Malignant peripheral nerve sheath tumors (MPNST) are aggressive sarcomas arising from Schwann cells or neurofibromas, comprising ∼10% of soft tissue sarcomas. Found in 8% to 13% of neurofibromatosis type 1 patients, they typically show spindle cells expressing S100 and SOX10. Some display heterologous differentiation (bone, cartilage, vessels, or glands). When rhabdomyosarcomatous features are present, they are called malignant peripheral nerve heath tumor with heterologous rhabdomyoblastic differentiation (malignant triton tumors), which are more prone to recurrence, metastasis, and worse outcomes. Epithelial differentiation does not affect prognosis. Despite advances in understanding MPNST biology, many pathophysiological mechanisms remain unclear. This review highlights their histopathology, focusing on malignant triton tumor.

Malignant triton tumor: A rare subtype of malignant peripheral nerve sheath tumor – A 20-year retrospective review

Reporting the clinical course and management of a skull base malignant triton tumor in a child. An 11-year-old female patient initially presented at the age of 7 with left parotid gland swelling, exhibiting symptoms similar to parotitis. Magnetic resonance imaging (MRI) of the head performed at an external hospital suggested a neoplastic lesion in the left parotid gland and the left parasellar region. Six months later, a parotid gland biopsy was conducted. Postoperative pathology confirmed the diagnosis of embryonal rhabdomyosarcoma. Following the biopsy, the patient underwent one year of radiotherapy and chemotherapy. A follow-up head MRI examination revealed that the lesions in the parotid gland and the left parasellar region had completely resolved. The patient did not adhere to a regular schedule of follow-up examinations. At the age of 10, a follow-up head MRI revealed recurrence of the lesions in the left parotid gland and the left parasellar region. The patient subsequently underwent resection of the left parotid gland lesion at an external hospital. Postoperative pathologic analysis once again indicated embryonal rhabdomyosarcoma. The patient underwent genetic testing, which revealed a germline pathogenic mutation: NF1 p.L952Ffs*2, suggesting an inherited form of NF1. Chemotherapy was subsequently continued. A follow-up MRI performed 5 months after the second surgery showed no recurrence of the left parotid gland lesion; however, the left parasellar region lesion remained unchanged in size. A follow-up head MRI at 9 months postsecond surgery indicated an increase in the size of the left parasellar region tumor. By 10 months postsecond surgery, a follow-up head MRI showed a reduction in the left parasellar region lesion, with no recurrence of the left parotid gland lesion, leading to the discontinuation of chemotherapy. At 14 months postsecond surgery, a follow-up MRI revealed an enlargement of the left parasellar region lesion. The patient received 2 courses of chemotherapy, but a subsequent MRI showed continued growth of the left parasellar region lesion, accompanied by abnormal enhancement of the parotid gland lesion. The patient was then transferred to our department, where they underwent a left temporo-occipital craniotomy for tumor resection. Postoperative pathologic examination confirmed the diagnosis of a malignant triton tumor. Molecular pathologic testing was also performed. The patient recovered well and was discharged successfully. The patient died from cachexia caused by widespread dissemination of the parotid tumor 4 months after discharge. Pediatric skull base malignant triton tumors lack specific imaging manifestations. Radiotherapy and pharmacotherapy are insufficient to control tumor growth. Surgical resection remains the primary treatment method, yet the overall prognosis is poor.

Malignant triton tumor (MTT) is a rare subset (5%) of malignant peripheral nerve sheath tumors (MPNSTs), classified as soft-tissue sarcomas. MTT is an orphan disease characterized by rhabdomyoblastic differentiation, therapeutic resistance, and a sinister prognosis. The neoplasms classically arise at the trunk, head and neck region, and extremities. In 50% of the cases, MTT is associated with neurofibromatosis type 1 (NF1), a relatively common autosomal dominant cancer-prone disorder of the central nervous system. Few cases of MTT in the gastrointestinal tract have been published, including esophagus, duodenum, and rectum. In this article, we present what we believe to be the first report of MTT in the common bile duct. A multidisciplinary approach was the key in establishing this particular diagnosis, and workup included endoscopic ultrasound, endoscopic retrograde cholangiopancreatography, pathological staining, and genetic testing. Literature focusing on MTT remains scarce, and patients with MTT are often included with other subtypes in broader studies of MPNST. Therefore, our literature review covers MPNST and focusses on MTT where appropriate. It provides the current understanding of tumor epidemiology, genetics, and diagnostic workup, and discusses therapeutic challenges and future perspectives. Our case report underlines the value of cholangioscopy-guided biopsies, and honoring patient's autonomy in end-of-life setting.

Malignant Triton Tumors (MTTs) are rare, high-grade malignant peripheral nerve sheath tumors (MPNSTs) frequently associated with Type 1 Neurofibromatosis (NF1). NF1, an autosomal dominant disorder, predisposes approximately 10% of affected individuals to developing MPNSTs, with 50% of these tumors occurring in NF1 patients, while others arise sporadically or in association with radiation exposure. MTTs predominantly affect anatomical regions rich in large nerves, such as the limbs, spinal root, and cranial nerves. Mediastinal presentations are exceedingly rare, posing significant diagnostic and therapeutic challenges. Current treatment strategies include surgical resection, chemotherapy, radiotherapy, and lung-sparing procedures for metastatic disease. Molecular studies of MPNSTs have revealed that NF1 mutations lead to dysregulation of the RAS signalling pathway, while epigenetic alterations (e.g., SUZ12/EED mutations) further contribute to tumor progression. Dysregulated phylogenetically conserved pathways, including Wnt/beta-catenin and non-canonical SHH signalling, play a role in sarcoma progression and Schwann cell transformation. Recent advances in miRNA research highlight their involvement in tumor invasion and progression, with dysregulated miRNA expression and chromatin remodeling contributing to the pathogenesis of these neoplasms. However, the distinct molecular profiles for MTTs remain incompletely understood. Further investigation of the genetic and epigenetic landscape is essential for improving our understanding and identifying potential therapies. Herein, we present a single-center retrospective case series of three patients with an intrathoracic triton tumor treated at our University Hospital between 2000 and 2024, serving as a starting point for future insights into MPNST pathobiology.

Background/AimA malignant Triton tumor (MTT) is a rare and aggressive soft tissue sarcoma associated with poor prognosis and with no established treatment protocol.Case ReportA 38-year-old man presented with severe right thigh pain and limited hip motion. Since childhood, the patient had a mass on their thigh, accompanied by café-au-lait spots. Upon admission, a biopsy confirmed MTT that had metastasized to the lungs. Preoperative radiation therapy was administered to reduce the tumor size; however, the tumor did not shrink. Extensive resection was not feasible because of the tumor size and location, prompting a decision to perform volume reduction surgery aimed at alleviating the patient’s pain and improving mobility. Although the surgery provided temporary relief from the symptoms, the patient died two weeks later.ConclusionMTT requires a multidisciplinary approach that includes surgery, chemotherapy, and radiation therapy; however, in advanced cases such as this one, palliative measures may be more appropriate. This case underscores the challenges in managing MTT and highlights the potential role of volume reduction surgery in improving the quality of life of patients with significant symptoms. Despite the poor prognosis, symptom palliation during the two weeks leading up to the patient’s death was significant, illustrating the importance of addressing pain and mobility issues while considering overall treatment strategies in such complex cases. These findings emphasize the need for further research on effective management options for MTT to improve patient outcomes.

Although malignant transformation of benign vestibular schwannoma (VS) preceded by irradiation has been well documented, few studies have demonstrated malignant transformation in the absence of radiation. Here, we present a rare case of the malignant transformation of a benign VS to a malignant peripheral nerve sheath tumor (MPNST) in the absence of prior irradiation. Additionally, we conducted a literature search to identify all other reported cases of MPNST arising from VS under similar conditions. A 75-year-old female presented to the hospital with a 1-month history of left-sided facial numbness, loss of taste on the left side of her tongue, severe dysarthria, and recent-onset cranial nerve VI and VII palsies. MRI of the brain with and without contrast demonstrated an enlarging cerebellopontine angle mass and signs of brainstem compression. The patient underwent a left retrosigmoid craniotomy and surgical resection. Pathology and immunohistochemistry sequencing findings were consistent for MPNST with rhabdomyoblastic differentiation (malignant triton tumor). An outside review of the case by a large academic institution concurred with the diagnosis. The patient did not report any previous history of irradiation. A total of 11 cases, including ours, have appropriate S-100 immunochemical reactivity to confirm malignant transformation. Due to the limited number of reported cases of MPNST arising from VS without prior irradiation, information regarding pathogenesis and pathological diagnosis is scarce. We provide valuable additions to the literature, including next-generation sequencing data, to identify potentially targetable genetic changes and help elucidate the pathogenesis of MPNST.

Malignant Triton tumor (MTT) is a rare variant of Malignant Peripheral Nerve Sheath Tumors (MPNST) with striated muscle formation. The diagnosis of MTT must meet the diagnostic criteria of MPNST and proven rhabdomyoblast differentiation. This case is discussed because of its rare incidence, which is 5-10% of all MPNSTs. The prognosis in most MTT patients is poor due to its rarity. Malignant Triton tumor (MTT) is a rare variant of malignant peripheral nerve sheath tumor. A 34-year-old woman came to the Head and Neck Surgery clinic of RSUD Dr. Soetomo Surabaya with complaints of a lump on the left upper front neck. This painless lump was small, marble-sized, skin-colored, and had enlarged rapidly over the last year. On physical examination, a skin-colored mass was found in the anterior colli region sinistra, which extended to the infraauricula sinistra, measuring approximately 20 x 20 x 15 cm with a hard solid consistency, partially spongy, flat surface, and indistinct borders. The patient underwent wide excision, vascular exploration, and continued with radiotherapy. The prognosis in most MTT patients is poor, and due to its rarity, studies with a large number of cases are lacking. MTT is a rare variant of MPNST with rhabdomyoblastic differentiation that behaves more aggressively than typical MPNST, thus having a worse prognosis. Treatment modalities, especially in advanced and metastatic cases, still lack standardized management or guidelines for the management of MTT. Until now, surgical excision and adjuvant radiotherapy have been the main therapeutic options for MTT.

Malignant peripheral nerve sheath tumor (MPNST) is a rare, often high-grade sarcoma. A small subset of MPNST shows evidence of heterologous rhabdomyoblastic differentiation, also known as malignant triton tumor (MTT). Immunohistochemical loss of histone 3 lysine 27 trimethylation (H3K27me3) has previously been described as a reliable marker for both MPNST and MTT. To assess the loss of H3K27me3 as a potential tool for discriminating MTT from embryonal rhabdomyosarcoma (ERMS). We studied the immunohistochemical expression of H3K27me3 in 23 pediatric cases of confirmed ERMS. Of the 23 patients, 21 were male and 2 were female, with an age range of 2 months to 18 years (median, 5 years). Most of the tumors arose in the paratesticular soft tissue (n = 14), with other locations including the pelvis (n = 3), thigh (n = 2), abdomen (n = 1), orbit (n = 1), prostate gland (n = 1), and parotid gland (n = 1). All cases had characteristic morphologic features of ERMS. By immunohistochemistry, all tested cases expressed desmin (18 of 18), myogenin (20 of 20), and MyoD1 (5 of 5). More than half of the cases (12 of 23; 52%) showed loss (nuclear absence) of H3K27me3, defined as staining in less than 5% of the tumor cells. The remaining cases demonstrated some degree of partial staining with H3K27me3, ranging from 5% to 40% of the tumor cells. No significant correlation between H3K27me3 expression and clinicopathologic features was identified. Loss of H3K27me3 frequently occurs in ERMS (52%) and is not reliable in distinguishing ERMS from MTT.

Background/AimMalignant triton tumor (MTT) is a rare, highly aggressive malignant nerve sheath tumor with rhabdomyoblastic differentiation. The overall 5-year survival rate is extremely low, and no standardized treatment exists. We report a case of MTT in the distal femur that was treated with surgery and chemotherapy.Case ReportA 16-year-old male was referred to our hospital due to severe pain during physical activity and difficulty in walking. He showed no café-au-lait spots and no family history of Neurofibromatosis-1. He underwent an incisional biopsy and was diagnosed with MTT of the distal femur. After administering preoperative chemotherapy using adriamycin, ifosfamide, and cisplatin, wide resection surgery was performed for MTT. Subsequently, postoperative chemotherapy using methotrexate, in addition to the agents mentioned above, was administered. One and a half years after the surgery, he can walk without pain, and there are no signs of local recurrence or metastasis.ConclusionThe combined modality treatment, integrating chemotherapy and surgery, has successfully prevented local recurrence and accomplished favorable outcomes without lung metastasis.

Malignant Triton Tumor: A Narrative Review of Current Evidence and a Single Center Experience

A 28-year-old female, a known case of neurofibromatosis 1, presented to the respiratory medicine department with complaints of breathlessness and cough for 2 weeks’ duration. Clinical examination revealed right-sided moderate pleural effusion. Computed tomography (CT) chest revealed a large anterior mediastinal mass with chest wall infiltration. Histopathology showed neoplasm with epithelioid cells, arranged as sheets and interlacing spindle cells with a moderate amount of eosinophilic cytoplasm and inconspicuous nucleoli. Histopathological examination of excised specimen showed a malignant peripheral nerve sheath tumor with rhabdomyoblastic differentiation also known as malignant triton tumor. After palliative chemotherapy, later on follow-up, CT-guided biopsy from right side chest wall lesion also showed the same. Because of this rare presentation, we are reporting this case.

e23562 Background: Malignant peripheral nerve sheath tumor with rhabdomyoblastic differentiation, also called a malignant triton tumor (MTT) is both a rare and aggressive form of cancer with both the features of peripheral nerve sheath tumors as well as rhabdomyoblasts with high recurrence rates. There is a higher risk of patients with neurofibromatosis type 1 (NF1) developing MTT. Radiation can be used to excise higher grade large MTT, however, chemotherapy still has no consensus on efficacy. Despite the rarity of MTT with rhabdomyoblastic differentiation, increased efforts to understand epidemiological trends could increase overall understanding of the malignancy. Methods: We extracted data from 50 patients diagnosed with MTT(ICD-9561-3) using the 2004-2020 National Cancer Database (NCDB) to perform a retrospective cohort analysis. We focused on various demographic factors including age, sex, race, Hispanic status, income status, educational status, insurance status, facility type and location, distance from facility, and Charleson-Deyo score using descriptive statistics. Regression analysis was used to identify incidence trends. Results: In our study of 50 patients diagnosed with MTT, a majority of the patients were male (62%), identified as White, and were of non-Spanish/non-Hispanic (90%) ethnicity. The average age at diagnosis was 49 years (SD = 20, range = 3-90) most and patients were treated in academic/research facilities (32%) or integrated network cancer programs (18%). Most patients (48%) had private insurance, with a significant number relying on government-funded programs (44%). The majority of patients (88%) underwent surgery as their primary treatment, with 30% having no residual tumor post-surgery. Additional treatments included radiation therapy (38%), chemotherapy (34%) and the most frequent primary site was the retroperitoneum (30%).The average survival time post-treatment was 35 months, with a survival rate of 43% at 2 years, 23% at 5 years, and a 15% at 10 years. Patients qualified for the top quartile of median housing income( $74,063 ≈). Conclusions: This study is the first analysis of patients with MTT, using the NCDB. It fills a gap in our understanding of this rare and aggressive disease. The majority of MTT patients were male, Caucasian, with an average age at diagnosis of 49 years, which supports previous case report descriptions. In addition, this study reveals the socio-economic factors associated with these patients who mostly earned a median income of $74,063 or more, were insured primarily by private insurance or managed programs (48%), and were treated predominantly in academic or research institutions (32%). It is necessary to continue research to further understand the influence of demographic and socio-economic factors on the diagnosis, treatments, and overall survival of patients with MTT.

Pleomorphic rhabdomyosarcoma (PRMS) is a rare and highly aggressive sarcoma, occurring mostly in the deep soft tissues of middle-aged adults and showing a variable degree of skeletal muscle differentiation. The diagnosis is challenging as pathologic features overlap with embryonal rhabdomyosarcoma (ERMS), malignant Triton tumor, and other pleomorphic sarcomas. As recurrent genetic alterations underlying PRMS have not been described to date, ancillary molecular diagnostic testing is not useful in subclassification. Herein, we perform genomic profiling of a well-characterized cohort of 14 PRMS, compared to a control group of 23 ERMS and other pleomorphic sarcomas (undifferentiated pleomorphic sarcoma and pleomorphic liposarcoma) using clinically validated DNA-targeted Next generation sequencing (NGS) panels (MSK-IMPACT). The PRMS cohort included eight males and six females, with a median age of 53 years (range 31-76 years). Despite similar tumor mutation burdens, the genomic landscape of PRMS, with a high frequency of TP53 (79%) and RB1 (43%) alterations, stood in stark contrast to ERMS, with 4% and 0%, respectively. CDKN2A deletions were more common in PRMS (43%), compared to ERMS (13%). In contrast, ERMS harbored somatic driver mutations in the RAS pathway and loss of function mutations in BCOR, which were absent in PRMS. Copy number variations in PRMS showed multiple chromosomal arm-level changes, most commonly gains of chr17p and chr22q and loss of chr6q. Notably, gain of chr8, commonly seen in ERMS (61%) was conspicuously absent in PRMS. The genomic profiles of other pleomorphic sarcomas were overall analogous to PRMS, showing shared alterations in TP53, RB1, and CDKN2A. Overall survival and progression-free survival of PRMS were significantly worse (p < 0.0005) than that of ERMS. Our findings revealed that the molecular landscape of PRMS aligns with other adult pleomorphic sarcomas and is distinct from that of ERMS. Thus, NGS assays may be applied in select challenging cases toward a refined classification. Finally, our data corroborate the inclusion of PRMS in the therapeutic bracket of pleomorphic sarcomas, given that their clinical outcomes are comparable.

Alterations of the NF1 tumor suppressor gene is the second most frequent genetic event in embryonal rhabdomyosarcoma (ERMS), but its associations with clinicopathologic features, outcome, or coexisting molecular events are not well defined. Additionally, NF1 alterations, mostly in the setting of neurofibromatosis type I (NF1), drive the pathogenesis of most malignant peripheral nerve sheath tumor with divergent RMS differentiation (also known as malignant triton tumor [MTT]). Distinguishing between these entities can be challenging because of their pathologic overlap. This study aims to comprehensively analyze the clinicopathologic and molecular spectrum of NF1-mutant RMS compared with NF1-associated MTT for a better understanding of their pathogenesis. We investigated the clinicopathologic and molecular landscape of a cohort of 22 NF1-mutant RMS and a control group of 13 NF1-associated MTT. Cases were tested on a matched tumor-normal hybridization capture-based targeted DNA next-generation sequencing. Among the RMS group, all except one were ERMS, with a median age of 17 years while for MTT the mean age was 39 years. Three MTTs were misdiagnosed as ERMS, having clinical impact in one. The most frequent coexisting alteration in ERMS was TP53 abnormality (36%), being mutually exclusive from NRAS mutations (14%). MTT showed coexisting CDKN2A/B and PRC2 complex alterations in 38% cases and loss of H3K27me3 expression. Patients with NF1-mutant RMS exhibited a 70% 5-year survival rate, in contrast to MTT with a 33% 5-year survival. All metastatic NF1-mutant ERMS were associated with TP53 alterations. Patients with NF1-mutant ERMS lacking TP53 alterations may benefit from dose-reduction chemotherapy. On the basis of the diagnostic challenges and significant treatment and prognostic differences, molecular profiling of challenging tumors with rhabdomyoblastic differentiation is recommended.

Background and aims. Immunocompromised pediatric patients with cancer are more susceptible to experiencing severe COVID-19 infection compared to other children. In a global registry study of childhood cancer with COVID-19, involving 1500 patients, severe of critical infections were detected in 20 % of the cases. The mortality rate of 4 % excelled that of the general pediatric population. Data about the development of COVID-19 complications in children with cancer remains limited and varies across different countries. This study aims to describe the incidence and characteristics of COVID-19 infection in children with cancer in Armenia.Methods. A prospective analysis was conducted on PCR-confirmed cases of COVID-19 infection in children with cancer aged 0–18 years from 2020 to 2022 at the Pediatric Cancer and Blood Disorders Center of Armenia, Yeolyan Hematology Center, the only pediatric hematology/ oncology institution in our country.Results. Between June 2020 and March 2022, we studied 201 children with cancer in Armenia, of whom 35 cases of COVID-19 infection were confirmed. The median age was 8.4, and the male/female ratio was 1.3. Among the COVID-19-positive patients, 15 had acute lymphoblastic leukemia, 5 had lymphomas, 4 patients had neuroblastoma, and 2 each had medulloblastoma, rhabdomyosarcoma and Ewing sarcoma. There were single cases of osteosarcoma, acute myeloid leukemia and malignant triton tumor. Twenty patients (57 %) were asymptomatic, and the rest presented with fever, sore throat, and cough. Among the patients with hematological malignancies, four developed pneumonia, and two of them experienced cancer progression subsequently. Additionally, four patients had pancytopenia/thrombocytopenia, likely due to the infection with the Omicron in the last three months of the mentioned period. Overall, the incidence of COVID-19 complications was 11 %, and mortality was zero.Conclusion. This is the first nationwide report on COVID-19 in children with cancer in Armenia. The findings indicate lower rates of severe infection and mortality among compared to global estimates. Further studies are emerging to explore these differences.

Malignant triton tumors (MTTs) are a rare and aggressive type of malignant peripheral nerve sheath tumor identified histologically by focal rhabdomyoblastic differentiation. A 37-year-old female with a prior history of Hodgkin lymphoma presented with acute-onset confusion, cognitive deficits, and weakness. Brain magnetic resonance imaging revealed a hemorrhagic intracranial mass later confirmed to be a malignant triton tumor. The patient underwent two resections and several courses of chemoradiation for multiple tumor recurrences and metastases. Unfortunately, despite extensive treatment, she died 2 years after initial presentation from complications of this tumor. Her overall survival (OS) of 26.7 months was double that reported in historical cohorts (OS ∼13 mos). The diagnosis and treatment of central nervous system MTTs are difficult and require a multidisciplinary team of neurosurgeons, radiologists, and oncologists. Histopathological analysis is required for confirmation of diagnosis. Gross-total resection of tumor and adjuvant radiation therapy have been shown to give patients the highest rates of survival and improved outcomes. Further studies and clinical trials are warranted to investigate the efficacy of chemotherapeutic agents like temozolomide, bevacizumab, and abemaciclib.

Malignant newt tumor (MNT) is a highly aggressive malignant neoplasm classified as a variant of malignant peripheral nerve sheath tumor (MPNT) with rhabdomyoblast differentiation. MDRF with divergent (heterologous) differentiation with the presence of a rhabdoid component is extremely rare, accounting for 5 % of all MRRF, which accounts for approximately 2 % of all soft tissue sarcomas. A subgroup of tumors in which malignant Schwann cells coexist with malignant rhabdomyoblasts is called malignant newt tumor (MNT) [10]. In most published clinical observations, newt tumor malignancy occurs in the head, neck, limbs, and trunk [15]. Limited reports of OST are available in the neurooncological literature and are most commonly described as sporadic newt tumor malignancy in the setting of neurofibromatosis type 1 (NF1). A rare clinical case of surgical treatment of OST, Th5 spinal root in a 61-year-old woman is described.

An atypical location for Malignant Triton Tumor – case report

A systematic review of reported clinical cases and treatment strategies was performed to better understand the prognostic factors and to develop the best possible treatment option for a 16-year-old patient diagnosed with a malignant triton tumor in the lower extremity with distant metastases in the lungs.