Retinoblastoma - Hyperexcision

Last updated: November 14, 2024

Retinoblastoma is a neuroectodermal malignancy arising from retinal cells. It is one of the small round blue cell tumors of childhood. It is caused by a mutation of the retinoblastoma gene (RB1) located on chromosome 13q14. Children born with germline mutations of RB1 are also at risk of other primary malignancies (e.g. Osteosarcoma). The best initial step in diagnosing retinoblastoma is an immediate ophthalmoscopic examination under general anaesthesia. Biopsy of the tumor is not performed due to the risk of seeding the vitreous.

Type	Pathogenesis	Presentation
Heritable Retinoblastoma	The child is born with one germline mutation of the RB1 gene. The other is acquired after birth resulting in a tumor (Two-hit hypothesis).	Presents earlier and tends to be bilateral.
Non-heritable Retinoblastoma	The child is born with no RB1 mutation and acquires somatic mutations of both RB1 genes after birth	Presents relatively later and tends to be unilateral.

Accounts for about 2.5% of all childhood cancers from birth to 14 years. Affects 1 in 15,000 children. Median age of diagnosis is 15 months of age. 90% of cases are diagnosed before 5 years of age. Overall, 70-80% are unilateral. 20-30% are bilateral. Of heritable retinoblastoma, 90% of inherited mutations develop spontaneously. 10% of inherited mutations come from the parent.

What are the other small round blue cell tumors of childhood?
- Neuroblastoma
- Hepatoblastoma
- Wilm’s tumor
- Rhabdomyosarcoma
- Ewing’s sarcoma
- Retinoblastoma
Signs and symptoms
- Leukocoria (60%; Retinoblastoma unless proven otherwise)
- Strabismus (20%)
- Proptosis
- Ocular asymmetry
- Deterioration in vision
- Eye pain
- Glaucoma
- Orbital cellulitis
- Orbital invasion
- Hyphema (due to destruction of the anterior chamber)
Investigations
- Ophthalmoscopic examination under general anesthesia
  - The tumor appears as a whitish-pink creamy mass
- CT-scan or MRI of the orbit: to determine extra-ocular extension, infiltration, and involvement of the optic nerve
- Bilateral Bone Marrow Biopsy: for prognosis after diagnosis
- CSF cytology: for prognosis after diagnosis
Treatment
- External beam radiation
  - Neoadjuvant chemotherapy can be used to reduce tumor bulk before radiation (using Carboplatin, Vincristine, and Etoposide)
- Chemotherapy for metastatic disease
- Enucleation if radiation and chemotherapy fail or if there is no vision in the affected eye (non-salvageable)
5-years survival
- 90% if confined to the orbit
- 40% if invades the optic nerve (CN II)
- Rare if there are distant metastasis

Leukocoria with tumor visible through the right pupil. Source:New York Eye Cancer Center

Hyphema can be seen if the tumor invades the anterior chamber. Source: Tim Root Virtual Eye Professor

Orbital invasion of the right eye. Source- Treatment of advanced retinoblastoma in Children evacuated from Low-Income Countries

Retinoblastoma left-eye seen on T2-weighted MRI. Source: Radiopaedia

Reference Intervals ›

Biochemistry

ACTH	P: <80 ng/L
ALT	P: 5–35 U/L
Albumin	P: 35–50 g/L
Aldosterone	P: 100–500 pmol/L
Alk. phosphatase	P: 30–130 U/L
α-Amylase	P: 0–180 IU/dL
α-Fetoprotein	S: <10 kU/L
Angiotensin II	P: 5–35 pmol/L
ADH	P: 0.9–4.6 pmol/L
AST	P: 5–35 U/L
Bicarbonate	P: 24–30 mmol/L
Bilirubin	P: 3–17 μmol/L
BNP	P: <50 ng/L
CRP	P: <10 mg/L
Calcitonin	P: <0.1 mcg/L
Calcium (ionized)	P: 1.0–1.25 mmol/L
Calcium (total)	P: 2.12–2.60 mmol/L
Chloride	P: 95–105 mmol/L
Cholesterol	P: <5.0 mmol/L
VLDL	P: 0.128–0.645 mmol/L
LDL	P: <2.0 mmol/L
HDL	P: 0.9–1.93 mmol/L
Cortisol AM	P: 450–700 nmol/L
Cortisol Midnight	P: 80–280 nmol/L
CK ♂	P: 25–195 U/L
CK ♀	P: 25–170 U/L
Creatinine	P: 70–100 μmol/L
Ferritin	P: 12–200 mcg/L
Folate	S: 2.1 mcg/L
FSH	P: 2–8 U/L ♂; >25 menopause
GGT ♂	P: 11–51 U/L
GGT ♀	P: 7–33 U/L
Glucose (fasting)	P: 3.5–5.5 mmol/L
Growth hormone	P: <20 mu/L
HbA1C (DCCT)	B: 4–6%
HbA1C (IFCC)	B: 20–42 mmol/mol
Iron ♂	S: 14–31 μmol/L
Iron ♀	S: 11–30 μmol/L
Lactate (venous)	P: 0.6–2.4 mmol/L
Lactate (arterial)	P: 0.6–1.8 mmol/L
LDH	P: 70–250 U/L
LH	P: 3–16 U/L
Magnesium	P: 0.75–1.05 mmol/L
Osmolality	P: 278–305 mosmol/kg
PTH	P: 0.8–8.5 pmol/L
Potassium	P: 3.5–5.3 mmol/L
Prolactin ♂	P: <450 U/L
Prolactin ♀	P: <600 U/L
PSA	P: 0–4 mcg/mL
Protein (total)	P: 60–80 g/L
Red cell folate	B: 0.36–1.44 μmol/L
Renin (erect)	P: 2.8–4.5 pmol/mL/h
Renin (recumbent)	P: 1.1–2.7 pmol/mL/h
Sodium	P: 135–145 mmol/L
TBG	P: 7–17 mg/L
TSH	P: 0.5–4.2 mU/L
T4	P: 70–140 nmol/L
Free T4	P: 9–22 pmol/L
TIBC	S: 54–75 μmol/L
Triglycerides	P: 0.50–2.3 mmol/L
T3	P: 1.2–3.0 nmol/L
Troponin T	P: <0.1 mcg/L
Urate ♂	P: 210–480 μmol/L
Urate ♀	P: 150–390 μmol/L
Urea	P: 2.5–6.7 mmol/L
Vitamin B12	S: 0.13–0.68 nmol/L
Vitamin D	S: 50 nmol/L

Arterial Blood Gases

pH	7.35–7.45
PaCO₂	4.7–6.0 kPa
PaO₂	>10.6 kPa
Base excess	±2 mmol/L

Urine

Cortisol (free)	<280 nmol/24h
Hydroxyindole acetic acid	16–73 μmol/24h
Hydroxymethylmandelic acid	16–48 μmol/24h
Metanephrines	0.03–0.69 μmol/mmol cr.
Osmolality	350–1000 mosmol/kg
17-Oxogenic steroids ♂	28–30 μmol/24h
17-Oxogenic steroids ♀	21–66 μmol/24h
17-Oxosteroids ♂	17–76 μmol/24h
17-Oxosteroids ♀	14–59 μmol/24h
Phosphate (inorganic)	15–50 mmol/24h
Potassium	14–120 mmol/24h
Protein	<150 mg/24h
Protein/creatinine ratio	<3 mg/mmol
Sodium	100–250 mmol/24h

Haematology

WCC	4.0–11.0 ×10⁹/L
RBC ♂	4.5–6.5 ×10¹²/L
RBC ♀	3.9–5.6 ×10¹²/L
Hb ♂	130–180 g/L
Hb ♀	115–160 g/L
PCV ♂	0.4–0.54 L/L
PCV ♀	0.37–0.47 L/L
MCV	76–96 fL
MCH	27–32 pg
MCHC	300–360 g/L
RDW	11.6–14.6%
Neutrophils	2.0–7.5 ×10⁹/L (40–75%)
Lymphocytes	1.0–4.5 ×10⁹/L (20–45%)
Eosinophils	0.04–0.44 ×10⁹/L (1–6%)
Basophils	0–0.10 ×10⁹/L (0–1%)
Monocytes	0.2–0.8 ×10⁹/L (2–10%)
Platelets	150–400 ×10⁹/L
Reticulocytes	0.8–2.0% / 25–100 ×10⁹/L
Prothrombin time	10–14 s
APTT	35–45 s

Paediatric

Pulse Rate (bpm)
Neonate	140–160
Infant <1yr	120–140
1–5 years	110–130
5–12 years	80–120
>12 years	70–100
Respiratory Rate (tachypnoea)
0–2 months	≥60/min
2–12 months	≥50/min
1–5 years	≥40/min
>5 years	≥30/min
Blood Pressure (mmHg)
Term	65/45
1 year	75/50
4 years	85/60
8 years	95/65
10 years	100/70
Weight Formulas
3–12 months	(a + 9)/2 kg
1–6 years	2a + 8 kg
>6 years	(7a − 5)/2 kg
Haemoglobin (g/dL)
Term newborn	13–20
1 month	11–18
2 months	10–15
1–2 years	10–13
>2 years	11–14
MUAC (6 months–5 years)
Obese	>17.5 cm
Normal	13.5–17.4 cm
At risk	12.5–13.4 cm
Moderate malnutrition	11.5–12.4 cm
Severe malnutrition	<11.5 cm
Developmental Milestones
Social smile	1.5 months
Head control	4 months
Sits unsupported	7 months
Crawls	10 months
Stands unsupported	10–12 months
Walks	12–13 months
Talks	18 months
CSF WBC (/mm³)
Term newborn	0–25
>2 weeks	0–5

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