Successful conservative treatment of primary endometrial marginal zone lymphoma (MALT type): A case report and review of the literature.

RATIONALE: Primary endometrial marginal zone lymphoma (mucosa-associated lymphoid tissue [MALT] type) is a rare histological type of non-Hodgkin lymphoma (NHL); therefore, this disease is challenging to diagnosis and treatment. PATIENT CONCERNS: A 61-year-old (gravidity 2, parity 2) female was admitted complaining of postmenopausal vaginal bleeding for 2 months. DIAGNOSES: An ultrasound revealed a slightly thickened endometrium. Histology revealed a dense lymphoid infiltrate in the endometrium, which was suggestive of an NHL. The atypical lymphocytes were positive for CD20 and BCL-2. Moreover, the PCR demonstrated monoclonal heavy chain gene rearrangement. Taken together, the diagnosis of primary endometrial marginal zone lymphoma (MALT type) was established. According to Ann Arbor criteria, the disease was staged IEA. INTERVENTIONS: Dilatation and curettage was performed, and no additional surgery or radiotherapy and chemotherapy was administered. OUTCOMES: The patient was alive with no evidence of cancer for ≥41 months. LESSONS: Primary endometrial marginal zone lymphoma (MALT Type) is a very rare indolent tumor, and its prognosis seems to be good. Thus, conservative treatment and no further therapy were suggested based on the tumor biology.

Mucosa-associated lymphoid tissue lymphoma with unusual 18F-FDG hypermetabolism arising at the colorectal anastomosis.

Mucosa-associated lymphoid tissue (MALT) lymphoma usually originates from the stomach and presents with low 18F-fluorodeoxyglucose (FDG) avidity with average maximum standard uptake value of 3.6. Colorectal MALT lymphoma is a rare entity that contributes to 1.6% of all MALT lymphomas and < 0.2% of large intestinal malignancies. The case reported herein firstly revealed stage IIE MALT lymphoma with unexpected higher 18F-FDG avidity of 18.9 arising at the colorectal anastomosis in a patient with a surgical history for sigmoid adenocarcinoma, which was strongly suspected as local recurrence before histopathological and immunohistochemical examinations. After accurate diagnosis, the patient received four cycles of standard R-CVP regimen (rituximab, cyclophosphamide, vincristine and prednisone), combined target therapy and chemotherapy, instead of radiotherapy recommended by National Comprehensive Cancer Network guidelines. He tolerated the treatment well and reached complete remission.

Best case series program supportive cases of Cordyceps militaris- and panax notoginseng-based anticancer herbal formula.

OBJECTIVE: The major aim of this study was to present 2 cancer cases treated with anticancer herbal formula Panax notoginseng and Cordyceps militaris. METHODS: Two patients, with pancreatic adenocarcinoma and mucosa-associated lymphatic tissue type lymphoma, respectively, were treated with P notoginseng and C militaris herbal formula without conventional treatments. Their tumor masses were compared using computed tomography during early and later periods of herbal formula treatment. RESULTS: On computed tomography, reduction in tumor mass in both patients after 17 and 13 months of herbal treatments was noted, and the patients maintained stable disease and good quality of life until the last contact in November 2008. CONCLUSION: C militaris and P notoginseng are potential anticancer herbal prescriptions for adenocarcinoma and mucosa-associated lymphatic tissue type lymphoma.

MALT1 protease: a new therapeutic target in B lymphoma and beyond?

The identification of mucosa-associated lymphoid tissue lymphoma translocation 1 (MALT1) as a gene that is perturbed in the B-cell neoplasm MALT lymphoma, already more than a decade ago, was the starting point for an intense area of research. The fascination with MALT1 was fueled further by the observation that it contains a domain homologous to the catalytic domain of caspases and thus, potentially, could function as a protease. Discoveries since then initially revealed that MALT1 is a key adaptor molecule in antigen receptor signaling to the transcription factor NF-κB, which is crucial for lymphocyte function. However, recent discoveries show that this function of MALT1 is not restricted to lymphocytes, witnessed by the ever-increasing list of receptors from cells within and outside of the immune system that require MALT1 for NF-κB activation. Yet, a role for MALT1 protease activity was shown only recently in immune signaling, and its importance was then further strengthened by the dependency of NF-κB-addicted B-cell lymphomas on this proteolytic activity. Therapeutic targeting of MALT1 protease activity might, therefore, become a useful approach for the treatment of these lymphomas and, additionally, an effective strategy for treating other neoplastic and inflammatory disorders associated with deregulated NF-κB signaling.

[Six cases of pulmonary MALT lymphoma: a heterogeneous therapeutic management]. / Six cas de lymphomes pulmonaires de type MALT : une prise en charge thérapeutique hétérogène.

Pulmonary mucosa-associated lymphoid tissue lymphomas (PMALT) account for around 1% of lymphomas. Clinical and radiological presentations, and the treatment of six PMALT were collected from 1993 to 2008. All patients received chemotherapy before disease progression. Two patients had a lobectomy and one received thoracic radiotherapy. In 2008, all the patients were alive and three were in remission. A "watch and wait" strategy is widely accepted for stable, asymptomatic patients and patients with low tumour mass. Surgery may be proposed for symptomatic patients who have localised PMALT. When a chemotherapy treatment is to be suggested, chlorambucil-based chemotherapy is preferred. There may be room for rituximab alone or in combination, but this remains to be precisely defined. Several larger studies are currently ongoing to assess the role of monoclonal antibodies and chemotherapy in MALT lymphomas. Subgroup analysis should help us to define the optimal treatment for PMALT.

High-dose therapy/autologous hematopoietic stem cell transplantation in relapsed or refractory marginal zone non-Hodgkin lymphoma.

The optimal therapy for patients who have relapsed or refractory marginal zone lymphoma has not been defined. We analyzed the clinical outcomes of 14 patients who had relapsed or refractory marginal zone lymphomas and underwent high-dose therapy/autologous hematopoietic stem cell transplantation (HDT/AHSCT) at the University of Nebraska from August 1992 to August 2008. The median age of patients was 48 years (range, 29 to 62 years). All patients had relapsed or refractory disease. There were three treatment-related deaths within 100 days of transplantation. With a median follow-up of 138 months, the median duration of failure-free survival is 108 months, and the median duration overall survival is 120 months. Only two patients have relapsed. Secondary malignancies were seen in three patients (myelodysplastic syndrome, n = 2; gastric carcinoma. n = 1). We conclude that HDT/AHSCT is feasible in patients who have relapsed/refractory marginal zone lymphomas. Approximately one- third of patients can achieve long-term disease-free survival.

Protease activity of the API2-MALT1 fusion oncoprotein in MALT lymphoma development and treatment.

Gastric mucosa-associated lymphoid tissue (MALT) lymphoma is a prototypical cancer that occurs in the setting of chronic inflammation and an important model for understanding how deregulated NF-κB transcriptional activity contributes to malignancy. Most gastric MALT lymphomas require ongoing antigenic stimulation for continued tumor growth, and Stage I disease is usually cured by eradicating the causative microorganism, Helicobacter pylori, with antibiotics. However, in a subset of MALT lymphomas, chromosomal translocations are acquired that render the lymphoma antigen-independent. The recurrent translocation t(11;18)(q21;q21) is associated with failure to respond to antibiotic therapy and increased rate of dissemination. This translocation creates the API2-MALT1 fusion oncoprotein, which comprises the amino terminus of inhibitor of apoptosis 2 (API2 or cIAP2) fused to the carboxy terminus of MALT1. A common characteristic of chromosomal translocations in MALT lymphoma, including t(11;18), is that genes involved in the regulation of the NF-κB transcription factor are targeted by the translocations, and these genetic perturbations thereby result in deregulated, constitutive NF-κB stimulation. In the last decade, great insights into the roles of API2 and MALT1 in NF-κB signaling have been made. For example, recent pivotal studies have uncovered the long sought-after proteolytic activity of MALT1 and have demonstrated its critical involvement in the survival of certain lymphomas. Here, we review the current understanding of the role of MALT1 in normal lymphocyte function and lymphomagenesis. We then highlight our recent work that has revealed an intriguing link between the proteolytic activity of the API2-MALT1 fusion and its ability to influence lymphomagenesis by cleaving a key NF-κB regulatory protein, NF-κB-inducing kinase.

Stage IV marginal zone B-cell lymphoma--prognostic factors and the role of rituximab: Consortium for Improving Survival of Lymphoma (CISL) study.

Stage IV marginal zone B-cell lymphomas (MZL) are detected in more than 25% of lymphoma patients. In this study, we conducted retrospective analyses of specific cases of stage IV MZL in order to assess their clinical features, as well as the treatments and prognoses of these cases. A total of 94 patients with histological diagnosis of stage IV-MZL from 17 different institutions in Korea were included. Multiple-mucosa-associated lymphoid tissue (MALT)-organs-involved MZL (M-MZL) was detected in 34 patients (36.2%). Bone-marrow-involved stage IV MZL (BM-MZL) was detected in 33 patients (35.1%). Median time to progression (TTP) was 2.4years (95% CI, 1.9-2.9). Five- and 10-year overall survival rates were 84.5% and 79.8%, respectively. Patients with lymph node involvement in stage IV MZL appeared to have worse prognoses in TTP (P=0.015). Thirty-one patients were treated with a regimen including rituximab (CTx-R[+]), and 31 with a regimen that did not include rituximab (CTx-R[-]). The CTx-R(+) group showed better responses than the CTx-R(-) group (83.9%versus 54.8%, P=0.026). However, no differences in TTP duration were detected (P=0.113). Stage IV MZL tend to follow an indolent disease course. Therefore, lymph node involvement is a more valuable prognostic factor for TTP. Rituximab appears to contribute to better responses, but not in cases of TTP.

Treatment of splenic marginal zone lymphoma: splenectomy versus rituximab.

Splenic marginal zone lymphoma (SMZL) is an uncommon indolent B-cell lymphoma causing marked splenic enlargement with CD20-rich lymphoma cells infiltrating blood and bone marrow. In the pre-rituximab era, the treatment of choice for patients with symptomatic splenomegaly or threatening cytopenia was splenectomy, since chemotherapy had limited efficacy. Responses to splenectomy occurred in approximately 90% of patients. However, SMZL patients are often elderly and poor surgical risks. Since approval of rituximab, treatment of such patients with the anti-CD20 antibody both alone or in combination with chemotherapy has shown remarkable responses. In retrospective series of rituximab monotherapy totaling 52 patients, including both chemotherapy-naive and -refractory patients, overall responses of 88% to 100% were noted with marked and prompt regression of splenomegaly and improvement of cytopenias. Sustained responses occurred both with and without rituximab maintenance in 60% to 88% of patients at 3 years. Relapsed patients responded to second courses of rituximab monotherapy. Overall survival was comparable to that reported following splenectomy. Rituximab in combination with purine nucleosides may provide further improvement in progression-free survival; however, confirmatory prospective trials are necessary. These results suggest that splenectomy should no longer be considered as initial therapy for SMZL but rather as palliative therapy for patients not responsive to immunotherapy with or without chemotherapy.

Antibodies to Helicobacter pylori and CagA protein are associated with the response to antibacterial therapy in patients with H. pylori-positive API2-MALT1-negative gastric MALT lymphoma.

The aim of this study was to clarify predictive factors for response to eradication therapy in cases of Helicobacter pylori (H. pylori)-positive API2-MALT1-negative gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Sixty-six patients who were examined for H. pylori infection and the presence of the API2-MALT1 chimeric transcript and who underwent H. pylori eradication therapy as first-line therapy, were enrolled in this study. Immunohistochemical markers (p53, Ki-67, and BCL10), microsatellite instability, loss of heterozygosity, serum levels of antibodies (anti-H. pylori and anti-CagA), and markers for gastritis (gastrin and pepsinogens) were examined, and the results were compared between patients whose tumors regressed completely after eradication therapy (responders) and patients whose tumors did not regress (non-responders). Of the 66 patients with localized gastric MALT lymphoma, 47 (71.2%) showed complete remission after eradication therapy. None of the H. pylori-negative (n = 9) and/or API2-MALT1-positive (n = 7) patients responded to antibacterial treatment. Of 44 patients with H. pylori-positive API2-MALT1-negative gastric MALT lymphoma, 38 (86.4%) showed complete remission after eradication therapy. Titers of antibodies against H. pylori and CagA protein were significantly higher in the responders than in the non-responders (P = 0.0235 and 0.0089, respectively). No significant difference between the groups was observed for the other factors. In conclusion, measurement of titers of serum antibodies to H. pylori and CagA protein may be useful for predicting the response to eradication therapy in patients with H. pylori-positive API2-MALT1-negative gastric MALT lymphoma.

Maltoma de localización gástrica: a propósito de un caso / Maltoma of gastric localization: a case report

Se presenta un caso de un varón mestizo de 12 años de edad, que aquejaba decaimiento y pérdida de peso de dos meses de evolución, con antecedentes de hipotiroidismo, que fue atendido en el Hospital Pediátrico Hermanos Cordové de Manzanillo. Se le realizaron varios estudios: Rx Colon por enema, Rx esófago-estómago-duodeno, TAC. En la Endoscopía: se observa a nivel del fondo gástrico y tercio superior del cuerpo, una extensa lesión ulceronecrótica de fondo sucio y bordes congestivos que sangran con facilidad, sin peristaltismo. Esófago normal. Estudio histológico: Linfoma no Hodgkin difuso de mediano grado de malignidad a células pequeñas y grandes. Infiltración de epiplón y ganglios linfáticos. Estadio: E II. Se le realizó una Gastrectomía total más esplenectomía con omentectomía. Esofagoyeyunostomía en asa de Brown anticólica aniso peristáltica y yeyuno-yeyuno más tratamiento quimioterápico con citostáticos. Hasta el momento el niño evoluciona satisfactoriamente(AU)

It was presented a case of a 12 year old mestee boy who presented symptoms of weakness and weight loss with antecedents of hypothyroidism and he was assisted in Hermanos Cordové Pediatric Hospital, Manzanillo. Some studies were carried out, such as: Colon XR for enema, esophagus XR-stomach- duodenum, CAT. In the endoscopy, it was observed in the gastric fondus level and upper third of the body an ulceronecrotic extensive lesion of dark fondus and congestive borders that bleed easily without peristalsis. Normal esophagus. Histological study: diffuse non- Hodgkins lymphoma of average level of damage to small and big cells infiltration of omentum and lymphatic ganglion. Stage: IIE. It was developed a total gastrectomy and splenectomy with omentectomy. Esophagojejunostomyin brown asa anticolic aniso peristalsis jejunum jejunum and chemotherapy treatment with cytostatic.The kid has been recovered well(EU)

Ocular adnexal MALT lymphoma: an intriguing model for antigen-driven lymphomagenesis and microbial-targeted therapy.

Non-Hodgkin's lymphomas constitute one half of malignancies arising in the orbit and the ocular adnexae. Mucosa-associated lymphoid tissue (MALT)-type lymphoma is the most common histological category in this anatomic region. The incidence of ocular adnexal lymphoma of mucosa-associated lymphoid tissue-type (OAML) is increasing and recent studies offered new relevant insights in molecular, pathogenetic and therapeutic issues on these neoplasms. A pathogenetic model of antigen-driven lymphoproliferation similar to that reported for Helicobacter pylori-related gastric MALT lymphomas has been hypothesized for OAML. This notion is supported by the association between OAML and Chlamydophila psittaci infection, an association that is of likely pathogenetic relevance and may influence both the biological behavior and the therapeutic management of these neoplasms. However, this association displays evident geographical variability indicating that other etiopathogenic agents could be involved. These recent acquisitions coupled with the occurrence of chromosomal translocations and other genetic alterations, as well as additional risk factors like autoimmune disorders have contributed to render OAML an exciting challenge for a broad group of physicians and scientists. OAML is an indolent and rarely lethal malignancy that, in selected patients, can be managed with observation alone. Lymphomatous lesions are frequently responsible for symptoms affecting patient's quality of life, requiring, therefore, immediate treatment. Several therapeutic strategies are available, often associated with relevant side-effects. However, the therapeutic choice in OAML is not supported by consolidated evidence due to the lack of prospective trials. In this review, we analyze the most relevant biological, molecular, pathological and clinical features of OAML and propose some therapeutic guidelines for patients affected by this malignancy.

Therapy of gastric mucosa-associated lymphoid tissue lymphoma.

Mucosa-associated lymphoid tissue (MALT) lymphoma is a relatively common lymphoma and comprises approximately 7% of all newly diagnosed non-Hodgkin's lymphoma. It is mainly located in the stomach and has become a focus of interest due to its unique pathophysiological link with Helicobacter pylori (HP) and the consecutive response to HP eradication therapy. In view of this, HP eradication has become standard treatment for patients with localised disease, and recent data have suggested that HP-negative patients might benefit from antibiotic treatment. In case of non-response, however, the standard approach in such patients is unclear. Both radiation and chemotherapy have shown promising results, and at present there is only one randomised study, which nevertheless suggests chemotherapy as management of choice. The objective of this review is, therefore, to summarise and evaluate the data available for treatment of gastric MALT lymphoma and to highlight potential focus for further research.

Mucosa associated lymphoid tissue lymphoma of the lung: the Royal Marsden Hospital experience.

Mucosa associated lymphoid tissue (MALT) lymphoma of the lung is a rare disease with an indolent clinical behaviour. This single centre retrospective analysis evaluates the treatment strategies and clinical outcome for these patients. A total number of ten patients (7 male/3 female) were identified between January 1997 and October 2005 and their records analysed. At diagnosis the patients presented with unspecific symptoms (cough, shortness of breath and lower respiratory chest infection) which were further evaluated. Six patients had stage IAE disease, two patients stage IIAE and in two patients disease was stage IV. The initial treatment consisted of surgery alone (3 patients), chemotherapy +/- rituximab (5/1 patients), single agent rituximab (1 patient) and wait & watch strategy (1 patient). After a median follow-up time of 3.4 years the overall survival was 90% at 3 years. In conclusion, our data suggest that most of the patients with MALT of the lung had localized disease which generally responded well to systemic or local therapy and resulted in favourable long-term outcome underlining the indolent course of this disease.

[A case of MALT lymphoma of the liver treated by RFA and Rituximab].

A 69 years old man was admitted to our hospital for further examinations of the liver tumor October, 2003. No underlying liver disease was found. Two tumors in the liver, 2cm in diameter respectively, were detected by abdominal ultrasonography and MRI scan. Ultrasonogram-guided needle biopsy from the liver tumor showed diffuse infiltration of CD20 positive, small lymphocytes. A distinct single band demonstrating clonal JH gene rearrangement was detected by southern blot analysis using tissues by needle biopsy. Thus, the patient was diagnosed with primary hepatic MALT lymphoma in the normal liver. These tumors were treated with percutaneus radiofrequency ablation (RFA), followed by Rituximab administration. No relapse has been noted until September, 2005.

The clinical characteristics and treatment results of ocular adnexal lymphoma.

PURPOSE: To assess the clinical pattern, the histopathological findings, the response to treatments, the recurrence pattern and the prognosis of malignant lymphoma in the ocular adnexa. METHODS: This study was performed on 22 total eyes from 17 patients who were diagnosed with ocular adnexal malignant lymphoma. We retrospectively analyzed the medical records for patient information including the histological classification based on age, the gender of each patient, the symptoms and signs at the initial diagnosis, the presence of binocular invasion, the findings of the surgical biopsy, the clinical stage of each patient's tumor, and the treatment methods used and their effectiveness. The mean follow-up period was 24.8 months. RESULTS: The mean age of patients studied was 46.8 years old. Six females and 11 males were included in the study. Fifteen cases consisting of 20 total eyes represented extranodal marginal zone B cell lymphoma of mucosa-associated lymphoid tissue (MALT). Five of seven patients (71.4%) whose lymphoma occurred within the conjunctiva relapsed after irradiation or chemotherapy, and four of the relapsed patients were salvaged with further therapy. CONCLUSIONS: Extranodal marginal zone B cell lymphoma of mucosa-associated lymphoid tissue (MALT) constituted 88.2% of all lymphomas involving the ocular adnexa. Lymphoma in the ocular adnexa responded well to conventional treatment, but the recurrence rate of lymphoma in the conjunctiva was significantly high.

Conservative treatment of primary gastric low-grade B-cell lymphoma of mucosa-associated lymphoid tissue: predictive factors of response and outcome.

OBJECTIVES: Primary gastric low-grade B-cell lymphoma of mucosa-associated lymphoid tissue may regress with conservative treatment such as anti-Helicobacterpylori therapy or monochemotherapy. The aims of the present study were to analyze the predictive factors of response to anti-H. pylori treatment, to assess the effects of an adjuvant therapy in responding patients, and to evaluate an alternative therapy in nonresponding patients. METHODS: From 1995 to 2000, 48 H. pylori-infected patients with localized primary gastric low-grade B-cell lymphoma of mucosa-associated lymphoid tissue were treated with anti-H. pylori therapy. Endoscopic and endoscopic ultrasonography features and histological grading of large cells' proportion were analyzed. Eradication of H. pylori and tumoral response were assessed at 2 and 6 months, respectively. From 1996, patients in remission at 6 months were randomized to receive either chlorambucil p.o. for 6 months or no treatment. Patients who did not respond to H. pylori eradication received chlorambucil p.o. for 1 yr. RESULTS: Among the 48 treated patients, 33 (69%) were in complete (n = 28) or in partial (n = 5) remission, and 15 (31%) were in treatment failure at 6 months. H. pylori was eradicated in 47 patients. The response was not correlated with the endoscopic features or with the histological grade. In contrast, it was related to ultrasonographic features: remission was achieved in 76% of patients when no perigastric lymph node was detected versus only 33% when endoscopic ultrasonography showed presence of lymph nodes (p = 0.025). All responding patients remained in remission (median 34 months) whatever the treatment they received (no treatment or chlorambucil). Remission could be achieved with chlorambucil in 58% of the nonresponding patients to anti-H. pylori treatment. CONCLUSIONS: The major negative predictive factor of the tumoral response to anti-H. pylori treatment in patients with primary gastric low-grade B-cell lymphoma of mucosaassociated lymphoid tissue was the presence of perigastric lymph nodes on endoscopic ultrasonography. In responding patients, remission remained stable, suggesting that adjuvant chemotherapy was not useful. In patients who failed to respond to H. pylori eradication, monochemotherapy with chlorambucil proved to be efficient, but new therapeutic modalities should be evaluated to improve the control of the tumoral process.

Treatment of primary gastric lymphoma: experience in the National Cancer Center Hospital, Tokyo.

The single institutional experience of the treatment of primary gastric lymphoma is presented in chronological order. Between 1963 and 1986, 74 patients were treated with various uncontrolled methods and resection line involvement was seen in seven cases. Between 1987 and 1995, a prospective study was conducted employing total gastrectomy with systematic lymphadenectomy, followed by chemotherapy for cases with lymph node metastasis. Fifty patients were enrolled and the 5-year survival rate was 86%. Thorough histological examinations of the resected specimens revealed multiple foci in the stomach and nodal involvement in 36% and 50% of cases, respectively. Since 1995, the effects of eradication of Helicobactor pylori have been examined in association with the introduction of the histological diagnosis of mucosa-associated lymphoid tissue (MALT) lymphoma. Special attention should be paid to the elevated type tumors because they could metastasize to lymph nodes preserving the features of "low-grade" MALT lymphoma.

Treatment of relapsed non-Hodgkin's lymphoma after BEAM chemotherapy and autologous transplantation by BU/CY chemotherapy and salvage transplantation.

We report a patient with centroblastic non-Hodgkin's MALT lymphoma of the stomach treated initially with surgery and post-operative chemotherapy and radiotherapy. First relapse was treated with high-dose BEAM chemotherapy and autologous peripheral blood stem cell transplantation (PBSCT). Second, systemic relapse was treated with high-dose BU/CY and second PBSCT. Today, the patient is in complete remission at 27+ months. The case indicates a curative potential for high-dose BU/CY chemotherapy as salvage therapy for relapsed high-grade lymphoma after BEAM and autologous PBSCT. This may have implications for the prevention as well as for the management of lymphoma relapse after high-dose chemotherapy (HDC) and autologous PBSCT.