL) are rare hematological neoplasms. pcDLBCL category includes primary cutaneous large B-cell lymphoma "leg type" (pcDLBCL-LT), characterized by a particularly unfavorable outcome, and primary cutaneous large B-cell lymphoma "not otherwise specified" (pcDLBCL-NOS), a widely debated sub-entity with a more indolent course. The negative prognostic impact of double expressor status (DE status, given by coexpression of MYC and BCL2) and double/triple hit status (DH/TH status, given by translocations of MYC and BCL2 and/or BCL6) in nodal DLBCL is well-known; however, no unanimous conclusions regarding relevance of DE and DH/TH status have been reached in pcDLBCL. Therefore, our purpose has been to investigate the presence and prognostic relevance of DE and DH/TH status among a retrospective multicentric cohort of 16 pcDLBCL-LT and 17 pcDLBCL-NOS. All cases were thoroughly re-evaluated, both on a morphological and immunoistochemical level, and tested by means of fluorescence hybridization in situ for MYC, BCL2 and BCL6 rearrangements. DE status was observed in 69% of pcDLBCL-LT and in 24% of pcDLBCL-NOS; however, it did not impact on prognosis in any of the groups examined. Combining molecular results, we highlighted a relevant fraction of DH pcDLBCL (three pcDLBCL-LT and one pcDLBCL-NOS) and the very first case of TH pcDLBCL-LT reported to date. All DH cases were characterized by MYC and BCL6 rearrangements. Overall, DH/TH cases represented 15% (5/33) of all pcDLBCLs and were mostly pcDLBCL-LTs. DH/TH status and DH status alone were associated with poorer OS and DSS (both p<0,05) among all pcDLBCLs, without reaching statistical significance in pcDLBCL-LT and pcDLBCL-NOS groups. In conclusion, MYC, BCL2 and BCL6 cytogenetical testing could be useful in identifying a putative subset of more aggressive pcDLBCLs, although this observation has to be confirmed by further studies.noneLucioni, Marco; Pescia, Carlo; Bonometti, Arturo; Fraticelli, Sara; Moltrasio, Chiara; Ramponi, Antonio; Riboni, Roberta; Roccio, Stefano; Ferrario, Giuseppina; Arcaini, Luca; Goteri, Gaia; Berti, Emilio; Paulli, MarcoLucioni, Marco; Pescia, Carlo; Bonometti, Arturo; Fraticelli, Sara; Moltrasio, Chiara; Ramponi, Antonio; Riboni, Roberta; Roccio, Stefano; Ferrario, Giuseppina; Arcaini, Luca; Goteri, Gaia; Berti, Emilio; Paulli, Marc

Double expressor and double/triple hit status among primary cutaneous diffuse large B cell lymphoma: A comparison between leg type and NOS Subtypes

Primary cutaneous diffuse large B-cell lymphomas (pcDLBCL) are rare hematological neoplasms. pcDLBCL category includes primary cutaneous large B-cell lymphoma "leg type" (pcDLBCL-LT), characterized by a particularly unfavorable outcome, and primary cutaneous large B-cell lymphoma "not otherwise specified" (pcDLBCL-NOS), a widely debated sub-entity with a more indolent course. The negative prognostic impact of double expressor status (DE status, given by coexpression of MYC and BCL2) and double/triple hit status (DH/TH status, given by translocations of MYC and BCL2 and/or BCL6) in nodal DLBCL is well-known; however, no unanimous conclusions regarding relevance of DE and DH/TH status have been reached in pcDLBCL. Therefore, our purpose has been to investigate the presence and prognostic relevance of DE and DH/TH status among a retrospective multicentric cohort of 16 pcDLBCL-LT and 17 pcDLBCL-NOS. All cases were thoroughly re-evaluated, both on a morphological and immunoistochemical level, and tested by means of fluorescence hybridization in situ for MYC, BCL2 and BCL6 rearrangements. DE status was observed in 69% of pcDLBCL-LT and in 24% of pcDLBCL-NOS; however, it did not impact on prognosis in any of the groups examined. Combining molecular results, we highlighted a relevant fraction of DH pcDLBCL (three pcDLBCL-LT and one pcDLBCL-NOS) and the very first case of TH pcDLBCL-LT reported to date. All DH cases were characterized by MYC and BCL6 rearrangements. Overall, DH/TH cases represented 15% (5/33) of all pcDLBCLs and were mostly pcDLBCL-LTs. DH/TH status and DH status alone were associated with poorer OS and DSS (both p<0,05) among all pcDLBCLs, without reaching statistical significance in pcDLBCL-LT and pcDLBCL-NOS groups. In conclusion, MYC, BCL2 and BCL6 cytogenetical testing could be useful in identifying a putative subset of more aggressive pcDLBCLs, although this observation has to be confirmed by further studies