Primary thyroid marginal zone B-cell lymphoma MALT-type in a patient with rheumatoid arthritis

Autoimmune diseases are defined as specific, adapted immune reactions against self antigens. Immune mechanism deficiency is a causal factor for B-cell lymphoma in primary Sjögren’s syndrome and autoimmune thyroid disease. Thyroid mucosa-associated lymphoid tissue (MALT) lymphoma is a 67-fold and parotid lymphoma is a 44-fold increased risk in Sjögren’s syndrome and thyroiditis. MALT lymphoma was not reported in rheumatoid arthritis. We herein report the case of a 56-year-old woman with maltoma of thyroid in rheumatoid arthritis patient.     

T-cell/histiocyte-rich large B-cell lymphoma: a distinct clinicopathologic entity.

PURPOSE: Although it has proven difficult to delineate diagnostically reproducible and clinically relevant subgroups, the heterogeneity of diffuse large B-cell lymphomas (DLBCL) is widely acknowledged. In 1992, we reported on six cases that suggested that large B-cell lymphoma rich in stromal histiocytes and T cells may be identified as a distinct clinicopathologic entity within DLBCL. PATIENTS AND METHODS: An integrated clinicopathologic study of 40 cases of this DLBCL subtype is presented. RESULTS: Distinguishing a DLBCL rich in histiocytes and reactive T cells, designated T-cell/histiocyte--rich large B-cell lymphoma (THR-BCL), may be justified from a clinical point of view. The disease typically affects middle-aged male patients who usually present with advanced-stage disease that is not adequately managed with current therapeutic strategies. Whereas proliferation fraction and p53 overexpression, in addition to the clinical variables incorporated in the International Prognostic Index (IPI), significantly correlate with response to treatment and survival in a univariate analysis, only the IPI score identifies relevant prognostic THR-BCL subpopulations in a multivariate model. The morphologic and immunophenotypic profile of the neoplastic B cells in THR-BCL suggests that they may originate from a germinal center ancestor. CONCLUSION: THR-BCL constitutes a distinct clinicopathologic entity that is characterized by an aggressive behavior. Experimental therapeutic strategies may be indicated to obtain a more favorable response to treatment in this disease.     

结节性淋巴细胞为主型霍奇金淋巴瘤和富于T细胞和(或)组织细胞的B细胞淋巴瘤的鉴别诊断

目的 探讨结节性淋巴细胞为主型霍奇金淋巴瘤（NLPHL）和富于T细胞和（或）组织细胞的B细胞淋巴瘤（TCRBCL）的鉴别诊断。方法 按照WHO淋巴瘤新分类法,对15例NLPHL和16例TCRBCL的组织学和免疫表型进行分析,并分别对其中3例NLPHL和4例TCRBCL进行了EBERl／2原位杂交和IgH基因重排检测。结果 组织学上,NLPHL和TCRBCL均表现为小淋巴细胞背景中散在分布的肿瘤性大细胞。NLPHL的肿瘤性大细胞形态特征以L＆H细胞（即爆米花细胞）为主,TCRBCL的肿瘤性大细胞以中心母细胞类型为主,两者都可伴有其他变异形态。免疫表型上,NLPHL和TCRBCL的肿瘤性大细胞都呈CD20、CD79a、bcl-6和EMA阳性,CD3、CD45RO、CDl5和CD30阴性,背景小淋巴细胞以T淋巴细胞为主。但在NLPHL中,CD57阳性细胞明显多于TIA-1阳性细胞,小B淋巴细胞呈小灶状或弥漫散在分布;而在TCRBCL中,TIA-1阳性细胞明显多于CD57阳性细胞,小B淋巴细胞非常稀少。CD21检测显示,NLPHL的结节呈CD21阳性滤泡树突细胞（FDC）网架结构,而TCRBCL以及NLPHL的弥漫类型或弥漫区域中,FDC网架缺乏。NLPHL和TCRBCL都呈EBER1／2阴性,IgH基因重排可检测到80～120bp的单克隆条带。结论 NLPHL和TCRBCL有组织学和免疫表型特征的相似性,诊断和鉴别诊断必须结合形态学和瘤细胞、背景细胞的免疫表型特征。     

T-cell/histiocyte-rich B-cell lymphoma: biology, diagnosis, and management

T-cell/histiocyte-rich B-cell lymphoma (T/HRBCL) is an uncommon morphologic variant of diffuse large B-cell lymphoma (DLBCL). Pathologically, it is distinguished by <10% malignant B cells amid a majority population of reactive T lymphocytes and histiocytes. Diagnosis of this entity is occasionally difficult, as it may appear similar to other lymphoid diseases, such as nodular lymphocyte-predominant Hodgkin's lymphoma and classic Hodgkin's lymphoma. Accurate diagnosis therefore rests with careful immunohistochemical analysis of the tumor cells and the inflammatory microenvironment. Clinically, T/HRBCL occurs in younger patients, predominantly affects men, and involves the liver, spleen, and bone marrow with greater frequency than traditional DLBCL. Despite the unique clinical features and robust host inflammatory response, T/HRBCL follows a natural history similar to those of other DLBCLs and responds similarly to therapy. Recent gene expression analysis demonstrates that a productive relationship with the host immune response may extend beyond this small DLBCL variant to include as many as one third of all DLBCLs. At present, T/HRBCL should be treated similarly to other stage-matched DLBCLs, though future therapies will likely be targeted at the relationship of the tumor cells with their inflammatory microenvironment.     

Pediatric EBV-positive T-cell/histiocyte-rich large B-cell lymphoma with clonal cells in the bone marrow without overt involvement

T-cell/histiocyte-rich large B-cell lymphoma (TCHRLBCL) is a variant of large B-cell lymphoma only rarely encountered in children. Here we report the case of an 8-year-old African American boy with Epstein-Barr virus (EBV)-positive TCHRLBCL who initially presented with right submandibular, anterior cervical and supraclavicular lymphadenopathy. Cytogenetic analysis of the lymph node revealed a near-triploid karyotype with complex chromosomal aberrations. Although morphologically the bone marrow was normal, the same cytogenetically abnormal clone was detected. The patient responded to chemotherapy with CHOP (doxorubicin, cyclophosphamide, vincristine and prednisone) therapy, with disappearance of the abnormal clone from the bone marrow. The patient remains in remission 26 months after the initial diagnosis.     

Primary cutaneous aspergillosis in a patient with cutaneous T-cell lymphoma

We present a case of primary cutaneous aspergillosis caused by Aspergillus terreus in a patient with cutaneous T-cell lymphoma. A 41-year-old woman bruised her left shin and presented with a 1 × 2 cm ecchymosis on the upper third of the left shin for over 6 months. Before mycological examination and sequential biopsies, the patient was erroneously treated with antibiotics and local debridement. After final diagnosis of cutaneous aspergillosis caused by A. terreus cutaneous T-cell lymphoma on the basis of mycological, histopathological and immunohistochemical findings, the patient responded well to oral itraconazole and chemotherapy for over 1 month.     

结节性淋巴细胞为主型霍奇金淋巴瘤向富含T细胞/组织细胞的大B细胞淋巴瘤样转化一例并文献复习

目的:探讨结节性淋巴细胞为主型霍奇金淋巴瘤（NLPHL）经治疗后复发并向富含T细胞/组织细胞的大B细胞淋巴瘤（THRLBCL）样转化患者的临床特点,提高对NLPHL和THRLBC鉴别诊断与治疗的认识。方法:回顾性分析复旦大学附属华东医院2019年10月收治的1例NLPHL治疗后复发并向THRLBCL样转化患者的治疗经过,并进行相关文献复习。结果:该患者经ABVD方案治疗后复发,再次经病理活组织及免疫组织化学检查诊断为THRLBCL样转化,经R-CHOP方案治疗后完全缓解。结论:NLPHL化疗效果不佳时需考虑是否存在向THRLBCL样转化的可能,需及时行活组织病理检查,调整治疗方案。     

T-cell/histiocyte-rich B-cell lymphoma: Clinical presentation, management and prognostic factors: report on 61 patients and review of literature

T-cell/histiocyte-rich B-cell lymphoma (TC/HRBCL) is a rare subtype of diffuse large B-cell non-Hodgkin's lymphoma (DLBCL) with characteristic morphologic and immunophenotypic features, often misdiagnosed as Hodgkin's lymphoma and peripheral T-cell lymphoma. Few and conflicting clinical data are available in the literature addressing optimal treatment, prognosis and outcome. We retrospectively reviewed all patients diagnosed and managed at our institution between 1995 and 2004 diagnosed with T-cell-rich-B-cell lymphoma by WHO criteria. Sixty-one patients were identified. Initial pathology was incorrect in 82% of referred cases. The median age was 30 years. Seventy-one patients were males. Stage distribution was I - II in 21 patients, and III - IV in 40. Fifty-two percent of patients (32) had splenic involvement and thirty-seven patients (61%) presented with extranodal disease (22 ≥ 2 sites). The International Prognostic Index (IPI) score was ≥2 in 62% of patients. All 59 newly diagnosed TC/HRBCL patients were treated with CHOP or R-CHOP combination chemotherapy +/- radiation therapy. The overall response rate was 85% and nine patients progressed on therapy. Fourteen patients relapsed with a median time of relapse of 6 months (range, 2 - 28). At a median follow-up of 22 months (range 1 - 132); 32 patients (52%) are alive with no evidence of disease. The 5-year overall survival and event free survival rates were 46% and 39% respectively. To conclude, TC/HRBCL is difficult to recognize without immunohistochemistry. It has an aggressive course and poor outcome; with most of patients presenting with advanced disease stage together with high IPI score. Treatment outcome seems to be similar to IPI matched DLBCL counterpart.     

Monocytoid B-cell lymphoma arising in extranodal organs

Six cases of monocytoid B-cell lymphoma (MBCL) developing in extranodal sites (thyroid, three; stomach, two; rectum, one) are described. Patients were all women aged 46 to 65 years (median, 53 years). Three patients with thyroid lymphoma presented with an increasing goiter, two with positive serum antithyroid antibodies, and one patient had chronic lymphocytic thyroiditis (CLTH). The histologic type of surgically resected specimens was a diffuse proliferation of atypical lymphoid cells with monocytoid appearance, i.e., abundant pale cytoplasm with distinct cell border and small reniform nucleus. These cells were CD20+, 22+, 24-, 9- showing their B-cell origin. The monoclonal nature of the proliferating cells was confirmed by restricted expression of immunoglobulin (Ig) light chain and/or gene rearrangement study in three cases. Two cases of thyroid lymphoma in which the monoclonality could not be confirmed had histologic appearances characteristic of malignant lymphoma. All three patients with gastric or rectal lymphoma had reactive lymphoid hyperplasia (RLH) near the tumors. These findings showed presence of MBCL in the extranodal sites with invariable coexistence with lymphoid follicles formed by CLTH in thyroid or RLH in stomach and rectum.     

T-cell/histiocyte-rich large B-cell lymphomas and classical diffuse large B-cell lymphomas have similar outcome after chemotherapy: a matched-control analysis.

PURPOSE: Because it is unclear whether T-cell/histiocyte-rich large B-cell lymphomas (H/TCRBCL) should be considered as a true clinicopathologic entity, we conducted a matched-control analysis comparing patients with H/TCRBCL and patients with diffuse large-B cell lymphoma (B-DLCL). PATIENTS AND METHODS: More than 4,500 patients were enrolled onto non-Hodgkin's lymphoma trials conducted by the Groupe d'Etude des Lymphomes de l'Adulte. After histologic review, 50 patients were subclassified as H/TCRBCL. They were matched to 150 patients with B-DLCL for each of the factors of the International Prognostic Index (IPI). RESULTS: Clinical characteristics of H/TCRBCL patients showed a male predominance and a median age of 47 years. Performance status was normal in 89% of patients, whereas lactate dehydrogenase level was increased in 60% of patients. The disease was disseminated in 81% of patients, and 48% had two or more involved extranodal sites. The IPI score was >or= 2 in 53% of patients. The complete response rate to chemotherapy was 63%, and 5-year overall survival (OS) and event-free survival (EFS) rates (mean +/- SD) were 58% +/- 18% and 53% +/- 16%, respectively. The matched-control analysis showed a trend toward a better response to chemotherapy for patients with B-DLCL (P =.06), whereas no difference was observed in OS (P =.9) and EFS (P =.8). CONCLUSION: H/TCRBCL is an aggressive disease that often presents with adverse prognostic factors. However, when treatment is adapted to the disease risk, outcome is equivalent to that observed in patients with B-DLCL. Thus H/TCRBCL should be considered a pathologic variant that belongs to the B-DLCL category.     

Epstein-Barr virus positive large B-cell lymphoma arising in a patient previously treated with Cladribine for hairy cell leukemia

We describe the case of a patient treated with 2-chloro-2'-deoxyadenosine, CdA or Cladribine for hairy cell leukemia who subsequently developed an Epstein Barr virus (EBV)-positive polymorphous large B-cell lymphoma (p-LBCL). The time interval between Cladribine therapy and development of p-BCL was 11 months and morphologically resembled an EBV-positive post transplant lymphoproliferative disorder (PTLD). Molecular genetic studies for EBV-clonality by Southern blot hybridization showed a clonal population of infected cells, implying that this was an EBV induced lesion. The chronology of events suggest that Cladribine, a purine analog which has been previously described to induce long-lasting immunodeficiency, can, in some cases, weaken the host defense mechanism to a level at which an innocuous EBV infection may transform the normal lymphoid cells into an aggressive neoplasm. Unlike most methotrexate-related lymphoproliferative disorders (LPDs), which undergo spontaneous remission after discontinuation of therapy, LPDs secondary to purine analogs often fails to resolve after discontinuation of therapy and requires additional therapy. Our patient was treated with rituximab following the diagnosis of p-LBCL, with the goal of improving the pancytopenia to permit chemotherapy. However, the patient failed to show any dramatic improvements in counts, developed systemic symptoms and progressive ascites. He expired 3 weeks after a second dose of rituximab. Cladribine is a potent immunosuppressive agent and should be included with the list of immunosuppressive agents that may be associated with EBV-related B-cell lymphoproliferative disorders.     

Antihuman T-cell leukemia/lymphoma virus antibodies in three patients with primary cutaneous B-cell lymphoma

In 3 patients suffering from follicular center-cell-derived B-cell lymphoma with primary cutaneous manifestation, antiadult T-cell leukemia-associated antigen antibodies were detected by the ELISA. In one of the patients, the husband and the dog had died from thymoma and from malignant lymphoma, respectively.     

Primary low grade B-cell lymphoma of the dura in an immunocompetent patient

Primary central nervous system lymphomas (PCNSL) represent only 1% of all non-Hodgkin's lymphomas (NHLs). A 66 year-old woman was hospitalized due to multiple episodes of syncope and seizures which occurred the week before admission to the hospital. A computerized tomography (CT) scan of the brain showed a right parietal lesion suggesting a subdural effusion. The patient was operated and a dural lesion extending to the epidural space and cerebral cortex was excised. Histologic findings suggested diagnosis of a low-grade lymphoma of the mucosa associated lymphoid tissue (MALT) type. The patient was treated with radiation therapy and has now completely recovered 12 months after surgery.     

B-cell lymphoma possessing t(14;18)(q32;q21)in a patient with rheumatoid arthritis receiving methotrexate treatment

There is evidence of a slight increase in malignant lymphoma among rheumatoid arthritis(RA)patients receiving methotrexate( MTX). Increased rates of lymphoma have been attributed to reactivation of the Epstein-Barr virus(EBV). A 72-yearold woman was admitted to our hospital for generalized lymph adenopathy. She suffered from RA and has been treated with MTX for 7 years; the total amount of MTX received was around 2, 700 mg. The cervical lymph node revealed a diffuse proliferation of large atypical lymphocytes. An immunophenotype revealed CD10+, CD19+, CD20+, and k+. The chromosome analysis showed a complex abnormality containing t(14;18)(q32;q21). The tumor cells were positive for EBV sequences by in situ hybridization(ISH). A rituximab containing regimen was effective, but a systemic relapse occurred 4 years later. The biopsied sample was diagnosed as diffuse large B-cell lymphoma. FISH analysis revealed positive for t(14;18)(q32;q21), however, EBV was negative using ISH. In general, the concurrence of t(14;18)(q32;q21)and EBV in the B-cell lymphoma is rare. In addition, the negative change in EBV in the relapsed lymphoma cells revealed a quite rare phenomenon.     

Epstein-Barr virus (EBV) genome carrying monoclonal B-cell lymphoma in a patient with adult T-cell leukemia-lymphoma.

A Japanese patient with adult T-cell leukemia-lymphoma (ATL) showed a disease progression from the smoldering type to the chronic type and finally to the acute type. The patient was variously treated, including 2'-deoxycoformycin, with some beneficial effects. During the chronic type he developed a composite lymphoma consisting of T-cell lymphoma (ATL) of medium-sized cells and B-cell lymphoma of diffuse large cell type. At that time, he also suffered from miliary tuberculosis and adenovirus type 11-induced hemorrhagic cystitis, indicating that he was in a marked immunodeficient state. Southern-blot analysis revealed that the two malignancies have distinct clonal origin on the basis of the following results: (1) clonally rearranged T-cell receptor beta-chain gene (TcR-beta gene) and germline configuration of immunoglobulin heavy chain gene (IgH gene) in ATL leukemic cells, (2) clonal rearrangement of IgH gene in lymphoma cells, indicating a monoclonal B-cell lymphoma, (3) monoclonal integration of HTLV-I provirus in ATL leukemic cells, (4) definite presence and monoclonal origin of EBV genome in lymphoma cells. This is the first report of secondary EBV genome carrying monoclonal B-cell lymphoma in an ATL patient. It is suggested that the immunodeficient state in the patient with ATL allows the emergence of EBV-related B-cell lymphoma.     

Immunoglobulin and T-cell receptor gene-gene rearrangement in pleural cavity-based T-cell rich B-cell lymphoma in an immunocompetent patient

Body cavity-based lymphomas are fluid-based lymphomas that are not associated with a tumor mass or adenopathy which could explain the origin of the lymphomatous effusion. A distinct lymphoma that grows in the body cavity as a lymphomatous effusion in the absence of a tumor mass has been identified as a primary effusion lymphoma. This almost exclusively occurs in patients with acquired immunodeficiency syndrome (AIDS), who invariably have a history of Kaposi sarcoma. We report a rare case of a recurrent pleural effusion in an immunocompetent patient. There was no evidence of lymphadenopathy or an associated mass on computerized tomography of the chest, abdomen and pelvis. Serology for HIV, HHS-8, EBV and HTLV-1 were negative. Cytologic examination of the pleural fluid showed an elevated white cell count with 97% lymphocytes, mostly with T-cell markers. Bone marrow aspirate and biopsy were negative and bronchoscopy was unrevealing. Pleural biopsy was significant for >70% T-lymphocytes and some large atypical cells. Which had CD19, CD20 and weak bcl-2 positivity. Kappa and lambda light chains did not show distinct clonality. A preliminary diagnosis of T-cell rich B-cell lymphoma (TCRBCL) of the pleural cavity was made. The diagnosis was confirmed with DNA studies done on the pleural biopsy specimen using PCR and southern blot. Dual rearrangement of Ig heavy chain region and TCR-beta genes were identified. The patient responded to combination chemotherapy with cyclophosphamide, adriamycin, vincristine and prednisone. Our case is the first known case of pleural cavity-based TCRBCL and illustrates the role of gene rearrangement studies in such patients.