黏膜相关淋巴组织淋巴瘤

在呼吸道、消化道、泌尿生殖道黏膜及黏膜下存在无结构、散在的淋巴细胞。有结构的黏膜相关淋巴组织主要存在于回肠末端及支气管黏膜下。其最具特征的结构为Peyer斑（Peyer’s patches,1667年首先由Peyer描述而得名）。有结构的黏膜相关淋巴组织与淋巴结的淋巴组织结构相似,但无包膜。单个Peyer斑呈卵圆形,由生发中心、帽区及宽阔的边缘带B细胞构成。其外围为相邻的副皮质区样的T细胞区。边缘区的B细胞可进入覆盖Peyer斑的圆顶区上皮内（这些上皮内的B细胞与小肠其他部位上皮内的T细胞有别）。此外,固有膜内的浆细胞也是黏膜相关淋巴组织的一个组成成分。概括起来,     

Mucosa-associated lymphoid tissue lymphoma in conjunctiva

A case of primary mucosa-associated lymphoid tissue (MALT) lymphoma (marginal zone B-cell lymphoma of MALT according to WHO classification) in conjunctiva, which presented as a slowly growing salmon-colored mass at limbus of left eye is reported. Histological examination revealed a diffuse low-grade lymphoma. Immunohistochemical analysis using monoclonal antibodies showed that the tumor cells are leukocyte common antigen (CD45)+, CD20+, CD3-, CD5-, CD10- and CD43-, which confirmed the B-cell lineage of lymphoma. The case is being reported for its rarity and clinical importance of recognizing such cases because of excellent prognosis.     

Mucosa-associated lymphoid tissue lymphoma of the esophagus coexistent with bronchus-associated lymphoid tissue lymphoma of the lung

Non-Hodgkin's lymphoma very rarely involves the esophagus, occurring in less than 1% of patients with gastrointestinal lymphoma. A few cases of mucosa-associated lymphoid tissue (MALT) lymphoma of the esophagus have been reported in the English literature. To our knowledge, there has been no report of MALT lymphoma of the esophagus coexistent with bronchus-associated lymphoid tissue lymphoma (BALT) of the lung. This report details the radiological and clinical findings of this first concurrent case.     

Mucosa-associated lymphoid tissue lymphoma in the conjunctiva of a child

Marginal zone lymphoma of the mucosa-associated lymphoid tissue (MALT) occurring in the conjunctiva has yet not been described in pediatric patients. We present a case of a 10-year-old girl with a MALT lymphoma involving the conjunctiva. The tumor consisted of plasma cells and marginal zone cells with discrete epitheliotropism. Immunohistochemical studies revealed positivity for CD20 and cytoplasmic immunoglobulin light chain restriction. Polymerase chain reaction-based molecular analysis of the infiltrate showed a monoclonal rearrangement for the hypervariable complimentary determining region III immunoglobulin region; whereas, a polyclonal pattern was seen for the T-cell receptor chain. Extensive further examination, including molecular techniques, revealed that the lymphoma was restricted to the conjunctiva (stage IA) and was not associated with any specific infection. The patient was treated with surgery and additional local cryotherapy. After 15 months of follow-up, the patient remains in complete remission.     

Mucosa-associated lymphoid tissue lymphoma: molecular pathogenesis and clinicopathological significance

Mucosa-associated lymphoid tissue (MALT) lymphoma is a low-grade tumor closely associated with chronic inflammation such as that of Helicobacter pylori gastritis, Sjogren's syndrome, and Hashimoto's thyroiditis. Tumor regression by H. pylori eradication alone is well known in gastric MALT lymphoma, but some tumors occur in the absence of pre-existing chronic inflammation. The understanding of MALT lymphoma biology has significantly improved, and recurrent cytogenetic alterations have been detected. These include the trisomies 3 and 18, and the translocations t(11;18)(q21;q21), t(1;14)(p22;q32), t(14;18)(q32;q21), and t(3;14)(p14.1;q32). At least some of these alterations result in the constitutive activation of the nuclear factor (NF)-kappaB pathway, and may exert anti-apoptotic action. Apoptosis inhibitor 2-MALT lymphoma-associated translocation 1 (API12-MALT1) fusion, resulting from t(11;18)(q21;q21), is specific to, and is the most common in, MALT lymphomas, and its clinicopathological significance has been studied extensively. The focus of the present review is on the recent progress made in elucidating MALT lymphomagenesis and its clinicopathological impact, especially in terms of the effect of API2-MALT1 fusion on this unique tumor.     

乳腺粘膜相关型淋巴瘤临床病理观察

目的：探讨乳腺粘膜相关性淋巴瘤（MALT-ML）的病理特征。方法：对4例乳腺MALT-ML的手术根治及（或）活检标本做常规石蜡切片、HE染色和免疫组化ABC法标记。结果：4例乳腺MALT-ML中2例为CCL细胞型,1例为CCL细胞型向母细胞样转化,另1例炎单核样B细胞型。4例均显示B细胞单克隆性及滤泡克隆化和淋巴上皮病变。结论：乳腺MALT-ML有与其他部位MALT-ML相似的形态特征。     

黏膜相关淋巴组织淋巴瘤和凋亡相关基因

细胞凋亡受抑是黏膜相关淋巴组织(mucosa-associated lymphoid tissue, MALT)淋巴瘤发生的重要机制。MALT淋巴瘤凋亡相关基因的研究逐渐引起了重视。API2-MALT1融合基因和bcl-10过表达分别激活NF-κB,以NF-κB激活为核心,涉及到p53,Fas,API2,MALT1等凋亡相关基因,导致细胞凋亡受抑。     

Mucosa-associated lymphoid tissue (MALT) lymphoma: a practical guide for pathologists

Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) is the third most common non-Hodgkin lymphoma subtype, accounting for around 6-8% of all non-Hodgkin lymphomas in the Western hemisphere. Although MALT lymphomas are clinically indolent, the disease is typically chronic, requiring long-term clinical surveillance and, often, repeated biopsies. Pathologists thus play a central role in the diagnosis and management of these patients. The optimal diagnosis and management of a MALT lymphoma requires careful integration of morphological, immunohistochemical and molecular information, together with close cooperation with the clinician treating the patient. This review discusses recent developments in the molecular pathogenesis of MALT lymphoma and provides strategies for integrating this information into daily pathological practice.     

Mucosa-associated lymphoid tissue (MALT) Iymphoma

Isaacson et al. defined MALT lymphoma as a neoplasm that mimics MALT lymphocytes, which are normally present in the small intestine. However, there are various problems with this definition of MALT lymphoma. First, the incidence of MALT lymphoma is not high in sites where MALT lymphocytes are normally present. Lymphoepithelial lesions are most common in the small intestine and the tonsil, but MALT lymphoma is rare in these sites. In contrast, MALT lymphoma is frequent in the tissue in which MALT lymphocytes are not normally present, such as the stomach, the breasts, the lungs, and orbital tissue. In these tissues or organs, chronic infections, such as chronic gastritis, lymphocytic mastopathy, Hashimoto's thyroiditis, and myoepithelial sialoadenitis (or Sjögren's syndrome), can be a precursor condition of lymphoma. These findings suggest that in pathological conditions MALT lymphoma arises, not from MALT tissue normally present, but from the lymphoid tissue. Also evidence is lacking that lymphoepithelial lesions imitate the normal function of MALT lymphocytes. Arber et al. Found no difference in the frequency of lymphoepithelial lesions between primary and secondary breast lymphomas, suggesting that lymphoepithelial lesions may merely reflect the aggressiveness of the tumor. We have not observed proliferating monotypic plasma cells in the dome epithelium merging with the underlying CCL cells. Isaacson et al. reported that MALT lymphoma is characterized by a good prognosis. However, extranodal lymphomas generally have a good prognosis and it remains to be determined if MALT lymphoma has a better prognosis than other extranodal lymphomas. There are reports indicating that the stage is a more important prognostic indicator than the grade in thyroid and stomach lymphomas. Hyjek et al. identified the presence or absence of capsular invasion as the most important prognostic indicator of thyroid lymphoma. We suggest that the relative prognoses of extranodal lymphomas should be determined by comparing various types of lymphomas at the same stage. Monocytoid B cell lymphoma in the salivary gland does not have a good prognosis. If MALT lymphoma and monocytoid B cell lymphoma are the same disease, then the prognosis of MALT lymphoma would be expected not to be very good. Despite the unresolved issues concerning Isaacson's definition of MALT lymphoma, Isaacson et al.'s characterization of MALT lymphoma should be highly evaluated in that it has disproved the theory that all B cell lymphomas are of FCC origin and suggested the existence of B cell lymphomas associated with an interfollicular pattern of spread. In addition to the stomach, the thyroid, the lung, and orbital tissue, MALT lymphoma can occur in the kidney, the breast, and the urinary bladder. However, it is doubtful that immune mechanism of MALT exists in these tissues under normal conditions. Tissues adjacent to the epithelium are exposed to massive antigenic stimulation when the epithelium is disrupted. MALT lymphocytes and monocytoid B cells may be B lymphocytes responding to such massive antigenic exposure. Further studies are needed to clarify the nature and histogenesis of MALT lymphoma.     

Low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) of thymus

This report describes a low-grade B-cell lymphoma of mucosa associated lymphoid tissue (MALT) involving the thymus of a 63-year-old woman with features suggestive of a connective tissue disease. Sections of the thymic lesion and of a lung biopsy performed at the same operation were examined histologically and by immunohistochemistry using the monoclonal antibodies CD45, CD20, CD79a, CD3, CD45RO, and AE1/AE3. Polymerase chain reaction (PCR) for immunoglobulin heavy chain gene rearrangement was also performed. The dense infiltrate of small lymphoid cells intimately admixed with ramifying epithelial elements, some of which had undergone cystic change, closely resembled a thymoma. The lymphoid infiltrate comprised centrocyte-like cells, small lymphocytes, plasma cells, and blasts. Most of the lymphoid cells were immunoreactive with the B-cell markers CD20 and CD79a, and PCR showed clonal immunoglobulin heavy chain gene rearrangement. The lung biopsy showed dense infiltration by small lymphoid cells, morphologically suggestive of lymphoid interstitial pneumonia. However, PCR showed a weak band in the amplification for immunoglobulin heavy chain gene rearrangement, identical to that within the thymus and suggesting either recirculation of cells to accumulated MALT or subhistological lymphoma. MALT lymphoma may rarely involve the thymus, and pathologists should be aware of this to avoid misdiagnosis as a thymoma. Immunohistochemical and/or molecular studies are of value in this regard. MALT lymphomas of the thymus, common with those arising in other organs, may develop in the setting of a connective tissue disease.     

Mucosa-associated lymphoid tissue lymphoma coexisting with epithelioid granulomas in the stomach of a patient with systemic sarcoidosis

Malignant lymphoma arising in the stomach of a 23-year-old Japanem man with systemic sarcoldosis is presented. The patient was followed because of systemic sarcoidosis involving the lungs, eyes, and lymph nodes. Biopsy specimens from the stomach were repeated because of recurrent eplgastraigia and multiple ulcerations. Some of the specimens revealed epithelloid granuiomas with no caseous necrosis, which confirmed gastric involvement of sarcoidosis. Three years after the initial diagnosis, biopsy specimens taken from the stomach were diagnosed as malignant lymphoma of the large cell type. The resected stomach revealed muiticentric mucosa-associated type malignant lymphoma of low-grade B cell type, with foci of high-grade transformation coexisting with numerous epithelioid granulomas with no caseous necrosis. Epithelloid granulomas were observed in all the respected lymph nodes, liver, and appendix, which had been obtained at operation, whereas malignant lymphoma was limited to the stomach. Hellcobacter pylori (H. pylori ) infection was also observed in the stomach. Consequently, the present report is a rare case of coexistence of malignant lymphoma and involvement of sarcoidosis in the stomach. Both H. pylori infection and active sarcoid noduies may play a role in the development of malignant lymphoma, although the exact mechanism remains undear.     

Heparin-induced hyperplasia of lymphoid tissue

Experiments on newborn and sexually mature mice and rats showed that repeated injection of heparin leads to an increase both in the number of lymphocytes in the thymus and spleen and in the number of hematopoietic stem cells forming endogenous colonies in the spleen. The lymphoid tissue and the pool of colony-forming units are conjecturally under the regulatory influence of the adrenocortical hormones and of the product of the mast cells-heparin.     

Localized lymphoid hyperplasia of the rectum resembling polypoid mucosa-associated lymphoid tissue lymphoma: a report of three cases

Histologically, benign lymphoid hyperplasia of the rectum is usually characterized by large lymphoid follicles with active germinal centers and by a narrow surrounding mantle zone and marginal zone (MZ). We report here three cases of benign lymphoid hyperplasia of the rectum associated with prominent marginal zone hyperplasia, which caused serious difficulty in the differential diagnosis from the polypoid type of mucosa-associated lymphoid tissue (MALT) lymphoma. Colonoscopy demonstrated small sessile polyps in all three cases. Histologically, the lesions were characterized by a hyperplastic germinal center and expanded MZs. The expanded MZs contained numerous monocytoid B-cells (MBC) and scattered large transformed B-cells. Initially, combined colonoscopic and histological findings strongly supported a diagnosis of polypoid MALT-type lymphoma of the rectum. However, there were neither colonized lymphoid follicles nor lymphoepithelial lesions in any of the three lesions. MBCs and large transformed B-lymphocytes were CD43- and bcl-2-. Moreover, immunohistochemical and genotypic studies proved the polytypic nature of the B-lymphocytes in all three lesions. The present cases indicated that benign lymphoid hyperplasia of the rectum should be included in the differential diagnosis for polypoid MALT-type lymphoma of the rectum.     

Isolated lymphoid hyperplasia of the bone marrow simulating malignant lymphoma.

Lymphoid hyperplasia of the bone marrow occasionally resembles malignant lymphoma and may lead to confusion in bone marrow interpretation. The case of a patient with an unusual variant of isolated bone marrow lymphoid hyperplasia in which histologic overlap with lymphoma was found is presented. The case illustrates the difficulties in bone marrow interpretation that lymphoid hyperplasia can present. One cannot always rely on the number, size, or general pattern of lymphoid nodules to determine whether a lesion is benign or malignant. We suggest that when isolated lymphoid hyperplasia is composed of mature lymphocytes and confined to the marrow, a diagnosis of malignant lymphoproliferative disease should not be made.     

Low-grade B cell lymphoma of mucosa-associated lymphoid tissue in the thymus of a patient with rheumatoid arthritis

The majority of thymlc lymphomas are either lymphoblastic lymphoma, large B cell lymphoma or Hodgkin's disease, and other types of non-Hodgkin lymphoma are rare. A case of low-grade B cell lymphoma of mucosa-associated lymphoid tissue (MALT) In the thymus is reported. A 55-year-old Japanese female with a history of rheumatoid arthritis (RA) complained of back pain. A mediastinal tumor was identified by computerized tomography and magnetic resonance imaging, and the thymus was resected through median sternotomy. The solid and nodular tumor had several small satellite extensions and was completely confined to within the thymus. Hlstologically, monotonous medium-sized centrocyte-like cells occupied the medulla of the thymus and Infiltrated Hassan's corpuscles (lymphoepithellal lesions). Immunohistochemically, tumor cells were positive for CD20 and CD79a. IgA and kappa light chain restriction were also found in plasmacytoid cells in the tumor. Clonal rearrangement of the immunoglobulin heavy chain gene was demonstrated by polymerase chain reaction. This case was diagnosed as MALT-type low-grade B cell lymphoma In the thymus. This is the first report of low-grade B cell lymphoma In the thymus associated with RA. As autoimmune diseases are known to be associated with lymphoid neoplasms, It is suggested that the RA played an Important role in the development of malignant lymphoma in this case.     

Malignant lymphoma of mucosa-associated lymphoid tissue

Lymphomas of the gastrointestinal tract, salivary glands, lung and thyroid are grouped together as tumours arising in mucosa-associated lymphoid tissue. The great majority of them are of B-cell origin but distinctive T-cell lymphomas are also recognized in the gastrointestinal tract. These lymphomas tend to remain localized for prolonged periods but, whereas the B-cell group respond favourably to local therapy, the T-cell group are associated with severe morbidity and their overall prognosis is extremely poor. Accepted histological classifications of non-Hodgkin's lymphomas are difficult to apply to these tumours. In this paper their morphological features are reviewed; recent findings based on immunohistochemistry and DNA analysis are presented; and the biological behaviour of these tumours is discussed insofar as they offer insight into mucosal immunological mechanisms.     

Primary hepatic B-cell lymphoma of mucosa-associated lymphoid tissue.

Mucosa-associated lymphoid tissue (MALT) lymphomas are low-grade B-cell lymphomas that occur in a variety of extranodal sites but rarely as a primary hepatic lymphoma. We describe the histological findings, immunophenotype, and immunohistochemistry of one such lymphoma found incidentally in a 69-year-old woman. The lymphoid infiltrate invaded the liver in a serpiginous configuration with entrapment of nodules of normal liver. Reactive follicles were surrounded by intermediate-sized lymphoid cells with slightly irregular nuclei and pale cytoplasm. Only a few scattered lymphoepithelial lesions were identified since most of the bile ducts were destroyed. The immunophenotype determined by flow cytometry identified the lymphoid cells as being CD19, CD20 positive and exhibiting lambda light chain restriction. CD5, CD10, and CD23 were negative. Immunohistochemistry showed the neoplastic cells to be positive for CD20 (L-26) and bcl-2. The reactive follicles were negative for bcl-2. CD3 showed only a few scattered T cells. Cyclin D1 did not stain the neoplastic cells. Cytokeratin (AE1/AE3) highlighted the lymphoepithelial lesions and residual bile ducts. MALT lymphomas need to be recognized and distinguished from other B-cell lymphomas, particularly mantle cell lymphomas, because of the difference in behavior and treatment.