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@I 1990 The Japanese Society of Pathology

Malignant Schwannoma Arising in the Intracranial Trigeminal Nerve A Report of an Autopsy Case and a Review of the Literature

Yasushi Horie', Seiji Akagi', Kohji Taguchi', Tadashi Yoshino2, Kazuhiko Hayashi2, Kiyoshi Takahashi2, and Tadaatsu Akagi2

An autopsy case of malignant schwannoma arising in the intracranial trigeminal nerve is reported. The tumor involved the right cerebellopontine angle of the brain stem in an 18-year-old man. The spindle-shaped tumor cells with eosinophilic cytoplasm proliferated in fascicles and exhibited hypercellularity, pleomorphisrn, increased mitotic activity and invasive growth. Ultrastructurally, inter- digitating cytoplasmic processes and a few fragmented basal lamina-like structures were observed. lrnmunohis- tochemically, some tumor cells were reactive with conven- tional anti-S-100 protein antibody, but negative for p subunit. Most tumor cells were positive for LY subunit of S-100 protein. This is the eighth reported case of malig- nant schwannoma arising in the intracranial trigeminal nerve. Acta Pathol Jpn 40: 219-225, 1990.

We report a case of malignant schwannoma of the intracranial trigeminal nerve and discuss its clinical course and histological findings. The English literature is also reviewed.

CASEREPORT

An 18-year-old man complained of numbness on the right side of the face in March, 1985. He was admitted to the Department of Neurosurgery, Okayama University Hospital, in May, 1985. The family history showed no evidence of von Recklinghausen's disease. Neuro- physiological examinations revealed olfactory distur- bance, bleeding of the optic disc, diplopia, gustatory

Key words : Malignant schwannoma, intracranial neoplasm, lmmunohistochemistry, S-100 protein

INTRODUCTION

Benign trigeminal schwannomas are rare tumors, com- prising only 0.2-0.4% of all intracranial neoplasms and 2-3% of all intracranial primary schwannomas (1-4). About 200 cases have been reported in the English literature. The majority of cases develop at the Gasser- ian ganglion (3). Malignant schwannomas arising in the intracranial trigeminal nerve are even rarer, and so far only 7 case reports have appeared since Cuneo et a/. reported the first case in 1952 (5-9). Received September 9, 1989. Accepted for publication December 4, 1989. 'Department of Pathology, Okayama University Hospital, Okayama. 3econd Department of Pathology, Okayama University Medical School, Okayama. Mailing address: Yasushi Horie, (%$I a), Department of Figure 1. Postcontrast CT scan. A large well demarcated Pathology, Okayama University Hospital, 2-5-1 Shikata-cho, high-density area is seen a t the right cerebellopontine angle. Okayama 700, Japan. The tumor showed almost homogeneous enhancement.

220 Malignant lntracranial Trigeminal Schwannoma (Horie et a/.)

disturbance, and hearing loss on the right side. Cerebel- lar ataxia and left -sided hemiparesis were also found. A CT scan showed a well demarcated high-density area in the posterior fossa at the right cerebellopontine angle (Fig. 1). The lesion showed almost homogeneous en- hancement. Cerebral angiography revealed hypovas- cularity and mass effect sign, although no tumor stain was observed. Immediately after admission, the patient’s consciousness level deteriorated progressively, and bila tera I su bocci pita1 cra niectomy was performed. A red- brown tumor was located at the right root of the intracranial trigeminal nerve, and was fed by the right anterior intercerebra I communicating artery. During surgery, bleeding from the tumor continued, and swelling of the cerebellar hemispheres occurred. Partial removal of the tumor, cerebellar hemispherectomy, and external

Figure 2. a. Macroscopic view of the base of the brain a t autopsy. A large, ill-bor- dered mass occupies the right cerebel- lopontine angle. b. Sagittal aspect of the left brain viewed from the right side. Note intraventricular bleeding and hematoma formation in the cerebellar area.

decompression were performed. After the operation, the patient remained in a deep coma, and subsequently died due to re-bleeding of the tumor in July, 1985.

At autopsy, the brain was swollen, soft and heavy, weighing 1,950 g. Diffuse intraventricular bleeding and hematoma formation in the cerebellar hemisphere were noted (Figs. 2a, b). The tumor was located at the right cerebellopontine angle and showed marked hemorrhage and necrosis. It had invaded the brain stem, making the border unclear. Tumor invasion into the right Gasserian ganglion was visible macroscopically. The left Gasseri- an ganglion was intact and spared. No invasion into the skull was found. Examination of organs other than the brain was not allowed.

Acta Pathologica Japonica 40 (3) : 1990 22 1

Figure3. a. Microscopic features of the autopsy specimens taken from the right trigeminal nerve root area. Spindle-shaped tumor cells with elongated and hyper- chromatic nuclei proliferate, forming vague fascicles. HE. b. Tumor cells showing pleomorphism. HE. c. High-power view of the tumor cells. A mitotic figure is seen (arrow). HE. d. Tumor cells invading the trigeminal ganglion region. Non-neoplastic ganglion cells (arrows) are seen among the infiltrating tumor cells. HE.

222 Malignant lntracranial Trigeminal Schwannoma (Horie et a/.)

MATERIALS AND METHODS

Both the surgical and autopsy specimens were examined by light and electron microscopy and immuno- histochemistry. For light microscopy, specimens were stained with hematoxylin-eosin (HE). For electron microscopy, materials were fixed in buffered 2.5% glutar- aldehyde, post fixed in 1% osmium tetroxide, and embed- ded in epoxy resin. Ultrathin sections were examined according to the conventional method. For immunohis- tochemist ry, 1 0% buffered f ormalin-fixed, pa raff i n-em- bedded materials were stained by the peroxidase-antiper- oxidase (PAP) method using rabbit antibodies against S- 100 protein (1 : loo), LY or p subunit of S--100 protein (20/1g/ml) or glial fibrillary acidic protein (GFAP) (1 : loo), or by the avidin-biotin-peroxidase complex (ABC) method using monoclonal antibodies against Leu 7 (1 : 20) and myelin basic protein (MBP) (1 : 100). Rabbit antibodies against S-100 protein and GFAP and a monoclonal antibody against MBP were purchased from DAKO Co., Denmark, and a monoclonal antibody against Leu 7 was obtained from Becton Dickinson, USA.

Affinity-purified rabbit antibodies monospecific for the S-- 1 0 0 ~ ~ or p subunit were prepared as described previously (10).

PATHOLOGIC EXAMINATION OF THE TUMOR

1. Histological findings

There was no difference in histology between the surgi- cal and autopsy materials. The tumor showed an inter- weaving fascicular pattern of spindle-shaped tumor cells with elongated and hyperchromatic nuclei and slightly eosinophilic cytoplasms (Figs. 3a-c). Hypercellularity, pleomorphism, and increased mitotic activity (1 -3/10 high-power fields) were observed. No tendency of nuclear palisading, like that in Antoni type A schwan- nomas, or other findings suggestive of benign schwan- noma were observed. In the right Gasserian ganglion, the tumor cells had invaded around the remaining non- neoplastic ganglion cells (Fig. 3d).

li

b

Figure 4. a. Most of the tumor cells are positive for S-100a subunit. PAP stain. b. In the lower field, none of the tumor cells are positive for S--1OOp subunit, while normal nerve sheath cells are positive in the upper field. PAP stain.

Acta Pathologica Japonica 40 (3): 1990 223

2. lmmunohistochemical f indings

Some tumor cells were reactive with the conventional anti-S-100 protein antibody, but all were totally nega- tive for p subunit (Figs. 4a, b). Most of the tumor cells were positive for the LY subunit of S-100 protein, but none were positive for Leu 7, MBP or GFAP.

3. The ultrastructure of both the surgical and autopsy

materials was poorly preserved because of massive necrosis, and therefore the electron micrographs were obscured by artifacts. The nuclei of the tumor cells were slightly irregular and had 1-2 nucleoli and a moder- ate amount of heterochromatin. In the cytoplasm, lysosomes, rough endoplasmic reticulum, and pinocytotic vesicles were seen. Intermediate-sized filaments (9-1 0 nm) were also detected in the cytoplasm. Between the cells, interdigitating cytoplasmic processes were well developed, and a few primitive junctions were found. Some fragmented basal lamina-like structures were partially noted. In the stroma, collagen fibers were scattered among the tumor cells.

Electron microscopic findings (Fig. 5)

DISCUSSION

Most intracra nia I t rigeminal schwannomas a re benign

Figure 5. Electron microscopic view of the tumor cells. Note abundant interdigitating cytoplas- mic processes. Fragmented basal lamina-like structures are seen occasionally (arrow). B a r = l pm.

(1-4). Up to now, there have been only 7 reported cases of intracranial trigeminal malignant schwannoma (5-9) (Table 1). The age distribution of the patients ranged from 18 to 67 (average 48) years, the present patient being the youngest. None of the reported patients had von Recklinghausen’s disease. On the other hand, malignant schwannomas arising in peripheral branches of the extracranial trigeminal nerve are also very rare, about 20 cases having been reported in the English l iterature (1 1, 12). Moreover, malignant schwannomas arising in other intracranial nerves and the cerebrum have been reported, although they are extreme- ly rare( l3 , 14).

The nomenclature and histogenesis of malignant schwannoma is still controversial, and the terms used previously to describe this entity have included malig- nant neurofibroma, neurifibrosarcoma, neurosarcoma, neurogenic sarcoma, malignant neurilemmoma, and malignant nerve sheath tumor. In this report, we have chosen to use the term “malignant schwannoma” accord- ing to the choice of Enzinger et a/. (15).

I t is well known that malignant schwannomas are closely associated with von Recklinghausen’s disease. However, it is interesting that all reported cases of intra- cranial trigeminal malignant schwannomas were not associated with this disease. There is general agree- ment that malignant schwannomas arise either de novo or through malignant transformation of pre-existing

224 Malignant lntracranial Trigeminal Schwannoma (Horie et a/.)

Table 1. Cases of Malignant lntracranial Trigeminal Schwannoma

Patient Case

Age Sex

1

2

3

4a

5

6

7

8

Surgery Radiotherapy Outcome (Follow up period)

37 male subtotal removal

53 male subtotal removal

50 male transnasal biopsy

49 male subtotal removal

61 male subtotal removal

67 female complete removal

49 male transnasal biopsy

18 male subtotal removal

none

51.75 Gy

54 Gy

66 Gy

60 Gy

none

60 Gy

none

-

None of the patients had von Recklinghausen’s disease. a Bilateral case of “trigeminal neurofibrosarcoma”.

benign neurofibromas or schwannomas, although the latter cases are very rare (13, 15, 16). The present case could be considered a de novo malignant schwan- noma because no histologic features suggestive of apparently benign schwannoma were noted.

Light microscopic features of malignant schwannoma are characterized by (a) high cellularity, (b) pleomor- phism, (c) increase of mitotic figures, (d) presence of necrosis and (e) presence of histological invasion (15, 17). However, there are some cases that are difficult to classify as benign or malignant even if pathologists consider these histologic features. Especially, it should be borne in mind that (a) and (b) are frequently seen in benign schwannoma, typically in the so-called ancient type. The present case was definitely malignant because the histological features were compatible with all items (a)-(e). Electron microscopic features sugges- t ive of Schwannian cell origin are interdigitating cyto- plasmic processes, scanty intercellular junctions, focal basal lamina, and interstitial collagen fibers (18-20), which were also observed in the present case. The im- munohistochemical markers of schwannoma have been studied by many pathologists. These include S-100 protein, Leu 7 and MBP (21-25). In particular, there have been many studies on the S-100 protein positivity of malignant schwannoma, revealing that about 50- 70% of malignant schwannomas are positive for S-100 protein (1 5, 20, 21) although it has often been difficult to obtain a definite result. In the present case, only a few tumor cells were positive for S-100 protein. Moreover,

alive 3 months alive 18 months alive 14 months died 4 years alive 10 months died of probable post operative sepsis 1 month alive not described died 2 months

Authors

-

Cuneo and Rand (5)

Hedeman et a/. (6)

Hedeman et a/. (6)

Liwnicz (7)

Levy et a/. (8)

Levy et a/. (8)

Maroun et a/. (9)

Present case

almost all of the tumor cells were positive for S-100a subunit and negative for S-loop subunit. The remain- ing normal nerve sheath cells in the trigeminal root part of the tumor were positive for S-100 protein and S- l oop subunit, and were negative for S - 1 0 0 ~ subunit. There have been no definite opinions as to the positivity of malignant schwannoma cells for S-1 00 protein subunits. Hayashi et a/. reported that in 4 cases of malignant schwannoma associated with von Reckling- hausen’s disease the tumor cells were immunohisto- chemically positive for Q subunit but negative for p subunit, whereas Schwann cells in normal nerves and neurofibromas were positive for S-loop subunit (25). The significance of reverse expression of S-100 protein subunits in malignant schwannomas still remains to be clarified, although the present result is in line wi th Haya- shi’s report.

Acknowledgements : The authors wish to thank Prof. Katsuo Ogawa, Second Department of Pathology, Okayama Univer- sity Medical School, for his advice, and Mr. Seiji Awai, Okayama University Hospital, for technical assistance.

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