Retinoblastoma

Retinal tumors account for 1/3 of all intraocular neoplasms.

Benign tumors (hemangioma, astrocytic hamartoma) are extremely rare. The main group is represented by the only malignant retina of the retina in children - retinoblastoma.

[1], [2], [3], [4], [5]

Causes of retinoblastoma

The doctrine of retinoblastoma has more than four centuries of history (the first description of retinoblastoma was given in 1597 by Petraus Pawius from Amsterdam). For many years, she was referred to a rare tumor - no more than 1 case per 30 000 live births. In recent years there has been an increase in the incidence of retinoblastoma by more than 3 times. According to the European Association of Ophthalmologists, its frequency in the population is 1 per 10 000 - 13 000 live births.

Two forms of the disease are distinguished: hereditary and sporadic. In 10% of patients, retinoblastoma is accompanied by chromosomal pathology (deletion of the chromosome 13ql4.1), in others - structural and functional disorders in the RB1 gene, which in recent years has been isolated and cloned due to the use of molecular markers. The protein product of this gene functions in normal tissues and other tumors, and only with retinoblastoma is it changed. Thus, predisposition to the emergence of retinoblastoma is currently associated with the presence of a terminal mutation in one of the alleles of the RB1 gene, which is inherited in an autosomal dominant type and is found in 60-75% of patients.

[6], [7], [8], [9]

Symptoms of retinoblastoma

The tumor develops in young children (up to 1 year). In 2/3 patients with hereditary form of retinoblastoma, it is bilateral. In addition, in family forms of retinoblastoma, the gene RB1 is damaged in all somatic cells, therefore, in such patients, the risk of tumors of other localizations is high (about 40%). At present, the study of point mutations in the gene of retinoblastoma by chromosome analysis allows not only to confirm or exclude the hereditary form of this tumor in families with weighed heredity by retinoblastoma, but also to explain the development of this form in children with healthy parents. The detection of retinoblastoma in a child under the age of 10 months indicates its inherent nature, retinoblastoma, the symptoms of which appeared after 30 months, can be regarded as sporadic. The sporadic form is about 60% of all retinoblastomas, always unilateral, occurs 12-30 months after birth as a result of de novo mutations in both alleles of the RB1 gene located in the retina cells.

Retinoblastoma develops in any part of the optically active part of the retina, at the beginning of its growth it looks like a violation of the clarity of the reflex on the fundus. Later, a grayish, muddy, flat hearth with fuzzy outlines appears. In the future, the clinical picture changes depending on the characteristics of the growth of retinoblastoma. Isolate endophytic, exophytic and mixed character of tumor growth.

Endophytic growing retinoblastoma occurs in the inner layers of the retina and is characterized by growth in the vitreous. Surface of the tumor is tuberous. The thickness of the node gradually increases, the color remains whitish-yellow, the vessels of the retina and the own vessels of the tumor are not visible. In the vitreous body above the tumor appear conglomerates of tumor cells in the form of stearin drops, stearin pathways. Rapid growth of the tumor, accompanied by a violation in it of metabolic processes, leads to the appearance of necrosis zones with curdled decay, subsequently calcified with the formation of calcifications. When the tumor is localized in the preequatorial zone, its cells, settling in the posterior and anterior chambers of the eye, create a picture of a pseudohypopion whose color, unlike the color of the true hypopion, is whitish-gray. Early turning of the pupillary pigment border occurs. On the surface of the iris - nodules of the tumor, massive synechia, newly formed vessels. The anterior chamber becomes smaller, its moisture becomes turbid. Increasing in size, the tumor fills the entire cavity of the eye, destroys and germinates the trabecular apparatus, resulting in increased intraocular pressure. In young children, a bufalm develops, a thinning of the sclerolimbic zone occurs, which facilitates the spread of the tumor beyond the eye. When the scleral tumor grows behind the equator, a cellulitis pattern develops, the frequency of which rises from 0.2 to 4.6%.

Exotically growing retinoblastoma occurs in the outer layers of the retina and extends under the retina, which leads to its massive detachment, the dome of which is visible behind the transparent lens. In ophthalmoscopy, the tumor is identified as one or more delimited nodes with an even surface. To the tumor fit drainage dilated and convoluted retinal vessels. On the surface of the tumor, gentle crimped, chaotically located newly formed vessels are seen.

Retinoblastoma is characterized by multifocal growth. The nodes of the tumor are localized at different sites of the fundus, have a round or oval shape, their thickness varies. Sometimes hemorrhages on the surface of the tumor merge and completely cover the tumor. In such cases, with the peripheral location of retinoblastoma, the first symptom may be a "spontaneously" arisen hemophthalmos.

Mixed retinoblastoma is characterized by a combination of ophthalmic symptoms characteristic of the two described forms. Well-known signs of retinoblastoma - the "glow" of the pupil and strabismus, heterochromia or iris rubeosis, microphthalmus, bufalm, hyphema, hemophthalmus - should be regarded as indirect, which can be observed in other diseases. In 9.4% of patients, retinoblastoma occurs without indirect signs and is usually detected during preventive examinations.

Retinoblastoma in older children is characterized by decreased visual acuity. In the clinical picture, signs of sluggish uveitis, secondary aching glaucoma, retinal detachment, rarely develop retinal angiomatosis. The appearance of retinoblastoma at this age, when the probability of its development is small, complicates the diagnosis.

Trilateral retinoblastoma is regarded as a bilateral tumor, combined with an ectopic (but not metastatic!) Intracranial tumor of primitive neuroectodermal origin (pinealoblastoma). The third tumor, as a rule, is localized in the pineal gland, but it can also occupy the middle structures of the brain. Clinically, the tumor manifests itself 2-3 years after the detection of bilateral retinoblastoma by signs of intracranial neoplasm. Trilateral retinoblastoma is detected in children in the first 4 years of life. In young children, signs of intracranial lesion can be observed before the appearance of visible signs of eye damage.

Retinocyte is regarded as a rare variant of retinoblastoma with a benign course in connection with the incomplete mutation of the retinoblastoma gene. The prognosis with retinocytoma is more favorable due to the presence of clear signs of differentiation in the form of formation of true rosettes and a tendency to spontaneous regression.

Diagnosis of retinoblastoma

For the diagnosis of retinoblastoma, ophthalmoscopy is used, which should be performed with the maximum dilatation of the pupil, and in young children - during a medical sleep. When examining the fundus in the extreme periphery, it is necessary to apply sclerocompression, which allows us to examine in greater detail these areas that are difficult to access for visual inspection. Conduct ophthalmoscopy follows all meridians (!). In difficult cases with a preequatorial location of the tumor or the presence of pseudohypopion is shown thin needle suction biopsy. Ultrasound scanning allows you to determine the size of retinoblastoma, confirm or exclude the presence of calcifications.

[10], [11], [12], [13], [14], [15]

Treatment of retinoblastoma

Treatment of retinoblastoma is complex, it is aimed at preserving the life of a sick child and his eyes, always individual, it is planned depending on the stage of the process, the general condition of the child, the risk of second malignant tumors and the ultimatum requirement of parents to keep their eyesight. With small tumors, the use of local destruction methods allows to save the eye in 83% of cases, and in combination with polychemotherapy - to achieve a 5-year survival rate of almost 90%. With large tumors, conducting polychemotherapy in combination with enucleation provides a 4-year survival rate of more than 90%. Retinoblastoma is disseminated along the optic nerve along the intercellular space, hematogenically spreads into the bones, brain, lymphogenous way - into the regional lymph nodes.

The prognosis for life with retinoblastoma depends on a number of factors (the location of the tumor anterior to the dentate line, the presence of multiple tumor nodes, the total diameter of which is more than 15 mm, the tumor volume reaching half the volume of the eye cavity and more, the spread of the tumor into the vitreous or orbit, tumor growth in the choroid, the optic nerve). The risk of metastasis rises to 78% when the tumor spreads into orbit. Of course, hereditary burden also applies to risk factors. The standardized mortality rates from retinoblastoma in her hereditary forms in recent years have increased from 2.9 to 9, while in sporadic cases of retinoblastoma, their decrease from 1.9 to 1.0 was noted.

For the purpose of revealing early relapses of a tumor after enucleation of the eyeball or the appearance of a tumor in the pair eye, a control examination of the child is mandatory. With monolateral retinoblastoma, it should be carried out every 3 months for 2 years, with bilateral - for 3 years. In children older than 12 months after the end of treatment, once a year, it is advisable to conduct a computerized tomography of the head, which will allow monitoring the state of soft tissues of orbits and exclude tumor metastasis in the brain. Healed children should be under the follow-up care for life.