Malt Lymphoma: Symptoms, Types, Causes and Treatment

Mucosa-associated lymphoid tissue (MALT) lymphoma is a unique and intriguing form of non-Hodgkin lymphoma that often presents subtly but can have wide-ranging effects on the body. Understanding its symptoms, types, causes, and treatment options is crucial for patients and caregivers navigating this diagnosis. This comprehensive guide breaks down the current evidence about MALT lymphoma, making complex science accessible and actionable.

Symptoms of Malt Lymphoma

MALT lymphoma can be particularly challenging to recognize early, as its symptoms are often non-specific and may mimic common conditions. Many patients initially experience mild or ambiguous complaints, leading to delays in diagnosis. However, an understanding of hallmark symptoms and warning signs can prompt timely investigation and improved outcomes.

Symptom	Description	Common Sites	Source(s)
Fatigue	Persistent tiredness	General	1
Weight Loss	Unintentional, often gradual	General	1
Anorexia	Reduced appetite	Gastrointestinal	1
Abdominal Pain	Discomfort or bloating	Stomach, bowel	1, 7
Anemia	Low hemoglobin, weakness	General	1
Swelling	Abdominal distention, effusion	Abdomen, chest	1
Lymphadenopathy	Enlarged lymph nodes	Abdomen, chest	1
Site-Specific	e.g., eye swelling, dry mouth	Ocular, salivary	4, 13

Table 1: Key Symptoms

Non-Specific and Overlapping Symptoms

MALT lymphoma typically grows slowly and may not cause obvious symptoms in its early stages. Fatigue and unintentional weight loss are common but can be mistaken for other health issues. Some patients experience anorexia or a persistent feeling of malaise, which may be overlooked, especially if occurring over months or years 1.

Gastrointestinal Manifestations

When MALT lymphoma affects the stomach or intestines, symptoms can include:

• Abdominal discomfort or pain
• Bloating and a sense of fullness
• Nausea or mild digestive upset
• Rarely, gastrointestinal bleeding

Endoscopic examination might reveal features such as prominent gastric folds or mucosal changes, and biopsies are essential for diagnosis 1, 7.

Systemic and Site-Specific Features

Beyond the digestive system, MALT lymphoma can manifest depending on its location:

• Ocular (eye): Swelling, vision changes
• Salivary glands: Swelling, dry mouth
• Lung: Persistent cough, shortness of breath
• Thyroid: Neck mass, hoarseness 4, 13

In advanced cases, swelling from fluid accumulation (effusions) or enlarged lymph nodes may be detected on examination or imaging 1.

Types of Malt Lymphoma

MALT lymphoma encompasses a diverse group of diseases, defined by both their site of origin and their molecular characteristics. Understanding the different types is vital for tailoring diagnosis and treatment.

Type	Main Location(s)	Unique Feature	Source(s)
Gastric	Stomach	Strong H. pylori association	1, 4, 7, 8
Extragastric	Lung, eye, thyroid, etc.	May be linked to other microbes	4, 10
Low-grade	Various	Indolent, slow-growing	2, 5
High-grade	Various	Aggressive, rare in MALT	2, 8

Table 2: MALT Lymphoma Types

Gastric MALT Lymphoma

The stomach is the most common site, making up about half of all MALT lymphomas. Gastric MALT lymphoma is closely linked to chronic infection by Helicobacter pylori. It often presents as a low-grade, slowly advancing malignancy that may remain localized for years 1, 7, 8.

Extragastric MALT Lymphoma

MALT lymphomas can arise virtually anywhere mucosa-associated lymphoid tissue is found, especially in organs that develop MALT as a response to chronic inflammation. Common extragastric sites include:

• Lungs
• Ocular adnexa (eye region)
• Salivary glands
• Thyroid
• Skin
• Breast
• Small intestine (rare) 1, 4, 5, 10

Some forms, such as those in the ocular adnexa, may be linked to specific infectious agents like Chlamydia psittaci 4, 10.

Low-Grade vs. High-Grade

Most MALT lymphomas are low-grade, meaning they grow slowly and are less likely to spread quickly. High-grade transformation is uncommon but can occur, marked by more aggressive cellular features and a poorer prognosis 2, 8.

Unusual Presentations

Rarely, MALT lymphoma can involve multiple sites simultaneously or present in locations like the small bowel, sometimes with atypical features such as elevated tumor markers (e.g., Ca125) 1.

Causes of Malt Lymphoma

The development of MALT lymphoma is intimately linked to chronic immune stimulation. Both infectious and genetic factors contribute to its emergence, with the underlying biology varying by tumor location.

Cause	Mechanism	Associated Site(s)	Source(s)
H. pylori	Chronic inflammation	Stomach	1, 4, 7, 8, 11
Other Infections	Microbial antigen stimulation	Eye, skin, intestine	4, 10
Genetic Changes	Chromosomal translocations	Various	2, 3, 6, 9, 10, 11
Chronic Inflammation	Autoimmune or irritant	Salivary, thyroid, others	4, 5

Table 3: Major Causes and Risk Factors

Infectious Triggers

Helicobacter pylori infection is the single most important risk factor for gastric MALT lymphoma. The bacterium colonizes the stomach, prompting the formation of MALT in tissue that normally lacks it. Chronic immune stimulation by the bacteria supports the proliferation of B cells, which may eventually transform into lymphoma cells 4, 7, 8, 11.

Other microbes have been implicated in extragastric MALT lymphomas:

• Chlamydia psittaci: ocular adnexa
• Borrelia burgdorferi: skin
• Campylobacter jejuni: small intestine

The evidence for these associations is strongest in certain regions and is still being investigated 4, 10.

Genetic and Molecular Abnormalities

Specific chromosomal translocations play a key role in the pathogenesis of MALT lymphoma. The most well-characterized include:

• t(11;18)(q21;q21): Fuses API2 and MALT1 genes, leading to activation of the NF-κB pathway. Common in gastric and pulmonary MALT lymphomas and associated with resistance to antibiotic therapy 2, 3, 6, 7, 9, 10, 11.
• t(1;14)(p22;q32): Involves the BCL10 gene.
• t(14;18)(q32;q21): Involves IGH-MALT1; more frequent in extragastric sites 3, 6, 9, 10, 11.
• Other aberrations: Trisomy 3 and 18, t(3;14)(q27;q32), and rare rearrangements involving FOXP1 6, 9, 10, 11.

Chronic Inflammation and Autoimmunity

Some MALT lymphomas develop in the context of chronic autoimmune conditions or persistent irritation, especially in the salivary glands (as seen in Sjögren syndrome) and thyroid gland (as seen in Hashimoto thyroiditis) 4, 5.

Treatment of Malt Lymphoma

The management of MALT lymphoma is tailored to its location, stage, and underlying biology. Many forms are highly treatable, with excellent long-term outcomes, especially when detected early.

Treatment	Indication	Outcome Highlights	Source(s)
Antibiotic Therapy	H. pylori+ gastric cases	Remission in ~70–75%	4, 7, 8, 10, 11
Radiotherapy	Localized disease	High local control, curative	4, 13
Chemotherapy	Advanced, unresponsive cases	High remission rates	12, 15
Immunotherapy	CD20+ disease (e.g., rituximab)	Disease stabilization, some responses	1, 14
Surgery	Rare, for complications	Reserved for select cases	12

Table 4: Treatment Modalities in MALT Lymphoma

Eradication of Infectious Triggers

For gastric MALT lymphoma associated with H. pylori, triple antibiotic therapy is the first-line treatment. Eradication of the bacteria leads to lymphoma regression in approximately 70–75% of cases 4, 7, 8, 10, 11. Similar approaches are being explored in extragastric sites, such as doxycycline for ocular adnexal MALT lymphoma with Chlamydia psittaci infection, though the evidence is less definitive 4, 10.

Radiotherapy

Moderate-dose radiotherapy (RT) is highly effective for localized (stage I/II) MALT lymphoma, achieving local control rates above 95% and high cure rates, particularly for gastric and thyroid sites 13. RT is generally well-tolerated and offers a non-surgical curative option for many patients.

Chemotherapy

Systemic chemotherapy is reserved for patients with disseminated disease, resistance to primary therapy, or high-grade transformation. Both single-agent (e.g., chlorambucil, cyclophosphamide) and combination regimens (e.g., mitoxantrone, chlorambucil, and prednisone [MCP]; R-CHOP) have demonstrated high response rates and durable remissions 1, 12, 15. Continuous low-dose oral chemotherapy can be a viable alternative to surgery in some settings 12.

Immunotherapy

Rituximab, a monoclonal antibody targeting the CD20 antigen on B cells, can induce remission or disease stabilization in MALT lymphoma, especially in advanced or relapsed cases. Its efficacy may be somewhat limited in gastric MALT due to poor penetration into certain tissue sites, but it remains an important option, particularly for those unsuitable for chemotherapy 1, 14.

Surgical Intervention

Surgery is now rarely performed, reserved mainly for complications such as bowel obstruction or for diagnostic purposes. Historically, gastrectomy was common but is now largely replaced by less invasive options 12.

Treatment Personalization

Treatment decisions should be individualized, taking into account disease site, stage, patient preferences, and the presence of specific genetic alterations (such as t(11;18)), which can predict resistance to antibiotics 4, 7, 11. Multidisciplinary care and regular follow-up are essential for optimal management 5.

Conclusion

MALT lymphoma is a distinct, generally indolent B-cell lymphoma that arises in mucosal sites, frequently in the context of chronic infection or inflammation. Its subtle symptoms and diverse presentations underscore the importance of awareness and careful diagnostic workup. Advances in understanding the molecular and microbial drivers of this disease have led to effective, often less invasive treatments, with excellent outcomes for most patients.

Key Takeaways:

• Symptoms are often non-specific and can include fatigue, weight loss, and site-specific complaints such as abdominal pain or swelling 1.
• Types of MALT lymphoma vary based on location and grade, with gastric and extragastric subtypes showing different associations and clinical behaviors 1, 4, 5.
• Chronic infection (especially H. pylori) and genetic changes (notably certain chromosomal translocations) are central to pathogenesis 4, 7, 9, 10.
• Treatment is highly effective and tailored to disease site, extent, and molecular features, with antibiotics, radiotherapy, chemotherapy, and immunotherapy all playing roles 4, 7, 8, 13, 14, 15.

Early recognition and multidisciplinary management are the cornerstones for ensuring the best possible outcomes in MALT lymphoma.