Clinical and Experimental Vision and Eye Research

Show Contents

Pediatric orbital tumors - An overview
  CLEVER
REVIEW ARTICLE
Pediatric orbital tumors - An overview
Rachna Meel, Pallavi Singh
Department of Oculoplasty and Ocular Oncology Services, Dr. Rajendra Prasad Centre for Ophthalmic Sciences, New Delhi, Delhi, India
Address for correspondence: Department of Oculoplasty and OcularOncology Services, Dr. Rajendra Prasad Centrefor Ophthalmic Sciences, New Delhi, Delhi,India.
E-mail: dr.rachnameel@gmail.com
Received 16 April 2018;
Accepted 30 June 2018
doi: 10.15713/ins.clever.8
 
ABSTRACT
The spectrum of pediatric orbital tumors differs from that of adults and further variesaccording to age. Tumors seen in teenage are similar to those seen in adults, whilecongenital space-occupying lesions such as colobomatous cyst and teratoma form anentity unique to infancy and early childhood. There is a vast difference in the managementof orbital disease in children as opposed to adults in view of the different challenges faced.
Keywords: Pediatric, orbital, tumors
How to cite this article: Meel R. Pediatric orbital tumors - Anoverview. Cli Exp Vis Eye Res J 2018;1(1): 38-43.
 
 

Introduction

The spectrum of pediatric orbital tumors differs from that ofadults and further varies according to age. Tumors seen inteenage are similar to those seen in adults, while congenital spaceoccupyinglesions such as colobomatous cyst and teratoma forman entity unique to infancy and early childhood.

The incidence of various space-occupying lesions of pediatricorbit, as reported in literature, is extremely variable. The reportingfacility (pathology or ophthalmology), location of the facility,and interest of the treating specialist affect the outcome of suchstudies.[1,2] However, most studies show that benign lesions are morecommon; rhe most common being cystic lesions comprising mainlyof dermoids and/or vascular lesions [Table 1].[3-5] Studies from thedeveloping world report a greater percentage of malignant lesionsin pediatric orbit as compared to North America and Europe.[6,7]This could perhaps be explained because most inflammatory causesof proptosis such as orbital cellulitis are not biopsied and/or thereis in fact a greater incidence of pediatric orbital malignancies; forexample, orbital retinoblastoma constitutes nearly 50% of all casesof retinoblastoma in India, while in the western world, it constitutes< 10%.[8] Therefore, orbital retinoblastoma constitutes a largepercentage of childhood orbital lesions in our country. A report froma tertiary care center of our country shows that rhabdomyosarcomaand orbital retinoblastoma are the most common malignant lesionsin the pediatric orbit, while dermoid cyst and lymphangiomaconstitute the most common benign lesions.[6]

 
Diagnosis

Although benign lesions are more common in the pediatricorbit, if not managed on time, they may cause severe morbidityfrom amblyopia, corneal exposure, or optic nerve damage.[1,3,8-10]Malignant lesions, on the other hand, if not diagnosed and treatedin time will affect survival.

Difficulties peculiar to pediatric orbital lesions

The examining ophthalmologist faces difficulties that are typical topediatric age; for example, the child may not be able to report all thesymptoms, and investigations like imaging (magnetic resonanceimaging [MRI] and computed tomography [CT] scan) and biopsymay require general anesthesia. Apart from these problems, the riskof amblyopia is typical to children < 9 years of age and is a majorcause of morbidity in cases of benign lesions of pediatric orbit.

When a child presents with proptosis, the following mayindicate malignancy:
  1. Acute onset/rapidly progressing proptosis
  2. History of leukocoria
  3. History of recurrent fever, bone pains, bleeding, or any otherextraorbital masses like in the abdomen
  4. Family history of childhood malignancy.

38 Clinical and Experimental Vision and Eye Research, January-June, Vol 1, 2018

Pediatric orbital tumors - An overview Meel

Table 1: Incidence of pediatric orbital space occupying lesions
Pediatric orbital tumors - An overview


However, one should remember that acute onset proptosismay also result from benign lesions such as orbital cellulitis,orbital cysticercosis, or hemorrhage in a pre-existing orbitallymphangioma.[11]

Imaging Techniques

Ultrasonography (USG): Orbital USG is a very useful tool inmaking a differential diagnosis. Ultrasound reveals the natureand location of the lesion. The lesion may be cystic, solid,or mixed, infiltrative, or well defined. In case of solid spaceoccupyinglesions, USG reveals the internal architecture of thetumor (regular or irregular, high or low internal reflectivity),presence of calcifications, and effect of the tumor on adjacentorbital structures (whether the space-occupying lesionconforms to the shape of the globe or causes globe indentation,if the mass is arising from the globe or is confined to one of theorbital structures such as extraocular muscle, lacrimal gland, oroptic nerve).

On USG, cystic lesions such as cysticercus cyst and hydatidcyst have characteristic features and dermoid cysts are seenas cystic lesions with irregular, high internal reflectivity. Aninfiltrative lesion with multiple, variable sized cysts on USG anda typical history of recurrent proptosis associated with upperrespiratory tract infection is diagnostic of lymphangioma.

CT scan

CT scan of orbit must be done in all cases of orbital tumors.It provides useful information about the bony orbit. Itdemonstrates whether the lesion is arising from bone oris causing secondary bone changes like erosion (sign ofmalignancy) or remodelling (seen in long-standing masses).The exact location, internal architecture, and calcificationmay be better appreciated on CT scan. Any extension fromor into adjacent intracranial space, paranasal sinuses, or nosemay be detected. The effect of contrast on the lesion providesinformation regarding vascularity of the tumor; for example,lymphangioma usually enhances minimally with contrastwhile capillary hemangioma will show feeder vessels with goodcontrast enhancement.

 
MRI

MRI is an extremely useful tool for orbital imaging, especiallyin cases of orbital tumors. Due to better soft tissue contrastand no risk of radiation, it has become an indispensablemodality for characterization of orbital lesions. It is idealfor visualization of the entire course of the optic nerve andthe pituitary gland. Thus, it has a central role to play in thediagnosis and prognostication of retinoblastoma. It is also themodality of choice in imaging of non-vascular tumors such aspseudotumor, orbital cellulitis, and orbital cysticercosis. MRIalso helps to diagnose any extension of the lesion to the orbitalapex, optic canal, or brain. However, it is expensive and cannotbe performed in patients with any metallic implants/foreignbodies.

The Common Benign and Malignant Orbital Lesions of
Pediatric Age Group


The list of pediatric orbital space-occupying lesions is long, buthere is a brief clinical, imaging, and treatment outline for the mostcommonly encountered lesions of pediatric orbit.

Cystic lesions

Dermoid cyst

These are the most common cystic lesions of the pediatric orbit.[3]They present as long-standing, slowly growing hard masses thatare located at the external angle of eye (lacrimal fossa) [Figure 1a].Occasionally, they may rupture secondary to trauma and presentwith acute inflammation. On USG, they are characteristicallyseen as cystic lesions with variable internal reflectivity that is highto moderate and often harbors the areas of calcification. CT scanis performed to look for bone remodeling and rule out intracranialinvolvement. Fat shadows are usually seen as dark areas withinthe cyst. Simple excision of the intact cyst is the treatment ofchoice.[12]

Clinical and Experimental Vision and Eye Research, January-June, Vol 1, 2018 39

Meel Pediatric orbital tumors - An overview

Pediatric orbital tumors - An overview
Figure 1: ???

Parasitic cysts

A. Cysticercosis
Parasitic cysts of ocular adnexa and orbit are commonly seenin the developing world.[13] Cysticercosis of orbit typicallyaffects young individuals and has a wide spectrum of clinicalmanifestations. It most commonly involves anterior orbit(extraocular muscles), followed by subconjunctival space,eyelid, and posterior orbit.[13] The affected child presentswith acute onset, painful diplopia, squint, or proptosis. Visualacuity may be affected when the cyst involves the orbital apexor the globe. There may be single or multiple cysts. On USG,they appear as cystic lesions with a single spike of high (100%)reflectivity [Figure 1b]. A CT scan of the brain and indirectophthalmoscopy should be done in all cases to rule outneurocysticercosis and intraocular cysticercosis, respectively.

 
A stool test may be done to rule out autoinfection. The choiceof treatment is medical therapy with the antihelminthic drugalbendazole (15 mg/kg body weight in two divided dosesfor 6-8 weeks) given under the cover of oral steroids[14]. Thechanges in the USG characteristics of the cysticercus cyst inresponse to medical therapy have been described in literature.[15] In case of subconjunctival cysticercus cysts or residualcysts after medical therapy, one may excise the cyst. Theinflammation associated with cysticercus cysts may be clinicallyconfusing and a misdiagnosis of orbital cellulitis is oftenmade.[16] Therefore, in all cases of orbital cellulitis, imagingshould be carefully evaluated to rule out any cysticercus cyst,in which case, there will be no/poor response to systemicantibiotics and anti-inflammatory medications alone. In casesassociated with neurocysticercosis, the treatment is guided byneural involvement. Despite resolution of cysticercosis withmedical management, a significant proportion of patients willhave residual functional deficits.[13]

B. Hydatid cyst
Hydatid cyst of orbit may be seen in pediatric orbit, especiallyin countries endemic for this disease. Around 1% of all casesinvolve orbit. The affected child presents with a long-standing,slowly increasing, painless proptosis [Figure 1c]. Ultrasoundfeatures are characteristic and reveal an anechoic cyst withtwo highly reflective linings (double wall sign).[17] A historyof contact with dogs is usually present. CT scan shows a cysticlesion with orbital expansion and bone remodeling due to longstandingnature of the lesion [Figure 1d]. Globe indentationleads to refractive changes, which if not taken care of may leadto anisometropic amblyopia. Unlike in cysticercosis, wherethe management of choice is medical therapy, the treatmentof choice for a single orbital hydatid cyst is surgical excision.Hydatid cyst is lined by three layers: The endocyst, ectocyst,and pericyst. The aim of surgical excision is to remove theendocyst (that harbors the daughter cysts) intact after incisingthe pericyst and the ectocyst. Cryoprobe is helpful in holdingand delivering the endocyst which has very thin and delicatewalls.[17] A leak from the endocyst during the surgery willinvariably lead to daughter cyst implantation and result intomultiple recurrences in the orbit. In cases of recurrence ormultiple cysts, oral treatment with albendazole may be tried ascomplete surgical excision is difficult.[18,19]

Vasculogenic tumors

These include lymphangioma, capillary hemangioma, varicoseveins, and cavernous hemangioma. Of these, lymphangioma andcapillary hemangioma occur very commonly in pediatric orbitand are discussed here.

Lymphangioma/combined venous-lymphatic vascular malformation

Apart from cystic lesions, lymphangioma is the most commonvasculogenic benign orbital space-occupying lesion of the pediatricorbit, reported from our country.[6] According to the ISSVAclassification for vascular tumors, the preferred terminology forthis lesion is no flow vascular malformation.[20] The patient usuallypresents with a long-standing proptosis or eyelid swelling thathas suddenly increased in size. The swelling characteristicallyincreases in size following an episode of cough and cold andresponds dramatically to oral steroids [Figure 1e]. Sometimes,massive hemorrhage may occur within the lymphangioma thatmay require urgent surgical intervention to decompress theorbit.[21] Indications for such an urgent surgical drainage includeoptic nerve compromise (suggested by appearance of relativeafferent pupillary defect and/or deterioration of vision) orcorneal exposure due to lagophthalmos. The acute presentationin such cases may often confuse the treating clinician who maymisdiagnose it as a malignancy. However, a careful history takingand clinical examination will usually lead to correct diagnosis.

40 Clinical and Experimental Vision and Eye Research, January-June, Vol 1, 2018

Pediatric orbital tumors - An overview Meel

Clinical examination on slit lamp may reveal clear lymphaticfluid-filled cysts in the subconjunctival space. USG shows diffuseinfiltrative lesion with multiple variable sized cysts. CT scanorbit, similarly, shows an infiltrative, ill-defined orbital lesionwith minimal/no contrast enhancement, as it is isolated withrespect to the vascularity. Many times, large cysts may be seenwith fluid-fluid levels [Figure 1f].

Being an infiltrative lesion, complete surgical excision is usuallynot possible. Surgical intervention may cause more hemorrhagein the lymphangiomatous tissue. Hence, of late, sclerosing agentsare at the forefront of therapy for lymphangiomas. Intralesionalbleomycin has been successfully used in a dose of 0.5 IU/kgbody weight (with a maximum of 15 IU/mL).[22,23] Oral steroidsare also used to manage any increase in the size of lesion. Surgicalexcision is restricted for large orbital lymphangiomas that arecosmetically disfiguring. As patients reach the second decade oflife, some lymphangiomas may show regression or may stabilize.

Capillary hemangioma

It is the most common congenital vascular tumor in the periocularregion.[24] They are benign vasoproliferative tumors of vascularendothelial cells that are defined by their unique histology andevolution. Most of them are located in the head and neck region[Figure 1g]. When located around the orbit, they can causesignificant cosmetic deformity and amblyopia, the latter due toastigmatism or mechanical ptosis causing visual deprivation.[25,26]Orbital involvement may lead to proptosis, exposure keratopathy,or compressive optic neuropathy. Although the natural course ofdisease in capillary hemangioma is spontaneous regression, manychildren still require treatment. Many therapeutic options havebeen used, including intralesional or systemic steroids, surgery,embolization, radiation, interferon therapy, and laser therapy.[26-29]Systemic therapy with propranolol was serendipitously found toinduce involution in capillary hemangiomas and is now popularlybeing used as a first-line treatment, especially for deep orbitallesions. The most common dose used is 2 mg/kg/day.[30]

Orbital malignancies

Rhabdomyosarcoma

It is the most common orbital malignancy of childhood. Around5% of cases occur in orbit. It usually presents at a mean ageof 7.5 years.[31] The patient presents with a rapidly increasingproptosis or an upper eyelid mass. Clinical examinationreveals a firm orbital mass with variable consistency, usuallyinvolving superior orbit. Clinically, it may mimic orbitalcellulitis. On imaging, a well-defined heterogeneous masscan be seen which involves the extraocular muscle, mayhave calcification, and is usually associated with erosion ofadjacent bony orbit. There is variable contrast enhancementand globe indentation but intraocular structures are normal.

 
An incision biopsy confirms the diagnosis in most cases.Sometimes histopathology may only reveal features of a roundcell tumor; in such cases, further immunohistochemical stainingis required to reach a diagnosis. Other round cell tumors thatare differentiated on immunohistochemical staining includeretinoblastoma, medulloepithelioma, Ewing's sarcoma,granulocytic sarcoma, and neuroectodermal tumor. Of these,retinoblastoma is a common cause of orbital tumor in pediatricorbit in developing countries.

The current standard of treatment for rhabdomyosarcomais chemoradiotherapy. The majority of patients are cured withthe use of both chemotherapy and radiation therapy, but aconsiderable number experience late sequelae of treatment.The 10-year event-free and overall survival reported are77% and 87%, respectively, for primary orbital RMS.[32] Thechallenge with current therapy is to reduce undesirable effectsof radiotherapy.

Retinoblastoma

Retinoblastoma is the most common intraocular malignancyof childhood worldwide; furthermore, it is an important causeof orbital malignancy of pediatric orbit in developing world.[8]Along with rhabdomyosarcoma, it constitutes the most commoncause of orbital malignancy in the pediatric age group in India.[6]The clinical presentation is similar to rhabdomyosarcoma thatis a rapidly increasing proptosis. However, parents will usuallygive a history of leukocoria preceding the orbital symptoms.Such a history should always be elicited in all the cases of rapidlyprogressing childhood proptosis.

USG reveals an intraocular mass filling the globe withintralesional calcification. CT scan orbit and brain should bedone in all cases which reveal a heterogeneous mass lesionwithin the globe with areas of calcification and extendinginto the orbit either as an extraocular mass or as thickenedoptic nerve [Figure 1h]. It may also reveal any intracranialextension. Locally invasive and malignant retinoblastomaconstitutes nearly half of all cases of retinoblastoma in ourcountry.[8] The survival prognosis is only 50% at 5 years forlocally invasive retinoblastoma.[33,34] Diagnosis is evident onimaging and is confirmed by histopathological examinationin cases of doubt.

Currently, the standard line of treatment of locally invasiveretinoblastoma comprises of neoadjuvant chemotherapy(3 cycles) with standard VEC regimen followed by limitedsurgery (enucleation) and adjuvant chemotherapy (9 cycles)and radiotherapy.

Clinical and Experimental Vision and Eye Research, January-June, Vol 1, 2018 41

Meel Pediatric orbital tumors - An overview

Granulocytic sarcoma

Leukemia is the most common malignancy of childhood.Around 15-20% of cases of leukemia are myelogenetic and8% of these develop extramedullary solid tumors of primitivegranulocyte precursor cells known as granulocytic sarcoma/myeloid sarcoma/chloroma. These occur more commonly inchildren, are typically multifocal, and have a predilection foroccurrence in orbit and orbital bones. They present as a rapidlyexpanding orbital mass at a mean age of around 7-8 years[Figure 1i].[35] The temporal association with systemic diseasemay be variable, but they usually present 2 months to 3 yearsbefore systemic disease becomes advanced. Symptoms ofsystemic disease such as paleness, lethargy, or epistaxis maysuggest the diagnosis. Orbital granulocytic sarcoma mayoccur bilaterally in 10% of cases. They usually arise in thesubperiosteal region of the osseous wall of the orbit. CT scanshows a homogeneous mass usually in the lateral orbit whichis iso/hypodense to extraocular muscle and hypodense tosclera and enhances uniformly with contrast [Figure 1j]. Theyusually do not cause bone destruction and mold to one or moreorbital walls.[36,37] Incision biopsy is diagnostic and may showfeatures of small round cell tumor. Staining for Auer rods in thecytoplasm is diagnostic.

In cases of acute onset bilateral proptosis/orbital masses inchildren, granulocytic sarcoma should be suspected. In suchcases, a peripheral blood film and/or bone marrow biopsy shouldalways be done to rule out leukemia. This may preclude the needfor a biopsy. Although granulocytic sarcoma is highly responsiveto chemotherapy and local radiotherapy, survival prognosis isuniversally poor. Sometimes, orbital granulocytic sarcoma mayoccur in isolation.[38]

Other causes of acute proptosis in setting of acute leukemiainclude hemorrhage and orbital abscess. However, these can bedifferentiated on imaging. Less commonly acute lymphocyticleukemia may also infiltrate orbit or eyeball.

To conclude, pediatric orbital tumors constitute a clinicallydistinct entity from that of adult orbital tumors and posesome unique challenges to the treating ophthalmologist. Thetreating ophthalmologist/oculoplastic surgeon should beaware of conditions that may require early medical/surgicalintervention.

References
  1. Templeton AC. Orbital tumours in African children. Br JOphthalmol 1971;55:254-61.
  2. Moss HM. Expanding lesions of the orbit. A clinical study of 230consecutive cases. Am J Ophthalmol 1962;54:761-70.
  3. Shields JA, Bakewell B, Augsburger JJ, Donoso LA, Bernardino V.Space biopsies occupying orbital masses in children. A review of250 consecutive cases. Ophthalmology 1986;93:379-84.
  4. Kodsi SR, Shetlar DJ, Campbell RJ, Garitty JA, Bartley GB, et al.A review of 340 orbital tumors in children during a 60-yearperiod. Am J Ophthalmol 1994;117:177-82.
  5. Bullock JD, Goldberg HS, Rakes SM. Orbital tumors in children.Ophthal Plast Reconstr Surg 1989;5:13-6.

 
  1. Bajaj MS, Pushker N, Chaturvedi A, Betharia SM, Kashyap S,Balasubramanya R, et al. Orbital space-occupying lesionsin Indian children. J Pediatr Ophthalmol Strabismus2007;44:106-11.
  2. Gunalp I, Gunduz K. Pediatric orbitaltumors in Turkey. OphthalPlast Reconstr Surg 1995;11:193-9.
  3. Bakhshi S, Gupta S, Gogia V, Ravindranath Y. Compliance inretinoblastoma. Indian J Pediatr 2010;77:535-40.
  4. Eldrup-Jorgensen P, Fledelius H. Orbital tumours in infancy.An analysis of Danish cases from 1943-l962. Acta Ophthalol1975;53:887-93.
  5. Porterfield JF. Orbital tumors in children: A report on 214 cases.Int Ophthalmol Clin 1962;2:319-35.
  6. Harris GJ, Sakol PJ, Bonavolonta G, De Conciliis C. An analysisof thirty cases of orbital lymphangioma: Pathophysiologicconsiderations and management recommendations.Ophthalmology 1990;97:1583-92.
  7. Sherman RP, Rootman J, La Pointe JS. Orbital dermoids:Clinical presentation and management. Br J Ophthalmol1984;68:642-52.
  8. Rath S, Honavar SG, Naik M, Anand R, Agarwal B, Krishnaiah S,et al. Orbital cysticercosis: Clinical manifestations, diagnosis,management, and outcome. Ophthalmology 2010;117:600-5.
  9. Sihota R, Honavar SG. Oral albendazole in the management ofextraocular cysticercosis. Br J Ophthalmol 1994;78:621-3.
  10. Pushker N, Meel R, Bajaj MS, Kashyap S, Khuriajam N, Gupta S,et al. Orbital abscess with unusual features. Ophthal PlastReconstr Surg 2009;25:450-4.
  11. Betharia SM, Sharma V, Pushker N. Ultrasound findings inorbital hydatid cysts. Am J Ophthalmol 2003;135:568-70.
  12. Gehad E, Nahri. A simplified technique for removal of orbitalhydatid cysts. Br J Ophthalmol 1991;75:743-5.
  13. Sihota R, Sharma T. Albendazole therapy for a recurrent orbitalhydatid cyst. Indian J Ophthalmol 2000;48:142.
  14. Papathanassiou M, Petrou P, Zampeli E, Vergados I, Paikos P.Disseminated hydatid disease in a child: Albendazole treatmentof orbital cyst. Eur J Ophthalmol 2008;18:1034-6.
  15. ISSVA Classification of Vascular Anomalies©2014 InternationalSociety for the Study of Vascular Anomalies; 2014. Availablefrom: http://www.issva.org/classification. [Last accessed on2018 Apr 10].
  16. Woo YJ, Kim CY, Sgrignoli B, Yoon JS. Orbital lymphangioma:Characteristics and treatment outcomes of 12 cases. Korean JOphthalmol 2017;31:194-201.
  17. Raichura ND, Alam MS, Noronha VO, Mukherjee B.A prospective study of the role of intralesionalbleomycin inorbital lymphangioma. J AAPOS 2017;21:146-51.
  18. Suzuki Y, Obana A, Gohto Y, Miki T, Otuka H, Inoue Y.Management of orbital lymphangioma using intralesionalinjection of OK-432. Br J Ophthalmol 2000;84:614-7.
  19. Garg R, Gupta N, Sharma A, Jain R, Beri S, D'Souza P. Acquiredcapillary hemangioma of the eyelid in a child. J PediatrOphthalmol Strabismus 2009;46:118-9.
  20. Fay A, Nguyen J, Jakobiec FA, Meyer-Junghaenel L, Waner M.Propranolol for isolated orbital infantile hemangioma. ArchOphthalmol 2010;128:256-8.
  21. Maguiness SM, Frieden IJ. Current management of infantilehemangiomas. Semin Cutan Med Surg 2010;29:106-14.
  22. Ceisler E, Blei F. Ophthalmic issues in hemangiomas of infancy.Lymphat Res Biol 2003;1:321-30.

42 Clinical and Experimental Vision and Eye Research, January-June, Vol 1, 2018

Pediatric orbital tumors - An overview Meel

  1. Apfelberg DB, Maser MR, White DN, Lash H, Lane B, Marks MP.Benefits of contact and noncontact YAG laser for periorbitalhemangiomas. Ann Plast Surg 1990;24:397-408.
  2. Tronina SA, Bobrova NF, Khrinenko VP. Combined surgicalmethod of orbital and periorbital hemangioma treatment ininfants. Orbit 2008;27:249-57.
  3. Cornish KS, Reddy AR. The use of propranolol in themanagement of periocular capillary haemangioma--a systematicreview. Eye (Lond) 2011;25:1277-83.
  4. Knowles DM, Jakobiec FA, Potter GD, Jones IS. Ophthalmicstriated muscle neoplasms. Surv Ophthalmol 1976;21:219-61.
  5. Oberlin O, Rey A, Anderson J, Carli M, Raney RB, Treuner J,et al. Treatment of orbital rhabdomyosarcoma: Survival and lateeffects of treatment--results of an international workshop. J ClinOncol 2001;19:197-204.
  6. Bakhshi S, Meel R, Mohanti BK, Naqvi SG. Treatment andoutcome of nonmetastatic extraocular retinoblastoma witha uniform chemotherapy protocol. J Pediatr Hematol Oncol2010;32:e42-5.

 
  1. Matsubara H, Makimoto A, Higa T, Kawamoto H, Sakiyama S,Hosono A, et al. A multidisciplinary treatment strategy thatincludes high-dose chemotherapy for metastatic retinoblastomawithout CNS involvement. Bone Marrow Transplant2005;35:763-6.
  2. Zimmerman LE, Font RL. Ophthalmologic manifestationsof granulocytic sarcoma (myeloid sarcoma or chloroma):The third Pan American Association of Ophthalmology andAmerican Journal of Ophthalmology Lecture. Am J Ophthalmol1975;80:975-90.
  3. Pui MH, Fletcher BD, Langston JW. Granulocytic sarcomain childhood leukemia: Imaging features. Radiology1994;190:698-702.
  4. Chung EM, Murphey MD, Specht CS, Cube R,Smirniotopoulos JG. From the archives of the AFIP.Pediatricorbit tumors and tumorlike lesions: Osseous lesions ofthe orbit. Radio Graph 2008;28:1193-214.
  5. Kumar J, Seith A, Bakhshi S, Kumar R, Kumar A, Sen S. Isolatedgranulocytic sarcoma of the orbit. Eur J Haematol 2007;78:456.

Clinical and Experimental Vision and Eye Research, January-June, Vol 1, 2018 43