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Retinoblastoma remains the most common primary intraocular malignancy of infancy and childhood.1
It is a tumour of primitive neuroectodermal tissue mainly from the nuclear layers of the retina.2 Most retinoblastoma are composed of undifferentiated cells with hyperchromatic nuclei and very scanty cytoplasm and a high mitotic rate.
Studies have evaluated histological factors that affect the prognosis of retinoblastoma.3 4 Such parameters include growth pattern, the degree of differentiation, the presence of necrosis, rosettes, extension into the anterior chamber, invasion of the optic nerve and choroids. The most important prognostic finding from such previous studies was the extent of optic nerve involvement.
We reviewed the experience of the University College Hospital, Ibadan, Nigeria, on the histopathological profiles associated with fatal outcome among cases of retinoblastoma seen in the Eye Clinic of the hospital.
A retrospective chart review was conducted of all patients with a histological diagnosis of retinoblastoma from January 1981 to January 2005 at the Eye Clinic of the University College Hospital, Ibadan, Nigeria.
The charts were reviewed for demographic information and histopathology reports, with emphasis on the degree of differentiation, the presence and type of rosette, degenerative changes and the level of optic nerve involvement.
Patients with incomplete charts and histopathology reports and those who were lost to follow-up within 3 year of diagnosis were excluded. Patients who failed to complete their cycles of chemotherapy and radiotherapy but presented later with fatal outcomes were excluded, as well as those with fatal outcomes attributable to such secondary causes as overwhelming sepsis, chest infection and gastroenteritis. This is because there was no postmortem examination on the patients.
Cases included in the review completed the full cycle of radiotherapy of 30–40 Gy in 15 alternate day fractions and also a 3-weekly course of chemotherapy (vincristine 0.05 mg/kg, doxorubicin 0.67 mg/kg, cyclophosphamide 20–40 mg/kg) over a 56-week period. An intrathecal injection of methotrexate (10 mg), ara-C (50 mg) and dexamethasone (4 mg) was included for cases with positive cerebrospinal fluid smears.
The histological pattern of those with fatal outcomes while on treatment or within 3 years of diagnosis was compared with the histological type seen in those who survived for 3 years or more after diagnosis. The histological slides of cases included were reassesed by a senior consultant pathologist (EEUA).
An analysis of the parameters was performed using SPSS version 12 and is presented in table 1. The level of association was taken to be statistically significant at a p value of less than 0.05.
Of the 94 cases of retinoblastoma diagnosed and treated during the period under review, only 19 met the inclusion criteria for the review. The charts for 32 cases could not be retrieved, 37 cases defaulted within 3 years of diagnosis (see fig 1).
The mean age of the cases reviewed was 32.3 months (SD 17.7). There were 11 (57.9%) males and eight (42.1%) females.
Thirteen of the cases were alive at 3 years of follow-up, whereas six had a fatal outcome.
The mean age of the group with fatal outcomes was 29.2 months, whereas for the surviving group it was 33.3 months. The difference in the mean age of the two groups was not statistically significant (p = 0.607 Student’s t-test).
Five (55.5%) of those with a fatal outcome had poorly differentiated tumour, whereas only four (45.5%) among those surviving had a poorly differentiated histological pattern. The difference was close to being statisically significant (p = 0.057, two-tailed Fisher’s exact test; χ2 = 4.55).
None of the cases with fatal outcomes had well differentiated tumours (see table 1).
Histopathology remains the mainstay of confirming the diagnosis of retinoblastoma, although a good clinical evaluation is equally important.
Mortality from retinoblastoma in this review was strongly associated with optic nerve involvement beyond the laminar cribrosa with a poor degree of tumour differentiation and the presence of perivascular tumour cuffing. The first two criteria had been widely reported except for perivascular tumour cuffing. The poor prognosis associated with the presence of perivascular tumour sleeves may be an indication of the high angiogenic nature of these tumours, thus encouraging early tumour seeding, because five out of these six cases had a positive cerebrospinal fluid smear. These same cases also exhibited significant tumour necrosis, which may be an indication of their high mitotic activity thus outgrowing their blood supply rather than a factor of the tumour size. There was no difference in the size of the tumours between the groups with and without perivacular tumour cuffing when measured on the slide. Being a retrospective review, there was limited information on the degree of vascularity of these tumours. Futhermore, the number of cases may be too small to allow conclusions to be drawn. A logistic regression analysis would have been more informative but this is limited by the small size of the study.
Although optic nerve involvement is said to indicate poor prognosis, some studies3 5 have shown that involvement of the optic nerve anterior to the lamina cribrosa corresponding to a grade 2 Khelfaoui classification6 does not significantly increase mortality and this was also demonstrated in this review.
Retrolaminar optic nerve involvement and the presence of perivascular tumour cuffing are strongly associated with the poor survival of patients with retinoblastoma seen in the Eye Clinic of the University College Hospital, Ibadan, Nigeria.
Competing interests: None declared.