Unilateral Eye Findings: A Rare Herald of Acute Leukemia

Transcription

1 Cse Series nd Brief Reports Received: Septemer 10, 2015 Accepted fter revision: Novemer 20, 2015 Pulished online: Jnury 13, 2016 Unilterl Eye Findings: A Rre Herld of Acute Leukemi Avni V. Ptel John B. Miller, Rjneesh Nth c Helen A. Shih d Michel K. Yoon, e Suznne K. Freitg, e George Ppliodis, f Teres C. Chen, g Den Eliott, Ivn K. Kim, Deprtment of Ophthlmology, Hrvrd Medicl School, nd Retin Service, Msschusetts Eye nd Er Infirmry, Boston, Mss., c Deprtment of Hemtology/Oncology, UMss Memoril Medicl Center nd University of Msschusetts Medicl School, Worcester, Mss., d Deprtment of Rdition Oncology, Msschusetts Generl Hospitl nd Hrvrd Medicl School, e Deprtment of Ophthlmic Plstic Surgery, f Oculr Immunology nd Uveitis Service, nd g Glucom Service, Msschusetts Eye nd Er Infirmry, Boston, Mss., USA Key Words Choroidl infiltrtion Leukemi Oculr mnifesttions of leukemi Oculr oncology Rdition Astrct Bckground/Aim: Unilterl choroidl infiltrtion s the initil mnifesttion of leukemic relpse in dults is rre, prticulrly fter n extended period of remission. This report descries this unique ophthlmic presenttion, highlights the ssocited dignostic chllenges, nd reviews the literture. Methods: Two cses re descried nd n extensive literture review ws conducted. Results: A 59-yer-old mle with cute lymphoid leukemi, in remission for 18 months, presented with unilterl scleritis, exudtive retinl detchment, nd choroidl thickening. A 57-yer-old mle with history of cute myeloid leukemi, in remission for 4 yers, presented with unilterl choroidl thickening leding to secondry ngle closure. In oth cses, there ws significnt lg from the onset of eye symptoms to estlishing systemic dignosis of cute leukemi, leding to dely in definitive systemic tretment, despite high suspicion of disese sed on ophthlmic findings. Conclusions: These two cses illustrte the fundus findings consistent with leukemic choroidl infiltrtion tht cn represent the first sign of relpsed leukemi. The successful tretment of these ptients hinges on collortion etween ophthlmologists nd oncologists to optimize ptient outcomes, highlighting the need for oth groups to e wre of this rre ophthlmic presenttion S. Krger AG, Bsel Introduction While ophthlmic involvement is well-documented compliction of leukemi, it is rre for ophthlmic findings to e the initil mnifesttion of new or relpsed disese [1, 2]. Additionlly, when eye findings re present, they usully mnifest simultneously nd ilterlly in systemic diseses such s leukemi. We report two cses of unilterl oculr involvement s the initil mnifesttion of relpsed leukemi in two ptients without prior evidence of centrl nervous system involvement. Additionlly, thorough literture serch ws conducted (PuMed, keywords: leukemi, oculr, eye, nd E-Mil krger@krger.com S. Krger AG, Bsel /16/ $39.50/0 Ivn Kim Msschusetts Eye nd Er Infirmry 243 Chrles Street Boston, MA (USA) E-Mil meei.hrvrd.edu

2 Fig. 1. Fundus photo of the ptient s left eye (cse 1) shows n inferior serous retinl detchment with choroidl thickening nd effusions. Anterior segment photo of the ptient s left eye (cse 1) demonstrting the lood-tinged leukemic hypopyon with the dshed line outlining hypopyon. dult ) to review the vriety of presenttions of oculr leukemic disese nd highlight the uncommon fetures of these cses. These exmples emphsize the need for ophthlmologists nd oncologists like to e wre of the full spectrum of oculr signs of leukemi, s prompt nd thorough systemic workup nd tretment in these cses my not only slvge the ptient s sight ut lso e lifesving. Color version ville online A 59-yer-old mle physicin with Phildelphi chromosome (BCR-ABL)-positive cute lymphoid leukemi (ALL), in complete remission fter myeloltive chemotherpy nd mtched relted donor hemtopoietic stem cell trnsplnt 18 months prior, presented with progressive irrittion, redness, nd decresed vision in his left eye over 1 month. His pst oculr history ws notle for recent episodes of nterior uveitis nd scleritis in the left eye only, which were previously treted with topicl nd systemic steroids, difluprednte nd prednisone, respectively. He ws lso on imtini mesylte (Gleevec, Novrtis Phrmceuticl Corp., Est Hnover, N.J., USA) s mintennce therpy for his hemtologic disese. On presenttion to our clinic, his est-corrected visul cuity ws 20/20 in the right eye (OD) nd counting fingers in the left eye (OS). His introculr pressures were 24 mm Hg OD nd 20 mm Hg OS. The slit-lmp exmintion of the right eye ws unremrkle. The left eye hd rre cells in the nterior chmer, mild nucler sclerotic ctrct, nd 2+ vitreous cells. The fundus exm ws notle for retinl detchment with shifting suretinl fluid, with inferior choroidl thickening nd effusions ( fig. 1 ). Centrl serous retinopthy ws n initil considertion for this ptient s presenttion, ut most concerning to the ophthlmologist ws the potentil dignosis of leukemic infiltrtion cusing the choroidl thickening nd serous detchment given the ptient s pst medicl history. However, the ptient s one mrrow iopsy 3 months prior did not show ny signs of recurrence, nd moleculr studies showed tht BCR-ABL or the Phildelphi chromosome, fusion gene of chromosomes 9 nd 22 present in this ptient s form of ALL, ws not detected. Given this recent negtive testing, these eye findings lone were not ccepted s signs of relpsed ALL y his oncologist. One month lter, the ptient returned with worsening scleritis, uveitis, nd lood-tinged hypopyon with neovsculriztion of the iris ( fig. 1 ). At this time, he hd totl retinl detchment with persistent choroidl effusions further incresing the ophthlmologist s suspicion for leukemic recurrence. However, the ptient s oncologists remined uncertin tht the oculr mnifesttions could e sign of relpsed disese given the lck of systemic findings. He ws followed with repet BCR-ABL testing every few months, which remined negtive. Over the next 6 months, the ptient s vision continued to deteriorte to light perception, nd the possiility of mlignnt infiltrtion ws discussed repetedly; however, the ptient deferred iopsy or surgicl intervention for his oculr mnifesttions. When the eye ecme pinful, enucletion of the eye ws considered; however, prior to the procedure, he presented to the emergency room with severe hedche, ftigue, nd weight loss. Cererospinl fluid smpling t tht time showed cler evidence of centrl nervous system leukemi, with over 3,000 white cells, 72% of which were lsts. At this time, he received intrthecl chemotherpy nd high-dose methotrexte. Systemic therpy with dstini (Sprycel, Bristol-Meyers Squi, Princeton, N.J., USA) ws lso initited, nd rdition tretment of 20 Gy to the left orit ws delivered. His vision remined 20/25 in the right eye without ny fundus chnges nd light perception in the left eye without pin. He is currently receiving ongoing neuro-oncologic tretment for his relpsed disese. Cse 1 Cse 2 A 57-yer-old mle with history of cute myeloid leukemi (AML; norml cytogenetics with Flt-3 nd NPM-negtive), in complete remission for 4 yers fter induction chemotherpy with dunoruicin nd high-dose cytrine (HIDAC), consolidtion chemotherpy with 3 cycles of HIDAC nd utologous stem cell trnsplnt followed y mintennce 5-zcytdine, ws dmitted to n outside hospitl with progressive right eye pin, redness, nd swelling. He ws presumed to hve right oritl cellulitis, ut lck of improvement on rod-spectrum ntimicroils prompted trnsfer to our institution. On presenttion, the ptient s visul cuity ws decresed to 20/200 OD nd stle t 20/20 OS. His introculr pressure ws elevted t 49 mm Hg OD nd norml t 17 mm Hg OS. Slit-lmp exmintion ws notle for right perioritl erythem nd edem, diffusely injected conjunctiv, microcystic cornel edem, nd shllow nterior chmer. Exmintion of the left eye ws unremrkle, including deep nd quiet nterior chmer. Gonioscopy reveled no visile ngle structures OD, consistent with closed ngle, while OS, the ngle ws open to sclerl spur 360. A B-scn ultrsound showed diffusely thickened choroid, nd ultrsound iomicroscopy confirmed secondry ngle closure due to nterior rottion of the lens-iris diphrgm. Introculr pressure-lowering medictions nd cyclopentolte were strted. After the introculr pressure egn to improve, diffuse irregulr choroidl elevtion ws seen on fundus exmintion of the right eye. Fluorescein ngiogrphy showed pinpoint lekge in the inferotemporl periphery nd diffuse lte suretinl lekge (fig. 2 ). Unilterl Eye Findings: A Rre Herld of Acute Leukemi 167

3 Color version ville online Before rdition After rdition Fig. 2. Fundus photo of the ptient s right eye (cse 2) showing diffuse, irregulr choroidl elevtion nd rre intrretinl hemorrhges. Arrows help demrcte res where prominent elevtion is seen. Fluorescein ngiogrphy (cse 2) demonstrting pinpoint lekge in the inferotemporl periphery, shown with rrows. Fig. 3. B-scn ultrsonogrphy imges of the ptient s right eye (cse 2) efore ( ) nd fter rdition ( ) with resolution of the diffuse choroidl thickening with rdition tretment. Arrows delinete thickening in the ultrsound imge efore rdition. As the ptient s leukocyte count ws elevted to 33,700 with numerous monocytes nd rre lsts on peripherl smer, leukemic recurrence ws of concern to oth the ophthlmology nd oncology tems. An initil one mrrow iopsy, cytogenetics nd next-genertion sequencing did not show ny signs of relpsed or new leukemic disese. Lumr puncture nd CT-PET scn to evlute for extrmedullry disese were negtive nd systemic chemotherpy ws deferred. As choroidl thickening progressed nd given the high suspicion for leukemic involvement, the ptient ws offered choroidl iopsy ut deferred in fvor of empiric rdition tretment. Irrdition to the right eye ws initited 2 weeks fter symptom onset for totl of 20 Gy delivered over 10 frctions with drmtic improvement in his visul cuity to 20/15, normliztion of his introculr pressure, nd resolution of the choroidl thickening y dy 3 of tretment ( fig. 3 ). Two weeks fter eginning rdition to the right eye, the ptient developed similr symptoms nd choroidl thickening in the left eye s well s worsening thromocytopeni. A repet hemtologicl evlution showed findings consistent with chronic myelomonocytic leukemi. He susequently hd rdition therpy with 20 Gy delivered to the left eye. He ws strted on decitine for worsening thromocytopeni. After 4 cycles of tretment, the ptient presented with recurrent left eye conjunctivl injection nd choroidl thickening. Bone mrrow iopsy reveled 5% lsts nd new muttion. He ws re-induced with HIDAC nd within week, his eye symptoms nd choroidl thickening resolved. However, repet one mrrow iopsy performed 4 weeks lter reveled trnsformtion to AML with 29% lsts. The ptient underwent n unrelted donor stem cell trnsplnt nd is currently in remission 9 months lter. Discussion nd Review of the Literture In oth of the ove-descried cses, unilterl oculr involvement ws the initil mnifesttion of relpsed cute leukemi tht ws otherwise thought to e in complete remission. Serous retinl detchment is n uncommon presenttion of new or relpsed leukemic disese, ut it hs een previously reported in cses of ALL nd AML in the dult popultion. In the mjority of reported cses of serous retinl detchment or choroidl infiltrtion, the systemic disese hd een dignosed prior to the development of oculr symptoms [3 9]. A review of the literture reveled only 5 cses of decresed vision nd serous retinl detchment s initil presenting signs of new leukemi in n dult ptient [10 14]. Kim et l. [10] nd Yoshid et l. [11] oth descried dult women presenting with ilterl serous retinl detchments s the initil sign of Phildelphi chromosome-positive ALL. In oth cses, the serous detchments completely resolved with full recovery of vision once systemic chemotherpy ws promptly initited. Riss et l. [12] nd Cillux et l. [13] descried similr presenttions of ilterl serous detchments reveling new dignosis of AML in two dult ptients. In ll of these cses, the ptients presented with ilterl simultneous serous retinl detchments while in oth of our ptients, the initil ophthlmic involvement ws unilterl. There re dditionlly four cses in the literture of retinl involvement in dults s the initil sign of relpsed leukemic disese s in our ptients. However, ll prior cses hd much shorter time from remission to retinl infiltrtive disese s mrker of relpse, with only 3 5 months of disese-free period compred to the 18 months nd 4 yers seen in ech of our ptients [14 17]. Wu et l. [15] descried 30-yer-old womn with AML type M4 M5 who ws in complete remission documented y one mrrow spirtion nd presented with decresed vision, ilterl serous retinl detchments, nd choroidl infiltrtion 3 months lter. As she hd no systemic evidence of relpsed disese, oncology initilly de- 168 Ptel/Miller/Nth/Shih/Yoon/Freitg/ Ppliodis/Chen/Eliott/Kim

4 ferred tretment. Only fter choroidl iopsy nd repet one mrrow workup 3 months lter demonstrted relpsed disese ws chemotherpy restrted [15]. Similrly, three other cses re reported in the literture, one with ilterl choroidl elevtion nd two with ilterl simultneous serous retinl detchments. The time from remission to presenttion with oculr symptoms rnged from just few weeks to 5 months fter remission in these cses [14, 16, 17]. Further, choroidl infiltrtion cusing ngle closure, s in our second cse, is exceedingly rre. There is only one other report of ptient who presented with ilterl ngle closure nd proptosis due to uveosclerl thickening in the setting of leukemi [18]. This ptient lredy hd n estlished dignosis of AML t the time of visul symptoms, nd his presenttion ws ilterl. In the cse of our ptient, the disese ws in remission for severl yers, nd he did not develop symptoms in the second eye until fter rdition tretment ws initited for the first eye. In oth cses presented in this report, the unilterlity of symptoms nd findings mde the dignosis of relpsed disese prticulrly chllenging. Oculr mnifesttions of leukemi my present s direct infiltrtion of the conjunctiv, uve, optic nerve or orit or s secondry chnges due to the hemtologic chnges ssocited with leukemi such s nemi, thromocytopeni, hyperviscosity, nd opportunistic infections [2, 19]. Studies hve shown vrying prevlence of leukemic involvement of the eye rnging from 50 80% with higher incidence of involvement in histopthologic postmortem studies [1, 20]. This is likely explined y the often sutle clinicl signs tht my indicte oculr involvement, prticulrly choroidl involvement. A higher incidence of oculr involvement, including choroidl infiltrtion, is seen in eyes with cute leukemi compred to chronic leukemi: 80 versus 29% [20]. If cliniclly evident choroidl infiltrtion is present, it most often presents with retinl pigmentry chnges, thickening, nd serous retinl detchment in the most conspicuous cses [1]. Serous retinl detchment is thought to occur due to direct leukemic infiltrtion of the choroid cusing decresed lood flow in the choriocpillris, resulting in ischemi to the overlying retinl pigment epithelium (RPE) nd disrupting intercellulr tight junctions nd the ility of the RPE to effectively pump fluid [21, 22]. Specil ncillry tests, such s fluorescein ngiogrphy nd B-scn ultrsonogrphy, my e especilly helpful in mking the dignosis of choroidl infiltrtion. Fluorescein ngiogrphy revels diffuse pinpoint lekge, while B-scn ultrsonogrphy my revel serous detchment or choroidl thickening [22, 23]. Introculr mnifesttions of leukemi such s those descried in these cses should prompt thorough systemic workup. Systemic tretment is recommended first in these cses, ut if not n option or if the oculr disese is not responsive, oculr rdition my e implemented. The dose of externl em rdition required in these cses is usully lower thn tht required for lymphom nd is most commonly 20 Gy delivered t frctions of Gy dily [24]. If left untreted, leukemic oculr infiltrtive disese my cuse significnt visul loss; however, it is usully very responsive to systemic tretment with chemotherpy, locl rdition tretment to the eye, or comintion of oth. Physicins should e wre tht unilterl eye findings cn e n initil mnifesttion of recurrent leukemi, nd in ptients with pst history of leukemi, prctitioners must mintin heightened wreness for relpsed hemtologic disese. Both of these cses show tht leukemic involvement of the eye my mimic other disese, such s centrl serous retinopthy in the first cse or infectious cellulitis in the second cse, nd the unilterl nture of symptoms my mke the dignosis of systemic etiology prticulrly difficult. Prompt referrl to n ophthlmologist will help determine if there is high suspicion for relpsed leukemi nd systemic tretment is often integrl to resolution of the oculr prolems. Sttement of Ethics This study ws conducted in complince with the rules nd regultions of the Helth Insurnce Portility nd Accountility Act s well s in dherence to the Declrtion of Helsinki nd ll other relevnt federl nd stte lws. Disclosure Sttement The uthors hve no finncil disclosures or conflicts of interest to report. Unilterl Eye Findings: A Rre Herld of Acute Leukemi 169

5 References 1 Kincid MC, Green WR: Oculr nd oritl involvement in leukemi. Surv Ophthlmol 1983; 27: Schcht AP: Ophthlmic mnifesttions of leukemi. Arch Ophthlmol 1989; 107: Ghosh K, Mitr S, Hiwse D: Choroidl infiltrtes simulting fundl chnges of cute leukemi during hemtologicl recovery following high-dose chemotherpy in cute myelomonocytic leukemi in remission. Am J Hemtol 2000; 63: Mdjlessi F, Dnn K, Althus C, Sundmcher R, Meckenstock G: Choroid infiltrtion in myelodysplstic syndrome. Klin Monl Augenheilkd 1998; 213: Krtş M, Altn Yycıoğlu R, Boğ C, Ulş B: Akut myeloid lösemiye ğlı ilterl seröz mkül dekolmnı. Türk Oftlmol Derg 2014; 44: Burns CA, Blodi FC, Willimson BK: Acute lymphocytic leukemi nd centrl serous retinopthy. Trns Am Acd Ophthlmol Otolryngol 1965; 69: Murphy JA, Pitts JF, Dudgeon J, Hogg RB, Hrnett AN: Retinl detchments due to chronic lymphocytic leukemi. Clin L Hemtol 1991; 13: Hine JE, Kinghm JD: Myelogenous leukemi nd ilterl exudtive retinl detchment. Ann Ophthlmol 1979; 11: Cndoni A, Simeone E, Bndello F, Fnin R: Leukemic infiltrtion of the retin t onset of Phildelphi-positive cute lympholstic leukemi reveled y strtus opticl coherence tomogrphy. Br J Hemtol 2006; 133: Kim J, Chng W, Sgong M: Bilterl serous retinl detchment s presenting sign of cute lympholstic leukemi. Koren J Ophthlmol 2010; 24: Yoshid A, Kwno Y-I, Eto T, et l: Serous retinl detchment in n elderly ptient with Phildelphi-chromosome-positive cute lympholstic leukemi. Am J Ophthlmol 2005; 139: Riss JM, Kplnski G, Righini-Chossegros M, Hrle JR, Escoffier P, Srcco JB: Bilterl serous detchment of neuroepithelium of the posterior pole disclosing cute leukemi. J Fr Ophtlmol 1990; 13: Cillux V, Querques G, Rmhefsolo C, Drugr A, Souied EH: Bilterl mculr serous retinl detchment reveling cute myelolstic leukemi. Retin Cses Brief Rep 2013; 7: Fckler TK, Berelly S, Odom T, Fekrt S, Cooney MJ: Acute lympholstic leukemi presenting s ilterl serous mculr detchments. Retin 2006; 26: Wu L, Clderón M, Hernández G, Mris J, Rmírez V: Bilterl exudtive retinl detchment s the first sign of relpsing cute myelogenous leukemi. Clin Experiment Ophthlmol 2006; 34: Chng WJ, Mow BM, Sundr G: Leukemic infiltrtion of the choroid. Eur J Hemtol 2005; 74: Goln S, Goldstein M: Acute lymphocytic leukemi relpsing s ilterl serous retinl detchment: cse report. Eye (Lond) 2011; 25: Tumuluri K, Woo T, Crowston J, Heley PR, Gottlie D, Mloof AJ: Bilterl leukemic oritl infiltrtion presenting s proptosis nd nrrow-ngle glucom. Ophthl Plst Reconstr Surg 2004; 20: Shields JA, Shields CL: Introculr Tumors: An Atls nd Textook. Phildelphi, Lippincott Willims & Wilkins, Allen RA, Strtsm BR: Oculr involvement in leukemi nd llied disorders. Arch Ophthlmol 1961; 66: Stewrt MW, Gitter KA, Cohen G: Acute leukemi presenting s unilterl exudtive retinl detchment. Retin 1989; 9: Miymoto K: Serous retinl detchment cused y leukemic choroidl infiltrtion during complete remission. Br J Ophthlmol 2000; 84: Armson DH, Jere B, Wollner N, Murphy L, Ellsworth RM: Leukemic ophthlmopthy detected y ultrsound. J Peditr Ophthlmol Strismus 1983; 20: Brdy LW, Shields JA, Augsurger JJ, Dy JL: Mlignnt introculr tumors. Cncer 1982; 49: Ptel/Miller/Nth/Shih/Yoon/Freitg/ Ppliodis/Chen/Eliott/Kim