Malignant peripheral nerve sheath tumor mimicking carotid body tumor, a rare case report and review of literature.

INTRODUCTION AND IMPORTANCE: Malignant Peripheral Nerve Sheath Tumor (MPNST) is a rare type of soft tissue sarcoma. It is an aggressive tumor with high rates of local recurrence and distant metastasis. MPNST rarely occurs in the neck. We present a case of cervical MPNST manifesting as Carotid Body Tumor (CBT). CASE PRESENTATION: A 67-year-old man presented with a neck mass. The mass was rapidly enlarging and imaging studies favored CBT. A previous attempt at surgical resection failed, and the compressive symptoms were progressive during recent weeks. After multidisciplinary discussion, the tumor was resected and pathological evaluation confirmed the diagnosis of MPNST. Post-operative metastatic work-up showed lung metastasis, and the patient died approximately one year after surgery. CLINICAL DISCUSSION: Cervical MPNST is rare, and surgery is the mainstay of its treatment. Pre-operative tissue diagnosis is recommended when possible, and immunohistochemical staining is necessary for prompt diagnosis. Adjuvant therapy may be helpful in metastatic cases or incomplete resection. Nevertheless, local recurrence and distant metastasis especially to the lungs are common, as in our case. CONCLUSION: MPNST is one of the potential causes of cervical masses and considering its invasive behavior, surgical resection is recommended as soon as the diagnosis is made.

Radiation-Induced Intraosseous Malignant Peripheral Nerve Sheath Tumor: A Case Report.

INTRODUCTION: The significance of radiation therapy in cancer treatment comes with associated complications, including fibrosis, osteonecrosis, and the development of secondary malignancies, such as malignant peripheral nerve sheath tumors (MPNSTs). We emphasize the importance of understanding these complications for an effective patient management. METHODS: We report a 47-year-old man with a history of squamous cell carcinoma of the tongue, treated with surgery, chemotherapy, and radiation therapy. The patient later presented with symptoms that led to the discovery of an intraosseous MPNST. RESULTS: Histopathological examination revealed characteristic features of MPNST, including spindle cells arranged is sweeping fascicles with contrasting hypercellular and hypocellular areas, producing a marble-like pattern, with atypical wavy, buckled, hyperchromatic nuclei, and brisk mitotic activity. Immunohistochemical analysis showed patchy positive staining for S100 and SOX10, and a complete loss of H3K27me3 expression. This report underscores the challenge of diagnosing secondary malignancies post-radiation therapy and the importance of careful histological examination to differentiate them from other conditions. CONCLUSIONS: In conclusion, radiation-induced secondary malignancies are a significant late side effect of radiation therapy that can profoundly impact treatment decision-making and requires a high index of suspicion during post radiation surveillance. Malignant peripheral nerve sheath tumor serves as a pertinent example, highlighting the importance of considering long-term risks when developing optimal management plans for cancer patients.

Multiple sporadic schwannomas in a previously radiated field.

Peripheral nerve sheath tumors are a heterogenous group of predominantly benign tumors of neurogenic origin that arise outside of the central nervous system and include schwannomas and neurofibromas. These tumors often occur sporadically, however multiple lesions are generally associated with genetic syndromes such as neurofibromatosis (type 1 and 2) and schwannomatosis, and occasionally these tumors and their malignant variations are associated with a history of radiation treatment. Multiple benign schwannomas in an irradiated field have seldom been reported in the literature. We describe a case of a 49-year-old male with a history of right sided irradiated testicular cancer who presented with 2 histologically confirmed benign schwannomas in the right pelvic wall and right psoas muscle.

Rare Hybrid Perineurioma and Granular Cell Tumor: A Pediatric Case.

We present a case of a 13-year-old patient with a distinct tumor with both granular cell and perineurial elements, located on the lower lip. The patient presented with a long-standing lip mass that was clinically felt to most likely represent a mucocele. Following surgical excision, histopathological examination revealed a well-circumscribed tumor composed of granular cells with positive S100 protein staining and spindled cells positive for EMA and GLUT-1, confirming mixed neuroectodermal and perineurial origin. This is the first case documenting a perineurial-granular cell hybrid tumor in a patient under 18 years old, and the first to be reported in the head and neck. This case expands our understanding of hybrid PNSTs, emphasizing the importance of considering diverse clinical presentations, especially in the context of rare pediatric occurrences in atypical locations.

Schwannoma of the Lower Limb: A Case Report.

Schwannoma is a benign tumor of the peripheral nerve sheath and is a unique clinical entity when localized to a lower limb. Growing as a painless nodule, it might be misdiagnosed by many medical professionals as another benign soft tissue skin condition, such as lipoma, myxoma, or ganglion cyst. Definitive diagnosis of peripheral schwannoma is made by biopsy and histopathologic evaluation, followed by surgical excision, which is the definitive treatment of the tumor. Classic symptoms of schwannoma of the lower limb are peripheral neuropathy (tingling, burning sensations) and motor impairment (weakness, paralysis of the affected limb). MRI imaging and biopsy are the most useful diagnostic methods for peripheral schwannoma, followed by surgical excision, which is the treatment of choice. Postoperative complications, if present, are minimal and rare. Because of the slow-growing nature of the tumor and the complexity of the lower limb's nervous and structural network, it is often asymptomatic and is challenging to diagnose at a primary stage. That is why we want to spread awareness and draw the reader's attention to this rare case of a patient with schwannoma on the left lower limb.

Primary Aortic Malignant Peripheral Nerve Sheath Tumor.

A 74 year-old woman suffering 1 month persisting lumbago was referred with diagnosis of thoracic aortic aneurysm. Blood examinations indicated slightly or moderately elevated noradrenaline, dopamine, and homovanillic acid with normal-range vanillylmandelic acid. Contrast-enhanced CT scans revealed a tumor, protruding both intra- and extra-luminally, in the wall of the distal descending thoracic aorta without any primary focuses in the whole body. Primary aortic sarcoma or periaortic catecholamine-producing paraganglioma infiltrating the aorta was suspected. The tumor with the normal proximal and distal aorta 2-3 cm apart from it was completely resected under femoro-femoral partial cardiopulmonary bypass. Macroscopically, the tumor was originated from the aortic wall and protruded both intra- and extra-luminally. Immunohistochemically, positive S-100 and vimentin; Ki67 levels of 40%; and negative CD34, CK AE1/AE3, and SMA were identified. The aforementioned findings definitively diagnosed primary aortic malignant peripheral nerve sheath tumor, which has been never reported in the literature.

NSD3::NUTM1 Fusion Sarcoma Mimicking Malignant Peripheral Nerve Sheath Tumor with Prolonged Survival.

Nuclear Protein in Testis (NUT)-rearranged tumors comprise predominantly NUT carcinoma but also include certain lymphomas, leukemias, skin appendage tumors, and sarcomas. Although histologically diverse, all are genetically identified by oncogenic rearrangement in the NUTM1 gene. Many fusion partners occur, and NSD3 is NUT carcinoma's third most common partner. Herein, we present a case of a 26-year-old man with an NSD3::NUTM1 fusion sarcoma. The patient presented at the age of 13 months with a scalp nodule. Over the next 24 years, he experienced five local recurrences and ultimately expired of a rapidly progressive recurrence. His treatment included surgical resections, radiation, and various chemotherapies. Deceptively, the clinical presentation and histopathology aligned with a malignant peripheral nerve sheath tumor, a diagnosis rendered at initial resection with concurrence by a national soft tissue tumor expert. The patient's exceptionally long survival could be due to NSD3 as the fusion partner, aided by the initial small tumor size and young patient age. Thus, this case expands NUT fusion sarcomas' histologic and immunohistochemical profile to include mimicking a malignant peripheral nerve sheath tumor (MPNST). Additionally, it indicates that the NSD3::NUTM1 fusion can drive sarcoma genesis.

Denosumab combined with chemotherapy followed by anlotinib in the treatment of multiple metastases of malignant peripheral nerve sheath tumor: a case report and literature review.

Primary intraosseous malignant peripheral nerve sheath tumors (MPNSTs) are rare yet highly aggressive neoplasms originating from peripheral nerves. Typically manifesting as soft tissue masses accompanied by pain or functional impairment, these tumors pose significant challenges in management. Surgical intervention remains the cornerstone of treatment for patients with MPNST lacking distant metastasis, with generally modest success rates. In cases of recurrence and metastasis, the pursuit of effective systemic therapies has been a focus of clinical investigation. Herein, we present a case study involving an elderly female patient with refractory MPNST. In light of surgical limitations, a multimodal therapeutic approach combining chemotherapy, denosumab, and subsequent administration of anlotinib was pursued following collaborative consultation. This regimen yielded noteworthy clinical benefits, exemplifying a promising avenue in the management of challenging MPNST cases.

A rare Encounter with Pediatric Malignant Peripheral Nerve Sheath Tumor in Nasal Sinuses and Orbit.

This case report explores a rare and aggressive Malignant Peripheral Nerve Sheath Tumor (MPNST) in a 7-year-old child affecting nasal sinuses, maxilla, and orbit, an exceptionally uncommon pediatric manifestation unrelated to Neurofibromatosis 1. The child presented with alarming symptoms-nasal obstruction, snoring, epistaxis, and difficulty swallowing-underscoring the case's urgency. Non-contrast computed tomography revealed an extensive mass infiltrating nasopharynx, nasal cavity, maxillary sinus, ethmoid sinuses, and orbit, causing destructive consequences. Histopathology confirmed a high-grade MPNST, marked by rapid growth and early metastasis, highlighting management challenges. The rarity of pediatric MPNST in the nasal cavity is discussed, emphasizing the need for a broad differential diagnosis. Treatment involves surgical resection and adjuvant chemoradiation with a grim prognosis due to diagnostic complexities and morphological mimicry in young patients.

Orbital malignant peripheral nerve sheath tumor: A case report and review.

Malignant peripheral nerve sheath tumor of the orbit is an exceedingly rare entity. These tumors exhibit locally aggressive behavior, recurrences, distant metastasis, and poor response to existing treatment protocols. Orbital nerve sheath tumors are often associated with neurofibromatosis 1, and malignant transformation of neurofibroma into malignant nerve sheath tumor has also been seen. The recommended treatment for localized disease is radical or wide surgical excision to achieve negative margins followed by chemoradiation. For extensive disease, chemotherapy and radiotherapy can be utilized to stabilize the disease. Due to poor response and outcomes with current regimens, the focus has been shifted to approaches utilizing molecular targets and immunological agents. Despite all the advancements, the outcomes still remain discouraging for moderate- to high-grade lesions and thus necessitate studies to design promising treatment modalities.

Imaging findings of type I neurofibromatosis with outcome of malignant peripheral nerve sheath tumor in the right lower extremity.

Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder caused by mutations of the NF1 tumor suppressor gene, characterized by café-au-lait spots, neurofibromas, and Lisch nodules. Malignant peripheral nerve sheath tumor (MPNST) is an extremely rare malignancy with neural differentiation potential. The lifetime risk of developing MPNST in NF-1 patients is 8%-13%.

Malignant Transformation of Plexiform Neurofibroma Due to Neglected Giant Soft Tissue Swelling of the Back: A Case Report.

Neurofibromatosis type 1 can be severe and associated with malignant transformation. Proper follow-up and monitoring are very important in preventing the malignant transformation of neurofibromatosis. We encountered a case of malignant transformation of plexiform neurofibroma into neurofibrosarcoma (also known as malignant peripheral nerve sheath tumor). She had been presenting with a large mass on her back for a few years, which was also associated with an ulcer. She underwent a wide-excision biopsy of her back, and the histopathology examination (HPE) came back with a malignant peripheral nerve sheath tumor. This case concludes that any patient with a known case of neurofibromatosis should undergo follow-up to detect any malignant transformation of the disease. Early detection of the malignant transformation of neurofibromatosis can help prevent the disease's progression. The main treatment is surgical resection; however, the risk of local recurrence is higher, especially in patients with neurofibromatosis type 1.

Contemporary surgical management of pediatric non-rhabdomyosarcoma soft tissue sarcoma.

Non-rhabdomyosarcoma soft tissue sarcoma (STS) comprises most STS in pediatric patients. It is a diverse set of over 30 histologic subtypes. Treatment is based on risk group determined by tumor size, grade, and the presence of metastases. Surgical resection is a cornerstone of therapy, as tumors are often resistant to chemotherapy or radiation. While patients with isolated tumors less than 5 cm may undergo upfront resection, strong consideration should be given to neoadjuvant chemoradiotherapy to ensure negative margins at surgical resection and optimal outcomes. Sentinel lymph node biopsy is strongly recommended for clear cell and epithelioid sarcomas. The most common metastatic site is the lung, and metastases should be resected at the end of therapy, when feasible. Unfortunately, many high-risk patients progress on therapy, and alternative strategies including earlier metastatic control require investigation.

Rare primary intrapulmonary malignant peripheral nerve sheath tumor showing significant response to sintilimab: A case report and literature review.

Primary pulmonary malignant peripheral nerve sheath tumor (MPNST) is a rare soft tissue sarcoma with a low incidence, poor prognosis and limited treatment options. The present study reported a case of lung MPNST in a 63-year-old male patient without any pulmonary symptoms. Immunohistochemical analysis of the tumor indicated a programmed death-ligand 1 (PD-L1) expression tumor proportion score of 60%. A total of six courses of sintilimab were used in this patient and a remarkable response was achieved. In summary, sintilimab single-agent immunotherapy may be a novel treatment for pulmonary MPNST. When encountering analogous cases in the future, oncologists can test for the expression of PD-L1 in patients to guide the therapy's design.

Rapid Progression of a T3-T4 Paraspinal Schwannoma in a Young Female.

This case report presents an unusual incidence of a T3-T4 paraspinal schwannoma in a 22-year-old female, highlighting its clinical significance due to its atypical presentation and growth rate. Schwannomas, benign peripheral nerve sheath tumors, are typically slow-growing and present with minimal or no neuropathic symptoms. However, this case deviated from the norm, with the patient experiencing significant neuropathic pain and rapid tumor growth from 37 mm to 55 mm over a period of six months, necessitating surgical intervention. Unique to this case was the presence of a positive Tinel sign and localized neuropathic back pain, features not commonly associated with paraspinal schwannomas. Through MRI and histological evaluation, the diagnosis of schwannoma was confirmed, underlining the necessity of considering paraspinal schwannomas in differential diagnoses for patients presenting similar symptoms. This case contributes to the medical literature by emphasizing the variability in presentation and growth rates of schwannomas, reinforcing the need for a thorough evaluation and an individualized approach to management in young patients presenting with neuropathic pain and positive neurological signs.

Corrigendum: Myelomodulatory treatments augment the therapeutic benefit of oncolytic viroimmunotherapy in murine models of malignant peripheral nerve sheath tumors.

[This corrects the article DOI: 10.3389/fimmu.2024.1384623.].

Solitary neurofibroma confined to inferior rectus muscle tendon: a case report.

The present study reports a case of solitary neurofibroma attached to the Inferior Rectus (IR) muscle tendon in a 24-year-old healthy woman and reviews the relevant literature regarding the clinical presentation, diagnosis, and management of this uncommon tumor. The patient underwent successful surgical resection of the tumor, leading to the resolution of associated symptoms (left lower eyelid protrusion and redness). Pathological examination confirmed the diagnosis of neurofibroma based on characteristic histopathological and immunohistochemical markers. This case report underscores the rarity of solitary neurofibromas and primary neoplasms of orbit and ocular adnexa. We also discuss the background of solitary neurofibromas originating from orbit and ocular adnexa. The successful management of this case through surgical resection highlights the importance of accurate diagnosis and tailored treatment strategies. To the best of our knowledge, this is the first reported solitary neurofibroma confined solely to the IR tendon.

The Use of Hexokinase 2-Displacing Peptides as an Anti-Neoplastic Approach for Malignant Peripheral Nerve Sheath Tumors.

Malignant Peripheral Nerve Sheath Tumors (MPNSTs) are aggressive sarcomas that can arise both sporadically and in patients with the genetic syndrome Neurofibromatosis type 1 (NF1). Prognosis is dismal, as large dimensions, risk of relapse, and anatomical localization make surgery poorly effective, and no therapy is known. Hence, the identification of MPNST molecular features that could be hit in an efficient and selective way is mandatory to envision treatment options. Here, we find that MPNSTs express high levels of the glycolytic enzyme Hexokinase 2 (HK2), which is known to shield cancer cells from noxious stimuli when it localizes at MAMs (mitochondria-associated membranes), contact sites between mitochondria and endoplasmic reticulum. A HK2-targeting peptide that dislodges HK2 from MAMs rapidly induces a massive death of MPNST cells. After identifying different matrix metalloproteases (MMPs) expressed in the MPNST microenvironment, we have designed HK2-targeting peptide variants that harbor cleavage sites for these MMPs, making such peptides activatable in the proximity of cancer cells. We find that the peptide carrying the MMP2/9 cleavage site is the most effective, both in inhibiting the in vitro tumorigenicity of MPNST cells and in hampering their growth in mice. Our data indicate that detaching HK2 from MAMs could pave the way for a novel anti-MPNST therapeutic strategy, which could be flexibly adapted to the protease expression features of the tumor microenvironment.

Survival after resection of malignant peripheral nerve sheath tumors: Introducing and validating a novel type-specific prognostic model.

Background: This study aimed to assess the performance of currently available risk calculators in a cohort of patients with malignant peripheral nerve sheath tumors (MPNST) and to create an MPNST-specific prognostic model including type-specific predictors for overall survival (OS). Methods: This is a retrospective multicenter cohort study of patients with MPNST from 11 secondary or tertiary centers in The Netherlands, Italy and the United States of America. All patients diagnosed with primary MPNST who underwent macroscopically complete surgical resection from 2000 to 2019 were included in this study. A multivariable Cox proportional hazard model for OS was estimated with prespecified predictors (age, grade, size, NF-1 status, triton status, depth, tumor location, and surgical margin). Model performance was assessed for the Sarculator and PERSARC calculators by examining discrimination (C-index) and calibration (calibration plots and observed-expected statistic; O/E-statistic). Internal-external cross-validation by different regions was performed to evaluate the generalizability of the model. Results: A total of 507 patients with primary MPNSTs were included from 11 centers in 7 regions. During follow-up (median 8.7 years), 211 patients died. The C-index was 0.60 (95% CI 0.53-0.67) for both Sarculator and PERSARC. The MPNST-specific model had a pooled C-index of 0.69 (95%CI 0.65-0.73) at validation, with adequate discrimination and calibration across regions. Conclusions: The MPNST-specific MONACO model can be used to predict 3-, 5-, and 10-year OS in patients with primary MPNST who underwent macroscopically complete surgical resection. Further validation may refine the model to inform patients and physicians on prognosis and support them in shared decision-making.