A Review of Primary Thyroid Lymphoma: Molecular Factors,Diagnosis and Management

Purpose/aim: To focus on current aspects of primary thyroid lymphoma (PTL), which is a rare clinical entity usually manifested by a rapidly growing mass in the neck that can cause pressure symptoms.

Materials and Methods: Relevant papers in PubMed published through June 2017 were selected to track updated information about PTL with an emphasis on diagnosis and novel therapeutic management.

Results: The most frequent cases include non-Hodgkin lymphoma derived from B-cells, mainly diffuse large B-cell lymphoma (DLBCL) followed by mucosa-associated lymphoid tissue (MALT) lymphoma or a mixed type. Other subtypes are less common. Lymphomas derived from T-cells and Hodgkin lymphomas are extremely rare. Hashimoto's autoimmune thyroiditis has been implicated as a risk factor for lymphoma. At the molecular level, the Wnt5a protein and its receptor Ror2 are involved in the course of the disease. Ultrasonography, fine needle aspiration (FNA) biopsy, and core or open biopsy combined with new diagnostic facilities contribute to an accurate diagnosis. An increased potential exists for a cure without the need for a radical surgical procedure. Modern chemoradiation therapy plus the monoclonal antibody rituximab, which acts against CD20, have limited the need for surgical interventions and provide an excellent outcome in most cases. However, some cases have resulted in treatment failure or recurrence.

Conclusions: A multidisciplinary approach must be used to define the management policy in each case. Future efforts by researchers are likely to be focused on the molecular level.     

Immunoglobulin heavy chain Diversity genes rearrangement pattern indicates that MALT-type gastric lymphoma B cells have undergone an antigen selection process

Gastric MALT lymphoma usually develops from chronic gastritis, the vast majority of which (>90%) is associated with Helicobacter pylori infection. We sequenced the third complementarity determining region (CDR3) of immunoglobulin heavy chain genes in 19 gastric MALT lymphoma clones to determine the pattern of variable (V), diversity (D) and joining (J) gene utilization during immunoglobulin gene rearrangement.
DNA was extracted from paraffin-embedded sections and the rearranged CDR3 regions were amplified using a semi-nested polymerase chain reaction (with primers complementary to the conserved framework-three segment of the variable region [FR3A] and J regions). The DNA used for cloning and sequencing was obtained after purification of monoclonal bands excised from polyacrylamide gels. The N-D-N region specific to each clone was compared with known germline D sequences.
Similarly to that observed in normal and leukaemic B cells, our series of gastric MALT lymphomas showed apparent preferential utilization of genes from the DXP family. In two cases no similarity between the CDR3 nucleotide sequences of the neoplastic clones and the known germline D sequences could be found. In 10/19 analysed alleles the lymphoma B-cell clones appeared to contain two D gene segments (D-D recombination), a rare occurrence in normal individuals but one which has been described as a significant event in the determination of idiotype expression and antigen-binding affinity. Remarkably, despite the use of different D and J segments, the resultant amino acid sequences matched in two patients, suggesting the presence of a common selecting antigen.
The observed pattern of D gene rearrangement suggests that MALT lymphoma B-cell clones have undergone antigen selection, which seems to indicate that the antigen stimulation plays a pivotal role in the development of the lymphoma.     

原发性胃肠道粘膜相关淋巴组织淋巴瘤47例临床病理分析

目的 探讨原发性胃肠道粘膜相关淋巴组织淋巴瘤(GIL-MALT)的临床病理特点。方法 回顾性分析1990～2000年我院经手术及病理证实的47例胃肠道MALT患者临床病理资料。结果 47例患者平均年龄57．2岁，男女比例2．1：1。以腹痛和发热为主。病变分布为胃32例，小肠4例，回盲部及盲肠5例，大肠6例。内窥镜下息内型15例，溃疡型25例，弥漫型7例。除1例为T细胞淋巴瘤，其余均为B细胞淋巴瘤。结论 胃肠道粘膜相关淋巴瘤以中老年为主，男性居多，临床误诊率较高。内窥镜下多次多点活检、深凿活检可提高本病的确诊率。     

良性淋巴上皮病、淋巴上皮癌、MALT淋巴瘤的关系

良性淋巴上皮病(benign lymphoepithelial lesion)、淋巴上皮癌(lymphoepithelial carcinoma)、黏膜相关淋巴组织型结外边缘区B细胞淋巴瘤(MALT淋巴瘤)(extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue,MALT lymphoma)是3种性质不同但又存在某些关联的病变,本文对3种病变的病因、组织病理学表现及三者之间的关系进行了介绍,并结合叶为民等论文中的一些内容进行了简要探讨。     

Expression of adhesion molecules in primary B-cell gastric lymphoma and lymphoid follicles

To determine whether primary B-cell gastric lymphoma (GL) is one entity, we examined the expression of three adhesion molecules in the microvasculature of lymphomas. Stromal cells, including vascular endothelial cells, within lymphoid follicles of the gastric mucosa were also investigated. Twenty-two surgical specimens of GL were classified into low-grade malignant lymphoma arising from mucosa-associated lymphoid tissue (low-grade lymphoma, n=9), and high-grade malignant lymphoma with (secondary high-grade lymphoma, n=6) or without (primary high-grade lymphoma, n=7) a low-grade component. The proportion of venules positive for ELAM-1 or VCAM-1 was significantly higher (P<0.001) in primary high-grade lymphoma than in low-grade and secondary high-grade lymphomas. In gastric lymphoid follicles, the stromal cells of the germinal centre (GC) were positive for ICAM-1, ELAM-1, and VCAM-1, but the stromal cells of the marginal zone (MZ) were positive only for ICAM-1. We found two patterns of adhesion molecule expression in gastric lymphoid follicles, the MZ pattern and the GC pattern. Low-grade and secondary high-grade lymphomas, which had the MZ pattern, might be of MZ-cell lineage, but most primary high-grade lymphomas, which had the GC pattern, might be of follicular centre cell lineage.     

Marginalzonenlymphome: extranodale vom MALT-Typ, nodale und splenische

Marginal zone B-cell lymphomas (MCL) of extranodal, nodal and splenic origin appear to be different lymphoma entities with a similar growth pattern in the marginal zone of the B-follicles. Decisive for the detection of MCL as a distinct lymphoma entity was the "MALT concept" for lymphoid infiltrates in the gastric and intestinal mucosa as described by Isaacson et al. in the 1980's. Immunohistological stainings for the immunoglobulin light and heavy chains and molecular pathological studies of the immunoglobulin heavy chain gene configuration have subsequently confirmed the neoplastic nature of the extranodal infiltrates and differentiated marginal zone cells from mantle zone cells. In 1994, the MCL of MALT type as well as of nodal and splenic origin were included in the REAL classification and in 1998 in the new WHO classification for lymphomas. Meanwhile extranodal MCL of MALT-type have been observed in almost every organ and site of the body, by far most frequently in the gastric mucosa. Beside the typical growth pattern, lymphoepithelial lesions are a distinct diagnostic feature of extranodal MCL. Clinically, the small cell extranodal MCL show a very good prognosis with regression after treatment. As for nodal and splenic MCL, we need further studies to evaluate the prognostic aspects and to compare them with other B-cell lymphomas. The same is true for primary extranodal large B-cell lymphomas or blastic transformation to a large cell lymphoma; in these tumors the diagnosis of a MALT type lymphoma should only be made if a small cell component with MALT-specific criteria can be proved.     

Follicular dendritic cells in extranodal non-Hodgkin lymphomas of MALT and non-MALT type

Extranodal lymphomas of the thyroid (n=19), kidney (n=15) and testis (n=30) were investigated histologically and immunohistochemically for follicular dendritic cell pattern using the monoclonal antibody Ki-FDC1P. This recognizes follicular dendritic cells in paraffin sections. Follicular dendritic cells were most predominant in lymphomas of the thyroid. These thyroid lymphomas showed the morphological features of mucosa-associated lymphoid tissue (MALT) type lymphomas in 18 of 19 cases and were classified as high-grade malignant lymphoma of MALT type with evidence of a low-grade malignant component (n=18). Ten of these cases contained destroyed reactive follicles of follicular dendritic cells. In 6 of these 10 cases follicular dendritic cells occurred in a pattern of tumour-associated abortive follicle type. The remaining lymphoma of the thyroid was an immunoblastic lymphoma of B-cell type showing no detectable follicular dendritic cells. In extranodal lymphomas of non-MALT type follicular dendritic cells occurred in only two cases where immunocytoma involved the kidney. Malignant lymphomas of the kidney (chronic lymphocytic leukaemia,n=2; immunocytoma,n=4; centroblastic lymphoma,n=9) and of the testis (immunocytoma,n=2; centroblastic lymphoma,n=27; immunoblastic lymphoma of B-cell type,n=1) revealed no characteristics of MALT type lymphoma, cytologically or with respect to follicular dendritic cells. Classical lymphoepithelial lesions formed by centrocyte-like cells, a hallmark of MALT, occurred exclusively in thyroid lymphomas of MALT type. Although occurrence of classical lymphoepithelial lesions formed by centrocyte-like cells was limited to thyroid lymphomas of MALT type, a growth pattern of lymphoid blasts, with formation of lesions mimicking lymphoepithelial lesions superficially, was found in 6 of 27 testicular centroblastic lymphomas. Follicular dendritic cells in non-Hodgkin's lymphomas of MALT type show distinct follicular patterns not found in other extranodal lymphomas such as those found in the kidney and testis.     

CD44S和CD44V6在胃淋巴瘤中的表达及意义

目的：探讨ＣＤ４４Ｓ和ＣＤ４４Ｖ６在胃淋巴瘤中的表达特征及其临床意义。方法：采用ＨＥ染色、ＣＤ３、ＣＤ２０、ＣＤ４４Ｓ和ＣＤ４４Ｖ６的经法观察４７全。 低度恶 胃淋巴瘤中的阳性率为工恶生为６２％,差异显著（Ｐ＝０．０２）,ＣＤ４４Ｖ６在低度胃淋巴瘤中的阳性率为６％,高度恶性为３８％,差异显著（Ｐ＝０．０１）。ＣＤ４４Ｓ在临床１期的阳笥率为３０％,２～４期为７５％,差异显著（Ｐ－０－．００２）。结论     

Nongastrointestinal mucosa-associated lymphoid tissue (MALT) lymphomas: Clinical and therapeutic features of 24 localized patients

Background: Peripheral B-cell lymphoma of the marginal zone (MALT, low-grade), presenting as localized, extranodal disease, usually affects the elderly. The gastrointestinal tract is the most frequently involved extranodal location, representing 70% of all MALT lymphomas. Recently, numerous other extranodal sites involved by MALT lymphomas have also been described.Patients and methods: From January 1990 to October 1995, 24 patients with untreated nongastrointestinal low-grade MALT lymphoma were submitted to treatments ranging from the local approach of radiotherapy and local -interferon (-IFN) administration to chemotherapy. The tumours were located in the lung (seven cases), conjunctiva (four cases), lachrymal gland and orbital soft tissue (four cases), salivary glands (three cases), skin (three cases), breast (two cases)' and thyroid (one case). All patients had low-grade stage IE tumours.Results: Chemotherapy was administered in 11 patients (six with lung, three with salivary gland, one with breast, and one with thyroid locations); radiation therapy was employed in seven patients (three with lachrymal gland, three with skin, and one with breast locations); local -IFN administration was administered in five patients (four with conjunctival, and one with lachrymal gland sites); and surgery was employed in one patient with a lung tumour. All patients achieved complete remissions; three local recurrences and two relapses in other sites were observed. The global five-year survival rate was 100% with a relapse-free survival rate of 79%.Conclusions: These data confirm the significant efficacy of different therapeutic approaches to specific sites inbes obtaining a good remission rate for nongastrointestinal localized low-grade MALT lymphomas.