Waldeyer’s ring marginal zone B cell lymphoma: are the clinical and prognostic features nodal or extranodal? A study by the Consortium for Improving Survival of Lymphoma (CISL)

There has been controversy surrounding Waldeyer??s ring (WR), especially focused on the question of whether it should be regarded as a nodal or an extranodal site. We conducted retrospective analyses of marginal zone B cell lymphomas involving WR (WR-MZLs) to observe their clinical features and prognosis, with specific regard to the nodal-or-extranodal question. A total of 52 patients with histological diagnosis of WR-MZL were retrospectively analyzed. The most common involvement site was the tonsil (40.4?%). Ann Arbor stage III/VI disease was present in 48.1?% (25 of 52). The response rate of the 27 stage I/II patients was 88.9?%, with 21 complete remissions and three partial remissions. The median time to progression (TTP) was 3.7?years (95?% CI 2.5?C4.9?years). The estimated 5-year TTP and overall survival rates were 39.4 and 90.5?%, respectively. In a comparison with the historical data regarding extra-WR MALT lymphoma and nodal MZL (N-MZL), MALT lymphoma showed better TTP results than did WR-MZL and N-MZL (P?<?0.001).     

Clinical features and outcomes of abdominal tuberculosis in southeastern Korea: 12 years of experience

Background

Abdominal tuberculosis (TB) is an uncommon form of infection with Mycobacterium tuberculosis in Korea. In this study, we aimed to highlight the clinical features, diagnostic methods, and outcomes of abdominal TB over 12?years in Southeastern Korea.

Methods

A total of 139 patients diagnosed as having abdominal TB who received anti-TB medication from January 2005 to June 2016 were reviewed. Among them, 69 patients (49.6%) had luminal TB, 28 (20.1%) had peritoneal TB, 7 (5.0%) had nodal TB, 23 (16.5%) had visceral TB, and 12 (8.6%) had mixed TB.

Results

The most frequent symptoms were abdominal pain (34.5%) and abdominal distension (21.0%). Diagnosis of abdominal TB was confirmed using microbiologic and/or histologic methods in 76 patients (confirmed diagnosis), while the remaining 63 patients were diagnosed based on clinical presentation and radiologic imaging (clinical diagnosis). According to diagnostic method, frequency of clinical diagnosis was highest in patients with luminal (50.7%) or peritoneal (64.3%) TB, while frequency of microscopic diagnosis was highest in patients with visceral TB (68.2%), and frequency of histologic diagnosis was highest in patients with nodal TB (85.2%). Interestingly, most patients, except those with nodal TB, showed a good response to anti-TB agents, with 84.2% showing a complete response. The mortality rate was only 1.4% in the present study.

Conclusions

Most patients responded very well to anti-TB therapy, and surgery was required in only a minority of cases of suspected abdominal TB.

     

The Molecular Basis for the Generation of Hodgkin and Reed-Sternberg Cells in Hodgkin’s Lymphoma

Hodgkin's lymphoma (HL) is a lymphoid neoplasm with a low frequency of malignant tumor cells, known as Hodgkin and Reed-Sternberg (H-RS) cells, in a background of mixed cellular infiltrates. Despite extensive studies on H-RS cells, the molecular mechanisms of their growth and regulation have remained uncertain for a long period. Recently, constitutively activated nuclear factor-kappaB (NF-kappaB) was reported to be a unique and common characteristic of H-RS cells that prevents the cells from undergoing apoptosis. NF-kappaB triggers proliferation and provides a molecular basis for these cells' aberrant growth and cytokine gene expression. In HL pathogenesis associated with Epstein-Barr virus infection, the activation of NF-kappaB is induced by viral latent membrane protein 1 (LMP1). Coupled with recent insights into the molecular mechanisms of activation of NF-kappaB signaling in H-RS cells, this review discusses a linkage between LMP1 and HL via CD99, which has recently been reported to be down-regulated by LMP1 through the NF-kappaB signaling pathway. This down-regulation leads to the generation of cells with H-RS phenotypes related to the clinical and histologic characteristics of HL.     

Adoptive Immunotherapy for Hodgkin’s Lymphoma

Adoptive transfer of tumor-specific T-cells is an attractive strategy for the treatment of patients with refractory or relapsed Hodgkin's lymphoma. However, Hodgkin's lymphomas possess a range of tumor-evasion mechanisms, which must be overcome before the full potential of immunotherapies can be achieved. In this article, we discuss the promise of Epstein-Barr virus-specific cytotoxic T-lymphocytes, the roles of cytokines, and other strategies for overcoming the immune-evasion mechanisms in Hodgkin's lymphoma.     

Genomic Alterations in Hodgkin’s Lymphoma

Cytogenetic analysis of Hodgkin’s lymphoma (HL) is hampered by the scarcity of neoplastic cells within a sea of reactive cells. There is accumulating evidence that HL represents 2 disease entities, classic HL (cHL) with its morphologic variants and nodular lymphocyte predominant HL (NLPHL). This subdivision, initially worked out in morphologic and immunohisto-chemical studies, has been further substantiated by molecular cytogenetic investigations. Two recurrent chromosomal aberrations, namely gains of 2p13–p16 and 9p24, have been found by comparative genomic hybridization analysis in microdissected cells from cHL patients as well as in cHL cell lines, but not in NLPHL cells. The available cHL cell lines are remarkably heterogeneous in their karyotypes, suggesting profound genomic instability leading to numeric chromosomal aberration and multiple chromosomal breaks and translocations. In this article, we review genomic aberrations that may contribute to the development and maintenance of the morphologic and clinical presentation of these B-cell lymphoma entities. Furthermore, we delineate current data on the genomic changes observed in the neoplastic cells of HL that are created by epigenetic mechanisms, which are alternative mechanisms that regulate the expression of relevant genes.     

Classical Hodgkin’s lymphoma: the Lymphoma Study Association guidelines for relapsed and refractory adult patients eligible for transplant

The Hodgkin’s Lymphoma Committee of the Lymphoma Study Association (LYSA) gathered in 2012 to prepare guidelines on the management of transplant-eligible patients with relapsing or refractory Hodgkin’s lymphoma. The working group is made up of a multidisciplinary panel of experts with a significant background in Hodgkin’s lymphoma. Each member of the panel of experts provided an interpretation of the evidence and a systematic approach to obtain consensus was used. Grades of recommendation were not required since levels of evidence are mainly based on phase II trials or standard practice. Data arising from randomized trials are emphasized. The final version was endorsed by the scientific council of the LYSA. The expert panel recommends a risk-adapted strategy (conventional treatment, or single/double transplantation and/or radiotherapy) based on three risk factors at progression (primary refractory disease, remission duration < 1 year, stage III/IV), and an early evaluation of salvage chemosensitivity, including ¹⁸fluorodeoxy glucose-positron emission tomography interpreted according to the Deauville scoring system. Most relapsed or refractory Hodgkin’s lymphoma patients chemosensitive to salvage should receive high-dose therapy and autologous stem-cell transplantation as standard. Efforts should be made to increase the proportion of chemosensitive patients by alternating non-cross-resistant chemotherapy lines or exploring the role of novel drugs.     

Clinical features of Behcet’s disease in Egypt

Behcet's disease (BD) is a chronic relapsing multisystem disease of unknown etiology. Ethnic origin is one of the factors that may modulate the prevalence and the expression of BD. To study the clinical characteristics of Egyptian patients with BD, and compare the pattern of the disease in Egyptians with studies from other countries. Sixty-three patients with BD were studied over a 4-year period. A rheumatologist, dermatologist, neurologist and other specialists as indicated assessed the patients clinically. Laboratory and radiological examinations were done to confirm the diagnosis to rule out any condition that may mimic BD. Sixty-one patients were men, two were women, the mean age of the patients was: 32.8 +/- 8.3 years, age of onset of the disease varied between 17 and 37.4 years. The initial presenting manifestation was oral ulcers in 39.7% of patients, followed by orogenital ulcers in 23.8%, followed by deep venous thrombosis in 7.9% Throughout the study period, the commonest manifestation was oral ulcers (100%), followed by genital ulcers (96.8%), vascular lesions (57.1%), cutaneous (55.5%), ocular (47.6%), joint (36.5%), neurological (34.9%), gastrointestinal (19%) and cardiac (6.3%). BD in Egyptians shows higher male-to-female ratio and higher incidence of vascular and neurological lesions.     

Non-Hodgkin’s lymphoma in southeast Turkey: clinicopathologic features of 490 cases

We have carried out a retrospective analysis of 490 non-Hodgkins lymphomas (NHLs), followed at our clinic, with the purpose of evaluating the clinicopathologic features of these patients. The patients were assessed with regard to their characteristics including age, gender, histologic distribution, stage, extranodal involvement, presenting symptoms, and biopsied site. Of the patients 314 (64%) were male and 176 (36%) were female. The overall median age was 43 years (range: 14–90). The patients were classified according to the Working Formulation (WF) system: 71 (14.4%) were low grade, 342 (69.8%) were intermediate grade, 43 (8.7%) were high grade, and 34 (6.7%) had other lymphomas. Intermediate-grade non-Hodgkins lymphomas formed the largest group, of whom 320 patients paraffin blocks were available for Revised European and American lymphoma (REAL) classification: 78% were B-cell lymphomas, whereas 16% were T/NK lymphomas. Six percent of cases were unclassified lymphomas. Diffuse large B-cell lymphoma (DLBCL) was the most commonly observed histopathologic type in 132 (41%) patients. Extranodal involvement was found in 218 (44.5%) patients. The most commonly affected extranodal sites were small bowel, stomach, and tonsil in 72 (33%), 63 (29%), and 19 (8.7%) patients, respectively. According to the Ann Arbor staging system, the vast majority of patients (89.4%) were advanced stage. In conclusion, the characteristics of NHLs in our region show some differences from the other sites of Turkey and the world.     

Clinico-pathologic profile of Hodgkin’s lymphoma in a rural medical college

Purpose of study

A prospective study was done at North Bengal Medical College and Hospital (NBMCH), Darjeeling, West Bengal, which caters predominantly to the rural and hilly population. All patients diagnosed as Hodgkin’s lymphoma (HL) were analyzed for clinical presentation, histological classified and staging.

Results

Total of 48 cases reported for HL were studied (n=48). A lower median age of onset (28.1year) and higher male to female ratio (3.8:1) as compared to western countries were observed. We found neck swelling was the commonest presenting symptom (58.28%) and peripheral lymphadenopathy was the commonest sign (83.33%). “B symptoms” was noted in 79.17% cases. Cervical lymph nodes were commonly involved (79.17%), followed by inguinal (45.83%) and axillary (29.17%). Thoracic lymph nodes and abdominal lymph nodes were enlarged in 29.17% of the cases and 25% of the cases respectively. Eosinophilia was noted in 29.17% of cases. Marrow involvement by neoplastic process was observed in 8.33% of cases and reactive changes in the marrow were observed in 12.5% of cases. We found mixed cellularity subtypes was the commonest (45.83%) followed by nodular sclerosis subtypes (33.33%). At presentation 54.17% of cases were of advanced stage of disease (stage III and IV).

Conclusion

We noticed a distinct geographical pattern of HL in respect of age, sex, presentation, histological typing and staging of the disease, which is comparable to some other Indian studies but is noticeably different from patterns noted in Western countries.

     

Increased Risk of Second Lung Cancer in Hodgkin’s Lymphoma Survivors: A Meta-analysis

Background

Patients treated for Hodgkin’s lymphoma (HL) have a higher risk of developing second lung cancer (SLC) compared with the general population. The aim of this meta-analysis was to quantify such risk and to analyze contributing risk factors in HL survivors.

Methods

According to predefined selection criteria, a literature search identified 21 studies that were included in the analysis.

Results

After eliminating overlapping or duplicate data, 793 (76 % males) incidences of SLC were encountered in 74,831 patients (58 % males) with HL over a median follow-up of 11.5 years. The median age at HL diagnosis and the median age at SLC diagnosis were 33.0 and 45.9, respectively. The mean latency between treatment of HL and development of SLC was 11.5 years. The pooled relative risk (RR) of SLC was 4.62 (95 % confidence interval [CI], 3.18–6.70], I ² = 98 %), with a median absolute excess rate of 10.4 per 10,000 person-years. RR was positively related to study size, male-to-female ratio, institutional versus population-based data sets, and the use of any radiotherapy (RT) or combined modality therapy (CMT), while age at diagnosis of HL was not significant. The highest risk was shown among patients aged 15–24 years (RR = 8.76 [95 % CI, 4.55–16.89]), while the lowest risk occurred in patients ≥55 years at primary treatment (RR = 2.88 [95 % CI, 2.33–3.56]). RR increased by increasing duration of follow-up, reaching the highest value at 10–14 years (RR = 4.17 [95 % CI, 3.62–8.81]), but did not increase after ≥15 years (RR = 4.01 [95 % CI, 2.68–5.98]). RT only, CMT, or chemotherapy only was associated with RR (95 % CI) of 4.88 (3.14–7.60), 5.15 (4.08–6.50), and 2.39 (1.60–3.55), respectively. Patients with SLC demonstrated poor prognosis.

Conclusions

The current meta-analysis provided a detailed estimate of the risk of SLC among HL survivors. The obtained results may provide guidelines concerning lung cancer screening for this population.     

Clinical features and oncological outcomes of intestinal cancers associated with ulcerative colitis and Crohn’s disease

Journal of Gastroenterology - Patients with longstanding inflammatory bowel disease are at high risk of developing intestinal cancers. In this study, we aimed to elucidate the differences between...     

Clinical features of Behcet’s disease in Mongolia: a multicenter study

Clinical Rheumatology - The aim of the present study is to investigate the clinical features of patients with Behcet’s disease (BD) in Mongolia. Patients were identified and examined from six...     

Composite diffuse large B-cell lymphoma and classical Hodgkin’s lymphoma of the stomach:Case report and literature review

The combination of classical Hodgkin’s lymphoma(cHL)and non-Hodgkin lymphoma coexisting in the same patient is not common,especially in one extranodal location.Here we present a rare case of composite diffuse large B-cell lymphoma(DLBCL)and cHL occurring simultaneously in the stomach of a 53-year-old female who presented with upper abdominal discomfort and gas pain.Surgery was performed and the disease was diagnosed pathologically as composite lymphoma of DLBCL and cHL using hematoxylin-eosin and immunohistochemical staining.Epstein-Barr virus(EBV)infection was not detected by in situ hybridization for EBV-encoded RNA or immunohistochemistry for EBV latent membrane protein-1.Polymerase chain reaction analysis from the two distinct components of the tumor demonstrated clonal immunoglobulinκlight chain gene rearrangements.The patient died approximately 11 mo after diagnosis in spite of receiving eight courses of the CHOP and two courses of the rituximab-CHOP(RCHOP) chemotherapy regimen.This case report showed that the two distinct components,DLBCL and cHL,appeared to originate from the same clonal progenitor cell,and that EBV infection was not essential for transformation during the course of tumorigenesis.     

Sperm quality before treatment in patients with early stage Hodgkin’s lymphoma enrolled in EORTC-GELA Lymphoma Group trials

Background

Although widely recommended, cryopreservation of sperm is sometimes not performed for patients with Hodgkin’s lymphoma because of presumed poor sperm quality related to the disease. We investigated sperm quality and factors determining it in untreated patients with early stage Hodgkin’s lymphoma.

Design and Methods

Of 2362 males who participated in EORTC H6–H9 trials, 474 (20%) had data available. Sperm quality was defined according to World Health Organization guidelines. Determining factors were studied by logistic regression analysis.

Results

The median sperm concentration was 40×10⁶/mL (range, 0–345×10⁶/mL) and the median motility 50% (range, 0–90%). Sperm quality was good (concentration ≥20×10⁶/mL and motility ≥50%), intermediate (concentration ≥5×10⁶/mL) and poor (concentration <5×10⁶/mL but >0) in 41%, 49% and 7% of patients, respectively. Three percent of the patients were azoospermic. No relation was found between sperm quality and age or clinical stage of the Hodgkin’s lymphoma, but B-symptoms and elevated erythrocyte sedimentation rate predicted poor sperm quality. The odds ratios for the association of poor sperm quality with the variables examined were: presence of B-symptoms, 2.77 (95% CI, 1.50–5.12; p=0.001); erythrocyte sedimentation rate of 50 mm/h or greater, 2.35 (95% CI, 1.24–4.43; p=0.009); fever, 3.22 (95% CI, 1.41–7.33; p=0.005), and night sweats, 3.78 (95% CI, 1.97–7.26; p<0.001). There was no relation between sperm quality and pre-treatment follicle stimulating hormone level.

Conclusions

In this large study of males with Hodgkin’s lymphoma, 90% had good or intermediate sperm quality. Three percent were azoospermic. There was an association between sperm quality and the presence or absence of B-symptoms, in particular fever and night sweats. With modern fertilization techniques, in most patients with early-stage Hodgkin’s lymphoma sperm quality before treatment is good enough for future fatherhood.