An unusual case of malignant pilocytic astrocytoma
occurring in the eye Alessandra Canesso & Marina Gardiman & Roberto Salmaso & Rita Alaggio & Vito Ninfo Received: 18 September 2005 / Accepted: 10 April 2006 / Published online: 20 May 2006 # Springer-Verlag 2006 Abstract Pilocytic astrocytoma is a central nervous system neoplasia that arises during pediatric age. Only few cases have been documented in patients older than 50 years old. It is a low-grade lesion that can rarely undergo malignant changes presenting the histologic features of a high-grade glioma. We report a case of a pilocytic astrocytoma arising in the eyeball of a 53-year-old man affected by glaucoma that underwent malignant evolution. Keywords Pilocytic astrocytoma . Glioma . Malignant evolution Introduction Pilocytic astrocytoma is a low-grade neoplasia of the central nervous system that occurs in pediatric age without any sexual distinction. Some cases have also been detected in young adults and only rarely after fifth decade [14]. It is located more frequently in the cerebellum, where it grows as a quite well-restricted mass, often cystic with mural nodule. Other possible locations are the chiasmatic hypothalamic region, the optic nerve and, rarely, the cerebral emispheres and the spinal cord. Its typical imaging shows hypointensive images in T1 sequences and hyperintensive images in T2 sequences with enhancement of the tumoral nodule after administration of contrast material [4]. Its clinical course is generally favorable. Even after a subtotal resection, its growth is slow and leptomeningeal spread is rare. Some cases have been reported, however, in which pilocytic astrocytoma underwent malignant evolu- tion presenting the histologic features of high-grade malignant glioma, including palisading necrosis, vascular proliferation, and mitotic index increase [14]. We report a case of a pilocytic astrocytoma with histologic features of malignancy occurring in the eyeball of a 53-year-old man with a clinical history of glaucoma. Case report Clinical history A 53-year-old man underwent an enucleation and an endoprosthesis implant for a glaucoma of the right eye. He had undergone a surgical operation for a congenital cataract when he was 6 years old and another one for glaucoma at the age of 45. There are no previous tumor diagnosis Surgical specimen showed deformed eyeball with diffuse increased consistency and scleral darkening; crystalline lens was entirely embebbed in a relatively friable yellowish mass. On cut surface, the tumor occupied the whole posterior chamber of the eye replacing the vitreous body and infiltrating the optic nerve and the iris that appeared pale. No preoperative RMN of the facial bones was carried out, while postoperative RMN, with and without administration of contrast material, revealed that the extrinsic muscle structures and part of the optic nerve were normal and there Virchows Arch (2006) 449:248252 DOI 10.1007/s00428-006-0224-3 A. Canesso (*) : M. Gardiman : R. Salmaso : R. Alaggio : V. Ninfo Section of Pathology, Department of Oncological and Surgical Sciences, University of Padova, Via Gabelli 61, Padova 35100, Italy e-mail: canalex@hotmail.it were no signs of chiasma alteration. Sixteen months after the operation, the patient is alive and free of disease. Methods The material obtained from the eyeball was fixed in formalin, embedded in paraffin and stained with hematox- ylin and eosin using standard methods. The following immunohistochemical stainings were performed: MIB-1 (Neomarkers, dilution 1:20), glial fibrillary acidic protein (GFAP) (Novocastra, dilution 1:100), S100 protein (Neo- markers, dilution 1:1,200), HMB-45 (Novocastra, dilution 1:60), AE1/AE3 (Neomarkers, dilution 1:500), and p53 (Novocastra, dilution 1:100). Results Microscopically, the lesion showed different areas: typical features of pilocytic astrocytoma associated with foci of necrosis with pseudopalisading (Fig. 1). Areas of pilocityc astrocytoma were focally evident and characterized by the classic byfasic pattern formed by compact piloid tissue intermingled with calcification and microcysts (Fig. 2a). Rosenthal fibers were prominent in solid areas, whereas granular bodies were easily detected in the cystic compo- nent (Fig. 2b). Most of the tumor was composed by highly cellular areas of spindle cells with oval hyperchromatic and pleomorphic nuclei; in this areas, more than one mitosis/ 10 HPF were detected (average two mitosis/10 HPF) as well as vascular proliferation and necrosis with pseudo- palisading (Fig. 3). Vascular proliferation was characterized by medium-sized vascular channels with multilayered endothelial cells around foci of necrosis. Typical glomer- uloid vasculature of pylocitic astrocytoma was not present. The immunohistochemical stainings showed a strong and diffuse positivity for S-100 protein, GFAP, and p53 especially in the compact fibrillar areas (Figs. 4 and 5). Mib-1 highlighted the different proliferative rate in the area of classic pilocytic astrocytoma (6.97%) and in area of malignant transformation (19.52%) (evaluation with Roche Image Analysis System) (Fig. 4). Fig. 2 Typical features of pilocytic astrocytoma: calcification (a) and microcystic areas with granular bodies (arrow, b). H&E, 12; 15 Fig. 1 Tumor shows a typical area of pilocytic astrocytoma (on the left) composed of spindle cells arranged in fascicles with calcifications associated with foci of necrosis with pseudopalisading (on the upper right). H&E, 3 Virchows Arch (2006) 449:248252 249 Cytokeratins and HMB-45 were negative. Our final diagnosis was pilocytic astrocytoma with malignant trans- formation. Discussion A wide range of neoplasia occur in the orbit such as soft tissue tumor, lymphoid tumor, metastatic tumor, glioma, and meningioma. Soft tissue tumor are infrequent; the list includes fibrous histiocytoma (the most commonly diagnosed mesenchymal lesion at this anatomic site) hemangioma, hemangiopericy- toma and solitary fibrous tumor, giant cell angiofibroma, rhabdomyosarcoma, particularly in childhood, and a variety of soft tissue lesions [5, 10]. Lymphoid tumors generally develop in the course of a previously recognized non-Hodgkins malignant lymphoma or leukemia [10]. Direct spread from adjacent structures can occur with primary intraocular tumors such as retinoblastoma or Fig. 3 Areas of necrosis with peripheral palisading mimicking glioblastoma multiforme (right) and rich vascular proliferation (left). H&E, 12 Fig. 4 Strong and diffuse positivity for GFAP (left). Mib 1 staining highlights the different proliferative rate in the area of classical pilocytic astrocytoma (upper right) and in area of malignant transformation (down) (6; 25) 250 Virchows Arch (2006) 449:248252 uveal malignant melanoma. Hematogenous metastases to the orbit may be seen: carcinoma of the breast, bronchus, kidney or prostate in adults, and neuroblastoma in children [10]. Most optic gliomas are low grade pilocytic astrocytoma [8]. Typically make their presence with minimal exophtal- mos, optic nerve atrophy or papilledema. Generally, these tumors can be adequately managed by surgical [10]. Pilocytic astrocytoma is a slowly growing neoplasia defined a low-grade malignancy in WHO classification [14] characterized by rare leptomeningeal spread and recurrences after an incomplete resection. Transformation into high- grade astrocytoma is even a rarer occurrence. Only few cases of cerebellar [13, 7, 12] and chiasmatichypothalamic [6, 9, 15] pilocytic astrocytomas had recurrences within 4 to 48 years after the original diagnosis manifesting the histologic features and the clinical behavior of glioblastoma multiforme or anaplastic astrocytoma. All initial lesions occurred during pediatric age and were treated by surgical excision and/or radiation therapy. The histologic examination showed neoplasias with the typical features of pilocytic astrocytoma, e.g., solid areas alternat- ing with microcystic areas, spindle-shaped monomorphous cells, eosinophilic granular bodies, and Rosenthal fibers. Recurrent lesions occurred in the same locations as the initial ones, except one reported by Yukitaka et al. [13], but their morphological features only partly reminded those of a low-grade astrocytoma [15]; this was due to their high- cellular polymorphism, endothelial proliferation, brisk mitotic index, and palisading necrosis. Only one case showed areas formed by small cells mixed with others typical features of pilocytic astrocytoma, which were considered as anaplastic astrocytoma [9]. In most cases, the authors linked the malignant evolution of the low-grade initial lesions to radiation therapy that can be also involved in the development of some other types of tumors such as meningiomas, astrocytomas, and fibrosarcomas [12]; on the other hand, malignant evolution seems almost unlikely in patients who did not receive any radiation therapy. The case described herein can be included in those reported by literature because it shows the features of pilocytic astrocytoma, such as the typical cellularity located in some areas of the neoplasia, eosinophile granular bodies, Rosenthal fibers, and calcification as well as palisading necrosis, vascular endothelial proliferation, and nuclear abnormalities. These last morphological findings are in favor of the diagnosis of malignancy. Vascular proliferation is common in pilocytic astrocytoma and numerous eosinophilic hyaline droplets were described in glioblastoma multiforme [11]. In our case, vascular proliferation was characterized by medium-sized vascular channels with multilayered endothe- lial cells around foci of necrosis. Typical glomeruloid vasculature of pylocitic astrocytoma was not present. Eosinophilic granular bodies are an important diagnostic feature of several neoplasms including ganglion cell tumors, pleomorphic xanthoastrocytoma, and pilocytic astrocytoma [14]. Sasaki et al. [11] reported a case of glioblastoma multiforme with unusual histological features in a 79-year-old woman. In the tumor, there were marked nuclear atypism, frequent mitotic figures, small areas of necrosis with pseudopalisading, microvascular prolifera- tion, and numerous eosinophilic round bodies within the cytoplasm of large neoplastic cells. Nevertheless, there are no areas of low-grade astrocytoma. For these reasons, we concluded for a diagnosis of malignant pilocytic astrocytoma and not for glioblastoma multiforme despite the presence of vascular proliferation and presence of eosinophile granular bodies. The difference from the cases reported by literature lies in the fact that neoplasia underwent malignant evolution even though this was not induced by typical factors such as radiation therapy. We can hypothesize that the only symptom was treated by surgery but not the growing neoplastic mass that was overlooked and remained in the eyeball. Longstanding tumor mass with an inadequate treatment can have induced malignant transformation in an otherwise typical pilocytic astrocytoma. In conclusion, if this kind of low-grade lesions are not diagnosed because their locations allow them to grow without manifesting clear symptoms, in time, they can undergo malignant transformation even in absence of an history of radiation therapy. Acknowledgement Special thanks to Ms. Elena Leonardi for the linguistic revision of this text. References 1. Alpers CE, Davis RL, Wilson CB (1982) Persistence and late malignant transformation of childhood cerebellar astrocytoma. Case report. J Neurosurg 57:548551 2. Bernell WR, Kepes JJ, Seitz EP (1972) Late malignant recurrence of childhood cerebellar astrocytoma. Report of two cases. J Neurosurg 37:470474 Fig. 5 Positivity for p53 in compact fibrillar areas (40) Virchows Arch (2006) 449:248252 251 3. Budka H (1975) Partially resected and irradiated cerebellar astrocytoma of childhood: malignant evolution after 28 years. Acta Neurochir (Wien) 32(12):139146, Abstract 4. Burger PC, Scheithauer BW (ed) (1994) Atlas of tumors pathology: tumors of the central nervous system. Armed Forces Institute of Pathology, Washington, DC, pp 7796 5. Dei Tos AP, Seregard S, Calonje E et al (1995) Giant cell angiofibroma a distinctive orbital tumor in adults. Am J Surg Pathol 19(11):12861293 6. Dirks PB, Jay V, Becker LE et al (1994) Development of anaplastic changes in low grade astrocytomas of childhood. Neurosurgery 34(1):6878 7. Kleinman GM, Schoene WC, Walshe TM et al (1978) Malignant transformation in benign cerebellar astrocytoma. Case report. J Neurosurg 49:111118 8. Marquardt MD, Zimmerman LE (1982) Histopathology of meningiomas and gliomas of the optic nerve. Human Pathol 13 (1):226235 9. Nishio S, Takeshita I, Fukui M et al (1988) Anaplastic evolution of childhood optico-hypothalamic pilocytic astrocytoma: report of an autopsy case. Clin Neuropathol 7(5):254258 10. Rosai J (2004) Rosai and Ackermans surgical pathology, vol 2, pp 27252730 11. Sasaki A, Yoshida S, Kurihara H et al (2001) Glioblastoma with large numbers of eosinophilic hyaline droplets in neoplastic astrocytes. Clin Neuropathol 20(4):156162 12. Schwartz AM, Ghatak NR (1990) Malignant transformation of benign cerebellar astrocytoma. Cancer 65:333336 13. Yukitaka U, Norio A, Toshiki Yet al (1987) Malignant recurrence of childhood cerebellar astrocytoma: case report. Neurosurgery 21 (2):251255 14. WHO Classification of Tumors (ed) (2000) Pathology and genetic of tumors of the nervous system. IARC Press, Lyon, pp 4749 15. Wilson WB, Feinsod M, Hoyt WF et al (1976) Malignant evolution of childhood chiasmal pilocytic astrocytoma. Neurology 26:322325 252 Virchows Arch (2006) 449:248252
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