MALT lymphoma

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MALT lymphoma
Gastric MALT lymphoma 2.jpg
Endoscopic image of gastric MALT lymphoma taken in body of stomach in patient who presented with upper GI hemorrhage. Appearance is similar to gastric ulcer with adherent clot.
Specialty Oncology   Blue pencil.svg

MALT lymphoma (MALToma) is a form of lymphoma involving the mucosa-associated lymphoid tissue (MALT), frequently of the stomach, but virtually any mucosal site can be afflicted. It is a cancer originating from B cells in the marginal zone of the MALT, and is also called extranodal marginal zone B cell lymphoma.

Lymphoma hematologic cancer that affects lymphocytes that reside in the lymphatic system and in blood-forming organs

Lymphoma is a group of blood cancers that develop from lymphocytes. The name often refers to just the cancerous versions rather than all such tumors. Signs and symptoms may include enlarged lymph nodes, fever, drenching sweats, unintended weight loss, itching, and constantly feeling tired. The enlarged lymph nodes are usually painless. The sweats are most common at night.

The mucosa-associated lymphoid tissue (MALT), also called mucosa-associated lymphatic tissue, is a diffuse system of small concentrations of lymphoid tissue found in various submucosal membrane sites of the body, such as the gastrointestinal tract, oral passage, nasopharyngeal tract, thyroid, breast, lung, salivary glands, eye, and skin. MALT is populated by lymphocytes such as T cells and B cells, as well as plasma cells and macrophages, each of which is well situated to encounter antigens passing through the mucosal epithelium. In the case of intestinal MALT, M cells are also present, which sample antigen from the lumen and deliver it to the lymphoid tissue.

Stomach digestive organ

The stomach is a muscular, hollow organ in the gastrointestinal tract of humans and many other animals, including several invertebrates. The stomach has a dilated structure and functions as a vital digestive organ. In the digestive system the stomach is involved in the second phase of digestion, following mastication (chewing).

Contents

Diagnosis and staging

MALT lymphoma is an often multifocal disease in the organ of origin and is frequently macroscopically indistinguishable from other disease processes in the GI tract. Endoscopy is key to diagnosing MALT lymphoma, with multiple biopsies of the visible lesions required, as well as samples of macroscopically normal tissue, termed gastric mapping. Histologically, there is expansion of the marginal zone compartment with development of sheets of neoplastic small lymphoid cells. [1] The morphology of the neoplastic cells is variable with small mature lymphocytes, cells resembling centrocytes (centrocyte like cells), or marginal zone/monocytoid B cells. Plasmacytoid or plasmacytic differentiation is frequent. Lymphoid follicles are ubiquitous to MALT lymphoma but may be indistinct as they are often overrun or colonized by the neoplastic cells. Large transformed B cells are present scattered among the small cell population. If these large cells are present in clusters or sheets, a diagnosis of associated large B-cell lymphoma should be considered. A characteristic feature of MALT lymphoma is the presence of neoplastic cells within epithelial structures with associated destruction of the glandular architecture to form lymphoepithelial lesions. [2]

Endoscopy medical procedure

An endoscopy is used in medicine to look inside the body. The endoscopy procedure uses an endoscope to examine the interior of a hollow organ or cavity of the body. Unlike many other medical imaging techniques, endoscopes are inserted directly into the organ.

MALT lymphoma may be difficult to distinguish from reactive infiltrates, and in some cases, multiple endoscopies are required before a confident diagnosis is reached. The Wotherspoon score, which grades the presence of histological features associated with MALT lymphoma, is useful in expressing confidence in diagnosis at presentation. Immunohistochemistry can be used to help distinguish MALT lymphoma from other small B-cell NHLs. B-cell-associated antigens such as CD19, CD20, CD22, and CD79a are usually expressed. In contrast to small lymphocytic lymphoma and MCL, staining for CD5 is usually negative, and these lymphomas can be further distinguished with CD23 (positive in small lymphocytic lymphoma) and CyclinD1 (positive in MCL). [3]

Associations

Gastric MALT lymphoma is frequently associated (72–98%) with chronic inflammation as a result of the presence of Helicobacter pylori , [4] potentially involving chronic inflammation, or the action of H. pylori virulence factors such as CagA. [5]

Inflammation signs of activation of the immune system

Inflammation is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants, and is a protective response involving immune cells, blood vessels, and molecular mediators. The function of inflammation is to eliminate the initial cause of cell injury, clear out necrotic cells and tissues damaged from the original insult and the inflammatory process, and initiate tissue repair.

<i>Helicobacter pylori</i> Species of bacteria

Helicobacter pylori, previously known as Campylobacter pylori, is a Gram-negative, microaerophilic bacterium usually found in the stomach. It was identified in 1982 by Australian scientists Barry Marshall and Robin Warren, who found that it was present in a person with chronic gastritis and gastric ulcers, conditions not previously believed to have a microbial cause. It is also linked to the development of duodenal ulcers and stomach cancer. However, over 80% of individuals infected with the bacterium are asymptomatic, and it may play an important role in the natural stomach ecology.

Helicobacter pylori virulence factor CagA is a 120–145kDa protein encoded on the 40kb cag pathogenicity island (PAI). H. pylori strains can be divided into CagA positive or negative strains. Approximately 60% of H. pylori strains isolated in Western countries carry cag PAI, whereas almost all of the East Asian isolates are cag PAI-positive

The initial diagnosis is made by biopsy of suspicious lesions on esophagogastroduodenoscopy (EGD, upper endoscopy). Simultaneous tests for H. pylori are also done to detect the presence of this microbe.

Biopsy medical test involving sampling of cells or tissues for examination

A biopsy is a medical test commonly performed by a surgeon, interventional radiologist, or an interventional cardiologist involving extraction of sample cells or tissues for examination to determine the presence or extent of a disease. The tissue is generally examined under a microscope by a pathologist, and can also be analyzed chemically. When an entire lump or suspicious area is removed, the procedure is called an excisional biopsy. An incisional biopsy or core biopsy samples a portion of the abnormal tissue without attempting to remove the entire lesion or tumor. When a sample of tissue or fluid is removed with a needle in such a way that cells are removed without preserving the histological architecture of the tissue cells, the procedure is called a needle aspiration biopsy. Biopsies are most commonly performed for insight into possible cancerous and inflammatory conditions.

Esophagogastroduodenoscopy

Esophagogastroduodenoscopy, (EGD) also called by various other names, is a diagnostic endoscopic procedure that visualizes the upper part of the gastrointestinal tract down to the duodenum. It is considered a minimally invasive procedure since it does not require an incision into one of the major body cavities and does not require any significant recovery after the procedure. However, a sore throat is common.

In other sites, chronic immune stimulation is also suspected in the pathogenesis (e.g. association between chronic autoimmune diseases such as Sjögren's syndrome and Hashimoto's thyroiditis, and MALT lymphoma of the salivary gland and the thyroid).

Hashimotos thyroiditis autoimmune disease

Hashimoto's thyroiditis, also known as chronic lymphocytic thyroiditis and Hashimoto's disease, is an autoimmune disease in which the thyroid gland is gradually destroyed. Early on there may be no symptoms. Over time the thyroid may enlarge, forming a painless goiter. Some people eventually develop hypothyroidism with accompanying weight gain, feeling tired, constipation, depression, and general pains. After many years the thyroid typically shrinks in size. Potential complications include thyroid lymphoma.

Salivary gland exocrine gland that produces saliva also it reduces bleeding in mouth

The salivary glands in mammals are exocrine glands that produce saliva through a system of ducts. Humans have three paired major salivary glands as well as hundreds of minor salivary glands. Salivary glands can be classified as serous, mucous or seromucous (mixed).

Thyroid lymphoma is a rare malignant tumor constituting 1% to 2% of all thyroid malignancies and less than 2% of lymphomas. Thyroid lymphomas are classified as non–Hodgkin's B-cell lymphomas in a majority of cases, although Hodgkin's lymphoma of the thyroid has also been identified.

Treatment

Due to the causal relationship between H. pylori infection and MALT lymphoma, identification of the infection is imperative. Histological examination of GI biopsies yields a sensitivity of 95% with five biopsies, [6] but these should be from sites uninvolved by lymphoma and the identification of the organism may be compromised by areas of extensive intestinal metaplasia. As proton-pump inhibition can suppress infection, any treatment with this class of drug should be ceased 2 weeks prior to biopsy retrieval. Serology should be performed if histology is negative, to detect suppressed or recently treated infections. [7] Following the recognition of the association of gastric MALT lymphoma with H. pylori infection, it was established that early-stage gastric disease could be cured by H. pylori eradication, which is now the mainstay of therapy. Fifty to 95% of cases achieve complete response (CR) with H. pylori treatment. [8] [9]

A t(11;18)(q21;q21) chromosomal translocation, giving rise to an API2-MLT fusion gene, [10] is predictive of poor response to eradication therapy. [11]

Radiotherapy

Radiotherapy is a valid first option for MALT lymphoma. It provides local control and potential cure in localized gastric stage IE and II 1E disease with 5-year EFS of 85-100% reported in retrospective studies. [12] [13] However, the irradiation field is potentially large as it must include the whole stomach, which can vary greatly in size and shape. Irradiation techniques have improved considerably in the last 20 years, including treating the patient in a fasting state, decreasing the irradiated field and required dose. The moderate dose of 30 Gray (Gy) of involved-field radiotherapy administered in 15 fractions (doses) can be associated with tolerable toxicity and excellent outcomes. Hence, radiotherapy is the preferred approach for local disease where antibiotic therapy has failed, or is not indicated. Evidence also suggests that radiotherapy can be utilized to control localized relapses outside the original radiation field. [14]

Chemotherapy

MALT lymphoma is exquisitely immunotherapy sensitive. Chemotherapy is reserved for those uncommon patients with disseminated disease at presentation or lack of response to local treatment. Rituximab, the anti-CD20 chimeric antibody, is a key component of therapy. Responses vary from 55% to 77% with monotherapy and 100% in combination with chemotherapy. [15] [16] Oral alkylating agents such as cyclophosphamide or chlorambucil have been administered for a median duration of 12 months with high rates of disease control (CR up to 75%) but appear not to be active in t(11;18) disease. [17] The purine nucleoside analogs fludarabine and cladribine also demonstrate activity, [18] the latter conferring a CR rate of 84% (100% in those with gastric primaries) in a small study. [19] A pivotal study of rituximab plus chlorambucil compared with chlorambucil alone (IELSG-19 study, n = 227) demonstrated a significantly higher CR rate (78% vs. 65%; p = 0.017) and 5-year EFS (68% vs. 50%; p = 0.024) over chlorambucil alone. However, 5-year OS was not improved (88% in both arms). First-line treatment of choice is generally rituximab in combination with single alkylating agents or fludarabine, or a combination of all three drugs. The final results of this study, including the later addition of a rituximab-alone arm, are pending. [20]

Two other genetic alterations are known:

These seem to turn on the same pathway as API2-MLT (i.e., that of NF-κB). They both act upon IGH, [21] which is at the locus 14q32.

Epidemiology

Of all cancers involving the same class of blood cell, 8% of cases are MALT lymphomas. [22]

See also

Related Research Articles

Peptic ulcer disease Ulcer of an area of the gastrointestinal tract

Peptic ulcer disease (PUD) is a break in the inner lining of the stomach, first part of the small intestine or sometimes the lower esophagus. An ulcer in the stomach is called a gastric ulcer, while that in the first part of the intestines is a duodenal ulcer. The most common symptoms of a duodenal ulcer are waking at night with upper abdominal pain or upper abdominal pain that improves with eating. With a gastric ulcer the pain may worsen with eating. The pain is often described as a burning or dull ache. Other symptoms include belching, vomiting, weight loss, or poor appetite. About a third of older people have no symptoms. Complications may include bleeding, perforation and blockage of the stomach. Bleeding occurs in as many as 15% of people.

Non-Hodgkin lymphoma cancer of lymph in humans

Non-Hodgkin lymphoma (NHL) is a group of blood cancers that includes all types of lymphoma except Hodgkin's lymphomas. Symptoms include enlarged lymph nodes, fever, night sweats, weight loss and tiredness. Other symptoms may include bone pain, chest pain or itchiness. Some forms are slow-growing, while others are fast-growing.

Tumors of the hematopoietic and lymphoid tissues tumor that affect the blood, bone marrow, lymph, and lymphatic system

Tumors of the hematopoietic and lymphoid tissues or tumours of the haematopoietic and lymphoid malignancies are tumors that affect the blood, bone marrow, lymph, and lymphatic system. As those elements are all intimately connected through both the circulatory system and the immune system, a disease affecting one will often affect the others as well, making myeloproliferation and lymphoproliferation closely related and often overlapping problems.

Gastritis stomach disease that is an inflammation of the lining of the stomach.

Gastritis is inflammation of the lining of the stomach. It may occur as a short episode or may be of a long duration. There may be no symptoms but, when symptoms are present, the most common is upper abdominal pain. Other possible symptoms include nausea and vomiting, bloating, loss of appetite and heartburn. Complications may include bleeding, stomach ulcers, and stomach tumors. When due to autoimmune problems, low red blood cells due to not enough vitamin B12 may occur, a condition known as pernicious anemia.

Atrophic gastritis Human disease

Atrophic gastritis (also known as type A or type B gastritis) is a process of chronic inflammation of the gastric mucosa of the stomach, leading to a loss of gastric glandular cells and their eventual replacement by intestinal and fibrous tissues. As a result, the stomach's secretion of essential substances such as hydrochloric acid, pepsin, and intrinsic factor is impaired, leading to digestive problems. The most common are vitamin B12 deficiency which results in a megaloblastic anemia and malabsorption of iron, leading to iron deficiency anaemia. It can be caused by persistent infection with Helicobacter pylori, or can be autoimmune in origin. Those with the autoimmune version of atrophic gastritis are statistically more likely to develop gastric carcinoma, Hashimoto's thyroiditis, and achlorhydria.

Gastric lymphoma Human disease

Primary gastric lymphoma is an uncommon condition, accounting for less than 15% of gastric malignancies and about 2% of all lymphomas. However, the stomach is a very common extranodal site for lymphomas. It is also the most common source of lymphomas in the gastrointestinal tract.

Ménétriers disease Human disease

Ménétrier disease is a rare, acquired, premalignant disease of the stomach characterized by massive gastric folds, excessive mucous production with resultant protein loss, and little or no acid production. The disorder is associated with excessive secretion of transforming growth factor alpha (TGF-α). It is named after a French physician Pierre Eugène Ménétrier, 1859–1935.

Intravascular large B-cell lymphoma

Intravascular large B-cell lymphoma (ILBCL), also referred to as angiotropic large-cell lymphoma, angiotropic large-cell lymphoma, intralymphatic lymphomatosis, intravascular lymphomatosis, and, less specifically, intravascular lymphoma and malignant angioendotheliomatosis is a rare form of lymphoma.

Timeline of peptic ulcer disease and <i>Helicobacter pylori</i> timeline of the events relating to the discovery that peptic ulcer disease and some cancers are caused by H. pylori

This is a timeline of the events relating to the discovery that peptic ulcer disease and some cancers are caused by H. pylori. In 2005, Barry Marshall and Robin Warren were awarded the Nobel Prize in Physiology or Medicine for their discovery that peptic ulcer disease (PUD) was primarily caused by Helicobacter pylori, a bacterium with affinity for acidic environments, such as the stomach. As a result, PUD that is associated with H. pylori is currently treated with antibiotics used to eradicate the infection. For decades prior to their discovery, it was widely believed that PUD was caused by excess acid in the stomach. During this time, acid control was the primary method of treatment for PUD, to only partial success. Among other effects, it is now known that acid suppression alters the stomach milieu to make it less amenable to H. pylori infection.

Cancer bacteria are bacteria infectious organisms that are known or suspected to cause cancer. While cancer-associated bacteria have long been considered to be opportunistic, there is some evidence that bacteria may be directly carcinogenic. The strongest evidence to date involves the bacterium H. pylori and its role in gastric cancer.

Marginal zone B-cell lymphoma B-cell lymphoma that is characterized by initial formation in the marginal zones of lymph tissue

Marginal Zone B-cell Non-Hodgkins Lymphoma (NHL) is a type of lymphoma that affects B-cells in the marginal zones of various areas. Marginal zone lymphomas are slow growing and make up about 12% of all B-cell NHL. The median age for diagnosis is 65 years old and is primarily present in the stomach, intestines, salivary glands, lung, thyroid gland, lacrimal gland, conjunctiva, bladder, kidney, skin, soft tissue, thymus gland, and breast. The three types of marginal zone lymphomas include extranodal marginal zone lymphoma (MALT), nodal marginal zone lymphoma, and splenic marginal zone lymphoma. Marginal zone lymphomas are those that develop in the marginal zone or edge of the lymphoid tissue where B-cells are located. All marginal zone lymphomas are low-grade B-cell NHL. Nodal MZL makes up less than 2 in 100 NHL cases, MALT lymphoma makes up 1 in 13 NHL cases, and splenic marginal zone NHL makes up less than 2 in 100 NHL cases. Symptoms tend to vary from each individual patient and are often not enough to make an immediate diagnosis, as this cancer may have similar symptoms to other diseases. Prognosis and treatment are dependent on the location of the cancer and the stage of diagnosis.

Lymphoepithelial lesion

In pathology, lymphoepithelial lesion refers to a discrete abnormality that consists of lymphoid cells and epithelium, which may or may not be benign.

Helicobacter felis is a bacterium in the Helicobacteraceae family, Campylobacterales order. It can be pathogenic. It is part of the gastric mucosa of cats, and is Gram-negative, microaerophilic, urease-positive, and spiral-shaped. Its type strain is CS1T.

Chronic gastritis Inflammation of the stomach that is chronic in nature

Chronic gastritis is a chronic inflammation of the gastric mucosa.

Primary cutaneous follicle center lymphoma is a type of lymphoma. It was recognized as a distinct disease entity in the 2008 WHO classification. PCFCL had been previously conceived as a variant of follicular lymphoma (FL).

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