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Show f. elin. Nturo-ophthQlmol. 4: 173-180, 1984. Orbitocalvarial Swelling and Proptosis as an Early Manifestation of Systemic Lymphoma JAMES R. corrETO, M.D. MARIO L. R. MONTEIRO, M.D. THOMAS GRECO, M.D. DANTE B. CANNAROZZI, M.D. BERTRAND BISSON, M.D. Abstract A 67-yeu-old wom~n hold acutely diminished vision olnd polinful proptosis of the left eye amidst .I bolckground of chronic heoldolche, sc~lp tenderness, proximoll myoilgiols, intermittent fever, anema. ud elented erythrocyte udllnentoltion roltes. All symptoms olnd signs were exquisitely corticosteroid-responsive. She underwent two negoltive temporal utery biopsies olnd severoll extensive negoltive eVolluoltions for systemic diseol5e. Ultimoltely deep scollp biopsy, bone biopsy, olnd bone murow ~spiration were performed, ~nd .Ill revealrd. a. histologically well-differentiolted Iymphomol. Introduction Patients with visual dysfunction, headache, scalp tenderness, proximal extremity myalgias, and elevated erythrocyte sedimentation rates (ESRs) are frequently referred for ophthalmologic consultation and temporal artery biopsy. The ophthalmologist's knowledge of the ocular manifestations of systemic disease and his particular familiarity with the varied presentations of giant cell arteritis (GCA) make him uniquely valuable in evaluating such cases. Therefore, we report a case whose overall presentation closely mimicked that of GCA, but several of whose orbitocalvarial features were sufficiently atypical to prompt an intensive investigation which eventually disclosed disseminated lymphoma. The importance of early detection and specific treatment of lymphoma augments the significance of this unusual case. From tht Dl'putmtnt of Ophlh.illmology (lRC MLRM), URi· ~~ty 01 Connecticut Mtdiol Cenltr, F<1nnington, Conn«t· 1C\It; Y;a~ University School of Medicint' (TG, D8C 88), New H;avft\. Connecticut; Ind SL M;ary's Hospilal ORCTG, OBe, 88). Wlterbury. Conn«ticul. September 1984 Case Report In July 1982, a 67-year-old, while physician's wife was referred for ophthalmologic evaluation because of an II-month history of intermittent conjunctival injection and eyelid swelling left eye culminating in the sudden appearance of proptosis and visual loss left eye, severe left headache, chills, and fever. Past history was remarkable for 4 years of intermittent migratory, occipital and temporalparietal scalp tenderness and swelling. and a persistently elevated Westegran ESR (50-100 mm/hour). The areas of scalp tenderness and swelling were broad, indurated, and urticarial. They would appear suddenly and would resolve gradually and completely with corticosteroid therapy. In 1979, a firm, tender swelling over the left temporal area had prompted a temporal artery biopsy (negative) and comprehensive evaluation for inflammatory, metabolic, toxic, and neoplastic diseases including radiographic and radionuclide scanning of her skeletal system, serum complement determinations, rheumatoid factor, ANA, lupus erythematosis preparations, and cryo~ lobulins. No systemic disease was found. Since 1979, it had been necessary to maintain her on 7.5-60 mg of Prednisone a day for control of headaches and myalgias and normalization of her ESR. At no time could Prednisone be reducf'd below 10 mg a day without a flare-up of her scalp symptoms and elevation of her ESR. Since early 1980, she had recurrent, severe weakness. tenderness and pain of both thighs especially the left, partially relieved by Nalfon, but making it impossible for her to walk for weeks at a time. She had similar episodes involving her shoulders. She had chronic sinusitis. Her husband had a well·controlled lymphoma. On general physical examination, in July 1982, she had bilat~ eral calf tenderness and bilateral femoral and carotid bruits. 173 Calvarial Swelling Figure 1. Left frontotemporal swelling, cutaneous. Ophthalmologic examination performed by her previous ophthalmologists was allegedly normal in the right eye. Vision in the left eye was reduced to 20/30 and she confused colors. especially reds. She had "nasal field constriction" in the left eye. Pupils were 4 mm right eye and 3 mm left eye with an affarent pupillary defect in the left eye. There was moderate diffuse swelling of the left upper and lower eyelids with conjunctival injection and subconjunctival hemorrhage. Eye movements were normal. Exophthalmometry was 19 mm right eye and 22 mm left eye. The left globe was slightly difficult to reposit. Fundi were normal. She had a 5 X 5 cm area of left temporalparietal cutaneous edema which was slightly tender and exhibited no epidermal atrophy (Fig. 1). Prednisone was immediately increased to 80 mg a day with reversal of all symptoms and signs within 24 hours except for the persistence of 2 mm of proptosis left eye. Extensive evaluation for systemic disease was repeated and was again negative except for a mild normochromic normocytic anemia and ESR of 66 mm/hour. A repeat left temporal artery biopsy was negative. 174 Prednisone was tapered to 10 mg a day. Over the next 4 months, Prednisone had to be intermittently increased to control headaches, malaise, and scalp tenderness associated with elevation of the ESR. Ophthalmologically, she remained in complete remission. She was referred for neuro-ophthalmic consultation in November 1982. At that time she was taking Prednisone 20 mg/day. Examination was completely within normal limits except for 11h mm of relative proptosis in the left eye. Her cranial CT scan was reviewed, and orbital cuts suggested inflammation of the left orbit with swelling of the left lateral rectus muscle and a probable thickening of the adjacent orbital wall (Fig. 2). Prednisone was stopped, and the patient was told to report back if scalp swelling or tenderness recurred. Eight weeks later, she reported that she had discovered a slightly tender -lump" on her scalp. She believed she may have had it "for a long time: On examination, there was a shallow 3-cm convex, firm subcutaneous mass over the vertex apparently fixed to bone. No other masses could be palpated. Skull radiographs taken tangentially to the scalp lesion showed the Journal of Clinical Neuro-ophthalmology Figure 2. Cranial CT illustrating proptosis, enlargement of proximal left lateral rectus muscle, and probable nodule on and thickening of adjacent orbital waiL lesion to be slightly denser than scalp and adjacent to bone. Anavicular incision was made over the anterior edge of the lesion, and a wedge of scalp removed down to the periosteum which included a pieshaped area of the lesion. The entire lesion was not excised because of its relatively large size. The skin and subcutaneous tissue looked grossly normal, but the deep tissue was partly replaced by a yellow gelatinous plaque which was loosely adherent to the periosteum. Approximately 1/. of the lesion was thereby removed. Histopathology (Figs. 3 and 4) via Hand E revealed a thin, atrophic stratified squamous epithelium overlying a somewhat condensed superficial dennis. Generalized vascular engorgement was present in the dennis, and the lymphatics were found to be uniformly dilated. There was no evidence of vascular inflammatory reaction, fibrinoid necrosis nor granuloma, and only sparse cellular infiltrate was present in the superficial dermis. Occupying the deeper dermis were several nodular aggregates of highly vascularized inflammatory tissue consisting of a background of histiocytes and exuberant endothelial channels irregularly infiltrated by cords and focal aggregates of lymphocytes. The fringes of each aggregate were rather discrete, although in some sections directly contiguous with adipose tissue. The adipose tissue itself contained only a single patch of inflammatory reaction, predominantly lymphocytes. There were no germinal centers, necrosis, eosinophilia, or vasculitis; and virtually no plasma cells, granular leukocytes, or fibrosis. September 1984 COppelO et al. The sections were reviewed by three dermatopathologists, including an authority on lymphoid tumors of the orbit and ocular adnexae. All felt that the lesions represented a collection of uniformly mature lymphocytes without any suggestion of anaplasia. Their diagnosis was subcutaneous ·pseudotumor· or ·pseudolymphoma.w This histological description worried us because of the absence of reports of multicentric subcutaneous pseudotumors with or without orbital involvement, the known difficulty in differentiating between pseudolymphoma and lymphoma without immunohistochemical analysis, and the propensity for hyperplastic lymphocytic lesions to belie ultimate lymphomas. Therefore, the search was intensified for an underlying lymphoma. Radiographs of the left hip taken for an acute exacerbation of pain in the left thigh revealed a femoral osteoblastic lesion. Bone biopsy of that lesion as well as bone marrow aspiration revealed well-differentiated lymphoma replacing marrow elements (Figs. 5 and 6). The patient was treated with chemotherapy with resolution of orbitaL scalp, and femoral lesions. Discussion This case's course suggested the diagnosis of GCA by the presence of headache, long-standing proximal extremity myalgias, an elevated ESR, tender scalp nodules, visual loss, a negative evaluation for other inflammatory or disseminated neoplastic processes, and an exquisitely prompt and complete response of most symptoms and signs to systemic corticosteroids. However, the orbitocalvarial manifestations were sufficiently atypical to prompt neuro-ophthalmic consultation, which concluded that the scalp lesions were not typical of GCA because they actually consisted of recurrent areas of diffuse, firm urticarial swelling, and not hardened arterial cords. Moreover, although proptosis probably may occur as a complication of acute infarction of orbital tissue in GCA, a corticosteroid titratable inflammatory orbitopathy is inconsistent with that diagnosis. I Finally, the orbital CT scan suggested a periosteal inflammatory process in the lateral wall of the orbit rather than infarction of orbital tissue. Therefore, deep biopsy of the subcutaneous nodule adjacent to the skull periosteum was performed, and this provided the first due to the correct diagnosis. Proptosis is rarely associated with subcutaneous nodules. When it is, it may be secondary to metastatic carcinoma or sarcoma, leukemia or lymphoma, neuroblastoma, collagen vascular disease, Weber-Christian panniculitis, multifocal fibrosc1erosis, pseudosarcomatous fasciitis, sarcoidosis, tuberculosis, and fatal disseminated allergic angiitis. 1 - 7 The histopathology of our pa- 175 Calvarial Swelling Figurt J. Scollp biopsy. (H&:E. x40.) Nodub'r ol~tt'5 involving tht deep dtrmis olnd ~dipost~. tient's subcutaneous nodule was not typical of any of these lesions. Instead, it was characterized. by all reviewers as a subcutaneous pseudolymphoma. The tenn ·pseudolymphoma· refers to a group of benign pseudotumors that include a variety of dennatoses such as actinic reticulosis, lymphoid papulosis, lessner's lymphocytic infiltration, arthropod bites and stings, drug eruption, and lymphocytoma. Lymphocytoma (pseudolymphoma of Spiegler-Fendt) usually presents as a small nod- 116 ule or large plaque on the face or scalp. The histopathology, as in our case, is a heavy infiltrate of lymphocytes and histiocytes in the dennis, usually separated from the epidermis by a zone of nonnal collagen. In larger lesions, the inftltrate may extend into the subcutaneous tissue. Lymphoid- follicle-like arrangements may also be present., ·9 Although lymphocytoma is usually benign, any persistent lesion may ultimately prove to be malignant lymphoma. Identification of lymphocy- Journal of Clinical Neuro-ophthalmology Coppeto et al. FigUft' 4. Scalp biopsy. (H&E, xIOO.) Mature lymphocytes and hisriocytes. toma as distinct from malignant lymphoma is easy if a distinct follicular arrangement is present in some portion of the infiltrate. The presence of atypical histiocytes intermingled with lymphocytes or a monomorphous infiltrate of small, welldifferentiated lymphocytes is suspicious for, but not diagnostic of, malignant lymphoma.'·9 Although only about 1/4 of the nodule was excised in our case, all the histiocytes were normal- appearing, and all the lymphocytes were mature; therefore, supporting the diagnosis of lym- September 1984 phocytoma. However, the specter of malignant lymphoma was raised by the absence of germinal centers and the scarcity of plasma cells, granular leukocytes, and fibrous proliferation. If such a tissue had come from an orbital biopsy, it probably would have been designated inflammatory pseudotumor of the orbit of the ~reactive lymphocytic hyperplastic· type.l This type of orbital pseudotumor carries a more guarded prognosis in the absence of an admixture of plasma cells, granular leukocytes, and fibrous tissue; yet, even 177 Calvarial Swelling •'\> •' -• • -.. FiguTl!' 5. Bon~ biopsy. (H&E, )(100.) Mature lymphocytic «'lis replacing marrow ~Iements. left fnnuf. the presence of such features does not guarantee a benign prognosis. I Recent developments in the immunohistochemical characterization of innammatory orbital lesions are relevant to the present case. Lesions of the 'lymphocytic hyperplastic' type, particularly in the orbit, probably can be separated into lymphoma or pseudolymphoma on the basis of immunohistochemical analysis which suggests predominantly monoclonal (malignant) versus polydonal (benign) immunoglobulin-producing 178 cell lines. 10. 11 However, the possibility that even polydonal cell lines can ultimately revert into predominantly monoclonal cell lines characteristic of lymphoma is real. In fact, there is evidence that, over time, increasing numbers of such patients do eventually develop disseminated Iymphoma. 11 In our patient, immunohistochemical analysis probably would have pointed toward the diagnosis of lymphoma. However, such tissue analysis is not currently available at most hospitals and Journal of Clinical Neufo-ophthalmology Coppeto et al. -.\ •., -,. , - I.. : Figur~ 6. Bon~ biopsy. (H&E, x400.) Well·di(f~ntiiltedmalignant small cell lymphoma. •• • • • was not done on the present specimen. Nevertheless, our opinion was that the presumption of multicentric (scalp and orbit) pseudolymphoma was probably not justified, and this prompted the search for lymphoma. In conclusion, the presence of proptosis and scalp nodules may require an attempt to demonstrate radiographically the precise depth of the scalp nodule. and if necessary. biopsy deeply in order to obtain appropriate tissue. Fresh, unfixed tissue should be sent 10 an institution that does immunohistochemical analysis. Moreover, an aggressive search for disseminated neoplasm should be pursued, and bone marrow aspiration is probably justified in every case where primary neoplasm is othenvise not demonstrable. References 1. Jakobiec, F.A.. and Jont'S, 1.5.: Orbital innammation. In ClinicQI OphthQlmology. Vol. 2, T.O. September 1984 179 Calvarial Swelling Duane, Ed, Harper & Row, Hagerstown, 1980, chap. 35. 2. Henderson, J.W.: Orbital Tumors (2nd ed.). Thieme-Stratton, New York, 1980, chap. 21. 3. Ross, M., Cohen, K., Peiffer, R., and Crimson, B.: Episcleral and orbital pseudorheumatoid nodules. Arch. aphtha/mol. 101: 418-421, 1983. 4. Brenner, E., and Shock, J.P.: Proptosis secondary to systemic lupus erythematosis. Arch. Ophthalmol. 910: 81-82, 1974. 5. Nowinski, T., Bernardino, Y., Naidoff, M., and Parris, R.: Ocular involvement in lupus erythematosis profundus (panniculitis). Oph/halm%gy 89: 1149-1154,1982. 6. Brownstein, M.H., and Helwig, E_R.: Patterns of cutaneous metastasis. Arch. Derma/ol. 105: 862868,1972. 18<) 7. Rosen, T.: Cutaneous metastases. Med. Gin. North Am. 64: 885-900,1980. 8. Montgomery, H.: Derma/opathology, Vol. 2, Harper & Row, New York, 1967, 730-732; 1227-1229. 9. Rosai, J.: Ackerman's Surgical Pathology. C. Y. Mosby Co., St. Louis, 1981, pp. 138-143. 10. Knowles, D., Jakobiec, F., and Halper, J.: ImmunologiC characterization of ocular adnexal Iymphoid neoplasms. Am. J. Ophthalmol. 87: 603-619, 1978. 11. Knowles, D., and Jakobie-c, F.: Quantitative determination of T cells in ocular lymphoid infiltrates. Arch. Oph/ha/mol. 99: 309-316, 1981. 12. Morgan, C.. and Harry, J.: Lymphocytic tumors of indeterminate nature: A 5 year follow up of 98 conjunctival and orbital lesions. Br. J. Oph/halmol. 62: 381-383, 1978. Journal of Clinical Neuro-ophthalmology |
