Germinal center cell lymphomas: Prognostic significance of their histopathological differentiation

Summary Clinical data of 48 patients with centrocytic, 83 patients with centroblastic/centrocytic and 64 patients with centroblastic lymphoma who had entered a prospective multicenter study of the Kiel Lymphoma Study Group since October 1975 were compared. Advanced (stage IV) disease at time of diagnosis, predominantly due to bone marrow infiltration, was most frequent in centrocytic (69% of patients) and in centroblastic/centrocytic (51% of patients) lymphomas as compared to only 28% of patients with centroblastic lymphoma. High survival probability of patients with localized centrocytic and centroblastic/centrocytic lymphomas after radiotherapy, contrasting with a worse prognosis of corresponding patients with centroblastic lymphoma, is compatible with the classification of these lymphoma entities as neoplasias of low-grade malignancy. However, as shown by this prospective and previous retrospective trials overall survival probability of patients with advanced centrocytic lymphoma was inferior to that observed in corresponding patients with centroblastic/centrocytic lymphoma. These findings suggest the possibility that patients with advanced centrocytic lymphoma occupy an intermediate position between typical low-grade and typical high-grade malignant non-Hodgkin lymphomas.Supported by the Deutsche Krebshilfe e. V., BonnPresented in part at the 5th Meeting of the International Society of Haematology, European and African Division, Hamburg, August 26–31, 1979     

Primary gastric non-Hodgkin's lymphoma: a clinicopathological study of 41 patients

Pathological findings in 41 patients (male/female ratio: 1.3/1) with primary localized gastric non-Hodgkin's lymphoma (NHL) were retrospectively studied and correlated with survival. The median observation period after diagnosis was 32 (0–189) months. Nineteen patients were low-grade NHL, all but one B-cell lymphomas of the mucosa-associated lymphoid tissue (MALT) type. Twenty-two patients had primary (n-7) or secondary (n=15) high-grade lymphomas; Musshoff stage IE was found in 29 and II E in 12 cases. The median age at diagnosis was 61 years (range, 26–88 years), and proliferation, measured by the number of mitosis and Ki-67 antigen positivity (MIB-1), was high or moderately high in 24 cases and low in 17 cases. Follicular lymphatic hyperplasia could be found in 25 of 34 evaluable cases, more often in low-grade than in high-grade NHL. Most of the patients were treated by resective surgery and additional ratio- or chemotherapy. Thirteen patients (31%) died (median survival: 10 months), 5 of them within 3 months after surgery owing to postoperative complications. Survival was superior, though not statistically significant, in low-grade lymphomas. Our retrospective anlysis of heterogeneously treated gastric lymphomas reveals that gastric lymphomas, especially of the low-grade MALT type, often remain a localized disease with a good long-term prognosis. Our study confirms previous reports indicating that lymphomas of the MALT type represent a specific clinicopathological entity.     

Clinical and prognostic heterogeneity of non-hodgkin lymphomas of high-grade malignancy

Summary Comparison of clinical data of 64 patients with centroblastic lymphoma, 55 patients with immunoblastic lymphoma and 31 patients with lymphoblastic lymphoma not only confirmed the original assumption of high-grade malignancy as proposed by the concept of the Kiel classification but also demonstrated distinct clinical differences, particularly between lymphoblastic lymphoma and the two other entities. Rapid lymph node enlargement as well as steep fall of survival curves within the first year after diagnosis were common characteristics. Bimodal age distribution, predominance of males and early generalization of disease were typical features of lymphoblastic lymphoma; elderly patients and patients with the unclassified subtypes of lymphoblastic lymphoma exhibited the worst prognosis. Whereas patients with centroblastic and immunoblastic lymphomas showed similar distribution of age, sex and initial stage of disease, patients with immunoblastic lymphoma presented more frequently with a reduced performance status and showed a poorer response to radio- and chemotherapy resulting in a worse prognosis discernible after the first year of follow-up. Generalization during course of the disease was significantly more frequent in immunoblastic than in centroblastic lymphoma.Supported by the Deutsche Krebshilfe e. V., BonnPresented in part at the 5th Meeting of the International Society of Haematology, European and African Division, Hamburg, August 26–31, 1979     

胃原发性肠病相关型T细胞淋巴瘤1例报道

本文报道1例胃原发性肠病相关型T细胞淋巴瘤。患者为1例22岁年轻女性,初始临床分期为Ⅳ期,首先采取了CHOP、GDP、HD-MTX、IEO、DHAP方案序贯化疗,然后行远端胃切除术与淋巴结清扫术,为获得较长的生存期还进行了局部姑息性放疗。治疗取得了良好的疗效,患者的生存期已超过2年,并且生活质量较高。本病例强调了在高侵袭性结外淋巴瘤的治疗中外科手段的重要性。     

Primary diffuse large B-cell lymphoma of the fallopian tube treated with a combination of surgery and chemotherapy: Case report

Rationale:Primary female genital tract lymphomas are sporadic neoplasms, accounting for 0.2% to 1.1% of all cases of extranodal lymphoma. The most common genital localizations are the cervix, the uterine corpus and the ovary, while primary lymphomas of the fallopian tube are quite unusual. According to literature searching in PubMed, this is the first reported case of primary diffuse large B-cell lymphoma of the fallopian tube.Patient concerns:A 52-year-old woman presented with a more than 2 months history of intermittent lower abdominal pain. The gynecological examination showed that the uterus, as big as 3 months of pregnancy, had weak activity and no tenderness. The uterine rectum lacuna was like a hard nodule of about 3 × 2 cm, and an irregular solid mass was fixed and inactive in the right adnexa.Diagnoses:In accordance with Ann Arbor staging system, a stage IE primary diffuse large B-cell lymphoma of fallopian tube was diagnosed for this patient, based on the tumor pathology, the results of bone marrow biopsy and computed tomography (CT) scan.Interventions:After gynecological/urinary ultrasound, blood test, pelvic contrast enhanced CT scan and CT angiography of iliac artery, exploratory laparoscopy and following hysterectomy with bilateral salpingo-oophorectomy were performed. After the surgery, the patient was treated with combined Rituximab and chemotherapy and got complete response (CR).Outcomes:After the operation and R-CHPOP, following up for more than 1 year so far, the patient has no tumor recurrence and is still in good condition.Lessons:It is very difficult to diagnose the primary diffuse large B-cell lymphoma of fallopian tube, not only because of its rarity, but also because of its non-specific clinical manifestations. It easily be treated as late ovarian cancer by gynecologist. So the pathology diagnosis and surgeons’ decision is very important. Because lymphoma is pretty sensitive to chemotherapy and easy to get complete response, so we no need to do an operation like ovarian cancer and should put chemotherapy as a primary method for lymphomas of the female genital tract.     

Primary Hepatic Low-Grade B-Cell Lymphoma of the Mucosa-Associated Lymphoid Tissue Type: A Case Report and Review of the Literature

Primary hepatic lymphoma, mostly diffuse large B-cell lymphoma, is a rare disease. We describe an extremely rare case of low-grade B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT) type occurring in the liver. A 61-year-old man with a history of hepatitis A presented with early gastric cancer and a liver mass. Needle biopsy of the liver tumor suggested low-grade B-cell lymphoma by histology and polymerase chain reaction of the immunoglobulin heavy chain gene. The tumor (3.4 x 2.8 x 2.4 cm) was completely resected from the anterior segment of the right lobe of the liver. Atypical lymphoid cells of small to intermediate size proliferated in the tumor, and lymphoepithelial lesions were recognized. Immunohistochemically, lymphoma cells were positive for CD20 and negative for CD5, CD10, and cyclin D1. Staging procedures showed no lymphoma lesion other than the liver tumor. Thus, the patient was diagnosed with low-grade hepatic marginal zone B-cell lymphoma of the MALT type. The patient has been followed up for 1.5 years since surgical resection with no recurrence. The clinicopathologic characteristics and management of this rare disease are discussed.     

Diagnosis and management of follicular lymphoma: A comprehensive review

Follicular Lymphoma (FL) is an indolent lymphoma and may have various clinical courses. Worldwide, FL is the second most common non‐Hodgkin lymphoma (NHL) type after diffuse large B‐cell lymphoma. In this review article, the author is discussing relevant diagnostic tools, prognostic factors, and updated study results on the management of patients with newly diagnosed and relapsed/refractory FL. Controversies in the treatment, maintenance therapy, stem cell transplantation, and novel treatment approaches will be comprehensively discussed.     

Composite and sequential lymphoma between classical Hodgkin lymphoma and primary mediastinal lymphoma/diffuse large B-cell lymphoma,a clinico-pathological series of 25 cases

Composite and sequential lymphomas involving both classical Hodgkin lymphoma (CHL) and primary mediastinal B-cell lymphoma (PMBCL) are rare phenomena. Beyond the relevant biological interest raised by these cases, treatments and outcome data are poorly covered in the recent literature. This retrospective analysis describes the pathological and clinical characteristics of 10 composite and 15 sequential cases included after a central pathological review. At diagnosis, 70% of the composite lymphomas presented a disseminated and extranodal disease. Among the 15 sequential lymphomas, 12 were CHL at first occurrence and three were PMBCL. Based on their clinical evolution, these sequential lymphomas could be divided into early (i.e., diagnosis of second lymphoma within a year) and late [(i.e., a second lymphoma occurrence occurring after a long period of complete remission]). All composite cases were alive in complete remission after a median follow-up of 34 months. If the early sequential lymphoma presented a particularly poor outcome with a median overall survival shorter than one year, the late cases were efficiently salvaged. Further molecular studies are needed to describe the underlying biology of these rare diseases, possibly representing the extreme of tumour cell plasticity found in grey-zone lymphoma.     

A study of lymphoma of large granular lymphocytes with modern modalities: report of two cases and review of the literature.

Two cases of lymphoma of large granular lymphocytes are reported. The first case expressed natural killer (NK) cell, some T-cell (CD 2, CD 5, CD 8), and HLA-DR antigens, but was negative for other T-cell (CD 3, CD 4, CD 7), T-cell receptor (TCR), B-cell, and myeloid antigens. Germline configuration was demonstrated for TCR, and immunoglobulin heavy and light chain genes. The second case expressed NK cell, some T-cell (CD 3, CD 7, CD 8), and TCR antigens, but was negative for other T-cell (CD 4, CD 5), B-cell, myeloid, and HLA-DR antigens. Rearrangement of TCR alpha and beta chains were detected. Thus, the findings of case 1 were consistent with true NK cell lineage and case 2 with NK-like T-cell lineage. Our report underscores the heterogeneity of this newly recognized lymphoma, which nevertheless carries a consistently poor prognosis and is probably more prevalent in the Asian population. This study also provides information concerning immunophenotypes of cellular infiltrates in internal organs and cytogenetic abnormalities in this lymphoma; neither has been reported frequently in the literature. The importance of detecting cytoplasmic granules in tissue imprints or electron micrographs for differentiating other T-cell lymphomas is emphasized, and the classification of large granular lymphoproliferative disorders is discussed.     

Age of onset evidence for anticipation in familial non-Hodgkin's lymphoma

Anticipation, a phenomenon in which an inherited disease is diagnosed at an earlier age in each successive generation of a family, has been demonstrated in certain neurological and haematological disorders. This study was conducted to determine whether anticipation occurs in familial non-Hodgkin's lymphoma (NHL). Eleven published reports of multigenerational familial NHL were analysed for evidence of anticipation, together with 18 previously unreported families with familial NHL. Differences in disease-free survival between generations were determined. The difference between age at onset for each affected parent-child pair was tested against the null hypothesis that there was no difference in age at onset. These analyses were also performed separately using only parent-child pairs with age of onset > 25 years to avoid ascertainment bias. In addition, the age at onset distribution of the studied cases was compared with that of the Surveillance Epidemiology and End Results (SEER) Program using data for 1973-98. The median ages at onset in the child and parent generations of all families (48.5 and 71.3 years respectively) and in the selected pairs (52.5 and 71.5 years respectively) were significantly different (P < 0.000002 and P < 0.000001 respectively). The null hypothesis was rejected for all (P < 0.000001) as well as selected pairs (P < 0.000003). A significant difference was observed between the ages of onset of the child generation and the SEER population (P < 0.009), but not between the parent generation and the SEER population. Anticipation occurs in familial NHL, which suggests a genetic basis for it.     

How we diagnose and treat vitreoretinal lymphoma

The eye is a rare site for the development of malignant lymphoma. Based on cell type and involved intraocular structures, which as a whole represent an immune‐privileged site, several subtypes of primary intraocular lymphoma need to be discerned. Primary vitreoretinal lymphoma (PVRL), the most common form, is an aggressive B‐cell malignancy and considered a subtype of primary central nervous system (CNS) lymphoma. Ocular symptoms are non‐specific and often mimic uveitis, frequently resulting in delayed diagnosis. Bilateral ocular involvement and dissemination/relapse in the CNS are common. Diagnosis of PVRL is usually based on the analysis of vitreous biopsy material. In addition to cytological and immunocytochemical examination, measurements of cytokine levels and molecular determination of B‐cell clonality and recurrent mutations increase the diagnostic yield. Both systemic chemotherapy and exclusively local treatment, including ocular radiotherapy and intravitreal chemotherapy, are successful approaches for the management of PVRL, although it is currently not predictable which patients require systemic treatment in order to avoid cerebral dissemination, a complication associated with a considerably worse prognosis.     

Presence of a high-grade component in gastric mucosa-associated lymphoid tissue (MALT) lymphoma is not associated with an adverse prognosis

Gastric mucosa-associated lymphoid tissue (MALT) lymphoma and diffuse large B cell lymphoma (DLBCL) show a spectrum of disease characterized by varying proportions of low-grade and high-grade components. While the natural history and optimum treatment for low-grade gastric MALT lymphoma and DLBCL is well established, the prognosis and optimal treatment of patients with both low- and high-grade components is not well established. The purpose of our study was to evaluate the clinical characteristics, survival outcomes, and prognostic factors of patients with gastric MALT lymphoma and gastric DLBCL. A retrospective review of patients with gastric MALT lymphoma, gastric DLBCL, or MALT lymphoma with a high-grade component treated at our centers from 1994 to 2006 was performed. Patients were divided into three categories: “pure MALT lymphoma,” “MALT lymphoma with high-grade component” (mixed), and “pure DLBCL.” Seventy-six patients were included in our study—26 with pure MALT, 22 with MALT with high-grade component (“mixed”), and 28 with pure DLBCL. Pure MALT lymphoma and mixed lymphoma patients had similar clinical characteristics, whereas pure DLBCL patients had less favorable disease characteristics with significantly poorer performance status, higher number of extranodal sites of disease, higher stage, and larger proportion of bone marrow involvement and international prognostic index (IPI) scores compared with mixed lymphoma. The majority of mixed lymphoma (72.7%) and DLBCL patients (71.4%) were treated with chemotherapy. Of patients receiving chemotherapy, a higher proportion of mixed lymphoma and DLBCL patients received anthracycline-based combination chemotherapy regimens compared with MALT lymphoma (73% vs 71% vs 8%) whereas the proportion of mixed lymphoma and DLBCL patients was similar (p = 0.919). At a median follow-up of 37 months, the 5-year overall survival was 66.9%. The 5-year overall survival was 78% for MALT lymphoma, 84% for mixed lymphoma, and 45% for DLBCL. On univariate analysis, DLBCL histology, age, performance status, serum albumin, lactate dehydrogenase, bone marrow, number of extranodal sites, stage, and IPI score were prognostic for inferior survival. On multivariate analysis, DLBCL histology remained significantly prognostic for inferior survival, independent of chemotherapy regimen (hazard ratio (HR) 6.66, 95% confidence interval (CI) 2.01–21.41, p = 0.001). Mixed histology was not prognostic for inferior survival (HR 1.13, 95% CI 0.28–4.54, p = 0.868). Other factors prognostic for inferior survival were serum albumin <37 g/L (HR 3.22, 95% CI 1.11–13.22, p = 0.034) and treatment with non-cyclophosphamide, doxorubicin, vincristine, and prednisolone chemotherapy (HR 4.89, 95% CI 1.67–14.36, p = 0.004). In conclusion, the clinical characteristics of mixed histology MALT lymphoma are similar to low-grade MALT lymphoma and significantly different from pure DLBCL. The prognosis of mixed histology MALT lymphoma is significantly better than pure DLBCL, independent of IPI and chemotherapy regimen, and pure DLBCL histology is independently prognostic of inferior survival outcome.     

Intravascular lymphoma: clinical presentation, natural history, management and prognostic factors in a series of 38 cases, with special emphasis on the 'cutaneous variant'

Despite its recognition as a distinct, extremely rare entity, no large studies of intravascular lymphoma (IVL) have been reported. The clinico-pathological characteristics of 38 human immunodeficiency virus-negative patients with IVL diagnosed in Western countries were reviewed to better delineate clinical presentation, clinical variants, natural history and optimal therapy. The IVL is an aggressive and usually disseminated disease (Ann Arbor stage IV in 68% of cases) that predominantly affects elderly patients (median age 70 years, range: 34-90; male:female ratio 0.9), resulting in poor Eastern Cooperative Oncology Group Performance Status (ECOG-PS >1 in 61%), B symptoms (55%), anaemia (63%) and high serum lactate dehydrogenase level (86%). The brain and skin are the most common sites of disease. In contrast to previous reports, hepatosplenic involvement (26%) and bone marrow infiltration (32%) were found to be common features in IVL, while nodal disease was confirmed as rare (11% of cases). Patients with disease limited to the skin ('cutaneous variant'; 26% of cases) were invariably females with a normal platelet count, and exhibited a significantly better outcome than the remaining patients, which deserves further investigation. Overall survival was usually poor; however, the early use of intensive therapies could improve outcome in young patients with unfavourable features. ECOG-PS >1, 'cutaneous variant', stage I and chemotherapy use were independently associated with improved survival.     

Vitreoretinal lymphoma occurring after systemic chemotherapy for primary conjunctival diffuse large B cell lymphoma: A case report

Introduction:Ocular adnexal lymphoma and vitreoretinal lymphoma are rare forms of non-Hodgkin lymphoma. They are regarded as distinct disease entities due to the differences in molecular mechanism, management, and outcome. We present a rare case of conjunctival diffuse large B cell lymphoma (DLBCL) that developed to vitreoretinal lymphoma after systemic chemotherapy.Patient concerns:A 60-year-old man presented with a left salmon-colored conjunctival mass.Diagnosis:A biopsy was performed, and histopathologic examination showed DLBCL. Immunohistochemical staining was positive for CD20 with increased κ to λ light chain ratio.Interventions:Bone marrow biopsy also revealed DLBCL. Gallium-67 scintigraphy showed abnormal uptake only in the left orbital lesion. Ann Arbor stage was estimated as IV. The patient underwent systemic combination chemotherapy and immunotherapy.Outcomes:Four months after the last course of chemotherapy, primary conjunctival DLBCL relapsed, manifesting vitreous opacity. Diagnostic vitrectomy confirmed a diagnosis of vitreoretinal lymphoma.Lessons:Conjunctival DLBCL and vitreoretinal lymphoma are both DLBCL. After systemic chemotherapy for conjunctival DLBCL, the lymphoma may relapse in intraocular sites as secondary vitreoretinal lymphoma.     

Clinical features,management and prognosis of multifocal primary bone lymphoma: a retrospective study of the international extranodal lymphoma study group (the IELSG 14 study)

‘Multifocal bone lymphoma’ or ‘polyostotic lymphoma’ is a neoplasm with exclusive multifocal involvement of the skeleton, without affecting lymph nodes or other soft tissues. Knowledge on this uncommon condition is limited because the related literature is sparse and fragmentary. We reviewed cases of multifocal bone diffuse large B‐cell lymphoma (MB‐DLBCL) registered in a clinico‐pathological database of the International Extranodal Lymphoma Study Group that includes 499 cases of bone lymphoma. Clinical features, management and prognosis of 37 MB‐DLBCL patients and 63 ‘controls’ (stage‐IV DLBCL and skeletal involvement) were analysed. Presentation and treatment of MB‐DLBCL and controls were identical. At a median follow‐up of 52 months (10–189), MB‐DLBCL patients exhibited a significantly better response rate (92% vs. 65%; P = 0·002), progression‐free survival (5‐year: 56 ± 9% vs. 34 ± 6%; P = 0·003) and overall survival (5‐year: 74 ± 8% vs. 36 ± 7%; P = 0·002). Among MB‐DLBCL patients, the use of post‐chemo radiotherapy was associated with better overall survival (5‐year: 83 ± 12% vs. 55 ± 16%; P = 0·003). Two MB‐DLBCL patients (5·4%) with spine and skull involvement experienced central nervous system (CNS) relapse. Thus, MB‐DLBCL patients exhibit a significantly better prognosis compared to patients with advanced‐stage DLBCL, and should be treated with conventional anthracycline‐based chemotherapy, keeping intensified treatment for relapsing cases, considering involved‐field radiotherapy, and CNS prophylaxis in high‐risk patients.     

Diffuse large B-cell lymphoma: is morphologic subdivision useful in clinical management?

Abstract: The diffuse large B-cell lymphoma category of the REAL classification encompasses different morphologic lymphoma subtypes in a single entity. The aim of this study is to determine the influence of the morphologic subdivision within this category with respect to clinical features and response to treatment. From January 1993 to October 1996, 132 patients were diagnosed de novo with diffuse large B-cell lymphoma in our institution. All cases were classified according to the REAL and the Updated Kiel classifications, and immunohistochemical study was performed in all of them. Sixty-three per cent of patients received chemotherapy with a curative approach. Of the 105 assessable patients, 80 cases (74%) were classified as centroblastic (CB) and 25 cases (26%) as immunoblastic (IB), according to the updated Kiel classification. These 2 subsets of lymphomas did not differ with respect to major clinical features and laboratory parameters. Both groups had a similar complete response rate with a uniform therapeutic approach and the overall 2-yr survival did not show statistical differences (49% in CB vs. 45% in IB). In conclusion, for clinicians, morphologic subdivision of the diffuse large B-cell lymphoma category into CB and IB subtypes has little clinical and prognostic significance.     

原发骨淋巴瘤42例临床分析

目的探讨原发骨淋巴瘤(PBL)的临床特点及预后。方法入选西京医院2006年至2014年期间收治的PBL患者42例,男24例,女18例,中位年龄45.6(11~78)岁,收集患者的临床资料,包括性别、年龄、有无全身症状、发病部位、临床分期、病理类型、治疗方案、疗效评价等,进行回顾性分析,通过电话和门诊随访至2015年3月。结果 42例患者均以病变部位疼痛或牵涉性麻木为首发临床表现。病理分型均为非霍奇金淋巴瘤(NHL),50%(21/42)为弥漫大B细胞淋巴瘤(DLBCL)。其中17例患者接受了治疗,5例放化疗联合,12例单纯化疗,两组比较,近期疗效差异无统计学意义(P0.05)。4个疗程后评估近期疗效,年龄、性别、分期、乳酸脱氢酶(LDH)水平、有无全身症状、病理分型、美国东部肿瘤协作组(ECOG)评分、国际预后指数(IPI)评分、是否应用利妥昔单抗治疗、是否联合放疗等对完全缓解率(CR)的影响无统计学意义(P0.05)。中位随访时间13(2~48)个月,无进展生存期3年的4例患者中3例应用了利妥昔单抗。结论 42例PBL患者病理类型主要为DLBCL,治疗以化疗为主,联合放疗未明显提高疗效,应用利妥昔单抗可能会改善预后,尚需扩大样本量进行研究。