Spontaneous Hyphema and Secondary Glaucoma

Romanian Journal of Ophthalmology, Volume 61, Issue 3, July-September 2017. pp:229-236

CASE REPORT

Iris juvenile xanthogranuloma in an infant - spontaneous hyphema and secondary glaucoma

Pantalon Anca*, Ștefănache Tudor* **, Danciu Mihai***, Zurac Sabina****, Chiseliță Dorin* ** *Opthalmology Clinic, “Sf. Spiridon” University Hospital, Iași, Romania **Ophthalmology Unit, “Gr. T. Popa” University of Medicine and Pharmacy, Iași, Romania ***Department of Pathology, “Gr. T. Popa” University of Medicine and Pharmacy, Iași, Romania ****Department of Pathology, Faculty of Dental Medicine, “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania

Correspondence to: Pantalon Anca, MD, PhD,

MobileOphthalmology phone: +40740 Clinic, “Sf. 686 Spiridon” 865, E-mail: University [email protected] Hospital, Iaşi, 1 Independenței Square, Code 700115, Iaşi, Romania, Accepted: September 9th, 2017

Abstract

Juvenile xanthogranuloma (JXG) is a benign histiocytic skin disorder mainly encountered complications,during infancy specif and childhood. Although with multiple potential localizations, less than eye1% disease. of the cases exhibit ocular manifestations. Some of these might lead to serious ically, secondary glaucoma that can result in severe and blinding

The aim of the present case report was to demonstrate typical clinical features, emphasize the difficulties attributed when managing these patients and literature review. We present the case of 4 months old female baby with spontaneous hyphema and secondary unilateral glaucoma due to oculared to JXG.other severe conditions that resembled The natural history and treatment of the condition were extremely difficult to handle due to multiple opinions in histopathology relat recognitionwith the lesions of this detected condition in is this important case: myelomonocytic bec leukemia and Langerhans cell histiocytosis. Although a minority of patients with JXG have ocular involvement, differential diagnosis represents the key to a properause a treatmentmanagement delay plan can in leadthese to patients, serious bothcomplications, on short and such long as term.glaucoma “Triple and dis spontaneous hyphema, as in our case. A thorough 1 (NF- ease” defined as JXG plus neurofibromatosis type Keywords1) and juvenile chronic myelogenous leukemia (JCML) has been reported, but it hyphemawas not confirmed in our patient. : juvenile xanthogranuloma, secondary glaucoma, infant, spontaneous

Introduction 1]. In 5– 17% of the cases, the skin lesions may appear occurring in the first2]. 9 months of life [ non- affectingJuvenile infants xanthogranuloma and children, 75% (JXG) of is the a benign cases soon after birth [ 1About]. 10% of the cases can Langerhans histiocytic skin disorder mainly manifest in adulthood, being known as “adult xanthogranuloma” [ The etiology is unknown, Romanian Society of Ophthalmology 229 © 2017 doi:10.22336/rjo.2017.41 Romanian Journal of Ophthalmology 2017; 61(3): 229-236

3,4 lesions above-mentioned changes (photophobia, althoughare asymptomatic it may represent and agenerally reactive processappear addressed an ophthalmologist, who found the (physical or infectious) [ ]. Cutaneous reddish- epiphora,tertia and spontaneous hyphema) at the andspontaneously neck region. during The the general first year tendency of life asis clinical examination and sent the child to a yellow nodules, most often in the head ry center for further investigations. The general Fig. clinical 1a,b,c examination), varying in color was 3- - 3 completely normal, except for the numerous towards spontaneous resolution until the age of cutaneous nodules ( lesions 6 years old [ ]. Extra cutaneous JXG most from yellowish to bright red, mostly spread onto involvementcommonly affects (iris, thechoroid, eye butretina, can optic involve nerve, the the head/ neck region and thorax. Fewer brain, lungs, liver, spleen, and other sites. Eye were noted on the arms and legs. All further investigations (complementary exams, and orbit) has5 been reported to occur in laboratorylesions onto findings, the internal and imaging organs, scans) nor werethe 60approximately– 0.3% to1 10% of the children with withinpresence the of normalany other limits systemic and a revealedlteration. neither hascutaneo beenus most JXG [commonly]. Solitary involved; lesions are some found cases in 82% of the cases [ ]. Among ocular sites, iris might lead to serious complications, e. from spontaneous intraocular hemorrhages, secondary glaucoma to blinding eye diseas Contrary to other xanthomatous 6 diseases, JXG has not been associated with lipid disturbances or metabolic disorders [ ], but a variety of systemic diseases, includingciated neurofibromatosis type 1 and juvenile chronic myelogenous leukemia, which may be asso Fig. 1 a,b,c management.with juvenile xanthogranuloma. Patients with this combination of findings require special Numerous cutaneous nodules, varying in color from yellowish to bright red, mostly Case report spread onto the head/ neck region and thorax; fewer lesions were noted on the arms and legs 4 months old

We present the case of a femalephot baby referred to our ophthalmology unit In the ophthalmology exam,-OD = we25 mmHg found byhyphema a fellow (OD). colleague As a personal for unilateral history, soon red after eye, visual acuity in both eyes “fixes and follows” and, ophobia, epiphora, and spontaneous underincreased general in OD anesthesia, (12 mm) and IOP normal in OS (10 - and IOP OS =12 mm Hg. Corneal diameter was birth (at 2 weeks), the mother recalled the appearance of few red orange cutaneous nodules mm), aspect which coincided with increased (thorax, head, neck); in time, lesions became axial lengths in OD (19.12 mm) compared to OS more numerous and some changed aspect due to (18.49 mm) by “A” scan ultrasound methods. crust formation or mild superficial hemorrhages. Anterior segment examination found all Asdiagnosis such, a establisheddermatologist by was several consulted pathologists and skin structuresepithelial withcorneal normal edema, appearance peripheral in OS, whileiris biopsies from the lesions were indicated. The insynechiae/ OD there 36 were0*, thick visible fibrinoid changes membrane such as: mild on histiocytosis to mye varied greatly, from Langerhans cells -4 o’clock lomonocytic leukemia or themeridians) surface of– Fig.the iris, 2 2mm hyphema and a wide juvenile xanthogranuloma (JXG). Due to this blood clot on the surface of the iris (11 situation, the baby underwent a bone marrow . Fundus examination couldscan biopsy that excluded any malignant process and not be performed in OD due to low visibility, pleadedAt 3 for months, cutaneous the mother JXG. At noticed this stage, a color no abnormalitieswhereas OS in aspect the choroid, was normal. retina, or B optic changetreatment in wasthe indicated,OD appearance except infor her observation. baby and ultrasoundnerve (Fig. 3). examination in OD detected no

severe complications in this child. mandatory in order to avoid future and more

In this respect, augmented trabeculectomy with2016. mitomycinFig. 4 C (0.02%, 3 minutes) and trabeculotomy were performed in November is presented indepicts Fig. 5 the. most important surgical steps. Surgery was uneventful and the outcome

Fig. 2 Anterior segment (OD)

Fig. 3 OD-

choroid, opticB scan nerve revealed normal structures; no Fig. 4 JXG suggestive lesions appeared in the retina, OD Augmented trabeculectomy with mitomycin C (0.02%, 3 minutes) and trabeculotomy; difficult rotation in the anterior the diagnosis of OD - Pediatric secondary fibrinoid membrane adherent to the iris root in thechamber AC angle; of the removal trabeculotomes of the iris due fibrinoid to the Based on all these findings we established membrane, mild hemorrhage after removal,

patient 12 o’clock peripheral iridectomy inflammatory glaucoma in the context of juvenile xanthogranuloma with ocular (iris) involvement. Short course of topical corticosteroids (dexamethasone) and close monitoring for the nextand persistent 3 weeks hyphema, was fibrinoid indicated. iris membrane Since no The thick plaque extracted from the surface improvement was detected within this interval ofsent the iristo together with the tissue resulted from the peripheral iridectomy (at 12 o’clock) were (more dense in inferonasal quadrant) were histology examination, including present, surgical intervention became immunohistochemistry markers. 231 Romanian Society of Ophthalmology © 2017 Romanian Journal of Ophthalmology 2017; 61(3): 229-236

Early post operation 5 topical t non- “clinically silent” (Fig. 6 steroidal anti- medication included months after surgery, the OD was phenylephrineobramycin, dexamethasone day to and prevent ); no local recurrences bleedinginflammatory in the anterior drugs chamber, 5x/ . day;IOP were noted and the IOP was 10 mmHg without was added x3/ een 8-10 any medication. General status wassts stationary,performed recurrent since no new skin lesions on the internal organs wasC well controlled in OD (range betw were detected at the ancillary te mmHg) during the follow up visits. regularly (abdominal/ pelvic ultrasound clinicalorticosteroids were slowly tapered in the next examination, transfontanellar ultrasound and months, until complete cessation with favorable laboratory blood tests). Fundus examination was evolution. normal in both eyes; glaucoma damage was not found in OD (C/ D ratio = 0.2). of myelomonocyticInitial pathology proliferation examination appeared required in the further investigations, as a temporary suspicion

biopsiedCD68 intensely iris tissue.positive Ain the thorough area of active pathology cell examinationproliferation, andfactor specific XIIIa IHC– intensely markers positive, such as Vimentine – mildly positive in the area of active cell proliferation, confirmed the XJG diagnosis.

T311, MITF – - Langerine, CD1a, MPO, CD15, S100, HMB45, were all negative in the analyzed tissues (skin and iris) and excluded other diagnosis (Langerhans histiocytosis, myelomonocytic leukemia, etc.). Fragments of Fig. 5 deep adipose tissue included dense cellular intervention; mild hemorrhage in the AC after proliferation,dissecting from without place toa clear place demarcation collagen lamellas zone, removalOD of the aspect iris membrane at the end of the surgical extending also towards the periadnexal space, morphology, scarce areas of epithelioid (deep expansive pattern growth with spindle cell mitosis (21 mitosis/ 10HFP); minimal proliferationinflammatory with infiltrate medium/ – largelymphocytes cells); frequent and eosinophils. This description pleaded for a

prominent spindle cell morphology. Some details nonlipidized, Fig. mitotically 7a,b,c,d and active Fig. 8 . JXG, with

are shown in

Fig. 6 OD aspect at 5 months post operation. Thin, visible in

avascular- filtering bleb, rare microcysts the superior sector on the conjunctiva, diffuse SIPs);sub conjunctival no active bleeding filtration; is visible clear in the AC, cornea, nor Fig. 7a giant cells tractioned pupil (the inferior quadrant by small -eosin (HE) stain Cutaneous JXG with Touton remnant/ new membranes; transparent lens displayed by hematoxylin 232 Romanian Society of Ophthalmology © 2017 Romanian Journal of Ophthalmology 2017; 61(3): 229-236

Fig. 7b Fig. 8 -

Cutaneous JXG with CD68 +++ IHC stain Histology exam (iris) biopsy. Hematoxylin Eosin (HE) staining, ×25; detail, ×200). Diffuse iris

(histiocytes)infiltration of lymphocytes (monocytes); nodular aggregates on the anterior surface of the iris

Discussions

Histiocytic disorders consist m

non- ainly- in two types: Langerhans cell histiocytosis (LCH) and amongLangerhans the non- cell histiocytosis (non LCH). JXG is5 a rare disorder, but it is the most commonst year LCH forms, with benign evolution [ ]. Lesions appear spontaneously, during the 1 of life; as it was the case of our patient, and -100 negative IHC Fig. 7c resolve spontaneously later in childhood. The stain Cutaneous JXG with S most frequent3,5 ]. areas Organ involved involvement are the is headvery rare and andneck happensregion, but predom extracutaneous lesions are also described [ hereby 7]. inantly in patients with multiple skin nodules, as the case we presented [ The majority of the patients with ocular lesions are young children typicallysions younger than 1 year, similar to the 4 months old reportedbaby, subject in the of thisorbit, case optic report. nerve, Ocular retina, le and usually involve8,9]. theIridocyclitis, iris, but havehyphema, also beenand

choroid10 ] [ secondary glaucoma are frequent presenting signs [ and11]. representZimmerman serious identified complications 5 clinical that may cause blindness if unrecognized or left untreated [ Fig. 7d patterns for intraocular involvement in infants stains Cutaneous JXG with CD1a negative IHC and young children: asymptomatically localized or diffuse iris tumor, unilateral glaucoma, spontaneous hyphema, red eye with signs of uveitis and congenital/ acquired 233 iris Romanian Society of Ophthalmology © 2017 Romanian Journal of Ophthalmology 2017; 61(3): 229-236

12 - and CD1a – heterochromia.Microscopically, All these the signsocular [ tumor] were cells found are monocytes (CD68+++ndetermined and CD14+), cells, Langerinethat are in our patient. could exclude- HCL or another tumor - with dendritic u - richkidney in -cytoplasm,shaped. Mostwhich isof light the and eosinophiliccells are usually Langerine , but CD1a+. Spindle cell or fine granular like. The nucleoli are round or morphology, corroborated with fascein+, FXIIIa could exclude a myelomonocytic proliferation. decreasedmononuclear, compared and some to s kin can JXG see lesions two or or threeeven Third and most comprehensive IHC evaluation unclear nucleoli. The number of Touton cells13 is]. showed positive markers such as- CD 68 (+++), factor XIIIa(++), Vimentine (+), whereas- missing; inflammatory cells are also rare [ Langerine, CD1a, MPO, CD15, S 100, HMB45, This couldMicroscopy lead to of some skin lesions degree in of JXG confusion describes for a characteristics.T311, MITF were all negative. All the above inexperienced pathologists. mentioned IHC markers are consistent-100 protein with JXG is accompanied by a sma diffuseand eosinophils invasion that of can numerous be seen tissuein the early cells In most cases with JXG, S ll amount of lymphocytes non reactive, but scattered cells may show weak16]. cytoplasmic reactivity, unlike the more diffuse stage of JXG. Some tissue cells have light and and intense reaction of Langerhans cells [ hollow cytoplasm, and the nucleus is small ins Probably this was the reason for the initial 3- round or ovoid shape without atypia. In some confusion that was made with malignancies that cells.cells, theInvasion nuclear of groovefoam cells, and anforeign unclear body nucleu giant requiredJXG a lesionsbone marrow beyond biopsy skin in have this childdifferent at can be seen, which are often absent in Touton 4 weeks after birth. garlandcells and- Touton giant cells can be seen in histological characteristics17 with cutaneous JXG, mature stage. The nucleus of Touton cell is and are easy to be confused with Langerhans cell are visiblelike, at whichthe late is stage,the typical and fibrosischaracteristic replaces of histiocytosis (LCH) [ ], therefore the confusion juvenile xanthogr13anuloma. A lot of fibroblasts in this case, when 18an ].iris A “triplefragment disease” was analy (18%zed; of from different stages of the skin lesions might yet, JXG and LCH might be found simultaneous in leadthe infiltrationto different descriptions [ ]. Collecting in the tissue same samplespatient, typethe same 1 (NF patient- [ the cases) defined as JXG plus neurofibromatosis The differential diagnosis relies on the not confirm1) and juvenile chronic myelogenous as it was in our case. leukemiaFrom (JCML) the threehas been characteristic reported, buthistologic it was patterns of edJXG: in ourearly patient. JXG (EJXG), classic JXG immunohistochemical -M1P study. and JXGanti F lesionsXIIIa, 19,20 classicallyvimentin and stain often with anti macrophage- markers including CD68 or Ki (CJXG), and transitional JXG (TJXG) [ ], we CD1a. -100CD4. protein As and such, CD1a, JXG histifound elements consistent for all forms in our expresses CD68, lysozyme and FXIIIa, but not predominancepatient: CJXG due toof abundant spindle vacuolated,-shaped foamycells LCH expresses S ocytes with Touton giant cells, TJXG due to but not CD68, lysozyme- and FXIIIa.14]. CD1a is a relatively specific marker for LCH and it is not resembling benign fibrous histiocytoma with expressed in non LCH diseases [ foamy histiocytes and EJXG forms due to cells AccordingIn our to case,Dehner, multiple neither biopsies factor wereXIIIa with little lipid and- relatively more mitoses than negativity,collected and nor various S- interpretations were given. the others. The high number of mitosis found in 15]. Therefore, the first our case of non lipidized JXG could be explained 100 positivity should preclude by the immature or evolving characterpatients of this the diagnosis of JXG [ histologic subtype. attempt to characterize the ed, skin based biopsy on Regarding the therapeutic options, CD68+++,fragments CDwas 45+, made, MPO+, a diagnosis CD1a-, S -of100 Lanherhans-, desmin - with a single or only a few lesions need no Cells, MY14 Histiocytosis- was discuss blindingtherapy; excisionalcomplications, biopsy treatment can be consi ofdered, iris JXGbut only for cosmetic reasons. Due to potential . Further IHC exams stated that elements 234such as positive markers for histiocytes and should be promptly considered. Usually, Romanian Society of Ophthalmology © 2017 Romanian Journal of Ophthalmology 2017; 61(3): 229-236 corticosteroids are the main stay of treatment, aryngology. 2012; variant– with a potential diagnostic pitfall. International therefore an escalation of treatment needs to be 2. Journal of Pediatric Otorhinol but refractory cases have been described, and76:295 histological299. findings in 64 patients. Pediatr and the disease progresses despite conventional Dermatol.Cohen BA, Hood A.6:262Xanthogranuloma:–6. report on clinical approached, if the patient’s status deteriorates 3. 1989; Seo IS, Min KW, Mirkin LD. Juvenile–5. xanthogranuloma. treatment. Surgery serves both diagnosis ande 4. Ultrastructural and immunocytochemical studies. Arch treatment, since it provides a tissue specimen21]. Pathol Lab Med. 1986; 110:911 and excisional biopsy is curative, since th Esterly NB, Sahihi T, Medenica M.–102.Juvenile lesions once excised do not recur [ 5. xanthogranuloma. An atypical case with study of Involvingultrastructure. the Eye Arch an Dermatol. 1972; 105:99 Refractory cases or for the patients who have 122(10):2130Samara Wasim–2138. A et al. Juvenile Xanthogranuloma systemic22 disease require radiotherapy (low 6. - d Ocular Adnexa. Ophthalmology.- dose) or chemotherapy similar to LCHhe irisprotocols JXG in D et al. this[ ]. patient, Glaucoma and surgery prevented (trabeculectomy complications and of histiocyticSzczerkowska disorder.Dobosz Advances A, Kozicka in D, Dermatology Purzycka Bohdan and trabeculotomy) was “curative” for t Juvenile xanthogranuloma: a rare . benign2014; 31( -200. 7. Allergology/PostȩpyDermatologii i Alergologii intraocular inflammation and increased IOP. 3):197 Postoperatory management included only andChang assessment MW, Frieden of risk.IJ, Good J Am W. AcadThe Dermatol. risk intraocular topical corticosteroids andither NSAID local with or systemic positive 34juvenile:445– xanthogranuloma:. survey of current practices 8. Solitary orbital1996; outcome during the follow up period. We 9 Arch Ophthalmol. recordedneeded in nothis recurrence, child. e Shields1081587 CL,- Shields JA, Buchanon HW. in this patient, but still, a close monitoring is involvement with JXG. JXG 1990;of the optic nerve,1589. disc, retina, and choroid. Ophthalmology. Conclusions 9. Wertz FD, Zimmerman-1335. LE, McKeown CA et al. 10. Zimmerman Am J 1982;Ophthalmol. 891331 -1035. 11. LE. Ocular lesions of JXG. mitotically active JXG in iris and skin that 1965; 601011 We presented a difficult case of a andChang assessment MW, Frieden of risk.IJ, Good J Am W. Acad The Dermatol. risk intraocular an ophthalmologist, pathologist, pediatrician, 34juvenile:445– xanthogranuloma:. survey of current practices requested multidisciplinary approach, involving 12. Zimmerman LE. Ocular lesions of juvenile1996; xanthogranuloma9 dermatologist, etc. After treating the ocular Ophthalmol -35. -term prognosis 13. . Nevoxanthoedothelioma. Am J complication, the situation was declared . 1965 Dec; 60(6):1011 Arch temporarily stable, but the long Ophthalmol.Parmley VC, George DP, – Fannin LA. Juvenile is yet guardedsome andhistological further monitoring aspects ismight needed. be 14. Xanthogranuloma of the Iris in an Adult. -cell Although JXG is described as a benign 1998; 116(3):377 379. 7; Carstensen H,- 83. Ornvold K, Ugeskr L. Langerhans tumor, 15. histiocytosis (histiocytosis X in children). 1993 Jun - confounders for inexperienced pathologists; 155(23):1779100 protein in histiocytic neoplasms. therefore, the definitive diagnosis should the be Tomaszewski25 – MM,135. Lipton GP. Unusual expression of S made only by IHC markers just to avoid errors. 16. J Cutan Pathol. 1998;decades :129of life. A clinicopathologic As general recommendation we advice Dehner LP. Juvenile xanthogranuloma in the first ophthalmology fellows to consider the JXG – study of 174 cases diagnosis in every case of spontaneous hyphema 17. with cutaneous an extracutaneous manifestations.. Am J they find in infants and young children, since Surg Pathol. 2003; 5:579 593. 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