Journal of Pediatric Ophthalmology and Strabismus

Diagnosis and Management of Iris Juvenile Xanthogranuloma

Zeynel A Karcioglu, MD; Paul B Mullaney, FRCSI, FRCOphth

Abstract

ABSTRACT

Background: Juvenile xanthogranuloma is a benign, self-limiting cutaneous disorder most commonly encountered during infancy. Approximately 10% of cases may develop ocular or adnexal involvement, most commonly in the iris.

Methods: We review clinical and morphological features of four cases of iris juvenile xanthogranuloma that reflect the diagnostic and therapeutic spectrum.

Results: Tissue diagnosis was confirmed in all cases; in one case, the disease was diagnosed with a skin biopsy and treated with local and systemic steroids, and its persistence in the iris was confirmed with a second tissue specimen obtained five months after systemic steroid treatment.

Conclusion: The diagnosis and treatment of juvenile xanthogranuloma may be straightforward, particularly in cases when the ocular lesion receives early attention and responds well to topical steroids, and when there is no hyphema. However, in other instances, this entity may be difficult to manage and may necessitate iris biopsy for diagnosis and radiation therapy for treatment.

Abstract

ABSTRACT

Background: Juvenile xanthogranuloma is a benign, self-limiting cutaneous disorder most commonly encountered during infancy. Approximately 10% of cases may develop ocular or adnexal involvement, most commonly in the iris.

Methods: We review clinical and morphological features of four cases of iris juvenile xanthogranuloma that reflect the diagnostic and therapeutic spectrum.

Results: Tissue diagnosis was confirmed in all cases; in one case, the disease was diagnosed with a skin biopsy and treated with local and systemic steroids, and its persistence in the iris was confirmed with a second tissue specimen obtained five months after systemic steroid treatment.

Conclusion: The diagnosis and treatment of juvenile xanthogranuloma may be straightforward, particularly in cases when the ocular lesion receives early attention and responds well to topical steroids, and when there is no hyphema. However, in other instances, this entity may be difficult to manage and may necessitate iris biopsy for diagnosis and radiation therapy for treatment.

INTRODUCTION

Juvenile xanthogranuloma is a self-limiting disorder of the skin and subcutaneous tissues involving a benign lesion primarily composed of round histiocytic cells.1

The etiology of juvenile xanthogranuloma is poorly understood; it is considered a "reactive inflammatory lesion" by some2 and a "benign neoplasm" by others.3'4 Rarely, this condition may present with ocular or adnexal involvement, particularly in the iris.5'7 Juvenile xanthogranuloma iris involvement may be nodular or sessile, or may present as segmental thickening that varies in color from yellow-orange to tan-brown. A mottled appearance may be present secondary to denser areas within the lesion, or it may be due to blood staining from previous hemorrhages. The presence of blood in the anterior chamber makes the differential diagnosis significantly difficult, not only because it blocks visibility of the underlying lesions but because it causes increased intraocular pressure and corneal haze with or without endothelial staining.

In the differential diagnosis of iris juvenile xanthogranuloma, causes of hyphema in childhood8 and iris mass lesions should be taken into account.9 The diagnosis of juvenile xanthogranuloma usually is rather straightforward, especially when the patient presents with hyphema and typical skin lesions. A punch biopsy of skin confirms the diagnosis, and most lesions respond very well to systemic or local steroids10 or low-dose radiotherapy (300 to 500 cGy).11 However, when the skin lesions are not readily identifiable or are absent, the diagnostic work up may take a more cumbersome course and affect the final visual outcome negatively, as early diagnosis is essential.

We sought to review four cases of juvenile xanthogranuloma that reflect the diagnostic and therapeutic spectrum. The varied diagnostic workup and clinical outcome illustrate difficulties that may be encountered with this entity.

CASE REPORTS

Case 1

A 19-month-old boy presented to the dermatology clinic with yellowish, nodular skin lesions on his face and extremities. Diagnosis of juvenile xanthogranuloma was confirmed with a punch biopsy of the skin by a dermatologist (Fig 1). Although the family gave no indication of ocular involvement, the patient was sent to the eye clinic for a consultation.

On examination, the child was alert and appeared to have good vision in both eyes. He had steady fixation and followed well with each eye. The pupils were round, equal in size, and reactive to direct light, but the right pupil was slightly irregular in shape secondary to a flat, segmental iris lesion located between 11 o'clock and 2 o'clock. When the child was examined under sedation with slit lamp, the involved area was found to be thick, mottled, tannishbrown in color, and devoid of iris clefts. Gonioscopic examination could not be done, but the periphery of the lesion had the same appearance with slightly increased vascularity. No increased pigmentation or synechiae could be seen elsewhere in the anterior chamber, which was deep and contained very few cells. The rest of the eye examination and the fellow eye were within normal limits.

The intraocular pressure (IOP) was 17 mm Hg in both eyes. Considering that the patient had ocular involvement as well as skin lesions, topical and systemic prednisone (1 mg/kg) treatments was given, and the eye condition was followed closely. The topical and systemic steroids gradually were tapered off; the iris and skin lesions gradually regressed and disappeared in 3.5 and 6 months, respectively. The patient has not experienced any recurrent lesions during the next 5 years.

Case 2

A 4-montn-old boy was referred to the ophthalmology clinic with a tentative diagnosis of retinoblastoma in the right eye. He was the product of a term, uncomplicated pregnancy; family history was noncontributory. One month previously, the parents noted "blood in the eye" following mild, self-induced ocular trauma. Subsequently, heterochromia was observed, described by the parents as a blue or gray reflex from the right eye.

The child was extremely photophobic in the affected eye, with mild lid and corneal edema and chemosis. Horizontal corneal diameters were 12.75 mm in the right eye and 12.00 mm in the left eye. Slit lamp examination revealed a cloudy anterior chamber, with fibrinous strands with an organized blood clot band traversing the anterior chamber. Irregular, diffuse, yellowish material was adherent to the inferior iris, encroaching onto the adjacent corneal endothelium (Fig 2A). The lens was clear and a hazy view of a normal posterior pole was obtained. The IOP was 21 mm Hg in the right eye and 20 mm Hg in the left eye. Bscan echography revealed a normal posterior pole. Computed tomography (CT) demonstrated normal ocular, orbital, and brain structures. The left eye was normal.

The patient's white cell count was 13,500. Juvenile xanthogranuloma was suspected although no pathognomonic skin lesions were seen. Two cafe-au-lait spots were noted. An anterior chamber paracentesis was performed to confirm the diagnosis. Cytospin smears were prepared from the aspirate, which revealed numerous histiocytic cells interspersed with occasional giant cells consistent with juvenile xanthogranuloma (Fig 2B). Inferior orbital and subconjunctival methylprednisolone 30 mg was injected. Following surgery, the infant was commenced on neomycin/dexamethasone/polymyxin B drops 4 times a day and ointment at night to this eye.

When the child was seen 6 weeks later, his fixation was uncentral, unsteady, and unmaintained in the right eye due to amblyopia; and central, steady, and maintained in the left eye. Under sedation, slit lamp examination revealed clear cornea and quiet anterior chamber with no evidence of iris lesions or deposits. The IOP was 15 mm Hg in both eyes. The lens was clear apart from mild haze on the anterior capsule. Fundus examination was within normal limits with no evidence of optic nerve cupping seen on follow up. Topical steroids were tapered over 5 weeks.

Fig 1: The histopathologic appearance of the skin biopsy with diffuse infiltration of round histiocytic cells and scattered lbuton giant cells (arrowheads) (hematoxylin-eosin, XlOO). Insert - The clinical appearance of a typical maculopapular lesion (arrow) of juvenile xanthogranuloma from patient 1.

Fig 1: The histopathologic appearance of the skin biopsy with diffuse infiltration of round histiocytic cells and scattered lbuton giant cells (arrowheads) (hematoxylin-eosin, XlOO). Insert - The clinical appearance of a typical maculopapular lesion (arrow) of juvenile xanthogranuloma from patient 1.

No iris tumor was seen nine months after initial presentation. Minimal posterior synechiae in association with anterior capsular fibrosis coinciding with the original site of juvenile xanthogranuloma were observed. Visual acuity has improved with occlusion of the contralateral eye to the point where the child fixates and picks up 3 mm pieces of paper.

CaseS

A 3-year-old boy presented to the ophthalmology clinic with hyphema of the right eye. Although there was no convincing history of trauma, this could not be ruled out because of the hyperactive behavior of the child. The conjunctiva was moderately chemotic and hyperemic.

The ophthalmic examination was difficult because of the photophobia and hyperactivity. A small, inferiorly located hyphema was noted, and the iris was lighter in color on the temporal side. Juvenile xanthogranuloma was considered; a thorough examination of the skin by a dermatologist was done, but no typical skin lesions could be seen. The examination under sedation revealed diffuse, yellowish-white thickening of the temporal aspect of the right iris. The hyphema was partially resolved; only a small amount of residual blood was seen inferiorly. Small fibrinous bands between the organized clot and the iris lesion were observed.

The IOP was 24 mm Hg. Funduscopic examination revealed an irregular pupil with limited dilatation of the iris temporally and a small anterior subcapsular opacity on the lens located inferotemporally; otherwise, the globe was within normal limits, without any evidence of glaucomatous cupping. The examination of the fellow eye was within normal limits with an IOP of 15 mm Hg.

The child was placed on topical and systemic steroids and topical glaucoma medication and followed at weekly intervals. Within a month, the hyphema was totally resolved and the cornea was clear, but the iris lesion was unchanged. The IOP reduced to 21 mm Hg with the use of timolol maléate gtts. 0.5% twice a day. The family complained about the difficulty of instilling the eye drops, and compliance with therapy was considered poor. Radiation therapy was entertained. Repeated skin examinations, including shaving of the head, failed to reveal any skin lesions.

Fig 2: A (top)-Inferiorly located yellowish-white, friable iris lesion and partially organized blood clot in the anterior chamber (patient Z). B (bottom)- Cytospin preparation from anterior chamber paracentesis depicting numerous round histiocytic cells scattered among red cells (hematoxylin-eosin, X 250). Insert- TEM photograph of a histiocytic cell, recovered from Cytospin preparation, with a round nucleus and two prominent nucleoli. Cytoplasmic oacuolizatian may be secondary to ischemia within the anterior chamber (X 8200).

Fig 2: A (top)-Inferiorly located yellowish-white, friable iris lesion and partially organized blood clot in the anterior chamber (patient Z). B (bottom)- Cytospin preparation from anterior chamber paracentesis depicting numerous round histiocytic cells scattered among red cells (hematoxylin-eosin, X 250). Insert- TEM photograph of a histiocytic cell, recovered from Cytospin preparation, with a round nucleus and two prominent nucleoli. Cytoplasmic oacuolizatian may be secondary to ischemia within the anterior chamber (X 8200).

Fig 3: A (top) - The gonioscopic appearance of the flat, whitish-gray iris lesion (arrow) in patient 3. B (bottom) -Histiocytic cell infiltration in iris biopsy from patient 3 (hematoxylin-eosin, X 250).

Fig 3: A (top) - The gonioscopic appearance of the flat, whitish-gray iris lesion (arrow) in patient 3. B (bottom) -Histiocytic cell infiltration in iris biopsy from patient 3 (hematoxylin-eosin, X 250).

Iris biopsy was planned to provide histologie diagnosis prior to radiation treatment. The gonioscopic examination prior to biopsy revealed the same type of thickened appearance in the angle from 1 o'clock to 6 o'clock positions without prominent vessels (Fig 3A). An iris biopsy was performed, which revealed a diffuse infiltrate of round histiocytes. Although giant cells were absent, the histiocytic infiltrate was consistent with the diagnosis of juvenile xanthogranuloma (Fig 3B). Following the histopathologic confirmation of the diagnosis, 400 cGy was delivered to the eye in fractions.

Examination after 2 months revealed significant regression of the lesion; the IOP was down to 18 mm Hg. The antiglaucoma therapy was discontinued. After 6 months, the lesion totally regressed, and the iris was normal in color and appearance other than slight irregularities of the crypts; the IOP was 16 mm Hg. However, the anterior subcapsular opacity enlarged over 9 months and extended toward the visual axis. The child eventually required cataract extraction.

Case 4

A 2-month-old boy was referred to the emergency department with hyphema and a yellow-white deposit on the inferior iris of the left eye. The referring diagnosis was either retinoblastoma or endophthalmitis. B-scan echography revealed a normal posterior pole. The right eye was within normal limits. The patient was thought to have traumatic hyphema and was given a follow-up appointment for the pediatrie clinic.

Fig 4: A- Two maculopapular lesions of juvenile xantkogranuloma in the scalp (arrows) from patient 4. Insert- Histopathologic appearance of the skin biopsy from the same patient depicting round histiocytic infiltrate scattered among collagen of dermis (hematoxylin-eosin, X 25OJ.

Fig 4: A- Two maculopapular lesions of juvenile xantkogranuloma in the scalp (arrows) from patient 4. Insert- Histopathologic appearance of the skin biopsy from the same patient depicting round histiocytic infiltrate scattered among collagen of dermis (hematoxylin-eosin, X 25OJ.

Fig 4: B-Histopathology preparation depicting diffuse, monotonous histiocytic cell infiltrate within iris tissue from the same patient (hematoxylin-eosin, X 100).

Fig 4: B-Histopathology preparation depicting diffuse, monotonous histiocytic cell infiltrate within iris tissue from the same patient (hematoxylin-eosin, X 100).

The child returned to the emergency department 3 days later because the parents felt he was in pain. He was admitted for evaluation because of an IOP of 43 mm Hg in the left eye. In the hospital, maculopapular skin lesions were noted on the face, scalp, and abdomen (Fig 4A). Biopsy of the abdominal lesion revealed an infiltrate of histiocytes and giant cells within the dermis and subcutaneous tissues compatible with juvenile xanthogranuloma (Fig 4A, insert). Examination under anesthesia confirmed elevated IOP of the left eye, measuring 35 mm Hg. The left cornea was enlarged and diffusely hazy; its horizontal diameter was 13 mm. Again, yellowish deposits were noted on the inferior iris. The patient was discharged on acetoazolamide 25 mg four times a day, and betaxolol hydrochloride 0.5%, dipivefrin HCl 0.1%, and atropine sulfate 1% drops, all twice a day. Prednisolone acetate 1% drops also were to be administered four times a day.

Because no clinical improvement was noted and the IOP remained elevated 1 month later, the child was commenced on prednisolone 5 mg orally daily for 1 week, followed by 2.5 mg orally for another week. Following this treatment, the IOP fell to 22 mm Hg, and the anterior chamber activity disappeared. The systemic steroids were discontinued, and the child was maintained on the same regime of oral and topical antiglaucoma medications.

However, on the next monthly clinic visit, the IOP had returned to 35 mm Hg and remained at this level until a trabeculectomy was performed 4 months later. The diffusely edematous cornea measured 15 mm in horizontal diameter. The anterior chamber was deep and quiet. No iris nodularity was seen; however, a swathe of peripheral anterior synechiae stretched from 2 o'clock to 8 o'clock. Both anterior and posterior subcapsular lens opacities were present. Histologie examination of the peripheral iridectomy specimen obtained at the time of trabeculectomy again documented the presence of histiocytic cells within the iris stroma (Fig 4B). Four months later, the IOP again had increased to 30 mm Hg. The child was restarted on betaxolol hydrochloride 0.5% and dipivefrin HCl 0.1% drops twice daily; at a later stage, acetoazolamide 60 mg orally twice a day was added. One year after trabeculectomy, a Krupin valve was placed in this eye to control the IOP

When last measured at 3 years of age, the IOP was 20 mm Hg. The axial length in the left eye measured 28.75 mm with a refractive error of -22.00 sphere. A cup-to-disc ratio of 0.8 was observed. Both anterior and posterior subcapsular lens opacifìcations were present and appeared to be nonprogressive. The child was deeply amblyopic with poor light projection vision.

DISCUSSION

Juvenile xanthogranuloma is a rare disorder that presents predominantly with skin lesions during infancy; more than 80% of the cases occur during the first year of life.1 Although only 10% of the cases develop ocular involvement, the management of these lesions, particularly the iris juvenile xanthogranuloma, requires prompt diagnosis and intervention, because unnecessary delay in treatment may lead to a significant increase in morbidity.7 This is significant particularly if one keeps in mind that the lesion is benign in the absolute sense and responds well to a number of modalities if treated prior to the development of complications.

The diagnosis and management of these cases may range from easy to difficult, as our series reflects. If juvenile xanthogranuloma is discovered coincidentally during a routine eye examination, or in a consultation from another service such as dermatology, pediatrics, etc, before it leads to hyphema, prognosis is very good. If the child also has typical skin manifestations, diagnosis can be confirmed easily, and steroid treatment or low dose radiation can be applied with good results as was the case in our first patient.

In a majority of the cases, the cutaneous manifestations of juvenile xanthogranuloma attract attention to the child. In dermatologie literature, juvenile xanthogranuloma is known as a benign nevoid histiocytosis not related to histiocytosis-X syndrome. Its yellowish maculopapular lesions are self-healing- they wrinkle, then flatten out, and in approximately 40% of the cases, leave no trace without any treatment.12 The skin condition has been reported more frequently in boys, but the ocular involvement appears to be equally distributed between sexes.12·13 Although all the patients reported hi this paper are boys, our series is not large, and this may be a chance occurrence.

The head and neck area, including the scalp, is involved most frequently, but the lesions, which vary in size from 5 mm to 10 mm in diameter, also may be seen on the skin of the trunk and extremities. Although in many instances the skin lesions develop within the early months of childhood, there may be exceptions, and the lesions may present in later months. Skin lesions of juvenile xanthogranuloma in infancy and early childhood generally are self-limited although they may persist or continue to recur for years, particularly in patients who develop the first lesions in late childhood.14 If the typical skin lesion is not detected initially, the parents should be instructed to look for their subsequent development. Association between juvenile xanthogranuloma and neurofibromatosis has been reported.15 In one series, 8 of 45 children with juvenile xanthogranuloma also had cafe-au-lait spots12; one of our cases (patient 2) also had cafe-au-lait lesions, but no other stigmata of neurofibromatosis syndrome, type I.

The cutaneous lesions are considered reactive proliferations of histiocytes. Histiocyte is defined as a mobile tissue macrophage that derives from monocyte precursors in the bone marrow.16·17 Although the circumstances that trigger this proliferation are not known, juvenile xanthogranuloma is considered within the spectrum of benign and atypical histiocytic skin diseases such as congenital self-healing histiocytosis,18 regressing atypical histiocytosis,19 and primary cutaneous atypical histiocytosis. 17i2° Even the true neoplastic nature of some of these entities is uncertain. A number of histiocytic reactions (non-X histiocytoses) of infectious or foreign body etiology that mimic benign neoplasms are known.21 The juvenile xanthogranuloma lesions, both in the skin and in the eye, present with rather typical histopathology, which is quite helpful in the confirmation of the diagnosis of this entity. The histopathology of juvenile xanthogranuloma consists of a proliferation of round histiocytes intermixed with multinucleated giant cells, lymphocytes, and occasional polymorphonuclear cells. Langerhans cells, which are found consistently in histiocytosis X, react to S-IOO, a brain-specific protein; the non-X histiocytic syndromes, however, including juvenile xanthogranuloma, do not stain with anti-S-100 antibody.22

It has been demonstrated recently that the iris of a juvenile xanthogranuloma patient is infiltrated with macrophages and T helper lymphocytes hi clinically involved and noninvolved areas.23 DeBarge and coauthors suggested that the presence of CD 4+ cells, multinucleated giant cells, and the expression of MHC class II antigens within the iris indicated that the inflammatory response that leads to the development of juvenile xanthogranuloma is T lymphocyte-dependent.23 The exact mechanism of giant cell formation is not known, but it has been postulated that monocyte precursors stimulated by a putative giant cell protein (GCP), elaborated by antigen- and mitogen-stimulated lymphocytes, develop into multinucleated giant cells. Although the giant cells of the Teuton type classically have been described as the trademark of juvenile xanthogranuloma, in many instances of juvenile xanthogranuloma, the giant cells may have a haphazard multilobulation of the nuclei instead of a perfect peripheral alignment, typical of Teuton giant cells. In other cases, the giant cells may be extremely sparse or nonexistent, as was the case in the iris biopsy of patient 3. Although useful for immediate recognition, the morphologic diagnosis of juvenile xanthogranuloma is not dependent on the presence of the giant cells, as the histiocytic infiltrate is quite pathognomonic in both histologie and cytologie preparations.

Juvenile xanthogranuloma should be considered in the differential diagnosis of discrete iris lesions with or without uveitis, "spontaneous" hyphema, and heterochromia during infancy and early childhood.8'9 Trauma is, of course, the most common cause of hyphema in any age group. Therefore, the spontaneous nature of the bleeding, particularly in this age group, may be difficult to establish as was the case in patients 2 and 4. Furthermore, a minor trauma, such as in patient 2, may be the triggering insult to cause bleeding in many instances. Therefore, the wellestablished term "spontaneous hyphema" may be misleading. History of significant trauma should be investigated carefully.

Because the most frequently presenting sign in iris juvenile xanthogranuloma is hyphema, immediate attention should be directed to the differential diagnosis and management of this problem. Even if the spontaneous nature of the bleeding can be established beyond any doubt, other causes should be considered in the differential diagnosis of hyphema of infancy and early childhood. Hyphema may be seen hi retinoblastoma secondary to iris neovascularization.2·25-26 Any vascular abnormality or other pathologies leading to rubeosis iridis in this age group should be taken into account in the differential diagnosis of juvenile xanthogranuloma.8 Persistent hyperplastic primary vitreous (PHPV), retinopathy of prematurity (ROP), vascularized pupillary membrane, iris hemangioma, and fetal distress syndrome have been associated with early childhood hyphema.27·28 Other neoplastic conditions, such as medulloepithelioma,29 leukemia and other blood dyscrasias,30 and metastatic childhood tumors may lead to hyphema.31

Heterochromia irides noticed by parents may be the initial sign in juvenile xanthogranuloma cases. Heterochromia may be the result of the iris mass, in which case the involved eye appears lighter in color; or may be secondary to blood staining after resolved hyphema(s), in which case the involved eye appears darker in color. In many instances, however, when the family recognizes a color difference between the two eyes, it is due to the blood and inflammatory reaction within the anterior chamber. Extreme photophobia is another noteworthy sign.

Some entities in the differential diagnosis, such as retinoblastoma, can be ruled out fairly easily. Although some retinoblastoma cases develop hyphema, these usually are the advanced ones, and a simple ultrasound or CT scan examination would reveal the underlying pathology. Primary or metastatic tumors of the iris and vascular abnormalities, however, are more difficult to evaluate, as in many instances the blood in the anterior chamber and corneal edema with or without staining obstruct the vision and make the examination difficult. Fortunately, iris tumors in this age group, and vascular malformations in general, are rare. Iris lesions, particularly in this age group, usually are too small to be demonstrated with ordinary ultrasonography, CT, or even MRI. High frequency ultrasound biomicroscopy, on the other hand, may be of some help, as it can provide information about the iris structure hidden by the blood.32·33

Iris fiuorescein angiogram also is not very helpful when there is hyphema and hazy cornea; even in cases where the visibility is optimal, all it reveals is leakage of the iris tumor, indicating abnormal vascularity.34 Documentation of the leakage is not helpful for differential diagnosis as many other primary and metastatic iris tumors and vascular abnormalities also leak fluorescein.

The clinical suspicion of juvenile xanthogranuloma can be substantiated best by the cytologie examination of the anterior chamber material obtained with paracentesis.10'35 The material obtained can be prepared quickly with Cytospin centrifuge technique and stained with a quick hematoxylin-eosin or Papanicolaou stain or can be prepared with membrane filter. A portion of the paracentesis fluid can be saved for further evaluation (immunohistochemistry, TEM, etc) if necessary (Fig 2B). The main advantage of the Cytospin technique, however, is the rapid preparation of the slides; with this technique and quick cytology staining, the results may be available within 15 to 20 minutes while the patient is still under anesthesia, and the management plan can be based on morphologic confirmation.

In patient 2, the diagnosis of juvenile xanthogranuloma was confirmed within 20 minutes while the patient was still under general anesthesia, and subconjunctival steroid injections were administered. Consequently, the patient was spared iris biopsy. The iris biopsy should be used as a last resort as these lesions are very vascular and bleed massively. At the time of management of patient 3, for example, the Cytospin instrument was not available, and an iris biopsy was performed. Although the diagnosis was confirmed histopathologically, the lesion bled profusely; the procedure might have easily contributed to the advancement of the cataractous change.

It should be understood that the paracentesis procedure in juvenile xanthogranuloma is different from fine needle aspiration biopsy technique, which has been suggested by some authors.2 In many instances, the juvenile xanthogranuloma lesion is flat and hidden behind blood clots without forming a discrete mass. Even if a distinct mass can be identified, it is best not to stick a needle into the lesion because of its enormous propensity to bleed. The best approach is to enter the anterior chamber at the limbus with a 25-gauge needle close to the edge of the lesion and inject a very small amount of balanced salt solution (BSS) to slough off some cells and aspirate following this maneuver. Bleeding may be encountered as a result of paracentesis because of the friable nature of the lesion, just as we experienced a considerable amount of bleeding during paracentesis in patient 2. Anterior chamber volume should be replaced with BSS, and a small air bubble may be placed into the anterior chamber for hemostasis. The cautious use of Healon to form the chamber is advised as it may further compromise the trabecular meshwork in an eye with hyphema.

Once the diagnosis is established, treatment should be undertaken rapidly. Several modalities of treatment have been recommended for juvenile xanthogranuloma, ranging from local excision8 to the use of local and systemic corticosteroids10'36 and irradiation.37 Although the true nature of this lesion is not known, its response to local and systemic corticosteroid use has been experienced widely in the past.10·36'38 Cases with mild intraocular involvement may resolve with topical or a short course of systemic corticosteroids; however, not every iris juvenile xanthogranuloma, no matter how small, responds to a regimen of corticcsteroids. It is very important to adjust the treatment according to clinical status of the eye as early tumor response to treatment will eliminate complications that can lead to uncontrolled glaucoma and eventually to blindness.

If the lesion is not associated with hyphema and does not respond to a therapeutic trial with topical steroids, an anterior chamber tap should be performed for cytologie diagnosis, and if positive, a subconjunctival corticosteroid cocktail should be injected during the same session of general anesthesia. Treacy and coworkers suggest a mixture of 2 mL of dexamethasone (4 mg/mL) and betamethasone suspension (6 mg/mL) in a 50:50 mixture.39 These investigators reported successful treatment with a single subconjunctival injection of this combination. Casteels and coworkers treated four patients (free of secondary glaucoma) with subconjunctival injections of 30 mg methylprednisolone.10 In their series, one patient responded well to a single injection; two needed to be injected twice; and the fourth needed three injections prior to regression of iris lesions.

If hyphema with secondary glaucoma is present, the treatment also should include aggressive antiglaucoma therapy with eye drops and oral acetazolamide if necessary.40 Systemic steroids can be tried in nonresponsive cases, but the glaucomatous and cataractous effect of the corticosteroid treatment and its systemic side effects, particularly in this young age group, should be taken into account; consultation with a pediatrician or a neonatalogist is helpful for the long-term maintenance and tapering of medications. If no response is experienced with the summarized therapeutic modalities, low dose radiation therapy ranging from 300 to 500 cGy, by itself or combined with steroids, may be initiated.11·41

Table

Table 1: Deasion-malung tree for juvenile Xanthogranuloma diagnosis and treatment

Table 1: Deasion-malung tree for juvenile Xanthogranuloma diagnosis and treatment

CONCLUSION

The literature and our experience indicate that juvenile xanthogranuloma responds to radiation and steroid treatment within weeks to months in a gradual fashion.10·11 It is conceivable to assume that certain elements of the lesion, such as multinucleated cells, disappear before other cell types, as is the case in other granulomatous reactions such as giant cell arteritis. This was evident in patient 4. The classical histologie appearance of juvenile xanthogranuloma with histiocytes and giant cells was documented in this case with a skin biopsy, and the skin and iris lesions responded well to prednisolone treatment with decreased anterior chamber inflammation and IOP. Following the discontinuation of systemic steroid treatment, however, the IOP increased again, and the iris biopsy at the time of trabeculectomy confirmed the persistence of juvenile xanthogranuloma.

To the best of our knowledge, a follow-up biopsy in a case of juvenile xanthogranuloma never has been reported in the literature prior to this paper. The peripheral iridectomy specimen obtained from the iris at the time of trabeculectomy (5 months after prednisolone treatment) revealed a histiocytic infiltrate although the giant cells were not present. It is significant from the management standpoint to keep in mind that the iris lesions of juvenile xanthogranuloma may respond partially to treatment and persist at a subclinical level with a normal slit lamp examination. Therefore, it may be difficult to determine the end point of treatment. However, if the anterior chamber is quiet and IOP is controlled, aggressive treatment probably is not indicated.

In summary (Table), the diagnosis and treatment of juvenile xanthogranuloma may be straightforward in cases when the ocular lesions are given early attention and respond well to topical steroids, and when there is no hyphema. However, in other cases, this entity may be extremely difficult to manage and may necessitate iris biopsy for diagnosis and radiation therapy for treatment. In certain instances, ocular juvenile xanthogranuloma lesions may be resistant to treatment, resulting in poor vision secondary to uncontrolled glaucoma, corneal staining, cataract formation, and amblyopia. The four cases reported in this paper represent the clinical spectrum of diagnosis, treatment, and complications in iris juvenile xanthogranuloma.

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Table 1: Deasion-malung tree for juvenile Xanthogranuloma diagnosis and treatment

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