Extranodal Mucosa-associated Lymphoid Tissue Lymphoma Research Articles

A rare cause of hematochezia: colonic extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALToma): A case report and literature review.

Colonic extranodal mucosa-associated lymphoid tissue lymphoma as a cause of hematochezia is rare. Here, we report a case of colonic extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALToma) with presentation of freshy bloody stool and successfully treated by endoscopic mucosal resection. This case was a 69-year-old woman with history of hypertension, reflux esophagitis, and peptic ulcer. She had several episodes of hematochezia and thus sought medical attention at the outpatient clinic. Colonoscopy revealed a 12-mm semipedunculated lesion in the ascending colon. Histopathological examination and immunochemistry were compatible with colonic extranodal mucosa-associated lymphoid tissue lymphoma. Endoscopic mucosal resection was done for tumor removal and hemoclipping was done to achieve hemostasis. The patient remained well without recurrence during 3 years of outpatient follow-up. Colonic MALToma is a rare disease, and could present as hematochezia. En bloc endoscopic resection could achieve long-term remission. The prognosis of colonic MALToma is excellent with its indolent characteristics.

Is There a Role for [18F]FDG PET-CT in Staging MALT Lymphoma?

Simple SummaryMALT lymphoma represents a relatively rare lymphoma subtype that arises in different extranodal anatomic locations. In the current paper we summarize our experience in assessing disease extent and metabolic characteristics of MALT lymphomas with [18F]FDG PET-CT at staging, and aim to highlight the strengths and challenges this imaging modality poses. In our data, all extranodal lesions located in subcutaneous-tissue, lung and liver were detected on PET, while some of those located in other tissues (such as along the digestive tract) were not detected on PET. We also evaluated the predictive role of PET in these patients, and found that increased [18F]FDG-uptake in extranodal lesions was associated with worse disease progression.The role of 18F-fluorodeoxyglucose ([18F]FDG) positron emission tomography—computed tomography (PET-CT) in assessing mucosa-associated lymphoid tissue (MALT) lymphoma is debatable. We retrospectively explored the role of [18F]FDG PET-CT in staging and predicting progression-free-survival (PFS) of patients with newly-diagnosed MALT lymphoma. Sixty-six studies were included. The maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were documented in the “hottest” extranodal and nodal lesions. Extranodal lesions and accompanying nodal disease were detected on PET in 38/66 (57.6%) and 13/66 (19.7%) studies, respectively. Detection rate of extranodal lesions differed significantly between those located in tissues with high/heterogeneous (e.g., stomach) vs low/homogenous (e.g., subcutaneous-tissue, lung) physiologic [18F]FDG-uptake (40.4% vs. 100%, p < 0.01). Nodal lesions had significantly lower SUVmax, MTV and TLG compared with extrandodal lesions in the same patients. Detection and [18F]FDG-avidity of extranodal lesions were higher in patients with advanced, bulky disease and concomitant marrow/nodal involvement. Increased SUVmax of extranodal lesions predicted shorter PFS (HR 1.10, 95% CI 1.01–1.19, p = 0.02). Higher SUVmax and TLG showed trends towards shorter PFS in patients with localized disease. In conclusion, detection rate of extranodal MALT lymphoma lesions located in tissues with low/homogeneous physiologic [18F]FDG-uptake is excellent on [18F]FDG PET-CT. When detected, SUVmax of extranodal lesions may predict PFS.

A Case Report of Non-Hodgkin Low-grade B-cell Mucosa-associated Lymphoid Tissue Lymphoma Presenting as a Suspected Endodontic Lesion

Extranodal mucosa-associated lymphoid tissue lymphoma is a rare oral disease. This case report describes a 71-year-old woman who presented for endodontic evaluation and treatment for swelling on the right posterior palatal. The case details the evaluation and diagnostic processes and treatment course. The case report draws attention to the importance of performing a biopsy, having proper sampling, and the additional steps sometimes required to arrive at a definitive diagnosis. This case report is the first to document a definitive low-grade B-cell mucosa-associated lymphoid tissue lymphoma mimicking endodontic pathology. The case shows the importance of proper examination, clinical imaging, and pathologic testing to arrive at a definitive diagnosis. It highlights that collaboration with other medical and dental specialties is essential for appropriate diagnosis and treatment and describes the “buttonhole” diagnostic strategy.

MRI and PET/MRI in hematologic malignancies

The role of MRI differs considerably between the three main groups of hematological malignancies: lymphoma, leukemia, and myeloma. In myeloma, whole‐body MRI (WB‐MRI) is recognized as a highly sensitive test for the assessment of myeloma, and is also endorsed by clinical guidelines, especially for detection and staging. In lymphoma, WB‐MRI is presently not recommended, and merely serves as an alternative technique to the current standard imaging test, [18F]FDG‐PET/CT, especially in pediatric patients. Even for lymphomas with variable FDG avidity, such as extranodal mucosa‐associated lymphoid tissue lymphoma (MALT), contrast‐enhanced computed tomography (CT), but not WB‐MRI, is presently recommended, despite the high sensitivity of diffusion‐weighted MRI and its ability to capture treatment response that has been reported in the literature. In leukemia, neither MRI nor any other cross‐sectional imaging test (including positron emission tomography [PET]) is currently recommended outside of clinical trials. This review article discusses current clinical applications as well as the main research topics for MRI, as well as PET/MRI, in the field of hematological malignancies, with a focus on functional MRI techniques such as diffusion‐weighted imaging and dynamic contrast‐enhanced MRI, on the one hand, and novel, non‐FDG PET imaging probes such as the CXCR4 radiotracer [68Ga]Ga‐Pentixafor and the amino acid radiotracer [11C]methionine, on the other hand. Level of Evidence: 5 Technical Efficacy Stage: 3J. Magn. Reson. Imaging 2020;51:1325–1335.

CHRONIC PARENCHYMAL INFILTRATION FROM MALT LYMPHOMA: DIAGNOSIS BY ENDOBRONCHIAL ULTRASOUND

SESSION TITLE: Lung Pathology 2 SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/09/2018 01:15 PM - 02:15 PM INTRODUCTION: Mucosa-associated lymphoid tissue (MALT) lymphoma is a rare cause of pulmonary infiltrate. The lung accounts for only 4% of all extra-nodal marginal zone MALT lymphomas [1] and presents mostly as an incidental finding or with non-specific symptoms. CASE PRESENTATION: A previously healthy 59-year-old man presented with chest pain in 2013. A chest radiograph noted bilateral infrahiliar masses. Computed tomography (CT) of the chest showed bilateral lung consolidations (Figure 1). He was treated with antibiotics and lost to follow up. Five years later the patient presented with transient stroke-like symptoms and a chest x-ray showed a persistent infiltrate. CT chest noted large bibasilar consolidations with air bronchograms and dilated bronchi (Figure 2). These infiltrates were hypermetabolic on positron emission tomography (PET) with a maximum standardized uptake value (SUV) of 6.4. The patient underwent bronchoscopy with endobronchial ultrasound guided transbronchial 19 gauge needle aspiration (EBUS-TBNA) of the consolidative lesions. Immunohistochemistry and flow cytometry confirmed a diagnosis of MALT lymphoma. He was referred to oncology and initiated on rituximab and bendamustine. DISCUSSION: MALT lymphoma of the lung is a relatively rare disease that has been associated with chronic antigen stimulation in the context of infection, autoimmune disease and toxic exposure. The clinical presentation and radiographic findings are varied and can be mistaken for more common entities. Lesions are usually bilateral and often have associated air bronchograms and bronchiectasis [2]. The disease usually has an indolent course with a favorable prognosis. In most reported cases, diagnosis was achieved with open lung or CT-guided biopsy. The role of EBUS-TBNA for pulmonary MALT lymphoma has been previously described in mediastinal lymphadenopathy and was found to be useful [3]. To our knowledge, this is the first case of EBUS-TBNA of lung infiltrates to diagnose this condition. CONCLUSIONS: MALT lymphoma is a rare lung malignancy that should be considered in the differential diagnosis of non-resolving pulmonary lesions. Minimally invasive approaches such as bronchoscopy and EBUS-TBNA can retrieve sufficient tissue for diagnosis. Reference #1: Schreuder MI, Van den Brand M, Hebeda K, et al. Novel developments in the pathogenesis and diagnosis of extranodal marginal zone lymphoma. J Hemathopatol. 2017; 10: 91-107. Reference #2: Wislez M, Cadranel J, Antoine M, et al. Lymphoma of pulmonary mucosa-associated lymphoid tissue: CT scan findings and pathological correlations. Eur Respir J. 1999; 14: 423-429. Reference #3: Nunez AL, Jhala NC, Carroll AJ, et al. Endoscopic ultrasound and endobronchial ultrasound-guided fine-needle aspiration of deep-seated lymphadenopathy: Analysis of 1338 cases. Cytojournal. 2012;9:14. DISCLOSURES: Consultant relationship with Boston Scientific Please note: $1-$1000 Added 03/02/2018 by Alex Chee, source=Web Response, value=Consulting fee No relevant relationships by Isabel Londono Marulanda, source=Web Response Consultant relationship with Boston Scientific Please note: $5001 - $20000 Added 03/04/2018 by Adnan Majid, source=Web Response, value=Consulting fee Consultant relationship with Olympus Please note: $5001 - $20000 Added 03/04/2018 by Adnan Majid, source=Web Response, value=Consulting fee No relevant relationships by Mihir Parikh, source=Web Response No relevant relationships by Andrew Schissler, source=Web Response

Non-Hodgkin lymphoma in South East Asia: An analysis of the histopathology, clinical features, and survival from Thailand.

Systemic reports on the descriptive epidemiology of non-Hodgkin lymphoma (NHL) from Southeast Asia are scarce. A nationwide multi-institutional registry was conducted to compare the histopathology, clinical features, and survival of Thai adult patients with NHL using large registries, especially those from Far East Asia (FEA). Using a web-based registry system, 13 major medical centers from the 4 geographic regions of Thailand prospectively collected, from 2007 to 2014, the diagnostic pathology, according to the World Health Organization classification, 2008, clinical features and survival of 4056 patients who were newly diagnosed with NHL. The median age of the patients was 56years (range, 16-99years). The male-to-female ratio was 1.3:1. From the total of 4056 patients, T/NK-cell lymphoma (TNKCL) accounted for 12.6% of cases, and 5.1% had human immunodeficiency virus-associated lymphoma. The four leading histological subtypes were diffuse large B-cell lymphoma, not otherwise specified (58.1%); follicular lymphoma (5.6%); extranodal mucosa-associated lymphoid tissue lymphoma (5.2%); and peripheral T-cell lymphoma, not otherwise specified (4.0%). With a median follow-up duration of 46.1months, the median overall survival of B-cell NHL was significantly longer than that of patients with TNKCL (76.5 vs 28.8months, P=.0001). Compared to FEA, the Thai registry had an approximately one-half lower relative frequency of TNKCL; the prevalence of extranodal mucosa-associated lymphoid tissue lymphoma was much lower than in Korea, and the frequency of extranodal TNKCL, nasal type, was strikingly low compared to China. It is concluded that while the median age of Thai patients with NHL was approximately a decade younger than for Caucasians, the long-term survival rates for most histological subtypes were comparable. While the histological distribution generally complied with the characteristic Asian features, some differences from FEA were observed.

Underutilization of radiation therapy in early-stage marginal zone lymphoma negatively impacts overall survival

PurposeMultiple population-based studies have suggested increasing omission of radiation therapy in favor of alternative treatment strategies in lymphomas, with an associated negative impact on survival. Radiation therapy has long been considered the standard management for many mucosa-associated lymphoid tissue lymphomas. Thus, we aimed to evaluate patterns of treatment utilization and survival. Methods and materialsA retrospective analysis based on the National Cancer Database was performed on 22,378 patients with splenic, nodal, or extranodal stage I-II marginal zone lymphoma diagnosed between 1998 and 2012. A logistic regression model was used to assess the association between sociodemographic, tumor, and treatment characteristics and the utilization of radiation therapy. Multivariate propensity score-adjusted Cox proportional hazards models were performed to identify factors independently associated with overall survival (OS). ResultsOf 22,378 patients, 82% had stage I disease, 77% had extranodal mucosa-associated lymphoid tissue lymphoma, 5% had splenic marginal zone lymphoma, and 64% were older than 60 years. Radiation therapy utilization decreased from a peak of 39% in 2007 to 33% in 2011 (P < .001), with a corresponding significant increase in systemic therapy utilization. Radiation therapy was associated with a 5- and 10-year OS of 86.7% and 68.8% compared with 78.3% and 54.3% for no radiation therapy (P < .001). On multivariate propensity score-adjusted survival analysis, radiation therapy remained independently associated with improved OS (hazard of death, 0.75; 95% confidence interval, 0.65-0.85; P < .001). ConclusionsAlthough clinical guidelines endorse radiation therapy as the preferred initial therapy for early-stage nongastric and Helicobacter pylori–negative gastric mucosa-associated lymphoid tissue lymphoma, radiation therapy is underused. Radiation therapy with or without systemic therapy was associated with a significant improvement in OS and should remain standard of care.

Primary MALT Lymphoma of the Bile Duct

Introduction: Primary Non-Hodgkin's lymphoma (NHL) of the common bile duct (CBD) is a rare disease that usually presents with obstructive jaundice. We present the case of a patient who developed painless jaundice and a biliary stricture suspicious for cholangiocarcinoma. He underwent a pancreaticoduodenectomy (Whipple procedure). Post-surgical pathology of bile duct was diagnostic of extranodal mucosa-associated lymphoid tissue (MALT) lymphoma. Case presentation: A 63-year-old male with a history of arthritis, hypertension, COPD, and coronary artery disease was admitted with obstructive jaundice. The preoperative abdominal MRI showed soft tissue prominence around the mid and distal portions of the CBD. This area restricted on the diffusion weighted phase and was concerning for cholangiocarcinoma. The patient underwent a Whipple procedure. Post-surgical pathology from the stricture revealed a dense, nodular infiltrate of small lymphoid cells. These cells were strongly positive for CD45, CD20, PAX5, and BCL2. Many of them expressed kappa light chain with fewer lambda positive cells. The morphologic and immunophenotypic features were diagnostic of low-grade B-cell lymphoma. The lack of CD10 and BCL6 positivity did not favor follicular lymphoma. The low-grade cytologic features of the cells and presence of disrupted expanded follicular dendritic cells favored extranodal MALT lymphoma. In the absence of systemic disease, this represented a primary biliary MALT lymphoma. Discussion: Primary bile duct lymphomas are extremely rare. Most of them are diffuse large B-cell lymphomas. However, some are extranodal marginal zone B-cell lymphomas (as in our case) or follicular lymphomas. Only a few cases of primary MALT bile duct lymphomas have been described. Primary bile duct lymphomas account for less than 1% of all extranodal lymphomas. They typically present with obstructive jaundice. Clinical and radiological features are similar to extrahepatic cholangiocarcinomas. There are no standard treatments given the rarity of the disease. Multiple, deep biopsies from the suspected lesion are necessary for definitive diagnosis. Complications of curative surgery for biliary lymphomas, such as bile leak, hemorrhage, and cholangitis, are associated with a high morbidity rate of 13-42%. Primary NHL of the extrahepatic bile duct should be considered in the differential diagnosis when a patient with obstructive jaundice presents with discrepant imaging findings on CT or MRI and ERCP. An accurate histopathologic diagnosis and surgical resection, if feasible, combined with chemotherapy with or without radiotherapy may be the approach to offer a chance for cure.

Sequential Occurrence of a Splenic Marginal Zone Lymphoma, Extranodal MALT Lymphoma, and Hodgkin Lymphoma

Although Hodgkin lymphoma (HL) has been rarely reported to occur simultaneously with non-HLs (NHLs) in “composite lymphomas,” the sequential occurrence of HL after splenic marginal zone lymphoma (SMZL) is extremely rare. In this situation, the lymphomas could be clonally unrelated and represent an incidental simultaneous occurrence, or can be clonally related and represent transformation of 1 lymphoma to the other or the development of both lymphomas from a common precursor. The development of laser capture microdissection (LCM) techniques and polymerase chain reaction (PCR) amplification allow study of the immunoglobulin (Ig) gene rearrangements and somatic mutations, therefore facilitating the elucidation of the clonal relations between these lymphomas. We describe the sequential occurrence of SMZL, extranodal mucosa-associated lymphoid tissue (MALT) lymphoma, and HL in the same patient over a 12-year period and discuss the clonal relation between these lymphomas.

A rare case of BALT lymphoma treated successfully with radiotherapy

Bronchus-associated Lymphoid Tissue (BALT) lymphoma is a rare type of extranodal marginal zone lymphoma. It is defined as subgroup of B-cell non-Hodgkin’s lymphoma typically with an indolent clinical course. Often the clinical symptoms of pulmonary mucosa-associated lymphoid tissue (MALT) lymphomas are highly heterogeneous with more than half of the patients initially suffering from multiple manifestations. Due to the rarity of this tumour and lack of randomized data, the optimal therapeutical pathway remains controversial. We report a case of this rare tumour with characteristic histological features. The patient complained about severe hemoptysis caused by an isolated tracheobronchial manifestation. According to treatment recommendations of extranodal MALT lymphomas, curative radiotherapy was administered, resulting in a complete and sustaining tumour remission and relief of symptoms.

Gastric diffuse large B-cell lymphoma after the diagnosis of primary MALT lymphoma of the breast—One case report

Primary breast and gastric lymphomas as manifestations of primary extranodal lymphomas are rare malignancies, and their diagnosis, prognosis, and treatment modalities remain unclear. We report for the first time the simultaneous co-occurrence of these diseases in one patient. A 60-year-old woman was diagnosed with gastric diffuse large B-cell lymphoma (DLBCL) 2.5 years after she was found to have primary mucosa-associated lymphoid tissue (MALT) lymphoma of the breast. Although the patient underwent chemotherapy, she died of leukemia that caused irreversible cytopenia of three lineages. The data show that her MALT lymphoma apparently transfigured into gastric DLBCL. This case highlights the importance of evaluating patients for Helicobacter pylori infection when they present with extranodal MALT lymphomas, except gastric ones. Positive test findings should prompt anti-H. pylori therapy to prevent MALT lymphomas from transforming into DLBCLs.

Subglottic stenosis induced by extranodal mucosa-associated lymphoid tissue lymphoma

Mucosa-associated lymphoid tissue (MALT) lymphoma is usually associated with a chronic inflammatory disease or autoimmune disorders from which lymphoid tissue of MALT type arises as a prerequisite for lymphoma proliferation. Primary hematopoietic neoplasms of the larynx are rare. MALT lymphomas of the larynx are believed to arise from preexisting or acquired lymphoid tissue of the upper airway which is documented in the supraglottic region. Therefore, these are mainly located in the supraglottic and glottic areas, with only a few reported in the subglottic region. We report on a 50-year-old woman with a hoarseness, stridor, and developing exertional dyspnea. On indirect laryngoscope, multiple nodular lesions with smooth surface over the subglottis with subglottic steonsis was found. The biopsy confirmed the diagnosis of a MALT lymphoma. We hope to promote awareness and consideration of MALT lymphoma in the differential diagnosis in subglottic steonsis.

Multifocal colonic mucosa-associated lymphoid tissue lymphoma with synchronous tubular adenoma: a coincidental association?

Dear Editor: Primary colorectal lymphoma is a rare condition, accounting for 10% to 20% of all gastrointestinal lymphomas and 0.2% to 0.6% of all large bowel malignancies. Most colonic lymphomas are non-Hodgkin's lymphomas and include diffuse large B-cell lymphoma, follicular lymphoma, small lymphocytic lymphoma, Burkitt's lymphoma, and mantle cell lymphoma. Mucosa-associated lymphoid tissue (MALT) lymphoma is one of the less common histological types and is mostly restricted to one segment of colon. We herein present a case of multifocal colonic MALT lymphoma, with concomitant tubular adenoma, with undistinguishable endoscopic features. A 52-year-old man was referred to our department after colonic polyps were diagnosed in a screening colonoscopy. He was asymptomatic, and his past medical history was irrelevant. His mother died at the age of 72 due to colorectal cancer, and his 54-year-old brother had already been treated for the same condition. Physical examination was unremarkable. Total colonoscopy was performed, revealing three polypoid lesions: two sessile polyps, measuring 15 mm, located in the transverse and descending colon; and a pedunculated polyp, measuring 12 mm in the sigmoid colon. En bloc snare polypectomy of all polyps was performed without complications. Histological study of both sessile polyps revealed colonic mucosa with marked expansion of the lamina propria by atypical lymphoid cells, of small to intermediate size and irregular nucleus with dense chromatin. Sparse lymphoepithelial lesions were also observed. On immunohistochemistry, tumor cells were positive for CD20, CD79a, and BCL2, but negative for CD5, CyclinD1, CD10, and CD23 markers. A diagnosis of MALT lymphoma was made. The pedunculated polyp was a tubular adenoma with low-grade dysplasia. Based on this unexpected information, staging work-up was performed. β2-microglobulin titer was within normal range. Whole-body computed tomography (CT) scan showed neither lymphadenopathy, nor involvement of the liver or spleen. Bone marrow biopsy and aspirate were normal. Upper endoscopy revealed no remarkable findings. Gastric biopsy specimens from antrum and corpus showed no signs of lymphoma and were positive for Helicobacter pylori (H. pylori) infection. Based on these findings, a final diagnosis of primary extranodal MALT lymphoma stage IE-A from modified Ann Arbor staging system was made. The patient was treated with H. pylori eradication therapy (esomeprazole–amoxicillin–clarithromycin) and 6 cycles of chemotherapy (cyclophosphamide, vincristine, adriamicine, prednisolone, and rituximab). Three months later, a urea breath test was negative, and a follow-up colonoscopy showed no signs of disease. R. Ferreira (*) : J. Torres :M. J. Pereira : J. Carvalheiro : S. Mendes :M. Ferreira : C. Agostinho :M. J. Campos Gastroenterology Service of the Hospitalar Center of Coimbra, Coimbra, Portugal e-mail: rosa.l.ferreira@gmail.com

Consolidation Radiotherapy for a Rare Case of Extranodal Mucosa-Associated Lymphoid Tissue Non-Hodgkin's Lymphoma Synchronous with Prostate Adenocarcinoma

Nongastric primary extranodal mucosa-associated lymphoid tissue (MALT) lymphomas are uncommon, with around 0.1% occurring in the prostate. Even less frequent is the presence of MALT lymphoma synchronous with another type of neoplasm in the same organ, especially the prostate. Only a single case of concurrent adenocarcinoma and MALT lymphoma of the prostate has been reported in the literature. We report a rare case of primary extranodal marginal zone MALT lymphoma incidentally diagnosed during radical prostatectomy for an adenocarcinoma of the prostate in a 53-year-old patient. Fourteen months later a recurrence of the MALT lymphoma involving both sides of the diaphragm was found and was treated with chemoimmunotherapy. High-dose radiotherapy was delivered to residual bulky disease in the pelvic region. At 18 months from the end of radiation treatment the patient was without signs of relapse of MALT lymphoma. This preliminary result confirms that rare cases of MALT lymphoma of the prostate should be discussed and treated under the collaborative supervision of hematologists and medical and radiation oncologists. In fact, at an advanced stage of the disease, a chemotherapy regimen with additional consolidation radiotherapy could be an effective strategy, as in all other lymphomas.

Combination therapy with rituximab and intravenous or oral fludarabine in the first‐line, systemic treatment of patients with extranodal marginal zone B‐cell lymphoma of the mucosa‐associated lymphoid tissue type

Currently, there are no consensus guidelines regarding the best therapeutic option for patients with extranodal marginal zone lymphomas of the mucosa-associated lymphoid tissue (MALT) type. Patients with systemically untreated or de novo extranodal MALT lymphoma received rituximab 375 mg/m(2) intravenously on Day 1 and fludarabine 25 mg/m(2) intravenously on Days 1 through 5 (Days 1-3 in patients aged >70 years) every 4 weeks, for 4 to 6 cycles. After the first cycle, oral fludarabine could be given orally at 40 mg/m(2) on the same schedule. After 3 cycles, a workup was done. Patients who achieved a complete remission (CR) received an additional cycle, and patients who achieved a partial remission (PR) received a total of 6 cycles. Twenty-two patients were studied, including 12 patients with gastric lymphoma and 10 patients with extragastric MALT lymphoma. Six patients (27%) had stage IV disease. In total, 101 cycles were administered (median, 4 cycles per patients). After the third cycle, 13 patients (62%) achieved a CR, and 8 patients (38%) achieved a PR. Primary extragastric disease was an adverse factor to achieve CR after 3 cycles of chemotherapy (hazard ratio, 23.3; 95% confidence interval, 2.0-273.3). At the end of treatment, the overall response rate was 100%, and 90% of patients achieved a CR. The progression-free survival rate at 2 years in patients with gastric and extragastric MALT lymphoma was 100% and 89%, respectively. Toxicities were mild and mainly were hematologic. Combination therapy with rituximab and fludarabine is a very active treatment with favorable safety profile as first-line systemic treatment for patients with extranodal MALT lymphoma.

First-Line Treatment with Rituximab Combined with Intravenous or Oral Fludarabine for Patients with Extranodal Mucosa Associated Lymphoid Tissue (MALT) Lymphoma.

Backgroud: Synergistic antitumor effect with combination of fludarabine and rituximab has been demostrated on MALT cells. Addition of rituximab to other drugs has improved outcomes in several types of NHL without a significant addition of toxicity. Our aim was to evaluate the safety and efficacy of rituximab combined with fludarabine (RF) in first-line therapy for extranodal MALT lymphoma.Patients and methods: Adult patients with untreated extranodal MALT lymphoma who were included and received rituximab 375 mg/m intravenously (IV) on day 1 and fludarabine 25 mg/m (IV) given on days 1–5 (days 1–3 in > 60 years), every 4 weeks; after the first cycle, oral fludarabine was permitted. After 3 cycles, a work-up was done. Patients in complete remission (CR) received an additional cycle and, if partial remission (PR), a total of 6 cycles.Results: 22 patients were included. Characteristics: median age: 60 years (32–83); 45% male; PS 0–1 (100%); site of lymphoma origin: gastric (61%) and extragastric (39%); stage: I (45%), II1 (23%), II2 (5%) and IV (27%). A total of 101 cycles of RF were administered and 21 pts were evaluable for response. After the third cycle, 13 pts (62%) achieved CR and 8 pts (38%) PR. At the end of therapy, 19 pts (90%) achieved CR and 2 pts (10%) PR. Univariate analysis identified primary extragastric disease as an adverse factor to reach CR after 3 cycles of RF (HR 23.3 (95% CI, 2.0–273.3)). The median follow-up time was 23 months (95% CI, 18–27 months). Progression free survival (PFS) at 24 months was 88 % (95% CI, 80–100%). PFS at 24 months in gastric and extragastric MALT lymphoma were 100% and 79%, respectively. Tolerance to oral fludarabine was excellent. Mild neutropenia was the most common toxicity, usually presenting after the third cycle and 2 pts had prolonged mild thrombocytopenia. No grade 3–4 infections were observed.Conclusions: Immunochemotherapy with RF, either with intravenous or oral fludarabine, achieves a high CR rate in both gastric and extragastric MALT lymphoma, although the firsts responded faster. With only four cycles of RF, two thirds of patients achieves CR. RF is associated with a good safety profile being mild granulocytopenia and thrombocytopenia the main adverse events. The long-term benefit of this therapy will require prolonged follow-up.

First-line treatment with rituximab combined with intravenous or oral fludarabine for patients with extranodal mucosa associated lymphoid tissue (MALT) lymphoma

8608 Background: The addition of rituximab to other drugs has improved outcomes in several types of NHL without a significant addition of toxicity. Our aim was to evaluate the safety and efficacy of rituximab combined with fludarabine in first-line therapy for extranodal MALT lymphoma. Methods: This study enrolled adult patients with untreated extranodal MALT lymphoma who were candidate to receive systemic treatment. Patients received rituximab 375 mg/m2 intravenously (IV) on day 1 and fludarabine 25 mg/m2 (IV) given on days 1–5 (days 1–3 in > 60 years), every 4 weeks; after the first cycle, oral fludarabine was allowed to be given orally at 40 mg/m2 with the same schedule. After three cycles, a work-up was done. Patients in CR received an additional cycle and, if PR, a total of 6 cycles was recommended. Use of G-CSF and prophylactic antibiotics was optional. Results: 22 patients have been included and started on therapy. Characteristics of the first 18 pts: median age: 59 years (range: 32–83); 7 male, 11 female; PS 0 (94%); site of lymphoma origin: stomach (61%), skin (16%), lung (11%), parotid gland (11%); stage: I (66%), II (16%) and IV (16%). A total of 82 cycles of R-F were administered; 2 pts received 2 cycles, 9 pts 4 cycles, 7 pts 6 cycles. 17 pts are evaluable for response. Overall response rate was 100% with 94% achieving CR. One pt relapsed. Median follow-up from starting treatment is 15 m (range: 17–27). PFS rate is 93% (CI95%: 79–100%) at 12 m and OS rate is 100% at 12 m. Tolerance to oral fludarabine was excellent with most patients preferring this formulation. Mild neutropenia was the most common toxicity, usually presenting after the third cycle. No blood transfusions were required. 3 pts developed grade 2 respiratory infection, but none pt had to be admitted. Conclusions: These preliminary data indicate that the RF regimen, either with intravenous or oral fludarabine, was well tolerated even in elderly patients. This combination is very active for the treatment of untreated extranodal MALT lymphoma, even with fewer cycles than initially planned. Updated data will be presented. No significant financial relationships to disclose.

Indolent Stage IE Non-Hodgkin’s Lymphoma of the Orbit: Results after Primary Radiotherapy

Aims: Primary non-Hodgkin’s lymphoma (NHL) of the orbit is uncommon, representing approximately 8% of extranodal NHLs. Twenty-two patients with indolent stage IE NHL were reviewed retrospectively to analyze the outcome and late effects of primary local radiotherapy. Materials and Methods: The median age at first diagnosis was 63.5 years (range 24–82 years). Extranodal mucosa-associated lymphoid tissue lymphoma (n = 15) was the most common histological subtype of NHL, followed by follicular (n = 6) and lymphoplasmacytic lymphoma (n = 1). Radiotherapy was performed using a linear accelerator. The median radiation dose was 40 Gy (range 30–46 Gy). None of the patients received chemotherapy before irradiation. The follow-up period was 62 months (range 8–136 months). Results:A complete response was achieved in all patients. The 5-year local control rate was 100%. Distant relapse occurred in 2 patients, resulting in a 5-year distant relapse-free survival rate of 88%. The 5-year overall survival rate was 89%; there were no lymphoma-related deaths. No serious acute complications (grade 3/4) were observed. Grade 1/2 late effects were documented in 44% of patients. Grade 3 complications (cataract: 2, dryness: 2) were observed in 4 patients (18%). Conclusions: Indolent early stage orbital NHL can be controlled with local radiotherapy. Morbidity is low. Regular follow-up examinations are necessary to detect rare cases of distant relapse.

Diagnostic accuracy of PET/CT in patients with extranodal marginal zone MALT lymphoma

(18)Fluoro-2-deoxyglucose ((18)FDG) positron emission tomography (PET) is widely used for initial staging and follow-up in patients with malignant lymphoma. While earlier studies suggested a limited role for PET in extranodal marginal zone mucosa-associated lymphoid tissue (MALT) lymphoma patients due to their non-FDG avidity, more recent reports have suggested that the issue is controversial. In the present study, we evaluated the diagnostic accuracy of PET integrated with CT (PETCT) in patients with MALT lymphoma and assessed its reliability in clinical staging and monitoring response. Thirty-three patients with biopsy proven MALT lymphoma in 37 sites, who underwent PET/CT at diagnosis, were enrolled. Medical records, PET/CT findings and data obtained by other diagnostic procedures were reviewed. Common sites of MALT lymphoma were the stomach (18), lung (5), orbit (4), and parotid gland (3). PET/CT detected active disease in 18 of 33 patients (54.5%) at diagnosis. Sensitivity in gastric MALT (38.9%) was lower when compared with non-gastric MALT (75%). PET/CT detected active disease in 100% patients with advanced disease (stage III-IV) but only in 42.3% with early stage disease (I-II). The incidence of gastric FDG uptake was higher in patients showing gastric ulcer on gastroscopy than in subjects with minimal or no macroscopic findings. Of the 33 patients in the study cohort, 12 had a follow-up PET/CT which detected relapse in three patients. These data suggest that PET/CT is a useful tool for both, initial staging and follow-up after therapy in patients with MALT lymphoma. Its sensitivity depends on disease location and stage at initial diagnosis.

HP34P EXTRANODAL MARGINAL ZONE B‐CELL LYMPHOMA OF MUCOSA ASSOCIATED LYMPHOID TISSUE (MALT) TYPE OF THE GALLBLADDER

Purpose Extranodal marginal zone B‐cell lymphoma of mucosa associated lymphoid tissue (MALT) type of the gallbladder is rare. We described a case of MALT lymphoma of the gallbladder with splenic and pulmonary dissemination, followed by a review of similar cases reported in English literature.Background A 60 year old woman presented to our surgical unit with abnormal liver function tests and gallbladder thickening on ultrasonography. Cholecystectomy revealed a chronically inflamed gallbladder with multiple gallstones. Histology showed abnormal sheets of small B lymphoid cells which were CD 20 positive, consistent with a diagnosis of MALT lymphoma. Staging CT showed bilateral pulmonary nodules and mild splenomegaly. PET scan demonstrated increase uptake in lung fields and normal uptake in spleen, bone marrow and lymph node. Bone marrow examination was negative. Final diagnosis is Stage 4 extranodal MALT. She remained in remission on three‐month review. No additional chemotherapy or radiotherapy was administered.Discussion Extranodal MALT lymphoma of the gallbladder has similar epidemiological features with other extranodal MALT lymphomas. Most patients present with symptoms consistent with cholecystitis. As the gallbladder does not normally contain lymphocytes, persistent lymphoid proliferation due to chronic inflammation may represent a critical step in the development and progression of MALT lymphoma (1). Cholecystectomy without adjuvant therapy is appropriate first line treatment if there is no other symptomatic disease (2). Long term surveillance for relapse and second lymphoma should be considered.