Multiple Neurofibromas Research Articles

Fluorescein-guided resection of plexiform neurofibromas: how I do it

Plexiform neurofibromas (PN) can determine pain, nerve function impairment, and, when extremely large, also deformity. Surgical is often partial, with possible recurrence, and the risk of malignant transformation. We describe the surgical strategy in a case of huge multiple plexiform neurofibromas of the left arm. We attempted to achieve a safe resection under the intraoperative guidance of fluorescein, with a dedicated microscope filter (YELLOW560). This technique can be also applied to other locations. Fluorescein-guided surgery, coupled with intraoperative neurophysiological monitoring, increases the safe resection rate, considering the risks of neurological deficits and the possible malignant transformation.

Robust surgical approach for cutaneous neurofibroma in neurofibromatosis type 1.

Cutaneous neurofibromas (cNF) are physically disfiguring, painful, and cause extensive psychologic harm in patients with neurofibromatosis type 1 (NF1). There is currently no effective medical treatment and surgical procedures are inaccessible to most NF1 patients globally. While research is underway to find an effective medical treatment for cNF, there is an urgent need to develop surgical approach that is accessible to all NF1 patients in the world with the skill set and equipment found in most general medical office settings. Here, we present a robust surgical approach to remove cNF that does not require sterile surgical field, utilizes accessible clinical equipment, and can be performed by any health care providers including family practitioners, and physician assistants. In a prospective case-series, patients with NF1 underwent this surgical procedure which removes multiple cutaneous neurofibromas. The Dermatology Life Quality Index was given to subjects before and after the procedure as surrogate for patient satisfaction. 83 tumors were removed throughout the body from twelve individuals. Examination at follow-up visits revealed well-healed scars without infection or adverse events including aberrant scarring. Patient satisfaction with the procedure was high with significant improvements in symptoms, daily activities, leisure, personal relationships, and treatment experience (P = 0.00062). This study demonstrates a robust surgical approach to management cutaneous neurofibromas which can be accessed world-wide to individuals with NF1 and performed by a wide-variety of medical specialists with high clinical efficacy and patient satisfaction.

Multiple Neurofibromas with Hypertrichosis in a Filipino Patient with Neurofibromatosis 1

This is a case of an 11-year-old male who presented with multiple neurofibromas with hypertrichosis. Classic cutaneous neurofibromas, café-au-lait macules, axillary freckling, Lisch nodules, and scoliosis were also present fulfilling a diagnosis of Neurofibromatosis type 1. This is the first report of multiple neurofibromas with hypertrichosis in the Philippines. Hypertrichosis overlying a neurofibroma is rarely reported and the mechanism remains to be elucidated.

From process to progress-2017 International Conference on Neurofibromatosis 1, Neurofibromatosis 2 and Schwannomatosis.

The neurofibromatoses are inherited, tumor suppressor disorders that are characterized by multiple, benign peripheral nerve sheath tumors and other nervous system tumors. Each disease is associated with a distinct genetic mutation and with a different pathogenesis and clinical course. Neurofibromatosis 1 (NF1) is common and epitomized by multiple neurofibromas with widespread complications. NF2 and schwannomatosis are rare diseases that are typified by multiple schwannomas that are particularly painful in people with schwannomatosis. Since 1985, the Children's Tumor Foundation (formerly the National Neurofibromatosis Foundation) has hosted an international Neurofibromatosis Conference, bringing together international participants who are focused on NF research and clinical care. The 2017 Conference, held in Washington, DC, was among the largest gatherings of NF researchers to date and included presentations from clinicians and basic scientists, highlighting new data regarding the molecular and cellular mechanisms underlying each of these diseases as well as results from clinical studies and clinical trials. This article summarizes the findings presented at the meeting and represents the current state-of-the art for NF research.

Metachronous bilateral triple-negative breast cancer associated with neurofibromatosis type 1: A case report.

The present study reports a case of metachronous bilateral breast cancer associated with neurofibromatosis type 1 (NF1). A 67-year-old female, who had undergone a radical mastectomy of the left breast 34 years ago due to breast cancer, presented with a tumor of the right breast. The clinical stage of the original breast cancer was T2N0M0 stage IIA and adjuvant chemotherapy had not been not administered. With regard to the right-sided breast tumor, on physical examination, multiple neurofibromas and café-au-lait spots were found to be scattered over the skin. A 2-cm tumor was palpable. The preoperative histopathological diagnosis of the right-sided breast tumor was invasive ductal carcinoma, T2N0M0 stage IIA, with negative results for hormone receptors and human epidermal growth factor receptor 2. The patient underwent a modified radical mastectomy and axillary node dissection, and received adjuvant chemotherapy. The bilateral tumors were similar in histology and immunophenotype, each being histological grade 3, triple-negative and with a basal-like subtype. Based on a literature review of 90 breast cancers in 84 patients with NF1 (84 patients, 90 breasts), younger age onset, advanced clinical stage and hormone receptor negativity were characteristic features. Bilateral cancer occurred in 8.3% of patients and was characterized by ER negativity, earlier stage and younger age compared with patients with unilateral cancer.

Utility of MRI neurography in neurofibromatosis type I: Case example and review of MRI neurography literature

Background:Neurofibromatosis is an autosomal dominant disorder of the nerves, resulting in café-au-lait spots, axillary freckling, macules, and neurofibromas throughout the nervous system. Diagnosis of this condition has in the past been mainly clinical, but the usage of magnetic resonance imaging neurography (MRN) is a new diagnostic modality. Here, we report on a case of neurofibromatosis type I (NF-1) that was diagnosed using MRN after a protracted clinical course.Case Description:A 23-year-old female presented with several months of worsening right upper and lower quadrant abdominal pain. The patient underwent computed tomography (CT) of the abdomen and pelvis demonstrating multiple neurofibromas involving the psoas muscle and mesentery of the lower abdomen. Subsequent total neuronal axis magnetic resonance imaging (MRI) using the neurography protocol (MRN) showed multiple neurofibromas in both the right brachial plexus and lumbar plexus.Conclusion:We present a case of NF-1 that was diagnosed using MRN following a protracted clinical course. MRN is a diagnostic modality for NF-1 and other peripheral nerve disorders.

Lumbar plexiform neurofibroma, short stature, and kyphoscoliosis in neurofibromatosis-1: A Rare entity

The incidence of neurofibromatosis (NF), comprising NF-1 and NF-2, seems to be rising in Nigeria. The features of NF-1 have not been completely identified in the country. This case report documents a rare massive lumbar plexiform neurofibroma in NF-1, associated with short stature and kyphoscoliosis. The patient was a 38-year-old man who presented on account of a lumbar swelling for 2 months. He has multiple café-au-lait hyperpigmented lesions, multiple neurofibromas, a massive plexiform neurofibroma in the left lumbar area, a short stature, and kyphoscoliosis. His nephew has a similar skin lesion but has no plexiform neurofibroma. Computed tomography scan showed a massive neurofibroma in the lumbar region without evidence of malignant transformation. Concomitant occurrence of a massive plexiform neurofibroma, short stature, and skeletal abnormalities in NF-1, though rare, was presented. The patient had a massive lumbar plexiform neurofibroma, short stature, and kyphoscoliosis in NF-1.

Pneumonia Recurrence Was Possibly Prevented by Oral Care in a Patient with Multiple Primary Tracheal Neurofibromas Treated with Endotracheal Stenting

Pneumonia Recurrence Was Possibly Prevented by Oral Care in a Patient with Multiple Primary Tracheal Neurofibromas Treated with Endotracheal Stenting

A treatable hypertrophic neuropathy

A 42-year-old woman was referred to our institution with 5 years of progressive proximal and distal weakness, distal paresthesia in lower and upper limbs, severe shocking pain radiating from the...

Primary Meningeal Rhabdomyosarcoma of the Spinal Cord of a Young Dog with Neuromelanocytosis and Multiple Cutaneous Neurofibromas

A 7-week-old male black Labrador retriever puppy was presented for post-mortem examination following progressive hindlimb paralysis and multiple masses within the skin. A highly compressive and infiltrative intradural mass was found within the T9-T11 spinal cord. Microscopical and immunohistochemical analysis revealed features compatible with spindle cell rhabdomyosarcoma (RMS). The adjacent spinal cord had numerous melanin-containing cells, arranged in small nodules, predominantly within the grey matter (proposed term of 'micronodular neuromelanocytosis') and the left lateral thorax had multifocal dermal neurofibromas. In this case, the constellation of proliferative/neoplastic lesions represents a unique case presentation with unclear aetiology. Primary canine meningeal RMS of the spinal cord has not been reported previously and represents a novel differential diagnosis for spinal tumours of young dogs. Moreover, such cases should be assessed for the presence of additional congenital abnormalities.

Oral Manifestation of Neurofibromatosis Type I: a Case Report

Neurofibromatosis is a hereditary condition with at least 8 identified forms; neurofibromatosis type I is the most common. The type I form is characterized by multiple café-au-lait spots and cutaneous neurofibromas, freckles in the axillary and inguinal regions, a brownish spot on the iris, skeletal dysplasias, benign and malignant nervous system tumor growth, and usually a first-degree relative with the same condition. A 35-year-old woman presented with café-au-lait spots and multiple cutaneous neurofibromas, with the oral manifestation as nodules in the palate, alveolar ridge, buccal mucosa, and tongue. A panoramic radiography analysis did not show any change. The histological evaluation of an incisional biopsy of the palate lesion was compatible with the neurofibromatosis diagnosis. Due to difficulty in swallowing caused by the palate lesion, it was surgically removed and a histological evaluation confirmed the diagnosis. The patient continues to be under follow-up with the oral medicine team.

Advanced Hepatocellular Carcinoma in a Patient with Type 1 Neurofibromatosis

The rare case is reported of advanced hepatocellular carcinoma (HCC) in a 50-year-old male with type 1 neurofibromatosis (NF 1). The patient presented in the surgical outpatient department with a 4-year history of multiple neurofibromas over the trunk and complaints of pain in the right upper abdomen for 4 months, progressive weight loss and loss of appetite. Investigation for both the abdominal complaints and the multiple neurofibromas led to the diagnosis of advanced HCC (according to the Barcelona Clinic Liver Cancer Sstaging and Treatment Strategy) with NF 1, and the patient is being managed on oral Sorafenib as palliative treatment. NF 1 occurs due to mutation in the NF 1 gene located on 17q, which codes for the protein neurofibromin, which has a tumor suppressor function. NF1 presents rarely with malignancy, in which case tumors of the central nervous system are the most common type. To the best of our knowledge this is only the second documented case of NF 1 presenting with HCC.

Three Novel NF1 Gene Mutations in a Cohort of Bulgarian Neurofibromatoses Patients

Neurofibromatosis (NF) is a clinically heterogeneous autosomal dominant disorder. Three distinct forms have been identified: neurofibromatosis type 1 (NF1), type 2 (NF2) and schwannomatosis. In the present study, we report clinical and genetic findings in the NF1 and NF2 genes in a cohort of 27 Bulgarian patients, with 18 cases (67%) genetically verified. Both NF1 and NF2 genes were screened by Sanger sequencing on DNA samples. The Sanger negative samples were screened by Multiplex Ligation-dependent Probe Amplification (MLPA) for deletions and duplications. The results from genetic testing revealed three novel mutations and fifteen previously reported ones (13 in the NF1 gene and 2 in the NF2 gene). The novel variants in the NF1 gene are a splice site mutation c.4725-1G>A, a small deletion of five bases c.823delATCTT, p.Leu275ValfsTer14, and a single base duplication c.6547dupC, p.Arg2183ProfsTer11. The novel splice site mutation is manifested by multiple “cafe au lait” macules and neurofibromas. Both novel out of frame mutations were found in patients with multiple “cafe au lait” spots and focal epilepsy. A segmental neurofibromatosis (SNF1) is restricted to one or more body segments. Here we present a case with SNF1 caused by a somatic deletion of exons 1 to 12 of the NF1 gene which is manifested by multiple neurofibromas in the right hand. Two nonsense mutations are found in the NF2 gene. Our study adds three novel mutations to the NF1 mutation spectra and contributes to the clinical-genetic NF1-characterization. Here we report strikingly different phenotypic spectra caused by the same mutation in a single family. Our findings contribute to the genotype- phenotype correlations which are difficult to establish, due to the extremely complex NF phenotype being a combination of clinical features.

Neurofibroma in the head-and-neck region: Our experience

Neurofibroma in the head-and-neck region is a rare entity. It can occur either as a solitary, slowly progressive tumor or as part of neurofibromatosis. We here report three cases of neurofibroma in the head-and-neck region. Case 1 is a 20-year-old female with a solitary neurofibroma in trachea. Case 2 is a 35-year-old male with neurofibromatosis type 1 and spontaneous hemorrhage in the neurofibroma of the facial region. Case 3 is a 25-year-old female with a solitary neurofibroma in the left posterior triangle of the neck. Multiple neurofibroma in the head-and-neck region may occur in the skin as part of neurofibromatosis and as solitary lesions in intratracheal to posterior triangle region of the neck.

0078 - The Treatment of Rotatory Dislocation of the Spine in a Patient With Dystrophic Kyphoscoliosis Secondary to Neurofibromatosis Type I

ABSTRACT: We present a patient with neurofibromatosis type 1 followed in our clinic since the age of 8.9 years who developed a right upper thoracic kyphoscoliosis. The scoliosis was 14o and the kyphosis 40o at initial presentation. The patient was asymptomatic with normal neurological examination. His MRI showed paraspinal neurofibromas in the upper thoracic region. He remained under close monitoring and at age 16.9 years his kyphosis was 47° and scoliosis 21°. He was skeletally mature (Risser 5) and in the absence of symptoms he decided against our recommendation for a posterior instrumented spinal fusion. The patient then failed to attend for 2 years and returned at age 19 years with a progressive deformity (scoliosis: 65° - kyphosis: 62°) and segmental rotatory dislocation at the T2-T3 level. He remained neurologically intact and a repeat MRI demonstrated dural ectasia across the cervical/thoracic spine with multiple paraspinal neurofibromas.

THSD7A-associated membranous nephropathy in a patient with neurofibromatosis type 1

Target antigens in idiopathic membranous nephropathy (MN) include the phospholipase A2 receptor (PLA2R), and in some cases, the thrombospondin type 1 domain-containing 7A (THSD7A). A notable phenomenon is the high rate of cancer (reported to be as high as 20%) in patients with THSD7A-associated MN. Neurofibromatosis type 1 (NF1) is an autosomal dominant disease caused by NF1 gene mutation, and clinically characterized by multiple cutaneous neurofibromas and café-au-lait spots. In this article, we report a patient with NF1 who developed THSD7A-associated MN when the NF1 skin lesions deteriorated. The patient, a 62-year-old male, was referred to us for nephrotic syndrome for 6 months. Physical examination revealed multiple cutaneous nodules throughout the entire body, and the patient noted recent increase in the numbers of these skin lesions. Cutaneous nodules excisional biopsy suggested NF1 and Sanger sequencing using genomic DNA extracted from peripheral blood revealed a previously reported heterozygous frameshift NF1 mutation (c.1541_1542delAG, p. Gln514fs). Renal biopsy revealed MN and immunohistochemistry (IHC) showed enhanced staining of THSD7A as well as PLA2R along the glomerular basement membrane whereas the serum level of THSD7A and PLA2R were both within normal range. The neurofibroma tissues were positive for THSD7A but not for PLA2R on IHC. The patient did not respond to 6-month treatment with glucocorticosteroid and cyclophosphamide. In this exceptional case, strong positive staining of THSD7A in both skin and renal biopsy samples, together with the temporal association between nephrotic syndrome and skin lesions and lack of treatment response, suggested the possibility that MN could be the result of immune response to THSD7A in NF1. This report may improve understanding of the mechanistic link between MN and cancer.

Rectal carcinoma and multiple gastrointestinal stromal tumors (GIST) of the small intestine in a patient with neurofibromatosis type 1: a case report

BackgroundNeurofibromatosis type 1 (NF1) is an autosomally dominant inherited disorder characterized by multiple pigmented skin spots (café-au-lait spots) and neurofibroma. NF1 is associated with a wide variety of benign or malignant tumors. We report a NF1 patient who received surgical treatment for rectal carcinoma and multifocal small intestinal gastrointestinal stromal tumors (GISTs).Case presentationA 70-year-old female patient with NF1 was referred to our hospital after a positive fecal occult blood test. Locally advanced rectal carcinoma was detected in the upper rectum using colonoscopy. A submucosal tumor 20 mm in diameter was detected in the duodenal bulb during the upper gastrointestinal endoscopy. The biopsy specimen from the duodenum was GIST with positive immunostaining of KIT and CD34 microscopically. Laparoscopic low anterior resection for rectal carcinoma and local excision of the duodenal GIST were performed successfully. During the operation, five white small nodules were found on the serosa of the jejunum. One nodule was excised for histological examination. The resected rectal tumor was a well-differentiated adenocarcinoma with multiple lymph nodes metastases according to the histology. The duodenal tumor was found to be low-risk GIST. Moreover, the nodule from the jejunum was very low risk GIST. An excised skin wart was neurofibroma according to the histology.ConclusionsGIST or carcinomas have been reported to occasionally occur in the digestive tract of the patients with NF1. We present a rare case of a NF1 patient with GISTs and colorectal carcinoma.

Histopathologic evaluation of atypical neurofibromatous tumors and their transformation into malignant peripheral nerve sheath tumor in patients with neurofibromatosis 1—a consensus overview

Patients with neurofibromatosis 1 (NF1) develop multiple neurofibromas, with 8% to 15% of patients experiencing malignant peripheral nerve sheath tumor (MPNST) during their lifetime. Prediction of transformation, typically from plexiform neurofibroma, is clinically and histologically challenging. In this overview, after a consensus meeting in October 2016, we outline the histopathologic features and molecular mechanisms involved in the malignant transformation of neurofibromas. Nuclear atypia alone is generally insignificant. However, with atypia, loss of neurofibroma architecture, high cellularity, and/or mitotic activity >1/50 but <3/10 high-power fields, the findings are worrisome for malignancy. We propose the term "atypical neurofibromatous neoplasms of uncertain biologic potential (ANNUBP)" for lesions displaying at least 2 of these features. This diagnosis should prompt additional sampling, clinical correlation, and possibly, expert pathology consultation. Currently, such tumors are diagnosed inconsistently as atypical neurofibroma or low-grade MPNST. Most MPNSTs arising from neurofibromas are high-grade sarcomas and pose little diagnostic difficulty, although rare nonnecrotic tumors with 3-9 mitoses/10 high-power fields can be recognized as low-grade variants. Although neurofibromas contain numerous S100 protein/SOX10-positive Schwann cells and CD34-positive fibroblasts, both components are reduced or absent in MPNST. Loss of p16/CDKN2A expression, elevated Ki67 labeling, and extensive nuclear p53 positivity are also features of MPNST that can to some degree already occur in atypical neurofibromatous neoplasms of uncertain biologic potential. Complete loss of trimethylated histone 3 lysine 27 expression is potentially more reliable, being immunohistochemically detectable in about half of MPNSTs. Correlated clinicopathological, radiologic, and genetic studies should increase our understanding of malignant transformation in neurofibromas, hopefully improving diagnosis and treatment soon.

Nerve ultrasound: A useful screening tool for peripheral nerve sheath tumors in NF1?

To determine ultrasonographic peripheral nerve involvement in patients with asymptomatic neurofibromatosis type 1 (NF1). Thirteen asymptomatic and 4 minimally symptomatic patients with NF1 were included in this cross-sectional pilot study to detect asymptomatic abnormalities of the brachial plexus and upper and lower extremity nerves. Patients underwent clinical examination, nerve conduction studies (NCS), and high-resolution ultrasonography (HRUS). HRUS showed abnormalities in 16 patients (94.1%). Neurofibromas were identified in 10 patients (58.8%): localized neurofibromas were found in 3 patients (17.6%), plexiform neurofibromas in 3 (17.6%), and both in 4 (23.5%). In 6 patients (35.3%), only nerve enlargement without an abnormal fascicular pattern was observed. Severe involvement of the peripheral nervous system with multiple plexiform neurofibromas was observed in 7 patients (41.2%), while 4 patients (23.5%) had no or only minor involvement. Both NCS and HRUS were performed on 73 individual nerve segments. In 5.5%, abnormalities were found with both tests; in 50.7%, only with HRUS; and in 1.4%, only with NCS. HRUS frequently showed subclinical involvement of the peripheral nerves in NF1, also when NCS were normal. HRUS findings ranged from normal to widespread peripheral nerve involvement. Because the presence of plexiform neurofibromas and the benign tumor load are risk factors for the development of a malignant peripheral nerve sheath tumor, HRUS may be a useful tool to identify a subgroup of patients who could benefit from regular follow-up.

Multiple Plexiform Neurofibroma of the Hand Misdiagnosed as Ganglion Cyst.

Multiple Plexiform Neurofibroma of the Hand Misdiagnosed as Ganglion Cyst.