British Journal of Ophthalmology, 1987, 71, 279-284

Orbital involvement with desmoplastic melanoma*JERRY A SHIELDS,'4 DAVID ELDER,2 VIOLETTA ARBIZO,4THOMAS HEDGES,' AND JAMES J AUGSBURGER'

From the 'Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, the 'PigmentedLesion Group, Department of Dermatology and of Pathology and Laboratory Medicine, University ofPennsylvawa, the 'Department of Ophthalmology, Pennsylvania Hospital, and the 4Pathology Department,Wills Eye Hospital, USA.

SUMMARY A 79-year-old woman developed an orbital mass five and a half years after excision of acutaneous melanoma from the side of the nose. The initial orbital biopsy was interpretedhistopathologically as a malignant fibrous histiocytoma, but special stains and electron microscopyshowed it to be a desmoplastic malignant melanoma which had apparently spread to the orbit fromthe prioriskin lesion by neurotropic mechanisms. The occurrence of a desmoplastic neurotropicmelanoma in the orbit has not been previously recognised. The problems in the clinical andpathological diagnosis of this rare type of melanoma are discussed.

Orbital involvement with malignant melanoma mostoften occurs secondary to extrascleral extensionof posteribr uveal melanoma.' Primary orbitalmelanoma and metastatic cutaneous melanomato the orbit are extremely rare.2 Desmoplasticmelanoma is a rare form of cutaneous melanomawhich can extend from a superficial location into thedeep reticular dermis by neurotropic mechanisms.'4We report a unique case of desmoplastic melanomain which swgh a turnour extended from the nasal skininto the deep orbit, clinically simulating a primaryorbital tumour.

Case report

A 79-year-pld white woman was referred to theOncology Service at Wills Eye Hospital in April 1985because of a two-month history of proptosis, blephar-optosis, and blurred vision in the left eye. The patientgave a history of having had a 'basal cell carcinoma'removed from the left side of her nose in December1979, followed by a repeat biopsy and a definitivewide surgical excision. She was subsequentlyinvolved in an automobile accident and sufferedfractures of the left orbital floor and zygoma. InCorrespondence to Dr Jcrry A Shields, Oncology Service, Wills EyeHospital, Ninth and Walnut Streets, Philadelphia, PA 19107, USA.

*Presented at the Annual Meeting of the Eastern OphthalmicPathology Society, St Thomas, Virgin Islands, I November 1985.

August 1984 she had excision of scar tissue aroundthe left eye and biopsy of a 'cyst' in the left uppereyelid, which was diagnosed at another hospital as amalignant fibrous histiocytoma.A general physical examination gave essentially

normal results, and complete examination of theright eye revealed no abnormalities. Examination ofthe left eye disclosed diffuse thickening of the peri-ocular skin and upper eyelid with 2 mm of proptosisand 4 mm of blepharoptosis (Fig. 1). There was mild

Fig. 1 Facialphotograph ofpatientshowing proptosis andblepharoptosis on the left side.

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Fig. 2 Computed tomographyshowing irregularbutfairlywell circumscribed left orbital mass (arrow) A: Axial view.B: Coronal view.

scarring on the left side of the nose where the 'basalcell carcinoma' was previously excised,Computed tomography (CT) of the orbits showed

a large irregular mass filling most of the left orbitsuperonasally and posteriorly (Figs. 2A, B). Itappeared to extend to the orbital apex but showed no

evidence of bone destruction.In view of the patient's history and clinical findings

the initial differential diagnosis included orbitalrecurrence of basal cell carcinoma, orbital recurrenceof malignant fibrous histiocytoma, or possible granu-

lomatous inflammation related to prior trauma. The

Fig. 28

histopathological sections of the prior skin biopsieswere requested.

It was elected to perform a biopsy of the orbitalmass to determine which of the three diagnosticpossibilities was correct. Therefore an incisionalbiopsy of the mass was performed by way of asuperonasal brow incision and extraperiostealapproach. A wedge biopsy was taken from theanterior portion of a firm white orbital mass, and noattempt was made to excise it completely. Tissuesubmitted for routine frozen sections during surgeryshowed malignant spindle cells with considerableextracellular material. On frozen sections the speci-men was interpreted as a malignant spindle celltumour, most likely a malignant fibrous histio-cytoma.The permanent sections disclosed interlacing

bundles of spindle cells with pleomorphic hyper-chromatic nuclei, sometimes arranged in a storiform(closely packed in cartwheel) pattern, sometimeswith a foamy-appearing cytoplasm (see discussion ofpathology, below). The preliminary diagnosis wasrecurrent malignant fibrous histiocytoma of the leftorbit. On the day after surgery a copy of thepathology report of the prior biopsy of the lefteyebrow was received, and it also indicated a diag-nosis of malignant fibrous histiocytoma.On the following day we received word that

the patient had been seen in consultation by thePigmented Lesion Group at the University ofPennsylvania in December 1979. To our surprise thenasal skin lesion had been interpreted as lentigomaligna melanoma. Because the lesion had extendedclose to the surgical margins, a course of radio-therapy, giving 4920 rad over a 22-day period, hadbeen administered. The revised diagnosis by thePigmented Lesion Group was not indicated on ourreport from the other hospital, which still reflectedthe diagnosis of malignant fibrous histiocytoma.

In view of this new information the biopsy ofthe left upper eyelid and the orbital biopsy werereassessed. Both biopsies were finally diagnosed as adesmoplastic neurotropic melanoma (see followingdiscussion on pathology). The patient was readmit-ted to the hospital and underwent an orbital exen-teration with removal of the medial canthal area andupper eyelid. She is alive and well 14 months afterour initial examination.

PATHOLOGYA review of the initial shave biopsy of the originallesion from the left side of the nose demonstratedincreased numbers of atypical melanocytes in thebasal layers of the epidermis with evident desmo-plasia in the dermis (Fig. 3). The areas of desmo-plasia contained scattered atypical spindle shaped

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A. t .: 110 v W% A

Fig. 3 Photomicrograph ofthe original cutaneous lesionfrom the nose showing atypical melanocytes at the basal layerofthe epidermis, consistent with the radialgrowth phase oflentigo maligna melanoma. Note the actinic elastosis in thesuperficial dermis. Haematoxylin-eosin.

melanocytes which exhibited perineural and endo-neural involvement in the subcutaneous connectivetissues (Figs. 4 and 5). The diagnosis was lentigomaligna melanoma with a neurotropic desmoplasticreaction.The orbital biopsy and the subsequent orbital

exenteration specimen showed the tumour to becomposed of fascicles and cords of atypical spindlecells with a marked desmoplastic reaction identical tothat seen in the cutaneous tumour (Fig. 6A). In someareas the cells resembled fibroblasts, with ratheruniform nuclei, while in other areas the nucleishowed considerable pleomorphism with a vesicularappearance and prominent nucleoli (Fig. 6B).Particularly near the margins of the specimen therewas perineural and sometimes intraneural invasionby the spindle tumour cells. Fontana stains for

Ad ;-'-I t

Fig. 5 More detail ofdermal nervefrom primary tumour,showing permeation ofendoneurium andperineurium bycytologically atypical spindle cells (neurotropism) (arrows).Haematoxylin-eosin.

melanin were negative. The S-100 protein stain waspositive in many of the tumour cells (Fig. 7). V

The orbital lesion was processed for routineelectron microscopy. The tumour was composed ofspindle shaped fibroblast-like cells with abundantrough endoplasmic reticulum. Although some of thecells were void of melanosomes, a number of themcontained spheroidal granular melanosomes,typical of poorly differentiated melanosomes seen inmany melanomas (Fig. 8).The final diagnosis was orbital metastasis of

desmoplastic neurotropic melanoma arising fromcutaneous lentigo maligna melanoma.

Discussion

Desmoplastic malignant melanoma is a rare variantof cutaneous spindle cell melanoma which was first

Fig. 4 Photomicrograph ofsubcutaneous tissues deep to skinlesion showingperineural invasionby atypical melanocytes andinfiltration ofsubcutaneousfat by aspindle cell tumour with afibrousstroma, characteristic ofadesmoplastic and neurotropicmelanoma. Haematoxylin-eosin.

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Fig. 6AFig. 6 Photomicrograph oforbital mass showinghaphazardly arranged malignantspindle cells withdesmoplastic reaction. Haematoxylin-eosin. A: x20.B: x125.

described by Conley and associates in 1971.34 Inaddition to their seven original cases about 25 othercases have been reported.7 Most reported caseshave been in the head and neck region, with one caseinvolving the eyelid.'2 The case reported here isapparently the first to have deep orbital involvementand to produce ipsilateral proptosis.The typical evolution of a desmoplastic melanoma

is now relatively clear. Most reported cases havebeen preceded by a lentiginous or (less often) by asuperficial spreading melanoma in the face or neckregion. The skin lesions often appeared innocuousclinically and were not usually interpreted micro-scopically as being highly malignant, because thedesmoplastic and neurotropic components in the

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Fig. 7 S-100protein stain showingpositive cytoplasmicstaining in tumour cells (arrows).

deep reticular dermis were overlooked on micro-scopic examination.Approximately six months to two years after

excision of the initial lesion the patient characteristic-ally develops a slowly enlarging, firm, subcutaneousmass deep to the site of the primary lesion. Biopsy ofthe recurrent (or persistent) lesion demonstratesbundles of atypical spindle cells with varying degreesof malignancy and marked desmoplasia. Neuro-tropism of the tumour is often observed.14 1617Melanin pigment often cannot be demonstrated inthe deeper lesion, even with special stains andelectron microscopy, though it is usually evident inthe initial cutaneous lesion even by routine lightmicroscopy. A few desmoplastic melanomas havebeen completely amelanotic, though they show intra-dermal patterns otherwise characteristic ofmelanoma.The recurrent deeper lesion is often misdiagnosed

histopathologically as fibrosarcoma, fibromatosis,scar tissue, or (as in our case) fibrous histiocytoma.4In our case the Fontana-Masson stain for melaninwas negative, but the use of immunoperoxidasestains and electron microscopy were helpful in estab-lishing the diagnosis. Stains for S-100 protein werepositive (Fig. 7), suggesting a tumour of neural crestorigin, and electron microscopy showed spheroidalgranular melanosomes in the cytoplasm of thetumour cells. These features, combined with thehistory of a prior cutaneous melanoma, stronglysupported the diagnosis of melanoma, in spite of thefact that the diagnosis was less evident with routinelight microscopy.The mechanism of orbital spread in our case can be

deduced from the histopathology and from a reviewof the literature on desmoplastic melanomas. Both inthe original skin lesion and in the orbital recurrence

282

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Orbital involvement with desmoplastic melanoma

Fig. 8 Electron photomicrograph of the orbital tumour showing spheroidal granular melanosomes within cytoplasm oftumour cell (arrow). x 10 000.

there was marked perineural and intraneural involve-ment by tumour cells. It is recognised that the rarecase of melanoma which shows neurotropism has atendency toward desmoplasia (stimulation of fibro-sis).'' It is most likely that the neurotropic tendencyof our patient's tumour was responsible for spread ofthe tumour cells along peripheral nerves into theorbit, where they proliferated as a solid mass. Thiswould be consistent with other reported cases, wherethe deeper nodule seemed to occur from neuralspread of the melanoma to a deeper location. Reviewof the earlier biopsies in such circumstances mayreveal tumour within nerves at the margin of thespecimen, as was found in our case.The most important considerations in the differen-

tial diagnosis of an eyelid mass with secondary orbitalinvolvement are basal cell carcinoma and sebaceousgland carcinoma. The majority of such cases are basalcell carcinomas which have been neglected or inade-quately excised. Sebaceous gland carcinomas alsohave a marked tendency to invade the orbit, particu-

larly the fossa of the lacrimal gland, where they cansimulate a primary lacrimal gland tumour.'8 Malig-nant melanomas of the eyelid are rare and generallydo not secondarily invade the orbit. However, cer-tain cases of lentiginous or superficial spreadingmelanomas have a tendency to neurotropism. Whenlocated in the eyelid area such neurotropic mela-nomas can easily invade the orbit and simulatea primary orbital tumour, as occurred in ourcase. In such cases biopsy of the orbital mass maydisclose an amelanotic spindle cell tumour whichis not at first glance similar to the original skinlesion.The desmoplastic variety of melanoma should be

considered in the differential diagnosis of a spindlecell tumour of the orbit, especially if there has been aprior history of excision of a melanocytic tumour ofthe eyelid. In such cases a review of the originalbiopsy combined with the use of special stains andelectron microscopy may be helpful in establishingthe correct diagnosis.

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ADDENDUMWhile preparing the manuscript we believed that thiswas the only case on record of orbital spread ofdesmoplastic neurotropic melanoma. However, a

similar case was also presented at the 1985 EasternOphthalmic Pathology Society by Dr MouradKhalil. 9

The authors thank Dr Major Darst and Dr Wallace H Clark for theirassistance in the management of the patient.

This work was supported in part by the Ocular Oncology Fund andthe Oncology Research Fund, Wills Eye Hospital, and in part by theBlack Patch Invitational Golf Tournament, Downingtown, PA.

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3 Ainsworth AM, Folberg R, Reed RJ, Clark WH. Melanocyticnevi. melanocytomas, melanocytic dysplasias, and uncommon

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