Graefes Archiv Ophthalmologie

Albrecht v. GraefesArch. klin. exp. Ophthal. 207, 181-188 (1978)

for kllnische und experimentelle

9 by Springer-Verlag 1978

Granular Cell Tumor of the Optic Nerve W. Mtfller* and H.G. Dahmen Department of Pathology,Universityof Cologne(Director: Prof. Dr. R. Fischer),Joseph-StelzmannStr. 9, D-5000 K61n41, FederalRepublicof Germany

Summary.A case of a combined neurofibroma-granular cell tumor is presented. The tumor had developed in the left middle cranial fossa after an intracranial trigeminal nerve operation 23 years before. It had displaced and infiltrated the temporal lobe and expanded probably via the fissura orbitalis into the orbit. The thickened optic nerve revealed a marked widening of the subdural fissure by typical granular cells. The cufflike tumor cell aggregation in the subdural fissure had compressed the optic fascicle, thereby inducing a demyelinisation and axonal degeneration. A reactive gliosis in the optic fascicle masks the typical pattern of the optic nerve atrophy. The gangliocytes of the third retinal neuron are atrophic and replaced by reactively proliferated fibrillary astrocytes. A short review of the literature and theories concerning histogenesis of the granular cell tumor (neurogenic or mesodermal) is given. An intermediary type of neurofibromatous and granular cells which we found motivates us to agree with a mesodermal origin. Zusammenfassung. Es wird fiber eine kombinierte Geschwulst, Neurofibrom mit Granularzell Tumor, berichtet. Der Tumor hatte sich 23 Jahre nach einer intrakraniellen Trigeminusoperation in der linken mittleren Sch/idelgrube entwickelt, den linken Temporalpol verdr~ingt und infiltriert. Er war offenbar fiber die Fissura orbitalis in die Orbita eingewachsen. Der Subduralspalt des N.opticus war durch Granularzell Tumorgewebe erweitert. Durch Kompression des Fasciculus opticus war es zu einer Demyelinisierung und Axondegeneration gekommen. Eine reaktive Gliose kaschierte das sonst fibliche Bild der Opticusatrophie. Die Ganglienzellen des dritten Neurons der Retina waren retrograd weitgehend atrophiert. An ihrer Stelle fand sich eine ausgeprfigte fibrillgre Astrogliose. Ein Literaturfiberblick zu den Theorien der Histogenese des Granularzell Tumors (neurogen oder mesodermal) wird gegeben. Ein interrnedifirer Zelltyp zwischen Neurofibrom-und Granularzellen in unserem Falle veranlagt uns, eine mesodermale Abstammung anzunehmen. CorrespondingAuthor

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Fig. 1. Cross section of the left optic nerve: a total b sector. The subdural fissure is widened by granular cell tumor tissue; the pia-arachnoidal limiting membrane shows a marked reactive thickening. The atrophy of the optic fascicle is masked by a reactive gliosis. Azan staining; photographed through a red filter (Schottfilter R G 1-2 mm)

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Fig. 2. Section of the granular cell tumor in the subdural fissure of the optic nerve. Note the typical PASpositive intracytoplasmatic granules. PAS-reaction

Fig. 3. Reactive gliosis of the optic nerve with retraction balls. Left: silver impregnation according to Palmgren; right: PAS-reaction

Since the first description o f a granular cell t u m o r by Abrikossoff(1926), who called the t u m o r M y o b l a s t e n m y o m , the histogenesis (neurogenic or mesodermal) remained unclear in spite o f increasing numbers o f case reports and electron microscopic studies. We were able to explore a t u m o r o f the middle cranial fossa that had developed after an intracranial trigeminal nerve operation 23 years before. It is c o m p o s e d o f a n e u r o f i b r o m a part and a granular cell tumor. The granular cell t u m o r part had invaded the left temporal lobe; furthermore it had expanded via the fissura orbitalis into the orbit and infiltrated the optic nerve ibidem.

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Fig. 4. Section of the optic nerve. A distinct reactive gliosis and a plentiful diffuse infiltration with lymphocytes is visible. H.E.

As far as we know granular cell tumors of the eye region up to now have only been found in the lacrimal sac, the upper orbit, and the lid (yon Bahr, 1938; Cristini, 1946; Dunnington, 1948).

Case Report In 1953 the 52-year-old gunsmith fell ill with a trigeminal neuralgia. At that time and once more in 1970 a trigeminal operation was necessary. After the second operation a progressive left-sided deafness and loss of sight accompanied by speech defect developed. In January 1976 he was admitted to the Neurosurgical Department of the University Clinic of Cologne.

Hospital Findings. Left-sided blindness with atrophy of the optic nerve, ophthalmoplegia, and lack of corneal reflex.

Clinical Diagnosis. Obviously, a tumor of the cerebellopontine angle. Shortly before the operation the patient died of cerebral dysregulation with central cardiac and circulatory failure. Pathologic Findings Brain Dissection. Marked signs of intracranial hypertension. Bilateral cerebellar pressure cone. Large solid tumor infiltrating the surface of the left temporal lobe with marked edema and mass-shifting. Dissection of the skull: solid tumor in the left middle cranial fossa which had displaced and infiltrated the temporal lobe and upper pontine parts. Tumor expansion via the left fissura orbitalis into the orbit.

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Fig, 5, Longitudinal section of the optic nerve and the papilla. The central retinal vessels look inconspicuous. Azan staining; photographed through a red filter (Schottfilter RG 1-2 mm)

Histologic Findings The neurofibroma part in the left middle cranial fossa shows histological aspects of malignancy; the granular cell tumor with regard to its invasive growth can be also called malignant. In intermingling parts of the tumor transitional types of fiberlike and granular cells catch the eye. The temporal brain tissue next to the tumor shows both diffuse lymphocyte infiltration and reactively proliferated partly polynuclear astrocytes with the occasional phenomenon of lymphocyte emperipolesis1. The left orbit shows as well solid parts of the neurofibroma as infiltration of the adipose tissue by tumor cells. Macroscopically the optic nerve was thickened. In connection with the posterior bulb the optic nerve was examined in cross and longitudinal sections. The cross section (Fig. 1) already reveals a marked widening of the subdural fissure by granular cells. The granular cells have various size and acidophilic or PASpositive granules (Fig. 2). Sporadic mitoses are observed. The cross section furthermore shows a reactive These findings are subject of another detailed publication (in press)

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Fig. 6. Leptomeningeal vessels radiating into the nerve surrounded by tumor cells. PAS-reaction

Fig. 7. Retina with marked reactive gliosis of fibrillary astrocytes. Iron-hematoxylin according to Haidenhein

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fibrosis and thickening of the pia-arachnoidal limiting membrane which is also infiltrated by tumor cells. The peripheral region of the lamina cribrosa nervi optici has a sparse content ofmyelinated nerve fibers which disappears completely in the more proximal part of the nerve. Sections with silver impregnation show a total loss of axons. As a further sign of nerve fiber degeneration scattering so-called retraction balls are observed (Fig. 3). A remarkable reactive gliosis strikes the eye. The nuclei of the glia cells are of various sizes (Fig. 4). The iron-hematoxylin staining according to Heidenhain makes visible sporadic thick glia fibers. Furthermore the tissue is intermingled with plenty of lymphatic cells which sometimes form perivascutar infiltrations. The longitudinal section of the optic nerve (Fig. 5) makes it evident that the tumor infiltration of the subdural fissure varies in extent. Furthermore we want to point out the finding of an edema of the subdural fissure in the cone right next to the lamina cribrosa. The granular cells surround the radiating leptomeningeal vessels like cuffs (Fig. 6). Single tumor cells are found in the adjacent glial tissue. The examination of the retina shows an almost complete atrophy of the third neuron. Instead of the gangliocytes a marked reactive gliosis of fibrillary astrocytes strikes the eye (Fig. 7).

Discussion Until t o d a y the histogenesis o f granular cell t u m o r has remained unclear. Whereas Ule et al. (1975) suppose on the basis o f electron microscopic and histochemical results that granular cell tumors originate from various types o f cells, Fisher and Wechsler (1962), Probst and Weiser (1971), Sobel et al. (1971), Markesbery et al. (1973) and R o s e n b l o o m et al. (1975) are o f the opinion that the granular cells derive from Schwann cells and so are neurogenic. On the contrary Pearse (1950), Azzopardi (1956), and M o s c o v i c and A z a r (1967) think that the origin o f this t u m o r is mesodermal. In our case the intermediary type o f n e u r o f i b r o m a t o u s and granular cells we found motivates us to agree with such a mesodermal origin. The present t u m o r developed in the middle cranial fossa, possibly as a consequence o f two trigeminal operations 23 and 6 years before. It is obvious that the t u m o r penetrated via the fissura orbitalis into the orbit where the adipose tissue shows a t u m o r o u s invasion. The massive extension o f the t u m o r in the subdural fissure o f the optic nerve p r o b a b l y depends on - so to speak - h e m a t o g e n metastasizing f r o m the orbit via vessels radiating into the optic nerve. A n infiltration coming from the hypophyseal region which was almost completely replaced by t u m o r c a n n o t be excluded either. The cufflike t u m o r cell aggregation in the subduraI fissure and the resulting compression o f the optic fascicle had caused a demyelinization and axonal degeneration. A n a t r o p h y o f retinal gangliocytes (third neuron) accompanied by a distinct astrogliosis was a further consequence. A reactive gliosis with nuclear p o l y m o r p h i a and sporadic fiber production was also observed in the optic fascicle. This proliferation o f glia cells masks the typical pattern o f the optic nerve a t r o p h y and corresponds to the finding in the infiltrated temporal brain. Here and there one can suppose that the granular cells have simulated the proliferation o f glia cells. This idea is supported by an observation o f K e r n a n and C r a c o v a n e r (1935). They described a tesselated epithelial proliferation above a granular cell t u m o r o f the vocal cord, imitating a carcinoma. The intracytoplasmatic occurrence o f lymphocytes in astrocytes (emperipolesis) seen in the temporal brain was not f o u n d in the optic nerve. A lymphocytic infiltration in the absence o f an inflammatory substrate is remarkable however. A n i m m u n o r e a c t i o n would be a plausible interpretation indeed.

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References Abrikossoff, A.: ()ber Myome, ausgehend vonder quergestreiften willkiirlichen Muskulatur. Virchows Arch. path. Anat. 260, 215533 (1926) Azzopardi, J.G.: Histogenesis of the granular-cell myoblastoma. J. Path. Bact. 71, 85-94 (1956) Bahr, G. v.: A case of myoblastic myoma of the lacrimal sac. Acta Ophthmol. 16, 109-115 (1938) Cristini, G.: Mioblastoma della palpebra (Studio anatomo-clinico). Rassegna ital. d'ottal. 15, 207-223 (1946) Dunnington, J.H.: Granular cell myoblastoma of the orbit. Arch. Ophthmol. 40, 14-22 (1948) Fisher, E.R., Wechsler, H.: Granular cell myoblastoma - a misnomer. Cancer (Philad.) 15, 936-954 (1962) Kernan, J.D., Crancovaner, A.J.: Rhabdomyoma of the vocal cord - report of a case. Laryngoscope 45, 891-893 (1935) Markesbery, W.R., Duffy, P.E., Cowen, D.: Granular cell tumors of the central nervous system. J. Neuropath. exp. Neurol. 32, 92-109 (1973) Moscovic, E.A., Azar, H.: Multiple granular cell tumors ("myoblastoma"). Case report with EM observation and review of literature. Cancer 20, 2032-2047 (1967) Pearse, A.G.E.: Histogenesis of granular-cell myoblastoma (? granular-cell perineural fibroblastoma). J. Path. Bact. 62, 351-362 (1950) Probst, A., Weiser, G.: Das Granulgre Neurom Feyrters. Wien. klin. Wschr. 83, 31-33 (1971) Rosenbloom, P.M., Barrows, G.H., Kmetz, D.R., Canty, T.G.: Granular cell myoblastoma arising from the thoracic sympathetic nerve chain. J. Pediatr. Surg. 10, 819-822 (1975) Sobel, H.J., Marquet, E., Avrin, E., Schwarz, R.: Granular cell myoblastom. Am. J. Path. 65, 50-71 (1971) Ule, G., Tschahargane, C., Haag, D., Berlet, H., Volk, B.: Maligner Granularzelltumor des Grol3hirnmarks. Morphologische cytophotometrische und neurochemische Befunde. Acta Neuropathol. 32, 143-155 (1975)

Received May 24, 1978

Granular cell tumor of the optic nerve.

Graefes Archiv Ophthalmologie Albrecht v. GraefesArch. klin. exp. Ophthal. 207, 181-188 (1978) for kllnische und experimentelle 9 by Springer-Verla...
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