Adiktyoma, the embryonal type of medulloepithelioma, arising from the primitive medulloepitheIium at the anterior lips of the bilayered optic cup, is a relatively rare tumor, usually seen in young children. In 1904, Verhoeff1 suggested the name "teratoneuroma" for this lesion, because he found structures of nerve origin in it. In 1908, Fuchs,2 observing that the cells were arranged in interlacing rows or cords, creating the appearance of a lacework or network, coined the term "diktyoma" (from the Greek "diktyon," meaning "net"). In 1971, Zimmerman3 proposed distinguishing congenital from acquired neuroepithelial tumors of the ciliary body. The tumor that was formerly called a "diktyoma" is now referred to as a "medulloepithelioma." This tumor has been extensively studied by Andersen,4 Apt and associates,5 and Broughton and Zimmerman,6 among others.
The association between pineoblastomas and bilateral retinoblastomas has been well established.7 However, we report, to our knowledge for the first time, a pineoblastoma in association with a medulloepithelioma of the ciliary body.
FIGURE 1: Leukocoria of the right eye with inferonasal lenticular opacification.
In January 1986, the parents of an apparently healthy 2-year-old girl noted a leukocoria in her right eye. The child's gestation and delivery as well as growth and development to that point had been normal. There was no family history of ocular disease.
The child was able to fix and follow with each eye. No phoria or tropia was noted. Pupils were equal and reactive with normal accommodation. Extraocular movements showed a normal range of smooth pursuit and saccadic movements in all directions. Slit-lamp examination revealed leukocoria of the right eye, with a lenticular opacification involving the inferonasal half of the lens (Fig 1). Fine vessels coursing along the posterior aspect of the lens surface also were noted.
Ophthalmoscopic examination revealed a dragged retina with normal-appearing vasculature. Ultrasound examination of the right eye revealed no obvious ciliary body mass and a normal posterior segment. These findings were considered consistent with a diagnosis of persistent hyperplastic primary vitreous (PHPV) with a secondary cataract of the right eye.
The patient's left eye was patched, and she did well until May, when she began to suffer from headaches, tremulousness, weakness, and vomiting. She became more irritable, emotionally labile, and experienced a loss of appetite and a consequent weight loss of 5 pounds over a 2-week period. Ophthalmologic examination revealed bilaterally-reactive pupils and leukocoria of the right eye. The right fundus was not visualized; however, the left eye had florid papilledema. Nystagmus was noted, as was a slight right-sided facial palsy.
Computed tomography of the head revealed an enhancing mass in the pineal region, with massive hydrocephalus and periventricular edema (Fig 2). A cerebral angiogram demonstrated changes related to a mass effect in the pineal-third ventricle region, with faint tumor staining. Subsequently, the patient underwent craniotomy with removal of a pineal tumor.
FIGURE 2: Computed tomography showing contrast enhancement of a pineal region mass with hydrocephalus and periventricular edema.
Histologic examination of the tumor disclosed a small-cell neoplasm consistent with a pineoblastoma (Fig 3). Postoperatively, the child did well. Because of the possibility of meningeal seeding from the tumor, the child was treated over a 7-day period with 3600 cGy of radiation in a circular field of the pineal area.
Over the next 7 months, glaucoma secondary to synechial seclusion of the pupil, together with progressive cataractous changes, developed in the right eye. Also noted were a right exotropia of 10° and nystagmus. Fixation was poor with the right eye. Nasal retinal traction, but no apparent mass, was noted.
In October, the child underwent cataract extraction, anterior vitrectomy, and peripheral iridectomy in the right eye. Her eye was fitted with a contact lens, and she was able to fix and follow. Postoperative intraocular pressures were normal.
Subsequent ophthalmoscopic examination showed a retinal detachment nasally in addition to extensive fibrotic changes throughout the mid-vitreous cavity. Superonasally, the retina was drawn up into the vitreous in a tight knot-like mass. Additional surgery was not recommended, because the chances of improving her vision were considered small and because surgery could precipitate more fibrosis and a larger retinal detachment.
FIGURE 3: Photomicrograph of the pineal region tumor showing a poorly differentiated pineoblastoma with foci of dystrophic calcification (arrow) (hematoxylin-eosin, original magnification x 200).
In July 1987, a spontaneous hyphema was noted in the right eye. Visual acuity was light perception, tension by applanation tonometry was 12 mm Hg, and there were a few dilated iris vessels. The fundus was poorly visualized. Ultrasound revealed dense vitreous membrane formation with a funnel-shaped retinal detachment coming off the optic nerve. A number of vitreous membranes were noted; one large group was located anteriorly and inferiorly. There was no obvious evidence of an intraocular tumor or calcification.
One month later, the child was admitted for a pars plana vitrectomy and scleral buckling procedure. However, the surgery was complicated by extensive bleeding into the vitreous, as well as an extensive retinal detachment, with retinal tissue being drawn into the retroiridal plane as the vitreous was being removed. The retina could not be reattached.
Two weeks after surgery, the child's right eyelid was swollen and she seemed very uncomfortable. Corrected visual acuity of the right eye was questionable hand movement. Slit-lamp examination showed a total hyphema with significant blood staining of the cornea. The fundus could not be visualized.
On August 17, cranial magnetic resonance imaging showed a small right eye with increased signal in the anterior chamber, deficient lens signal, and increased signal in the vitreous (Fig 4). No ciliary body mass was noted. The apparent microphthalmia and vitreous abnormalities were considered consistent with the diagnosis of PHPV. An incipient phthisis of the right eye had developed and the eye was eviscerated.
The child tolerated the evisceration well; there were no intraoperative or postoperative complications. She was fit with an ocular prosthesis, which has been well tolerated. On follow-up examination, the patient has shown no sign of either orbital or intracranial recurrence of tumor. Recent contact with the child's primary physician revealed that she is doing well almost 4V2 years following the evisceration.
FIGURE 4: Magnetic resonance image of the right orbit showing increased signal in the anterior chamber and vitreous cavity, and decreased lens signal. There is a funnel-shaped retinal detachment present. No obvious ciliary body mass is noted.
Grossly, examination of the evisceration contents revealed a congealed black mass, with a 8 x 7millimeter opaque cornea along one surface and a 10 x 8 x 3-millimeter contracted mass of grayish tissue along the opposite surface. Transverse sections perpendicular to the long axis revealed the center of the mass to be composed of firm gray- white tissue, with a few areas of hemorrhage.
Microscopically, a dense fibrous cyclitic membrane was seen posterior to the iris and extending onto the surface of the ciliary body. Directly attached to this membrane was a large area of disrupted, gliotic retinal tissue showing multiple folds. The vitreous cavity was completely obliterated. The choroidal tissue had disrupted retinal pigment epithelium on the surface. A densely cellular mass of tissue arose from the ciliary body, with epithelium arranged in anastomosing cords and rarely forming rosettes (Figs 5-6). The cells, which were small, with inconspicuous cytoplasm and regular, smooth-contoured nuclei with coarse chromatin, were separated by hyaline eosinophilic bands containing numerous aggregates of melanin pigment. Islands of hyaline cartilage were seen within several portions of the mass, as were round plump rhabdomyoblasts (Figs 6-7). Based on the histopathologic features of the mass, a teratoid medulloepithelioma of the ciliary body was diagnosed.
FIGURE 5: Photomicrograph of the ciliary body tumor showing cords of epithelial cells (E) and rare rosettes (R) (hematoxylineosin, original magnification x 120).
FIGURE 6: Photomicrograph of the medulloepithelioma showing rosettes (R), hyaline cartilage (H), and rhabdomyoblasts (M) (hematoxylin-eosin, original magnification x 320).
Medulloepithelioma of the ciliary body is a rarely occurring tumor, seen most often in young children. The average age at the time of diagnosis ranges from 3 years 8 months to about 5 years (general range, 2 to 9 years).5'6,8 The tumor is unilateral and usually slow growing.9 Broughton and Zimmerman6 found the most common presenting signs and symptoms to be pain and poor vision, mass in the iris or ciliary body, and leukocoria.
FIGURE 7: Photomicrograph of the ciliary body tumor showing hyaline cartilage (H) and rhabdomyoblasts (M) (Masson's trichrome stain, original magnification x 320).
The differential diagnosis in a patient suspected of having a ciliary body medulloepithelioma should include: retinoblastoma (especially in the late stages), PHPV, peripheral uveitis (pars planitis), Toxocara canis infestation, nevi, and malignant melanoma.4-5 Generally, enucleation is required to make the definitive diagnosis. However, Jakobiec and colleagues 10 reported a case in which a cyst obtained from the anterior chamber was examined by electron microscopy, and the diagnosis of medulloepithelioma of the ciliary body was made without enucleation. Orellana and coauthors11 correctly diagnosed a medulloepithelioma using ultrasonography and cytologic examination of vitreous aspirate.
The clinical findings in PHPV have been well described by Haddad et al.12 Although distinct from medulloepithelioma, PHPV shares some common clinical features. Like medulloepithelioma, PHPV is often associated with leukocoria, microphthalmia, and cataract formation. On rare occasions, a medulloepithelioma may appear clinically similar to PHPV, as in the case reported here.
Medulloepitheliomas have several characteristic histopathologic findings that make diagnosis straightforward.13,14 The tumor consists of two cellular components - neuroepithelial tubules and a fibrillar mucoid matrix. Rows of poorly differentiated epithelial cells are arranged in convoluted patterns of elongated interlacing cords similar in appearance to embryonic retina. Sometimes the cells are arranged in a circular pattern around a lumen, forming a rosette-like structure. Typically, medulloepitheliomas show a loose stroma composed of delicate fibrils with abundant ground substance rich in hyaluronic acid that resembles the primitive vitreous.
Teratoid medulloepitheliomas, in addition to epithelial and stromal components, contain one or more heteroplastic elements. Hyaline cartilage is the most common such tissue seen.14 Andersen4 found cartilage in 20% of his cases. Other heteroplastic elements occasionally seen are brain tissue (mostly glial), ganglion cells, ependyma, choroid plexus, and other neuronal elements.6 In rare cases, rhabdomyoblastic elements may predominate. Zimmerman and associates15 described four cases of medulloepitheliomas that were found to contain rhabdomyosarcomatous elements as well as islands of hyaline cartilage. Finally, some medulloepitheliomas are more aggressive and have been classified as cytologically malignant.
Most medulloepitheliomas are relatively benign or only locally invasive, and thus generally have a good prognosis. The most important prognostic feature is extraocular extension.6 Radiation therapy has little or no beneficial effect for control of orbital recurrence4; therefore, treatment of medulloepitheliomas should be directed at early clinical recognition and surgical intervention.6 Patients are best treated by early enucleation after the tumor is diagnosed, and by orbital exenteration if there is orbital spread. In recent years, some authorities have advocated local resection of small, well-circumscribed tumors by iridocyclectomy or block excision.6
In retrospect, enucleation rather than evisceration should have been undertaken in this child with a medulloepithelioma. In spite of multiple preoperative diagnostic procedures, the medulloepithelioma was not suspected; rather, the diagnosis was PHPV. Evisceration in a patient with a medulloepithelioma increases the risk of persistent retained or intraorbital tumor. Fortunately, the child has shown no signs of recurrence 4V2 years following the surgery.
Primary tumors of the pineal gland are rare, constituting less than 2% of primary brain tumors.16 More than half of all pineal tumors are found in patients under 20 years old.17 Pineoblastomas and pineocytomas are true parenchymal tumors,18 and, while rare, are the most common pineal tumors encountered in children and young adults.
In 1980, Bader and colleagues19 noted an association of pineal tumors occurring simultaneously in some patients with bilateral retinoblastomas.7 Whittle and coauthors reported a case of concurrent unilateral retinoblastoma and a pineoblastoma in 1985.7
Histopathologic examination of pinealomas and pineoblastomas have revealed structural and antigenic similarities to the human retina. Isolated cells in normal pineal parenchyma have been shown to retain some of the cytochemical characteristics of retinal photoreceptor cells.7,20,21 Embryologically, the pineal gland, retinal photoreceptor cells, and the ciliary body (from which most medulloepitheliomas arise) originate from neuroectodermal structures.21
The medulloepithelioma reported here is unique in that to our knowledge no previous case of concurrent medulloepithelioma and pineoblastoma has been reported. It is interesting that the clinical and ultrasonic features suggested PHPV. A ciliary body lesion was not suspected prior to histopathologic examination of the evisceration specimen. Given the rarity of pineal gland lesions, as well as medulloepitheliomas, we cannot rule out the possibility that the association of these two lesions in this child was merely a chance occurrence. However, given the common embryologie origin of the pineal gland and much of the ciliary body from neuroectoderm, there seems to be some basis for arguing that these two lesions were in fact related.
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