Marginal zone B-cell lymphoma includes three pathological types: extra-nodal mucosa-associated lymphoma, intra-nodal marginal zone B-cell lymphoma, and splenic marginal zone B-cell lymphoma. The three pathological types have distinct clinical features and different prognoses, and the principles of treatment are different. Early-stage extra-nodal mucosa-associated lymphoma is treated primarily with radiation therapy.
I. Marginal zone and marginal zone cells
Secondary lymphoid follicles in the lymph nodes, spleen and extra-nodal lymphoid tissue comprise two morphologically and functionally identical regions: the follicular center and the set of cells, the latter forming the lymphatic crown and the marginal zone. Marginal bands are well developed in secondary lymphoid tissues such as splenic white marrow and Paired collection lymph nodes and in mesenteric lymph nodes, but are poorly developed in lymph nodes other than mesenteric lymph nodes, where distinct marginal band formation is rarely seen. The marginal zone includes a special group of lymphocytes called marginal zone B cells, which are characterized by abundant cytoplasm, pale and irregular nuclei, and a centrally located nucleus. Marginal zone B cells resemble central follicular cells and are also referred to as central cell-like cells. Marginal bands are poorly developed in most peripheral lymph nodes, but are common in reactive lymphadenitis. The marginal zone is located at or near the subepithelial lymphatic sinus, and some of the cells in these proliferative areas resemble B cells with monocyte-like features.
II. Concept of mucosa-associated lymphoid tissue
The concept of mucosal-associated lymphoid tissue (MALT) was first proposed by immunologists and refers to the scattered non-peritoneal lymphoid tissues under the lamina propria and epithelium of the mucosa of the respiratory, gastrointestinal and genitourinary tracts, as well as certain organized lymphoid tissues with germinal centers, such as the tonsils, the paired collections of the small intestine MALT consists of three components.
(1) Nasal-associated lymphoid tissue (NALT) including pharyngeal tonsils, palatine tonsils, lingual tonsils, and other lymphoid tissues in the posterior part of the nose.
(2) gut-associated lymphoidtissue (GALT) including paired collection lymph nodes, lymphoid follicles, interepithelial lymphocytes and lamina propria lymphatic tissue.
(3) Bronchial-associated lymphoidtissue (BALT) is mainly located in the subepithelium of the bronchial lobe of the lung, and its structure is similar to that of Pai’s pooled lymph nodes, and the lymphocytes in the follicles are often proliferated into germinal centers by antigen stimulation. In addition to the gastrointestinal tract and bronchi, other sites such as the parotid gland, thyroid gland and lung have similar structures. These extra-nodal MALT lymphomas share common pathological features and differ from other inert B-cell lymphomas in pathology, immunology and clinical presentation.
III. Immunophenotype of marginal zone B cells
The immunophenotype of marginal zone B cells is mostly similar to that of monocyte-like B cells, and both express B-cell antigens: CD20 and CD79a positive, but lack CD5, CD10, CD23 and CD43 expression. However, marginal zone B cells usually expressed IgM and Bcl-2, whereas monocyte-like B cells lacked IgM and Bcl-2 expression. Marginal zone B cells had low or negative IgD expression, which was different from the strong IgD expression of lymphocytes in the nucleus pulposus. The lack of CD5 and CD10 expression in MALT lymphoma can differentiate intra-nodal chronic B-cell leukemia/small lymphocytic lymphoma, follicular lymphoma and central cell lymphoma.
Pathological classification of marginal zone B-cell lymphoma
In the REAL classification, marginal zone B-cell lymphoma is considered to be a B-cell-derived NHL with distinct clinicopathologic features, which includes both extraneural marginal zone B-cell lymphoma (MALT-type inert B-cell lymphoma) and intraneural marginal zone B-cell lymphoma. The latter has also been described as monocyte-like B-cell lymphoma, and recent studies have shown that intra- and extra-nodal marginal zone B-cell lymphomas have different morphologic, immunophenotypic, and clinical features. The morphologic and clinical features of splenic marginal zone B-cell lymphoma are significantly different from the first two. Therefore, intra-nodal marginal zone B-cell lymphoma and splenic marginal zone B-cell lymphoma are included as a proposed classification in the REAL classification. In the new WHO classification, marginal zone B-cell lymphoma is divided into three separate pathological types: MALT-type extra-nodal marginal zone B-cell lymphoma, lymph node MZCL, and splenic MZCL.
V. Clinical features of extra-junctional mucosa-associated lymphoma
Extra-junctional mucosa-associated tissue (MALT) lymphomas account for 4-13% of all lymphomas. The most common primary site is the gastrointestinal tract, accounting for 45%-56% of all MALT lymphomas. Other more common sites include the lung, eye and conjunctiva, thyroid, parotid, skin, and breast. 66%-74% of patients have stage I-II. MALT lymphoma can metastasize to distant lymph nodes and other blood systems such as bone marrow, liver or spleen, but metastasis to peripheral lymph nodes is relatively uncommon. The median age is 60 years, and it is more common in women. Radiotherapy is the most important treatment for stage I-II extranodal MALT lymphoma, achieving both very good outcomes and preservation of organ function. In recent bulk literature, the 5-year survival rate of early-stage extra-nodal MALT lymphoma with radiotherapy alone is over 95% and the disease-free survival rate is 77%.
(i) Gastrointestinal MALT lymphoma
The gastrointestinal tract is the most common primary site, accounting for 50% of all MALT lymphomas, with the gastric primary being the most common. Gastric MALT lymphoma is often confined to the stomach and develops at an older age, with a median age of about 60-69 years. The most common symptoms are upper gastrointestinal bleeding, epigastric pain and dyspepsia, while group B symptoms are extremely rare. The most frequently invaded site is the gastric body (64%), followed by the gastric sinus (43%). 20-30% of patients present with multifocal lesions in the stomach. The tumor is often located in the submucosa and sometimes shows diffuse changes. When no obvious mass is formed, multi-point random biopsy should be done during endoscopy to improve the accuracy of diagnosis. In addition, immunohistochemical examinations, including H. pylori staining, should be routinely done after biopsy.
(ii) Orbit
The most common site of non-gastrointestinal primary site MALT lymphoma is the adnexa of the eye, including the conjunctiva and ocular soft tissues. Although there are many studies reporting primary ocular NHL, most report MALT lymphoma along with other pathological types. As a result, there is less information on the clinical presentation and treatment of ocular MALT lymphoma.
Of the 48 cases of ocular adnexal MALT lymphoma treated by MGH from 1974 to 2000, 75% of cases were confined to the orbit and 10% had concurrent bilateral orbital invasion. In the orbit, the most frequently invaded sites were the intraorbital soft tissue (70%), conjunctiva (40%), and lacrimal gland (20%). Because intraorbital invasion is common, CT and MRI scans are recommended to define the extent of the lesion.
(iii) Parotid and salivary glands
The salivary glands usually lack lymphatic tissue, and chronic inflammation leads to aggregation and hyperplasia of lymphatic tissue. MALT lymphoma of the salivary glands is often seen in the setting of a benign lymphoepithelial-like lesion, Myoepithelialsialadenitis (MESA), which is associated with Sjogren’s syndrome, characterized by dry keratoconjunctivitis, mucosal dryness, dilated facial capillaries, and bilateral enlargement of the parotid glands. The incidence of lymphoma in women with dry syndrome is 43.8 times higher than in women without the disease.
MALT lymphoma can occur in any major or minor salivary gland, with the parotid gland being the most frequent site of invasion. Patients often have prolonged enlargement of the parotid gland. Bilateral invasion is rare and most patients have a dry syndrome.
Primary pulmonary lymphoma is rare, accounting for approximately 1.1% of extranodal lymphomas, and the most common pathological type is MALT lymphoma. Most patients are asymptomatic and are often detected on physical examination of the chest. common symptoms include cough, shortness of breath, chest pain, and hemoptysis. radiographs show nodules or masses, most cases being solitary, with multiple masses in 5-10% of patients. A definitive pathological diagnosis of primary MALT lymphoma of the lung is usually obtained only after surgery, and the principles of treatment include surgery, radiotherapy and chemotherapy.
(V) Other sites
Other sites of lymphoma include thyroid, breast and skin. MALT lymphoma of the upper respiratory tract is rare and can be seen in the nasopharynx, larynx and trachea, while other sites include thymus, gallbladder, liver, prostate, kidney, intracranial dura mater and rectum. Radiation therapy is an effective treatment and can preserve organ function. Early stage patients do not need to combine extensive surgery and chemotherapy.