Ocular Oncology Basics: Salient Points from The Pandora's Box 

Bikramjit P Pal

 

RETINOBLASTOMA


Grouping:  Clinical determination of extent of disease with the focus being the eye. It is a pre operative evaluation with the main outcome being the salvagable status of vision or the eye.
Staging: It combines clinical, various imaging and  post-operative histopathological results to determine the extent of the disease. The main outcome is focussed on survival of the patient.

International classification of Retinoblastoma( grouping) [1]

Group A: Tumours smaller than 3mm or less

Group B: Tumours bigger than those in group A

Group C: Localized tumour dissemination

Group D: Diffuse tumour dissemination

Group E: Extensive disease

Nugget:

Mnemonic for Grouping of retinoblastoma
A: SmAll tumours
B: Bigger tumours
C: Confined tumours
D: Diffuse
E: Extensive

Nugget: 

Pseudoretinoblastomas : lesions simulating retinoblastoma [2]
Coats disease: most common pseudoretinoblastoma
Persistent fetal vasculature
Vitreous hemorrhage
Toxocariasis
Familial exudative vitreo retinopathy
Retinal detachment
Coloboma
Hamartoma of retina and RPE
Endogenous endophthalmitis
Cataract

Regression patterns in retinoblastoma [3,4]
Type 0: Regression without remnant
Type 1: Regression with mainly calcified remnant
Type 2: Regression with no calcified component
Type 3: Partially calcified mass
Type 4: Flat atrophic scar

Types of vitreous seeds  [5]
1) Dust : representing cellular infiltration
2) Cloud: representing tumour translocation
3) Spheres: representing clonal expansion of dust or cloud.

Regression patterns of vitreous seeds  [5]
Grade 0: Regression without any trace
Grade 1: Regression with calcified or refringent residues
Grade 2: Regression with amorphous remnant with or without pigmentary changes
Grade 3: Combination of 1 and 2

Grading of melphalan related retinal toxicity [5]
Grade 1: salt and pepper retinopathy < 2 clock hours anterior to equator
Grade 2: salt and pepper retinopathy > 2 clock hours anterior to equator
Grade 3: salt and pepper retinopathy posterior to equator not involving the macula
Grade 4: : salt and pepper retinopathy involving the macula
Grade 5: Optic atrophy

Nugget: Mnemonic for factors predictive of iris naevus developing melanoma [6]
( ABCDEF guide)
A: Age < 40
B: Blood ( presence of hyphaema)
C: Clock hours ( inferior location)
D: Diffuse ( diffuse flat configuration)
E: Ectropion uvae
F: Feathery ( lesion having feathery geographic margins)

Mnemonic for features predictive of transformation of a small choroidal naevus to melanoma [7]
To Find Small Ocular Melanoma-Using Helpful Hints Daily ( TFSOM-UHHD criteria)
T: Tumour margins < 2mm
F: subretinal Fluid ( presence of subretinal fluid)
S: Symptoms
O: Presence of Orange pigments
M: Margins close to optic nerve head
UH: Ultrasound Hollowness
H: absence of Halo
D: absence of Drusens

Classification of ciliary body and choroidal melanoma [8,9]
Classification is based on TNM classification ( currently 7th )
T : Tumour size based on thickness and largest basal diameter, graded from T1 to T4
N: lymph node involvement
M: presence or absence of metastasis
Once size of tumour is established along with its extent, imaging modalities and laboratory investigations are performed to rule out metastasis. Tumour is then staged which provides a survival estimate which helps in prognosticating a case.
Category of ' T ' and then the approximate staging is inferred from charts provided from current TNM staging charts which is shown below.

Collaborative Ocular Melanoma Study ( COMS) [10]


COMS study was a path breaking study, the results which dispensed some established ideas and provided the path for future.
Although the name has ocular mentioned, the study looked into melanomas of only choroidal in nature. Major exclusion criteria's were:( readers are requested to go through complete list of exclusion criteria from the referring source)

COMS divided choroidal melanomas into three categories based on largest basal diameter( LBD) and thickness.

The study protocol can be understood by the following chart:

Important : Results

Small Melanomas observational study

Enucleation versus plaque radiotherapy in medium sized melanomas

Pre-enucleation radiation versus enucleation alone in large melanomas
There was no statistical difference between survival rates when enucleation alone was compared to pre enucleation radiotherapy

Reference

1)  Grossniklaus HE. Retinoblastoma. Fifty years of progress. The LXXI Edward Jackson  Memorial Lecture. Am J Ophthalmol. 2014 Nov;158(5):875-9
2) Shields CL,  Schoenberg E,  Kocher K,  Shukla SY, Kaliki S , Shields JA .Lesions simulating  retinoblastoma (pseudoretinoblastoma) in 604 cases: results based on age at presentation. Ophthalmology. 2013 Feb;120(2):311-6
3) Shields CL, Palamar M, Sharma P et. al. Retinoblastoma regression patterns following chemoreduction and adjuvant therapy in 557 tumors. Arch Ophthalmol. 2009 Mar;127(3):282-90
4) Dunphy EB. The story of retinoblastoma. The XX Edward Jackson Memorial Lecture. Am J Ophthalmol. 1964 Oct;58:539-52
5) Munier FL. Classification and management of seeds in retinoblastoma. Ellsworth Lecture Ghent August 24th 2013. Ophthalmic Genet. 2014 Dec;35(4):193-207
6) Shields CL, Kaliki S, Hutchinson A et. al. Iris nevus growth into melanoma: analysis of 1611 consecutive eyes: the ABCDEF guide. Ophthalmology. 2013 Apr;120(4):766-72
7) Shields CL, Kels JG, Shields JA. Melanoma of the eye: revealing hidden secrets, one at a time. Clin Dermatol. 2015 Mar-Apr;33(2):183-96
8) Kivelä T, Kujala E. Prognostication in eye cancer: the latest tumor, node, metastasis classification and beyond. Eye (Lond). 2013 Feb;27(2):243-52
9) Finger PT. Do you speak ocular tumor? Ophthalmology. 2003 Jan;110(1):13-4
10) Singh AD, Kivelä T. The collaborative ocular melanoma study. Ophthalmol Clin North Am. 2005 Mar;18(1):129-42