Splenectomy allows remission of angioedema with acquired C1-INH deficiency associated with splenic marginal zone lymphoma.

Splenectomy may be considered as an alternative to rituximab in selected cases of acquired angioedema associated with splenic marginal zone lymphoma.

Clinicopathologic findings of splenic marginal zone lymphoma with gallbladder involvement that progressed to diffuse large B-cell lymphoma in a dog.

A 12-year-old spayed female Dalmatian presented with acute vomiting and anorexia. The clinicopathological and imaging abnormalities included icterus, biliary obstruction, and multiple diffuse splenic hypoechogenic nodules. Cholecystectomy was performed to remove the obstruction, followed by liver biopsy and splenectomy. Histopathological and immunohistology evaluation of the spleen, liver, and gallbladder revealed splenic marginal zone lymphoma (MZL) with gallbladder and hepatic infiltration of neoplastic CD20/CD79α-positive cells. Moreover, we observed clonal rearrangements of the immunoglobulin heavy-chain (IgH) gene in all three tissues. The dog was in good condition without chemotherapy. However, there was progressive elevation of liver enzymes, which could be attributed to neoplastic hepatic infiltration. Chlorambucil and prednisolone were administered until day 108, when the liver enzyme levels normalized. On day 156, the dog developed diffuse large B-cell lymphoma (DLBCL) of the peripheral lymph nodes. Sequence analysis of the clonally rearranged IgH gene revealed that all neoplastic cells in the spleen, gallbladder, and liver at initial presentation, as well as lymph nodes on day 156, possessed the same sequence identity of the amplified IgH fragments. This demonstrated that all neoplastic cells were derived from the same B-lymphocyte clone. The DLBCL was considered to have transformed from the splenic MZL, with gallbladder involvement. In cases of splenic MZL, it is important to consider gallbladder involvement and transformation to DLBCL. Moreover, gallbladder lymphoma should be included in the differential diagnosis of dogs with gallbladder abnormalities. Further studies are warranted to investigate the prognosis of splenic MZL.

Splenic Marginal Zone Lymphoma in a Patient With Antiphospholipid Syndrome Treated With Rituximab: A Case Report.

Splenic marginal zone lymphoma (SMZL) usually presents with splenomegaly or symptoms related to cytopenia. We report a case of a 56-year-old female with previously diagnosed antiphospholipid syndrome (APS) on warfarin therapy who initially presented with abdominal pain and was found to have massive splenomegaly and splenic infarction on CT imaging. Initial clinical presentations and imaging findings were attributed to the subtherapeutic coagulation profile. The patient was later diagnosed with SMZL following workup for pancytopenia including bone marrow biopsy, flow cytometry, and PET scan. Cytopenias, splenomegaly, and abnormal metabolic activity in the spleen on the PET scan improved after treatment with four cycles of weekly rituximab. Our report presents a case of a patient with longstanding APS presenting with splenic infarction and pancytopenia who was subsequently diagnosed with SMZL and successfully treated with rituximab.

Nodal Low-Grade B-Cell Lymphoma Co-Expressing CD5 and CD10 but Not CD23, IRTA1, or Cyclin D1: The Diagnostic Challenge of a Splenic Marginal Zone Lymphoma.

The diagnosis of lymphoma is based on histopathological and immunophenotypical features. CD5 and CD10 are traditionally considered a T-cell antigen and a germinal center B-cell antigen, respectively. It is very unusual for a low-grade B-cell lymphoma (BCL) to co-express CD5 and CD10. Although the biologic basis or clinical significance of such co-expression is unclear, this rare event may pose a significant diagnostic challenge. Here, we report a case of a 63-year-old male presenting with bilateral cervical lymphadenopathy and lymphocytosis. Histologically, the nodal tumor was largely diffuse with neoplastic small atypical lymphocytes co-expressing CD5, CD10, and CD20, but not CD23 or cyclin D1. The leukemic cells in the peripheral blood exhibited hairy projections. Taking together the marked splenomegaly, involvement of lymph nodes, bone marrow, and peripheral blood, a final diagnosis of splenic marginal zone lymphoma (SMZL) was reached. The patient was alive with partial response for 10 months after immunochemotherapy. The dual expression of CD5 and CD10 is extremely unusual for low-grade BCL and may lead to an erroneous diagnosis. Integrating the findings into peripheral blood smear tests, flow cytometry, histopathology, imaging, and clinical features is mandatory to exclude other lymphoma types and to reach a correct diagnosis, particularly for a case with nodal presentation.

Optical genomic mapping is a helpful tool for detecting CCND1 rearrangements in CD5-negative small B-cell lymphoma: Two cases of leukemic non-nodal mantle cell lymphoma.

Optical genome mapping (OGM) is a new DNA-based technology which provides comprehensive examination of the entire genome. We report two patients who presented with splenomegaly and leukocytosis with lymphocytosis including villous lymphocytes. Neither patient had lymphadenopathy. Bone marrow evaluation showed involvement by small B-cell lymphoma in a sinusoidal and interstitial distribution, and immunophenotypic analysis showed that the neoplastic cells were positive for B-cell markers and cyclin D1 but were negative for SOX11 and CD5. Initially, the clinicopathologic features in both patients were thought to be suspicious for hairy cell leukemia variant or splenic marginal zone lymphoma. However, OGM detected CCND1 rearrangement: t(2;11)/IGK::CCND1 in one case and t(11;14)/IGH::CCND1 in the other case. These cases illustrate the valuable role OGM can play in establishing the diagnosis of MCL. Case 1 also contributes to the paucity of literature on the rare occurrence of IGK::CCND1 in MCL.

Acquired Angioedema Associated with Lymphoproliferative Disorders.

Introduction: Acquired angioedema due to C1 esterase inhibitor deficiency (C1INH-AAE) is most associated with lymphoproliferative disorders (LPDs), particularly low-grade B-cell subtypes. The condition remains under-recognized with long diagnostic delays due to various challenges including a lack of awareness of the condition. Case Presentation: We discuss 4 cases of C1INH-AAE associated with low-grade B-cell LPDs, including various diagnostic and management challenges. As our cases illustrate, constitutional symptoms or overt manifestations of LPD at diagnosis are often absent. Hence, a comprehensive multimodal approach to screening for an underlying B-LPD is important when a diagnosis of acquired angioedema is made. Levels of complement C4, C1q, and C1INH are useful for diagnosing C1INH-AAE and for monitoring disease activity. Changes in these parameters may also indicate relapse of the underlying hematological malignancy. Treating the underlying disorder is important as this commonly leads to clinical improvement with decreased episodes of angioedema and normalization of complement studies. Conclusion: Awareness of C1INH-AAE can lead to an early diagnosis of hematological malignancies. The absence of constitutional symptoms emphasizes the need for a comprehensive multimodal approach to screening for LPD in C1INH-AAE. C4, C1INH level, and function are useful for monitoring disease activity.

Efficacy and Safety of Rituximab-Based Treatments in Angioedema With Acquired C1-Inhibitor Deficiency.

BACKGROUND: Angioedema (AE) due to acquired C1-inhibitor (C1-INH) deficiency (AAE-C1-INH) is related to excessive consumption of C1-INH or to anti-C1-INH antibodies, and is frequently associated with lymphoproliferative syndromes or monoclonal gammopathies. Standard of care for prophylactic treatment in this condition is not established. Rituximab may be effective to prevent attacks, especially if the lymphoid hemopathy is controlled, but data are scarce. OBJECTIVE: To evaluate efficacy of rituximab in AAE-C1-INH. METHODS: A retrospective multicenter study was carried out in France, including patients with AAE-C1-INH treated with rituximab between April 2005 and July 2019. RESULTS: Fifty-five patients with AAE-C1-INH were included in the study, and 23 of them had an anti-C1-INH antibody. A lymphoid malignancy was identified in 39 patients, and a monoclonal gammopathy in 9. There was no associated condition in 7 cases. Thirty patients received rituximab alone or in association with chemotherapy (n = 25). Among 51 patients with available follow-up, 34 patients were in clinical remission and 17 patients had active AE after a median follow-up of 3.9 years (interquartile range, 1.5-7.7). Three patients died. The presence of anti-C1-INH antibodies was associated with a lower probability of AE remission (hazard ratio, 0.29 [95% CI, 0.12-0.67]; P = .004). Relapse was less frequent in patients with lymphoma (risk ratio, 0.27 [95% CI, 0.09-0.80]; P = .019) and in patients treated with rituximab and chemotherapy (risk ratio, 0.31 [95% CI, 0.12-0.79]; P = .014). CONCLUSIONS: Rituximab is an efficient and well-tolerated therapeutic option in AE, especially in lymphoid malignancies and in the absence of detectable anti-C1-INH antibodies.

Optimal Rituximab Monotherapy in Splenic Marginal Zone Lymphoma (SMZL): A Case Report and Brief Review.

INTRODUCTION: Splenic marginal zone Lymphoma (SMZL) is a rare, chronic B lymphocyte proliferative disease. Generally, SMZL is accompanied by circulating atypical villous lymphocytes, known as SMZL with villous lymphocytes. Rituximab is a chimeric monoclonal antibody to CD20; recent but limited studies have confirmed its effectiveness in treating SMZL. Given the low incidence and selection of treatment, statistical comparisons of rituximab monotherapy with other available treatment options with the full range of data from previous clinical studies remain sparse. Here, we report a case of SMZL with villous lymphocytes treated by rituximab monotherapy, which is especially infrequently reported. CASE REPORT: A 63-year-old Chinese female was presented to the hospital with complaints of splenomegaly and pain in the spleen area. Immunohistochemistry analysis was positive for IGH, IGK, and IGL clonal rearrangement. Villous lymphocytes were found in peripheral blood and bone marrow, along with further immunotyping results. The case was considered as SMZL with villous lymphocytes. Based on the SMZLSG prognosis assessment, we applied rituximab monotherapy. After eight cycles of rituximab treatment, the patient's condition improved markedly, with blood constituent and size of the spleen returning to normal levels, achieving complete response, with no significant side effect observed. DISCUSSION: The patient provides a typical SMZL with villous lymphocytes case treated with rituximab monotherapy. Currently, the main treatment options include splenectomy and rituximab. After synthesizing a series of current views, we put forward our opinion about the selection of therapy for SMZL patients in order to gain maximum benefits for patients in need of treatment. CONCLUSION: Our analysis found no statistically significant difference between rituximab monotherapy and rituximab combined with chemotherapy, while rituximab treatments resulted in better therapeutic effects than chemotherapy. Rituximab monotherapy has favorable therapeutic effects and minor adverse effects (AEs) in treating SMZL.

The many faces of nodal and splenic marginal zone lymphomas. A report of the 2022 EA4HP/SH lymphoma workshop.

Session 3 of the lymphoma workshop of the XXI joint meeting of the European Association for Haematopathology and the Society for Hematopathology took place in Florence, Italy, on September 22, 2022. The topics of this session were splenic and nodal marginal zone lymphomas, transformation in marginal zone lymphomas, and pediatric nodal marginal zone lymphomas and their differential diagnosis as well as related entities. Forty-two cases in these categories were submitted to the workshop, including splenic lymphomas (marginal zone and diffuse red pulp lymphomas), transformed marginal zone lymphomas (splenic and nodal), nodal marginal zone lymphomas with increased TFH-cells, and pediatric nodal marginal zone lymphomas. The case review highlighted some of the principal problems in the diagnosis of marginal zone lymphomas, including the difficulties in the distinction between splenic marginal zone lymphoma, splenic diffuse red pulp lymphoma, and hairy cell leukemia variant/splenic B-cell lymphoma with prominent nucleoli which requires integration of clinical features, immunophenotype, and morphology in blood, bone marrow, and spleen; cases of marginal zone lymphoma with markedly increased TFH-cells, simulating a T-cell lymphoma, where molecular studies (clonality and mutation detection) can help to establish the final diagnosis; the criteria for transformation of marginal zone lymphomas, which are still unclear and might require the integration of morphological and molecular data; the concept of an overlapping spectrum between pediatric nodal marginal zone lymphoma and pediatric-type follicular lymphoma; and the distinction between pediatric nodal marginal zone lymphoma and "atypical" marginal zone hyperplasia, where molecular studies are mandatory to correctly classify cases.

Impending splenic rupture as indicator of atypical chronic lymphocytic leukemia: A case report from Saudi Arabia.

BACKGROUND: Chronic lymphocytic leukemia (CLL) is one of the hematological malignancies in which the bone marrow overproduces mature, dysfunctional lymphocytes. Affected lymphocytic cells can affect the lymph nodes, spleen, liver, bone marrow, and rarely other organs. Spontaneous rupture of the spleen is a rare health condition, with a few cases caused by CLL. Since the preliminary presentation of either impending or real splenic rupture is unusual and requires recording and reporting, this case report was developed. CASE REPORT: A 55-year-old male patient presented with a significant weight loss of 20 kg, loss of appetite, fatigue, abdominal pain, and early satiety. Clinical examination revealed massive splenomegaly 22 cm below the costal margin, otherwise unremarkable on systemic examination. The size and dimensions of the spleen were confirmed by computed tomography of the body. The patient underwent a bone marrow biopsy, which was suggestive of atypical CLL. Due to the rapid progression of the size of the spleen and the pattern of impending rupture of the spleen, an emergency splenectomy was performed, and the histopathological report confirmed low-grade B-cell non-Hodgkin's lymphoma, mostly typical of CLL. CONCLUSION: Given the rarity of cases, continuous data recording and reporting is required to enrich the scientific literature and share experiences from case to case. This will create a complete picture of this health condition across diverse regions and countries.

Splenic marginal zone lymphoma in Sweden 2000-2020: Increasing rituximab use and better survival in the elderly.

The treatment of splenic marginal zone lymphoma is debated: splenectomy (the old standard-of-care) is better than chemotherapy but maybe not better than rituximab-containing treatment. We examined all 358 patients diagnosed with splenic marginal zone lymphoma in Sweden 2000-2020. The median overall survival was 11.0 years. The median age was 73 years; 61% were women. Age was the only independently prognostic clinical characteristic. Eighty-six patients were started on wait-and-watch, 90 rituximab monotherapy, 47 rituximab-chemotherapy, 88 splenectomy, 37 chemotherapy, and 10 both systemic therapy and splenectomy. Overall survival was inferior in patients treated with chemotherapy, but equal in patients treated with rituximab, rituximab-chemotherapy and splenectomy. Patients treated with both systemic therapy and splenectomy showed good outcome, suggesting that surgery can be safely reserved for nonresponders. After adjustment for age, survival did not differ between patients started on wait-and-watch and those treated with splenectomy or rituximab-containing therapy. Over time, rituximab use and survival increased in patients ≥73 years. This is, to our knowledge, the largest population-based study of splenic marginal zone lymphoma patients treated with upfront rituximab. We conclude that wait-and-watch remains the most reasonable option in asymptomatic splenic marginal zone lymphoma patients. Symptomatic patients should be offered single-agent rituximab in first line.

Low-risk HPLLs/ABC score patients with splenic marginal zone lymphoma can be safely managed without treatment: Results from a prospective Spanish study.

The aims of our study were to analyse compliance with the 2014 GELTAMO SMZL Guidelines, in patients with splenic marginal zone lymphoma (SMZL), and to evaluate the outcome according to the HPLLs/ABC-adapted therapeutic strategy. Observational prospective multicenter study of 181 SMZL patients diagnosed between 2014 and 2020. Lymphoma-specific survival (LSS), composite event-free survival (CEFS) and response rates were assessed. 57% of the 168 patients included in the analysis followed the Guidelines. The overall response rate was higher in the rituximab chemotherapy and in the rituximab arms compared with the splenectomy arm (p < 0.001). The 5-year overall survival was 77% and the 5-year LSS of 93%. There were no differences in the 5-year LSS according to the treatment received (p = 0.68). The 5-year CEFS in the overall series was 45%, and there were significant differences between scores A and B (p = 0.036). There were no significant differences when comparing LSS and progression-free survival in patients treated with rituximab or rituximab chemotherapy at diagnosis or after observation. Our data support HPLLs/ABC score as a practical tool for the management of SMZL, observation as the best approach for patients in group A and rituximab as the best treatment for group B.

Concurrent Splenic Marginal Zone B Cell Lymphoma and Metastatic Pancreatic Adenocarcinoma Diagnosed on Splenectomy for Suspected Splenic Abscess.

Splenic marginal zone lymphoma (SMZL) is an uncommon low-grade B-cell lymphoma. It is an indolent lymphoma with a median survival rate of greater than 10 years. Most patients are asymptomatic, but some patients may present with upper abdominal pain and distention, while others may present with splenomegaly, emaciation, fatigue, or weight loss. Due to the long median survival, patients with SMZL may develop a second primary malignancy. Pancreatic adenocarcinoma is the most common malignant neoplasm of the pancreas. It has a poor prognosis with a five-year survival rate of 10%. Fifty percent of patients have metastatic disease on presentation. However, the spleen is not a common site of metastasis for malignant tumors from other primary sites including the pancreas. Here we present a case of a 78-year-old African American patient, who was found to have previously undiagnosed, concurrent metastatic pancreatic adenocarcinoma and SMZL diagnosed on splenectomy for a suspected splenic abscess.

The role of splenectomy in management of splenic B-cell lymphomas.

INTRODUCTION: Splenic B-cell lymphomas are rare and understudied entities. Splenectomy is frequently required for specific pathological diagnosis in patients with splenic B-cell lymphomas other than classical hairy cell leukemia (cHCL), and can be effective and durable therapy. Our study investigated the diagnostic and therapeutic role of splenectomy for non-cHCL indolent splenic B-cell lymphomas. METHODS: Observational study of patients with non-cHCL splenic B-cell lymphoma undergoing splenectomy between 1 August 2011 and 1 August 2021 at the University of Rochester Medical Center. The comparison cohort was patients categorized as having non-cHCL splenic B-cell lymphoma who did not undergo splenectomy. RESULTS: Forty-nine patients (median age 68 years) had splenectomy (SMZL n = 33, HCLv n = 9, SDRPL n = 7) with median follow up of 3.9 years post splenectomy. One patient had fatal post-operative complications. Post-operative hospitalization was ≤ 4 days for 61% and ≤ 10 days for 94% of patients. Splenectomy was initial therapy for 30 patients. Of the 19 patients who had previous medical therapy, splenectomy changed their lymphoma diagnosis in 5 (26%). Twenty-one patients without splenectomy were clinically categorized as having non-cHCL splenic B-cell lymphoma. Nine required medical treatment for progressive lymphoma and of these 3 (33%) required re-treatment for lymphoma progression compared to 16% of patients following first line splenectomy. CONCLUSION: Splenectomy is useful for the diagnosis of non-cHCL splenic B-cell lymphomas with comparable risk/benefit profile and remission duration to medical therapy. Patients with suspected non-cHCL splenic lymphomas should be considered for referral to a high-volume center with experience in performing splenectomies for definitive diagnosis and treatment.

Transformed Plasmablastic Lymphoma Presenting With Marked Lymphocytosis and Spontaneous Tumor Lysis Syndrome.

The clinicopathology entity of plasmablastic lymphoma (PBL), despite broad recognition by the World Health Organization (WHO), represents a diagnostic challenge due to its overlapping features and scarce occurrence. Often, PBL arises in immunodeficient, elderly male patients, most notably those who are human immunodeficiency virus (HIV)-positive. More infrequent, cases of transformed PBL (tPBL) evolved from another hematologic disease have been identified. Herein, we describe a case of a 65-year-old male transferred from a neighboring hospital with pronounced lymphocytosis and spontaneous tumor lysis syndrome (sTLS) presumed to be chronic lymphocytic leukemia (CLL). Utilizing a complete clinical, morphologic, immunophenotypic, and molecular evaluation, we arrived at a final diagnosis of tPBL with sTLS, suspected to have evolved from the NF-κB/NOTCH/KLF2 (NNK) genetic cluster of splenic marginal zone lymphoma (SMZL) (NNK-SMZL), a potential transformation and presentation, to our knowledge, not previously reported. However, definitive clonality testing was not performed. In this report, we also outline the diagnostic and educational considerations we faced in discerning tPBL from other more common B-cell malignancies which can present similarly, such as CLL, mantle cell lymphoma, or plasmablastic myeloma. We summarize recently reported molecular, prognostic, and therapeutic considerations for the treatment and recognition of PBL, including the successful implementation, in our patient, of bortezomib to an EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) regimen with prophylactic intrathecal methotrexate, who has since achieved complete remission (CR) and entered clinical surveillance. Lastly, this report briefly highlights the challenge we faced in this area of hematologic typification that necessitates additional review and discussion by the WHO: tPBL with potential double-hit cytogenetic versus double-hit lymphoma with a plasmablastic phenotype.

Incidental Splenic Marginal Zone Lymphoma With Extreme Macrocytosis After Hydroxyurea Use: A Case Report.

Splenic marginal zone lymphoma (SMZL) is a low-grade mature B-cell lymphoma that typically presents in the form of splenomegaly and lymphocytosis. The diagnosis is traditionally made through splenic histology, the presence of circulating villous lymphocytes, or bone marrow biopsy. Its treatment can be in the form of chemotherapy, such as rituximab, or active surveillance. This case presentation discusses a 76-year-old female with a long history of hydroxyurea use for an unknown reason presenting with atypical symptoms requiring bone marrow biopsy to diagnose SMZL. This unique case demonstrates the importance of further research and studies into atypical SMZL presentations and hydroxyurea's potential in precipitating secondary malignancies.

Rituximab-induced severe acute thrombocytopenia in a patient with splenic marginal zone lymphoma.

INTRODUCTION: Rituximab, which is widely used in the treatment of B-cell lymphoma, is a chimeric monoclonal antibody directed against the CD20 antigen. Rituximab has many side effects, mainly allergic and neurological. Rituximab may cause thrombocytopenia in the long term after administration. Rare cases of rituximab-induced acute thrombocytopenia have been reported in the literature. CASE REPORT: A 51-year-old female patient who was newly diagnosed with splenic marginal zone lymphoma received rituximab as first-line therapy. Petechiae occurred in the lower extremities on the day following rituximab administration. The blood test showed a severe drop in the platelet count from 112,000/µL to 5000/µL. Blood peripheral smear evaluation confirmed severe thrombocytopenia. MANAGEMENT AND OUTCOME: There was no change in hemoglobin or white blood cell levels. After the diagnosis of rituximab-induced acute thrombocytopenia, thrombocyte suspension was administered due to the risk of bleeding. Close clinical and laboratory observations were made. The platelet count began to rise gradually in the following period. Before the second week of rituximab administration, the platelet count was 122,000/µL. No complications developed after premedication and slow rituximab administration, and subsequent treatments were continued in the same way. DISCUSSION: Rituximab has widespread use, especially in malignancies and autoimmune diseases. Like many monoclonal antibodies, rituximab has several side effects. Thrombocytopenia is a long-term side effect associated with rituximab, and rituximab-induced severe acute thrombocytopenia has been rarely reported. Therefore, it should be kept in mind that severe acute thrombocytopenia may develop after rituximab administration.

[Warm autoimmune hemolytic anemia and IgM-monoclonal gammopathy following BNT162b2 COVID-19 vaccine in a patient with splenic marginal zone lymphoma].

There is currently no evidence that a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine might be associated with the development of autoimmune hemolytic anemia or disease progression in patients with mature B-cell neoplasm. Our patient was a 71-year-old man with indolent mature B-cell neoplasm who had been monitored for many years without treatment. After receiving the second dose of the BNT162b2 mRNA COVID-19 vaccine, he developed severe warm autoimmune hemolytic anemia. Although steroid therapy improved his anemia, he continued to develop IgM-monoclonal gammopathy, renal insufficiency, and splenomegaly. He was diagnosed with splenic marginal zone lymphoma after undergoing splenectomy. The splenectomy improved the patient's symptoms. We assessed his SARS-CoV-2 specific antibody response, but the patient's serologic response to the vaccine was impaired. In patients with mature B-cell neoplasm, a non-specific immune response after vaccination might be associated with paraneoplastic syndromes.

Extranodal localization of non-Hodgkin's lymphoma in systemic sclerosis: A diagnostic challenge and review of the literature.

Background: Systemic sclerosis is associated with an increased incidence of malignancies, in particular solid neoplasms. Hematological cancers have been also observed in autoimmune diseases, though rarely present with lung involvement. The latter may be misdiagnosed in systemic sclerosis patients, due to the frequent concomitant interstitial lung disease. Case description: Here, we present the case of a 63-year-old man affected by systemic sclerosis presenting with an atypical lung imaging and splenomegaly, who was diagnosed with splenic marginal zone lymphoma, thus raising the suspicion of lung secondarism. We discuss the diagnostic challenge of differential diagnosis in interstitial lung presentation and briefly review the available literature on this topic. Conclusion: Several reports have demonstrated an increased risk of malignancy in patients with systemic sclerosis. Still, the lack of concretely defined guidelines for systemic sclerosis, along with systemic sclerosis multifaceted organ involvement at presentation, may challenge diagnosis and management. Here, we remark the importance of clinical work-up and a multidisciplinary approach in systemic sclerosis, to early detect and treat concomitant hematological malignancies, especially during the first years of the disease.

Refractory Splenic Marginal Zone Lymphoma Responsive to Combination Venetoclax and Bortezomib (Velcade) (V2) Therapy.

Standard treatment regimens for the management of patients with refractory splenic marginal zone lymphoma (SMZL) are currently unavailable. Here, we report a case of SMZL, which, after failing multiple therapeutics, demonstrated an impressive clinical response to combined Venetoclax and Velcade (V2), a treatment combination currently being investigated in the setting of refractory multiple myeloma. We also report a unique histopathology and mutational profile that may have important implications for the characterization and prognosis of SMZL.