Microscopically, both undifferentiated and differentiated elements may be present. Undifferentiated elements appear as collections of small, round cells with hyperchromatic nuclei; differentiated elements include Flexner-Wintersteiner rosettes, Homer Wright rosettes,  and fleurettes from photoreceptor differentiation. Genetic testing
Identifying the RB1 gene mutation that led to a childs retinoblastoma can be important in the clinical care of  the affected individual and in the care of (future) siblings and offspring. It may run in the family. Bilaterally affected individuals  and 13-15% of unilaterally affected individuals, are expected to show an RB1 mutation in blood. By identifying the RB1 mutation in the affected individual, (future) siblings, children, and other relatives can be tested for the mutation; if they do not carry the mutation, child relatives are not at risk of retinoblastoma, so need not undergo the trauma and expense of examinations under anaesthetic. For the 85% of unilaterally affected  patients found not to carry either of their eye tumor RB1 mutations  in blood, neither molecular  testing nor clinical surveillance of siblings is required. If  the  RB1 mutation of an affected individual is identified, amniotic cells in an at-risk pregnancy can be tested for the family  mutation;  any fetus that carries the mutation can be delivered early, allowing early treatment of any eye tumors, leading to better visual outcomes. For cases of unilateral retinoblastoma where no eye tumor  is available for testing, if no RB1 mutation is detected in blood after high-sensitivity molecular testing (i.e.
Imipramine, sold under the brand name Tofranil, among others, is a tricyclic antidepressant (TCA) mainly used in the treatment of depression. It is also effective in treating anxiety and panic disorder. The drug is also used to treat bedwetting. Imipramine is taken by mouth. Common side effects of imipramine include dry mouth, drowsiness, dizziness, low blood pressure, rapid heart rate, urinary retention, and electrocardiogram changes. Overdose of the medication can result in death. Imipramine appears to work by increasing levels of serotonin and norepinephrine and by blocking certain serotonin, adrenergic, histamine, and cholinergic receptors. Imipramine was discovered in 1951 and was introduced for medical use in 1957. It was the first TCA to be marketed. Imipramine and the other TCAs have decreased in use in recent decades, due to the introduction of the selective serotonin reuptake inhibitors (SSRIs), which have fewer side effects and are far safer in overdose. Medical uses
Imipramine is used in the treatment of depression and certain anxiety disorders. It is similar in efficacy to the antidepressant drug moclobemide. It has also been used to treat nocturnal enuresis because of its ability to shorten the time of delta wave stage sleep, where wetting occurs. In veterinary medicine, imipramine is used with xylazine to induce pharmacologic ejaculation in stallions. Blood levels between 150 and 250 ng/mL of imipramine plus its metabolite desipramine generally correspond to antidepressant efficacy. Available forms
Imipramine is available in the form of oral tablets and capsules. Contraindications
Combining it with alcohol consumption causes excessive drowsiness. It may be unsafe during pregnancy.