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Juvenile Xanthogranuloma of the Orbit
J U V E N I L E XANTHOGRANULOMA O F T H E ORBIT P H I L I P M.
GAYNES, M.D.,
AND GORDON S.
COHEN,
M.D.
Neiv Haven, Connecticut A n uncommon cause of fever and proptosis is juvenile xanthogranuloma of the orbit. Also known as nevoxanthoendothelioma, this lesion is most often seen in ophthalmologic practice as an iris lesion. Juvenile xanthogranuloma usually manifests itself as a benign, dermatologie disease of children. Systemic manifestations are rare. Zimmer man, 1 emphasized that ocular manifestations are the only significant complication of this otherwise completely benign disease. It is the purpose of this publication to report a case of juvenile xanthogranuloma presenting with fever and severe proptosis. C A S E REPORT
S. W., an eight-month-old girl (64-41-57) was admitted to the Pediatrie Service of the YaleNew Haven Medical Center on June 17, 1965, with a one-week history of left proptosis and fever of 100°F to 101°F. There was no history of trauma and prior to this episode the child en joyed excellent health. Physical examination re vealed an active, well-developed child in no ap parent distress. Facial asymmetry with a left proptosis was present. A 2.0 by 3.0 cm firm mass lateral to the left external canthus was palpated (fig. 1). Lids, lacrimai apparatus and pupils were otherwise normal. The extraocular muscles showed limitation of abduction of the left eye. The anterior segment of the eye, including the iris, was nor mal. Dilated funduscopic examination revealed no abnormalities. The general physical examination, including inspection of the skin, was normal. The temperature was 38.5°C, pulse 120 and respiration 30. Laboratory data included WBC of 26,000 with 39% segmented forms, 8% band forms, 31% lym phocytes, 12% monocytes, 2% atypical lympho cytes and 8% eosinophils. The hematocrit was 28%. Cultures of the left cul-de-sac, nose, throat and blood were negative. Stools were negative for ova and parasites. X-ray films of the sinuses, skull and orbit were normal except for soft-tis sue swelling about the left orbit. No evidence of bone destruction was seen at this time. A tenta tive diagnosis of orbital cellulitis was made and the patient was started on intravenous sodium oxacillin (Prostaphlin), warm compresses and topi-
Fig. 1 (Gaynes and Cohen). Patient, age eight months, with proptosis of the left eye.
cal antibiotics to the left eye. After one week of therapy the patient's condition was unchanged and a diagnosis of orbital malignancy was considered. Consultation with the ophthalmology service was obtained. Repeat facial bone X-ray films showed some outward rotation of the zygomatic portion of the left orbit with separation of the zygomatic-frontal suture. An intravenous pyelogram was nor mal. Bone-marrow examination was unremarkable. (The patient had a microcytic, hypochromic anemia.) Iron dextran injection (Imferon) thera py resulted in a reticulocyte response of 4%; however, the hematocrit remained at 28% to 30%. The patient was then transfused with 120 cc of packed red cells with a resultant febrile reaction. On June 30, 1965 (two weeks after admission), a left orbital biopsy was performed. A modified Krönlein incision was made and the temporal muscle retracted laterally, revealing a cavity filled with blood, necrotic debris, tumor and fat. This material was sent for pathologic examination and the preliminary diagnosis was that of a benign From the Section of Ophthalmology, Depart lesion. ' ment of Surgery, and the Department of Pathol Repeat roentgenograms on July 3, 1965, showed ogy, Yale-New Haven Medical Center. mild irregular radiolucent areas in the left malar 755
756
AMERICAN JOURNAL OF OPHTHALMOLOGY
APRIL, 1967
ment of the extraocular motion including full left eye abduction. Following cessation of steroid therapy, repeat roentgenograms demonstrated rela tive remineralization of the previously involved bone. The several small, irregular, bloody fragments of tissue received for pathologic examination mi croscopically revealed a predominance of large cells with abundant foamy cytoplasm and large vesicular nuclei usually containing prominent eosinophilic nucleoli, interpreted as histiocytes. Scat tered among these histiocytes were numerous giant cells with the same nuclear morphology (fig. 3). In some of these, nuclei were arranged in a rosettelike pattern reminiscent of Touton giant cells. Numerous thin-walled blood vessels and fibroblasts were also present. Cellular pleomorphism was not a conspicuous feature. On the borders of some tissue fragments, extensive foci of hemorrhage were noted. Mitotic figures were rare. The final pathologic diagnosis was juvenile xanthogranuloma. DISCUSSION
Fig. 2 (Gaynes and Cohen). Demineralization of the left malar eminence. eminence (fig. 2). While awaiting a definitive decision from the pathologists, a therapeutic trial with radiation was begun on July S, 196S. The initial dose was 75 rads with progressive daily increases, totalling 700 rads. The 9-mm proptosis was not affected. On July 13, 1965, the final histologie diagnosis of juvenile xanthogranuloma was arrived at. The patient was treated with systemic steroids (Prednisone 10 mg four times a day). Within 36 hours the proptosis measured four mm. After four days of steroid therapy, the soft tissue mass had markedly reced ed and the proptosis was minimal. Limitation of abduction persisted. At the end of a four-month course of systemic steroids, marked clinical regression of the lesion was noted, with improve
Fig. 3 (Gaynes and Cohen). A representative area of the orbital tumor, demonstrating the extreme vascularity and multinucleate giant cells.
Juvenile xanthogranuloma (nevoxanthoendothelioma) is a lesion found predomi nantly in children, one week to 16 years of age. I t most often occurs as an elevated, asymptomatic, yellow-tan skin nodule about the neck or extremities. Multiple lesions are not uncommon. Those individuals affected show no alteration of serum lipids. Rarely, juvenile xanthogranuloma may occur intraocularly within the iris. 2 Secondary glauco ma may result from intraocular lesions when hyphema occurs. Histologically, juvenile xanthogranulomas are characteristically composed of large
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JUVENILE XANTHOGRANULOMA
lipid-laden histiocytes in a vascular fibrous stroma. Foreign body and Touton giant cells are present. Mitotic figures are not uncom mon. Although xanthogranulomas usually do not exceed five cm in size and are invari ably benign, Helwig and Hackney 3 reported a child who at autopsy had multiple cuta neous, pulmonary and testicular xantho granulomas. While it is not our purpose to discuss the histogenesis of this lesion, it should be pointed out that some authors do not regard it as a specific disease entity and they have implied that juvenile xanthogranuloma may represent a localized form of Hand-Schüller-Christian disease.4'5 Orbital lesions with bony involvement have been reported in only one previous case.6·7 Our case represents the second such report. Generally bone destruction has been interpreted roentgenologically as either di rect invasion or consequent to the effects of localized hyperemia. The latter is clearly consistent with the histologie pattern. Fever and hepatosplenomegaly are rare systemic complications. Fever in our case may have been a response to massive intraorbital hem orrhage and necrosis. Maumenee and others8"10 have reported the benefit of radiation therapy in intraocu lar lesions. While a tentative clinical diag nosis of a malignant orbital tumor was con sidered, radiation therapy in a total dose of 700 rads was given without effect. This casts doubt upon the efficacy of radiation therapy for this disease. However, 36 hours following the onset of steroid therapy, there was a measurable decrease in proptosis. It is possible, therefore, that high steroid doses
may represent adequate initial therapy for orbital juvenile xanthogranuloma although, as is'well known, the lesions commonly un dergo spontaneous regression. SUMMARY
The second case of juvenile xanthogranu loma of the orbit with bony involvement is reported in an eight-month-old girl. This lesion presented with fever and proptosis. An excellent response to steroid therapy resulted in restoration of normal appearance and function of the eye, muscles and orbit. 333 Cedar Street (06510) REFERENCES
1. Zimmerman, L. E. : Ocular lesions of juve nile xanthogranuloma (nevoxanthoendothelioma). Tr. Am. Acad. Ophthal. Otolaryn. 69 :412, 1965. 2. Moore, J. G. and Harry, J. : Juvenile xan thogranuloma. Brit. J. Ophth. 42:71, 1965. 3. Helwig, E. B. and Hackney, V. C. : Juvenile xanthogranuloma (nevoxanthoendothelioma). Ab stract Am. J. Path. 30:625, 1954. 4. 'Crocker, A. C. : Skin xanthomas in child hood. Pediatrics, 8:573, 1951. 5. Thannhauser, S. J. : Lipidoses. New York, Grune & Stratton, 1958, ed. 3, pp. 362-364. 6. Sanders, T. E. and Miller, J. E.: Infantile xanthogranuloma of the orbit: Report of a case. Tr. Amer. Acad. Ophthal. Otolaryng. 69:458, 1965. 7. Staple, T. W. McAlister, W. H., Sanders, T. E. and Miller, J. E. : Juvenile xanthogranuloma of the orbit: Report of a case with bone destruc tion. Am. J. Roentgen. 91:629, 1964. 8. Maumenee, A. E. and Longfellow, D. W. : Ocular lesions of nevoxanthoendothelioma (juve nile xanthogranuloma). Am. J. Ophth. 49:1, 1960. 9. Hedges, C. C, Jr. : Nevoxanthoendothelioma of the eye treated with superficial X-ray therapy. Am. J. Ophth. 47:683, 1959. 10. Cleasby, G. W. : Nevoxanthoendothelioma (juvenile xanthogranuloma) of the iris: Diagnosis by biopsy and treatment with X-ray. Arch. Ophth. 66:26, 1961.
GAYNES, M.D.,
AND GORDON S.
COHEN,
M.D.
Neiv Haven, Connecticut A n uncommon cause of fever and proptosis is juvenile xanthogranuloma of the orbit. Also known as nevoxanthoendothelioma, this lesion is most often seen in ophthalmologic practice as an iris lesion. Juvenile xanthogranuloma usually manifests itself as a benign, dermatologie disease of children. Systemic manifestations are rare. Zimmer man, 1 emphasized that ocular manifestations are the only significant complication of this otherwise completely benign disease. It is the purpose of this publication to report a case of juvenile xanthogranuloma presenting with fever and severe proptosis. C A S E REPORT
S. W., an eight-month-old girl (64-41-57) was admitted to the Pediatrie Service of the YaleNew Haven Medical Center on June 17, 1965, with a one-week history of left proptosis and fever of 100°F to 101°F. There was no history of trauma and prior to this episode the child en joyed excellent health. Physical examination re vealed an active, well-developed child in no ap parent distress. Facial asymmetry with a left proptosis was present. A 2.0 by 3.0 cm firm mass lateral to the left external canthus was palpated (fig. 1). Lids, lacrimai apparatus and pupils were otherwise normal. The extraocular muscles showed limitation of abduction of the left eye. The anterior segment of the eye, including the iris, was nor mal. Dilated funduscopic examination revealed no abnormalities. The general physical examination, including inspection of the skin, was normal. The temperature was 38.5°C, pulse 120 and respiration 30. Laboratory data included WBC of 26,000 with 39% segmented forms, 8% band forms, 31% lym phocytes, 12% monocytes, 2% atypical lympho cytes and 8% eosinophils. The hematocrit was 28%. Cultures of the left cul-de-sac, nose, throat and blood were negative. Stools were negative for ova and parasites. X-ray films of the sinuses, skull and orbit were normal except for soft-tis sue swelling about the left orbit. No evidence of bone destruction was seen at this time. A tenta tive diagnosis of orbital cellulitis was made and the patient was started on intravenous sodium oxacillin (Prostaphlin), warm compresses and topi-
Fig. 1 (Gaynes and Cohen). Patient, age eight months, with proptosis of the left eye.
cal antibiotics to the left eye. After one week of therapy the patient's condition was unchanged and a diagnosis of orbital malignancy was considered. Consultation with the ophthalmology service was obtained. Repeat facial bone X-ray films showed some outward rotation of the zygomatic portion of the left orbit with separation of the zygomatic-frontal suture. An intravenous pyelogram was nor mal. Bone-marrow examination was unremarkable. (The patient had a microcytic, hypochromic anemia.) Iron dextran injection (Imferon) thera py resulted in a reticulocyte response of 4%; however, the hematocrit remained at 28% to 30%. The patient was then transfused with 120 cc of packed red cells with a resultant febrile reaction. On June 30, 1965 (two weeks after admission), a left orbital biopsy was performed. A modified Krönlein incision was made and the temporal muscle retracted laterally, revealing a cavity filled with blood, necrotic debris, tumor and fat. This material was sent for pathologic examination and the preliminary diagnosis was that of a benign From the Section of Ophthalmology, Depart lesion. ' ment of Surgery, and the Department of Pathol Repeat roentgenograms on July 3, 1965, showed ogy, Yale-New Haven Medical Center. mild irregular radiolucent areas in the left malar 755
756
AMERICAN JOURNAL OF OPHTHALMOLOGY
APRIL, 1967
ment of the extraocular motion including full left eye abduction. Following cessation of steroid therapy, repeat roentgenograms demonstrated rela tive remineralization of the previously involved bone. The several small, irregular, bloody fragments of tissue received for pathologic examination mi croscopically revealed a predominance of large cells with abundant foamy cytoplasm and large vesicular nuclei usually containing prominent eosinophilic nucleoli, interpreted as histiocytes. Scat tered among these histiocytes were numerous giant cells with the same nuclear morphology (fig. 3). In some of these, nuclei were arranged in a rosettelike pattern reminiscent of Touton giant cells. Numerous thin-walled blood vessels and fibroblasts were also present. Cellular pleomorphism was not a conspicuous feature. On the borders of some tissue fragments, extensive foci of hemorrhage were noted. Mitotic figures were rare. The final pathologic diagnosis was juvenile xanthogranuloma. DISCUSSION
Fig. 2 (Gaynes and Cohen). Demineralization of the left malar eminence. eminence (fig. 2). While awaiting a definitive decision from the pathologists, a therapeutic trial with radiation was begun on July S, 196S. The initial dose was 75 rads with progressive daily increases, totalling 700 rads. The 9-mm proptosis was not affected. On July 13, 1965, the final histologie diagnosis of juvenile xanthogranuloma was arrived at. The patient was treated with systemic steroids (Prednisone 10 mg four times a day). Within 36 hours the proptosis measured four mm. After four days of steroid therapy, the soft tissue mass had markedly reced ed and the proptosis was minimal. Limitation of abduction persisted. At the end of a four-month course of systemic steroids, marked clinical regression of the lesion was noted, with improve
Fig. 3 (Gaynes and Cohen). A representative area of the orbital tumor, demonstrating the extreme vascularity and multinucleate giant cells.
Juvenile xanthogranuloma (nevoxanthoendothelioma) is a lesion found predomi nantly in children, one week to 16 years of age. I t most often occurs as an elevated, asymptomatic, yellow-tan skin nodule about the neck or extremities. Multiple lesions are not uncommon. Those individuals affected show no alteration of serum lipids. Rarely, juvenile xanthogranuloma may occur intraocularly within the iris. 2 Secondary glauco ma may result from intraocular lesions when hyphema occurs. Histologically, juvenile xanthogranulomas are characteristically composed of large
VOL. 63, NO. 4
757
JUVENILE XANTHOGRANULOMA
lipid-laden histiocytes in a vascular fibrous stroma. Foreign body and Touton giant cells are present. Mitotic figures are not uncom mon. Although xanthogranulomas usually do not exceed five cm in size and are invari ably benign, Helwig and Hackney 3 reported a child who at autopsy had multiple cuta neous, pulmonary and testicular xantho granulomas. While it is not our purpose to discuss the histogenesis of this lesion, it should be pointed out that some authors do not regard it as a specific disease entity and they have implied that juvenile xanthogranuloma may represent a localized form of Hand-Schüller-Christian disease.4'5 Orbital lesions with bony involvement have been reported in only one previous case.6·7 Our case represents the second such report. Generally bone destruction has been interpreted roentgenologically as either di rect invasion or consequent to the effects of localized hyperemia. The latter is clearly consistent with the histologie pattern. Fever and hepatosplenomegaly are rare systemic complications. Fever in our case may have been a response to massive intraorbital hem orrhage and necrosis. Maumenee and others8"10 have reported the benefit of radiation therapy in intraocu lar lesions. While a tentative clinical diag nosis of a malignant orbital tumor was con sidered, radiation therapy in a total dose of 700 rads was given without effect. This casts doubt upon the efficacy of radiation therapy for this disease. However, 36 hours following the onset of steroid therapy, there was a measurable decrease in proptosis. It is possible, therefore, that high steroid doses
may represent adequate initial therapy for orbital juvenile xanthogranuloma although, as is'well known, the lesions commonly un dergo spontaneous regression. SUMMARY
The second case of juvenile xanthogranu loma of the orbit with bony involvement is reported in an eight-month-old girl. This lesion presented with fever and proptosis. An excellent response to steroid therapy resulted in restoration of normal appearance and function of the eye, muscles and orbit. 333 Cedar Street (06510) REFERENCES
1. Zimmerman, L. E. : Ocular lesions of juve nile xanthogranuloma (nevoxanthoendothelioma). Tr. Am. Acad. Ophthal. Otolaryn. 69 :412, 1965. 2. Moore, J. G. and Harry, J. : Juvenile xan thogranuloma. Brit. J. Ophth. 42:71, 1965. 3. Helwig, E. B. and Hackney, V. C. : Juvenile xanthogranuloma (nevoxanthoendothelioma). Ab stract Am. J. Path. 30:625, 1954. 4. 'Crocker, A. C. : Skin xanthomas in child hood. Pediatrics, 8:573, 1951. 5. Thannhauser, S. J. : Lipidoses. New York, Grune & Stratton, 1958, ed. 3, pp. 362-364. 6. Sanders, T. E. and Miller, J. E.: Infantile xanthogranuloma of the orbit: Report of a case. Tr. Amer. Acad. Ophthal. Otolaryng. 69:458, 1965. 7. Staple, T. W. McAlister, W. H., Sanders, T. E. and Miller, J. E. : Juvenile xanthogranuloma of the orbit: Report of a case with bone destruc tion. Am. J. Roentgen. 91:629, 1964. 8. Maumenee, A. E. and Longfellow, D. W. : Ocular lesions of nevoxanthoendothelioma (juve nile xanthogranuloma). Am. J. Ophth. 49:1, 1960. 9. Hedges, C. C, Jr. : Nevoxanthoendothelioma of the eye treated with superficial X-ray therapy. Am. J. Ophth. 47:683, 1959. 10. Cleasby, G. W. : Nevoxanthoendothelioma (juvenile xanthogranuloma) of the iris: Diagnosis by biopsy and treatment with X-ray. Arch. Ophth. 66:26, 1961.