Malignant Triton Tumors in Sisters with Clinical Neurofibromatosis Type 1

Malignant triton tumors (MTTs) are rare and aggressive sarcomas categorized as a subgroup of malignant peripheral nerve sheath tumors (MPNSTs). MTTs arise from Schwann cells of peripheral nerves or existing neurofibromas and have elements of rhabdomyoblastic differentiation. We report the occurrence of MTTs in two sisters. The first patient is a 36-year-old female who presented with left sided chest wall swelling. She also had clinical features consistent with neurofibromatosis type 1 (NF-1). Debulking of the mass showed high-grade malignant peripheral nerve sheath tumor with skeletal muscle differentiation (MTT). The patient was treated with ifosfamide and adriamycin along with radiation. Four years after treatment, she still has no evidence of disease recurrence. Her sister subsequently presented to us at the age of 42 with left sided lateral chest wall pain. Imaging showed a multicompartmental retroperitoneal cystic mass with left psoas involvement. The tumor was resected and, similarly to her sister, it showed high-grade malignant peripheral nerve sheath tumor with rhabdomyoblastic differentiation (MTT). The patient was started on chemotherapy and radiation as described above.

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title: A–Z of malignant peripheral nerve sheath tumors
abstract: This article reviews the typical and atypical locations, imaging findings, local recurrence, and metastatic pattern of malignant peripheral nerve sheath tumors (MPNSTs). MPNSTs are rare soft tissue sarcomas, commonly occur in extremities, and are often associated with neurofibromatosis. Distinction between benign and malignant tumors can be challenging on imaging. MPNSTs have a poor prognosis; however, rhabdomyoblastic differentiation (malignant triton tumor), which has imaging features similar to MPNSTs, is associated with even more aggressive behavior.

title: Retroperitoneal Peripheral Nerve Sheath Tumour of Triton Type—A Case Report
abstract: The malignant peripheral nerve sheath tumour is the malignant counterpart to benign soft tissue tumours such as neurofibromas and schwannomas. Malignant Triton Tumour is a histological variant of malignant peripheral nerve sheath tumours with rhabdomyosarcomatous differentiation. They are known to develop in cases of neurofibromatosis type 1 (von Recklinghausen’s disease). Malignant peripheral nerve sheath tumor is biologically an aggressive tumour for which the treatment of choice is surgery. Here we report a rare case of malignant peripheral nerve sheath tumour, not associated with neurofibromatosis type 1 and arising in the retroperitoneum.

title: Malignant triton tumor of the anterior mediastinum: A case report
abstract: Malignant triton tumors (MTTs) are a rare subtype of malignant peripheral nerve sheath tumor (MPNST) showing rhabdomyoblastic differentiation, which have no treatment consensus and a poor prognosis. This case report presented the case of a 42-year-old male patient with a large MTT located in the anterior mediastinum. The patient underwent palliative chemoradiotherapy and interstitial chemotherapy and received traditional Chinese medicine. Localization of an MTT in the anterior mediastinum is extremely rare. To the best of our knowledge, this is only the fourth study of an MTT localized in the anterior mediastinum that has been documented in the English literature.

title: A Case of Malignant Peripheral Nerve Sheath Tumor with Rhabdomyoblastic Differentiation: Malignant Triton Tumor
abstract: Malignant peripheral nerve sheath tumors (MPNST) constitute a rare variety of soft tissue sarcomas thought to originate from Schwann cells or pluripotent cells of the neural crest. Malignant triton tumor (MTT), a very rare, highly aggressive soft tissue tumor, is a subgroup of MPNST and is comprised of malignant Schwann cells coexisting with malignant rhabdomyoblasts. We herein report the case of a 24-year-old man who presented a subcutaneous mass in his right thigh. The mass was removed surgically in its entirety and radiation therapy was applied locally to prevent tumor regrowth. Nonetheless, the patient died 10 months after surgery from metastases to the lung and brain. He presented neither cafe-au-lait spots nor cutaneous neurofibromas. The histopathology showed a transition from a neurofibroma to an MTT, making this the second report of an MTT arising from a neurofibroma without neurofibromatosis type 1, an autosomal dominant disorder with which 50-70% of tumors reported in previous studies were associated. A histopathological examination using immunostaining with desmin confirmed this diagnosis. MTT has a poorer prognosis than MPNST and should therefore be regarded as a distinct clinical entity.

title: Malignant triton tumor of the chest wall invading the lung. A case report and literature review.
abstract: Malignant triton tumor (MTT) is an histological deviation of malignant peripheral nerve sheath tumor with additional rhabdomyosarcomatous elements. It is very rare, profoundly aggressive, with a tendency to recur locally and metastasize early. If manifests itself more often in individuals with neurofibromatosis type I (NF-1) disease but also sporadically or post radiotherapy.  A 57-year-old male was admitted with a history of malignant triton tumor of the chest wall. Despite prior aggressive locoregional treatment including wide excision and adjuvant consolidating radiotherapy, the tumor recurred. The patient underwent a new operation and systemic chemotherapy, but expired a few months later due to disease progression.



MTT is exceedingly malignant requiring multimodality treatment. The cornerstone of management is radical surgical resection with clear margins. Nevertheless, the overall prognosis remains dismal.

title: Malignant triton tumor of the retroperitoneum: a case report and review of the literature
abstract: BackgroundMalignant triton tumors are relatively rare and highly aggressive tumors in which malignant schwannoma cells coexist with rhabdomyoblasts. Their occurrence in the retroperitoneum is uncommon and has been rarely reported.Case presentationWe present the case of a patient with a retroperitoneal malignant triton tumor. A 32-year-old male was referred with epigastric pain and an abdominal mass. Computed tomography revealed a huge soft tissue retroperitoneal mass that involved adjacent organs and vessels. Complete resection was undertaken. Pathological examination confirmed the presence of a malignant triton tumor. The patient died two and a half months after surgery, as a result of local recurrence.ConclusionMalignant triton tumors are uncommon sarcomas that are associated with a high incidence of developing local recurrence and distant metastases. Immunohistochemical staining showing nerve sheath differentiation with rhabdomyoblastic cells confirms the diagnosis. Complete excision of the tumor is the most effective treatment strategy for these retroperitoneal tumors.

title: Malignant peripheral nerve sheath tumor with rhabdomyosarcomatous differentiation (malignant triton tumor).
abstract: Malignant peripheral nerve sheath tumors arise from Schwann cells or within existing neurofibromas and have a strong association with type 1 neurofibromatosis. These tumors are histologically diverse and may contain malignant areas of divergent mesenchymal differentiation, the most common of which is skeletal muscle (rhabdomyosarcoma). Malignant peripheral nerve sheath tumor with rhabdomyosarcomatous differentiation is also known as malignant triton tumor. Malignant triton tumor has a worse prognosis than classic malignant peripheral nerve sheath tumor does, and the correct diagnosis requires attention to the clinical history and knowledge of the complexities regarding its differential diagnosis. In this review we discuss the clinical, histopathological, immunohistochemical, and prognostic features of this rare neoplasm.

title: Malignant triton tumors—complete surgical resection and adjuvant radiotherapy associated with improved survival
abstract: Malignant triton tumors (MTT) are a rare form of peripheral nerve sheath tumors that follows a particularly aggressive course. Given its rarity, only case reports and small series of patients have been published.

title: Malignant Peripheral Nerve Sheath Tumors (MPNST): The Mayo Clinic Experience
abstract: BackgroundMalignant peripheral nerve sheath tumors (MPNST) are a rare form of soft tissue sarcoma with few studies reporting on patient outcomes and prognostic variables.MethodsA retrospective review of 175 patients diagnosed with MPNST from 1985 to 2010 was performed. Patient, tumor, and treatment characteristics were evaluated to identify prognostic variables.ResultsThe median age of our study population was 44 years, and 51% were female. Median tumor size was 6 cm, and 61% of patients had high-grade tumors. Tumors were most commonly located on the extremities (45%), then trunk (34%) and head/neck (19%). The majority of patients underwent surgical resection (95%) and adjuvant treatment with chemotherapy (6%), radiation (42%) or both (22%). Margin status was R0 in 69%, R1 in 2%, R2 in 9%, and unknown in 20%. The local recurrence rate was 22%, and 5- and 10-year disease-specific survival (DSS) were 60% and 45%, respectively. On univariate analysis, no predictors for local recurrence were identified. Tumor size ≥5 cm, high tumor grade, tumor location, presence of neurofibromatosis type 1, local recurrence, and adjuvant chemotherapy were all associated with DSS. On multivariate analysis, size ≥5 cm [hazard ratio (HR) = 6.1, 95% confidence interval (CI) 1.5–25.0], local recurrence (HR = 4.4, 95% CI 1.7–11.4), high tumor grade (HR = 3.8, 95% CI 1.1–13.2), and truncal location (HR = 3.7, 95% CI 1.1–12.7) were poor prognostic indicators for DSS.ConclusionsHigh tumor grade and tumor size ≥5 cm predict adverse DSS for MPNST. In the context of a multidisciplinary treatment regimen, local recurrence and survival outcomes at 5 and 10 years were better than previously reported for MPNST.

title: Malignant Triton Tumor: A Rare Case
abstract: Malignant triton tumor (MTT) is a malignant peripheral nerve sheath tumor (MPNST) with rhabdomyoblastic differentiation. This rare tumor, with fewer than 100 cases reported in the literature, generally affects adult patients with neurofibromatosis 1 (NF-1). We report such a case in a 34-year-old man with NF-1 who presented with a mass over the medial side of the arm. Histopathologically finding of rhabdomyoblasts among malignant Schwann cells in a tumor arising from a peripheral nerve supported by immunostaining with S-100 protein and myogenin confirmed the diagnosis. MTT has a poor prognosis owing to its aggressive biological behavior. The fact that this tumor is extremely rare has prompted us to report this case.

title: Low-Grade Malignant Triton Tumor of the Neck: A Case Report and Review of the Literature
abstract: Rhabdomyoblastic differentiation in a malignant peripheral nerve sheath tumor (MPNST) is termed malignant triton tumor (MTT), a rare neoplasm that poses a diagnostic dilemma in the differential diagnosis of neck masses and portends poor prognosis. We report a sporadic case of MTT of the neck in a 23-year-old female. We present the pathological findings. Immunohistochemistry confirmed the neurogenic origin with S-100 expression and the rhabdomyoblastic differentiation with desmin and vimentin positivity. Radical surgical excision was done. After 4 years there were no signs of recurrence or distant metastasis. The clinical, microscopic, and long-term follow-up of this case are consistent with those of a low-grade malignancy.

title: Peripheral nerve tumors with rhabdomyosarcomatous differentiation (malignant “triton” tumors)
abstract: Three peripheral nerve sheath tumors are reported which showed an intermingling of schwannian elements and rhabdomyosarcoma, a type of compound tumor first described by Masson in 1932. One of the patients had von Recklinghausen's disease. The tumor in two patients showed pleomorphic rhabdomyosarcoma, while in a third patient it grew partially as an embryonal rhabdomyosarcoma. All three tumors contained areas of malignant schwannoma, but, in this latter case, the rhabdomyosarcoma appeared to arise from an area of benign Schwann cell growth. Two of the patients died following spread of the malignant muscle component. All previously reported examples of this tumor developed in individuals showing stigmata of von Recklinghausen's disease. Data from our three cases and from seven cases from the literature indicates the tumor to be highly malignant. Of the nine patients with follow‐up, seven were dead within 3 to 20 months of their diagnosis. Those recurrent tumors or metastases that were examined histologically (four cases) showed rhabdomyosarcoma.

title: Intraventricular Malignant Triton Tumour
abstract: Summary¶ The authors present the clinical and pathological features of a malignant triton tumour (MTT) in the lateral ventricle with neurofibromatosis type 1. A 57 year-old man presented with disorientation and memory disturbance. A Computed tomographic scan and magnetic resonance imaging studies revealed an enhancing lesion in the left lateral ventricle. A parieto-occipital transcallosal approach was taken and resection of the lesion was performed. The operative findings suggested that the tumour arose from the perivascular nerves. The final pathological diagnosis was a MTT. This is the first case of an intraventricular MTT. Aggressive treatment including radical surgery combined with radiochemotherapy is recommended for a MTT of the central nervous system.

title: Intracardiac malignant Triton tumor: a first presentation.
abstract: We present the first case of an intracardiac malignant peripheral nerve sheath tumor with rhabdomyoblastic differentiation (malignant Triton tumor) in a 63-year-old man who underwent elective, uncomplicated resection of his symptomatic left atrial mass.

title: Malignant "triton" tumors: a clinicopathologic and immunohistochemical study of nine cases.
abstract: Nine cases of malignant "triton" tumors, based on the coexistence of rhabdomyoblasts and Schwann cell elements, were analyzed clinicopathologically and immunocytochemically. All tumors were stained for myoglobin and S-100 protein by the immunoperoxidase technique. Six of the nine patients were in the third or fourth decade of life. Six cases were associated with von Recklinghausen's disease, and the tumors in two cases grew along nerve trunks. The malignant tumors showed a predilection for the thigh and buttock. Six of the seven deaths occurred within two years of the initial treatments. Strongly positive staining for S-100 protein was observed in three tumors, with transitional zones between the sarcomas and peripheral neurofibroma-like areas, as well as in two tumors composed predominantly of rhabdomyoblastic elements. In four other cases the tumors were only weakly positive for protein S-100. Intracytoplasmic myoglobin was present in all cases. Tumors composed predominantly of rhabdomyosarcomatous elements occurred in four patients, including two children with von Recklinghausen's disease. These results, considered with other findings, suggest that malignant "triton" tumors may not be as rare as previously believed.

title: Malignant Triton Tumor of the Sciatic Nerve as a Secondary Malignancy after Extended Field Radiotherapy and Chemotherapy of Hodgkin's Disease
abstract: Late effects of therapy for Hodgkin's disease include secondary malignancies like leukemia, lymphoma or solid tumors developing after long periods of latency. Ionizing radiation often causes the last group. The highest risks have been described for induced breast and lung cancers. We are the first to report a malignant triton tumor (MTT) as a secondary malignancy after radiotherapy and chemotherapy for Hodgkin's lymphoma. MTT is a very rare subtype of malignant peripheral nerve sheath tumors with rhabdomyoblastic differentiation and an aggressive course of disease.

title: Malignant triton tumour of the sinonasal tract: Case report and literature review☆
abstract: The objective is to report a rare tumour of the sinonasal tract and conduct a literature review. Malignant triton tumour is a subtype of malignant schwannoma with rhabdomyoblastic differentiation. It is a very rare tumour, with only 15 reported cases involving the sinonasal region.  Forty-seven years old female presented with a right-sided epistaxis, progressive right sided nasal obstruction and anosmia and a visible mass in the right nasal cavity. Imaging studies showed a mass extending from the piriform aperture to the nasopharynx in contact with the dura and the orbital content. The mass was biopsied and the result was consistent with malignant triton tumour. The patient refused the surgery at first so chemotherapy with MAID protocol was started. After the fourth course of chemotherapy the treatment was stopped due to patient intolerance and a thrombosis of the jugular vein. Patient then underwent surgery with frontal craniotomy and dural excision, endoscopic control was done at the end to insure a complete removal. The patient received Radiotherapy in the postoperative period (56 Greys). At 5 years of follow up the patient is doing fine with no signs of recurrence and normal ophthalmological findings.  Sixteen cases, including our case, have been reported to date in the literature. The mean age at presentation is 61 years. None of cases were associated with neurofibromatosis type 1. Eight patients were reported to be alive 5 years post-treatment, and 2 patients were reported to have died of the disease. The prognosis for triton tumours in the sinonasal tract is better than that for triton tumours in other locations.  Malignant triton tumour is a rare malignancy of the sinonasal tract. Otolaryngologists should be aware of this disease. The optimal treatment should include radical resection of the tumour.