Retinoblastoma视网膜母细胞瘤

Key facts

Definition of retinoblastoma (RB): Malignant primary neoplasm of the retina.

Classic imaging appearance: CT shows an intraocular enhancing retinal mass with calcification often with retinal detachment.

Most common intraocular tumor of childhood.

Presents with leukocoria.

Unilateral much more than bilateral (autosomal dominant).

Rarely trilateral or tetralateral (co-existing pineal and/or suprasellar primitive neuroectodermal tumor).

Imaging findings

General Features：Best imaging clue is calcified intraocular mass.

CT Findings：Characteristic puncate or finely speckled calcification (＜90%).

Moderate or markedly intense contrast enhancement is typical.

MR Findings: (1)T1WI: Variable intensity.(2)T2WI: Hypointense.(3)Enhaced T1WI: Moderate to marked enhancement.(4)Extraocular extension best seen.(5)Intra/extraocular (and intracranial) invasion occurs along optic nerve and significantly affects treatment planning and prognosis.(6)Retinal detachment occurs.

Imaging recommendations

In patients with family history of heritable retinoblastoma (RB), screening eye exam at birth and every 2～4 months in first years of life.In larger RB as seen by ophthalmic ultrasound.CT is used for verification of diagnostic calcification.MR shows extraocular spread and intracranial lesions.

Differential diagnosis: lesions causing leukocoria

Persistent hyperplastic primary vitreous: Small globe with increased vitreous density without calcification； tissue band may extend from lens to posterior retina.

Coats' disease: Density in all or part of vitreous in normal-sized globe, no calcification.

Pathology

General pathologic comments: Lymph drainage pathways of orbit allow mandibular metastases.

医学词汇注释与简要讲解

【suffix】-blastoma 母细胞瘤

osteoblastoma 骨母细胞瘤

glioblastoma 胶质母细胞瘤

retinal detachment 视网膜剥离

leukocoria= white pupil 白瞳症

trilateral RB：三侧性视网膜母细胞瘤，是一种特殊表现,表现为双侧眼球肿物同时伴发松果体肿瘤和/或鞍上的胚胎性肿瘤 （注：PNET已于 2016年WHO 中枢神经系统肿瘤分类中去除， 相应肿瘤归入胚胎性肿瘤)

suprasellar 鞍上的

intra/extraocular 眼球内外的

intracranial （眼）肌椎内的

persistent hyperplastic primary vitreous 原始永存玻璃体增殖症

Coats' disease (外层)渗出性视网膜病变

mandibular 下颌(骨)的

chromosome 染色体

【prefix】chromo- 色，有颜色的

chromophobe 嫌色细胞

chromogenesis 色素形成

autosomal dominant 常染色体显性遗传

neuroectodermal 神经外胚层的

endophytic form 内生型

exophytic form 外生型

diffuse form 弥漫型

rosettes 假菊团细胞

glaucoma 青光眼

anisocoria 瞳孔不等大

heterochromia 辨色异常

proptosis 突眼

cataract 白内障

nystagmus 眼球震颤

enucleation 眼球摘除术

photocoagulation 激光凝固法

Genetics

RB-1 gene: Chromosome 13 (q14 band) mutation.In all patients with bilateral disease and 15% with unilateral disease.Autosomal dominant,near complete penetrance.Produces RB in more than 80 % with gene and in 40% of offspring.

RB-1 gene: Carries information for making pRB protein.pRB protein regulates cell division, hence risk of other cancers.26% have second cancer within 30 years (average 10～13 years): Esp.osteogenic sarcoma (but others also reported).

A subset of patients with chromosome 13 (q14 band) mutations have chromosome 13q14.Deletion syndrome: Mental retardation, atypical face and RB.Slight increased risk in Down syndrome.

Embryology-anatomy

Malignant neoplasm that arises from retinal neuroectodermal cells.

Etiology-pathogenesis: RB when mutation occurs in both copies of RB-1 gene on chromosome 13.Either each copy spontaneous mutation OR."2-hit" process: First hit, defective copy (dominant allele) inherited from parent.Second hit, mutation in "good" copy develop to RB.

Epidemiology: Incidence of 1∶15 000 births (has increased in past 60 years).

Gross pathologic surgical features

White to pink retinal mass.Three growth patterns have been described.(1)Endophytic form: Protrudes into the vitreous.(2)Exophytic form: Grows subretinal causing retinal detachment.(3)Diffuse form: Grows along the retina in a plaque-like fashion, simulating other inflammatory or non-neoplastic conditions.

Microscopic Features: (1)Differentiated tumor shows Flexner-Wintersteiner rosettes.(2)Small round cells with scant cytoplasm and large nuclei.(3)Pineal and/or suprasellar "RB": Primitive neuroectodermal tumor (PNET).

Clinical presentation

Primary physical sign is leukocoria (loss of normal retinal red reflex).

Less common symptom is strabismus secondary to glaucoma.

Inflammation is about 10%.

Rare: Anisocoria, heterochromia, tears, proptosis, cataract, nystagmus.

Natural history

Congenital neoplasm that is present but not usually apparent at birth.

Average age of diagnosis, unilateral: 24 months.

Average age of diagnosis, bilateral: 13 months (earlier if positive family history and undergoing routine screening).

Intracranial tumor usually diagnosed late (after therapy ocular lesion).

Treatment

Enucleation if RB fills more than half ocular volume, with/without seeding or retinal detachment

External beam x-ray technique: Higher incidence second tumors (esp.if RB-1 Pos).

Plaque radiotherapy: Selected small solitary tumors.

Chemotherapy for "chemoreduction" allows more conservative therapies such as cryotherapy and photocoagulation.

Prognosis

Untreated tumor is fatal.

Unilateral tumor without invasion has excellent prognosis.

Trilateral/tetralateral RB or CSF spread: Dismal (＜24 months survival).