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 tumor of the retina in children - retinoblastoma.

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Causes of Retinoblastoma

The study of retinoblastoma has a history of more than four centuries (the first description of retinoblastoma was given in 1597 by Petraus Pawius from Amsterdam). For many years, it was considered a rare tumor - no more than 1 case per 30,000 live births. In recent years, the incidence of retinoblastoma has increased 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 (deletions of the chromosome region 13ql4.1), in the rest - by structural and functional disorders in the RB1 gene, which in recent years has been isolated and cloned using molecular markers. The protein product of this gene functions in normal tissues and other tumors, and only in retinoblastoma is it altered. Thus, the predisposition to the development 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 manner and is found in 60-75% of patients.

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Symptoms of retinoblastoma

The tumor develops in young children (up to 1 year). In 2/3 of patients with the hereditary form of retinoblastoma, it is bilateral. In addition, in familial forms of retinoblastoma, the RB1 gene is damaged in all somatic cells, so such patients have a high (about 40%) risk of developing tumors in other locations. Currently, the study of point mutations in the retinoblastoma gene by chromosomal analysis allows not only to confirm or exclude the hereditary form of this tumor in families with a burdened heredity for retinoblastoma, but also to explain the development of this form in children with healthy parents. Detection of retinoblastoma in a child under 10 months indicates its congenital nature, retinoblastoma, the symptoms of which appeared after 30 months, can be regarded as sporadic. The sporadic form accounts for about 60% of all retinoblastomas, is always unilateral, and occurs 12-30 months after birth as a result of de novo mutations in both alleles of the RB1 gene located in the retinal 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 in the fundus. Later, a grayish, cloudy flat focus with unclear contours appears. Subsequently, the clinical picture changes depending on the characteristics of the growth of retinoblastoma. Endophytic, exophytic and mixed nature of tumor growth are distinguished.

Endophytic retinoblastoma occurs in the inner layers of the retina and is characterized by growth into the vitreous body. The tumor surface is bumpy. The thickness of the node gradually increases, the color remains whitish-yellow, the retinal vessels and the tumor's own vessels are not visible. In the vitreous body above the tumor, conglomerates of tumor cells appear in the form of stearin drops, stearin tracks. Rapid tumor growth, accompanied by a violation of metabolic processes in it, leads to the appearance of necrosis zones with cheesy decay, subsequently calcifying 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 pseudohypopyon, the color of which, unlike the color of the true hypopyon, is whitish-gray. Eversion of the pupillary pigment border occurs early. On the surface of the iris - tumor nodules, massive synechiae, newly formed vessels. The anterior chamber becomes smaller, its moisture becomes cloudy. Growing in size, the tumor fills the entire eye cavity, destroys and grows into the trabecular apparatus, resulting in increased intraocular pressure. In young children, buphthalmos develops, the sclerolimbal zone becomes thinner, which facilitates the spread of the tumor beyond the eye. When the tumor grows into the sclera behind the equator, a picture of cellulitis occurs, the incidence of which ranges from 0.2 to 4.6%.

Exophytic retinoblastoma arises in the outer layers of the retina and spreads under the retina, which leads to its massive detachment, the dome of which is visible behind the transparent lens. During ophthalmoscopy, the tumor is detected as one or more delimited nodes with a smooth surface. Draining dilated and tortuous retinal vessels approach the tumor. Delicate tortuous, chaotically located newly formed vessels are visible on the surface of the tumor.

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

Mixed retinoblastoma is characterized by a combination of ophthalmologic symptoms common to the two forms described. Well-known signs of retinoblastoma - pupil "glow" and strabismus, heterochromia or rubeosis of the iris, microphthalmos, buphthalmos, hyphema, hemophthalmos - should be regarded as indirect, which can also 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. The clinical picture is dominated by signs of sluggish uveitis, secondary painful glaucoma, retinal detachment, and retinal angiomatosis rarely develops. The occurrence of retinoblastoma at this age, when the probability of its development is low, complicates diagnosis.

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

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

Diagnosis of retinoblastoma

To diagnose retinoblastoma, ophthalmoscopy is used, which should be performed with maximum pupil dilation, and in small children - during drug-induced sleep. When examining the fundus at the extreme periphery, sclerocompression should be used, which allows for a more detailed examination of these areas that are difficult to visually control. Ophthalmoscopy should be performed along all meridians (!). In difficult cases, with a preequatorial location of the tumor or the presence of pseudohypopyon, fine-needle aspiration biopsy is indicated. Ultrasound scanning allows for determining the size of the retinoblastoma, confirming or excluding the presence of calcifications.

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Treatment of retinoblastoma

Treatment of retinoblastoma is complex, aimed at preserving the life of the sick child and his eye, always individual, it is planned depending on the stage of the process, the general condition of the child, the risk of occurrence of second malignant tumors and the ultimate requirement of parents to preserve vision. In case of small tumors, the use of methods of local destruction allows to preserve the eye in 83% of cases, and in combination with polychemotherapy - to achieve a 5-year survival rate of almost 90%. In case of large tumors, polychemotherapy in combination with enucleation provides a 4-year survival rate of more than 90%. Retinoblastoma disseminates along the optic nerve through the interthecal space, spreads hematogenously to the bones, brain, and lymphogenously to the regional lymph nodes.

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

In order to detect early recurrences of the tumor after enucleation of the eyeball or the occurrence of a tumor in the fellow eye, a control examination of the child is mandatory. In case of unilateral retinoblastoma, it should be carried out every 3 months for 2 years, in case of bilateral retinoblastoma - for 3 years. In children over 12 months after the end of treatment, it is advisable to conduct a CT scan of the head once a year, which will allow monitoring the condition of the soft tissues of the orbits and exclude tumor metastasis to the brain. Cured children should be under dispensary observation for life.