The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, 1650 Orleans Street, CRB Room 388, Baltimore, MD 21231, USA.
Mucosa-associated lymphoid tissue (MALT) lymphomas occur in a variety of organs, including the orbit, conjunctiva, salivary glands, skin, thyroid gland, lungs, stomach, and intestine. These tumors are often localized and of indolent clinical behavior. Diagnosis is made by pathologic evaluation of a tissue biopsy. Careful staging is mandatory and tailored to the initial presentation. Staging includes a history and physical, chemistries, computed tomography scan, and bone marrow biopsy.
This information is supplemented with an ear, nose, and throat consultation, esophagogastro-duodenoscopy, colonoscopy, endoscopic ultrasound of the stomach, and cytogenetic/immunohistochemical analysis of the tumors. Treatment is tailored to organ involvement and stage at presentation. Eradication of Helicobacter pylori using a triple anti-H. pylori regimen approved by the US Food and Drug Administration is standard therapy for all H. pylori-positive gastric MALT lymphomas. Endoscopic ultrasound- and computed tomography-staged gastric MALT stage IE tumors will achieve a complete response with this approach in approximately 60% to 90% of patients (the more superficial the tumor, the better the response). Patients with tumors that are T4 node-positive Musshoff stage IIE1 and IIE2 or tumors with adverse cytogenetics should receive radiotherapy or surgery with or without radiotherapy. Tumors with a significant high-grade component or large cell tumors with a minor low-grade MALT component should receive CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone)-based chemotherapy. Localized MALT lymphomas of the orbit, conjunctiva, salivary glands, and thyroid gland are treated successfully with radiotherapy. Surgery as first-line therapy for gastric MALT lymphomas was replaced by attempts at organ preservation. In the past, margin-free surgical excision or tumor debulking followed by radiation therapy and chemotherapy has been highly effective for gastric MALT lymphomas.
Therefore, surgical excision of large cell or bulky tumors of the stomach, thyroid, lung, and salivary gland, followed by adjuvant radiotherapy or chemotherapy, may still be an important consideration in selected patients. Surgery still has a role for patients with relapsed or refractory low-grade disease and life-threatening hemorrhage. Disseminated MALT lymphomas are incurable and are treated primarily with chemotherapy according to symptoms.
A mass in the right upper lobe of the lung was observed in a chest X-ray examination of a 66-year-old woman. Pathological examination of the lung biopsy revealed a mucosa- associated lymphoid tissue (MALT) lymphoma within the lesion. A systemic survey demonstrated no other lesions, and the patient was diagnosed as having a solitary pulmonary MALT lymphoma (Stage IE). After 9 months of careful monitoring, progressive enlargement of the lung tumor and involvement of right hilar lymph nodes were observed using positron emission tomography-computed tomography. Therefore, surgical resection of the right upper lobe and right hilar lymph nodes was performed, and coexistence of MALT lymphoma with tuberculosis was identified by pathological investigations. The association of chronic inflammation with the development of MALT lymphomas has been widely accepted. In the present case, pulmonary tuberculosis may have played a role in the pathogenesis of pulmonary MALT lymphoma.
Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. firstname.lastname@example.org
A multicentre cohort follow-up study of a large number of patients with gastric mucosa-associated lymphoid tissue (MALT) lymphoma was conducted to elucidate the long-term outcome of the disease after Helicobacter pylori eradication.
420 patients with gastric low-grade MALT lymphoma who had undergone successful H pylori eradication and been followed up for at least 3 years were registered from 21 participating institutes. Responders to treatment were defined as patients whose post-treatment biopsies showed complete histological response (ChR) or probable minimal residual disease (pMRD). Treatment failure was defined as the status of progressive disease or lymphoma relapse after ChR/pMRD.
323 patients (77%) responded to H pylori eradication. A logistic regression analysis showed that absence of H pylori, submucosal invasion determined by endoscopic ultrasonography and t(11;18)/API2-MALT1 were independent predictors of resistance to H pylori eradication. During the follow-up periods ranging from 3.0 to 14.6 years (mean 6.5 years, median 6.04 years), the disease relapsed in 10 of 323 responders (3.1%) while progressive disease was found in 27 of 97 non-responders (27%). Thus, 37 of 420 patients (8.8%) were regarded as treatment failures. Of these 37 patients, transformation into diffuse large B celllymphoma occurred in nine patients. Among the non-responders and relapsed patients, 17 patients were subjected to a 'watch and wait' strategy while 90 patients underwent second-line treatments including radiotherapy (n=49), chemotherapy (n=26), surgical resection (n=6), chemoradiotherapy (n=5), antibiotic treatment (n=2), rituximab monotherapy (n=1) or endoscopic resection (n=1). Probabilities of freedom from treatment failure, overall survival and event-free survival after 10 years were 90%, 95% and 86%, respectively. Cox multivariate analysis revealed endoscopic non-superficial type to be an independent prognostic factor for adverse freedom from treatment failure, overall survival and event-free survival.
The excellent long-term outcome of gastric MALT lymphoma after H pylori eradication was confirmed by this large-scale follow-up study.
Department of Hematology, Peking University Third Hospita, Beijing 100083, China.
Mucosa-associated lymphoid tissue (MALT) lymphoma originated outside the lymph nodes is low grade malignant B celllymphoma. It is the most frequent type of marginalzone non-Hodgkin's lymphoma, that usually occurs in the stomach, salivary gland, thyroid gland and orbital adnexa. Gastric MALT lymphoma accounts for 50% of MALT lymphoma. GastricMALT lymphoma has been confirmed to relate with Helicobacter pylori (HP) infection, its main pathogenesis is immune reaction, but some patients with chromosome translocation have no response to HP eradication, suggesting presence of other unknow pathogenesis. The chromosome translocations in MALT lymphoma are t(11;18)(q21;q21), t(1;14)(p22;q32), t(14;18)(q32;q21), t(3;14)(p14.1;q32). Recent studies show some new chromosomal abnormalities such as 6q23.3/A20 and so on, which have some effects on clinical course and prognosis. MALT lymphoma with chromosome abnormalities usually activate common NF-κB molecular pathway, and persistent active NF-κB pathway drives tumor cell proliferative and active, resulting in lymphoma incidence. In this articl, the advances in the etiology and pathogenesis of MALT lymphoma were reviewed.
1Istituto di Ematologia "Seràgnoli" Università di Bologna, Bologna, Italy.
Indolent B-cell lymphomas that are supposed to derive from the marginalzone (marginalzone lymphomas [MZLs]) include 3 specific entities: extranodal marginalzonelymphoma (EMZL) or mucosa-associated lymphatic tissue (MALT) lymphoma, splenic MZL (SMZL), and nodal MZL (NMZL). The clinical and molecular characteristics are different for each entity, with some shared phenotypic and genetic features. EMZL is the most common entity, accounting for approximately 70% of all MZLs. These neoplasms can arise at virtually any extranodal site and are commonly associated with chronic antigenic stimulation either as a result of infection (eg, Helicobacter pylori in the stomach) or autoimmune disease (eg, Sjögren syndrome and salivary glands). Several chromosomal translocations were also identified in EMZL, accounting in the aggregate for approximately one-third of all cases. SMZL accounts for approximately 20% of all MZLs. Patients typically present with an enlarged spleen and involvement of abdominal lymph nodes and BM. Approximately 40%-50% of SMZLs are associated with deletions of chromosome 7q. NMZL is the less common entity, representing approximately 10% of all MZLs. Patients with NMZL, by definition, have lymph node-based disease without involvement of the spleen or extranodal sites. The molecular pathogenesis of NMZL is still unknown.
Institute of Hematology "L. e A. Seràgnoli", University of Bologna, Bologna, Italy. email@example.com.
Bronchial-associated lymphoid tissue (BALT) lymphoma is an extranodal primary pulmonary lymphoma. The optimal therapy for this rare disease is still debated, and few heterogeneous data are available in literature. The aim of our study was to critically review data of patients with BALT lymphoma treated in first-line therapy with fludarabine and mitoxantrone-containing regimens (with or without rituximab) to investigate the effectiveness and the safety of this approach and patients' survival. An observational retrospective study was performed on homogenous clinical data from 17 patients with biopsy-proven diagnosis of BALT. All the patients were treated with fludarabine and mitoxantrone-containing regimen therapy. Radiological findings were also reviewed to assess the role of (18) fluoro-deoxyglucose positron emission tomography in the initial assessment and in the monitoring of this extranodal lymphoma. A high percentage of response was observed: 82.3% of patients achieved a complete response, 11.8% a partial response. Furthermore, a very remarkable progression-free survival (71%) and overall survival (100%) were estimated at 14 years. No relevant toxicities were registered. Our results support the use of fludarabine and mitoxantrone-containing regimens as first-line therapy in the treatment of BALT lymphoma even if further data are necessary to consolidate our findings. Positron emission tomography scanning may provide additional valuable information in the assessment of BALT lymphoma
Department of Neurosurgery, Kagoshima City Hospital.
The authors present the case of a 65-year-old woman who initially was diagnosed as having intracranial dural B-cell malignantlymphoma. She survived more than 9 years after surgery and radiation. We re-examined the specimens pathologically. Histological findings confirmed an extranodal marginalzonelymphoma of mucosa-associated lymphoid tissue (MALT) that showed numerous IgG4-positive plasma cells. MALT lymphomas are already recognized as a distinct clinico-pathological entity. A primary dural MALT lymphoma is very rare and has a favorable clinical outcome, and patients are expected to have an excellent long-term survival with local therapy alone.
Associate Professor, Department of Oral Pathology, School of Dentistry, University of Buenos Aires, Buenos Aires, Argentina. Electronic address: firstname.lastname@example.org.
Mucosa-associated lymphoid tissue (MALT) lymphomas are known to occur in Sjögren syndrome (SS) patients, but reported cases in labial salivary glands (LSG) are rare. We report a case of 60-year-old female patient with SS who developed MALT lymphoma in the labial salivary glands during a 2-year time interval when she was participating in the Sjögren's International Clinical Collaborative Alliance, an ongoing longitudinal multisite observational study funded by the National Institutes of Health of the United States. At follow-up exam, LSG biopsy showed atypical diffuse infiltration by mononuclear cells of variable size and atypical nuclei affecting the whole specimen with destruction of glandular architecture, leading to a diagnosis of B-cellMALT lymphoma. Computerized tomography and bone marrow biopsy failed to show additional evidence of disease. Clinical, serologic, ocular, histologic and immunohistochemical findings are presented. A "watch and wait" policy was adopted with regular examinations.
Department of Internal Medicine, Bucheon St. Mary's Hospital, The Catholic University of Korea School of Medicine, Bucheon, Korea.
Pulmonary mucosa-associated lymphoid tissue-derived (MALT) lymphoma is a rare disease. This disorder is considered to be a model of antigen-driven lymphoma, which is driven either by autoantigens or by chronic inflammatory conditions. Low-gradeB-cellMALT lymphoma may develop from a nonneoplastic pulmonary lymphoproliferative disorder, such as lymphocytic interstitial pneumonitis (LIP). A recent estimate predicts that less than 5% of LIP patients acquire malignant, low-grade, B-celllymphoma. In Korea, there has been no previous report of malignant low-grade, B-celllymphoma, acquired from LIP. Here, we present the case of a patient with LIP that developed into pulmonary MALT lymphoma, six years after diagnosis.
Division of Molecular Histopathology, Department of Pathology, University of Cambridge, Cambridge, United Kingdom.
Splenic marginalzonelymphoma (SMZL) is an indolent B-cell lymphoproliferative disorder characterised by 7q32 deletion, but the target genes of this deletion remain unknown. In order to elucidate the genetic target of this deletion, we performed an integrative analysis of the genetic, epigenetic, transcriptomic and miRNomic data. High resolution array comparative genomic hybridization of 56 cases of SMZL delineated a minimally deleted region (2.8 Mb) at 7q32, but showed no evidence of any cryptic homozygous deletion or recurrent breakpoint in this region. Integrated transcriptomic analysis confirmed significant under-expression of a number of genes in this region in cases of SMZL with deletion, several of which showed hypermethylation. In addition, a cluster of 8 miRNA in this region showed under-expression in cases with the deletion, and three (miR-182/96/183) were also significantly under-expressed in SMZL relative to other lymphomas. Genomic sequencing of these miRNA and IRF5, a strong candidate gene, did not show any evidence of somatic mutation in SMZL. These observations provide valuable guidance for further characterisation of 7q deletion.
H Pylori: The silent killer living inside all of us
By Ritu Dokania, Friday magazine
Nov 7, 2012
It’s silent, insidious and is the cause of gastric symptoms that range from the antisocial to the downright dangerous. But why do so few people know of its existence? Ritu Dokania unveils the mysterious bacteria behind your most embarrassing symptoms...
Alisha, a 30-year-old sales manager, hated going out in public. She refused offers of evenings out with her friends, bypassed busy events and dreaded business meetings with a passion.
It wasn’t that she disliked socialising – she had always been quite gregarious at heart – but chronic gastric symptoms were making her life a misery and she preferred to hide herself away.
Although her symptoms were troublesome, ranging from bloating and mild stomach pain to flatulence and belching, they didn’t seem serious enough to seek medical advice. She did some research online and decided it could be aerophagia, which is caused by swallowing too much air, and tried to treat it by avoiding carbonated drinks and putting an end to her chewing gum and smoking habits. Yet nothing seemed to help.
Several months passed and Alisha was no longer just embarrassed by her symptoms, but was feeling uncomfortable throughout the entire day, while horrible abdominal cramps had started to keep her awake at night.She arranged an appointment with Dr Denesh Gopalan, a gastroenterologist at Welcare Hospital in Dubai. He decided to test her for the little-known bacteria, H Pylori. The diagnosis was positive.
“H Pylori is one of the most widespread infections in the world and around 60 per cent of the UAE population has it,” says Dr Gopalan. “Yet most people don’t know about this silent infection until they start suffering from gastritis or the painful effects of ulcers.”
Its presence is hard to detect, but delayed discovery can give rise to a number of problems as H Pylori is associated not only with ulcers, but also with stomach cancer and gastric malt lymphoma, which is a stomach cancer affecting the white blood cells of the immune system.
Thankfully, once the cause of Alisha’s problems had been pinpointed, her infection was easy to eradicate. “She was put on a course of antibiotics for 14 days, after which the symptoms she had been suffering from for so long subsided remarkably,” says Dr Gopalan.
H Pylori, short for Helicobacter Pylori, is a spiral-shaped bacterium that resides in the stomachs of humans and animals. Although our stomachs are lined with a protective coating to keep it safe from bacterial infections, H Pylori secretes an enzyme that neutralises stomach acid, enabling the bacteria to burrow deep into the walls of our stomachs, where it may survive undetected for decades.
The damage it causes to the mucous coating allows powerful stomach acid to get through to the sensitive lining beneath. Together, the stomach acid and H Pylori irritate the lining of the stomach or duodenum, which can cause ulcers and other complications.
The link between H Pylori and ulcers was a scientific breakthrough. Scientist Barry Marshall discovered it by deliberately ingesting broth infected with the bacteria in order to prove the connection, and in 2005 he and his colleague Robin Warren were awarded the Nobel Prize in Physiology or Medicine for their discovery, which reversed decades of doctrine that ulcers were caused by spicy food and stress.
The Centers for Disease Control and Prevention in Atlanta estimates that two-thirds of the world’s population is infected with the bacterium, making it the most widespread infection in the world.
It is most likely acquired by the ingestion of contaminated food or water, which can happen via faecal matter if food is prepared by people who do not wash their hands after using the bathroom, or in poor sanitary conditions. It can spread from person to person via saliva or by sharing food utensils and is most common in socio-economic groups characterised by crowded living conditions.
Symptoms and implications
H Pylori is often asymptomatic, meaning most people with the infection will never have any signs or symptoms. When symptoms do occur they may include burping, bloating, heartburn, oesophageal reflux, diarrhoea, constipation, flatulence and upper- and mid-abdominal pain. Difficulty losing weight may also be attributed to H Pylori, Dr Gopalan says. Having the infection causes stress and eventually cortisol.
H Pylori is also the leading cause of gastritis, an inflammation of the stomach lining. It is responsible for over 90 per cent of all duodenal ulcers and nearly 80 per cent of all gastric ulcers.
“This pernicious bacteria, which survives so easily in our stomachs, should be exterminated before it does serious harm,” says Dr Gopalan. “While it can remain in the human stomach for a long time without causing any symptoms, it may manifest into more serious diseases over time – one to two per cent of infected people are at risk of stomach cancer and the cancer gastric malt lymphoma is eight times more common in people with H Pylori than in those not infected.”
Apart from these diseases, medical researchers and doctors believe that H Pylori may be implicated in a number of non-digestive conditions including cardiovascular disorders, migraine and Raynaud’s disease (impaired circulation in the hands and feet). Surprisingly, it may also cause depression and anxiety. The happy chemical, serotonin, is largely seen in a healthy digestive system and damage to your stomach by H Pylori will lead to a shortage of this important chemical.
Detection, treatment and prevention
“When I tell my patients about this bacteria, seven out of ten of them will never have heard of it before,” says Dr Gopalan. “But I am more surprised to see that even physicians often do not think to test for this bacteria when a patient complains about the common symptoms of this infection.”
A patient’s breath can be a typical warning sign, says Dr Gopalan, as reflux directly from the stomach or higher levels of periodontal gum disease caused by the bacteria can give it a strong smell. Testing for H Pylori infection may be performed on blood, stool or breath samples or through biopsies of tissue from the lining of the gastrointestinal tract obtained during endoscopy.
H Pylori is successfully eradicated in 80 per cent of cases, but it can be a tough infection to treat, says Dr Gopalan, as it often resides in the deepest layers of the stomach. It is also important that the antibiotics are prescribed carefully.
“H Pylori quickly becomes resistant to several antibiotics when given one at a time,” says Dr Gopalan. For this reason, a ‘triple therapy’ is often employed, which consists of two types of antibiotics and a proton pump inhibitor (PPI), which is used to decrease the stomach’s acidity, allowing the inflamed stomach lining to heal. The treatment is given for ten to 14 days according to the presence and severity of the infection. After a month, the test is repeated to see if the infection has cleared.
“Some antibiotics that are recommended elsewhere in the world might not be suitable in UAE due to the bacteria’s resistance pattern here,” warns Dr Gopalan. “It is advisable to check with your doctor about whether the antibiotic prescribed is the correct one for your particular geographical area.”
Since the source of H Pylori is not yet fully known, recommendations for avoiding infection have not been made. In general, it is always wise to wash hands thoroughly, only eat food that has been hygienically prepared, and drink water from a safe, clean source.
Certain nutrients, especially vitamins A, C, and E, along with zinc, protect the stomach lining by combating free radicals, so ensure that you are not deficient in any of these. Certain probiotics (healthy bacteria) such as lactobacillus and bifidobacterium may also help protect you from H Pylori.
Am old enough to understand the difference between the Bay of Pigs - and roasting a pig at a epicurian feast. Been thru the hippy, yippie and yuppie years - always remaining who I am.
Very much believe in "Sing your own song - weave your own tapestry"
Am young enough to still know the thrill of new discoveries, the beauty of the evening, to celebrate the joy of another tommorow.
Survived these many decades with a severe medical problems. Sorting out the maze of now having two lymphomas and all their nasty little companions, but I continue.
Besides, being a simple iconoclastic eclectic, have been called many things. An incurable romanticist - with a strong touch of reality. Thinker, intellectual (God, how I hate that term) - been told I am a lion with the heart of the poet.
Know how to wage war and conquer my foes - but would rather be known as one who brings hope and life. To bring hope into anothers life is the ultimate of joys.
Life should be about bringing hope, peace, vision... a sense of purpose beyond yourself.