British Journal of Ophthalmology, 1985, 69, 861-864

Unilateral eyelid, conjunctival, and choroidal tumoursas initial presentation of diffuse large-cell lymphomaSTEVEN R LEFF,' JERRY A SHIELDS,' JAMES J AUGSBURGER,'ROBERT V MILLER,2 AND BENJAMIN LIBERATORE2

From the 'Oncology Service, Wills Eye Hospital, Jefferson Medical College, Thomas Jefferson University,Philadelphia, PA, and 2Newcomb Hospital, Vineland, NJ, USA

SUMMARY Simultaneous ipsilateral eyelid, conjunctival, and choroidal tumours developed in anotherwise healthy man. Biopsy of the eyelid mass led to the diagnosis of large-cell lymphoma.Further examination revealed systemic lymphoma. Although the ocular and adnexal lesionsresponded to systemic chemotherapy, additional skin tumours later developed. Large-celllymphoma (also called reticulum cell sarcoma and histiocytic lymphoma) is becoming increasinglyrecognised for its ophthalmic manifestations. The clinical signs, diagnostic investigations, andtreatment of this disease are discussed.

Large-cell lymphoma (also known as reticulum cellsarcoma and histiocytic lymphoma) has recentlygained considerable attention in the ophthalmicliterature. It is the lymphoma with the greatestfrequency of ocular involvement. There are basicallytwo forms of this malignancy. The first type, withfrequent intraocular involvement, is likely to presentas a persistent uveitis.' It is usually associated withcentral nervous system (CNS) tumour and nosystemic disease. However, the more common typeof large-cell lymphoma is the diffuse systemic form.Although ocular adnexal and orbital involvement isoften reported, intraocular manifestations are con-siderably less frequent.

It is well documented that patients with systemiclymphoma may present initially with eyelid involve-ment.23 However, we were unable to find any reportsof both intraocular and adnexal tumour togetherpreceding systemic signs. This paper describes apatient who we believe is the first to present initiallywith simultaneous eyelid, conjunctival, andchoroidal large-cell lymphoma before systemicdisease was obvious.

Case report

In September 1983, an 80-year-old previouslyhealthy white man was referred to the OncologyCorrespondence to Dr S R Leff, Oncology Service, Wills EyeHospital, Ninth and Walnut Streets, Philadelphia, PA 19107, USA.

Service of Wills Eye Hospital. His past ocular historywas negative except for uncomplicated intracapsularcataract extractions in 1959 and 1975 in the left andright eyes respectively, and ocular-sparing left facialherpes zoster in 1971. His family history wasunremarkable.

Eight weeks prior to our consultation he hadnoted slight tearing from his left eye. The patient'sophthalmologist noted a mass in the left brow andseveral ipsilateral fundus lesions. Metastaticcarcinoma was suspected, and a laboratory andradiological survey was ordered. However, chestx-ray, complete blood count, blood chemistry tests,_g_.~~~~; .................. .. :::

Fig. 1 Clinicalphotograph ofleft lower eyelidandconjunctiva demonstrating the area oftumour.

861

copyright. on January 22, 2021 by guest. P

rotected byhttp://bjo.bm

j.com/

Br J O

phthalmol: first published as 10.1136/bjo.69.11.861 on 1 N

ovember 1985. D

ownloaded from

Steven R Leff, Jerry A Shields, JamesJAugsburger, Robert V Miller, and Benjamin Liberatore

Fig. 2 Wideanglefundusphotograph ofchoroidaltumoursin the left eye. There is an incidental temporal island ofchorioretinal atrophy.

and computed tomography (CT) scan of head andbody were all negative.When first seen at our service the patient's best

corrected visual acuity was 6/5 in the right eye and 6/9in the left. A firm, non-tender, 3x2 cm nodule waspalpable beneath the left brow. A similar lesionmeasuring lxi cm involved the left palpebral andbulbar conjunctiva inferolaterally (Fig. 1). The intra-

wb.i....Syi.

lymphoid~~~~~>cell infiltatn normal

... ...

....z.,.- ...

browbiopsyspecimen. Note ~ w ''

lymphoid cells Infiltrating normal M....... .,,:^Sr.'>S::jtissue (Haematoxylin-eosin, 'x250).

ocular pressure was 17 mmHg in the right eye and 11in the left.

Biomicroscopy revealed normal anterior segmentsand aphakia in each eye. Vitreoretinal examinationwas normal in the right eye. In the left eye, however,multiple, slightly elevated yellow choroidal tumoursranging froml to 6 mm in diameter were present inthe posterior pole and pre-equatorial regions(Fig. 2). There was shallow subretinal fluid overlyingsome of the larger lesions. The optic disc was normaland the vitreous was clear. A preoperative physicalexamination gave normal findings except for slightcervical and inguinal lymphadenopathy.

It was decided to biopsy the large brow mass. Atsurgery an unencapsulated, grey tumour wasencountered and a wedge biopsy specimen taken.Histological examination showed a tumour com-posed predominantly of rather uniform largelymphocytes, which diffusely infiltrated the softadipose tissues and surrounding nerves and bloodvessels (Fig. 3). The nuclei were clear. From thenucleoli, which were large and irregularly shaped,emanated chromatin strands, which condensed alongthe nuclear rim. There were scattered benignlymphocytes as well. The pathological diagnosis waslarge-cell lymphoma.

Further systemic examination revealed noadditional evidence of lymphoma. Cyclic combina-tion chemotherapy with cyclophosphamide, adria-mycin, vincristine, and prednisone was begun, and all

i ~~~~WOom,.i

. Z ; -' i'aen ....................... s ' _

...E-Q,'5;,.:'.Off".7i %:o;.. X :+

862

:r.

copyright. on January 22, 2021 by guest. P

rotected byhttp://bjo.bm

j.com/

Br J O

phthalmol: first published as 10.1136/bjo.69.11.861 on 1 N

ovember 1985. D

ownloaded from

Unilateral eyelid, conjunctival, and choroidal tumours as initialpresentation ofdiffuse large-cell lymphoma 863

ig. 4 Post-treatment wiae anglepnotograpn ofte lejtfundus. Note regression oftumours.

known lesions including the lymphadenopathyregressed dramatically (Fig. 4). The visual acuity inthe left eye improved to 6/5.

Six months later and only several weeks after thepatient's sixth cycle of chemotherapy a new sub-cutaneous mass developed in the left breast. A slightswelling in the area of the right brow was alsoevident. A biopsy of the breast lesion was performedand a firm, walnut-sized nodule was removed. Atmicroscopic examination a tumour composed ofmonomorphic lymphoid cells infiltrating the normalfat and connective tissue of the breast was identified.A review of the slides from the previous lid specimenshowed the lesions to be histologically similar. Thebreast as well as the brow tumour also resolved onfurther chemotherapy. However, the patient

returned in August 1984 with a 1 x 1 cm right lower lidnodule (Fig. 5). Additional chemotherapy is beingundertaken.

Discussion

Large-cell lymphoma can be divided into two mainpresentation patterns. The first and most importantto ophthalmologists is the intraocular-centralnervous system (CNS) type. The combination ofthese two sites together 75% of the time clearly labelsthis as a distinct entity. There is only a 25% associa-tion with disseminated large cell lymphoma in thisform.4 Usually eye findings precede CNS clinicalsigns by an average of 21 months.56 However, CNSdisease rarely occurs before eye involvement. Aposterior uveitis or a vitritis with or without chorio-retinal involvement is the main feature.7 8

Diffuse systemic large-cell lymphoma is far com-moner than the ocular-CNS form. Mainly a diseaseof lymph nodes, spleen, and bone marrow, it can alsobegin in the viscera or skin. This form is not usuallyassociated with ophthalmic disease. However, whenit occurs, orbital or ocular adnexal involvements is farmore likely to be seen than intraocular lesions.9' ' Inaddition, intraocular involvement here is more likelyto be choroidal, as opposed to retinal or vitreal, asusually seen in the ocular-CNS form." Proptosis andperiorbital swelling are the typical presentingadnexal manifestations.'2Recent immunofluorescent techniques have

detected immunoglobulins on the surface of thecells.'I'5 It now appears that large-cell lymphomasare derived mostly from B lymphocytes and rarelyfrom T lymphocytes.Our patient with systemic lymphoma is unusual in

several respects. He represents one of the few cases

Fig. 5 Clinicalphotograph ofright lower lid nodule.

copyright. on January 22, 2021 by guest. P

rotected byhttp://bjo.bm

j.com/

Br J O

phthalmol: first published as 10.1136/bjo.69.11.861 on 1 N

ovember 1985. D

ownloaded from

Steven R Leff, JerryA Shields, James JAugsburger, Robert V Miller, and Benjamin Liberatore

of intraocular disease presenting in the systemic formof the malignancy. He is even more unusual in thathis choroidal tumours became manifest early in thecourse of his illness and before any systemic signs orsymptoms occurred. In addition he also had eyelidand conjunctival tumours, which prompted him toseek medical attention. The fact that his initialintraocular and periocular lesions were ipsilateralrather than contralateral may be coincidental, butthe ocular-CNS form of large-cell lymphoma doestend to be ipsilateral.'6 However, it is also curiousthat our patient's later tumour sites involved the rightperiorbita.Chemotherapy was used to good advantage in our

patient. Both the original ophthalmic tumours as wellas the later recurrences responded dramatically. Anyfuture site will be similarly treated, with local radio-therapy held in reserve. Unfortunately there is nocurative treatment for large-cell lymphoma, and theprognosis for our patient remains guarded.

This work was supported in part by the Ocular Oncology Fund,Wills Eye Hospital, the Oncology Research Fund, Wills EyeHospital, and in part by the Pennsylvania Lions Sight Conservationand Eye Research Foundation, Inc.

References

I Barr CC, Green WR, Paync JW, Knox DL, Jensen AO,Thompson RL. Intraocular reticulum ccll sarcoma. Clinico-pathologic study of four cases and review of the literature. SurvOphthalmol 1975; 19: 224-39.

2 Shields JA. Malignant lymphoma presenting as a unilateraleyelid mass. Ann Ophthalmol 1975; 7: 1689-91.

3 Jakobiec FA, Gibraltcr RA, Knowles OM, Iwamoto T.Lymphoid tumours of the lid. Ophthalmology (Rochester) 1980;85: 1058-64.

4 Char DH, Margolis L, Newman AB. Ocular reticulum cellsarcoma. Am J Ophthalmol 1981; 91: 480-3.

5 Sloas HA, Starling J, Harper DG, Cupples HP. Update of ocularreticulum cell sarcoma. Arch Ophthalmol 1981; 99: 1048-52.

6 Rosenbaum TJ, MacCarty CS, Buettner H. Uveitis and cerebralreticulum cell sarcoma (large-cell lymphoma): case report.J Neurosurg 1979; 50: 660-4.

7 Minckler DS, Font RL, Zimmerman LE. Uveitis and reticulumcell sarcoma of the brain with bilateral neoplastic seeding of thevitreous without retinal or uveal involvement. Am J Ophthalmol1975; 80:433-9.

8 Kennerdell JS, Johnson BL, Wisotzkey HM. Vitreous cellularreaction associated with reticulum cell sarcoma of brain. ArchOphthalmol 1975; 93: 1341-5.

9 Collyer R. Reticulum cell sarcoma of eye and orbit. Can JOphthalmol 1972; 7: 247-9.

10 Currey TA, Deutsch AR. Reticulum cell sarcoma of the uvea.South MedJ 1965; 58: 919-22.

11 Klingele TG, Hogan MJ. Ocular reticulum cell sarcoma. Am JOphthalmol 1975; 79: 39-48.

12 Jakobiec FA, Williams P, Wolff M. Reticulum cell sarcoma(histiocytic lymphoma) of the orbit. Surv Ophthalmol 1978; 22:255-69.

13 Kaplan H, Meredith TA, Aaberg TM, Keller RH. Reclassifica-tion of intraocular reticulum cell sarcoma (histiocyticlymphoma): immunologic characteristics of vitreous cells. ArchOphthalmol 1980; 89: 707-10.

14 Saga T, Ohno S, Matsuda H, Ogaswara M, Kikuchi K. Ocularinvolvement by a peripheral T-cell lymphoma. Arch Ophthalmol1984; 102: 399-402.

15 Michelson JB, Michelson PE, Bordin GM, Chisari FV. Ocularreticulum cell sarcoma: presentation as retinal detachment withdemonstration of monoclonal immunoglobulin light chains onthe vitreous cells. Arch Ophthalmol 1981; 99: 1409-11.

16 Qualman SJ, Mendelsohn G, Mann RB, Green WR. Intraocularlymphoma. Natural history based on clinico-pathologic study of8 cases and review of the literature. Cancer 1983; 52 878-86.

864

copyright. on January 22, 2021 by guest. P

rotected byhttp://bjo.bm

j.com/

Br J O

phthalmol: first published as 10.1136/bjo.69.11.861 on 1 N

ovember 1985. D

ownloaded from