Variety Of Nonmalignant Conditions Research Articles

A case report on a sporadic retroperitoneal malignant peripheral nerve sheath tumour mimicking a pelvic abscess

Soft tissue sarcomas (STS) are a diverse group of neoplasms with about 60 subtypes arising from a variety of anatomical structures across all age groups. The diagnosis of STS can prove to be challenging as it mimics a variety of non malignant conditions. Here we present one such case of a sporadic MPNST which was operated on with the main differential diagnosis of a Pelvic Abscess. Hence though STS is rare in general population it should always be kept in mind in cases of doubtful and confusing presentations.

Facilitating Cells: A Journey from Bench to Bedside

The development of safe conditioning protocols has reduced the morbidity and mortality of hematopoietic stem cell transplantation (HSCT), allowing broader application for treatment of a variety of non-malignant conditions including autoimmune diseases, hemoglobinopathies, metabolic disorders etc., as well as inducing tolerance to solid organ transplants. One of the most successful clinical trials using a facilitating cell enhanced HSCT paired with a kidney transplant has effectively induced tolerance in the absence of immunosuppressive drugs, maintaining the function of the transplanted kidney, and reconstituting the immunocompetence of the recipient. This novel protocol eliminates the need for immunosuppressive drugs, the key source of kidney and liver toxicity, increased malignancy, and shortened life span. CD8+ TCR facilitating cells (FC) are a population of tolerogenic cell which promote hematopoietic stem cell engraftment across human leukocyte antigen (HLA) barriers. In this review, we discuss the bench to bedside journey of FC, from discovery in mouse models, characterization of the subpopulations of FC, the mechanisms by which FC induce tolerance and clinical application. As a novel personalized medicine, FC may change the approach to overcoming HLA barriers for both HSCT and solid organ transplant recipients.

Incident cancers and late mortality in Australian children treated by allogeneic stem cell transplantation for non-malignant diseases.

Hematopoietic stem cell transplantation (HSCT) is a life-saving procedure for children with a variety of non-malignant conditions. However, these children face an increased risk of late death and incident cancers after HSCT, which may occur many years after their initial HSCT. We examined cancer occurrence and late mortality in a population-based cohort of 318 Australian children who underwent allogeneic HSCT for non-malignant disease. Standardized incident ratios (SIRs) and standardized mortality ratios (SMRs) were calculated and compared with population controls. We identified six (1.9%) cancers at a median 9.2 years post-HSCT. Cancer occurred 15 times more frequently than in the general population (SIR 15.4, 95% CI = 6.9-34.2). Of the 198 patients who survived for at least 2 years post-HSCT, 11 (5.6%) died at a median 7.5 years post-HSCT. The mortality rate was 17 times higher than in the general population (SMR 17.5, 95% CI = 9.7-31.2). Children transplanted for non-malignant conditions require evidence-based survivorship programs to reduce excess morbidity and mortality.

Autoimmune Myelofibrosis (AIMF) – Clinical Features, Course and Outcome

BackgroundBone marrow (BM) fibrosis is commonly recognized in the setting of primary myelofibrosis (PMF) and other myeloproliferative neoplasms. However, a variety of non-malignant conditions are associated with myelofibrosis (MF). While PMF is associated with a limited survival, other causes of MF such as AIMF appear to have a favorable clinical course (Pullarkat et al, Am J Hematol 2001;116:211). We conducted a retrospective chart review of patients diagnosed with non-malignant MF to investigate clinical presentations, therapies, and outcomes of AIMF. MethodsPatients diagnosed with MF were identified from pathology records at Los Angeles County-USC Medical Center from 1999-2013. Histories were reviewed for the clinical indication for BM biopsy, medical conditions known to be associated with MF, and clinical course. Patients were excluded if they met diagnostic criteria for PMF or other neoplastic hematologic disorders associated with MF. BM specimens were assessed as described by Pullarkat et al: (1) Presence of diffuse reticulin fibrosis (European Consensus Score; Thiele et al, Haematologica, 2005;90:1128).; (2) Lack of clustered or atypical megakaryocytes; (3) Lack of myeloid or erythroid dysplasia, eosinophilia, or basophilia; (4) Lymphocyte infiltration; (5) Lack of osteosclerosis; (6) Absent or mild splenomegaly; and (7) Presence of autoantibodies. ResultsThirteen patients with MF were identified (11 F, 2 M; 23-73 y.). The mean follow up was 3.7 years. 12 presented with both anemia and thrombocytopenia, and represented the most common indication for BM biopsy. 1 of 12 also had severe leukopenia. The remaining patient presented with thrombocytosis. Clinical presentation included symptoms of fatigue, fever, lightheadedness, chest pain, and dyspnea. The spleen was enlarged in 1 patient, borderline enlarged in 4, normal in 6, and unknown in 1. 1 patient had a history of splenectomy. All patients had one or more autoantibodies. These included: ANA (8 patients), dsDNA (1), RF (4), CCP (2), DAT (7), lupus anticoagulant (3), anticardiolipin (2), atypical pANCA (1), anti-MPO (1), anti-SMA (3), anti-SSA (2), and anti-SSB (2). Medical co-morbidities included systemic lupus erythematosus (2 patients), rheumatoid arthritis (2), autoimmune hepatitis and primary sclerosing cholangitis (1), dermatomyositis (1), antiphospholipid antibody syndrome (1), and autoimmune hemolytic anemia (AIHA) (7). 3 AIHA patients had Evan's syndrome.BM cellularity ranged from normocellular to markedly hypercellular. The reticulin stain showed mild to moderate increase in fibrosis (MF1-2/3). Megakaryocytes were increased in 8 patients, normal in 3 patients, and decreased in 2 patients. Megakaryocytes were normal in appearance and distribution. No myeloid or erythroid dysplasia, eosinophilia, or basophilia were noted. All cases demonstrated increased small lymphocyte infiltrates. IgG4 immunostaining was negative in 4 of 4 specimens tested.In 1 patient with Evan's syndrome, MF was attributed to chronic romiplostim administration. 1 patient with thrombocytosis was treated as JAK2-negative essential thrombocythemia with normalization of his platelet count after interferon therapy. 4 of 11 remaining patients had a resolution in their cytopenias with steroid treatment with or without additional immunosuppressive agents. Resolution of MF was seen on post-steroid therapy BM biopsy in 2 of these patients. 3 had partial response in their cytopenias when treated with similar immunosuppressive regimens. Thrombocytopenia improved in 1 patient after splenectomy done for an unclear indication. 3 patients died due to unrelated sepsis. ConclusionAIMF is an under recognized cause of MF in patients presenting with cytopenias that responds to steroids and has a good clinical outcome in the majority of patients. While the spectrum of clinical presentations is broad, the BM findings are similar between cases and different from those of PMF. The prognostic and therapeutic differences between AIMF and PMF make distinction between these entities imperative for the treating physician. Disclosures:No relevant conflicts of interest to declare.

Genetic variation in insulin-like growth factors and brain tumor risk

Many studies support a role for insulin-like growth factors (IGFs) in the regulation of tumor cell biology. We hypothesized that single-nucleotide polymorphisms (SNPs) in IGF genes are risk factors for glioma and meningioma. To test the hypothesis, we examined associations of brain tumor risk with nine variants in five IGF genes in a hospital-based case-control study. The study was conducted at hospitals in Boston, Phoenix, and Pittsburgh between 1994 and 1998. Eligible cases were individuals (18 years or older) newly diagnosed with glioma or meningioma. Controls were selected among patients who were admitted to the same hospitals for a variety of nonmalignant conditions and frequency matched to cases by hospital, age, sex, race, and distance from residence. The present analysis was restricted to non-Hispanic whites. DNA was extracted from blood samples collected from 354 glioma cases, 133 meningioma cases, and 495 control individuals. We evaluated nine SNPs in five IGF genes (IGF1, IGF1R, IGF2, IGF2R, and IGFBP3). The majority of the analyzed IGF SNPs did not display statistically significant associations with glioma or meningioma. For glioma, one IGF1R SNP (rs2272037) indicated a possible association. No indications of association were seen for glioblastoma, but for low-grade gliomas, the odds ratio under a dominant model was 0.56 (95% confidence interval [CI], 0.35-0.90) for IGF1 rs6220, 2.98 (95% CI, 1.65-5.38) for IGF1R rs2272037, and 1.60 (95% CI, 0.90-2.83) for IGF1R rs2016347. Overall, our results do not provide strong evidence of associations of brain tumor risk with IGF polymorphic variants but identify several associations for glioma that warrant further examination in other, larger studies.

State-of-the-art FDG-PET imaging of lung cancer

The D-glucose analog 2-(fluorine-18)-fluoro-2-deoxy-D-glucose (FDG) is the most commonly used radionuclide in positron emission tomography (PET) of lung cancer. FDG-PET is a molecular imaging technique that images the preferential accumulation of FDG in malignant tissues with increased metabolism. Although FDG-PET is sensitive in the detection of lung cancer, FDG is not tumor specific and may accumulate in a variety of nonmalignant conditions. Occasional false-negative results may also occur. Whole body FDG-PET is a useful noninvasive technique to stage known or suspected non-small-cell lung cancer. The results allow more efficient use of invasive methods for histopathological staging. The combined use of CT and PET in dual imaging increases the number of patients with correctly staged non-small-cell lung cancer. CT/PET is also useful in the assessment of recurrent or residual disease. Future imaging agents are being developed which may allow more selective accumulation of radiopharmaceutical in malignant tissues.

Study Design for a Case Control Investigation of Cellular Telephones and Other Risk Factors for Brain Tumors in Adults

The aetiology of brain tumours is poorly understood. Due, in part, to public concern about a postulated relationship between the use of cellular telephones or other increasingly prevalent environmental exposures and the incidence of brain cancer in adults, the National Cancer Institute is collaborating with three US hospitals in a comprehensive case-control study of malignant and benign brain tumours. Factors under consideration include use of cellular phones and other wireless communication devices, workplace exposures to chemical agents and electromagnetic fields, dietary factors, family history of tumours, genetic determinants of susceptibility, home appliance use, reproductive history and hormonal exposures, viruses, medical and dental exposure to ionising radiation, and other aspects of medical history. Approximately 800 newly diagnosed brain tumour cases and 800 controls were enrolled at hospitals in Boston, Phoenix and Pittsburgh from 1994 to 1998. Cases include all adults (age ≥ 18 y) newly diagnosed with a histologically confirmed intracranial glioma, histologically confirmed intracranial meningioma or acoustic neuroma. Controls are patients admitted to the same hospitals as the eases, and treated for any of a variety of non-malignant conditions. Key features of the study include its large size, the emphasis on rapid ascertainment of incident cases and interview of study subjects rather than surrogate respondents, the use of detailed, job-specific questions developed by industrial hygienists to ascertain occupational exposures, and the storage of blood samples for future evaluation of inherited susceptibility, biomarkers of exposure and gene-environment interactions.