orbital xanthogranuloma in adults - bmj

Britishournal ofOphthalmology, 1991,75,680-684

CASE REPORTS

Orbital xanthogranuloma in adults

Geoffrey E Rose, Bhupendra C Patel, Alec Garner, John E Wright

AbstractThe onset of periorbital xanthogranuloma inadults is rare and may be accompanied byhaematological abnormalities and malignancy.The appearance ofthe eyelid lesions is virtuallydiagnostic, producing readily recognisablediffuse, yellow plaques, and affected patientsshould be investigated and reviewed regularlyfor systemic disease. Three cases are des-cribed, in which periorbital cutaneous plaqueswere associated with abnormal tissues in thesuperior part of the orbit; these abnormaltissues caused displacement or restrictedmovement of the globe or upper eyelid. Thepossibility that two cases represent a necro-biotic type of xanthogranuloma is presented.Nine years after the onset of xanthogranulomaone patient developed non-Hodgkin'slymphoma. A multiple-drug regimen of sys-temic chemotherapy, given for lymphoma,caused a marked clinical reduction in theperiorbital xanthogranuloma.

Periorbital xanthogranulomas arising in adultsare rare and may be associated with the presence,

t'- i~~~~~~~~~~~~~.~~~~~~~~~~~~~~~~~~V

Figure I Case I at presentation.

Figures 2A, B Case 1.Orbital computedtomography, showing soft-tissue masses anteriorly in theupper parts ofthe affectedorbits (arrows).

or subsequent development, of a parapro-teinaemia,'- myeloma, 69 or leukaemia.' 6 Localor systemic steroids, chemotherapy, radio-therapy, and plasmapheresis have been used totreat these lesions or any underlying haemato-logical abnormality. The response to differentmodes of therapy are reported as being some-what variable.

Intraorbital involvement in adult-onsetxanthogranuloma has been reported in only a fewcases. In this paper we present three cases ofadult-onset xanthogranuloma, each with orbitalinvolvement as shown by computed tomography(CT) (two cases) and at anterior orbitotomy.Two had features of necrobiotic xantho-granuloma.

Case reports and histopathology

CASE 1A 22-year-old Greek male developed progressive,painless swelling of both upper eyelids. Biopsyshowed idiopathic orbital inflammation. Therewas some subjective improvement with systemicsteroid therapy, though this was discontinuedbecause of the onset of grand mal epilepsy. Ayear earlier he had developed adult-onset asthma,for which he received inhaled salbutamol andweekly injections of Alavac-S (a desensitisingvaccine). There was a past history of mildpoliomyelitis at the age of 3 and petit mal at 7years.On referral to this hospital at the age of 24 the

patient had normal vision and ocular motility.Prominent raised yellow plaques, involving theskin and underlying tissues ofboth upper eyelids,were present (Fig 1). The masses caused bilateralgravitational ptosis, though levator function wasgood. There was no relative proptosis, but botheyes were somewhat prominent (Hertel readings:21 mm either eye). There was no regional

was ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~.....

Orbital Clinic, MoorfieldsEye Hospital, City Road,London EC1V 2PDGE RoseB C PatelJ E Wright

Institute ofOphthalmology, CaytonStreet, London EC1V9ATA GarnerCorrespondence to:Mr G E Rose, FRCS,Moorfields Eye Hospital, CityRoad, London EC1V 2PD.Accepted for publication11 April 1991

680

on July 12, 2022 by guest. Protected by copyright.

http://bjo.bmj.com

/B

r J Ophthalm

ol: first published as 10.1136/bjo.75.11.680 on 1 Novem

ber 1991. Dow

nloaded from

http://bjo.bmj.com/


I

lymphadenopathy, and systemic examinationgave normal results.

Orbital CT scans showed a diffuse infiltrationof the eyelids and the upper part of each orbit(Figs 2A, B). Chest radiographs showed slightenlargement of the left hilum, not typical ofsarcoidosis.There was a mild eosinophilia (0*56 x l0/l)

and the erythrocyte sedimentation rate was

43 mm in the first hour (Westergren). With theexception of raised serum globulins (53 g/l;normal range 18-32), the levels of serum electro-lytes, hepatic enzymes, and lipids were normal.Plasma protein electrophoresis showed a markedand polyclonal increase ofgammaglobulins and a

mildly raised ca-2 globulin concentration. SerumIgG concentration was raised (36-4 g/l), IgAslightly low (0 65 g/l), and IgM within normalrange (0-62 g/l). Urinary protein concentrationswere normal and no Bence-Jones proteins were

detected. There were no detectable circulatingautoantibodies, and serum concentration of thethird component of complement was normal(C3=0 7 g/l). The fourth component was, how-

4.~ v _

k..̂ .

% -.

a .* to

Figure 5 Case 2 at presentation.

ever, slightly reduced (serum C4= 80 mgil), and

C-reactive proteins were slightly increased (I11- 2mgIl; normal range <10). The Treponema

pallidum haemagglutination test (TPHA) and

venereal disease research laboratory test (VDRL)

were negative, and fasting serum triglyceridesand cholesterol were within normal limits. Thefindings on bone marrow biopsy were normal.At orbital biopsy an abnormal yellow material

was present in eyelid skin, subcutaneous tissues,and orbicularis oculi, extending into the orbitalfat and connective tissues (Fig 3). The fasciaaround the lacrimal glands was affected, butthere was no involvement of the gland.

PATHOLOGYHistological examination of several biopsyspecimens revealed extensive infiltration of eye-

lid dermis and anterior orbital tissues withhistiocytes, many of which had voluminous,foamy cytoplasm (Fig 4). Scattered Touton giantcells were present, especially within the deeptissues, and there was patchy lymphocytic andplasma cell infiltration. The collagenous stromashowed foci of necrosis in the form of hyalinisa-tion, fragmentation, and acellularity. Eosino-phils were extremely rare and there were no

neutrophils. Immunohistochemical stainingreactions disclosed a polyclonal B-cell presence,with both x and k light chains being demon-strable, while occasional IgM-forming cells com-plemented the predominantly IgG-relatedplasma cells.

CASE 2A 37-year-old Caucasian female developeddiffuse swelling and yellow deposits within theskin and deeper tissues of both upper eyelids. At

rO.W..

I-.

f

Ii

0Figure 6 Case 2. Intraoperative view ofxanthogranulomainvolving postseptal orbital tissues.

Figure 3Case 1. Intraoperative viewofxanthogranulomainvolving postseptal orbitaltissues.

Figure 4 Case 1. Togetherwith large numbers ofcellswith voluminousfoamycytoplasm (closed arrow)there are scatteredinflammatory cells andfociofnecrobiotic fibrous tissue(open arrow). (H-E, x450.)

AtV

'

681

C."

{;


http://bjo.bmj.com

/B

r J Ophthalm


ber 1991. Dow

nloaded from

http://bjo.bmj.com/

Rose, Patel, Garner, Wright

A~ ~ALa

-'t.:,.vAP j

4' S -.. 4 {. ; _

A'4

'a "5MilBy, ear \ rt r k 4 W C s 4' I

.;..S

t

*.> .i * @ b ¢ v ' A *. t

ma a, _ -Of # .N, > 0% b ..t,: @

4ig N In* ta ., ,6.*o,-.'t= .. . @ a;*

--. .1,1% ..or, '

e !, ; ;:., ; r

n 56

thi Or hi Vie

>!> W t @ Be 'i

Figure 7 Case 2 The

orbital fat is infiltrated and

largely replaced byhistiocytes and scattered

giant cells are also present

(arrow). (H-E, x180.)

the referring hospital the condition was thoughtto be 'pseudotumour' (idiopathic orbital inflam-matory disease), and she was treated with sys-

temic steroids, without improvement.On referral, at age 43, she had yellow plaques

extending widely over both upper eyelids. Therewas bilateral ptosis, greater oli the right, levatorpalpebrae superioris function was moderate, andchanges in skin creases of the upper lid were

suggestive of bilateral disinsertion of the levatormuscle aponeurosis (Fig 5).

Orbital biopsy revealed abnormal yellowmaterial in the eyelid skin, in the orbicularisoculi muscles and in the orbital fat and connec-

tive tissues (Fig 6). The results of systemicinvestigation are not available for review.

PATHOLOGYMicroscopy showed massive infiltration andreplacement of orbital fat by histiocytes, withoccasional foreign-body and Touton giant cellforms (Fig 7). Intercellular borders were fre-quently indistinct and many histiocytes hadabundant foamy or vacuolated cytoplasm. Therewas a patchy lymphocytic infiltration, withoccasional germinal centres, but plasma cells

Figure 8 Case 3. Extensive xanthogranuloma ofright uppereyelid and orbit, causing 4 mm relative proptosis.

were sparse and eosinophils not observed.

Stromal necrosis was not a conspicuous feature.

CASE 3The right upper lid of a 50-year-old Caucasianmale developed a painless and slowly enlargingyellow lesion over a four-year period. This was

thought to be a xanthelasma and was partiallyresected.When first seen at this hospital at the age of 56

the right eye was displaced downwards by 2 mm,with 4 mm of relative proptosis. Supraductionand abduction of the right globe was slightlyrestricted. A large yellow plaque extendedwidely across the right upper lid, associated withpoor function of the levator muscle, 7 mm ofrelative ptosis, and secondary brow elevation on

the affected side (Fig 8). A mass was palpable,and visible through conjunctiva, in the supero-temporal quadrant ofthe orbit. CT scans showedthat it extended widely across the roof of theorbit (Figs 9A, B). Systemic examination, chestx ray, and serum electrolytes and lipids were allnormal. The leucocyte count was IOx 109/1, witha relative lymphocytopenia (1 x 109/1) and eosino-philia (1 -5 xI1091).At the age of 58, following transconjunctival

biopsy, the patient underwent debulking of thelesion. Abnormal yellow tissue extendedthroughout upper lid skin, orbicularis oculi, andinto the orbital fat and perilacrimal fascia.

Eighteen months later there was no pro-gression of the eyelid lesion, but the patientdeveloped extensive abdominal non-Hodgkin'slymphoma. The lymphoma was treated withmultiple cycles of systemic cyclophosphamide,vincristine, doxorubicin (Adriamycin), predni-solone, and methotrexate. Following systemic

-I. T 4..*w......

Figures 9A, BCase 3. Orbitalcomputed tomography,showing soft-tissue masses

anteriorly in the upper partsofthe affected orbit (arrows).

44I.,

St .0..4,.

''a- -

.j. * *.4 -,

S.

'Ie

682

:1

...

.I


http://bjo.bmj.com

/B

r J Ophthalm


ber 1991. Dow

nloaded from

http://bjo.bmj.com/


Figure 10 Case 3.Resolution ofproptosis andmarked regression ofeyelidlesion after systemicchemotherapy for abdominalnon-Hodgkin's lymphoma.

chemotherapy, there was a resolution of theproptosis and a marked reduction of the xantho-granuloma (Fig 10). A minor ptosis persisted andlevator muscle function remained very poor.

PATHOLOGYHistology of the excised tissue showed multiplefoci of lymphocytic infiltration with occasionalgerminal centres. Plasma cells, together withconsiderable numbers of eosinophils, sur-

rounded the centres of lymphoid activity, whilethe intervening stroma was largely replaced byhistiocytes with generally voluminous, foamycytoplasm (Fig 11). Touton giant cells were a

conspicuous finding and there was moderatestromal necrosis (Fig 12).

Figure I1 Case 3. Orbitalbiopsy showed histiocyteinfiltration with occasionalchronic inflammatory cellsand Touton giant cell(arrow). (H-E, x450.)

DiscussionXanthogranulomas are granulomas in whichthe constituent histiocytes are filled with a lipidmaterial. This material imparts a yellow colora-tion, both clinically for superficial lesions and on

gross examination of resected specimens.Touton giant cells are also characteristic, thesemultinucleate cells having nuclei arranged in a

'wreath' round a nidus of eosinophilic cytoplasmand separated from the cell membrane by a rimof translucent, foamy cytoplasm.

Several histiocytic tumour-like lesions have

9..... T.4

been described, including the various forms ofhistiocytosis-X, generalised eruptive histio-cytoma, reticulohistiocytoma, and some types offibrous histiocytoma that may appear xantho-matous. Periocular xanthomatous lesions, withprominent Touton giant cells, form three cate-gories - juvenile xanthogranuloma, necrobioticxanthogranuloma, and Erdheim-Chester disease.

Juvenile xanthogranuloma presents asmultiple skin or intraocular lesions and tends toresolve, either spontaneously or after systemicsteroid treatment or radiotherapy." '3 Occasion-ally the lesions may occur in adults,'4 but orbitalinvolvement, which is exceptionally rare, hasbeen reported almost exclusively in children. " "

Adult-onset xanthogranulomas may beassociated with extensive systemic disease, in-volving particularly skeletal, renal, and hepatictissues, being Erdheim-Chester disease or lipoidgranulomatosis. 16 Periocular involvement isunusual with Erdheim-Chester disease, thoughcases with proptosis have been reported.'17'9

In contrast, periorbital lesions, with atendency to ulceration, are a predominant featureof necrobiotic xanthogranuloma. '"'° Theselesions display, between the areas of histiocyticaccumulation and granuloma formation, apatchy hyaline necrobiosis with collagen destruc-tion.20

Haematological abnormalities are commonwith necrobiotic xanthogranuloma and mayinclude leucopenia, eosinophilia, a raisederythrocyte sedimentation rate, low serumcomplement, and occasionally a mild hyper-lipidaemia.'"'° Dysproteinaemia is almost uni-versal, often with a monoclonal IgG paraproteinand occasionally with cryoglobulinaemia.' 6

Indeed, Bullock and associates7 suggest thatserum immunoglobulins react with tissue lipids,these complexes being deposited in skin andeliciting a giant-cell foreign body reaction.Myeloma or chronic lymphatic leukaemia havealso been reported in association with thiscondition.' 69

It is possible that the three cases reported hererepresent the necrobiotic type of xantho-granuloma, though the evidence is not con-clusive. None had the systemic involvement orthe widespread cutaneous lesions of Erdheim-Chester disease. Two patients (cases 1 and 3) hadleucopenia or lymphocytopenia, eosinophilia,and a raised erythrocyte sedimentation rate.Case 1 also showed a polyclonal increase ofserumimmunoglobulin G, and, within the biopsieswhich displayed necrobiotic foci, there was apolyclonal lymphoid infiltration; x and k lightchains, frequent IgG-forming plasma cells andoccasional IgM-forming cells were identified.The third patient (case 3) had multiple areas ofnecrobiosis in the orbital biopsies and subse-quently developed an intra-abdominal non-Hodgkin's lymphoma.

Reported treatment for necrobiotic xantho-granuloma includes local excision, radiotherapy,plasmapheresis, locally injected or systemicsteroids, and the use of systemic or topicalchemotherapy, such as chlorambucil, nitrogenmustard, cyclophosphamide, or melphalan.''02'The orbital xanthogranuloma in our case 3resolved almost completely after potent multiple

683

. .... .... ..-,M-o


http://bjo.bmj.com

/B

r J Ophthalm


ber 1991. Dow

nloaded from

http://bjo.bmj.com/

684 Rose, Patel, Garner, Wright

e

r ,.

drug chemotherapy (Figs 8, 10), this being in

contrast to the rather variable response reportedafter other types of therapy.

It is imperative that the periorbital plaques of

xanthogranuloma are recognised, because theymay be part of a widespread systemic disease

(Erdheim-Chester disease) or linked to a plasmacell dyscrasia or malignancy (necrobiotic xantho-

granuloma). Unlike the thin lesions of periocularxanthelasma, periorbital xanthogranulomas

are often thicker, larger, and may extend deeplyinto orbital tissues. Patients with xantho-

granuloma should undergo systemic investi-

gation, and, particularly where biopsy of the

lesions shows hyaline necrobiosis, they shouldhave continued clinical review for the develop-ment of plasma protein or other haematologicalabnormalities.

We thank the surgeons who referred the cases, and the staff of theDepartment of Medical Illustration, Moorfields Eye Hospital, forthe clinical illustrations.

1 Kossard S, Winkelmann RK. Necrobiotic xanthogranulomawith paraproteinaemia. J Am Acad Dermatol 1980; 3: 257-60.

2 Codere F, Lee RD, Anderson RL. Necrobiotic xantho-granuloma of the eyelid. Arch Ophthalmol 1983; 101: 60-3.

3 Robertson DM, Winkelmann RK. Ophthalmic featuresof necrobiotic xanthogranuloma with paraproteinaemia.AmJi Ophthalmol 1984; 97: 173-83.

4 MacFarlane AW, Verbov JL. Necrobiotic xanthogranulomawith paraproteinaemia. BrJ Dermatol 1985; 113: 339-43.5 Holden CA, Winkelmann RK, Wilson-Jones E. Necrobiotic

xanthogranuloma: a report of 4 cases. BrJ Dermatol 1986;114: 241-50.

6 Finan MC, Winkelmann RK. Necrobiotic xanthogranulomawith paraproteinaemia. A review of 22 cases. Medicine 1986;65: 376-88.

7 Bullock JD, Bartley GB, Campbell RJ, Yanes B, Conelly PJ,Funkhauser JW. Necrobiotic xanthogranuloma with para-proteinemia. Case report and a pathogenetic theory.Ophthalmology 1986; 93: 1233-6.

8 Char DH, LeBoit PE, Ljung B-ME, Wara W. Radiationtherapy for ocular necrobiotic xanthogranuloma. Arch Oph-thalmol 1987; 105: 174-5.

9 Venencie PY, Puissant A, Verola 0, et al. Necrobioticxanthogranuloma with myeloma. A case report. Cancer1987; 59: 588-92.

10 Scupham RK, Fretzin DF. Necrobiotic xanthogranulomawith paraproteinaemia. Arch Pathol Lab Med 1989; 113:1389-90.

11 Zimmerman LE. Ocular lesions of juvenile xanthogranuloma:nevoxanthoendothelioma. Trans Am Acad OphthalmolOtolaryngol 1965; 69: 412-39.

12 Gaynes PM, Cohen GS. Juvenile xanthogranuloma of theorbit. AmJ7 Ophthalmol 1967; 63: 755-7.

13 Sanders TE. Infantile xanthogranuloma ofthe orbit: a report ofthree cases. AmJi Ophthalmol 1966; 61: 1299-306.

14 Tahan SR, Pastel-Levy C, Bhan AK, Mihm MC Jr. Juvenilexanthogranuloma: clinical and pathological characterisa-tion. Arch Pathol Lab Med 1989; 113: 1057-61.

15 Shields CL, Shields JA, Buchanon HW. Solitary orbitalinvolvement with juvenile xanthogranuloma. Arch Ophthal-mol 1990;108: 1587-9.

16 Molnar CP, Gottschalk R, Gallagher B. Lipid granulomatosis:Erdheim-Chester disease. Clin NuclMed 1988; 13: 736-41.

17 Palmer FJ, Talley NJ. Erdheim-Chester disease with bilateralexophthalmos and liver cell adenoma. Australas Radiol 1984;28: 305-10.

18 Rozenberg I, Wechsler J, Koenig F, et al. Erdheim-Chesterdisease presenting as malignant exophthalmos. BrJr Radiol1986; 59: 173-7.

19 Alper MG, Zimmerman LE, La Piana FG. Orbital manifesta-tions of Erdheim-Chester disease. Trans Am Ophthalmol Soc1983;81:64-85.

20 Finan MC, Winkelmann RK. Histopathology of necrobioticxanthogranuloma with paraproteinaemia. J Cutan Pathol1987; 14:92-8.

21 Finelli LG, Ratz JL. Plasmapheresis: a treatment modality fornecrobiotic xanthogranuloma. J Am Acad Dermatol 1987;17:351-4.

4w S J

rtP

Figure 12 Case 3. Foci ofstromal necrosis are seen(closed arrow), along withdiffuse lymphocyticinfiltration and aggregates offoamy histiocytes (openarrow). (H-E, x180.)

c.v -4

i,

1, 1"


http://bjo.bmj.com

/B

r J Ophthalm


ber 1991. Dow

nloaded from

http://bjo.bmj.com/

orbital xanthogranuloma in adults - bmj

Documents