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Acta Medica Iranica Jan 2017Splenic hamartoma is an unusual accidental finding with non-neoplastic feature that may be incidentally diagnosed because of its compression effect on surrounding...
Splenic hamartoma is an unusual accidental finding with non-neoplastic feature that may be incidentally diagnosed because of its compression effect on surrounding organs. The predominant pathological feature leading diagnosis is circumscribed, un-encapsulated bulging nodules with focal fibrosis or cyst. The histopathological feature of splenic hamartoma is the positivity for CD8, and occasionally for CD31, CD34, and CD68 biomarkers on vascular wall but the cells are frequently negative for CD21. Herein, we describe a case with initial diagnosis of nephrolithiasis due to abdominal pain that was finally confirmed as splenic hamartoma by histopathological assessments and detection of CD8, CD31, CD34, and CD68 positivity.
Topics: Biomarkers; Cysts; Diagnosis, Differential; Hamartoma; Humans; Male; Middle Aged; Splenic Diseases
PubMed: 28188948
DOI: No ID Found -
Alimentary Pharmacology & Therapeutics Feb 2015Cyst infection is a severe complication of hepatic cystic disease. However, an evidence-based treatment strategy is not available. (Review)
Review
BACKGROUND
Cyst infection is a severe complication of hepatic cystic disease. However, an evidence-based treatment strategy is not available.
AIM
To assess the available treatment strategies and provide a treatment advice for de novo hepatic cyst infection.
METHODS
We systematically searched PubMed (1948-2014), EMBASE (1974-2014), and the Cochrane Library (until 2014) for studies involving humans (≥18 years) treated for a hepatic cyst infection. We extracted data on patient characteristics, treatment and follow-up.
RESULTS
We identified 41 articles; all were case series or case reports, implicating a high risk of bias. We included 54 hepatic cyst infection cases (male 39%; mean age 63 ± 12 years; diabetes 6%; dialysis 19%; transplant recipients 30%). Initial therapy consisted of antimicrobial (56%), percutaneous (31%) or surgical treatment (13%). We identified 42 antimicrobial regimens consisting of 23 different combinations. Most used antibiotic classes were quinolones (34%) and cephalosporins (34%). Antimicrobials failed in 70% of cases, eventually requiring percutaneous or surgical treatment in, respectively, 37% and 27%. Recurrent hepatic cyst infection was frequent (20%). Median time to recurrence was 8 weeks (IQR 3-24 weeks). In 46%, recurrence occurred in renal transplant recipients. Cyst infection related deaths occurred in 9%, of whom 40% were on dialysis.
CONCLUSIONS
The literature shows that treatment of hepatic cyst infection is highly heterogeneous. We recommend first line treatment with oral ciprofloxacin. In case of failure, percutaneous cyst drainage needs to be considered.
Topics: Aged; Anti-Bacterial Agents; Cysts; Female; Humans; Liver Diseases; Male; Middle Aged; Renal Dialysis
PubMed: 25496117
DOI: 10.1111/apt.13047 -
Genetics in Medicine : Official Journal... Sep 2013The aim of this study was to analyze growth rate and identify prognostic factors for progression of postoperative plexiform neurofibromas in patients with...
PURPOSE
The aim of this study was to analyze growth rate and identify prognostic factors for progression of postoperative plexiform neurofibromas in patients with neurofibromatosis type 1.
METHODS
We measured postoperative tumor volume change per year on magnetic resonance imaging. Linear regression models were applied to identify risk factors for tumor progression.
RESULTS
Fifty-two patients (mean age: 25.4 years (3.2-64.2 years)) with 56 plexiform neurofibromas were analyzed. Initial median tumor volume was 40.3 ml (SD: 1,552 (0-10,800)). Surgical indications included disfigurement (n = 21), pain (n = 20), and functional deficits (n = 16). Sixteen percent of all cases experienced acute surgical complication, and 13% showed late complication. Eight patients (19%; 6 children and 2 adults) with residual tumor had repeat surgery for tumor progression. Median tumor progression was 0.6% change per year (SD ± 27.4; range: -59.2 to 88.1) and 2.9% from baseline (SD ± 163.9; range -1,001.3 to 81.8). Patients aged 21 years and younger had the highest progression rate (P < 0.01). For every year of age, the mean growth rate decreased by -0.463 mean percent (P = 0.03). With age as a continuous variable, age, the site of the tumor, and depth were the only factors associated with tumor progression. Fourteen plexiform neurofibromas (10 nodular and 4 diffuse) in 13 patients (5 children and 8 adults) were completely resected (by visualization) and did not relapse during observation (mean: 2.9 years; range: 1.1-5.8 years).
CONCLUSION
Age, tumor type, location, and depth are helpful to estimate the progression of plexiform neurofibromas after surgery. Patients benefit from elective surgery of small and completely removable plexiform neurofibromas.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Child, Preschool; Female; Head and Neck Neoplasms; Humans; Linear Models; Magnetic Resonance Imaging; Male; Middle Aged; Neoplasm Recurrence, Local; Neurofibroma, Plexiform; Neurofibromatosis 1; Retrospective Studies; Young Adult
PubMed: 23598713
DOI: 10.1038/gim.2013.30 -
ELife Mar 2022Neurofibromatosis type 1 (NF1) is characterized by nerve tumors called neurofibromas, in which Schwann cells (SCs) show deregulated RAS signaling. NF1 is also implicated...
Neurofibromatosis type 1 (NF1) is characterized by nerve tumors called neurofibromas, in which Schwann cells (SCs) show deregulated RAS signaling. NF1 is also implicated in regulation of cAMP. We identified the G-protein-coupled receptor (GPCR) P2ry14 in human neurofibromas, neurofibroma-derived SC precursors (SCPs), mature SCs, and mouse SCPs. Mouse SCP self-renewal was reduced by genetic or pharmacological inhibition of P2ry14. In a mouse model of NF1, genetic deletion of P2ry14 rescued low cAMP signaling, increased mouse survival, delayed neurofibroma initiation, and improved SC Remak bundles. P2ry14 signals via G to increase intracellular cAMP, implicating P2ry14 as a key upstream regulator of cAMP. We found that elevation of cAMP by either blocking the degradation of cAMP or by using a P2ry14 inhibitor diminished -/- SCP self-renewal in vitro and neurofibroma SC proliferation in in vivo. These studies identify P2ry14 as a critical regulator of SCP self-renewal, SC proliferation, and neurofibroma initiation.
Topics: Animals; Cell Self Renewal; Cell Transformation, Neoplastic; Cyclic AMP; Disease Models, Animal; Mice; Neurofibroma; Neurofibromatosis 1; Neurofibromin 1; Receptors, Purinergic P2Y; Schwann Cells
PubMed: 35311647
DOI: 10.7554/eLife.73511 -
Cancer Medicine Nov 2019Bevacizumab improves symptoms via reducing the peritumoral edema and/or normalizing blood brain barrier, and occasionally via reducing the tumor size. However, the...
BACKGROUND
Bevacizumab improves symptoms via reducing the peritumoral edema and/or normalizing blood brain barrier, and occasionally via reducing the tumor size. However, the effect against active cystic components has not been documented yet.
MATERIALS AND METHODS
Between 2008 and 2018, 139 patients with primary or metastatic brain tumors were treated with bevacizumab (BEV) in our institution. The images and symptoms before and after administration of BEV were examined, and changes in size of cysts were evaluated as follows: CR (complete disappearance), PR (reduction by ≥50%), MR (reduction by ≥25%), SD (size change <25%), PD (increase by ≥25%). The effect of BEV on tumor itself was determined according to Response Assessment in Neuro-Oncology criteria.
RESULTS
Of the 139 patients, 21 (15.1%) had cystic components. The best responses of cysts to BEV treatment were as follows: CR 6, PR 7, MR 4, SD 4. The group of patients with progressively increasing cysts prior to BEV treatment had significant cyst size reduction compared to stable cyst size groups, at initial imaging after BEV (mean 62.6% vs 22.5%, P = .0055) and at best response timing (mean 76.3% vs 32.8%, P = .0050). Patients with cysts showed significant improvement in symptoms after the treatment with BEV compared to patients without cysts (P = .0033). However, response rate was not different between patients with or without cysts. Overall survival after starting BEV was not different between glioblastoma patients with or without cysts.
CONCLUSION
Bevacizumab is effective against progressively increasing cysts. Although cysts reduction effect and tumor response and/or overall survival are independent, BEV may be effective in patients who are symptomatic due to cyst enlargement.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Agents, Immunological; Bevacizumab; Brain Neoplasms; Child; Child, Preschool; Cysts; Female; Humans; Infant; Male; Middle Aged; Survival Analysis; Tomography, X-Ray Computed; Treatment Outcome; Young Adult
PubMed: 31498567
DOI: 10.1002/cam4.2537 -
Journal of Neurosurgery. Pediatrics May 2022Colloid cysts (CCs) are rare at all ages, and particularly among children. The current literature on pediatric CC is limited, and often included in mixed adult/pediatric...
OBJECTIVE
Colloid cysts (CCs) are rare at all ages, and particularly among children. The current literature on pediatric CC is limited, and often included in mixed adult/pediatric series. The goal of this multinational, multicenter study was to combine forces among centers and investigate the clinical course of pediatric CCs.
METHODS
A multinational, multicenter retrospective study was performed to attain a large sample size, focusing on CC diagnosis in patients younger than 18 years of age. Collected data included clinical presentation, radiological characteristics, treatment, and outcome.
RESULTS
One hundred thirty-four children with CCs were included. Patient age at diagnosis ranged from 2.4 to 18 years (mean 12.8 ± 3.4 years, median 13.2 years, interquartile range 10.3-15.4 years; 22% were < 10 years of age). Twenty-two cases (16%) were diagnosed incidentally, including 48% of those younger than 10 years of age. Most of the other patients had symptoms related to increased intracranial pressure and hydrocephalus. The average follow-up duration for the entire group was 49.5 ± 45.8 months. Fifty-nine patients were initially followed, of whom 28 were eventually operated on at a mean of 19 ± 32 months later due to cyst growth, increasing hydrocephalus, and/or new symptoms. There was a clear correlation between larger cysts and symptomatology, acuteness of symptoms, hydrocephalus, and need for surgery. Older age was also associated with the need for surgery. One hundred three children (77%) underwent cyst resection, 60% using a purely endoscopic approach. There was 1 death related to acute hydrocephalus at presentation. Ten percent of operated patients had some form of complication, and 7.7% of operated cases required a shunt at some point during follow-up. Functional outcome was good; however, the need for immediate surgery was associated with educational limitations. Twenty operated cases (20%) experienced a recurrence of their CC at a mean of 38 ± 46 months after the primary surgery. The CC recurrence rate was 24% following endoscopic resection and 15% following open resections (p = 0.28).
CONCLUSIONS
CCs may present in all pediatric age groups, although most that are symptomatic present after the age of 10 years. Incidentally discovered cysts should be closely followed, as many may grow, leading to hydrocephalus and other new symptoms. Presentation of CC may be acute and may cause life-threatening conditions related to hydrocephalus, necessitating urgent treatment. The outcome of treated children with CCs is favorable.
Topics: Adult; Humans; Child; Child, Preschool; Adolescent; Colloid Cysts; Retrospective Studies; Treatment Outcome; Neurosurgical Procedures; Hydrocephalus
PubMed: 35148518
DOI: 10.3171/2021.12.PEDS21482 -
Glia Nov 2008Neurofibromas are benign tumors of peripheral nerve that occur sporadically or in patients with the autosomal dominant tumor predisposition syndrome neurofibromatosis... (Review)
Review
Neurofibromas are benign tumors of peripheral nerve that occur sporadically or in patients with the autosomal dominant tumor predisposition syndrome neurofibromatosis type 1 (NF1). Multiple neurofibroma subtypes exist which differ in their site of occurrence, their association with NF1, and their tendency to undergo transformation to become malignant peripheral nerve sheath tumors (MPNSTs), the most common malignancy associated with NF1. Most NF1 patients carry a constitutional mutation of the NF1 tumor suppressor gene. Neurofibromas develop in these patients when an unknown cell type in the Schwann cell lineage loses its remaining functional NF1 gene and initiates a complex series of interactions with other cell types; these interactions may be influenced by aberrant expression of growth factors and growth factor receptors and the action of modifier genes. Cells within certain neurofibroma subtypes subsequently accumulate additional mutations affecting the p19(ARF)-MDM2-TP53 and p16INK4A-Rb signaling cascades, mutations of other as yet unidentified genes, and amplification of growth factor receptor genes, resulting in their transformation into MPNSTs. These observations have been validated using a variety of transgenic and knockout mouse models that recapitulate neurofibroma and MPNST pathogenesis. A new generation of mouse models is also providing important new insights into the identity of the cell type in the Schwann cell lineage that gives rise to neurofibromas. Our improving understanding of the mechanisms underlying the pathogenesis of neurofibromas and MPNSTs raises intriguing new questions about the origin and pathogenesis of these neoplasms and establishes models for the development of new therapies targeting these neoplasms.
Topics: Animals; Cell Lineage; Cell Transformation, Neoplastic; Gene Expression Regulation, Neoplastic; Genetic Predisposition to Disease; Humans; Mutation; Neurofibromatosis 1; Peripheral Nervous System; Schwann Cells; Signal Transduction
PubMed: 18803326
DOI: 10.1002/glia.20776 -
European Journal of Medical Genetics May 2023Surgery is a treatment option for neurofibromatosis type 1 (NF1)-related plexiform neurofibromas (PN), but complete resection is often not feasible. Real-world studies...
Surgery is a treatment option for neurofibromatosis type 1 (NF1)-related plexiform neurofibromas (PN), but complete resection is often not feasible. Real-world studies are warranted to understand disease burden, progression, and need for medical treatment in patients with inoperable PN. CASSIOPEA was a retrospective study of French pediatric patients (aged ≥3 to <18 years) presenting at a national multidisciplinary team (MDT) review with NF1 and ≥1 symptomatic, inoperable PN. Medical records were reviewed from the time of MDT review and over a follow-up period of up to 2 years. Primary objectives were to describe patient characteristics and target PN-associated therapy patterns. A secondary objective was evolution of target PN-related morbidities. Patients with prior, ongoing, or MDT recommendation of mitogen-activated protein kinase kinase (MEK) inhibitor treatment were excluded. Overall, 78 target PN were identified in 76 patients. At MDT review, median age was 8.4 years, with approximately 30% of patients aged 3-6 years. Target PN were primarily internal (77.3%), and 43.2% were progressive. Target PN location was evenly distributed. 34 target PN had documented MDT recommendations; of these, a majority (76.5%) were for non-medication management, including surveillance. At least one follow-up visit was recorded for 74 target PN. Despite initially being considered inoperable, 12.3% of patients underwent surgery for target PN. At MDT review, most (98.7%) target PN were associated with ≥1 morbidity, primarily pain (61.5%) and deformity (24.4%); severe morbidities were identified in 10.3%. Of 74 target PN with follow-up data, 89.2% were associated with ≥1 morbidity, primarily pain (60.8%) and deformity (25.7%). Of 45 target PN associated with pain, pain improved in 26.7%, was stable in 44.4%, and deteriorated in 28.9%. Deformity improved in 15.8% and remained stable in 84.2% of 19 target PN associated with deformity. None deteriorated. In this real-world study in France, NF1-PN disease burden was considerable, and a considerable proportion of patients were very young. Most patients received only supportive care without medication for target PN management. Target PN-related morbidities were frequent, heterogeneous, and generally did not improve during follow-up. These data highlight the importance of effective treatments that target PN progression and improve disease burden.
Topics: Child; Humans; Adolescent; Neurofibromatosis 1; Neurofibroma, Plexiform; Retrospective Studies; Treatment Outcome; Mitogen-Activated Protein Kinase Kinases; Pain
PubMed: 36868501
DOI: 10.1016/j.ejmg.2023.104734 -
Genes Apr 2020The Genomics of Malignant Peripheral Nerve Sheath Tumor (GeM) Consortium is an international collaboration focusing on multi-omic analysis of malignant peripheral nerve...
The Genomics of Malignant Peripheral Nerve Sheath Tumor (GeM) Consortium is an international collaboration focusing on multi-omic analysis of malignant peripheral nerve sheath tumors (MPNSTs), the most aggressive tumor associated with neurofibromatosis type 1 (NF1). Here we present a summary of current knowledge gaps, a description of our consortium and the cohort we have assembled, and an overview of our plans for multi-omic analysis of these tumors. We propose that our analysis will lead to a better understanding of the order and timing of genetic events related to MPNST initiation and progression. Our ten institutions have assembled 96 fresh frozen NF1-related (63%) and sporadic MPNST specimens from 86 subjects with corresponding clinical and pathological data. Clinical data have been collected as part of the International MPNST Registry. We will characterize these tumors with bulk whole genome sequencing, RNAseq, and DNA methylation profiling. In addition, we will perform multiregional analysis and temporal sampling, with the same methodologies, on a subset of nine subjects with NF1-related MPNSTs to assess tumor heterogeneity and cancer evolution. Subsequent multi-omic analyses of additional archival specimens will include deep exome sequencing (500×) and high density copy number arrays for both validation of results based on fresh frozen tumors, and to assess further tumor heterogeneity and evolution. Digital pathology images are being collected in a cloud-based platform for consensus review. The result of these efforts will be the largest MPNST multi-omic dataset with correlated clinical and pathological information ever assembled.
Topics: Base Sequence; Computational Biology; DNA Methylation; Exome; Female; Genetic Heterogeneity; Genomics; Humans; Male; Neurofibromatosis 1; Neurofibromin 1; Neurofibrosarcoma; Proteomics; Transcriptome
PubMed: 32252413
DOI: 10.3390/genes11040387 -
Neurology Jul 2018Outside of procedural-based methods, there are currently no established medical treatments for cutaneous neurofibroma (cNF), which afflict up to 99% of patients with...
OBJECTIVE
Outside of procedural-based methods, there are currently no established medical treatments for cutaneous neurofibroma (cNF), which afflict up to 99% of patients with NF1. Further, adult patients often report cNF are the greatest burden of living with NF1. The Neurofibromatosis Therapeutic Acceleration Program (NTAP) launched a think tank to address core questions to facilitate development of effective therapeutics for cNF in people with NF1.
METHODS
Experts (with and without explicit experience with NF1 or cNF) from multiple scientific and medical disciplines, representing the ranks of academia, industry, and government agencies, were invited to become a member of a team addressing a specific subset of questions pertinent to cNF. Teams met monthly to review published and unpublished materials, and created summaries about the material known and unknown that may influence therapeutic development for cNF. Teams prioritized questions and organized supporting data, which was presented to the entire body of experts by each team at a research summit.
RESULTS
Four themes were identified as being relevant to creating a comprehensive research strategy for cNF: (1) establishing definitions of cNF, (2) determining the biology of cNF with respect to tumor initiation, progression, and maintenance, (3) outlining the factors that guide therapies development, and (4) defining core considerations for clinical trials design and optimization for cNF.
CONCLUSION
Considerations and key questions for each of the thematic areas were identified and provided basis for a request for applications launched by NTAP focused on cNF and are described in the accompanying articles of this supplement.
Topics: Clinical Trials as Topic; Dermatology; Humans; Neurofibroma; Neurofibromatosis 1; Neurology; Research Design; Skin Neoplasms
PubMed: 29987129
DOI: 10.1212/WNL.0000000000005789