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From the Departments of Otolaryngology (Nicolai, Tomenzoli, Berlucchi), Pathology (Facchetti, Morassi), and Radiology (Maroldi), Univer-sity of Brescia, Brescia, Italy.CORRESPONDENCE — Piero Nicolai, MD, Dept of Otolaryngology, University of Brescia, Piazza Spedali Civili 1, 25100 Brescia, Italy.

IMAGING CASE STUDY OF THE MONTH

MALIGNANT TRITON TUMOR OF THE ETHMOID SINUS AND NASALCAVITY

PIERO NICOLAI, MD DAVIDE TOMENZOLI, MD MARCO BERLUCCHI, MD

FABIO FACCHETTI, MD LAURA MORASSI, MD ROBERTO MAROLDI, MDBRESCIA, ITALY

TABLE 1. SUMMARY OF SINONASAL ANDNASOPHARYNGEAL NEOPLASMS TREATED BY

ENDOSCOPIC SURGERY (N = 51)

Neoplasm No. of Patients

Inverted papilloma 21Angiofibroma 13Osteoma 5Adenoid cystic carcinoma 2Esthesioneuroblastoma 2Plasmacytoma 2Transitional cell carcinoma 2Adenocarcinoma 1Basaloid squamous cell carcinoma 1Hemangiopericytoma 1Malignant triton tumor 1

INTRODUCTION

In 1932, Masson1 first described a lesion that con-sisted of a malignant schwannoma with rhabdomyo-blastic differentiation. Subsequently, Woodruff et al2coined the term “Malignant Triton Tumor” (MTT)to indicate such a neoplasm. The name refers to Lo-catelli’s experiment in which a sciatic nerve implantedonto the back of a Triton salamander caused thegrowth of a supernumerary limb made up of neuraland muscular tissue.3 Approximately 15% of MTTscontain additional mesenchymal or epithelial ele-ments and are therefore designated as having “pluri-directional differentiation.”4

Out of a series of 51 benign and malignant lesionsof the sinonasal tract or nasopharynx treated by anendoscopic approach in the period January 1992 toDecember 1999 (Table 1) at the Department of Oto-laryngology, University of Brescia, we herein reportthe case of an 81-year-old woman with an MTT ofthe nasal-ethmoid complex who is currently free ofdisease 36 months after surgery. A review of the lit-erature that focuses on incidence, histogenesis, diag-nosis, biological behavior, and treatment of MTTs

of the sinonasal tract is also included.

CASE REPORT

An 81-year-old woman was admitted to the De-partment of Otolaryngology of the University of Bres-cia with a history of right nasal cavity obstructionlasting several years, hypertension, and diabetes mel-litus. Three times previously, she had undergone re-moval of polyps from the right nasal cavity underlocal anesthesia, without histologic examination. Onendoscopy, the right nasal fossa was completely filledby a rose-gray, soft mass that apparently originatedfrom the middle turbinate. An enhanced computedtomography (CT) scan confirmed the presence of alesion that entirely filled the nasal cavity and the eth-moid sinus, protruded into the nasopharynx, and wascharacterized by a nonhomogeneous density. Themaxillary, frontal, and sphenoid sinuses were opaci-fied, suggesting the presence of an inflammatory fluidcollection. A marked bony thickening of the ethmoidsepta and middle turbinate was also evident, togetherwith a small dehiscence in the midportion of the foveaethmoidalis. There was no extension of the tumor tothe orbit or to the contralateral nasal cavity (Fig 1).The patient refused magnetic resonance imaging(MRI). A biopsy specimen was obtained, and a diag-nosis of malignant schwannoma with rhabdomyo-blastic differentiation was rendered. The family his-tory and an objective examination were negative forneurofibromatosis type 1 (NF-1), so no further radio-logic examination was performed. The findings ofroutine blood tests, urinalysis, and a chest X-ray werewithin normal limits.

Two surgical options were offered and discussedwith the patient: craniofacial resection and endoscop-ic removal. She elected to undergo the latter. Withthe patient under general anesthesia, the tumor wasfirst debulked to allow access to some important sur-

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881 Nicolai et al, Imaging Case Study of the Month 881

Fig 1. Computed tomography scans. A) Axial plane. Right nasal fossa is filled by solid mass enhanced after contrast agentadministration (asterisks). Lesion entirely surrounds dense and irregular structure resembling abnormal middle turbinate.Middle antral wall has been displaced by lesion (arrowheads), and dehiscent areas are seen at middle third. B) Coronal plane.“Bone” window enables detailed evaluation of bone structures. Mass occupies right ethmoid sinus and projects into nasalfossa. It extends mostly along vertical framework of middle turbinate. In fact, only minimal displacement of lamina papyraceaand of perpendicular lamina, which is partially eroded (arrows), can be observed. Right fovea (arrowhead) is also displacedand shows areas of erosion. One main finding of lesion consists of marked and irregular diffuse thickening of right middleturbinate (asterisks), which is rather enlarged and dense.

Fig 2. Endoscopic view (0° rigid fiberscope) of nasal cavi-ties 3 years after surgery. Wide communication of rightmaxillary sinus with nasal fossa, as well as patency ofsphenoidotomy, is clearly visible. No signs of recurrenttumor are evident.

gical landmarks: the uncinate process, the root of themiddle turbinate, the nasal septum, and the choana.After submucosal infiltration with 1% mepivacainehydrochloride with 1:200,000 epinephrine, an inci-sion was made along the area anterior to the unci-nate process, going up to the agger nasi and the roofof the nasal cavity anteriorly to the cribriform plate,and down to the adjacent nasal septum. The dissec-tion then proceeded laterally in an anteroposteriordirection to expose the maxillary sinus, which wasfilled by a dense inflammatory secretion and appar-ently was not involved by the tumor. The laminapapyracea, which was in close contact with the tu-mor, was resected, with care not to injure the ante-rior and posterior ethmoid arteries. Superiorly, the

dissection started at the agger nasi level and in frontof the lamina cribrosa and extended medially to in-clude the mucosa covering the upper third of the sep-tum. The middle turbinate was resected, and the le-sion was peeled off the roof of the ethmoid sinusand the lamina cribrosa. During these maneuvers, acerebrospinal fluid leak coming from a 5-mm bonydehiscence in the vertical lamella of the cribriformplate was observed.

The dissection was carried further posteriorly toinclude the superior turbinate and to reach the ante-rior wall of the sphenoid, which was full of inspis-sated mucus but was not involved by the tumor. Theresidual lesion was transorally removed en bloc withthe middle and superior turbinates, and multiple bi-opsy specimens were taken at the resection margins.Because the biopsy specimen obtained from the sep-tum showed tumoral tissue, a large area of the bonyand cartilaginous parts of the septum was resected.A composite graft harvested in the left nasal fossafrom the residual anterior part of the septum and madeof a small cartilaginous fragment with the overlyingmucosa was fixed in place with fibrin glue to sealthe cerebrospinal fluid leak. The nasal cavity wasleft packed with Lyofoam (Seton Healthcare Group,Oldham, England) for 4 days.

The postoperative course was uneventful, and thepatient was discharged from the hospital 6 days af-ter the operation. She underwent follow-up visits ev-ery 3 months and was free of disease at the last endo-scopic (Fig 2) and CT evaluations (Fig 3), 36 monthsafter surgery.

Microscopically, the tumor consisted of fascicles

882 Nicolai et al, Imaging Case Study of the Month 882

Fig 3. Follow-up computed tomography scan in coronalplane 3 years after surgery demonstrates reossificationof right fovea ethmoidalis (arrowhead) and thickeningof right lamina papyracea.

of closely packed spindle cells, with buckled nucleiand indistinct cytoplasmic borders. Focally roundedor strap-shaped rhabdomyoblasts with large, eosino-philic cytoplasm were present (Fig 4A). Focal glan-dular structures were also found. The mitotic indexwas low (1 mitosis per 10 high-power fields), andthere was no necrosis. A variable percentage of tu-mor cells were positive for S-100 protein; the rhab-domyoblasts showed an intense reactivity for desmin(Fig 4B) and muscle-specific actin.

DISCUSSION

The combination of a malignant peripheral nervesheath tumor with rhabdomyosarcomatous elementsis termed MTT.5 The tumor is a very rare clinicopath-ologic entity, with about 90 cases so far reported.6-12

According to the results of a world literature reviewmade by Woodruff and Perino,6 the tumor predomi-nantly affects young patients, with a mean age of 34years, and is associated in 57% of cases with NF-1.Patients with NF-1 appear to be slightly younger (31years) than patients without NF-1 (37 years).6 Thetumor has no peculiar site distribution and almostequally occurs in the limbs, head and neck, and trunk.

The histogenesis of MTT is controversial. On thebasis of Locatelli’s work,3 Masson and Martin13 pos-tulated that the endoneural cells in the tumor couldinduce the formation of muscle in a manner similarto that seen in supernumerary limb regeneration inthe Triton salamander. Further investigations, how-ever, showed that aneurogenic forelimbs of Tritonsmay also regenerate and that limb and muscle regen-eration in Tritons is independent of motor nerve in-nervation.14,15 A second and more widely acceptedhypothesis proposed by the same authors suggestedthat neoplastic Schwann cells directly transform intostriated muscle elements.14,15

A teratoid origin16,17 is less likely, because endo-dermal elements are absent, and all components ofthe tumor are obviously atypical. Finally, the theoryproposed by Holimon and Rosenblum18 and Naka etal,19 which unifies the embryogenesis and histogen-esis of the different mesenchymal elements presentin MTT, is based on the concept of “ectomesen-chyme”: the migratory cells of the neural crest showdivergent differentiation into mesenchyme (lepto-meninges, bone, cartilage, and muscle of head andface) and into neuroectodermal structures (mela-nocytes, ganglion cells, and Schwann cells) duringembryonic life. The cells, although widely presentthroughout the body, are believed to retain their ca-pacity for mesenchymal differentiation in adult life.The multiple differentiation capacity of neural crestcells is further illustrated by reports of tumors com-posed of mixed neural crest derivatives, as well asthe occurrence of neurosarcomatous transformationin a melanoma.20,21

Histopathologic criteria for MTT diagnosis, asestablished by Woodruff et al,2 require that the tu-mor 1) arise along the course of a peripheral nerve,or in a patient with NF-1; 2) largely show the growthcharacteristics of a Schwann cell tumor; and 3) con-tain bona fide neoplastic rhabdomyoblasts. Daimaruet al22 also regarded as MTTs tumors that arise in pa-tients without NF-1 that are microscopically compat-ible with malignant schwannoma with focal rhabdo-myoblasts, as well as tumors that occur within a nerveor in patients with NF-1 that show a predominantlyrhabdomyoblastic differentiation with focal Schwanncell elements.

Head and neck sites were involved in less than onethird of the MTTs reported in the literature: 8 patientshad the tumor localized in the neck,1,2,23-26 3 in thecerebellopontine angle,11,27,28 2 in the soft tissues ofthe face,21,29 2 in the parotid gland,10,23 2 in the thy-roid gland,30,31 and 1 each in the infratemporal fos-sa,12 oral cavity,32 and temporal fossa.33 Involvementof the sinonasal tract by MTT (Table 234-36) was firstdocumented by Shajrawi et al34 in a 75-year-old manwho was treated with a debulking procedure and com-plementary radiotherapy. The patient was free of dis-ease 6 months after a single recurrence 3 years afterthe first treatment. In a report by Bhatt et al,35 MTToccurred in a 66-year-old woman and was grosslyexcised through an extended external ethmoidectomyapproach. The patient was alive with disease 27months after surgery. The remaining 5 cases weredescribed by Heffner and Gnepp36 in 1992; they oc-curred in 4 men and 1 woman, ages 43 to 64 years.The initial treatment consisted of a partial removalof the tumor in 2 cases: 1 patient died of the disease26 months after surgery, and the other was alive with

B

A

883 Nicolai et al, Imaging Case Study of the Month 883

Fig 4. Histologic analysis. A) Densely intersect-ing spindle cells and myoid cells (H & E, origi-nal ×40). B) Rhabdomyoblasts (strongly des-min-positive) are clustered in focal areas of tu-mor (desmin stain, original ×20).

disease 27 months after treatment. The other 3 pa-tients underwent a more radical surgical approach,but 2 of them experienced a locoregional recurrencethat was controlled by rescue surgery. The 3 patientswere free of disease 8, 21, and 22 years after sur-gery. It is noteworthy that no case involving the sino-nasal tract, including ours, was associated with NF-1 or displayed histologic features of high aggressive-ness.

The endoscopic and radiologic appearance of MTTdid not differ significantly from that of other malig-nancies of the sinonasal tract. In the present case,only the finding on the CT scan of a marked and ir-regular bony thickening of the ethmoid septa andmiddle turbinate was peculiar, and it could suggest adiagnosis of osteogenic sarcoma. As with any othermass involving the nose and paranasal sinus, MRI isindeed the radiologic examination of choice, becauseit has the advantage over CT of allowing a multipla-

nar evaluation of the lesion, a better differentiationof neoplastic tissue from inflammatory changes, anda superior delineation of the relationship between themass and some important adjacent structures (ie, or-bit, dura, internal carotid artery).37

The prognosis of MTT has been analyzed by sev-eral authors,6,9 who found that the tumor is more ag-gressive than malignant peripheral nerve sheath tu-mors, with 5-year crude and specific survival ratesof 11% and 26%, respectively. Yakulis et al9 alsolooked at the impact on the survival rate of differentvariables such as location of the tumor, age, sex, andassociation with NF-1 by means of a Cox regressionanalysis. Lesions that occurred in the upper extremi-ties, lower extremities, and head and neck had a bet-ter outcome than those that arose in the retroperito-neum, buttocks, or trunk. The observation is sup-ported by a recent study of Victoria et al,12 who con-fined their review to head and neck patients and found

884 Nicolai et al, Imaging Case Study of the Month 884

TABLE 2. MALIGNANT TRITON TUMOR OF SINONASAL TRACT: REVIEW OF LITERATURE

Age SymptomsStudy (y) Sex NF-1 Site and Signs Treatment Re-treatment Outcome

Shajrawi et al34 75 M No Left max- Left epistaxis Debulking Removal of local Alive without(1989) illary, eth- and RT recurrence through evidence of disease,

moid, and Caldwell-Luc 6 mo aftersphenoid procedure, 36 mo re-treatmentsinuses

Bhatt et al35 66 F No Left nasal Left nasal Excision Alive without(1991) cavity, obstruction, through symptoms but with

ethmoid epistaxis extended CT evidence ofsinus, and external eth- tumor regrowth inorbit moidectomy posterior ethmoid,

27 moHeffner and Gnepp36 64 M No Left nasal Incomplete Dead of local recur-

(1992) cavity excision rence and pulmo-nary metastases,26 mo

58 M No Nasal Nasal Surgery Alive withoutcavity obstruction and RT evidence of disease,

48 mo56 F No Left nasal Nasal Local Removal of Alive without

cavity obstruction excision local recurrences evidence of disease,through fronto- 7 y after lastethmoidectomy, treatment11 and 15 y

59 M No Right nasal Epistaxis Transpalatal Alive withoutcavity excision evidence of disease,

and RT 7 y43 M No Right nasal Nasal Not known Recurrence (no Alive without

cavity obstruction information on evidence of disease,treatment), 15 y 7 y after

recurrencePresent case 81 F No Right nasal Nasal Endoscopic Alive without

cavity, obstruction excision evidence of disease,ethmoid 36 mosinus

NF-1 — neurofibromatosis type 1, RT — radiotherapy, CT — computed tomography.

a 26% overall 5-year survival rate. Even though mostof the authors emphasize the negative impact of theassociation with NF-1 on MTT prognosis,6,24 the con-cept was not confirmed by the statistical analysis madeby Yakulis et al.9 The rarity of the disease in the si-nonasal tract prevents us from drawing meaningfulconclusions on the prognosis. However, it is note-worthy that 6 of the 8 documented patients (Table 2)were alive without evidence of disease even after along follow-up.

It is always difficult to speculate on treatmentguidelines when dealing with a rare disease. How-ever, as with any other sarcoma, resection of the tu-mor with a wide margin followed by radiotherapy isgenerally recommended, and the role of chemother-apy has not yet been clearly defined.12 In the sino-nasal tract, treatment planning should be made ac-cording to tumor extent, involvement of vital struc-tures, histologic aggressiveness of the lesion, and pa-tient profile. In the case herein reported, the pres-

ence of an erosion of the anterior skull base and thelarge volume of the tumor suggested a craniofacialresection as the first-option treatment. However, thelow mitotic index of the tumor, the age of the pa-tient, and her desire for a less invasive procedure,together with our experience in the endoscopic treat-ment of selected benign and low-grade malignanttumors of the sinonasal tract and nasopharynx,prompted us to consider endoscopic removal as a sec-ond choice. Originally described in the late 1970s forthe treatment of inflammatory diseases of the sino-nasal tract,38 endonasal surgery with the help of rigidendoscopes or a microscope has expanded its indi-cations to include the treatment of inverted papillo-ma,39-44 juvenile angiofibroma,45-47 and selected ma-lignant lesions.47 In our experience, endoscopic sur-gery enables en bloc removal of small and medium-sized lesions. In larger tumors, particularly if malig-nant, debulking is first needed to expose the area inwhich the tumor arises and to judge the degree ofinvolvement of some critical areas, such as the lamina

885 Nicolai et al, Imaging Case Study of the Month 885

papyracea and the skull base, which may necessitateconversion to an external procedure. Magnificationand the close view of structures offered by rigid endo-scopes help to differentiate normal and diseased tis-sues, as well as to identify the relevant surgical land-marks, even those distorted by the pathological pro-cess. As with any surgical procedure performed fora tumor, the radicality of the resection should be eval-uated by multiple frozen sections. Furthermore, fre-quent endoscopic and radiologic follow-up evalua-tions are mandatory for early detection and conse-quent treatment of a recurrent tumor.

In conclusion, we have reported the eighth case of

MTT of the sinonasal tract, a rare disease that otolar-yngologists should be aware of and that must be in-cluded in the differential diagnosis of malignant le-sions involving the sinonasal tract. Clinical and radio-logic pretherapeutic evaluation is directed not onlyat defining the extent of the disease, but also at iden-tifying a possible association with NF-1. Although,in the present case, endoscopic surgery enabled a goodoncological result with minimal morbidity and a shorthospitalization, more extensive experience based ona large number of patients with adequate follow-upis certainly required to properly define the possibili-ties and limitations of endoscopic surgery in the treat-ment of neoplastic lesions of the sinonasal tract.

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