Association of plexiform and diffuse neurofibromas with malignant peripheral nerve sheath tumor in NF I patients: a whole-body MRI assessment.

OBJECTIVE: The aim of this study is to evaluate neurofibromatosis type 1 (NF1) patients with whole-body MRI (WBMRI) to investigate the frequency of plexiform neurofibromas (pNFs), diffuse neurofibromas (dNFs), and malignant peripheral nerve sheath tumors (MPNSTs). MATERIALS AND METHODS: In this retrospective cross-sectional study, between the years 2015 and 2023, 83 consecutive patients with known NF1 underwent a total of 110 WBMRI screenings for MPNST using a standardized institutional protocol. The lesions are categorized as discrete lesions, pNFs, dNFs, and MPNSTs. Histopathology served as the reference standard for all MPNSTs. RESULTS: Among the 83 patients analyzed, 53 (64%) were women and 30 were men (36%) of ages 36.94±14.43 years (range, 15-66 years). Of the 83 patients, 33 have a positive family history of NF1 and positive genetic studies. Seven of 83 (8%) have only dNF, 20/83 (24%) have pNF, 28/83 (34%) have both dNF and pNF, and 28/83 (34%) have neither. Of the 83 patients, eight (9.6%) were diagnosed with nine total MPNSTs. Age range for patients with MPNSTs at time of diagnosis was 22-51, with an average age of 33.4 years. Only one MPNST (11%) developed from underlying pNF 4 years after WBMRI along the right bronchial tree. Three of eight (37.5%) patients with MPNST died within 5 years of pathologic diagnosis. CONCLUSION: This study suggests the absence of a predisposition for development of MPNST from pNFs and dNFs in the setting of NF1. As such, these lesions may not need special surveillance compared to discrete peripheral nerve sheath tumors.

Malignant peripheral nerve sheath tumours in a patient with Neurofibromatosis-1.

Malignant peripheral nerve sheath tumour (MPNST) is an uncommon type of soft tissue tumour which most commonly arises in the setting of Neurofibromatosis-1 (NF-1) or in the presence of another nerve sheath tumour. NF-1 is an autosomal dominant syndrome which is diagnosed based on clinical criteria. People suffering from NF-1 are at a higher risk of developing tumours, especially MPNST. MPNST can occur anywhere along the distribution of nerve roots but most commonly involves the limbs and trunk. The prognosis of MPNST in the setting of NF-1 is grave as the distant metastasis develops earlier than non-syndromic cases. Pre-operative diagnosis is difficult as there is no gold standard radiologic technique or characteristic radiological features. The diagnosis is established after histological evaluation supplemented by immunohistochemistry of the tumour tissue. We present a case of a 38-year-old female, a known case of NF-1, who presented with a single, irregular, cystic swelling in the left flank which was increasing in size. The patient underwent complete surgical excision of a 6cm tumour which was diagnosed as MPNST after histopathological examination. The rare nature of this tumour makes the diagnosis and treatment extremely hard. Awareness regarding this disease should be increased so that proper treatment plans can be made.

Malignant peripheral nerve sheath tumor of the orbit: a case report and review of the literature.

Malignant peripheral nerve sheath tumor is a rare tumor which infrequently involves the orbit. They occur most often in the setting of neurofibromatosis 1 (NF1), and therefore the involvement of the orbit without a history of NF1 is even less common. Management of this tumor is fraught with a high rate of recurrences and metastases, with a high mortality rate. Primary surgical excision with tumor-free margins remains the primary treatment, while adjuvant modalities such as radiation and chemotherapy play a more minor role.

Circulating tumor DNA for malignant peripheral nerve sheath tumors in neurofibromatosis type 1.

PURPOSE: The leading cause of early death in patients with neurofibromatosis type 1 (NF1) is malignant peripheral nerve sheath tumor (MPNST). The principles of management include early diagnosis, surgical clearance and close monitoring for tumor recurrence. Current methods for diagnosis, detection of residual disease and monitoring tumor burden are inadequate, as clinical and radiological features are non-specific for malignancy in patients with multiple tumors and lack the sensitivity to identify early evidence of malignant transformation or tumor recurrence. Circulating tumor DNA (ctDNA) is a promising tool in cancer management and has the potential to improve the care of patients with NF1. In the following article we summarise the current understanding of the genomic landscape of MPNST, report on the previous literature of ctDNA in MPNST and outline the potential clinical applications for ctDNA in NF1 associated MPNST. Finally, we describe our prospective cohort study protocol investigating the utility of using ctDNA as an early diagnostic tool for MPNSTs in NF1 patients.

Functional imaging of RAS pathway targeting in malignant peripheral nerve sheath tumor cells and xenografts.

BACKGROUND: Malignant peripheral nerve sheath tumor (MPNST) is an aggressive form of soft-tissue sarcoma (STS) in children. Despite intensive therapy, relatively few children with metastatic and unresectable disease survive beyond three years. RAS pathway activation is common in MPNST, suggesting MEK pathway inhibition as a targeted therapy, but the impact on clinical outcome has been small to date. PROCEDURE: We conducted preclinical pharmacokinetic (PK) and pharmacodynamic studies of two MEK inhibitors, trametinib and selumetinib, in two MPNST models and analyzed tumors for intratumor drug levels. We then investigated 3'-deoxy-3'-[18 F]fluorothymidine (18 F-FLT) PET imaging followed by 18 F-FDG PET/CT imaging of MPNST xenografts coupled to short-term or longer-term treatment with selumetinib focusing on PET-based imaging as a biomarker of MEK inhibition. RESULTS: Trametinib decreased pERK expression in MPNST xenografts but did not prolong survival or decrease Ki67 expression. In contrast, selumetinib prolonged survival of animals bearing MPNST xenografts, and this correlated with decreased pERK and Ki67 staining. PK studies revealed a significantly higher fraction of unbound selumetinib within a responsive MPNST xenograft model. Thymidine uptake, assessed by 18 F-FLT PET/CT, positively correlated with Ki67 expression in different xenograft models and in response to selumetinib. CONCLUSION: The ability of MEK inhibitors to control MPNST growth cannot simply be predicted by serum drug levels or drug-induced changes in pERK expression. Tumor cell proliferation assessed by 18 F-FLT PET imaging might be useful as an early response marker to targeted therapies, including MEK inhibition, where a primary effect is cell-cycle arrest.

Triton tumor of the orbit.

A triton tumor is a malignant peripheral nerve sheath tumor (MPNST) with rhabdomyomatous differentiation These tumors account for 5% of MPNSTs and have an extremely poor prognosis. We describe the case of a 14-year-old girl who presented with a history of painful, progressive protrusion of her right eye with a diminution of vision for the past five years. She had been diagnosed as having an embryonal rhabdomyosarcoma of the right orbit, and she had undergone surgical debulking followed by chemotherapy and radiotherapy. Despite undergoing multiple modalities of treatment, she had several recurrences prior to this consultation. We reviewed her histology slides. HPE features were consistent with a malignant triton tumor with cartilage and osseous differentiation. Immunohistochemistry was done to confirm the diagnosis. In view of the aggressive nature of the tumor with multiple recurrences; she was advised palliative radical excision to reduce the tumor burden.

Primary malignant schwannoma of the heart.

Primary malignant schwannoma of the heart is an extremely rare disease. We, herein, report a 42-year-old female who underwent successful surgical excision of such a tumor.

Malignant peripheral nerve sheath tumour with perineurial differentiation and hyaline eosinophilic globules (thanatosomes): A rare tumour.

Malignant peripheral nerve sheath tumour (MPNST) with perineurial differentiation is a rare variant of MPNST. The pathological features and clinical significance of this variant remain to be characterised. We reported the clinicoradiological and pathological features of a case of recurrent right arm mass related to the ulnar nerve in a 42-year-old female patient. On pathological examination, the tumour showed dual features of conventional and perineurial MPNST which was proven by positive immunostaining for S-100 and EMA. The pathological diagnosis was MPNST with perineurial differentiation. In addition, a peculiar and rare finding of intracytoplasmic eosinophilic hyaline globules (thanatosomes) within tumour cells is reported. We document a rare tumour with hybrid features between conventional and perineurial MPNSTs. Further studies are needed to establish its biological behaviour.

Right Ventricular Involvement of an Aggressive Malignant Peripheral Nerve Sheath Tumor.

We present a case of a 58-year-old woman who had a painful right thigh mass for a few months. A transthoracic echocardiogram revealed no evidence of an intracardiac mass. She had a whole-body positron emission tomography/computed tomography scan two months later that revealed masses in her right lower extremity and a mass in her right ventricle that had not been initially reported. She had been initially diagnosed with an undifferentiated pleomorphic sarcoma, but this diagnosis was changed to a malignant peripheral nerve sheath tumor with repeat pathology. She was subsequently hospitalized. An echocardiogram showed a mass covering 80% of her right ventricle (RV). Serial cardiac magnetic resonance imaging revealed a 9.4 × 5.6 cm RV mass with vascular and avascular portions and inflow and outflow tract obstruction. Computed tomography showed no other metastases. Due to a delay in diagnosis and a decline in left ventricular ejection fraction, the patient could not undergo palliative chemotherapy or radiotherapy.

Metastatic malignant peripheral nerve sheath tumour in a patient with neurofibromatosis 1 and review of contemporary systemic treatments.

Malignant peripheral nerve sheath tumours are rare soft tissue sarcomas commonly seen in patients with neurofibromatosis type 1. They typically manifest in the fibrous sheaths of major nerve trunks in the extremities or in an axial location. Presenting symptoms are generally non-specific, including pain and weakness, and survival is dependent on size and location of the tumour. Surgical resection is the primary treatment modality followed by radiotherapy or chemotherapy; however, prognosis is poor. Medications such as tyrosine kinase inhibitors and mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway inhibitors are increasingly being recognised as potentially effective therapy for these malignancies. We report a case of a patient with neurofibromatosis type 1 presenting with a malignant peripheral nerve sheath tumour along the tibial nerve that was initially diagnosed as a muscle strain. We discuss the utility of diagnostic imaging and pathology in correctly identifying this aggressive tumour as well as review the drugs used in her care.

Lumbar malignant peripheral nerve sheath tumor: a rare case in a young patient.

Malignant peripheral nerve sheath tumor (MPNST) is a rare soft tissue sarcoma that originate from peripheral nerves or from cells associated with the nerve sheath. We report the case of a 30­year­old male patient with a history of neurofibromatosis type I (NF-1) and a MPNST located in the lumbar region. The mass was resecated but surgical margins weren't clear. Recurrence of disease was observed after few months. A close monitoring of subjects with NF-1 is crucial to diagnose MPNST at an earlier stage and allow a complete surgical resection.

Malignant Peripheral Nerve Sheath Tumors Without Muscle Weakness at Presentation: An Analysis of an Underappreciated Combination.

OBJECTIVE: Patients with malignant peripheral nerve sheath tumors (MPNSTs) of major motor nerves typically present with muscle weakness and pain. We aimed to analyze and characterize patients with MPNSTs of major motor nerves but without muscle weakness at initial presentation. METHODS: We performed a retrospective search of MPNSTs in a major nerve evaluated and/or treated at our institution from 1994 to 2019. Patients with no muscle weakness and available magnetic resonance imaging were analyzed. Clinical materials and magnetic resonance imaging and positron emission tomography scans were reviewed for features of malignancy. This group of patients was compared with patients who presented with MPNSTs and muscle weakness. RESULTS: Of 26 patients with MPNSTs who presented with no muscle weakness, 21 (81%) had a positive family history for malignancy. Only 16 (62%) magnetic resonance imaging scans were highly suspicious for malignancy. All 7 available positron emission tomography scans were highly suspicious for malignancy. Patients who presented with muscle weakness (n = 36) were more likely to have paresthesias and a history of neurofibromatosis 1 or radiation to the MPNST location (P < 0.05). CONCLUSIONS: MPNSTs of major motor nerves without muscle weakness represent an underappreciated subset of cases that have potential treatment and outcome implications. These patients presented with fewer symptoms and had fewer risk factors than patients with muscle weakness. Positron emission tomography should be considered as an additional method to try to anticipate the diagnosis of an MPNST.

Primary intraosseous malignant peripheral nerve sheath tumor of the mandible: An unusual presentation mimicking a benign lesion.

The malignant peripheral nerve sheath tumor (MPNST) is a rare, aggressive malignant tumor that usually develops in the context of neurofibromatosis type 1. In the oral cavity, these tumors are excelling rare, especially in intraosseous sites. Herein, we report an unusual presentation of intraosseous MPNST affecting the mandible posterior region in a 28-year-old male without neurofibromatosis type 1 discovered as an incidental find on imaging exam. CT scan evaluation showed a solitary, well-defined, round hypodense lesion in the posterior mandibular region extending from tooth 45 to 46. Microscopic evaluation showed a tumor composed of atypical spindle-shaped cells arranged in fascicles and a storiform pattern. Tumor cells were positive for S-100 protein. Epithelial membrane antigen (EMA), pan-cytokeratin AE1/AE3, desmin, alpha-smooth muscle actin (α-SMA), HMB-45, MART-1, MUC4, and CD56 were negative. The diagnosis was low-grade MPNST. The patient underwent wide surgical resection of the tumor. After three years of follow-up, the patient remained with no evidence of recurrence or metastatic disease. When an intraosseous neurogenic tumor is suspected based on radiological characteristics, despite the apparent benign nature, an incisional biopsy is mandatory to rule out malignancy before treatment planning to avoid inadequate conservative treatment.

Role of 18F-FDG PET/computed tomography in prognostication and management of malignant peripheral nerve sheath tumors.

AIM: Malignant peripheral nerve sheath tumors (MPNSTs) are rare tumors arising from a peripheral nerve or in extraneural soft tissue which shows high metastatic potential and poor prognosis. They can arise de-novo or through malignant transformation in neurofibromatosis (NF-1). The purpose of our study is to evaluate potential role of fluorodeoxyglucose (FDG) PET/computed tomography (CT) in prognostication and management of MPNSTs. MATERIALS AND METHODS: We have performed a retrospective analysis in patients of MPNSTs who underwent F-FDG PET/CT imaging for staging and restaging. Standardized uptake values (SUVmax and SUVmean) and texture parameters (calculated using radiomics package version 0.1.3) were measured for primary/recurrent lesions and were compared between two groups based on presence of event (recurrence/progression). Student t-test was applied for comparative analyses using the SPSS software package (version 23.0; IBM), with a significance level of 0.05. RESULTS: Thirty patients (17 male, 13 female; mean age 42.7 ± 15.66 years) were included, who underwent F-FDG PET/CT for staging (n = 10) and restaging (n = 20). Change in management was observed in four patients at baseline and in three patients in follow-up imaging for response assessment, who had progressive disease which prompted treatment intensification. SUVmax of primary/recurrent lesion showed correlation with histopathologic grade (r = 0.712, P = 0.034). Textural analysis showed more heterogeneity in lesions in the high-risk group with recurrence and progression. CONCLUSION: F-FDG PET/CT can be used for staging and restaging in MPNSTs leading to change in management. Texture analysis and quantitative F-FDG PET/CT parameters can help in prognostication at both baseline and relapse.

Giant Malignant Peripheral Nerve Sheath Tumor of the Scalp: Case Report and Review of the Literature.

BACKGROUND: Malignant peripheral nerve sheath tumors (MPNSTs) are rare nervous system tumors that rarely appear on the scalp. About half of the scalp MPNSTs described in the literature have reached giant dimensions at the time of diagnosis. The surgical treatment is the gold standard for this type of tumor. Some authors suggest adjuvant radiotherapy for local tumor control, although there is uncertainty about its advantages and its use is not without risks. CASE DESCRIPTION: We present the case of a 31-year-old man who presented with a large necrotic scalp tumor of the left frontoparietal convexity. magnetic resonance imaging showed a large extra-axial tumor, measuring 17 x 17 x 8 cm, centered on the soft tissues, with skull erosion and signs of dural invasion, although with no intradural component. The tumor was surgically removed and the osteocutaneous defect was reconstructed with a latissimus dorsi muscle free flap. The anatomopathologic diagnosis was MPNST. The patient then underwent adjuvant radiotherapy. After 7 months he developed a progressive right hemiparesis and magnetic resonance imaging showed results compatible with cerebral radiation necrosis. This motor deficit improved with corticotherapy. After 9 months the patient went back to his home country and was subsequently lost to follow-up. CONCLUSIONS: Giant MPNSTs of the scalp are highly aggressive lesions that should primarily be treated in a surgical fashion. Although adjuvant radiotherapy has been used routinely for local tumor control, there is uncertainty about its advantages.

Primary malignant peripheral nerve sheath tumors arising from the spinal canal invading the abdominal cavity in a dog.

A 9-year-old neutered male Wire Fox Terrier presented with an 1-month history of hindlimb paresis. Magnetic resonance imaging revealed a contrast-enhanced mass at the level of the L2 vertebral canal. The dog became paraplegic with no deep perception of the hindlimbs, and the mass was surgically removed. The histopathological diagnosis was of a malignant peripheral nerve sheath tumor (MPNST). The dog suffered a relapse of right hindlimb ataxia at 225 days after the surgery. The dog died 434 days after the surgery. Necropsy found a large mass in the abdominal cavity invading from the L2-nerve. This is the first report of MPNST invading the abdominal cavity through the nerve root.

Malignant peripheral nerve sheath tumor of the parapharyngeal space arising from cervical sympathetic chain: A rare entity.

Malignant peripheral nerve sheath tumors (MPNSTs) of parapharyngeal space are rare and if present are most often in association with neurofibromatosis type 1 (NF-1). Only a few cases of MPNST have been reported in the literature without coexisting NF. We report one such case of an MPNST of parapharyngeal space tumor in a 35-year-old female with no associated features of NF-1. She presented with right-sided neck swelling and ptosis. Magnetic resonance imaging showed a 7 cm × 8 cm × 11 cm irregular swelling in the right parapharyngeal space with invasion of surrounding muscles. The mass was excised using a transcervical approach. Postoperative histopathological examination of the specimen revealed MPNST possibly arising from the cervical sympathetic chain.

Overview of primary adult retroperitoneal tumours.

In front of a primary retroperitoneal tumour, it is necessary to have in mind all possible diagnoses in order to specify the diagnostic strategy and the treatment. According to the World Health Organization (WHO) classification of tumours, mesenchymal benign and malignant tumours (including sarcomas and, currently, neurogenic tumours), parasympathetic tumours, extragonadal germ cell tumours, and lymphoid tumours have been identified. By definition, primary retroperitoneal tumours start independently from the retroperitoneal organs. Secondary lesions, carcinoma metastasis, and adenopathy are excluded from this definition, but they can also develop in the retroperitoneal space and lead to misdiagnoses. In the absence of positive tumour markers or an evocative biology, percutaneous biopsy is necessary. Pathological diagnosis is necessary to decide whether surgery must be done, its timing among the other treatments, and its extension. This paper summarizes all the diagnostic possibilities.

Giant Melanotic Malignant Peripheral Nerve Sheath Tumor in the Pelvis: Contrast-Enhanced CT and 18F-FDG PET/CT Finding.

Melanotic malignant peripheral nerve sheath tumor is an extremely rare tumor, which originates from the neural crest, and more than half the cases are associated with Carney complex (myxomas, spotty pigmentation, and endocrine abnormalities). Herein, we have presented a case of a melanotic malignant peripheral nerve sheath tumor, which is not associated with Carney complex. The patient underwent preoperative nonenhanced CT, contrast-enhanced CT, and F-FDG PET/CT scans, which showed a large pelvic tumor with heterogeneous enhancement and increased F-FDG uptake. Subsequently, the patient underwent complete resection of the tumor.

Retroperitoneal Malignant Peripheral Nerve Sheath Tumor on 99mTc-DTPA Renal Scintigraphy.

Findings of Tc-DTPA renal scintigraphy of a retroperitoneal malignant peripheral nerve sheath tumor are reported here. The patient was a 48-year-old woman who presented discomfort and intermittent dull pain in the left upper quadrant of the abdomen for approximately 3 weeks.