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Juvenile Xanthogranuloma of the Optic Nerve, Disc, Retina, and Choroid
Juvenile Xanthogranuloma of the Optic Nerve, Disc, Retina, and Choroid FLEMING D. WERTZ, LtC, MC, USA,* LORENZ E. ZIMMERMAN, MD,t CRAIG A. McKEOWN, LtC, MC, USA,* JUAN O. CROXATTO, MD,t PAUL V. WHITMORE, Col, MC, USA,* FRANCIS G. LaPIANA, Col, MC, USA*
Abstract: A 20-month-old infant found to have a blind eye with neovascular glaucoma was thought to have a neoplasm of the optic nerve for which enucleation was performed with resection of a long segment of optic nerve. Microscopic examination revealed the enlarged optic nerve and optic papilla to be infiltrated densely by histiocytic cells, including Touton giant cells, all containing large amounts of neutral fat. The histologic picture was indistinguishable from that of juvenile xanthogranuloma. Occlusion of the central retinal vessels had led to hemorrhagic infarction of the retina and neovascular glaucoma. Thorough clinical and laboratory investigations repeated over a period of more than 2112 years failed to disclose any evidence of a systemic disease, and the child has remained in good health. This is believed to be a unique case of juvenile xanthogranuloma of the optic nerve and disc. [Key words: choroid, disc, juvenile xanthogranuloma, optic nerve, retina.] Ophthalmology 89: 1331-1335, 1982
Juvenile xanthogranuloma (JXG) is primarily a pediatric dermatologic disease characterized by nodular skin lesions occurring typically in infancy and early childhood. It is well known to ophthalmologists mainly because of the infrequently associated iridic lesions, which give rise to spontaneous hyphemas, secondary glaucoma, uveitis, and/or heterochromia iridis. Although the first reports of the skin lesions of JXG appeared early in this century, it was not until 1949 that the intraocular manifestations of this disease were recognized. 1 By 1960, 20 cases of iritraocular From the Ophthalmology Service, Walter Reed Army Medical Center, Washington, DC;* and the Department of Ophthalmic Pathology, Armed Forces Institute of Pathology, Washington, DC.t The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of the Army or the Department of Defense. Reprint requests to Lorenz E. Zimmerman, MD, Department of Ophthalmic Pathology, Armed Foroes Institute of Pathology, Washington, DC 20306.
0161-6420/82/1200/13311$1.05
© American Academy of Ophthalmology
JXG. had been described and successful therapeutic programs outlined. 2 Zimmerman, reporting on 53 cases from the Registry of Ophthalmic Pathology at the Armed Forces Institute of Pathology, described the various ocular manifestations and reviewed the histopathology of each. 3 Juvenile xanthogranuloma is a granulomatous disease characterized by the replacement of normal tissue by masses of benign histiocytes. Characteristically, the lesions contain Touton and other multinucleated giant cells and have a scattered background of other inflammatory cells, including a variable number of eosinophils. As noted, the most frequently involved organ is the skin where crops of small reddish-orange nodular lesions may be noted on the head and neck, upper trunk, and extremities. Organs other than the skin and eyes are rarely involved. There are case reports of histiocytic lesions in lungs, pericardium, viscera, testes, and bone. 4 - 6 Although fever and anemia have been reported, JXG is generally not considered to be a systemic disease. In reviewing the characteristic clinical picture of these patients, however, it has been 1331
OPHTHALMOLOGY • DECEMBER 1982 • VOLUME 89 • NUMBER 12
found that mariy have cafe-au-Iait spots, and some have a family history of neurofibromatosis. 7 - 10 Over 90% of these patients do well without systemic manifestations of either disease. Some who have the constellation of JXG, cafe-au-Iait spots and a family history of neurofibromatosis may manifest problems associated with neurofibromatosis or systemic illriesses consisting of fever, anemia, hepatomegaly, and mono myeloid blood changes. 7 Finally, JXG is differentiated from the disseminated histiocytosis (eg, Hand-SchOller-Christian disease, Letterer-Siwe disease, etc) by its typical lack of systemic signs or symptoms and cytologically by the lack of characteristic intracytoplasmic organelles (Langerhan's granules) in the histiocytes. l l Ocular manifestations of JXG include lesions of the iris, ciliary body, cornea, conjunctiva, eyelids, and orbit. 3 To the best of our knowledge, neither the brain nor the optic nerve have been involved in JXG. This report describes the case of a child with JXG apparently limited to the optic nerve, disc, and choroid of one eye.
CASE REPORT CLINICAL HISTORY A 20-month-old white girl was admitted to the Walter Reed Army Medical Center in Washington, DC, with a two-day history of a fixed dilated pupil in the right eye. The parents had also noted that the patient's normally blue right eye had become darker over the preceding ten days and that the child had been unusually irritable during the same period. The family history was unremarkable, and the infant had five healthy siblings. The growth and development were normal with timely immunizations and no known allergies. There was no history of trauma, and the patient was on no medications. Physical examination at the time of admission revealed a somewhat irritable, afebrile 20-month-old girl. The right eye appeared amaurotic with normal fixation in the left eye. The right pupil was fixed and dilated, lacking both direct and consensual responses to light. The left pupil reacted briskly to direct light but failed to react consensually. There was no nystagmus and no proptosis. Minimal resistance to retropulsion was present on the right. Ductions were normal in both eyes with no evidence of strabismus using Hirschberg's corneal reflex test. The lids and conjunctiva were normal bilaterally. The left anterior segment was normal with a blue iris, while the right eye showed a brownish-gray iris with biomicroscopic evidence of rubeosis iridis. The cornea and lens appeared normal. The left fundus was normal. The vitreous on the right was slightly hazy from intravitreal blood. The area normally occupied by the right optic disc revealed an elevated 'yellowish-white mass measuring approximately 4.5 mm vertically, 4.5 mm horizontally, and 3 mm in height (Fig 1). Telangiectatic vessels were present on the surface of the mass and the major retinal vessels were obscured by it. A "tomato-ketchup" fundus was present, believed to have been the result of central retinal vein obstruction. Obliteration of the retinal arteries, with retinal edema extending into tile far periphery was also observed. Intraocular pressure by Schitz tonometry was 20 mm Hg in the right eye. The remainder of the physical examination was normal.
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Laboratory studies revealed a hematocrit of 36.3%, with a hemoglobin of 12.2 gm; the white blood count was 11,000 with a normal differential. Urinalysis, serum lipid· determinations, and an ELISA test for toxocariasis revealed no abnormalities. Radiographs of the chest, skul~, and orbits were normal. Views of the right optic foramen revealed no abnormalities. Ultrasonography demonstrated a pattern consistent with a solid enlargement of the optic nerve and increased thickness of the posterior retina, associated with a serous detachment of the peripapillery retina (Fig 2). Computerized tomography of the head and orbits using second degeneration equipment revealed questionable enlargment of the optic nerve adjacent to the globe and contrast enhancement of the posterior uyeoscleral rim on the right. Because a neoplasm of the optic nerve was suspected, and because the eye was blind and painful, enucleation was performed approximately three weeks after onset of clinical manifestations. A 16-mm segment of optic nerve was removed with the globe (Fig 3). It contained a rubbery, fusiform, intradural mass that extended back 10 mm posterior to the globe and measuring 7 mm in its greatest thickness (Figs 3, 4). Longitudinal and transverse sections revealed the thickened distal part of the nerve to have a yellowish discoloration as compared with the ivory-colored tissues at the plane of surgical transection (Fig 4). The patient's postoperative course was uneventful. Thorough examination revealed no skin lesions, lymphadenopathy, or organomegaly. Additional clinical investigation, which included a liver-spleen scan, a gallium bone scan, a lumbar puncture, and bone marrow biopsy, all failed to reveal any evidence of a systemic disease. Her condition was reevaluated twice during the first 15 months after enucleation, and on neither occasion was there any evidence of systemic involvement or local recurrence. Growth and development continued to ge normal, and now, almost three years after enucleation, the child remains in good health. PATHOLOGIC FINDINGS
The enucleated eye, which measuring 22 x 20 x 20 mm, had a long segment of enlarged optic nerve attached (Fig 3). The distal half was markedly thickened but posteriorly it tapered to approximately normal thickness at the site of surgical transection (Fig 4). On transection through the markedly thickened distal segment, the nerve presented a homogenous yellowish appearance (Fig 4). The clear cornea measured 12 x 11.5 mm. The dilated pupil measured 8 mm. Upon opening the eye in the horizontal plane, the anterior chamber was 'found to be shallow. There was ectropion uveae, and the vitreous body had a diffuse brownish discoloration. Several prominent retinal hemorrhages radiated from the prominently swollen and very irregularly outlined optic nerve head (Fig 5). Inferiorly the retina was detached and proteinaceous exudate was present in the subretinal space. Histologic examination revealed massive proliferation of large histiocytic cells in the optic nerve, optic nerve head, andjuxtapapillary retina and choroid (Figs 6-8). Accompanying the large mononuclear cells were many multinucleated giant cells, some of which were the Touton variety (Figs 9-11). Some of the mononuclear cells and some of the giant cells had an abundance of pale-staining, vacuolated cytoplasm. Frozen sec-
Fig 1. Left, posterior pole of right eye. Intravitreal blood obscures elevated yellowish-white optic disc (AFIP Neg. 82-7472). Fig 2. Above, Bronson-Turner B-scan ofright eye. Intrascleral and retrobulbar portions of optic nerve are enlarged (single arrow). Peripapillary retina is thickened and detached (double arrow heads) (AFIP Neg. 82-7180).
Fig 3. Top left, enucleated right eye and attached portion of optic nerve demonstrating fusiform thickening of retrobulbar nerve (AFIP Neg. 82-7473). Fig 4. Top right, longitudinal and cross-section of thickened retrobulbar nerve demonstrating yellow homogeneous tissue (AFIP Neg. 82-7474). Fig 5. Bottom left, right eye opened in horizontal plane demonstrating enlarged optic disc, thickened and detached peripapillary retina, and intraretinal and perivascular hemorrhage (AFIP Neg. 82-7475). Fig 6. Bottom right, longitudinal histologic section of optic nerve corresponding to the longitudinal section shown in left half of Figure 4. The thickened distal portion is enlarged and replaced by histiocytic cells shown in Figures 9 and 10 (AFIP Neg. 79-12583).
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OPHTHALMOLOGY • DECEMBER 1982 • VOLUME 89 • NUMBER 12
Fig 7. Top left, massive infiltration and thickening of optic nerve head by histiocytic cells shown in Figure 11. A similar histiocytic infiltrate present in the choroid immediately to the right of the nerve head is shown at higher magnification in Figure 8. There is serous detachment of the peripapillary retina (AFIP Neg. 79-12582). Fig 8. Top right, histiocytic infiltration of juxtapapillary choroid (AFIP Neg. 79-12576). Fig 9. Second row left, the architecture of the optic nerve is obscured by the diffuse infiltration and replacement by histiocytic and other inflammatory cells (AFIP Neg. 79-12585. Fig 10. Second row right, a prominent Touton giant cell and many eosinophils are present among the predominating histiocytic cells in the optic nerve. (AFIP Neg. 79-12586). Fig 11. Third row left, Multinucleated giant cells and histiocytes in the swollen optic nerve head shown in Fig 7 (AFIP Neg. 79-12578). Fig 12. Third row right, frozen section stained with oil red 0 reveals an abundance of neutral fat within the histiocytic cells. The peripheral cytoplasm of a Touton giant cell is also filled with lipid (AFIP Neg. 79-13438). Fig 13. Bottom left, same field shown in Fig 12 photographed using polarized light reveals birefringent intracellular crystals (AFIP Neg. 79-13439). Fig 14. Bottom right, longitudinal section through collapsed central retinal vein reveals massive replacement of its walls by histiocytic cells among which are many multinucleated giant cells (AFIP Neg. 79-12589).
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WERTZ, et al • JUVENILE XANTHOGRANULOMA
tions stained for lipid with the oil red 0 stain revealed large amounts of neutral fat within the histiocytes and Touton giant cells (Fig 12), and with polarized light, birefringent crystals could be seen (Fig 13). In some foci, a light infiltrate of eosinophils was associated with the predominantly mononuclear infiltrate. There also were small foci of lymphoplasmacytic infiltration, particularly in the immediate vicinity of dilated blood vessels. This was observed most conspicuously at the posterior edge of the lesion where the process merged with comparatively normal optic nerve. While the leptomeninges were slightly involved, the abnormal cellular infiltrate was predominantly within the parenchyma of the optic nerve. No extradural involvement was observed, nor were any episcleral lesions identified. Electron microscopy was employed in an effort to demonstrate Langerhan's granules within the histiocytic cells, but none were found. The massive involvement of optic nerve and optic nerve head led to an obliteration of the lumens of the central retinal vein (Fig 14) and artery. The vessels on the disc were markedly engorged, and there was extensive hemorrhagic necrosis of the retina associated with extreme neovascularization of the iris and broad peripheral anterior synechias. There was also extensive serosanguineous detachment of the retina, and hemorrhage into the vitreous. Our histopathologic diagnoses were juvenile xanthogranuloma of the optic nerve, optic papilla, retina, and choroid, with hemorrhagic infarction of the retina, and neovascular glaucoma.
DISCUSSION This case was studied in consultation by several experienced pathologists in the AFIP's Departments of Neuropathology, Pediatric Pathology, Dermatopathology, and Infectious Diseases, as well as by the staff of the Department of Ophthalmic Pathology. It was the consensus of these reviewers that the histopathologic changes are consistent with those of juvenile xanthogranuloma, but that the possibility of
some form of "histiocytosis X" or other systemic disease would have to be considered. The absence of Langerhan's granules upon electron microscopic examination is consistent with juvenile xanthogranuloma but a strong point against Hand-SchullerChristian disease, J.etterer-Siwe disease, and related systemic histiocytoses as the histiocytes in these disorders characteristically contain these cytoplasmic organelles. l l None of the reviewers could recall having seen or heard of a similar case. Subsequent clinical, radiologic, and laboratory investigations failed to reveal any abnormalities, and the child's normal development would seem to have eliminated the possibility of a systemic disease, whether of an infectious, metabolic, or immunodeficiency disease.
REFERENCES 1. Blank H, Eglick PG, Beerman H. Nevoxantho-endothelioma with ocular involvement. Pediatrics 1949; 4:349-54. 2. Sanders TE. Intraocular juvenile xanthogranuloma (nevoxanthogranuloma): a survey of 20 cases. Trans Am Ophthalmol Soc 1960; 58:59- 74. 3. Zimmerman LE. Ocular lesions of juvenile xanthogranuloma. Nevoxanthoendothelioma. Trans Am Acad Ophthalmol Otolaryngol 1965; 69:412-42. 4. Helwig EB, Hackney VC. Juvenile xanthogranuloma (nevoxantho-endothelioma). Am J Pathol 1954; 30:625-6. 5. Lamb JH, Lain ES. Nevo-xantho-endothelioma. Its relationship to juvenile xanthoma. South Med J 1937; 30:585-94. 6. Webster SB, Reister HC, Harman LE Jr. Juvenile xanthogranuloma with extracutaneous lesions. A case report and review of the literature. Arch Dermatol 1966; 93:71-6. 7. Crocker AC. The histiocytosis syndromes. In: Fitzpatrick TB, Eisen AZ, Wolff K, et ai, eds. Dermatology in General Medicine, 2nd ed. New York: McGraw-Hili, 1979; 1171-81. 8. Marten RH, Sarkany I. Naevoxanthoendothelioma with pigmentary abnormalities. Br J Dermatol 1960; 72:308-11. 9. Jensen NE, Sabharwal S, Walker AE. Naevoxanthoendothelioma and neurofibromatosis. Br J Dermatol 1971; 85:326-30. 10. Newell GB, Stone OJ, Mullins JF. Juvenile xanthogranuloma and neurofibromatosis. Arch Dermatol 1973; 107:262. 11. Lever WF, Schaumburg-Lever, G. Histopathology of the Skin, 5th ed. Philadelphia, J.B. Lippincott, 1975; 372-9.
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Abstract: A 20-month-old infant found to have a blind eye with neovascular glaucoma was thought to have a neoplasm of the optic nerve for which enucleation was performed with resection of a long segment of optic nerve. Microscopic examination revealed the enlarged optic nerve and optic papilla to be infiltrated densely by histiocytic cells, including Touton giant cells, all containing large amounts of neutral fat. The histologic picture was indistinguishable from that of juvenile xanthogranuloma. Occlusion of the central retinal vessels had led to hemorrhagic infarction of the retina and neovascular glaucoma. Thorough clinical and laboratory investigations repeated over a period of more than 2112 years failed to disclose any evidence of a systemic disease, and the child has remained in good health. This is believed to be a unique case of juvenile xanthogranuloma of the optic nerve and disc. [Key words: choroid, disc, juvenile xanthogranuloma, optic nerve, retina.] Ophthalmology 89: 1331-1335, 1982
Juvenile xanthogranuloma (JXG) is primarily a pediatric dermatologic disease characterized by nodular skin lesions occurring typically in infancy and early childhood. It is well known to ophthalmologists mainly because of the infrequently associated iridic lesions, which give rise to spontaneous hyphemas, secondary glaucoma, uveitis, and/or heterochromia iridis. Although the first reports of the skin lesions of JXG appeared early in this century, it was not until 1949 that the intraocular manifestations of this disease were recognized. 1 By 1960, 20 cases of iritraocular From the Ophthalmology Service, Walter Reed Army Medical Center, Washington, DC;* and the Department of Ophthalmic Pathology, Armed Forces Institute of Pathology, Washington, DC.t The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of the Army or the Department of Defense. Reprint requests to Lorenz E. Zimmerman, MD, Department of Ophthalmic Pathology, Armed Foroes Institute of Pathology, Washington, DC 20306.
0161-6420/82/1200/13311$1.05
© American Academy of Ophthalmology
JXG. had been described and successful therapeutic programs outlined. 2 Zimmerman, reporting on 53 cases from the Registry of Ophthalmic Pathology at the Armed Forces Institute of Pathology, described the various ocular manifestations and reviewed the histopathology of each. 3 Juvenile xanthogranuloma is a granulomatous disease characterized by the replacement of normal tissue by masses of benign histiocytes. Characteristically, the lesions contain Touton and other multinucleated giant cells and have a scattered background of other inflammatory cells, including a variable number of eosinophils. As noted, the most frequently involved organ is the skin where crops of small reddish-orange nodular lesions may be noted on the head and neck, upper trunk, and extremities. Organs other than the skin and eyes are rarely involved. There are case reports of histiocytic lesions in lungs, pericardium, viscera, testes, and bone. 4 - 6 Although fever and anemia have been reported, JXG is generally not considered to be a systemic disease. In reviewing the characteristic clinical picture of these patients, however, it has been 1331
OPHTHALMOLOGY • DECEMBER 1982 • VOLUME 89 • NUMBER 12
found that mariy have cafe-au-Iait spots, and some have a family history of neurofibromatosis. 7 - 10 Over 90% of these patients do well without systemic manifestations of either disease. Some who have the constellation of JXG, cafe-au-Iait spots and a family history of neurofibromatosis may manifest problems associated with neurofibromatosis or systemic illriesses consisting of fever, anemia, hepatomegaly, and mono myeloid blood changes. 7 Finally, JXG is differentiated from the disseminated histiocytosis (eg, Hand-SchOller-Christian disease, Letterer-Siwe disease, etc) by its typical lack of systemic signs or symptoms and cytologically by the lack of characteristic intracytoplasmic organelles (Langerhan's granules) in the histiocytes. l l Ocular manifestations of JXG include lesions of the iris, ciliary body, cornea, conjunctiva, eyelids, and orbit. 3 To the best of our knowledge, neither the brain nor the optic nerve have been involved in JXG. This report describes the case of a child with JXG apparently limited to the optic nerve, disc, and choroid of one eye.
CASE REPORT CLINICAL HISTORY A 20-month-old white girl was admitted to the Walter Reed Army Medical Center in Washington, DC, with a two-day history of a fixed dilated pupil in the right eye. The parents had also noted that the patient's normally blue right eye had become darker over the preceding ten days and that the child had been unusually irritable during the same period. The family history was unremarkable, and the infant had five healthy siblings. The growth and development were normal with timely immunizations and no known allergies. There was no history of trauma, and the patient was on no medications. Physical examination at the time of admission revealed a somewhat irritable, afebrile 20-month-old girl. The right eye appeared amaurotic with normal fixation in the left eye. The right pupil was fixed and dilated, lacking both direct and consensual responses to light. The left pupil reacted briskly to direct light but failed to react consensually. There was no nystagmus and no proptosis. Minimal resistance to retropulsion was present on the right. Ductions were normal in both eyes with no evidence of strabismus using Hirschberg's corneal reflex test. The lids and conjunctiva were normal bilaterally. The left anterior segment was normal with a blue iris, while the right eye showed a brownish-gray iris with biomicroscopic evidence of rubeosis iridis. The cornea and lens appeared normal. The left fundus was normal. The vitreous on the right was slightly hazy from intravitreal blood. The area normally occupied by the right optic disc revealed an elevated 'yellowish-white mass measuring approximately 4.5 mm vertically, 4.5 mm horizontally, and 3 mm in height (Fig 1). Telangiectatic vessels were present on the surface of the mass and the major retinal vessels were obscured by it. A "tomato-ketchup" fundus was present, believed to have been the result of central retinal vein obstruction. Obliteration of the retinal arteries, with retinal edema extending into tile far periphery was also observed. Intraocular pressure by Schitz tonometry was 20 mm Hg in the right eye. The remainder of the physical examination was normal.
1332
Laboratory studies revealed a hematocrit of 36.3%, with a hemoglobin of 12.2 gm; the white blood count was 11,000 with a normal differential. Urinalysis, serum lipid· determinations, and an ELISA test for toxocariasis revealed no abnormalities. Radiographs of the chest, skul~, and orbits were normal. Views of the right optic foramen revealed no abnormalities. Ultrasonography demonstrated a pattern consistent with a solid enlargement of the optic nerve and increased thickness of the posterior retina, associated with a serous detachment of the peripapillery retina (Fig 2). Computerized tomography of the head and orbits using second degeneration equipment revealed questionable enlargment of the optic nerve adjacent to the globe and contrast enhancement of the posterior uyeoscleral rim on the right. Because a neoplasm of the optic nerve was suspected, and because the eye was blind and painful, enucleation was performed approximately three weeks after onset of clinical manifestations. A 16-mm segment of optic nerve was removed with the globe (Fig 3). It contained a rubbery, fusiform, intradural mass that extended back 10 mm posterior to the globe and measuring 7 mm in its greatest thickness (Figs 3, 4). Longitudinal and transverse sections revealed the thickened distal part of the nerve to have a yellowish discoloration as compared with the ivory-colored tissues at the plane of surgical transection (Fig 4). The patient's postoperative course was uneventful. Thorough examination revealed no skin lesions, lymphadenopathy, or organomegaly. Additional clinical investigation, which included a liver-spleen scan, a gallium bone scan, a lumbar puncture, and bone marrow biopsy, all failed to reveal any evidence of a systemic disease. Her condition was reevaluated twice during the first 15 months after enucleation, and on neither occasion was there any evidence of systemic involvement or local recurrence. Growth and development continued to ge normal, and now, almost three years after enucleation, the child remains in good health. PATHOLOGIC FINDINGS
The enucleated eye, which measuring 22 x 20 x 20 mm, had a long segment of enlarged optic nerve attached (Fig 3). The distal half was markedly thickened but posteriorly it tapered to approximately normal thickness at the site of surgical transection (Fig 4). On transection through the markedly thickened distal segment, the nerve presented a homogenous yellowish appearance (Fig 4). The clear cornea measured 12 x 11.5 mm. The dilated pupil measured 8 mm. Upon opening the eye in the horizontal plane, the anterior chamber was 'found to be shallow. There was ectropion uveae, and the vitreous body had a diffuse brownish discoloration. Several prominent retinal hemorrhages radiated from the prominently swollen and very irregularly outlined optic nerve head (Fig 5). Inferiorly the retina was detached and proteinaceous exudate was present in the subretinal space. Histologic examination revealed massive proliferation of large histiocytic cells in the optic nerve, optic nerve head, andjuxtapapillary retina and choroid (Figs 6-8). Accompanying the large mononuclear cells were many multinucleated giant cells, some of which were the Touton variety (Figs 9-11). Some of the mononuclear cells and some of the giant cells had an abundance of pale-staining, vacuolated cytoplasm. Frozen sec-
Fig 1. Left, posterior pole of right eye. Intravitreal blood obscures elevated yellowish-white optic disc (AFIP Neg. 82-7472). Fig 2. Above, Bronson-Turner B-scan ofright eye. Intrascleral and retrobulbar portions of optic nerve are enlarged (single arrow). Peripapillary retina is thickened and detached (double arrow heads) (AFIP Neg. 82-7180).
Fig 3. Top left, enucleated right eye and attached portion of optic nerve demonstrating fusiform thickening of retrobulbar nerve (AFIP Neg. 82-7473). Fig 4. Top right, longitudinal and cross-section of thickened retrobulbar nerve demonstrating yellow homogeneous tissue (AFIP Neg. 82-7474). Fig 5. Bottom left, right eye opened in horizontal plane demonstrating enlarged optic disc, thickened and detached peripapillary retina, and intraretinal and perivascular hemorrhage (AFIP Neg. 82-7475). Fig 6. Bottom right, longitudinal histologic section of optic nerve corresponding to the longitudinal section shown in left half of Figure 4. The thickened distal portion is enlarged and replaced by histiocytic cells shown in Figures 9 and 10 (AFIP Neg. 79-12583).
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OPHTHALMOLOGY • DECEMBER 1982 • VOLUME 89 • NUMBER 12
Fig 7. Top left, massive infiltration and thickening of optic nerve head by histiocytic cells shown in Figure 11. A similar histiocytic infiltrate present in the choroid immediately to the right of the nerve head is shown at higher magnification in Figure 8. There is serous detachment of the peripapillary retina (AFIP Neg. 79-12582). Fig 8. Top right, histiocytic infiltration of juxtapapillary choroid (AFIP Neg. 79-12576). Fig 9. Second row left, the architecture of the optic nerve is obscured by the diffuse infiltration and replacement by histiocytic and other inflammatory cells (AFIP Neg. 79-12585. Fig 10. Second row right, a prominent Touton giant cell and many eosinophils are present among the predominating histiocytic cells in the optic nerve. (AFIP Neg. 79-12586). Fig 11. Third row left, Multinucleated giant cells and histiocytes in the swollen optic nerve head shown in Fig 7 (AFIP Neg. 79-12578). Fig 12. Third row right, frozen section stained with oil red 0 reveals an abundance of neutral fat within the histiocytic cells. The peripheral cytoplasm of a Touton giant cell is also filled with lipid (AFIP Neg. 79-13438). Fig 13. Bottom left, same field shown in Fig 12 photographed using polarized light reveals birefringent intracellular crystals (AFIP Neg. 79-13439). Fig 14. Bottom right, longitudinal section through collapsed central retinal vein reveals massive replacement of its walls by histiocytic cells among which are many multinucleated giant cells (AFIP Neg. 79-12589).
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WERTZ, et al • JUVENILE XANTHOGRANULOMA
tions stained for lipid with the oil red 0 stain revealed large amounts of neutral fat within the histiocytes and Touton giant cells (Fig 12), and with polarized light, birefringent crystals could be seen (Fig 13). In some foci, a light infiltrate of eosinophils was associated with the predominantly mononuclear infiltrate. There also were small foci of lymphoplasmacytic infiltration, particularly in the immediate vicinity of dilated blood vessels. This was observed most conspicuously at the posterior edge of the lesion where the process merged with comparatively normal optic nerve. While the leptomeninges were slightly involved, the abnormal cellular infiltrate was predominantly within the parenchyma of the optic nerve. No extradural involvement was observed, nor were any episcleral lesions identified. Electron microscopy was employed in an effort to demonstrate Langerhan's granules within the histiocytic cells, but none were found. The massive involvement of optic nerve and optic nerve head led to an obliteration of the lumens of the central retinal vein (Fig 14) and artery. The vessels on the disc were markedly engorged, and there was extensive hemorrhagic necrosis of the retina associated with extreme neovascularization of the iris and broad peripheral anterior synechias. There was also extensive serosanguineous detachment of the retina, and hemorrhage into the vitreous. Our histopathologic diagnoses were juvenile xanthogranuloma of the optic nerve, optic papilla, retina, and choroid, with hemorrhagic infarction of the retina, and neovascular glaucoma.
DISCUSSION This case was studied in consultation by several experienced pathologists in the AFIP's Departments of Neuropathology, Pediatric Pathology, Dermatopathology, and Infectious Diseases, as well as by the staff of the Department of Ophthalmic Pathology. It was the consensus of these reviewers that the histopathologic changes are consistent with those of juvenile xanthogranuloma, but that the possibility of
some form of "histiocytosis X" or other systemic disease would have to be considered. The absence of Langerhan's granules upon electron microscopic examination is consistent with juvenile xanthogranuloma but a strong point against Hand-SchullerChristian disease, J.etterer-Siwe disease, and related systemic histiocytoses as the histiocytes in these disorders characteristically contain these cytoplasmic organelles. l l None of the reviewers could recall having seen or heard of a similar case. Subsequent clinical, radiologic, and laboratory investigations failed to reveal any abnormalities, and the child's normal development would seem to have eliminated the possibility of a systemic disease, whether of an infectious, metabolic, or immunodeficiency disease.
REFERENCES 1. Blank H, Eglick PG, Beerman H. Nevoxantho-endothelioma with ocular involvement. Pediatrics 1949; 4:349-54. 2. Sanders TE. Intraocular juvenile xanthogranuloma (nevoxanthogranuloma): a survey of 20 cases. Trans Am Ophthalmol Soc 1960; 58:59- 74. 3. Zimmerman LE. Ocular lesions of juvenile xanthogranuloma. Nevoxanthoendothelioma. Trans Am Acad Ophthalmol Otolaryngol 1965; 69:412-42. 4. Helwig EB, Hackney VC. Juvenile xanthogranuloma (nevoxantho-endothelioma). Am J Pathol 1954; 30:625-6. 5. Lamb JH, Lain ES. Nevo-xantho-endothelioma. Its relationship to juvenile xanthoma. South Med J 1937; 30:585-94. 6. Webster SB, Reister HC, Harman LE Jr. Juvenile xanthogranuloma with extracutaneous lesions. A case report and review of the literature. Arch Dermatol 1966; 93:71-6. 7. Crocker AC. The histiocytosis syndromes. In: Fitzpatrick TB, Eisen AZ, Wolff K, et ai, eds. Dermatology in General Medicine, 2nd ed. New York: McGraw-Hili, 1979; 1171-81. 8. Marten RH, Sarkany I. Naevoxanthoendothelioma with pigmentary abnormalities. Br J Dermatol 1960; 72:308-11. 9. Jensen NE, Sabharwal S, Walker AE. Naevoxanthoendothelioma and neurofibromatosis. Br J Dermatol 1971; 85:326-30. 10. Newell GB, Stone OJ, Mullins JF. Juvenile xanthogranuloma and neurofibromatosis. Arch Dermatol 1973; 107:262. 11. Lever WF, Schaumburg-Lever, G. Histopathology of the Skin, 5th ed. Philadelphia, J.B. Lippincott, 1975; 372-9.
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