Primary MALT lymphoma of the breast: pathological and radiological characteristics.

PURPOSE: Primary Mucosa-associated lymphoid tissue (MALT) lymphoma is a rare diagnosis in the breast, and clinical diagnosis based on radiological features is often challenging. This study aimed to evaluate the clinicopathological, and radiological characteristics of the patients diagnosed with primary breast MALT lymphoma. METHODS: This study examined 18 cases of primary MALT lymphoma of the breast diagnosed at a single tertiary center between January 2002 to December 2020. Medical charts, radiological imaging and original pathology slides were reviewed for each case. RESULTS: All cases were female (gender assigned at birth) and presented with a palpable mass or an incidental imaging finding. Imaging presentation ranged from mammographic asymmetries, circumscribed masses, and ultrasound masses lacking suspicious features. Seventeen cases were biopsied under ultrasound; one received a diagnostic excision biopsy. Microscopic examination of the breast specimens demonstrated atypical small lymphocyte infiltration with plasmacytoid differentiation and rare lymphoepithelial lesions. Immunohistochemistry was performed in all cases and established the diagnosis. Most patients were treated with radiotherapy, and only three were treated with chemotherapy. The median follow-up period was 4 years and 7.5 months, and all patients were alive at the last follow-up. CONCLUSION: Primary MALT breast lymphomas are usually indolent and non-systemic, and local radiotherapy may effectively alleviate local symptoms. Radiological findings show overlap with benign morphological features, which can delay the diagnosis of this unusual etiology. Although further studies involving a larger cohort could help establish the clinical and radiological characteristics of primary breast MALT lymphomas, pathology remains the primary method of diagnosis. TRIAL REGISTRATION NUMBER: University Health Network Ethics Committee (CAPCR/UHN REB number 19-5844), retrospectively registered.

Efficacy and Safety of Frontline Single-Agent Rituximab in Extranodal Marginal Zone Lymphoma.

First-line therapy for patients with extranodal marginal zone lymphoma (EMZL) is not well established, except for eradication therapy for Helicobacter pylori in early gastric MZL. Various regimens, for example, locoregional treatment and systemic chemo-immunotherapy, can be used depending on the site and stage of disease. Single-agent rituximab is a useful approach in the setting of localized, low-intermediate risk EMZL. The aim our research was to analyze the effectiveness and safety of single-agent rituximab (375 mg/m2 once weekly for 4 weeks) in naïve EMZL in a real-life setting. The primary endpoint was the overall response rate (ORR), secondary endpoints were progression-free (PFS), overall (OS) and disease-free survivals (DFS), and drug tolerability. Fifty-nine patients were analyzed. Median time between diagnosis and rituximab was 3.6 months. The ORR was 89.9%, with 67.8% complete response (CR). Median DFS and PFS were reached at 6.3 and 5.3 years, respectively. After a median follow-up of 5 years, median OS was not reached. The most common adverse event was infusion reaction, reported in 28 cases, mainly during the first infusion and easily manageable. Single-agent rituximab may represent a valid therapeutic option in the first-line treatment of EMZL, at least for localized disease, with a favorable toxicity profile.

An Unusual Case of Extranodal Marginal Zone Lymphoma Mimicking Abdominal Cocoon Syndrome in an Adolescent Patient.

Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) is an indolent non-Hodgkin lymphoma rarely seen in pediatric patients. MALT lymphoma most commonly involves the gastrointestinal tract or peri-orbital tissues, potentially as sequela of chronic antigenic stimulation or immune dysregulation. Rare cases of MALT lymphoma arising from the gynecologic tract have been reported in older adult patients. We present the unique case of a 16-year-old postpubescent female with MALT lymphoma localized to the gynecologic tract, who initially presented with abdominal fullness, abnormal uterine bleeding, and obstructive acute kidney injury secondary to urinary outflow obstruction. Intraoperatively, dense fibrosis of the uterus and left fallopian tube was noted which mimicked abdominal cocoon syndrome. She was treated with 6 cycles of bendamustine and rituximab with complete anatomic and metabolic remission. In this report we highlight a very unusual presentation of a rare malignancy in the pediatric population as well as unique treatment considerations given this patient's young age and tumor location.

Rare Orbital Involvement Originating from Extranodal Marginal Zone Lymphoma.

Ocular adnexa region (OAR) primary lymphomas are uncommon, accounting for 1-2% of non-Hodgkin lymphomas and 8% of extranodal lymphomas. Extranodal marginal zone lymphoma (EMZL) originates from several epithelial tissues, including the stomach, salivary gland, lung, small intestine, thyroid gland, and ocular adnexa region. Here, we report a 66-year-old female patient who was diagnosed with EMZL of OAR. In consideration of the possible side effect of radiotherapy, such as conjunctivitis, visual acuity impairment, and even retinal complications, she received six cycles of triweekly targeted chemotherapy with rituximab, cyclophosphamide, vincristine, and prednisone (R-CVP) without radiotherapy. Then, she remained in complete remission up to the present day.

MYC-targeted genes predict distant recurrence in patients with ocular adnexal extranodal marginal zone lymphoma.

Ocular adnexal extranodal marginal zone lymphoma (OA-EMZL) is the most frequent subtype of ocular adnexal lymphoma, with a high propensity for recurrence. Distant recurrence (DR) as an essential prognostic event has unique clinical risk factors, but whether distinct molecular features exist remains poorly understood. Here, we identified potential biomarkers using proteomic analysis of 27 OA-EMZL samples. The MYC-targeted genes PCNA, MCM6, and MCM4 were identified as candidates. MYC-targeted genes were further identified as the most significantly activated gene set in patients with DR. The candidate genes were verified in samples from 11 patients with DR and 33 matched controls using immunohistochemistry. The 3-year and 5-year AUC values of MCM6 (0.699 and 0.757) were higher than those of Ki-67 (0.532 and 0.592). High expressions of MCM6 and MCM4 were significantly associated with shorter distant recurrence-free survival (Log-rank p = 0.017, Log-rank p = 0.0053). Multivariate Cox regression identified MCM6 expression as an independent risk factor for DR (HR, 6.86; 95% CI, 1.32-35.79; P = 0.02). Knockdown of c-Myc in B cells resulted in decreased MCM6 and MCM4 expression and reduced proliferative capacity. Our results suggest that activation of the MYC-targeted gene is a distinct molecular feature of DR in OA-EMZL. MYC-targeted gene, MCM6, is a promising pathological biomarker for DR.

Diffuse large B cell lymphoma in a preceding IgG4-related disease with kidney restricted lambda light chain expression: case report and literature review.

BACKGROUND: IgG4-related disease (IgG4-RD) is a newly classified but poorly understood immune-medicated systemic disease. It causes potential fibroinflammation in one or more organs, characterized by tumescent organs and marked IgG4-positive plasma cells infiltration in the affected tissues. There have been a few cases revealing close relationship between IgG4-RD and formation of B cell lymphoma. Diffuse large B cell lymphoma (DLBCL) and extranodal marginal zone lymphoma (EMZL) of mucosa-associated lymphoid tissue are the most common sub-types ever described, whereas the exact mechanism remain unclear. CASE PRESENTATION: We report a 64-year old Chinese male who presented chronic kidney disease and was initially diagnosed typical IgG4-RD. Pathological findings revealed there was restricted expression of lambda light chain in the kidney. There was also elevated uptake abnormality observed in 18F-FDG-PET/CT. Prednisone combined with oral cyclophosphamide helped the patient to get a partial remission of renal function and an obvious decrease of IgG4 level. However, he developed DLBCL 16 months after IgG4-RD diagnosis. The DLBCL is speculated to transform from a pre-existing but possible missed diagnosed EMZL. CONCLUSIONS: Concurrent IgG4-RD with kidney-origin EMZL developing DLBCL has never been reported in the literature. Clinicians should keep in mind that lymphoma may occur in IgG4-RD. The mechanism of lymphomagenesis potential in IgG4-RD needs further study.

[Low-grade dural extranodal marginal zone lymphoma]. / Lymphome de la zone marginale localisé à la dure-mère.

Primary low-grade dural marginal zone lymphoma is an indolent low grade lymphoma occurring especially among middle-aged immunocompetent women, and is not associated to an infectious process, contrary to gastric or intestinal marginal zone lymphomas. Dural location is rare since only 105 cases have been reported so far. We report herein on two additional cases, a 72-year-old woman and a 36-year-old man whose lymphoma was revealed by partial seizures and headaches. Morphological analysis of surgical specimens displayed a tumoral proliferation made of small lymphocytes arranged in sheets or in nodules with CD20, CD79a and BCL2-immunopositivity, but CD5 and CD10 negativity. Molecular analysis using a panel of 34 genes involved in lymphomagenesis disclosed a deletion of SOCS1 and TNFAIP3 genes, implicated in the JAK/STAT and NFκB pathways respectively in the first patient that could explain unfavourable prognosis despite complementary radiotherapy. No anomaly was identified in the second patient who is alive with no recurrence or progression seven years after the diagnosis. Currently, there are no standardized treatment schedules, but the vast majority of patients are treated by surgery, then radiotherapy followed by adjuvant chemotherapy using methotrexate alone or in combination with rituximab. Literature review indicates that five-year survival has been estimated at 96.7%, suggesting a better prognosis compared to other locations.

A Unique Case of Primary Extranodal Marginal Zone Lymphoma of the Anal Canal.

Marginal zone lymphomas represent approximately 10-12% of all B-cell lymphomas. Extranodal marginal zone lymphomas (EMZL) or mucosa-associated lymphoid tissue (MALT) lymphomas are the most common subtype. Almost half of all MALT lymphomas arise in the gastrointestinal (GI) tract and, while the stomach is the most common site of GI involvement, the small and large intestines can also be involved. Rare cases of MALT lymphoma involving the rectum have been reported; however, to our knowledge, involvement of the anal canal has never been reported in the literature. Here, we describe a unique case of MALT lymphoma of the anal canal. Infectious agents have been implicated in the pathogenesis of MALT lymphomas, possibly through persistent antigenic stimulation of the area; however, in our case no such infection was documented.

A case of conjunctival MALT lymphoma: successfully treated with solely extended rituximab therapy.

PURPOSE: Primary ocular adnexal lymphomas are cured by radiotherapy; however, complications are frequent and relapses may occur. In this case, we aimed to report the efficacy and safety of extended systemic rituximab (anti-CD 20 monoclonal antibody) therapy of conjunctival mucosa-associated lymphoid tissue (MALT) lymphoma. METHODS: In the standard regimen, rituximab is used as four consecutive weekly infusions of 375 mg/m2 in patients with low-grade lymphomas. We treated a patient who had bilateral conjunctival MALT lymphoma with rituximab 375 mg/m2 intravenously once weekly for 10 weeks as a first-line therapy. RESULTS: During the examination of the sixth week, we observed partial response of the lesions in both eyes. At the end of the tenth cure, complete remission was achieved. No local or systemic adverse effect was observed. The patient has no signs of recurrence during the 22-months follow-up period. CONCLUSION: Extended rituximab therapy may be an effective and well-tolerated first-line treatment option for bilateral conjunctival MALT lymphoma.

An unusual presentation of primary pulmonary extranodal marginal zone lymphoma of mucosal associated lymphoid tissue: An autopsy case report.

A 40 year old female with no documented medical history presented to the Emergency Department with several days of lethargy and altered mental status. She was found to be anemic, thrombocytopenic, and hypotensive. The patient was found to be in severe metabolic acidosis, became bradycardic, and quickly deteriorated. Clinicians suspected thrombotic thrombocytopenic purpura, and the diagnosis was supported by ADAMTS13 testing. The clinicians attempted to place a Quinton catheter for emergent plasmapheresis, but the patient expired before definitive treatment could be initiated. Autopsy was obtained and revealed a right middle lobe consolidation grossly consistent with lymphoid tissue or tumor.

[MALT lymphoma accompanied by elevated serum IgM levels mimicking Waldenström's macroglobulinemia].

A 60-year-old man with chronic hepatitis C was referred to our hospital with significantly elevated total protein and serum IgM (9,500 mg/dl) levels identified via a routine checkup. Blood examination revealed increased serum IgM-monoclonal protein and serum-soluble IL-2 receptor (sIL2R) levels. Computed tomography and fluorodeoxyglucose positron emission tomography revealed pulmonary masses, abnormal soft tissue masses surrounding the bilateral kidneys, and thickened mucous membrane of the bladder with high fluorodeoxyglucose uptake. Pathological examination of the pulmonary mass revealed infiltration of medium-sized lymphocytes and plasma cells. Immunohistochemical analysis revealed tumor cells positive for CD138 and IgM, with a low positive rate of Ki-67 expression. Notably, the tumor cell-surrounding lymphocytes were positive for CD20. Although the patient was initially regarded as having Waldenström's macroglobulinemia owing to the significantly increased serum IgM levels, based on positive IgH-MALT1 translocation and negative MYD88 L265P mutation findings, he was further diagnosed with extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma). Complete remission was achieved following six cycles of rituximab + CHOP therapy. This study data suggest that analysis of the MYD88 L265P mutation in tumor cells is suitable for accurately diagnosing hematopoietic malignancies with increased IgM monoclonal protein.

Long-term safety and activity of cladribine in patients with extranodal B-cell marginal zone lymphoma of the mucosa-associated lymphoid tissue (MALT) lymphoma.

The purine analogue 2-chloro-deoxyadenosine (2-CDA, cladribine) +/- rituximab has been successfully tested in mucosa-associated lymphoid tissue lymphoma (MALT lymphoma) patients. However, studies using cladribine in other indications have reported the potential for prolonged hematological side effects and secondary hematologic and non-hematologic malignancies. To date, there have been no data on long-term effects of cladribine in MALT lymphoma patients. We have analyzed a large number of 49 patients treated with cladribine at our institution 1997-2011. All patients were treated within clinical trials and had undergone a standardized follow-up protocol minimizing a potential bias in the detection of late sequels and relapses. After a median follow-up time of 61 months (interquartile range: 43-72) for 49 analyzed patients, 35 (71%) are alive, while 14 (29%) have died. In the entire collective, three cases (6%) of prolonged pancytopenia including manifest myelodysplastic syndrome in one patient (2%), three cases (6%) of secondary lymphoid malignancies, and five cases (10%) of non-hematologic cancers were documented. In terms of outcome, 42/49 (86%) patients responded to cladribine-containing treatment, and only 10/42 (24%) responding patients needed further treatment after a median time to progression of 14 months (interquartile range, 8-34). Currently, 25/35 (71%) patients being alive are in ongoing complete remission and 2/35 (6%) in ongoing stable disease, respectively. Eight patients (23%) are free of lymphoma after second-line therapy, with the median overall survival not having been reached. Our data suggest that cladribine might be safely applied in patients with MALT lymphoma, also in terms of long-term toxicities. These data also confirm the potential of cladribine to induce durable remissions. Copyright © 2015 John Wiley & Sons, Ltd.

Chemoimmunotherapy for Mucosa-Associated Lymphoid Tissue-Type Lymphoma: A Review of the Literature.

BACKGROUND: Biological treatments, chemoimmunotherapy, and radiotherapy are associated with excellent disease control in both gastric and extragastric mucosa-associated lymphoid tissue (MALT) lymphomas. Systemic treatment approaches with both oral and i.v. agents are being increasingly studied, not only for patients with disseminated MALT lymphoma, but also for those with localized disease. To date, however, recommendations for the use of available systemic modalities have not been clearly defined. MATERIALS AND METHODS: The present report reviews the current data on systemic treatment options for patients with MALT lymphoma and provides recommendations for their use in everyday practice. RESULTS: Different chemotherapeutic agents, including anthracyclines, alkylators, and purine analogs, have been successfully tested in patients with MALT lymphoma. Reducing side effects while maintaining efficacy should be the main goal in treating these indolent lymphomas. From the data from the largest trial performed to date, the combination of chlorambucil plus rituximab (R) appears to be active as first-line treatment. Similarly, R-bendamustine also seems to be highly effective, but a longer follow-up period is needed. R-monotherapy results in lower remission rates, but seems a suitable option for less fit patients. New immunotherapeutic agents such as lenalidomide (with or without rituximab) or clarithromycin show solid activity but have not yet been validated in larger collectives. CONCLUSION: Patients with MALT lymphoma should be treated within prospective trials to further define optimal therapeutic strategies. Systemic treatment is a reasonable option with potentially curative intent in everyday practice. Based on the efficacy and safety data from available studies, the present review provides recommendations for the use of systemic strategies.

High-dose clarithromycin is an active monotherapy for patients with relapsed/refractory extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT): the HD-K phase II trial.

BACKGROUND: Clarithromycin displays immunomodulatory and antineoplastic properties. As single agent, this macrolide is associated with tumor responses in anecdotal cases of relapsed/refractory extranodal marginal zone lymphoma (rrEMZL), with a putative dose-dependent effect. Tolerability and activity of high-dose clarithromycin (HD-K) in patients with rrEMZL were addressed in a phase II trial (clinicaltrials.gov NCT01516606). METHODS: HIV-negative adults with rrEMZL and at least one measurable/parametrable lesion were enrolled and treated with four courses of oral clarithromycin 2 g/day, days 1-14, every 21 days. Activity (overall response rate, ORR) was the primary end point. RESULTS: Twenty-three patients were registered (median age 70 years, range 47-88 years; M:F ratio: 0.27). HD-K was given at greater than or equal to second relapse in 11 patients. Ocular adnexae were the most commonly involved organs. Five patients had hepatitis B virus/hepatitis C virus (HBV/HCV) infections; Helicobacter pylori and Chlamydophila psittaci infections were excluded at the time of patient registration.Tolerability was excellent, even among HBV/HCV-positive patients; only two patients had grade >2 toxicity (nausea). Six patients achieved a complete remission and six a partial response (ORR = 52%; 95% confidence interval 32% to 72%). Age, previous treatment and stage did not influence activity. At a median follow-up of 24 (16-33) months, only two patients with responsive disease experienced relapse, with a 2-year progression-free survival of 56 ± 10%; all patients are alive. CONCLUSIONS: HD-K is a safe and active salvage treatment in EMZL patients. This macrolide deserves to be further investigated in EMZL and other lymphoma categories.

A unique description of stage IV extranodal marginal zone lymphoma (EMZL) in an adolescent associated with gamma heavy chain disease.

Extranodal Marginal zone lymphoma (EMZL) is a rare, usually localized disease in children. Advanced stage EMZL in adults is considered incurable, with prolonged remissions after chemotherapy. Gamma heavy chain disease (γHCD) is a rare disease of adults associated with lympho-proliferative processes with no comparable reports in children. A case of stage-IV EMZL with γHCD in an adolescent is discussed including treatment with Bendamustine plus Rituximab. The patient remains disease free 18 months from diagnosis. This case highlights necessity for careful diagnostic work-up to identify indolent lymphomas in children which may respond to less toxic chemotherapy than used for common pediatric lymphomas.

Bendamustine and rituximab as frontline therapy in extranodal marginal zone lymphoma: a single-institution experience.

Extranodal marginal zone lymphoma (EMZL) encompasses 70% of cases of marginal zone lymphoma. Frontline bendamustine and rituximab (BR) were derived from trials involving other indolent non-Hodgkin's lymphomas. Only one trial has evaluated frontline BR prospectively in EMZL. This retrospective study reports outcomes among EMZL patients receiving frontline BR. Twenty-five patients were included with a median age of 69 years (40-81). Five (20.0%) patients had stage I/II disease, and 20 (80.0%) had stage III/IV disease. The median number of cycles was 6.0 (3.0-6.0). Maintenance rituximab was administered to 10 (41.7%) individuals. Overall response rate (ORR) was 100.0% (60.0% complete response, 40.0% partial response). Medians of overall survival and progression-free survival were not reached. The estimated 2-year progression-free survival was 85.2% and overall survival was 100.0%. Four (16.6%) patients had infections related to treatment; 3 (12.0%) transformed to diffuse large B-cell lymphoma; 5 (20.8%) had a relapse or progression of EMZL; and 3 (12.0%) died unrelated to BR. BR is an efficacious and well-tolerated front-line regimen for EMZL with response data consistent with existing literature.