Year : 2008 | Volume
: 25 | Issue : 1 | Page : 28--32
Squash preparation of a malignant triton tumor in a rare location
Sandhya Sundaram1, D Prathiba1, S Rajendiran1, Shalinee Rao1, K Ganesh2,
1 Department of Pathology, Sri Ramachandra Medical College and Research Institute, Sri Ramachandra University, Porur, Chennai - 600 116, India
2 Department of Neurosugery, Sri Ramachandra Medical College and Research Institute, Sri Ramachandra University, Porur, Chennai - 600 116, India
Department of Pathology, Sri Ramachandra Medical College and Research Institute, Sri Ramachandra University, Porur, Chennai - 600 116
Malignant peripheral nerve sheath tumors (MPNST) are rare malignant mesenchymal neoplasms of neural origin. Malignant peripheral nerve sheath tumors arising in a cranial nerve are rare with only a few cases being reported in literature. An MPNST with rhabdomyosarcomatous differentiation is also known as malignant triton tumor (MTT). MTT has a worse prognosis than the classic MPNST. The cytomorphological patterns of these tumors are insufficiently documented in literature. We present here the cytohistological features of an MPNST with focal rhabdomyomatous differentiation arising in the trigeminal nerve, which was confirmed by immunohistochemistry.
|How to cite this article:|
Sundaram S, Prathiba D, Rajendiran S, Rao S, Ganesh K. Squash preparation of a malignant triton tumor in a rare location.J Cytol 2008;25:28-32
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Sundaram S, Prathiba D, Rajendiran S, Rao S, Ganesh K. Squash preparation of a malignant triton tumor in a rare location. J Cytol [serial online] 2008 [cited 2020 Jul 10 ];25:28-32
Available from: http://www.jcytol.org/text.asp?2008/25/1/28/40656
Malignant peripheral nerve sheath tumors (MPNST) are soft tissue tumors of putative schwann cell lineage. These tumors are commonly seen in peripheral nerves usually in a setting of neurofibromatosis type 1 (NF-1). However, their occurrence in the head and neck region, particularly involving the intracranial nerve is rare and these are less commonly associated with NF-1. We document this case to highlight the rare occurrence of an MPNST with rhabdomyomatous differentiation without the stigmata of NF-1 in a cranial nerve.
A 30 year-old male presented with a two months' history of throbbing pain and reduced sensation in the left half of his face radiating to the left ear. The patient also had difficulty in chewing and reduced sensation in the side of the face.
Examination revealed loss of corneal and conjunctival reflexes. There was jaw deviation to the left temporal region and massetor muscle wasting was also evident. There was neither family history nor any stigmata of neurofibromatosis. Other cranial nerves were normal. Higher functions and gait were normal. No cerebellar signs were seen.
Pure tone audiometry showed bilateral, mild, conductive deafness.
For further evaluation, computed tomography (CT) of the brain was done using a contrast, which showed a mass attached to the trigeminal nerve [Figure 1]. Magnetic resonance imaging (MRI) of the brain showed a homogenous lesion invading into the brain tissue with fairly well demarcated margins. A diagnosis of a nerve sheath tumor was considered.
With the above diagnosis, the patient was taken up for surgery and per operatively the tumor was seen to invade the adjacent bone. A specimen was sent for intraoperative consultation. Both the frozen sections and squash preparation of the tumor were examined. Squash cytology preparation [Figure 2] showed a highly cellular tumor with spindle-shaped cells arranged both in clumps and discretely. The nuclei appeared pleomorphic and hyperchromatic. Occasional mitotic figures were also noticed. Frozen sections also showed spindle cells but the morphology could not be studied due to ice crystal artifacts.
In view of the per operative findings as well as the radiological and cytological features, a preliminary diagnosis was given of a spindle cell neoplasm suggestive of a peripheral nerve sheath tumor, suspicious of malignancy.
The tumor was radically removed and sent for histopathology. Grossly, this tumor was a gray-tan tissue measuring 3 cm × 2 cm × 1.5 cm with minimal foci of hemorrhage and necrosis. Microscopy showed a highly cellular tumor composed of spindle-shaped cells arranged haphazardly with wavy nuclei. In addition, a few large cells with bright eosinophilic cytoplasm were also seen [Figure 3]. There was a moderate degree of pleomorphism and mitosis was brisk (about 12/10 per high power field) with occasional atypical mitosis. At places, the lesion was seen invading into the adjacent brain tissue and the bone.
Immunohistochemical staining was done for S-100, glial fibrillary acidic protein (GFAP), desmin, and MIB-1.
There was focal positivity for S-100; GFAP was negative and MIB-1 labeling index (LI) was 18%. A surprising finding was the focal positivity for desmin especially in the larger cells representing rhabdomyoblasts [Figure 3], inset. In addition, immunostaining for p53 protein showed overexpression in tumor cells (55%).
So, a final diagnosis of an MPNST with focal rhabdomyomatous differentiation, i.e. , MTT was given. A few large cells with eosinophoilic cytoplasm [Figure 2], inset were seen on review of the squash preparation. These were perhaps the cells with rhabdomyomatous differentiation. The patient was discharged on the seventh postoperative day and referred to the oncologist for further treatment.
Malignant peripheral nerve sheath tumors are rare lesions usually arising in peripheral nerves or somatic soft tissues from schwann cells, which form the protective sheath around the nerves throughout the body. They constitute 5% of all sarcomas of which 70% are associated with neurofibromatosis type 1 (NF-1), the most common familial cancer-predisposing syndrome in humans. , Most MPNSTs are large, fleshy, often necrotic neoplasms that may involve proximal portions of major nerve trunks of the neck, extremities, retroperitoneum, mediastinum, and viscera. However, the sciatic nerve is the most frequently affected of all these.  Cranial nerves are rarely affected although tumors of the trigeminal and acoustic nerves have been reported. In our case, the tumor was seen attached to the trigeminal nerve. In a report of seven cases documented in literature, the trigeminal nerve was involved in five cases (one of which also involved cranial nerves 3, 4, and 6) and the facial and acoustic nerves in two cases each. It is noteworthy that none of the seven intracranial examples had NF-1 or any family history of NF-1, which is in sharp contrast to those arising in more peripheral sites.  Furthermore, intracranial involvement is associated with a poor prognosis and hematogenous metastasis is not uncommon. Literature also suggests that all head and neck lesions (intra- or extracranial) are less likely to be associated with NF-1 than lesions elsewhere in the body.  Our patient too, did not have any evidence of NF-1.
MPNST and its variants typically present with pain and abrupt neurological symptoms due to rapid enlargement. The infiltrating tumors cause a fusiform expansion of the involved nerves and are often bulky at the time of presentation, especially when growing in relatively unrestricting sites ( e.g. , retroperitoneum). On the other hand, MPNSTs affecting the cranial nerves are understandably smaller at the time of presentation. The tumor in our case was also small and was seen to extend into the adjacent brain tissue and underlying bone. Although these tumors usually appear well circumscribed, they are not truly encapsulated - a feature also noted by us. On microscopic examination, they are often observed to invade soft tissue and nerve fascicles.  The definitive diagnosis of MPNST is obtained by biopsy where the evaluation of mitotic activity is very pertinent. The MPNST shows anaplastic features in the form of high cellularity, cellular and nuclear pleomorphism, a high mitotic rate, and necrosis. In a study by Ogose et al.  the MIB-1LI ranged from 7 to 38% for MPNSTs while in benign nerve sheath tumors, it was consistently below 4%. Our tumor showed a MIB-1LI of 18% which was in favor of MPNST. There was also overexpression of p53 protein. Recent studies in literature have shown overexpression of p53 in MPNSTs and their variants, with or without the association of NF-1. This may also prove useful in distinguishing it from its benign counterparts which do not show overexpression. 
A malignant triton tumor (MTT) is a rare subtype of the malignant peripheral nerve sheath tumor with a characteristic histological finding of rhabdomyoblastic differentiation among schwannoma cells.  In 1932, Masson first described the lesion that consisted of a malignant schwannoma with rhabdomyoblastic differentiation.  It is a rare clinicopathological entity with about 90 cases reported so far.  Although this tumor has been noted predominantly in the head, neck, and trunk regions, Daimaru et al.  have shown predilection for the thigh and buttock regions. It is most often seen in the third decade of life with one-third of the cases associated with neurofibromatosis. 
These tumors grow in an expansive fashion, flattening the soft tissue structures around them in a concentric manner and creating a compression zone of condensed and atrophic tissue. Outside this zone lies edematous, neovascularized tissue, mostly evident around rapidly growing high-grade tumors. Together, the compression and reactive zones comprise a pseudocapsule structure that often creates a false impression of tumor circumscription. These tumors may extend in an infiltrative fashion, spouting small tentacles that extend from the main tumor mass and which may perforate the pseudocapsule. 
Although histopathological features of MPNSTs and their variants have been well described, there have been limited studies on their cytological features. In a retrospective analysis of aspiration cytology of eight confirmed cases of MPNSTs, the cardinal cytomorphological features noted were loosely cohesive clusters and fascicular arrangement of the spindle cells with rounded ends. Nuclear pleomorphism ranged from mild to moderate with one of the cases showing extensive pseudoinclusions. Mitosis was present in almost all cases. A fibrillary background was noted in two cases.  FNAC also proved useful in the diagnosis of MPNST in a 65 year-old patient with NF-1. 
Intraoperative evaluation of nerve sheath tumors is more challenging as benign tumors can display atypical cytology, cellular pleomorphism, necrosis, and infarction as a result of degenerative changes and can simulate malignancy. The present case showed spindle cells with pleomorphism and occasional mitosis. In addition, the tumor was per operatively seen to invade the adjacent bone. In view of the clinical and cytological picture, a diagnosis of a nerve sheath tumor suspicious of malignancy was made. The cells with rhabdomyomatous differentiation were identified only in paraffin sections and confirmed by immunohistochemistry using desmin. Although the cytological changes in benign and malignant nerve sheath tumors can be confusing, an interdisciplinary approach by correlating the clinical, pathological, and radiological findings can enhance the accuracy of diagnosis.  Imaging studies using contrast MRI show central enhancement in case of benign nerve sheath tumors, which is not noticed in a majority of the malignant lesions. 
Malignant triton tumor with von Recklinghausens neurofibromatosis shows a marked male predominance, predilection in young age groups, and common presentation in the head and neck. However, sporadic cases occur mostly in older age groups with female predominance located commonly in the trunk.  Although a few examples of intracranial MTT have been reported in the parietooccipital lobe, lateral ventricle, and cerebellopontine angle, MTT in the trigeminal nerve has not been documented in literature so far to the best of our knowledge. The biological behavior of this tumor is more aggressive than the classic MPNST. It shows rapid growth, early metastasis, and poorer prognosis.  The prognosis is better for the head and neck, upper and lower extremity lesions and worse for the buttock, trunk, and retroperitoneum. The prognosis is dependent upon the histological grade and the completeness of the surgical excision. 
The role of immunohistochemistry in MPNSTs and their variants is well established. Malignant triton tumors are stained for desmin, myoglobin, and S-100 protein by the immunoperoxidase technique. , In our case, S-100 was focally positive in keeping with the staining pattern of MPNST. The large cells seen in histology were positive for desmin, thus providing support for the neoplasm's rhabdomyomatous differentiation.
Recent work on the cytogenetics of these tumors has revealed complex karyotypes. Loss of chromosomes or chromosomal regions 1p36 (48%), 3p21-pter (52%), 9p23-pter (57%), 10 (48%), 11q23-qter (48%), 16/16q24 (62%), 17 (43%) and 22/22q (48%) and gains of 7/7q (29%), and 8/8q (29%) were most prominent. These gains and losses were distributed equally between MPNSTs and MTTs, demonstrating that these entities are similar with respect to recurrent genomic imbalances.  Acquisition of i (8q) seems to be an early event in malignant triton tumors.  MTT also shows a breakpoint involving 11p15, the region of myogenic differentiation 1 gene, which is probably responsible for rhabdomyoblastic differentiation in the tumor. Further amplification of c-myc has also been implied in MTT, accounting for its aggressive behavior. 
Like for any other soft tissue sarcoma, the recommended treatment for MTTs consists of radical excision, followed by high dose radiation, potentially preventing local recurrence and increasing the survival rate.  Wide excision or amputation (when extremities are involved) may be required in some cases. Recent reports have elaborated the role of neoadjuvant therapy and adjuvant chemotherapy for MTT to potentially facilitate subsequent surgery, eradicate micrometastatic lesions and, therefore, improve the therapeutical outcome. Integrated positron emission tomography/computed tomography (PET/CT) has emerged as an important diagnostic tool for the reliable assessment of MTT response and metabolic remission. 
It is essential to identify MTTs because the five years' survival rate of MTT is 3-10% whereas it is 50-60% in MPNSTs.  MTTs are very aggressive tumors with early metastasis and poor overall survival (26%). The prognosis not only depends on histology and extent of surgical resection but also on its association with NF-1. In a study of a small series of nine cases, it was observed that MTT with NF-1 had poorer prognosis than those without associated NF-1.  During the follow-up period of ten months, our patient has shown a favorable course with no recurrence or metastasis, which corroborates with the reported study mentioned earlier. MTTs carry a more ominous prognosis in comparison to the classical MPNSTs. Therefore, early diagnosis and correct treatment is of utmost importance.
To conclude, this case highlights the rare occurrence of malignant triton tumors in cranial nerve locations, which can be suspected on a well-prepared squash preparation.
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