Retinoblastoma: postenucleation orbital recurrence

Retinoblastoma: postenucleation orbital recurrenceMuhammad Arif,* FCPS; Ziaul Islam,{ FRCS

ABSTRACT N RESUME

Objective: The objective of this study was (i) to identify clinicopathological variables that significantly influence thefrequency of postenucleation orbital recurrence and (ii) to create an awareness regarding follow-up, to pre-emptorbital recurrence.

Design: Retrospective, case-controlled, longitudinal study.Participants:A total of 176 childrenwith retinoblastomawhowere admitted and treated at Khyber TeachingHospital

between August 1, 1978, and July 31, 1998.Methods: This study was undertaken by reviewing the appropriate charts. The data of children with primary enuc-

leation were analyzed to extract cases of orbital recurrence.Results: The mean age was 3.8 years (range 1–10 years). Of 176 patients, 83 (47.3%) presented with proptosis and

fungatingmass. Of 136 patients whowere enucleated, 80 (58.82%) presentedwith proptosis and fungatingmass. The31 patients who had been diagnosed as having had orbital recurrence had a mean age of 4.09 years. The durationbetween enucleation and orbital recurrencewas 1–12months in 28 patients (90.4%). Histopathology reports of only8 patients (26%) could be traced. Follow-up was recorded in only 9.6% of cases.

Conclusions: The failure to identify clinical and pathological parameters in the course of the disease in retinoblastomachildren results in human misery caused by poor follow-up and gross negligence.

Objet : La presente etude a donc pour objet (i) d’identifier les variables clinicopathologiques qui influent de faconsignificative sur la frequence de la recurrence orbitale apres enucleation et (ii) de creer une sensibilisation quant ausuivi pour prevenir la recurrence orbitaire.

Nature : Etude longitudinale retrospective avec cas-temoins.Participants : En tout, 176 enfants atteints de retinoblastome, admis et soignes au Khyber Teaching Hospital entre le

1er aout 1978 et le 31 juillet 1998.Methodes : Cette etude a commence par une revue des dossiers pertinents. Les donnees des enfants qui avaient eu

une enucleation primaire ont ete analysees pour en extraire les cas de recurrence orbitaire.Resultats : La moyenne d’age etait de 3,8 ans (ecart 1–10 ans). Parmi les 176 patients, 83 (47,3 %) avaient une

exophtalmie avec masse d’apparence fongueuse. Parmi les 136 patients qui avaient subi une enucleation, 80(58,82 %) presentaient une exophtalmie avec masse d’apparence fongueuse. Les 31 patients dont on avait diagnos-tique une recurrence orbitaire avaient 4,09 ans en moyenne. Le temps ecoule entre l’enucleation et la recurrenceorbitaire etait de 1–12 mois chez 28 patients (90,4 %). Les rapports hystopathologiques de seulement 8 patients(26 %) ont pu etre retraces. Le suivi avait ete pris en note dans 9,6 % des cas seulement.

Conclusions : Le manque de parametres cliniques et pathologiques dument identifies au cours de la maladie duretinoblasthome infantile entraine une misere humaine due a la pauvrete du suivi et a une negligence grossiere.

Retinoblastoma is the most common pediatric intra-ocular malignant tumour occurring in children

younger than 5 years of age. Although it appears as leuko-coria in 60% of patients, proptosis and fungating mass atinitial presentation are almost equally common in patientsin the underdeveloped world. Delay in diagnosis and treat-ment often results in poor outcome. In the current inter-national scenario, and specifically in developed countries,successful treatment of retinoblastoma is a real hope forthese children and their parents, in contrast to the possibilityof orbital recurrence, which continues to be a nightmare indeveloping countries. The advent of state-of-the-art equip-ment and high-tech machines provides great hope forimproved treatment, but it is not a substitute for the aware-ness and clinical acumen needed to forestall recurrence andmetastasis in postenucleated patients.

Many studies to date have focused on this unacceptableeventuality. Kim et al.1 and Shields et al.,2 in their work on alarge number of retinoblastoma patients, deliberated on thevariables leading to orbital recurrence. Their suggestionshave proved pivotal in preventing orbital recurrence afterprimary enucleation.The aim of our study was to report on the high fre-

quency of orbital recurrence and to try to find a correlationbetween independent variables and orbital recurrence,before and after enucleation, in retinoblastoma patients.

METHODS

Formal permission was obtained from the officer incharge of the Khyber TeachingHospital, Peshawar, Pakistanto review the charts of children with retinoblastoma who

From *the Department of Ophthalmology, KUST Institute of MedicalSciences, Kohat; and {the Department of Ophthalmology, Khyber GirlsMedical College, Peshawar, Pakistan

Originally received Sep. 14, 2009. Final revision Feb. 21, 2010Accepted Apr. 1, 2010Published online Oct. 12, 2010

Correspondence to Muhammad Arif, FCPS, Incharge Head Department ofOphthalmology, Kust Institute ofMedical Sciences, NWFPKohat, Pakistan;[email protected]

This article has been peer-reviewed. Cet article a ete evalue par les pairs.

Can J Ophthalmol 2010;45:606–9

doi:10.3129/i10-059

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had been admitted between August 1, 1978, and July 31,1998. Patients who underwent primary enucleation duringthis period were identified, and the baseline demographicdata of 176 patients were extracted. Data regarding age,clinical features, and surgical procedure were also retrieved.The medical records of patients who had orbital recur-

rence after primary enucleation were studied thoroughly.Data relating to age, laterality, mode of presentation, stageof tumour, schedule of enucleation, and availability ofhistopathological reports were extracted. The dates ofmicroscopic reports, tumour differentiation, and opticnerve invasion were noted. The follow-up visit calendarwas studied in relation to the date of enucleation and thehistopathology findings.The results of relevant investigations, including ultra-

sonography, CT scan, and bone marrow aspiration, wereexamined, where available, in the patient charts. Recordswere studied for clues about intracranial extension, lymph-adenopathy, and skeletal lesions.The treatment protocol, before and after recurrence, was

studied thoroughly. Referral notes for chemotherapy andradiotherapy were examined in the case of patients sent tothe oncology centre for treatment.

RESULTS

Charts of the retinoblastoma patients revealed that a totalof 176 patients were registered and treated during a period of20 years. Ninety-seven patients (55%) were male and 79(45%) were female. The mean age was 3.8 years (range 1–10 years). Seventy-eight patients (44.30%) presented with

leukocoria, 52 (29.5%) had proptosis, and 31 (17.76%) pre-sented with fungating mass. Four cases (2.2%) had sterileendophthalmitis, whereas 4 other patients (2.2%) had hyphe-ma. Five (2.84%) reported with squint and 2 (2.37%) haduveitis. Buphthalmos and raised intraocular pressure weredocumented in only 2 patients, who also had uveitis (Fig. 1).The 136 children undergoing enucleation had a mean

age of 3.9 years. Seventy patients (51%) were male and 66(48.52%) were female. Eighty (58.82%) presented withproptosis and fungating mass on initial presentation and41 (30.14%) presented with leukocoria. Four (2.94%) hadsterile endophthalmitis and 4 (2.94%) had hyphema. Fivepatients (3.7%) presented with squint and 2 (1.47%) caseshad uveitis (Table 1).Thirty-one patients (22.7%), who are the focus of this

study, developed orbital recurrence. The mean age was4.09 years, with a range of 1–10 years. Twenty-four(77.41%) were male and 7 (22.58%) were female. Twenty(64.51%) had unilateral tumours and 11 (35.4%) pre-sented with bilateral disease. Twenty-seven patients(87%) had stage VI tumours, and 4 patients (13%) wereplaced in stage VB (Reese-Ellsworth classification) (Fig. 2).The duration between enucleation and orbital recurrence

was 1 month in 3 cases (9.6%), 3 months in 6 patients(19.95%), 7–9 months in 14 patients (45%), 12 months in5 patients (16%), and 2 years in 3 patients (9.6%) (Table 2).There was associated intracranial extension and preauricularlymph node enlargement in 4 cases. Death was reported inthe case of 2 children who were registered for follow-up.Histopathology reports for only 8 patients (26%) were

available; the rest were missing. Four (13%) were reportedas optic nerve invasion, whereas the other 4 reports did notcomment on the optic nerve. The follow-up was found tobe recorded in only 3 cases (9.6%) and the follow-uprecords of 90.4% of patients were missing after diagnosisof orbital recurrence had been made.

DISCUSSION

Recurrence ofmalignancy is described as the reappearanceof tumour cells or disease when it had apparently been elimi-nated. The potential of even a single cell of retinoblastoma

Fig. 1—Photo with fungating mass in a child with retinoblastoma.

(A) Preoperative. (B) Postoperative.

Table 1—Clinical presentation in 136 retinoblastoma childrenwith primary enucleation

Presentation No. patients %

Proptosis and fungating mass 80 58.00

Leukocoria 41 30.14

Miscellaneous 15 11.02

Table 2—Duration between enucleation and orbital recurrence in31 patients with retinoblastoma

Duration No. cases %

1 mo 3 9.60

3 mos 6 19.95

7–9 mos 14 45.00

12 mos 5 16.00

2 y 3 9.60

Retinoblastoma: postenucleation orbital recurrence—Arif & Islam

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surviving and implanting in a new site means doctors mustbe alert and ready with emergency treatment.A 95% survival rate for retinoblastoma patients and pub-

lished reports of the successful management of children withorbital recurrence mostly occur in the developed world. Thehigh frequency of orbital recurrence and preventable mort-ality in developing countries is disgraceful. This devastation,if studied realistically, does not look to be unpreventable.The first study we found examining the recurrence of

retinoblastoma was done on patients enucleated between1878 and 1929. It was published by Algernon B. Reese,MD, and it gave a projected rate of orbital recurrence of72%. In particular, this report addressed the importance ofhistopathological data and the surgeon’s expertise.3

Although our present retrospective study gives the orbitalrecurrence rate as approximately 23%, the projected out-come looks to be not much different from the Reese3 study,given the misplaced histopathological reports and brokenfollow-up schedules we encountered in our study.A large retrospective study by Kim et al.1 reviewed 1674

retinoblastoma patients who underwent enucleation between1914 and 2006. Seventy-one cases (4.2%) of orbital recur-rence were identified. Ninety-seven percent of these patientswere diagnosed in the first 12 months. Eighty-five percent ofpatients studied before 1984 had metastatic disease and hadbeen followed over amean duration of 34.8months. A reporton a subgroup of patients treated after 1984 revealed a com-mendable survival rate of 91%.1

In our current study, 28 patients with orbital recurrence(90.4%) presented in the first 12 months after primaryenucleation. However, further follow-up was traced inonly 2 patients after diagnosis of recurrence. Extreme

poverty and low literacy rates in the families of these chil-dren hampered follow-up.Our other unpublished study, on 25 retinoblastoma

children and carried out between 2007 and 2009, revealed48% of cases of orbital recurrence, despite close follow-upand timely treatment. Four patients developed metastaticdisease. Spurious drugs and a poor standard of chemother-apeutic drug storage is another challenge.In our study, the advanced mean age of 4.09 years indi-

cates that children with retinoblastoma may be kept wait-ing for treatment by their families because of a lack ofresources. This is further compounded by possible incor-rect diagnosis and delayed treatment.A retrospective study by Shields et al.,2 which reviewed

the charts of 289 children with retinoblastoma treated withprimary enucleation, suggested a correlation betweenmetastasis and optic nerve invasion. This study did notidentify age and laterality as potential factors inmetastasis.2

In our study, proptosis and fungating mass were con-sidered factors that can result in orbital recurrence. Poordocumentation and lack of histology were major concernsin more accurately defining the risk factors.A study by Ronquillo4 that reviewed the records of 84

patients (93 eyes) over a 5-year period revealed a highproportion of unilateral cases. The age range was 7 monthsto 6 years, but the mean age was not mentioned. In thisseries, 13 of 84 patients (14%) developed orbital recur-rence. Surprisingly, only 3 cases with recurrence werereported to have received chemotherapy and radiotherapy.A 100% mortality in this study is no doubt a high figure.4

Honavar et al.,5 gave a guarded justification for intraocularsurgery in retinoblastoma, because of the inherent risks inthe form of orbital recurrence and systemic metastasis.In another study by Shields et al.,6 successful treatment

of retinoblastoma patients who inadvertently underwentvitrectomy (which is normally contraindicated) beforereferral to the oncology service is still more evidence that100% survival, even in mishandled cases, is not beyondreach. Goble et al.,7 also indicates the importance of iden-tifying and preventing the risks for orbital recurrence,which supports the point of view in our current study.Orbital recurrence is a priority issue for not only the

developing world but also the entire medical profession.Lack of awareness regarding close surveillance after prim-ary enucleation, made worse by substandard protocols oftreatment, adversely affects the lives of these children. It isthe joint responsibility of all stakeholders to help stop thisfate from befalling retinoblastoma patients.

The authors have no proprietary or commercial interest in any materialsdiscussed in this article.

REFERENCES

1. Kim JW, Kathpalia V, Dunkel IJ, Wong RK, Riedel E,AbramsonDH.Orbital recurrence of retinoblastoma followingenucleation. Br J Ophthalmol 2009;93:463–7.

Fig. 2—Photo with orbital recurrence in a child with retinoblastoma.

(A) Preoperative. (B) Postoperative.


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2. Shields CL, Shields JA, Baez KA, Cater J, De Potter PV. Opticnerve invasion of retinoblastoma. Metasatic potential and clin-ical risk factors. Cancer 1994;73:692–8.

3. Reese AB. Invasion of the optic nerve by retinoblastoma. ArchOpthal 1948;39:553–7.

4. Ronquillo YC, Retinoblastoma. A Clinico Pathologic Reviewof 93 Enucleated Eyes. Acta Medica Philippina 1994;2:186–9.

5. Honavar SG, ShieldsCL, Shields JA,DemirciH,Naduvilath TJ.Intraocular surgery after treatment of retinoblastoma. ArchOphthalmol 2001;119:1613–21.

6. ShieldsCL,Honavar SG, Shields JA,DemirciH,MeadowsAT.Vitrectomy in eyes with unsuspected retinoblastoma. Ophthal-mology 2000;107:2250–5.

7. Goble RR, McKenize J, Kingston JE, Plowman PN,Hungerford JL. Orbital recurrence of retinoblastoma success-fully treated by combined therapy. Br J Ophthalmol 1990;74:97–8.

Keywords: orbital recurrence, retinoblastoma, enucleation


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Retinoblastoma: postenucleation orbital recurrence