Pathologic Quiz Case: A 3-Year-Old Girl With Proptosis and Rapid Visual Loss

A 3-year-old girl presented with a 2-month history of right eye proptosis. The patient's perinatal and medical histories were unremarkable. The visual acuity was preserved in both eyes, extraocular motility was full, and the pupils were equal and reactive. Exophthalmometry measurements demonstrated 2 mm of right-sided proptosis. Dilated funduscopic examination revealed an elevated and edematous right optic nerve head and a normal left optic nerve head. There was no sign of retinal vascular compromise. Magnetic resonance imaging of the orbits and brain with and without gadolinium contrast revealed a 3 × 2 × 2-cm intraconal mass of the right orbit that surrounded the optic nerve (Figure 1, arrow) and extended from the optic disc to the optic canal, without evidence of intracranial extension (Figure 2; arrowhead, optic nerve; arrow, mass). During the next 2 weeks, the patient's visual acuity rapidly declined. Twenty-two days after presentation, the patient underwent total resection of the lesion via a right frontal craniotomy. Intraoperatively, the tumor extended into the medial rectus muscle and was found to compress the third cranial nerve and the optic nerve. Postoperatively, the patient developed a blind eye and a third cranial nerve palsy. No recurrences have been detected to date, 44 months after the surgery.Grossly, the specimen consisted of a firm, pink-to-brown mass that measured approximately 3 × 3 × 2 cm. Microscopic examination demonstrated a tumor that surrounded and compressed the optic nerve (Figure 3). The tumor was formed by rounded aggregates of cells with eosinophilic cytoplasm, round-to-oval uniform nuclei with rare mitotic figures (less than 1 per square millimeter) (Figure 3, inset). Immunohistochemical analysis revealed diffuse epithelial membrane antigen and progesterone receptor reactivity. The Ki-67 labeling index was 3.5% (Figure 4). The Bcl-2 labeling index was 15.6%.What is your diagnosis?Meningiomas comprise 15% to 20% of all intracranial neoplasms in adults. Despite the fact that childhood brain tumors are common, meningiomas are rare lesions that comprise less than 2% of pediatric intracranial tumors. Most intraorbital meningiomas represent invasion from primary intracranial tumors.1 Primary optic nerve meningiomas only account for 1% to 2% of all meningiomas and are the second most common optic nerve tumor after glioma.1 The mean age at presentation for primary optic nerve meningioma is 40.8 years, with a range of 2.5 to 78 years. Only 4% of these cases present before 20 years of age,1 with only 3 published cases in patients younger than 5 years.2–4Our 3-year-old patient presented with proptosis and developed rapid visual loss from a primary optic nerve meningioma. Although histologically the tumor appeared benign, with only rare mitoses observed, it compressed the optic nerve, likely causing the patient's visual loss. This meningothelial meningioma was a grade 1 according to the World Health Organization classification and was clearly distinguishable from atypical and malignant meningioma. Because of the rapid clinical progression of this particular neoplasm, we studied markers of proliferation and apoptosis that could explain its rapid growth. Many studies have identified a significant correlation between the clinical outcome of meningiomas and the Ki-67 labeling index. The reported labeling indexes are 0.7% to 2.2% for benign meningiomas, 2.1% to 9.3% for atypical meningiomas, and 11.0% to 16.3% for anaplastic meningiomas. Other studies cite the threshold for aggressive behavior at 3%, 3.2%, or 4.2%.5 Therefore, according to most studies, our tumor falls in the lower limits for proliferation and clearly does not place the tumor in ranges suggestive of malignancy. Bcl-2 expression has been reported in 43.5% of meningiomas by immunohistochemical analysis. A study of 60 meningiomas that compared the Bcl-2 expression between histologic grades found more than 10% Bcl-2–positive tumor cells in 22% of the benign, 20% of the atypical, and 46% of the malignant meningiomas.6 Roessler et al7 found an inverse correlation of tumor grade with Bcl-2 expression, where low-grade tumors tended to have less than a third of the cells label with Bcl-2. The Bcl-2 labeling index in our case was 15%, which puts this tumor in the lower end of expression of this marker. Progesterone receptors are found in up to 75% of human meningiomas. Meningiomas that express high progesterone levels have a better prognosis and higher survival rate.8 In this regard, our tumor has characteristics that place it again in a benign category. Despite evidence that pediatric optic nerve meningiomas are typically aggressive, their natural history is not known, and some advocate observation in absence of posterior progression.12 Our case confirms the observation that pediatric optic nerve meningiomas can be rapidly progressive, prompting a complete tumor resection. Although rare, meningiomas should be included in the differential diagnosis of childhood optic nerve masses, and their propensity for rapid progression should be kept in mind.