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Urology Aug 2023Intrascrotal neurofibromas are extensive tumors that grow from peripheral nerves within the scrotum and are exceedingly rare among the benign extratesticular tumors....
Intrascrotal neurofibromas are extensive tumors that grow from peripheral nerves within the scrotum and are exceedingly rare among the benign extratesticular tumors. Though the risk is low, potential for malignancy and patient discomfort make diagnosis and surgical evaluation imperative. Pediatric neurofibromas are typically only associated with neurofibromatosis type 1. However, herein, we describe a rare case of a benign, intrascrotal plexiform neurofibroma in a 10-year-old male who lacks any stigmata associated with this genetic disorder. Diagnostic and surgical challenges as well as histopathological findings are discussed.
Topics: Male; Humans; Child; Neurofibroma, Plexiform; Neurofibroma; Neurofibromatosis 1; Peripheral Nerves; Scrotum
PubMed: 37121356
DOI: 10.1016/j.urology.2023.04.015 -
The American Journal of Case Reports Aug 2023BACKGROUND Neurofibromatosis 1 is a neurocutaneous disorder with multisystemic manifestations. When patients are lacking overt cutaneous manifestations, diagnosis may be...
BACKGROUND Neurofibromatosis 1 is a neurocutaneous disorder with multisystemic manifestations. When patients are lacking overt cutaneous manifestations, diagnosis may be delayed and may complicate diagnosis and management of atypical presentations of this disease. It is thus important to strive to obtain relevant and/or complete history to arrive at the appropriate diagnosis. Furthermore, maintaining an index of suspicion in cases of vague abdominal pain may guide the clinician in establishing the correct diagnosis of mesenteric plexiform neurofibroma in the setting of known/presumed neurofibromatosis 1 patients presenting with acute and/or chronic vague abdominal symptoms. CASE REPORT This is a case of a teenage boy who presented with acute, vague abdominal pain over a period of 2 weeks. Laboratory tests and physical exam findings in primary and secondary care settings were unremarkable, and thus the patient was discharged home only to continue with abdominal pain, thus seeking additional medical care. After admission to our facility and exhaustive history taking, physical examination, and imaging, a prospective diagnosis of neurofibromatosis with mesenteric neurofibroma was made. Upon surgical exploration, a mesenteric mass with corresponding volvulized, ischemic small bowel was removed. Histopathology confirmed a plexiform neurofibroma. The patient recovered adequately and was discharged home without complications. CONCLUSIONS This case highlights the importance of exhaustive history taking to obtain an accurate diagnosis as well as the importance of a high index of clinical suspicion for mesenteric neurofibromatosis in patients with presumed or known neurofibromatosis and presenting with vague abdominal symptoms.
Topics: Male; Adolescent; Humans; Child; Neurofibromatosis 1; Neurofibroma, Plexiform; Intestinal Volvulus; Prospective Studies; Neurofibromatoses; Vascular Diseases; Abdominal Pain
PubMed: 37571808
DOI: 10.12659/AJCR.918041 -
International Journal of Surgery Case... Oct 2023Plexiform neurofibromatosis is a relatively rare manifestation of Type 1 neurofibromatosis (NF-1). This condition leads to gross disfiguration along with functional...
INTRODUCTION
Plexiform neurofibromatosis is a relatively rare manifestation of Type 1 neurofibromatosis (NF-1). This condition leads to gross disfiguration along with functional disability. We are presenting a case of 49 year male with Plexiform neurofibromatosis of lower back. The aim of this rare case report is also to discuss the management difficulties encountered.
PRESENTATION OF CASE
A 49 year male presented to us with gradually increasing swelling over the lower back which was present since his 10 years of age. He had already undergone debulking surgery for the same swelling 10 years back. For the last 2 years the swelling had increased in significant amount. He gave history of similar swellings in his father and grandfather. Proper examination revealed multiple café au lait macules, giant plexiform neurofibroma over lower back and multiple nodular swellings all over the body (neuroma). Biopsy report from previous surgery showed neurofibroma. He underwent debulking surgery. The procedure went for 12 h continuous. Intraoperatively, the mass was highly vascular and excessive bleeding was encountered. About 3 L of blood loss was there and patient received 12 units of blood products.
DISCUSSION
Plexiform neurofibromas are uncommon and may occur in around 30 % patients with NF-1. The genetic defect lies in chromosome 17 that encodes a protein neurofibromin. It causes disfiguration and severe distress to patients. Debulking surgery is one of the treatments to decrease the difficulties occurred from the mass. The aim of this report is to discuss the difficulties occurred in surgical intervention of this rare condition like excessive blood loss.
CONCLUSION
Although timely intervention could limit the disfigurement and morbidity associated with large lesion, due to unpredictable natural course and growth pattern, it is difficult to decide best time to intervene surgically. Registration of such rare case facilitates patient monitoring and development of appropriate treatment protocols.
PubMed: 37716061
DOI: 10.1016/j.ijscr.2023.108812 -
Frontiers in Oncology 2023Neurofibromatosis Type 1 (NF1) is one of the most common genetically inherited disorders that affects 1 in 3000 children annually. Clinical manifestations vary widely...
Single-cell RNA sequencing of neurofibromas reveals a tumor microenvironment favorable for neural regeneration and immune suppression in a neurofibromatosis type 1 porcine model.
Neurofibromatosis Type 1 (NF1) is one of the most common genetically inherited disorders that affects 1 in 3000 children annually. Clinical manifestations vary widely but nearly always include the development of cutaneous, plexiform and diffuse neurofibromas that are managed over many years. Recent single-cell transcriptomics profiling efforts of neurofibromas have begun to reveal cell signaling processes. However, the cell signaling networks in mature, non-cutaneous neurofibromas remain unexplored. Here, we present insights into the cellular composition and signaling within mature neurofibromas, contrasting with normal adjacent tissue, in a porcine model of NF1 using single-cell RNA sequencing (scRNA-seq) analysis and histopathological characterization. These neurofibromas exhibited classic diffuse-type histologic morphology and expected patterns of S100, SOX10, GFAP, and CD34 immunohistochemistry. The porcine mature neurofibromas closely resemble human neurofibromas histologically and contain all known cellular components of their human counterparts. The scRNA-seq confirmed the presence of all expected cell types within these neurofibromas and identified novel populations of fibroblasts and immune cells, which may contribute to the tumor microenvironment by suppressing inflammation, promoting M2 macrophage polarization, increasing fibrosis, and driving the proliferation of Schwann cells. Notably, we identified tumor-associated /CD274 ( dendritic cells, which represent the first such observation in any NF1 animal model and suggest the role of the upregulation of immune checkpoints in mature neurofibromas. Finally, we observed that cell types in the tumor microenvironment are poised to promote immune evasion, extracellular matrix reconstruction, and nerve regeneration.
PubMed: 37817770
DOI: 10.3389/fonc.2023.1253659 -
PloS One 2024Neurofibromatosis Type I (NF1) is a rare genetic disorder. NF1 patients frequently develop a benign tumor in peripheral nerve plexuses called plexiform neurofibroma. In...
Neurofibromatosis Type I (NF1) is a rare genetic disorder. NF1 patients frequently develop a benign tumor in peripheral nerve plexuses called plexiform neurofibroma. In the past two decades, tissue-specific Nf1 knockout mouse models were developed using commercially available tissue-specific Cre recombinase and the Nf1 flox mice to mimic neurofibroma development. However, these models develop para-spinal neurofibroma, recapitulating a rare type of neurofibroma found in NF1 patients. The NPcis mouse model developed a malignant version of neurofibroma called malignant peripheral nerve sheath tumor (MPNST) within 3 to 6 months but intriguingly without apparent benign precursor lesion. Here, we revisited the NPcis model and discovered that about 20% display clinical signs similar to Nf1 tissue-specific knockout mice models. However, a systematic histological analysis could not explain the clinical signs we observed although we noticed lesions reminiscent of a neurofibroma in a peripheral nerve, a cutaneous neurofibroma, and para-spinal neurofibroma on rare occasions in NPcis mice. We also observed that 10% of the mice developed a malignant peripheral nerve sheath tumor (MPNST) spontaneously, coinciding with their earring tag identification. Strikingly, half of the sciatic nerves from NPcis mice developed plexiform neurofibroma within 1-6 months when intentionally injured. Thus, we provided a procedure to turn the widely used NPcis sarcoma model into a model recapitulating plexiform neurofibroma.
Topics: Animals; Neurofibroma, Plexiform; Disease Models, Animal; Mice; Sciatic Nerve; Mice, Knockout; Neurofibromatosis 1; Neurofibromin 1
PubMed: 38900740
DOI: 10.1371/journal.pone.0301040 -
GMS Interdisciplinary Plastic and... 2023Neurofibromatosis type 1 (NF1) is an is an autosomal dominant heritable tumor predisposition syndrome.. Peripheral nerve sheath tumors (PNST) are a hallmark of NF1....
INTRODUCTION
Neurofibromatosis type 1 (NF1) is an is an autosomal dominant heritable tumor predisposition syndrome.. Peripheral nerve sheath tumors (PNST) are a hallmark of NF1. Plexiform neurofibromas (PNF) are neoplasms that are characteristic of NF1, often causing disfiguring effects (e.g., on the face), and are considered precancerous lesions. Previous studies have shown that facial PNF (FPNF) have an impact on the shape of facial bones. This study examines deviations of mandibular symmetry from cephalometric reference planes considering the topography of FPNF.
MATERIAL AND METHODS
The posterior-anterior (PA) cephalograms of 168 patients with NF1 were examined. We compared three groups: patients with FPNF (n=74), with disseminated cutaneous neurofibroma (DNF (n=94)), and control subjects without NF1 (n=23). The PNF group was subtyped with respect to facial PNST type and location. Typical mandibular cephalometric reference points were determined (condyle, antegonion, and menton).
RESULTS
The skeletal measurement points of the mandible in FPNF patients often differ significantly from those of the DNF group. It has been proven that typical asymmetries of the median-sagittal measurement points are indicators of PNF. Differences within the trigeminal tumor spread patterns are indicated in the measured values. A local tumor effect (PNF) on the relation of the measurement points to the reference planes is made plausible by the study results. The investigations prove that tumor type (FPNF) and the number of FPNF affected branches of the trigeminal nerve may correlate with significant deviations of mandible from symmetry on PA projections.
CONCLUSION
The presented study shows that characteristic patterns of mandibular deformity can be measured on standardized radiographs in NF1 patients with FPNF. Mandibular deformities imaged on standardized radiographs may be initial indicators of a previously unrecognized NF1. Tumor-associated alterations of the mandible should be considered in the classification systems of pathognomonic, diagnostically pioneering osseous findings in NF1. The radiological findings provide clues for planning mandibular osteotomies in NF1 patients, especially for assessing facial regions typically highly vascularized by tumor spread. Furthermore, the radiological findings are an indication of a tumor potentially invading and destroying adjacent masticatory and mimic muscle, findings that may have an influence on surgical measures (function, aesthetics, and wound healing).
PubMed: 38111842
DOI: 10.3205/iprs000181 -
International Journal of Surgery Case... Aug 2023This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on...
This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/policies/article-withdrawal.
PubMed: 38092617
DOI: 10.1016/j.ijscr.2023.108617 -
Clinical Trials (London, England) Apr 2024We developed an observer disfigurement severity scale for neurofibroma-related plexiform neurofibromas to assess change in plexiform neurofibroma-related disfigurement...
BACKGROUND/AIMS
We developed an observer disfigurement severity scale for neurofibroma-related plexiform neurofibromas to assess change in plexiform neurofibroma-related disfigurement and evaluated its feasibility, reliability, and validity.
METHODS
Twenty-eight raters, divided into four cohorts based on neurofibromatosis type 1 familiarity and clinical experience, were shown photographs of children in a clinical trial (NCT01362803) at baseline and 1 year on selumetinib treatment for plexiform neurofibromas ( = 20) and of untreated participants with plexiform neurofibromas ( = 4). Raters, blinded to treatment and timepoint, completed the 0-10 disfigurement severity score for plexiform neurofibroma on each image (0 = not at all disfigured, 10 = very disfigured). Raters evaluated the ease of completing the scale, and a subset repeated the procedure to assess intra-rater reliability.
RESULTS
Mean baseline disfigurement severity score for plexiform neurofibroma ratings were similar for the selumetinib group (6.23) and controls (6.38). Mean paired differences between pre- and on-treatment ratings was -1.01 (less disfigurement) in the selumetinib group and 0.09 in the control ( = 0.005). For the disfigurement severity score for plexiform neurofibroma ratings, there was moderate-to-substantial agreement within rater cohorts (weighted kappa range = 0.46-0.66) and agreement between scores of the same raters at repeat sessions ( > 0.05). In the selumetinib group, change in disfigurement severity score for plexiform neurofibroma ratings was moderately correlated with change in plexiform neurofibroma volume with treatment ( = 0.60).
CONCLUSION
This study demonstrates that our observer-rated disfigurement severity score for plexiform neurofibroma was feasible, reliable, and documented improvement in disfigurement in participants with plexiform neurofibroma shrinkage. Prospective studies in larger samples are needed to validate this scale further.
Topics: Child; Humans; Neurofibroma, Plexiform; Neurofibromatosis 1; Prospective Studies; Reproducibility of Results
PubMed: 37877369
DOI: 10.1177/17407745231206402 -
Current Medical Research and Opinion Apr 2024The objectives of this study were to retrospectively investigate the patient characteristics, treatment patterns, healthcare resource utilization (HCRU), and healthcare...
Patient characteristics, treatment patterns, healthcare resource utilization, and costs among patients diagnosed with neurofibromatosis type 1 with and without plexiform neurofibromas in Japan.
OBJECTIVES
The objectives of this study were to retrospectively investigate the patient characteristics, treatment patterns, healthcare resource utilization (HCRU), and healthcare costs related to management of neurofibromatosis type 1 (NF1) in Japan.
METHODS
Cohorts of NF1 patients with or without plexiform neurofibromas (PN) were identified from the Medical Data Vision database in 2008-2019. Baseline characteristics, NF1 medications, HCRU, and associated costs were assessed using descriptive statistics. All-cause HCRU and costs following the first confirmed NF1 diagnosis date were analyzed per patient per year (PPPY) in Japanese Yen (JPY) and United States Dollar (USD).
RESULTS
A total of 4394 NF1 patients without PN and 370 NF1 patients with PN were identified. The mean age was 35.0 and 36.9 years, respectively. The proportion of patients with PN treated with medications was higher than that in patients without PN (except for antirheumatic/immunologic agents). Analgesics/non-steroidal anti-inflammatory drugs were the most frequently prescribed NF1 medications (44.3% and 56.0% in patients without and with PN, respectively), followed by inpatient prescriptions of opioids/opioid-like agents (17.8% and 27.6%, respectively). Inpatient admissions accounted for the highest costs in both cohorts with the average cost PPPY being JPY 2,133,277 (USD 19,861) for patients without PN and JPY 1,052,868 (USD 9802) for patients with PN.
CONCLUSIONS
NF1 is treated primarily with supportive care with analgesics/non-steroidal anti-inflammatory drugs being the most frequently prescribed NF1 medications in Japan. Findings underscored the unmet need and substantial economic burden among patients with NF1 and highlighted the need for new treatment options for patients with this disease.
Topics: Humans; Adult; Neurofibromatosis 1; Neurofibroma, Plexiform; Japan; Retrospective Studies; Health Care Costs; Analgesics; Anti-Inflammatory Agents, Non-Steroidal
PubMed: 38404173
DOI: 10.1080/03007995.2024.2322698 -
Cureus Aug 2023Plexiform neurofibromas are benign tumors that arise from neuronal cells and are commonly associated with neurofibromatosis type 1 (NF1) patients. However, the...
Plexiform neurofibromas are benign tumors that arise from neuronal cells and are commonly associated with neurofibromatosis type 1 (NF1) patients. However, the occurrence of plexiform neurofibromas in the pharyngeal region is extremely rare. In this particular case, we report the successful diagnosis of a retropharyngeal plexiform neurofibroma in an adult male patient without a history of neurofibromatosis. The diagnosis was made using magnetic resonance imaging (MRI) and confirmed by a biopsy. Following the diagnosis, the tumor was surgically excised, resulting in a successful removal of the neurofibroma.
PubMed: 37711936
DOI: 10.7759/cureus.43480