mesectodermal leiomyoma of the ciliarybody

British Journal of Ophthalmology, 1989, 73, 12-18

Mesectodermal leiomyoma of the ciliary body:case reportVALERIE WHITE,' KATHERINE STEVENSON2, ALEC GARNER,'AND JOHN HUNGERFORD2

From the 'Department ofPathology, Institute ofOphthalmology, 17125 Cayton Street, London EC]V9A T, and2Moorfields Eye Hospital, City Road, London EC]V2PD

SUMMARY The clinical, light microscopical, and electron microscopical features of a mesecto-dermal leiomyoma of the ciliary body are presented. This exceptionally rare and apparently benigntumour is considered to be of neural crest origin. In the case described the tumour cells were seen tocontain thin filaments with focal densities and conspicuous numbers of mitochondria, and smoothmuscle protein was demonstrated by immunohistochemical means.

Smooth muscle tumours of the ciliary body areextremely rare. In 1977 and 1978 Jakobiec et al.reported three cases of an unusual 'hybrid' smoothmuscle and neuroectodermal tumour of the ciliarybody.'2 They proposed that the unusual neuralappearance of this smooth muscle tumour reflectedits origin from the neural crest cells that contribute tothe formation of bone, cartilage, connective tissue,and smooth muscle in the head and neck region.These neural crest derived tissues have been termed'mesectoderm', and hence the terminology ofJakobiec et al. for the ciliary body tumour- amesectodermal leiomyoma. The present report con-cerns a fourth example of this highly unusual tumourand highlights some histopathological differencesfrom the previously published cases.

Case report

HISTORY AND CLINICAL COURSEA previously fit 38-year-old male teacher was noticedto have an apparent iris tumour on routine visit to anoptician. Corrected visual acuity was 6/12 right eye,6/5 left eye. On closer inspection the tumour was seento be whitish, with overlying blood vessels, andappeared to be located within the ciliary body at 5 to 6o'clock with some displacement of the iris rootadjacent to its anterior edge (Fig. 1). The tumour did

Correspondence to Professor Alec Garner.12

not invade the angle but pushed against the lens.There was no cataract and the intraocular pressurewas normal. Fundus examination after full mydriasisshowed a rather more pigmented, ciliary bodytumour but no serous retinal detachment. The lefteye was normal. An ultrasound examination of theright eye was suggestive of a malignant melanoma ofthe ciliary body, but the overall clinical appearancewas atypical of this tumour. General physical exami-nation and laboratory investigations were normal.

In December 1986, four months after the tumourwas first noticed, the patient underwent an irido-cyclectomy, with excision of a clear margin of normalciliary body and iris surrounding the tumour. Thepostoperative course was uneventful and the patienthad 6/12 vision five months after surgery.

PATHOLOGYThe specimen was received in formalin fixative andconsisted of a sector of the ciliary body whichcontained a firm ovoid and whitish tumour measuring8x7x5 mm.

Light microscopy. Low power examination ofhaematoxylin and eosin stained sections revealed awell circumscribed tumour of the ciliary body whichwas situated where the normal ciliary muscle wouldhave been (Fig. 2). It was covered on one surface bythe pigmented and non-pigmented ciliary epitheliumand blended with normal ciliary muscle on anothersurface. The tumour consisted of sheets of polygonal

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Mesectodermal leiomyoma ofthe ciliary body: case report

Fig. 1 Clinicalphotograph ofpatient's right eye showingvascularised, whitish tumourimpinging on and displacing theinferior iris.

cells which tended to become fusiform at theperiphery (Fig. 3). The nuclei were central, oftenwith prominent nucleoli, but there were no mitoses.The cytoplasm was abundant and eosinophilic, andwhereas in some areas it had an irregular hyalineappearance, in others it appeared more fibrillary(Fig. 4). Large numbers of mast cells were scatteredthroughout the tumour. There was no staining of thetumour cells by the periodic acid-Schiff (PAS) tech-nique, although PAS positive material was presentaround many cells. Reticulin staining outlined manycells individually (Fig. 5a). Phosphotungstic acid-haematoxylin (PTAH) and Masson-trichrome stainsrevealed a few longitudinally orientated fibrils withinthe more peripherally placed spindle cells. AFontana-Masson stain for melanin was negative

within the tumour. Azure-A staining highlighted thenumerous mast cells (Fig. 5b).

Immunohistochemistry. Staining for cytokeratin,glial fibrillary acidic protein (GFAP), S100 protein,and desmin was carried out by a standard three-stageimmunoperoxidase technique. There was no stainingfor cytokeratin and GFAP. Staining for S100 proteinwas present in the overlying neuroepithelium andmelanocytes trapped within the ciliary muscle, butwas absent within the tumour. Antiserum againstdesmin reacted positively with both the normalciliary muscle and the tumour cells.

Transmission electron microscopy. Low powermagnification revealed angular and polygonal cells,many with blunt, irregular processes (Fig. 6a). Bloodvessels were scanty, but numerous mast cells were

Fig. 2 Low powerphotomicrograph to showplacement oftumour where normalciliary muscle would have been. It iscovered by normal ciliaryepithelium and blends into thesurrounding ciliary smooth muscle.

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HandE, x15-5.

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Valerie White, Katherine Stevenson, Alec Garner, andJohn Hungerford

Fig. 3 Cells ofthe tumour arepolygonal centrally, but tending tobecome fusiform at the periphery.Hand E, x120.

visible. Nuclei were pale with small clumps ofheterochromatin and prominent nucleoli (Fig.6b). The cytoplasm was about equally filled withabundant mitochondria and longitudinally placedthin filaments (Fig. 6c). The mitochondria were oftendensely packed and abnormally shaped, with occa-sional tubular forms (Figs. 7a and b), while the thin

Fig. 4 The nuclei are round, oftenwith prominent nucleoli.Cytoplasm is abundant,eosinophilic and hyaline in someareas, whilefibrillary in others.HandE, x450).

filaments measured 4-8 nm in diameter and con-tained irregularly placed focal densities (Fig. 7c).Only occasional Golgi bodies and endoplasmicreticulum were present. One cilium was seen. Eachcell was surrounded by an external lamina which wasfocally interrupted and focally duplicated. Occa-sional poorly formed junctions were present (Fig.

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Mesectodermal leiomyoma ofthe ciliary body: case report

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Fig. 5 a: Reticulin outlining ofindividual cells. Reticulin stain,throughout the tumour. Azure-A, x450).

6d). No melanosomes, neurotubules, neuronalwrappings, dense core granules, well-formeddesmosomes, or pinocytotic vesicles were seen.

Discussion

Light microscopic differential diagnosis of thisunusual tumour included epithelioid leiomyoma,amelanotic naevus or well differentiated melanoma,peripheral nerve tumour, paraganglioma orhaemangiopericytoma. The diagnosis of a type ofleiomyoma was supported by the electron micro-scopic demonstration of thin filaments with focaldensities and the merging of the tumour with thenormal musculature of the ciliary body. The demon-stration of desmin by immunohistochemistry con-stituted further evidence of a muscle tumour. Theconspicuously numerous mitochondria raised thepossibility of an oncocytoma, but this was notconsidered to be substantiated either by the positionof the tumour below the ciliary epithelium, within theciliary muscle, or by the lack of epithelial featuressuch as tight junctions and well formed desmosomeson electron microscopy.

In 1977 Jakobiec et al. described two cases of an

I

x 450. b: Large numbers ofmast cells are scattered

unusual tumour of the ciliary body which they termeda mesectodermal leiomyoma.' The light microscopicappearances of their cases had led them to think thatthey were neural tumours, in one case of glial organglionic origin and in the other case of peripheralnerve origin. On electron microscopy they found thincytoplasmic filaments with focal fusiform densitiesand focal and multilaminated external lamina,features of smooth muscle differentiation.3 Thefibrillary appearance was given by tangled cell pro-cesses containing thin filaments with focal densities.They postulated that these 'hybrid' smooth muscleand neural tumours could develop owing to the originof most of the ocular and periocular supportingtissues from the neural crest.4 Experiments in birdshave revealed that only the external ocular musclesand vascular endothelia arise from true mesoderm,while most of the other so called 'mesodermal'tissues, including the smooth muscle of the ciliarybody, arise from the neural crest.5 In 1978 Jakobiecand Iwamoto reported a similar tumour of the ciliarybody which was associated with a naevus, furtherevidence of a neural crest origin.2 A case of presumedmesectodermal leiomyosarcoma of the antrum whichinvaded the orbit has also been reported.6

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Fig. 6 a: Low magnification electron micrograph to show angular cells with blunt irregular processes. x5000. b: Nuclei areround and pale with prominent nucleoli. x4000. c: Cytoplasm is about equally filled with thin filaments and mitochondria.x25 000. d: Focally duplicated external lamina (asterisk), andpoorly formedjunctions are present (arrow). x17 000. Barmarkers=1 -0 wn.

The light microscopic appearance of the presentcase is not suggestive of a tumour of neural origin,and the most prominent feature is the manyabnormal mitochondria. Although Jakobiec et al. in

their second case comment on numerous degener-ated mitochondria, they do not display many in thepublished electron micrograph.' Oncocytic cells inthe thyroid, which are distinguished by a cytoplasm

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Fig. 7 a: Densely packed mitochondria. x34 000. b: An abnormal appearing mitochondrion. x50 000. c: Cell processcontaining thinfilaments with scatteredfocal densities. x100000. Barmarkers= 0 1 n.

full of mitochondria, have been shown to contain organelle hyperplasia in the face of decreased cellularincreased amounts of the oxidative enzymes iso- function.7 Whether this increase in oxidativecitrate dehydrogenase, succinate dehydrogenase, enzymes occurs in smooth muscle cells is unknown.and cytochrome oxidase, and are thought to reflect The similarities between the present case and those

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previously reported override the differences andinclude the round pale nuclei with prominentnucleoli, eosinophilic fibrillary background, blendingof the tumour into the normal ciliary muscle,numerous mast cells, cytoplasmic fibrils on PTAHstaining, reticulin outlining of single cells, and thethin cytoplasmic filaments with focal densities seenon electron microscopy. Micropinocytotic vesicles, ausual feature of smooth muscle cells, may be absentas in this case, and depend on the physiological stateof the cell.3Meyer et al. published the first case of a spindle cell

leiomyoma of the ciliary body to be studied byelectron microscopy.8 Light microscopic findingswere characteristic of leiomyomas seen elsewhere inthe body. Electron microscopy showed bundles ofthin filaments with focal densities orientated alongthe long axis of the cells, micropinocytotic vesicles,and external laminae. Smooth muscle tumours occur-ring in other ocular sites have been reported in thechoroid' and the orbit,'"'2 with electron microscopicverification. Although according to Green noleiomyomas of the iris have been reported includingelectron microscopic studies,'3 there is reason tobelieve that they occur.'4The present tumour was thought to be benign on

light microscopic appearance because of its circum-scription, cellular regularity, and lack of mitoticfigures. Two of the three reported cases of Jakobiec etal. have been followed up for 15 years after enuclea-tion and nine years after iridocyclectomy, with noresidual or metastatic disease.'2 Follow-up was notreported in the third case.

This case also highlights the dilemma for theclinician when faced with a patient with goodvision and a presumptive diagnosis of a malignantmelanoma. Should the patient be treated with con-servative or radical surgery? We would suggestcaution when faced with a tumour in any way atypicalon clinical examination and which is also amenable tolocal excision. In this case the rather whitish appear-ance of the tumour and the lack of any sentinel

vessels and angle involvement influenced thedecision to perform local excision.

In summary, we report a case of an extremely raretumour of the ciliary body, having features of bothneurectodermal tissue and smooth muscle. Webelieve this tumour is correctly termed a mesecto-dermal leiomyoma.

Dr Valerie White is the recipient of a fellowship award from theMedical Research Council of Canada.

References

1 Jakobiec FA, Font RL, Tso MOM, Zimmerman LE. Mesecto-dermal leiomyoma of the ciliary body. Cancer 1977; 39: 2102-13.

2 Jakobiec FA, Iwamoto T. Mesectodermal leiomyoma of theciliary body associated with a nevus. Arch Ophthalmol 1978; %:692-5.

3 Ghadially FN. Diagnostic electron microscopy of tumours. 2nded. London: Butterworths, 1985: 198-201.

4 Noden DM. Periocular mesenchyme: neural crest and meso-dermal interactions. In: Jakobiec FA, ed. Ocular anatomy,embryology and teratology. Philadelphia: Harper and Row,1982: ch. 3.

5 Johnston MC, Noden DM, Hazelton RD, Coulombre JL,Coulombre AJ. Origins of avian ocular and periocular tissues.Exp Eye Res 1979; 29: 27-43.

6 Jakobiec FA, Mitchell JP, Chauhan PM, Iwamoto T. Mesecto-dermal leimyosarcoma of the antrum and orbit. Am JOphthalmol 1978; 85: 51-7.

7 Kendall CH, McCluskey E, Naylor J, Eagles M. Oxyphil cells inthyroid disease: a uniform change? J Clin Pathol 1986; 39: 908-12.

8 Meyer SL, Fine BS, Font RL, Zimmerman LE. Leiomyoma ofthe ciliary body. Am J Ophthalmol 1968; 66: 1061-8.

9 Jakobiec FA, Witschel H, Zimmerman LE. Choroidalleiomyoma of vascular origin. Am J Ophthalmol 1976; 82:205-12.

10 Jakobiec FA, Jones IS, Tannenbaum M. Leiomyoma. Anunusual tumour of the orbit. Br J Ophthalmol 1973; 57: 825-31.

11 Jakobiec FA, Howard GM, Rosen M, Wolff M. Leiomyoma andleiomyosarcoma of the orbit. Am J Ophthalmol 1975; 80: 1028-42.

12 Sanborn GE, Valenzuela RE, Green WR. Leiomyoma of theorbit. Am J Ophthalmol 1979; 87: 371-5.

13 Green WR, Uveal tract, Tumors. In: Spencer WH, ed. Ophthal-mic pathology. Philadelphia: Saunders, 1986; 3: 1563.

14 Ashton N. Primary tumours of the iris. Br J Ophthalmol 1964;48: 650-68.

Acceptedfor publication 24 September 1987.

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