CASE 3 PRIMITIVE NEUROECTODERMAL TUMOR-PERIPHERAL NEUROEPITHELIOMA

Theodore J. Pysher, MD 0 Departments of Pathology and Pediatrics, Primary Children’s Medical Center and University of Utah School of Medicine, Salt Lake City, Utah 84103

Richard S. Boyer, MD 0 Departments of Radiology and Pediatrics, Primary Children’s Medical Center and University of Utah School of Medicine, Salt Lake City, Utah 84103

Marion L. Walker, MD 0 Departments of Surgery (Neurosurgery) and Pediatrics, Primary Children’s Medical Center and University of Utah School of Medicine, Salt Lake City, Utah 84103

CLINICAL HISTORY

A previously healthy 4-year-old Caucasian female had several episodes of otitis media involving the right ear. Therapy with erythromycin and trimethoprim-sulfamethoxazole caused vomiting. After one course of cefaclor, her mother reported that the right side of the patient’s face drooped and that there seemed to be decreased mobility of her right eye. These symptoms im- proved during the second 10-day course of cefaclor and were ascribed to virus- induced inflammation of the seventh nerve. Approximately 4 months later the child developed a broad-based, stumbling gait, right-sided morning head- aches, and intermittent nausea, vomiting, and enuresis. Right-sided enotro- pia prompted referral to an ophthalmologist, who ordered a C T scan that showed a large, enhancing, lobulated, right hemispheric tumor with periph- eral calcifications that compressed the lateral ventricle and seemed to arise from the apex of the right petrous temporal bone, where it had apparently replaced air spaces, destroyed the cortex, and elicited a spiculated reaction in the periosteum (Fig. 1). A right temporal-parietal-occipital craniotomy re- vealed marked thinning of the cranium and a large firm tumor in the poste- rior aspect of the right temporal fossa, involving the right temporal, parietal, and occipital lobes and extending through the dura into the underlying bone.

Address reprint requests to Theodore J. Pysher.

Pediatric Patholom, 9:185-191, 1989 - . . h _ ^ ^ ^ . _ _ . . - ... . . - 185

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FIGURE 1. Coronal noncontrast cranial computed tomograph showing a large right hemispheric tumor with peripheral calcification that has compressed the right lateral ventricle. Note the extensive destruction of the underlying temporal bone and radially distributed periosteal reaction in a pattern most consistent with an intraosseous origin of the tumor with extension to the cerebral hemisphere.

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PRIMITIVE NEUROECTODERMAL TUMOR 187

After recovering from the craniotomy, the patient received radiotherapy: 4600 rads to the tumor bed and 4000 to the remainder of the brain and spinal cord. Five months after the craniotomy and 2 months after completion of radiotherapy, the patient developed generalized seizures-at first continuous, but eventually responsive to anticonvulsants. A CT scan showed recurrent tumor. She received a 4-month course of “8-in-one” chemotherapy. However, CT scan revealed that the tumor had increased in size, and 1 1 months after her first craniotomy, the patient underwent a second operation to debulk the expanding mass. She then received a 2-month course of chemotherapy with VP-16. A third craniotomy was required 5 months after the second to again reduce the size of the tumor. Within 2 months the tumor had grown to nearly the same size it had been before the third operation, and the patient died 6 months later.

All three procedures yielded similar specimens. Grossly, the specimens were large, somewhat friable gray-tan masses with focal hemorrhage, necro- sis, and stippled calcification. Microscopically (Figs. 2 and 3), they showed nests, cords, and, most prominently, fields of interweaving pseudorosettes created by arrays of large, smooth-contoured nuclei around central anucleate zones formed by the blunt, polar cytoplasmic processes of the same cells.

FIGURE 2. The tumor is characterized by fields of interweaving pseudorosettes, X 25

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FIGURE 3. eccentric cytoplasm that forms the cores of the rosettes. X 250.

Tumor cells have smooth-contoured nuclei with clumped chromatin and small nucleoli, and

However, mats of fibrillary matrix, perivascular pseudorosettes, or ependymal rosettes were not seen. Tumor cell nuclei manifested clumped chromatin and frequent mitotic figures, but nucleoli were small. Large zones of hemorrhage and/or necrosis were noted throughout the tumor. Immunohistochemical studies showed focal cytoplasmic positivity for neuron-specific enolase but not glial fibrillary acidic protein or S- 100 protein. Ultrastructurally (Fig. 4), the cells showed polar cytoplasm, occasionally drawn into short, blunt projections and containing numerous polyribosomes, moderate numbers of mitochondria with platelike cristae, a few aggregates of monoparticulate glycogen, and rare nondilated profiles of rough-surfaced endoplasmic reticulum, lipid droplets, or primary lysosomes. Only a rare microtubule was noted, and no dense-core granules, junctional complexes, or external laminae were seen. Nuclei con- tained clumped heterochromatin and small nucleoli. The “cores” of rosettes were composed of the bodies of the surrounding cells, only rarely admixed with processes from other cells.

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DISCUSSION

The rosetting pattern, regular nuclei with clumped chromatin, polar eo- sinophilic cytoplasm, demonstration of neuron-specific enolase, and presence of rare microtubules in cytoplasmic processes identify this neoplasm as a neu- roectodermal tumor. However, while the extensive rosetting seen in this tumor is unusual in primitive neuroectodermal tumors (PNET) of the central ner- vous system'-3 or, for that matter, neuroblastoma, it has been described as a prominent feature in some reports of peripheral neuroepitheli~ma.~-*~ Coupled with the clinical history of early involvement of the right middle ear and the radiographic impression of origin in bone with extension to the brain, rather than the reverse, it seems likely (though it cannot be proved) that this is, in fact, not a central PNET but a neuroepithelioma arising in the petrous bone or adjacent tissues.

Cell culture" and cytogenetic studies" suggest that peripheral neuroepitheliomas are distinct from neuroblastomas and more closely related to Ewing's sarcoma. The relationship of rosetting neuroepitheliomas to the more diffuse neoplasms of probable neuroepithelial origin that involve the thoracopulmonary and other peripheral is uncertain, and recent reports make no distinction between them. Unfortunately, both rosett- ing and nonrosetting peripheral neuroepitheliomas have a dismal response to therapy, and therefore any subclassification is of little clinical consequence at present. Its only utility may be to enhance the recognition of peripheral neu- roectodermal tumors and thereby facilitate their study.

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