Malignancies Of Lymphoid Tissue Research Articles

B-NHL Cases in a Tertiary Pediatric Hematology-Oncology Department: A 20-Year Retrospective Cohort Study.

Non-Hodgkin lymphoma (NHL) is among the five most common pediatric cancer diagnoses in children and adolescents and consists of a heterogeneous group of lymphoid tissue malignancies -with B-cell-derived NHL accounting for nearly 80% of cases. Novel and high-throughput diagnostic tools have significantly increased our understanding of B-NHL biology and molecular pathogenesis, leading to new NHL classifications and treatment options. This retrospective cohort study investigated 17 cases of both mature B-cell NHL (Burkitt lymphoma or BL; Diffuse large B-cell lymphoma or DLBCL; Primary mediastinal large B-cell lymphoma or PMBCL; Follicular lymphoma or FL) and immature B-cell progenitor NHL (B-lymphoblastic lymphoma or BLL) that were treated in a tertiary Pediatric Hematology-Oncology Department during the last 20 years. Modern NHL protocols for children, adolescents, and young adults, along with the addition of rituximab, are safe and efficient (100% overall survival; one relapse). Elevated ESR was more prevalent than elevated LDH. Analyses have focused on immune reconstitution (grade ≥3 infections, lymphocyte and immunoglobulin levels recovery) and body-mass-index changes post-treatment, late effects (in 53% of patients), and the presence of histology markers BCL2, BCL6, CD30, cMYC, and Ki-67%. One patient was diagnosed with a second malignant neoplasm (papillary thyroid cancer).

Laying the groundwork for the Biobank of Rare Malignant Neoplasms at the service of the Hellenic Network of Precision Medicine on Cancer.

Biobanks constitute an integral part of precision medicine. They provide a repository of biospecimens that may be used to elucidate the pathophysiology, support diagnoses, and guide the treatment of diseases. The pilot biobank of rare malignant neoplasms has been established in the context of the Hellenic Network of Precision Medicine on Cancer and aims to enhance future clinical and/or research studies in Greece by collecting, processing, and storing rare malignant neoplasm samples with associated data. The biobank currently comprises 553 samples; 384 samples of hematopoietic and lymphoid tissue malignancies, 72 samples of pediatric brain tumors and 97 samples of malignant skin neoplasms. In this article, sample collections and their individual significance in clinical research are described in detail along with computational methods developed specifically for this project. A concise review of the Greek biobanking landscape is also delineated, in addition to recommended technologies, methodologies and protocols that were integrated during the creation of the biobank. This project is expected to re-enforce current clinical and research studies, introduce advances in clinical and genetic research and potentially aid in future targeted drug discovery. It is our belief that the future of medical research is entwined with accessible, effective, and ethical biobanking and that our project will facilitate research planning in the '-omic' era by contributing high-quality samples along with their associated data.

Hereditary cancer syndrome-associated pathogenic variants are common in patients with hematologic malignancies subsequent to primary solid cancer.

Background: As the number of long-term survivors of solid cancers keeps increasing, risk assessment of secondary hematologic malignancies is important for the prognosis of the patient. Germline genetic predisposition to secondary hematologic malignancy has been studied widely in myeloid neoplasms and rarely in lymphoid neoplasms. This study aimed to profile the mutational spectrums of patients with subsequent lymphoid tissue neoplasm to shed some light on the understudied area.Methods: In total, 39 patients who had primary solid cancer and subsequent hematologic malignancies were enrolled. We performed two next-generation sequencing (NGS) panel tests encompassing hereditary cancer predisposition genes and genes related to clonal hematopoiesis of indeterminate potential (CHIP). All statistical analyses were performed using R 3.5.1.Results: We found 8 of 39 patients with germline mutations in cancer predisposition genes; 4 of 18 patients had therapy-related myeloid neoplasms (22.2%); and 4 of 15 patients had secondary lymphoid malignancies (26.7%). Notably, of 14 patients who initially suffered from thyroid cancer, 5 patients (35.7%) had germline mutations. Malignancy of lymphoid tissue showed no association with radioactive iodine therapy but was observed to a greater extent in germline mutation-positive thyroid cancer patients regardless of their history of treatment. We observed that 24 of 39 patients (61.5%) were CHIP carriers. Patients who had secondary lymphoid malignancy were less likely to have CHIP than those who had myeloid malignancy.Conclusions: In patients with primary solid cancer who are planning to undergo cytotoxic chemotherapy, radiotherapy, or radioactive iodine therapy, an initial assessment with germline mutation testing using an expanded NGS panel, including low, moderate, and high-risk cancer-associated genes, and somatic CHIP mutation testing can screen the patients who are at risk of developing therapy-related myeloid and lymphoid malignancies. Through careful screening and monitoring throughout the treatment process, patients can benefit from the early detection of secondary malignancies and receive proper treatment.

P2.01-059 Breast Metastasis from Pulmonary Cancer: A Case Report. University Hospital “Shefqet Ndroqi” Tirana Albania 2008

Breast metastasis from the lung malignancy is very rare. An incidence of 0.1% to 1.6%. The most commonly of primary malignant diseases that metastasize to the breast are lymphoid tissue malignancy, malignant hemopoietic disease, and malignant melanoma. In our experience we have had only one case with breast cancer metastasis from primary lung cancer. A 56-year-old female ex-smoker manifested a right breast mass and lymphonodi in the right axillar region. She was treated for primary lung cancer stage IIB before 4 months. Although she was treated for right spontaneous pneumothorax six years ago through right posterolateral thoracotomy, wedge bullectomy superior dexter, fruotazh and pleural drainage. After 3 years she was treated and for metastasectomy left lung and lateral chest wall resection cost 6/7. The patient underwent right local mastectomy and right axillary dissection. After histological and immunohistochemical analyzes showed that breast mass was metastasis from a primary lung carcinoma Accuracy treatment and prognosis of the breast metastasis from primary lung cancer is differentiation from the primary breast cancer and is very important to do this differentiation.

Thiopurines and Methotrexate Use in IBD Patients in a Biologic Era.

Although we have been living in the era of biologic therapy for several decades, the use of immunomodulators (primarily thiopurines [azathioprine and mercaptopurine] and less so methotrexate) still remains an important component of the inflammatory bowel disease (IBD) pharmaceutical arsenal. Thiopurines as monotherapy exert corticosteroid-sparing effects and can maintain long-term remission in a considerable proportion of patients who have frequent relapses and are or have become mesalazine and/or corticosteroid intolerant or refractory. Withdrawal of thiopurines results in relapse of disease in a significant proportion of patients. Thiopurines enhance the induction effect of anti-TNFα biologics and can reinstate disease remission in patients who lose response to anti-TNF monotherapy. In thiopurine-naïve ulcerative colitis (UC) patients with iv corticosteroid-refractory disease, thiopurines offer an excellent maintenance strategy after cyclosporine rescue therapy. They also prevent the postoperative recurrence of Crohn's disease, especially in smokers, and can achieve response or remission in uncomplicated perianal fistulizing disease. Close monitoring of patients with sequential measurements of complete blood count, liver enzymes, serum and fecal biomarkers, and/or thiopurine metabolites is essential to assess efficacy, safety, and adherence to treatment. Adverse reactions are dose dependent or idiosyncratic. Idiosyncratic reactions to azathioprine, except pancreatitis, can be treated by switching to mercaptopurine or 6-thioguanine. Thiopurines increase the relative risk for skin, urinary tract, and lymphoid tissue malignancies but the absolute risk is low. Preventive measures include sunlight protection and annual Pap smears (females). The use of antimetabolite therapy in patients over the age of 65years is generally avoided. Methotrexate has advantages over thiopurines subsequent to its once weekly dosing, faster onset of action, and better safety profile relating to malignancies; however, its parenteral administration, contraindication in pregnancy and lactation, and its misconceptions particularly related to hepatotoxicity have reserved its use as a second-line therapy, i.e., when thiopurines fail. Yet, methotrexate in combination with a tapering dose of corticosteroids is an effective agent for active luminal Crohn's disease. In combination with infliximab is preferred for pediatric patients and adolescent IBD male patients who have not contracted the Epstein-Barr virus. Methotrexate also reduces the immunogenicity of infliximab. Folic acid supplementation and close monitoring with blood tests and renal and liver function tests are essential to prevent toxicity especially in patients with diabetes mellitus, non-alcoholic liver fatty disease (NAFLD), malnutrition, and renal function impairment.

GA-67 CITRATE SPECT AND 18-FDG PET/CT BENEFITS IN EVALUATION OF HODGKIN DISEASE SPREADING

Hodgkin disease is a malignancy of lymphoid tissue, at the age of 15 to 24 years it accounts for 1⁄6 of all oncology disease. The aim of the study was to evaluate the benefits of single-photon emission computed tomography (SPECT) with citrate gallium-67 and combined positron emission tomography (PET/CT) with 18-FDG in a patient with Hodgkin disease. Results: SPECT detected no affected cervical nodes that were found with PET/CT. Conclusion: presented in this article SPECT technique is not suitable for studying this patient. Limitations of the methods for this case and opportunities for overcoming the limitations are discussed.

Molecular Genetic Abnormalities in the Pathogenesis of Hematologic Malignancies and Corresponding Changes in Cell Signaling Systems

Hematological disorders include a wide spectrum of malignancies of hematopoietic and lymphoid tissues. The genetic changes underlying the pathogenesis of the diseases are specific for each disease. High incidence of chromosomal aberrations (deletion, translocation, insertion) is one of the principal characteristics of oncohematological diseases. In addition, mutations in individual genes or blocking of normal regulation of gene functioning in relation to epigenetic events can occur. Progression of oncohematological diseases could be a result of accumulation of different genetic abnormalities. Modern classification of malignancies of hematopoietic and lymphoid tissues is based on the analysis of clinical data, morphological and functional characteristics of tumor cells and identification of specific cytogenetic and molecular-genetic changes. A large number of genetic abnormalities specific for certain types of hematological malignancies has been discovered to date. It allows to optimize the treatment strategy, as well as to design, test and introduce to the clinical practice a number of targeted drugs (inhibitors of chimeric proteins formed as a result of trans-locations and triggering the malignant cell transformation). Drugs based on monoclonal antibodies (Rituximab, Alemtuzumab, etc.) or low molecular weight compounds (Imatinib, Bortezomib, Carfilzomib) form this group of medications. The knowledge about not only specific gene abnormalities but also about the corresponding changes in cell efferent signaling pathways could be of great interest for the development of new targeted molecules or the repurposing of known chemotherapeutic agents. The present review compares genetic aberrations in diseases listed in the 2008 WHO classification (amended in 2016) of hematopoietic and lymphoid tissue malignancies and main changes in cell signaling pathways associated with malignant transformation of hematopoietic cells.

Chromothripsis in Oncology: Literature Review and Case Report

The article presents a clinical case and literature review dwelling on the recently discovered chromothripsis phenomenon in oncology. Chromothripsis is a type of complex genome changes when a chromosome is first torn into dozens and even thousands of fragments, and then these fragments are bound in a random manner. Sometimes, several chromosomes are involved in the restructuring. As a result, genome mutant zones are formed which trigger malignancies and congenital diseases. In other words, the use of certain methodological approaches (multicolor fluorescence in situ hybridization, SKY technique, and some others) permits to observe under a microscope the splitting of two or more chromosomes and further reunification of these fragments into new unusual two- or multicolor structures, chromosomal markers. Chromothripsis is a rare phenomenon with a peculiar pattern observed in clones of cells of various tumors including hematopoietic and lymphoid tissue malignancies. There are published data on a higher incidence of this phenomenon in patients with myelodysplastic syndromes and bone tumors. TP53 gene mutations play an important role in the development of chromothripsis. The use of paired-sequencing DNA or SNP approaches in oncology is promising both in theoretical and clinical application. The first subject cohort should include patients with TP53 and MLL gene mutations, complex chromosomal aberrations, EVI-1 gene overexpression, and some others. The article presents the chromothripsis phenomenon in an 8-month-old girl with M7 acute myeloid leukemia.

Pathomorphological Diagnosis of Splenic Diffuse Red Pulp Small B-Cell Lymphoma

Background. Unclassifiable splenic B-cell lymphoma/leukemia is a rare and poorly studied disorder introduced in the WHO classification of hematopoietic and lymphoid tissue malignancies for the first time in 2008. This type of lymphoma requires differential diagnosing between hairy cell leukemia-variant (HCL-V) and splenic diffuse red pulp small B-cell lymphoma (SDRPL). Aim. To develop criteria for diagnosis of SDRPL by comparison of bone marrow biopsies (BMB) and surgical specimens of the spleen. Methods. In the Department of Morbid Anatomy of the Hematology Research Center, preoperative BMBs and surgical specimens of the spleen (2013-2015) were compared in 71 patients (men/women ratio 1:2.6, age range 44-81, median age 58 years) using morphological and extended immunohistochemical studies. Sanger sequencing and PCR assay were carried out to analyze the mutational status of IgHV and to identify mutations in MAP2K1, NOTCH, BRAF. Results. SDRPL was diagnosed in 5 (7 %) of 71 patients. In 2 groups of patients (with normal and high WBC count), the morphological features of spleen tissue were similar to those of a neoplastic substrate of HCL-V. The immunohistochemical assay demonstrates monomorphic expression of CD20 and DBA.44 and heterogeneous expression of CD11c, TRAP, CD103, CD123 in all cases. In none of the 5 cases, expression of CD25, CD27, Cyclin D1, Annexin-1 was found. In bone marrow (unlike HCL and HCL-V), predominantly interstitial and intravascular scant CD20+ lymphoid infiltration (4 of 5 cases) was found without detectable nucleoli in nuclei of small lymphoid cells. In 1 case, there was a combined lymphoid infiltration: CD20+ microfocalinterstitial infiltration with an intravascular component. No persistent molecular mutations in the spleen tissue specimens were found. Conclusion. SDRPL is diagnosed in 7 % of splenic B-cell lymphomas. It is a rare disorder, whose verification requires an integrated approach taking into account clini cal and laboratory data, results of flow cytometry, cytological, morphological, extended IHC and molecular biological studies.

Infection with Hepatitis B and C Viruses and Risk of Lymphoid Malignancies in the European Prospective Investigation into Cancer and Nutrition (EPIC)

Case-control studies suggested a moderate, but consistent, association of hepatitis C virus (HCV) infection with lymphoid tissue malignancies, especially non-Hodgkin lymphoma (NHL). More limited data suggested that hepatitis B virus (HBV) infection might also be associated with NHL. However, prospective studies on the topic are few. A nested case-control study was conducted in eight countries participating in the EPIC prospective study. Seven hundred thirty-nine incident cases of NHL, 238 multiple myeloma (MM), and 46 Hodgkin lymphoma (HL) were matched with 2,028 controls. Seropositivity to anti-HCV, anti-HBc, and HBsAg was evaluated and conditional logistic regression was used to estimate odds ratios (OR) and corresponding 95% confidence intervals (CI) for NHL, MM, or HL, and their combination. Anti-HCV seropositivity among controls in different countries ranged from 0% to 5.3%; HBsAg from 0% to 2.7%; and anti-HBc from 1.9% to 45.9%. Similar nonsignificant associations were found with seropositivity to HBsAg for NHL (OR = 1.78; 95% CI: 0.78-4.04), MM (OR = 4.00; 95% CI: 1.00-16.0), and HL (OR = 2.00; 95% CI: 0.13-32.0). The association between HBsAg and the combination of NHL, MM, and HL (OR = 2.21; 95% CI: 1.12-4.33) was similar for cancer diagnosed less than 3 and 3 or more years after blood collection. No significant association was found between anti-HCV and NHL, MM, or HL risk, but the corresponding CIs were very broad. Chronic HBV infection may increase the risk of lymphoid malignancies among healthy European volunteers. Treatment directed at control of HBV infection should be evaluated in HBsAg-seropositive patients with lymphoid tissue malignancies.

Spontaneous regression of an untreated lung cancer

Spontaneous regression of malignancies have been documented, but it is a rare phenomenon. Most of such cases have been neuroblastoma, renal cell carcinoma or lymphoid tissue malignancies. This phenomenon has been recorded in few cases of Lung cancer also. Here we present a case of small cell lung cancer which was diagnosed with certainty. Patient did not take any treatment except the symptomatic one. As patient kept on living, and also improving, he was further investigated. Follow up X-Ray chest, Computed tomography scan showed total clearance of the tumour. Immuno-histochemistry of previous histology slides reconfirmed the diagnosis of Lung cancer. Though 8 cases of spontaneous regression of lung cancer have been reported in world literature, this is the first case which diagnosis and regression of lung cancer are confirmed without any doubts by various modalities. Many theories have been propagated to explain this phenomenon but none is proven so far. If mechanism of this phenomenon could be known, we can hope to find the cure of cancer.

Structure of a trimeric variant of the Epstein–Barr virus glycoprotein B

Epstein-Barr virus (EBV) is a herpesvirus that is associated with development of malignancies of lymphoid tissue. EBV infections are life-long and occur in >90% of the population. Herpesviruses enter host cells in a process that involves fusion of viral and cellular membranes. The fusion apparatus is comprised of envelope glycoprotein B (gB) and a heterodimeric complex made of glycoproteins H and L. Glycoprotein B is the most conserved envelope glycoprotein in human herpesviruses, and the structure of gB from Herpes simplex virus 1 (HSV-1) is available. Here, we report the crystal structure of the secreted EBV gB ectodomain, which forms 16-nm long spike-like trimers, structurally homologous to the postfusion trimers of the fusion protein G of vesicular stomatitis virus (VSV). Comparative structural analyses of EBV gB and VSV G, which has been solved in its pre and postfusion states, shed light on gB residues that may be involved in conformational changes and membrane fusion. Also, the EBV gB structure reveals that, despite the high sequence conservation of gB in herpesviruses, the relative orientations of individual domains, the surface charge distributions, and the structural details of EBV gB differ from the HSV-1 protein, indicating regions and residues that may have important roles in virus-specific entry.

Survival from non-Hodgkin lymphoma in England and Wales up to 2001.

Non-Hodgkin lymphoma comprises a disparate set of malignancies of lymphoid tissue, other than Hodgkin's disease, with a wide variety of biological, clinical and prognostic features. The clinical classification of lymphomas has changed considerably in response to advances in medical knowledge, but it has been difficult to assimilate these changes into the International Classification of Diseases (ICD) for Oncology, used by population-based cancer registries for coding cases for international comparison of cancer incidence (Percy et al, 1984). The tenth revision of the ICD provided more rubrics for non-Hodgkin lymphoma (C82–C85, C91.4, C96) than the two available in ICD-9 (200, 202), but cancer registry data were only coded to ICD-10 from 1995 or later. As a result, it is not yet possible to provide long-term comparisons of incidence and survival trends for specific types of non-Hodgkin lymphoma with population-based data. This is also true of mortality data, which were only coded to ICD-10 from 2000 or later, and which are derived from the limited diagnostic information on death certificates, as opposed to the medical records used to register newly diagnosed cases. Mortality data are generally reported for all the non-Hodgkin lymphomas combined. We present survival trends for the same broad category of all the non-Hodgkin lymphomas combined. Non-Hodgkin lymphoma is the most common lympho-haemopoietic malignancy in adults. It ranks as the eighth most common malignancy with almost 8000 new cases diagnosed each year. The male–female ratio is approximately 1.5. Non-Hodgkin lymphoma has tripled in frequency in both sexes since the early 1970s (Quinn et al, 2001), an increase echoed in many countries (Coleman et al, 1993). More than 60% of cases arise in persons aged 60 years or more, and the increase in incidence has been up to five-fold in older men and women, with little change in young adults. Incidence is slightly higher in affluent than deprived men, but there is no difference for women. The causes of NHL are not well established, although solvents, pesticides and other chemicals have been implicated (Blair and Kazerouni, 1997; Lynge et al, 1997; Stellman, 1998). Certain viruses, such as Epstein–Barr virus, HIV and HTLV are known to be potentially lymphoma-inducing (IARC, 1996, 1998), whereas oncogenic viruses have recently been suspected (Metayer et al, 1998). We analysed the data for 78 894 patients registered with non-Hodgkin lymphoma as a first primary malignancy in England and Wales during the period 1986–1999, some 86% of those eligible. Nine per cent of cases were excluded from survival analysis because their recorded survival was zero (date of diagnosis same as date of death): most of these will have been registered from a death certificate only (DCO); hence, their date of diagnosis and their duration of survival were both unknown. These cases could not be reliably distinguished from cases with true zero survival in the national data. The proportion of cases excluded from analysis as DCO was similar in all deprivation groups, and this is unlikely to have had a material impact on estimates of trend or socioeconomic gradient in survival. A further 3% of patients were excluded because the lymphoma was not their first primary malignancy, along with 1.8% whose vital status was unknown at 5 November 2002, when the data were extracted for analysis.

Long-term Follow-up of Cancer Risk in Patients Treated with Short-term Cyclosporine

Cyclosporine increases the risk of skin and lymphoid tissue malignancies in organ transplant patients. A similar increase has been shown among psoriasis patients, but no data exist on the carcinogenic risk of cyclosporine monotherapy in skin diseases. We conducted a retrospective cohort study of 272 patients, all of whom had received at least one month of cyclosporine treatment. The cancer information on these patients was obtained from the Finnish Cancer Registry. The median follow-up time was 10.9 years and the median treatment time with cyclosporine was 8 months. We did not detect any increase in the risk of skin malignancies or lymphoma. The overall risk of cancer was almost identical to that expected in the general population (standardized incidence ratios (SIR) = 1.31, 95% confidence interval (CI) = 0.70-2.23). This study shows that short-term cyclosporine treatment is probably not related to subsequent malignancy. Since the CI of the SIR estimate was rather wide, larger studies are needed in the future.

Clinical characteristics of a group of adults with nodular lymphoid hyperplasia: A single center experience

To describe the clinical and histological characteristics of a group of adults with small-bowel nodular lymphoid hyperplasia (NLH). Patients were searched for five years in pathology records of our institution. The biopsy material was reassessed using strict histopathological criteria. Clinical data were obtained from medical records. Small-bowel NLH was diagnosed in 18 cases. The female: male ratio was 2:1. The most frequent symptoms were diarrhea (72%), involuntary weight loss (72%) and abdominal pain (61%). Nine patients (50%) had immunodeficiency. Small-bowel bacterial overgrowth was found in three (17%) cases. At small-bowel NLH diagnosis, three (17%) had associated lymphoma: two intestinal and one extra-intestinal lymphomas. In two patients with villous atrophy and anti-endomysial antibodies the diagnosis of celiac disease was established. Giardia lamblia infection was found in only one patient with hypogammaglobulinemia (Herman's syndrome). NLH is uncommon in adult patients. Associated diseases are immunodeficiency and lymphoid tissue malignancies.

Gastrointestinal: Burkitt's lymphoma

Lymphomas are solid malignancies of lymphoid tissue that can be categorized as either Hodgkin’s disease or nonHodgkin’s lymphoma. It is rare for Hodgkin’s disease to involve the gastrointestinal tract. Although the majority of non-Hodgkin’s lymphomas are thought to arise from lymph nodes, at least 30% arise in other organs and are called extranodal or primary lymphomas. Of these extranodal lymphomas, up to 40% are located in the gastrointestinal tract, particularly in the stomach and small bowel. Most of these lymphomas are of B-cell lineage. The most common are the diffuse large cell lymphoma and the marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma). Other B-cell lymphomas include Burkitt’s lymphoma, mantle cell lymphoma and follicular lymphoma. The images shown below were from a 76-year-old man who was admitted to hospital with malaise, weight loss and pain in the left flank. He subsequently had two significant episodes of hematemesis and melena. Upper gastrointestinal endoscopy revealed bleeding from multiple doughnut-like tumors in the body and antrum of the stomach (Fig. 1). He also had giant gastric folds. A computed tomography scan of the abdomen showed thickening of the wall of the jejunum and tumor infiltration of the left renal pelvis and parts of the right kidney. Histopathological examination of gastric biopsy specimens showed sheets of intermediate-sized lymphoid cells crowding between glands with an interspersed starry-sky pattern (Fig. 2; HE: ×200). Immunohistochemical stains were positive for CD20 (indicating B-cell lineage) and almost all cells were positive for Ki-67 (indicating an extremely high proliferation rate). The diagnosis was that of Burkitt’s lymphoma. Apart from Burkitt’s lymphoma, multiple gastric polypoid lesions with central ulceration can be seen in Kaposi’s sarcoma, stromal cell tumors, metastatic gastric tumors and other lymphomas. Although only 1‐2% of adult non-Hodgkin’s lymphoma are of the Burkitt’s variety, substantially higher percentages have been described in the pediatric setting and in patients with HIV. Blackwell Science, LtdOxford, UKJGHJournal of Gastroenterology and Hepatology0815-93192005 Blackwell Publishing Asia Pty LtdOctober 2005201016161616Images of Interest Images of InterestImages of Interest

657del5 mutation in the gene for Nijmegen breakage syndrome (NBS1) in a cohort of Russian children with lymphoid tissue malignancies and controls.

Nijmegen breakage syndrome (NBS, OMIM 251260) is a rare hereditary disease, characterized by immune deficiency, microcephaly, and an extremely high incidence of lymphoid tissue malignancies. The gene mutated in NBS, NBS1, was recently cloned from its location on chromosome 8q21. The encoded protein, nibrin (p95), together with hMre11 and hRad50, is involved in the double-strand DNA break repair system. We screened two Russian cohorts for the 657del5 NBS1 mutation and found no carriers in 548 controls and two carriers in 68 patients with lymphoid malignancies: one with acute lymphoblastic leukemia (ALL) and one with non-Hodgkin lymphoma (NHL). Several relatives of the second patient, who were carriers of the same mutation, had cancer (ALL, breast cancer, GI cancers). These preliminary data suggest that NBS1 mutation carriers can be predisposed to malignant disorders.

Liver disease in primary immunodeficiencies

Primary immunodeficiencies (PIDs) are heritable disorders of innate and/or acquired immunity, often complicated by severe, recurrent or unusual infections, chronic diarrhea with failure to thrive and malignancies of lymphoid tissue in long-term survivors.