Case 7 -

Intracranial Olfactory Neuroblastoma Dr. H.K. Ng Department of Pathology, Prince of Wales Hospital The Chinese University of Hong Kong

Case history: A 61-year-old taxi operator, a known alcoholic, presented to the Accident an Emergency Department following a minor head injury with drowsiness, confusion and double incontinence. Physical examination did not show any focal neurological defect at the Emergency Room. CT scan of the brain demonstrated a large left frontal tumour at the anterior cranial fossa. A left frontal craniotomy was subsequently performed. A fleshy haemorrhagic tumour was resected and the origin of the tumour was thought to be dural. Initial histologic diagnosis was metastatic carcinoma. As no obvious primary tumour was found after a series of investigations and imaging involving the respiratory and gastrointestinal systems, the patient was given a course of cranial radiotherapy. The patient developed epistaxis one month post-operation and ENT examination and sinus X-ray showed ethmoiditis. A course of antibiotics was given. At four months post-operation, recurrent epistaxis became a problem. ENT examination at this stage revealed a fungating tumour at the nasal cavity. MR and CT imaging showed large tumour in the nasal cavity with erosion of the cribriform plate. In the light of the clinical course and subsequent biopsy of the nasal tumour, histological material from the intracranial tumour was reviewed and the diagnosis was changed to olfactory neuroblastoma. A biopsy of the nasal mass shows similar histological tissues. Further operation was refused by the patient and he died six months after the initial craniotomy, of extensive intracranial and paranasal tumour recurrences. Case 7 - Figure 1 Click to view with ImageScope Click to view with a Web-Based Viewer Pathological findings Histological feature showed groups of anaplastic cells with hyperchromatic nuclei and scanty cytoplasm, well-demarcated from a moderately cellular stroma. The arranagement of the nuelci at the periphery of the cellular lobules and the abrupt interface of the neoplasm with the stroma gave a initial impression of a metastatic carcinoma. On closer examination, numerous epithelial-like rosettes were present, which in hind sight represent Flexner's rosettes or olfactory rosettes as described by Silva et al. (1982). The stromal cells actually showed marked pleomorphism and hyperchoimratisma nd possessed intercellular eosinophilic fibrillar material. In some foci, the stromal cells merged with the epithelia-like cells. Strong immunostaining for both epithelial-like and stromal cells is obtained for synaptophysin, NSE, and S100 protein. Focal positive staining for cytokeratin was obtained. Electron microscopy using retrieved paraffin embedded materials showed budding projections of cytoplasm with vesicular structures, neurosecretory granules and some microvilli. Discussion Olfactory neuroblastoma (or esthesioneuroblastoma) arise from the sensory mucosa of the roof othe nasal cavity or the maxillary and ethmoid sinus. The olfactory neuroepithelium extends from the roof of the nasal cavity to the midportion of the nasal septum. The age range affected is very broad. The diagnosis of those tumours can be difficult because, apart from the fact that they are usually poorly differentiated tumours, they exhibit a spectrum of morphologic appearance ranging from carcinoma-like to neuroblastoma-like. This is reflected in the confusing terminology that has been applied to these tumours. It commonly presents as a polypoid nasal tumour with nasal obstruction and epistaxis and the tumour may extend intracranially. Rarely, olfactory neuroblastoma presents primarily as intracranial tumour. The nasal portion is either inconspicuous by imaging or so small that it is missed [1, 2, 3, 4, 5]. Erosion of the cribriform plate or ethmoidal roof is present in about 60% of olfactory neuroblastoma and should be looked for for any unusual tumour located at the anterior cranial fossa [6]. When they do so, the histological pitfall as in this case is that a diagnosis of metastatic carcinoma will be made. The differential diagnosis can be made difficult as the histological appearance of olfactory neuroblastoma merges with those of the olfactory neuroendocrine carcinoma as described by Silva et al [7]. A careful evaluation of the imaging of the nasal and paranasal sinus is mandatory whenever a diagnosis of metastatic carcinoma is made at the base of skull. The Kadish staging system is often used : Stage A, disease confined to nasal cavity, stage B, disease confined to nasal cavity and one or more paranasal sinus and stage C disease extending beyond the nasal cavity or paranasal sinus [8]. Tumours encountered in surgical neuropathology will be stage C. Haymes has proposed grading system (grades I-IV) which, according to some, correlates with prognosis. In this scheme, low-grade tumour will have a lobular growth pattern. Grade I tumours are characterized by a prominent fibrillary matrix, uniform tumour nuclei, and presence of Homer-Wright rosettes but lack nuclear pleomorphism, mitotic activity and necrosis. Grade II tumours show low mitotic activity (1-2/HPF) and moderate pleomorphism. In contrast, grade III-IV tumours, respectively, show prominent to marked mitotic activity and nuclear pleomorphism, minimal to absent fibrillary matrix, and absence of rosettes [9]. A variety of tumour conditions occur at the base of skull. The differential diagnosis of those which have an epithelial-like appearance includes : Metastatic carcinoma Olfactory neuroblastoma Neuroendocrine carcinoma Dermoid / epidermoid cyst Carcinoma of the nasal and paranasal sinuses Nasopharyngeal carcinoma (in certain localities of the world) Chordoma Papillary endolymphatic sac tumour Paraganglioma Craniopharyngioma Very meningothelial forms of meningioma Large pituitary adenoma with local invasion Melanoma Other than metastatic carcinoma, they include a varieties of lesions that are extension lesions from a primary at the skull base or the head and neck region. Once these differential diagnoses have been kept in mind, the differential diagnosis is not so difficult and careful review of the clinical and radiological information will help to achieve a correct diagnosis. In some regions of the world, intracranial extension of nasopharyngeal carcinoma is a common terminal event but this tumour is not known to present as a primarily intracranial lesion. Meningiomas with very a very epithelial or meningothelial-like-like appearance strongly mimic a large pituitary adenoma with suprasellar extension and local invasion into cavernous sinus and the paranasal sinus. For the non-functioning pituitary adenoma without any staining for the pituitary hormones, distinction between the two may be even more difficult as the epithelial immunohistochemical markers may not distinguish between the two. Paraganglioma (glomus jugulare tumours) are vascular tumours causing destruction of the right jugular foramen and adjacent temporal bone and with their tight packaging, may mimic a meningioma or carcinoma. References Goldhammer Y, Sadeh M, Tadmor R, Leventon G. Intracrnail esthesioneuroblastoma associated with unilateral visual loss. J Neurosurgery 1980;53:836-40 Esposito S, Bruni P, Visca T et al. Primary intracranial esthsioneuroblastoma. Case report. J Neurosurg Sci 1985;29:25-30 Ng HK, Poon WS, Poon CYF, South JR. Intracranial neuroblastoma mimicking carcinoma : report of two cases. Histopathology 1988;12:393-403 Ho HW, Awward EE, Martin DS, et al. Olfactory neuroblastoma mimicking primary intracranial neoplasm. Comput Med Imaging Graph 1991;15:125-7 Meneses MS, Thurel C, Mikol J et al. Esthesioneuroblastoma with intracranial extension. Neurosurgery 1990;27:813-819 Lund VJ, Milroy C. Olfactory neuroblastoma : clinical and pathological aspects. Rhinology 1993;31:1-6 Silva EG, Butler JJ, Mackay B, Goeperth H. Neuroblastomas and neuroendocrine caqrcinoma of the nasal cavity. A proposed new classification. Cancer 1982;50:181-189 Kadish S, Goodman M, Wang CC. Olfactory neuroblastoma. A clinical analysis of 17 cases. Cancer 1976;37:1571-6 Haymes VJ, Batsakis JG, Michaels I. Tumors of the Upper Respiratory Tract and Ear. Second Series, Fascicle 25, Atlas of Tumor Pathology. Washington, DC : Armed Forces Institute of Pathology, 1988