Introduction

Mucosa-associated lymphoid tissue (MALT) lymphoma is a type of non-Hodgkin lymphoma, which is a cancer of the lymphatic system. It develops when white blood cells called B-lymphocytes, which are responsible for regulating the body’s immune response, become abnormal and spread uncontrollably around the body.¹ 

MALT lymphoma arises in the lymphoid tissue found in the mucosa. This is the moist lining of organs such as the stomach, lungs, mouth, eyes, and intestines, and it plays a vital role in immune protection at mucosal surfaces. The condition is also a type of marginal zone lymphoma (MZL) due to its ability to originate outside of the lymph nodes in a region of lymphoid tissue known as the marginal zone.¹ 

MALT lymphoma often affects people over the age of 60, and it begins in response to long-term inflammation in certain areas of the body due to infection or an autoimmune condition. For instance, chronic bacterial infection, caused by Helicobacter pylori (H. pylori), can give rise to MALT lymphoma in the stomach. Understanding the site-specific nature of the condition is key to recognising the varying features and associated symptoms, and can aid clinicians in carrying out suitable investigations, accurate diagnoses, and tailored treatment plans.¹ 

This article will explore the common sites of MALT lymphoma, their typical clinical features, and how this guides the diagnosis and treatment of people affected by the condition.

Common sites of MALT lymphoma and their clinical manifestations 

Stomach

The stomach is the most common site of MALT lymphoma, known as gastric MALT lymphoma, and accounts for about 40% of all MALT lymphoma cases. It most commonly develops in response to chronic infection with H. pylori, which causes stomach ulcers and inflammation. The persistent presence of this bacterium can cause genetic mutations to occur in B-lymphocytes, leading to their abnormal growth in the lining of the stomach.¹ Consequently, this can trigger a chronic immune response that encourages the growth of lymphoid tissue in the stomach (somewhere that this tissue type is not usually present) and can lead to gastric MALT lymphoma.²

Clinical features

• Indigestion
• Pain or discomfort in the stomach, like bloating
• Nausea
• Fever
• Loss of appetite
• Unintentional weight loss (less common)
• Fatigue, possibly due to anaemia (less common)^1,2 

As these symptoms can vary in severity and can overlap with the signs of other health conditions, gastric MALT lymphoma is frequently diagnosed during clinical investigations unrelated to stomach issues. Consulting your doctor about any unexplained gastric symptoms is crucial in enabling appropriate and timely testing to check for H. pylori infection and initiate treatment with antibiotics.¹ 

Salivary glands

The salivary glands are one of the most common sites of non-gastric MALT lymphoma, accounting for about 14% of all cases. Whilst only about 5–10% of salivary gland cancers are lymphomas. MALT lymphoma is the most common type of all lymphomas to occur specifically in these glands - MALT lymphoma makes up about half of these cases.³

The most commonly affected part of the salivary glands is the parotid glands, which are the largest of these glands and sit just in front of the ears. Salivary gland MALT lymphoma is strongly linked to Sjögren’s syndrome. This is an autoimmune condition that causes damage to the glands that produce fluid, like saliva and tears, and extensive dryness. Chronic inflammation in the salivary glands and damage to surrounding salivary tissue can lead to the development of lymphoid tissue in this area, which can give rise to MALT lymphoma over time.³

Clinical features

• A lump, swelling, or pressure in the jaw or cheek area, often painless
• Dry eyes or dry mouth due to Sjögren’s syndrome³

This type of MALT lymphoma usually remains localised for some time and is often detected early due to this pattern of occurrence, offering a positive outlook to those affected. However, it may also present mild or nonspecific symptoms, such as fatigue and fever. It is therefore crucial to consult your doctor about any persistent or worsening symptoms for timely investigation and targeted treatment, if required, such as surgery, radiotherapy, or immunotherapy.³ 

Eyes

MALT lymphoma that develops in the tissues surrounding the eyes, most commonly in the orbit that surrounds the eyeball, is known as ocular adnexal MALT lymphoma. This type of MALT lymphoma is the most common type of lymphoma affecting the eye area, accounting for about 55–70% of all ocular adnexal lymphomas. The condition usually affects one eye and is slow-growing, remaining confined to the eye area for several years.⁴

Clinical features

• Swelling or lumps around the eyes, often painless
• Redness or irritation
• Bulging of the eye
• Problems with vision, such as double vision⁴

As symptoms of ocular adnexal MALT lymphoma are often mild and progress gradually over time, this may lead to a delayed diagnosis. However, the outlook for the condition is relatively positive, especially when detected early, and localised treatment methods, such as radiotherapy, can be very effective.⁴

Thyroid gland

MALT lymphoma in the thyroid gland is rare, but it usually occurs in people affected by a chronic autoimmune condition called Hashimoto’s thyroiditis. Thyroid MALT lymphoma occurs in only about 0.5% of patients with Hashimoto’s thyroiditis. Thyroid MALT lymphoma tends to grow slowly and often remains confined to the thyroid or nearby lymph nodes for long periods, reinforcing the strong link between the inflammation caused directly by Hashimoto’s thyroiditis and the development of thyroid MALT lymphoma.^5,6

Most cases of MALT lymphoma are classified as primary thyroid lymphomas, accounting for about 10–23% of primary thyroid lymphomas. This means that the cancer grows in the thyroid gland first before spreading to the lymph nodes and then to other areas of the body.⁶

Clinical features 

• A lump or swelling in the neck, often painless
• Discomfort in the throat area or changes in the voice, like hoarseness
• Difficulty swallowing
• Difficulty breathing if the gland presses on the windpipe⁶

The rarity of this type of MALT lymphoma, as well as the overlap in symptoms with other thyroid conditions, highlights the importance of timely clinical investigations, such as biopsy or ultrasound scans, when a lump in the thyroid is noticed. It is crucial to distinguish this condition from the closely associated Hashimoto’s thyroiditis to ensure an accurate diagnosis and early management.^5,6

Lungs

MALT lymphoma can develop in the lungs, where it is referred to as primary pulmonary MALT lymphoma. It is a rarer type of non-Hodgkin lymphoma and makes up about 70–90% of all lymphomas that start in the lungs. The condition often affects people who have experienced persistent lung infections and those aged 50 to 70. It is also typically confined to the lungs over a long time; it can be asymptomatic, meaning it may not present any signs and is typically discovered during investigations for separate health concerns.^7,8

Clinical features

• Breathlessness
• Persistent cough
• Discomfort or pain in the chest⁷

Imaging scans are often carried out during clinical investigations, and pulmonary MALT lymphoma can appear as a single mass or multiple nodules. Scans can also depict more dense and solid areas that appear similar to infection or fluid in the lungs. Therefore, further imaging and tests are crucial in determining an accurate diagnosis and further management.^7,8

Skin 

MALT lymphoma rarely occurs in the skin and is known as primary cutaneous MALT lymphoma. It makes up about 20% of all primary cutaneous lymphomas, which represents a small group of skin lymphomas overall. The condition is a slow-growing type of lymphoma, and similarly to the other types of non-gastric MALT lymphomas covered in this article, it remains confined to the skin for several years.⁹

Clinical features

• Single or multiple small, raised, and painless lumps on the skin, known as papules (these resemble pimples)
• Red or purple patches that vary in size and often occur on the head, neck, back, arms or legs⁹ 

Lymphomas of the skin can appear similar to other common skin conditions like eczema or psoriasis, or even reactions to insect bites. They may be painless or asymptomatic, and as they are slow to develop, doctors often consider conservative treatment options, such as a ‘wait and watch’ approach, before radiation or surgical removal. Accurate investigations and diagnosis via skin biopsy are key in differentiating MALT lymphomas of the skin from other types of skin lymphomas and skin conditions. This is significant in supporting an optimal outlook of the condition.⁹

Intestines

MALT lymphoma accounts for approximately 5-8% of all non-gastric MALT lymphoma cases. It typically affects the small intestine, but MALT lymphoma can also occur in the colon - it makes up less than 1% of all colorectal cancers and is usually found during a routine colonoscopy.^10,11

Clinical features 

• Persistent abdominal pain or cramps
• Bloating
• Changes in bowel habits, like diarrhoea or constipation
• Occult gastrointestinal bleeding (internal bleeding in the small intestine detected via stool tests), or rectal bleeding from the colon (with blood visible in the stool)
• Unintentional weight loss or fatigue (especially in more advanced stages)¹¹

Intestinal MALT lymphomas differ from gastric MALT lymphomas of the stomach in that they are not associated with H. pylori infection. The diagnosis of intestinal MALT lymphomas typically consists of biopsy, imaging and an endoscopy or colonoscopy, depending on the area of the intestine affected. Treatment varies based on the extent of the condition and the symptoms presented, but it often consists of surgery or immunotherapy and presents a positive outlook when targeted early.^10,11 

Summary

MALT lymphoma is a rare but slow-growing type of cancer of the lymphatic system, affecting different parts of the body and presenting varying patterns of development. The varying clinical presentation and nonspecific symptoms of some MALT lymphoma types highlight the importance of an early diagnosis, which can be made through biopsy and imaging scans. It is imperative to consult with your doctor if you experience any unexplained or persistent symptoms. 

While MALT lymphoma generally has a positive prognosis due to its indolent nature, the outlook may differ depending on the site of the body and the differing clinical signs, as well as the response to treatment. If you or anyone you know may be affected, speak to your healthcare professional about the guidance and support networks available to help you through your journey.