Neuroblastoma is a malignant tumor of the primitive neuroblasts. It is the second most common orbital tumor in children, after rhabdomyosarcoma accounting for 10–15% of childhood tumors. Primary orbital neuroblastoma has been rarely reported in adults. Frequent sites of primary neuroblastoma are abdominal, thoracic, cervical, and pelvic locations. In more than 50% of cases, ophthalmic involvement occurs in due course. Ocular manifestations include orbital mass causing proptosis, ecchymosis, Horner's syndrome, papilledema, nystagmus, extraocular muscle palsy, ptosis, retinal striae. Primary orbital neuroblastoma constitutes 8% of cases. It is, especially refractory to treatment unlike those arising from sympathetic chain and adrenal gland. This is the first report on primary orbital neuroblastoma with intraocular extension.
A 2-year-old female child presented with rapid onset massive proptosis of the left eye with difficulty to close and move the eye. On examination, she had proptosis of 31 mm (exophthalmometry of right eye – 11 mm) with lid edema and ciliary congestion [Fig. 1]. Congested vessels were noted on the upper lid. There was a total restriction of extraocular movements. There was a 1 cm × 1 cm firm scleral nodule 3 mm temporal to limbus with bluish discoloration and hemorrhage in it [Fig. 2]. The anterior chamber had exudate and hyphema precluding visualization of the posterior segment. The corneal diameters of the right and left eye were 11 and 12 mm, respectively. The measured intraocular pressure was 17.3 mmHg in the right eye and unrecordably high in the left eye (Schiotz tonometry). On general examination, the child had good nourishment and was febrile. There was no palpable abdominal mass. The chest was clear, and the cardiovascular system was normal.
Computed tomography of orbit and brain revealed 4 cm × 3 cm × 2.5 cm heterogenous mass with intra- and extra-ocular component filling the left orbit [Fig. 3]. There were areas of coarse calcification. The optic nerve was encased within the mass with perineural spread up to optic chiasma. The floor of the orbit was thinned. Based on the tomography, finding retinoblastoma was suspected.
Histopathological examination of incisional biopsy of orbital mass showed small round tumor cells in sheets separated by incomplete fibrous septa under low power. Examination at higher magnification revealed round to polygonal cells with high nucleocytoplasmic ratio, palisading of nuclei, and delicate cytoplasmic processes. Gemistocytoid tumor cells were observed with eosinophilic cytoplasm. Few foci with central fibrillary material with tumor cells around giving vague appearance of rosettes (Homer Wright) were seen [Fig. 4]. Immunohistochemistry was positive for neuron specific enolase and chromogranin suggestive of neuroblastoma [Fig. 5].
Systemic evaluation for primary site was done. Ultrasound abdomen and chest X-ray were normal with no mass lesion. There was no evidence of mass lesion elsewhere by the whole body computed tomography. The child had hemoglobin of 12 g, total leukocyte count of 5400, and platelet count of 141,000. Peripheral smear showed lymphocytic preponderance with no abnormal cells. Bone marrow biopsy showed no abnormal cells. Cerebrospinal fluid examination by lumbar puncture showed no abnormal cells.
Hence, a diagnosis of primary orbital neuroblastoma with intraocular involvement was made. She was treated with three cycles of chemotherapy comprising vincristine 1.4 mg/m2, adriamycin 60 mg/m2, and cyclophosphamide 600 mg/m2. After completion of three cycles, the tumor melted completely, and the child was systemically well [Fig. 6].
Based on a clinical presentation on the day 1, this child was initially treated as a case of orbital cellulitis. Later, it was mistaken for retinoblastoma with orbital extension based on the age of the child and the presence of intraocular calcification. Neuroblastoma was not considered initially as there was no abdominal mass, and primary orbital neuroblastoma has never been reported to have intraocular extension. Intraocular neuroblastoma is always considered to be metastatic.
Orbital neuroblastoma in children commonly occurs due to metastasis with primary in the abdomen. Forty percent of orbital metastases are bilateral. Other solid tumors that metastasize to orbit are Wilms’ tumor, Ewings sarcoma, and testicular sarcoma. These tumors rarely metastasize to the eye itself. Primary orbital neuroblastoma arises from the ciliary ganglion, derived from neural crest cells. Differentiated neuroblastoma is made of mature ganglion cells, Schwann cells, and nerve bundles. Tumor cells form rosettes with central matrix composed of neural cell processes. Immunohistochemistry plays an important role in differentiating neuroblastoma from other small round cell tumors such as retinoblastoma, rhabdomyosarcoma, and lymphoma. Tumors cells are stained for neuronal markers such as neuron specific enolase, chromogranin, and synaptophysin which aids in the diagnosis of neuroblastoma.
Delayed diagnosis in a rapidly growing tumor would have led to intraocular extension of the tumor. Reports of tumor cells being found in the choroidal vasculature in histological section without obvious intraocular extension of solid tumors have been reported. The remote possibility of the tumor arising within the choroid and spreading out into the orbit may be considered. Bilateral choroidal neuroblastomas, diagnosed on histopathological examination, to be primary rather than metastatic, have been described.
The diagnosis of neuroblastoma is often delayed due to its varying and nonspecific presenting symptoms. The biologic puzzle of tumor behavior remains an enigma.
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