A solitary minute thyroid lymphoma of MALT-type without lymphoid thyroiditis

Most of the primary thyroid malignant lymphomas have been considered of mucosa-associated lymphoid tissue (MALT) type and arise from lymphocytic thyroiditis. We report an uncommon case of a 67-yr-old man who underwent total thyroidectomy for multinodular goiter with tracheal compression. At histopathologic examination, we discovered a minute (3-mm diameter) lesion of low-grade thyroid lymphoma of MALT type without any lymphocytic thyroiditis lesion on 33 section levels of the entire thyroid gland. No general inflammatory, autoimmune, or lymphomatous disorder has been evidenced both at staging and after 30 mo of follow-up. MALT-type low-grade lymphoma may, in some instances, develop de novo within the thyroid without an antecedent MALT-type lymphoma.     

Monocytoid B-cell lymphoma: morphological variants and relationship to low-grade B-cell lymphoma of the mucosa-associated lymphoid tissue

Twenty-eight cases of monocytoid B-cell lymphoma of lymph nodes and 16 lymph node metastases of primary gastric lymphomas, mostly low-grade B-cell lymphomas of mucosa-associated lymphoid tissue (MALT) type were investigated morphologically and immunohistochemically. Both groups showed the same morphological and immunohistochemical features: diagnostically important sites of infiltration were the sinuses and the marginal zones. The tumour cells were either medium-sized or small. The cytoplasm stained grey with Giemsa and was sometimes rather pale. In imprints the grey colour of the cytoplasm was a characteristic feature. The medium-sized cell type was more frequent; in one third of the cases it was combined with a prominent lymphoplasmacytic component from the same clone, and it resembled the monocytoid B-cells of the sinuses. The small cell type was less common, was not combined with a lymphoplasmacytic component and more closely resembled marginal zone cells. The difference was underlined by the negative reaction with the monoclonal antibody Ki-B3 in the small cell type, which, conversely, was positive in the medium-sized cell type and in the monocytoid B-cell reaction of the sinuses. Both of these cell types, however, showed a granular reaction with the new monoclonal antibody Ki-Mlp. The morphological and immunohistochemical parallels are arguments in favour of the assumption that monocytoid B-cell lymphoma is the nodal equivalent of low-grade B-cell lymphoma of MALT type. This is further supported by the fact that in nine of our 28 cases of monocytoid B-cell lymphoma, lymphomas were found simultaneously or subsequently in organs of the MALT. Monocytoid B-cell lymphoma must be differentiated from an infiltration that occurs in the form of clusters of monocytoid B-cells in other low-grade B-cell lymphomas, especially in immunocytoma with a high content of epithelioid cells.     

Low-grade gastric B-cell lymphoma of mucosa-associated lymphoid tissue (MALT): a multifocal disease

Gastrectomy specimens from five patients following gastroscopic biopsies which showed low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) were examined by serially sectioning and paraffin wax embedding using a 'swiss roll' technique. This procedure allowed the construction of a map of the specimen on which the distribution of the lymphoma could be plotted. In each case confluent lymphoma was identified. In addition small foci of lymphoma consisting of 1-4 lymphoid follicles surrounded by neoplastic centrocyte-like cells were seen. The positions of these 'micro-lymphomas' were plotted on the gastrectomy maps, showing multiple foci distributed throughout the gastric mucosa. The identification of these microscopic lesions may explain the development of local relapse, often after a long disease-free interval, in patients with gastric MALT lymphoma treated by partial gastrectomy where excision appears to have been complete. Patients treated in this way should, therefore, be followed-up indefinitely, with regular endoscopy and gastric biopsy, in order to identify early local disease relapse.     

Higher frequency of p53 gene mutations in diffuse large B-cell lymphoma with MALT component

p53 gene mutation is not a frequent event in the tumorigenesis of lymphomas and the expression of p53 protein is independent of p53 gene mutations. The present study aimed to investigate mutations in the p53 gene in a series of extranodal B-cell lymphomas, and its association with p53 protein expression. A total of 52 cases were graded histologically into Grade 1, Grade 2 and Grade 3 tumors and p53 protein expression was detected using immunohistochemistry. Mutations in the p53 gene were analyzed using polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) and mobility shifts were confirmed by direct sequencing. The tumors comprised 26 (50%) Grade 1, 9 (17%) Grade 2 and 15 (29%) Grade 3. A high proportion of Grade 2 (25%) tumors expressed p53 protein (P = 0.051) and carried p53 gene mutation (33%) (P = 0.218). However, p53 protein expression was not associated with p53 gene mutations (P = 0.057). Transversion mutations (88%) were more frequently detected than transition mutations (12%). The present study revealed that p53 gene mutations and p53 protein expression occurred in higher frequencies in Grade 2 tumors, which may be of pathogenetic importance. The high frequency of transversion mutations may reflect the influence of an etiological agent in the tumorigenesis of mucosa-associated lymphoid tissue (MALT lymphoma).     

Histiocyte-rich, T-cell-rich B-cell lymphoma: a distinct diffuse large B-cell lymphoma subtype showing characteristic morphologic and immunophenotypic features

AIMS: The clinicopathological features of histiocyte-rich, T-cell-rich B-cell lymphoma (HRTR-BCL) were first recognized in 1992. In this study, 60 cases of HRTR-BCL were analysed in order to provide a detailed morphological and immunophenotypical profile of the disorder. METHODS AND RESULTS: HRTR-BCL is easily distinguished from other B-cell lymphomas rich in stromal T-cells by (i) a diffuse or vaguely nodular growth pattern, (ii) the presence of a minority population of CD15-, CD20+ large neoplastic B-cells, (iii) a prominent stromal component composed of both T-cells and non-epithelioid histiocytes, and (iv) the scarcity of small reactive B-cells. These criteria also enable a reliable distinction from lymphocyte-rich classical Hodgkin's lymphoma (CHL), from lymphocyte-predominant Hodgkin's lymphoma (LPHL), paragranuloma type and from peripheral T-cell lymphoma. Based on the morphology of the neoplastic cells and on their frequent bcl-6 immunoreactivity, we speculate that HRTR-BCL may be derived from a progenitor cell of germinal centre origin. CONCLUSIONS: HRTR-BCL presents characteristic clinical features, affecting predominantly middle-aged men who present with advanced stage disease and are at high risk of treatment failure. Considering these distinctive clinicopathological features, recognizing HRTR-BCL as a lymphoma entity may be justified.     

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.     

Comparative clinicopathological study of primary CNS diffuse large B-cell lymphoma and intravascular large B-cell lymphoma

Primary CNS diffuse large B-cell lymphoma (CNS DLBCL) is confined to the CNS, and constitutes a distinct entity. In the present study a series of 40 Japanese patients with CNS DLBCL who presented with neurological, but not systemic symptoms, was reviewed. Median survival was 18.7 months. CD5, CD10, Bcl-6, MUM-1, and Bcl-2 were positive in 30%, 10%, 84%, 100%, and 93% of patients, respectively. All CD10-negative patients had non-germinal center B-cell type. There was no significant difference in survival among the immunophenotypic subgroups. CNS DLBCL appeared to be homogenous as a group, which prompted the comparison with another distinct extranodal entity, intravascular large B-cell lymphoma (IVLBCL) in Japanese patients. CNS DLBCL patients did not differ in age, sex, or immunophenotype, including CD5 positivity, from IVLBCL patients, but were significantly less likely to have poor prognostic parameters than IVLBCL patients: the international prognostic index score was low or low–intermediate in 86% of CNS DLBCL patients and high or high–intermediate in 98% of IVLBCL patients. Notably, despite this difference, their survival curves almost overlapped. The present study highlights the issue of clinical distinctiveness of aggressive extranodal lymphomas, the peculiar migration and localization of which should be further clarified.     

A study of the properties of a low-grade mucosal B-cell lymphoma using a monoclonal antibody specific for the tumour immunoglobulin

Primary low-grade B-cell lymphomas of mucosa-associated lymphoid tissue (MALT) are tumours with distinctive clinico-pathological characteristics, two of which are studied in this paper, namely the tendency of the tumours to remain localized and the morphologic and phenotypic resemblance of the malignant cells to splenic marginal zone B cells. We have made a detailed study of a small intestinal lymphoma and a gastric lymphoma, which together with the spleen were resected from the same patient. Using a monoclonal antibody (7G3) raised against a unique determinant on the small intestinal tumour, we were able to detect disseminated small intestinal tumour cells in the stomach and spleen. The tumour in the stomach was genetically related, but non-identical to that in the small intestine, and was not recognized by 7G3. Lymphocytes expressing the marker of the small intestinal tumour (7G3) were present in lymphoid nodules in the stomach, and 7G3+ plasma cells were present beneath the gastric epithelium. In the spleen, cells expressing 7G3 were present in the marginal zone and plasma cells expressing the same marker were present in the red pulp. These findings suggest that low-grade MALT lymphomas may migrate beyond the primary tumour site, but that tumour cells distant to the primary site may differentiate into mature, non-dividing plasma cells. The localization of small intestinal tumour cells in the splenic marginal zones reinforces the suggestion of lineage homology between these populations of cells.     

One patient with double lymphomas: simultaneous gastric MALT lymphoma and ileal diffuse large B-cell lymphoma

Multiple different lymphomas in a single person are very rare. The author herein reports the case of a 69- year-old Japanese woman with double gastrointestinal lymphoma. The patient presented with epigastralgia. Endoscopic examination revealed erosions and elevation of the gastric body and a large ulcerated tumor of the terminal ileum. Biopsies were obtained from these lesions. The gastric lesion was MALT lymphoma with monocytoid B-cell proliferation and lymphoepithelial lesions. Light chain restriction was present. Helicobacter pylori were present on Giemsa stain. The gastric lesions did not regress despite of therapy, which were confirmed by follow-up biopsy. The ileal lesion was obvious diffuse large B-cell lymphoma. The lesion regressed by chemotherapy. The patient is now alive 3 years after the first presentation.     

Primary malignant lymphoma of the thyroid-a tumour of mucosa-associated lymphoid tissue: review of seventy-six cases

Seventy-six cases of primary thyroid lymphoma have been reviewed employing the Kiel classification. These lymphomas are almost entirely of follicle centre cell origin, occur predominantly in elderly females, and are frequently associated with lymphocytic thyroiditis or Hashimoto's disease. The overall prognosis is variable, with long-term survival in a substantial number of cases following thyroidectomy and radiotherapy. Results of histological examination including immunoperoxidase studies are described. It is proposed that thyroid lymphoma represents a neoplasm of mucosa-associated lymphoid tissue (MALT), and the implications of this are discussed.     

胸腺原发黏膜相关淋巴组织淋巴瘤及淋巴上皮性涎腺炎样胸腺增生的临床病理分析

目的探讨胸腺原发黏膜相关淋巴组织(mucosa associated lymphoid tissue,MALT)淋巴瘤和淋巴上皮性涎腺炎(lymphoepithelial sialadenitis,LESA)样胸腺增生的临床病理学特征、两者相关性及鉴别诊断。方法分析3例胸腺MALT淋巴瘤和1例LESA样胸腺增生的临床病理学和免疫表型特征,并复习相关文献。结果 3例胸腺MALT淋巴瘤,其中2例伴Sj9gren综合征;镜下胸腺正常结构损毁,增生的淋巴滤泡间可见肿瘤性淋巴样细胞浸润伴明显的淋巴上皮病变,以中心细胞样和单核样B细胞形态为主。瘤细胞表达CD20、PAX-5和BCL-2,其中1例伴显著浆细胞分化者Lambda轻链限制性表达。3例胸腺MALT淋巴瘤免疫球蛋白(immunoglobulin,Ig)基因检测均示单克隆性重排。LESA样胸腺增生镜下胸腺分叶状结构大体尚存,可见包含增生滤泡的丰富淋巴细胞浸润,胸腺上皮增生伴显著淋巴上皮病变,未见有单核样B细胞形态。免疫组化染色示增生淋巴组织由B和T细胞混合;Ig基因重排检测示多克隆性增生。结论 LESA样胸腺增生和胸腺MALT淋巴瘤均是胸腺少见的淋巴增生性病变,两者具有相似的组织学和免疫表型特征;结合基因重排技术详细分析两者的鉴别要点,有助于鉴别。     

Amyloid deposition in primary pulmonary marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue

A rare association between primary pulmonary marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma), and pulmonary immunoglobulin light chain (AL) amyloidosis is described in a 65-year-old woman suffering from rheumatoid arthritis (RA). All four nodules in the resected upper lobe of the lung had a similar histological appearance. They were composed of small-medium-sized atypical lymphocytes. Centrocyte-like cells had lymphoepithelial lesions. Immunohistochemically, the tumor cells clonally expressed B-cell markers, and demonstrated clonal rearrangement of the immunoglobulin heavy chain gene on polymerase chain reaction. Based on these findings the diagnosis of primary pulmonary MALT lymphoma was made. In addition, uniform eosinophilic material deposition was identified randomly within the tumor. It was Congophilic and exhibited apple-green birefringence on polarizing microscopy, and remained unaffected by potassium permanganate digestion. Deposited material was immunoreactive to lambda light chain. It was concluded that this material was AL amyloid in primary pulmonary MALT lymphoma. Plasma cells with mRNA of lambda chain was found infiltrated along the border of amyloid deposition. Finally, it is speculated that primary pulmonary MALT lymphoma developing in an autoimmune setting, RA in the present case, is associated with overproduction and abnormal clearance of immunoglobulin by the tumor cells, resulting in AL amyloidosis within the tumor.     

唾腺粘膜相关型淋巴瘤与良性淋巴上皮病变的临床病理学

目的：探讨唾腺粘膜相关型淋巴瘤（MALT－ML）与良性淋巴上皮病变（LEL）的诊断、鉴别诊断及其发病机制。方法：手术切除标本常规石蜡切片和免疫组化ABC法标记。结果：17例唾腺MALT－ML16例为CCL细胞型，1例为淋巴浆细胞型，具有MATL－ML的共同特征，免疫组化示单克隆性，7例LEL示多克隆性。结论：Ⅰ级、Ⅱ级LEL为良性病变，Ⅲ级为交界性病变。Ⅳ级LEL即MALT－ML，因此唾腺MALT－ML与LEL密切相关。     

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.     

肺原发性非霍奇金淋巴瘤28例临床病理分析

目的：探讨肺原发性非霍奇金淋巴瘤( primary non-Hodgkin lymphoma, PNHL)的临床病理学特征。方法回顾性分析28例肺PNHL临床表现、影像学和病理学特征,并复习相关文献。结果28例肺PNHL中,男性18例,女性10例,年龄27~82岁,中位年龄57岁。28例均为非霍奇金淋巴瘤( non-Hodgkin lymphoma, NHL),其中黏膜相关淋巴组织结外边缘区淋巴瘤17例,弥漫性大B细胞淋巴瘤(diffuse large B cell lymphoma, DLBLC)5例,NK/T细胞淋巴瘤2例,间变性大细胞淋巴瘤(ana-plastic large cell lymphoma, ALCL)2例,套细胞淋巴瘤(mantle cell lymphoma, MCL)及外周T细胞淋巴瘤,非特指各1例。1/3肺PNHL患者无特异性临床症状,主要表现为咳嗽、胸痛、呼吸困难和乏力等。影像学检查多数表现为单肺或双肺阴影,孤立或多发结节,并可累及气管或支气管。随访16例,时间3~38个月,3例患者行肺叶切除术(2例术后辅助化疗),7例行单纯化疗,5例未行任何治疗。13例生存,2例死亡,1例术后2年出现左侧腹股沟淋巴结转移。结论肺PNHL的临床和影像学无特异性改变,以黏膜相关淋巴组织结外边缘区淋巴瘤最常见,其他少见的高度侵袭性淋巴瘤也可发生。确诊需依赖病理检查,免疫组化及分子病理学检测有助于该类型淋巴瘤的诊断。     

Composite primary breast diffuse large B-cell lymphoma and T lymphoblastic leukemia/lymphoma: report of a case and review of literature

We reported a rare case of composite diffuse large B-cell lymphoma and T lymphoblastic leukemia/lymphoma (T-LBL) in a 46-year-old woman with progressive enlargement of the breast lump. The patient initially sought care at a local hospital with a single left breast lump without any other physical examination findings. Histopathological analysis of which revealed a diffuse infiltration of tumor cells that were rich in cytoplasm with vesicular chromatin and prominent nucleoli. Further analysis of immunohistochemistry showed a cluster of neoplastic cells which express B-cell markers: CD19, CD20 (weak), CD79a, PAX5 and BCL-2, but negative for T-cell markers such as CD2, CD3, CD5 and CD7. PET-CT showed evidence of lymphadenopathy and splenomegaly, which may indicate lymphoma infiltration. Then a biopsy of bone marrow showed typical features of T-LBL. The aberrant terminal deoxynucleotidyl transferase (TDT) and cCD3 positive T-cell population that lack surface CD10 and CD19 were identified by flow cytometric immunophenotyping. Polymerase chain reaction analysis of the T-cell receptor gamma gene and IgH gene revealed a clonal rearrangement and confirming T-cell clonality. Fluorescence in-situ hybridization (FISH) revealed a deletion of the P53 gene in these T-neoplastic cells may indicate a bad outcome of such disease. Neither the large B-cells nor T-cells were positive for Epstein-Barr virus encoded RNA.     

Three cases of diffuse large B-cell lymphoma presenting as primary splenic lymphoma

Primary splenic lymphoma (PSL) is often defined as generalized lymphoma with splenic involvement as the dominant feature. It is a rare disease that comprises approximately 1% of all malignant lymphomas. We investigated three cases of non-Hodgkin's splenic lymphoma that had different clinical features on presentation. The patients' survival times from diagnosis ranged from 59 to 143 months, without evidence of relapse after splenectomy and chemotherapy, with or without radiotherapy. This data suggest that PSL is potentially curable. Further studies are needed to evaluate the impact that different treatment modalities without splenectomy have on patient survival.     

Plasmablastic lymphoma following combination treatment with fludarabine and rituximab for nongastric mucosa-associated lymphoid tissue lymphoma: a case report and review of literature

Plasmablastic lymphoma (PBL) is an uncommon malignancy which predominantly occurs in the oral cavity of human immunodeficiency virus (HIV)-positive patients. Sporadic cases have been published describing PBL in immunocompetent patients as well as in immunodeficient patients following immunosuppressive therapy or transplantation. We hereby reported a case of PBL in a 69-year-old, HIV-negative male subjected to combination treatment with fludarabine and rituximab for nongastric mucosa-associated lymphoid tissue (MALT) lymphoma. The diagnosis of PBL was made with tumor cells of immunoblasts or plasmablasts morphology strongly positive for MUM-1, EMA and CD138, and partly positive for CD38, and negative for CD20, BCL-6, and CD56, and approximately 80% of which were positive for Ki-67. The case presented PBL after MALT, and a history of chemotherapy including fludarabine and rituximab led to the potential immunocompromised state. The patient died 5 months after the diagnosis of PBL.