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Primary peripheral primitive neuroectodermal tumour of the orbit
Primary peripheral primitive neuroectodermal tumour of the orbit Cengaver Tamer,* MD; Huseyin Oksuz,* MD; Sibel Hakverdi,† MD; Sinem Karazincir,‡ MD; Ali Balci,‡ MD; Mehmet Yaldiz,† MD ABSTRACT • RÉSUMÉ
Case report: We present the clinical, radiologic, and histopathologic features of an orbital mass in a 10-yearold boy. Immunohistochemistry confirmed the diagnosis of primary peripheral primitive neuroectodermal tumour. Comments: This recently recognized rare tumour of the orbit should be considered in the differential diagnosis of hypercellular small round cell tumour of the orbit. Observation : Nous présentons les caractéristiques cliniques, radiologiques et histopathologiques d’une masse orbitaire chez un garçon de 10 ans. L’examen immunohistochimique a confirmé le diagnostic d’une tumeur neuroectodermique périphérique primitive. Commentaires : La reconnaissance récente de cette tumeur rare de l’orbite devrait être prise en considération dans le diagnostic différentiel de la tumeur hypercellulaire à petites cellules rondes de l’orbite.
P
rimitive neuroectodermal tumour (PNET) is a term used to describe a category of highly malignant small round cell tumours of neuroectodermal origin with variable cell differentiation. The majority of PNETs occur in the central nervous system (CNS). PNETs recognized outside of CNS are diagnosed as peripheral PNET (pPNET).1 pPNETs are rare but have been reported in various soft tissues,2–7 the most common site being the thoracopulmonary region.8 Primary orbital pPNET is extremely rare and only 8 cases have been reported previously.9–16 Herein we report the distinguishing microscopic and immunohistochemical features of an additional case. CASE
REPORT
A 10-year-old age boy was admitted to hospital because of progressive right eye medial and upward deviation together with vertical diplopia and exophthalmos developed over a 3-week period. He denied ocular pain,
blurred vision trauma, or other systemic symptoms. His ophthalmic examination did not reveal any additional pathology other than a localized mass. Computed tomography (CT) scans of the right orbit and brain disclosed a right intraorbital tumour located inferolaterally without evidence of bone erosion or defect (Fig. 1). Two weeks after his admission to hospital, en block excisional biopsy of the tumour was performed. Grossly, the tumour was well encapsulated and measured 2 cm × 2 cm × 2.5 cm with prominent vascularity. Pathologic findings
The formalin-fixed tissue fragment was white and firm. It was embedded in paraffin and sections were stained with hematoxylin–eosin and periodic acid-Schiff (PAS). Histopathologic examination of the tumour revealed scattered nests of small tumour cells with round to oval nuclei. The nuclear–cytoplasmic ratio was high,
From *the Departments of Ophthalmology, †Pathology, and ‡Radiology, Mustafa Kemal University School of Medicine, Antakya-Hatay, Turkey Originally received Jan. 18, 2006 Accepted for publication July 18, 2006 Correspondence to: Dr. Cengaver Tamer, MD, Mustafa Kemal University, School Medicine, Department of Ophthalmology, 31100 Antakya (Antioch)-Hatay, Turkey; fax 90 326 214 49 77; [email protected] This article has been peer-reviewed. Cet article a été évalué par les pairs. Can J Ophthalmol 2007;42:138–40 doi:10.3129/can.j.ophthalmol.06-095
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Neuroectodermal tumour of the orbit—Tamer et al
Fig. 1—Computed tomography scan showing a soft-tissue enhanced-mass lesion, inferolateral to the right orbit. The eyeball is displaced superomedially.
Neuroectodermal tumour of the orbit—Tamer et al
with occasional mitotic figures. There were focal areas of necrosis without rosette formation (Fig. 2). The PAS reaction was negative. Sections were studied immunohistochemically for neuron-specific enolase (NSE), vimentin, desmin, glial fibrillary acidic protein (GFAP), cytokeratin, epithelial membrane antigen (EMA), leucocyte common antigen (LCA), S-100 protein, musclespecific actin (MSA), and myoglobin using the avidin–biotin complex technique. These antibodies were applied synchronously with appropriate positive control slides. Immunohistochemical studies were positive only for NSE and S-100 (Fig. 3). Ultrastructurally, cytoplasmic filaments and neurosecretory granules were identified. On the basis of these findings, a diagnosis of primary primitive neuroectodermal tumour of the orbit
Fig. 2—The tumour was composed of small, round cells with large and hyperchromic nuclei arranged in an organoid pattern (hematoxylin– eosin; original magnification ×400).
was made. The patient’s diplopia resolved the day after the operation. He underwent complete systemic evaluation, the results of which were unremarkable, and as his parents did not accept chemotherapy, he received a course of radiotherapy to the operative field over 1 month. His regular follow-up visits for 8 months were uneventful, and orbital CT scans repeated every 3 months failed to show any signs of recurrence. COMMENTS
Peripheral PNET peaks in adolescence and has no sex predilection. pPNET shares a cytogenetic abnormality, that is, translocation t(11;22)(q24;q12), with Ewing sarcoma especially the extraosseous type.17 Microscopically, pPNETs are highly cellular and demonstrate a monotonous pattern of primitive, small round cells with hyperchromatic nuclei, and a high nuclear–cytoplasmic ratio with varying degrees of neuronal differentiation. This progressive process begins with NSE expressivity, followed by Homer–Wright rosette formation, phenotypic ganglion cell differentiation, and finally by neurofilament protein expression.18,19 If this sequence is taken into account, the current case may not be described as fully neuronally differentiated. The differential diagnosis of pPNET of the orbit includes the other small blue round cell tumours: lymphoma neuroblastoma, Ewing’s sarcoma, rhabdomyosarcoma, small cell osteogenic sarcoma, and mesenchymal chondrosarcoma. Although no rosettes were identified on light microscopy, establishing the neural differentiation immunohistochemically led to the diagnosis of pPNET. This recently recognized rare tumour of the orbit should be considered in the differential diagnosis of hypercellular small round cell tumours of the orbit and, because of its close relation with Ewing’s sarcoma, treatment is recommended to be aggressive. REFERENCES
Fig. 3—The tumour cells demonstrate neuronspecific enolase positivity (streptavidin–biotin stain; original magnification ×400).
1. Dehner LP. Primitive neuroectodermal tumor and Ewing’s sarcoma. Am J Surg Pathol 1993;17:1–13. 2. Shah N, Roychoudhury A, Sarkar C. Primitive neuroectodermal tumor of maxilla in an adult. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1995;80:683–6. 3. Charney DA, Charney JM, Ghali VS, Teplitz C. Primitive neuroectodermal tumor of the myocardium: a case report, review of the literature, immunohistochemical, and ultrastructural study. Hum Pathol 1996;27:1365–9. 4. Jurgens H, Bier V, Harms D, et al. Malignant peripheral neuroectodermal tumors. A retrospective analysis of 42 patients. Cancer 1988;61:349–57. 5. Sangueza OP, Sangueza P, Valda LR, Meshul CK, Requena L.
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Neuroectodermal tumour of the orbit—Tamer et al
6.
7.
8.
9.
10.
11.
12.
Multiple primitive neuroectodermal tumors. J Am Acad Dermatol 1994;31(2 Pt 2):356–61. Danner DB, Hruban RH, Pitt HA, Hayashi R, Griffin CA, Perlman EJ. Primitive neuroectodermal tumor arising in the pancreas. Mod Pathol 1994;7:200–4. Jones JE, McGill T. Peripheral primitive neuroectodermal tumors of the head and neck. Arch Otolaryngol Head Neck Surg 1995;121:1392–5. Miller JA, Tomkovich K, Romberger C. Primitive neuroectodermal tumour of the chest wall (Askin tumour): CT and roentgenographic findings in a 51-year-old male. Respir Med 1995;89:705–8. Kiratli H, Bilgic S, Gedikoglu G, Ruacan S, Ozmert E. Primitive neuroectodermal tumor of the orbit in an adult. A case report and literature review. Ophthalmology 1999;106: 98–102. Singh AD, Husson M, Shields CL, De Potter P, Shields JA. Primitive neuroectodermal tumor of the orbit. Arch Ophthalmol 1994;112:217–21. Wilson WB, Roloff J, Wilson HL. Primary peripheral neuroepithelioma of the orbit with intracranial extension. Cancer 1988;62:2595–601. Sen S, Kashyap S, Thanikachalam S, Betharia SM. Primary primitive neuroectodermal tumor of the orbit. J Pediatr Ophthalmol Strabismus 2002;39:242–4.
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13. Howard GM. Neuroepithelioma of the orbit. Am J Ophthalmol 1965;59:934–7. 14. Shuangshoti S, Menakanit W, Changwaivit W, Suwanwela N. Primary intraorbital extraocular primitive neuroectodermal (neuroepithelial) tumour. Br J Ophthalmol 1986;70:543–8. 15. Alyahya GA, Heegaard S, Fledelius HC, Rechnitzer C, Prause JU. Primitive neuroectodermal tumor of the orbit in a 5-yearold girl with microphthalmia. Graefes Arch Clin Exp Ophthalmol 2000;238:801–6. 16. Bansal RK, Gupta A. Primitive neuroectodermal tumour of the orbit: a case report. Indian J Ophthalmol 1995;43:29–31. 17. Fletcher JA, Kozakewich HP, Hoffer FA, et al. Diagnostic relevance of clonal cytogenetic aberrations in malignant softtissue tumors. N Engl J Med 1991;324:436–42. 18. Fletcher CDM, ed. Diagnostic Histopathology of Tumors. Vol 27. Edinburgh: Churchill Livingstone; 1995:1239–50. 19. Kleinert R. Immunohistochemical characterization of primitive neuroectodermal tumors and their possible relationship to the stepwise ontogenetic development of the central nervous system. 2. Tumor studies. Acta Neuropathol (Berl) 1991;82:508–15. Key words: orbita, primary primitive neuroectodermal tumor, immunohistochemical stains
Case report: We present the clinical, radiologic, and histopathologic features of an orbital mass in a 10-yearold boy. Immunohistochemistry confirmed the diagnosis of primary peripheral primitive neuroectodermal tumour. Comments: This recently recognized rare tumour of the orbit should be considered in the differential diagnosis of hypercellular small round cell tumour of the orbit. Observation : Nous présentons les caractéristiques cliniques, radiologiques et histopathologiques d’une masse orbitaire chez un garçon de 10 ans. L’examen immunohistochimique a confirmé le diagnostic d’une tumeur neuroectodermique périphérique primitive. Commentaires : La reconnaissance récente de cette tumeur rare de l’orbite devrait être prise en considération dans le diagnostic différentiel de la tumeur hypercellulaire à petites cellules rondes de l’orbite.
P
rimitive neuroectodermal tumour (PNET) is a term used to describe a category of highly malignant small round cell tumours of neuroectodermal origin with variable cell differentiation. The majority of PNETs occur in the central nervous system (CNS). PNETs recognized outside of CNS are diagnosed as peripheral PNET (pPNET).1 pPNETs are rare but have been reported in various soft tissues,2–7 the most common site being the thoracopulmonary region.8 Primary orbital pPNET is extremely rare and only 8 cases have been reported previously.9–16 Herein we report the distinguishing microscopic and immunohistochemical features of an additional case. CASE
REPORT
A 10-year-old age boy was admitted to hospital because of progressive right eye medial and upward deviation together with vertical diplopia and exophthalmos developed over a 3-week period. He denied ocular pain,
blurred vision trauma, or other systemic symptoms. His ophthalmic examination did not reveal any additional pathology other than a localized mass. Computed tomography (CT) scans of the right orbit and brain disclosed a right intraorbital tumour located inferolaterally without evidence of bone erosion or defect (Fig. 1). Two weeks after his admission to hospital, en block excisional biopsy of the tumour was performed. Grossly, the tumour was well encapsulated and measured 2 cm × 2 cm × 2.5 cm with prominent vascularity. Pathologic findings
The formalin-fixed tissue fragment was white and firm. It was embedded in paraffin and sections were stained with hematoxylin–eosin and periodic acid-Schiff (PAS). Histopathologic examination of the tumour revealed scattered nests of small tumour cells with round to oval nuclei. The nuclear–cytoplasmic ratio was high,
From *the Departments of Ophthalmology, †Pathology, and ‡Radiology, Mustafa Kemal University School of Medicine, Antakya-Hatay, Turkey Originally received Jan. 18, 2006 Accepted for publication July 18, 2006 Correspondence to: Dr. Cengaver Tamer, MD, Mustafa Kemal University, School Medicine, Department of Ophthalmology, 31100 Antakya (Antioch)-Hatay, Turkey; fax 90 326 214 49 77; [email protected] This article has been peer-reviewed. Cet article a été évalué par les pairs. Can J Ophthalmol 2007;42:138–40 doi:10.3129/can.j.ophthalmol.06-095
138
Neuroectodermal tumour of the orbit—Tamer et al
Fig. 1—Computed tomography scan showing a soft-tissue enhanced-mass lesion, inferolateral to the right orbit. The eyeball is displaced superomedially.
Neuroectodermal tumour of the orbit—Tamer et al
with occasional mitotic figures. There were focal areas of necrosis without rosette formation (Fig. 2). The PAS reaction was negative. Sections were studied immunohistochemically for neuron-specific enolase (NSE), vimentin, desmin, glial fibrillary acidic protein (GFAP), cytokeratin, epithelial membrane antigen (EMA), leucocyte common antigen (LCA), S-100 protein, musclespecific actin (MSA), and myoglobin using the avidin–biotin complex technique. These antibodies were applied synchronously with appropriate positive control slides. Immunohistochemical studies were positive only for NSE and S-100 (Fig. 3). Ultrastructurally, cytoplasmic filaments and neurosecretory granules were identified. On the basis of these findings, a diagnosis of primary primitive neuroectodermal tumour of the orbit
Fig. 2—The tumour was composed of small, round cells with large and hyperchromic nuclei arranged in an organoid pattern (hematoxylin– eosin; original magnification ×400).
was made. The patient’s diplopia resolved the day after the operation. He underwent complete systemic evaluation, the results of which were unremarkable, and as his parents did not accept chemotherapy, he received a course of radiotherapy to the operative field over 1 month. His regular follow-up visits for 8 months were uneventful, and orbital CT scans repeated every 3 months failed to show any signs of recurrence. COMMENTS
Peripheral PNET peaks in adolescence and has no sex predilection. pPNET shares a cytogenetic abnormality, that is, translocation t(11;22)(q24;q12), with Ewing sarcoma especially the extraosseous type.17 Microscopically, pPNETs are highly cellular and demonstrate a monotonous pattern of primitive, small round cells with hyperchromatic nuclei, and a high nuclear–cytoplasmic ratio with varying degrees of neuronal differentiation. This progressive process begins with NSE expressivity, followed by Homer–Wright rosette formation, phenotypic ganglion cell differentiation, and finally by neurofilament protein expression.18,19 If this sequence is taken into account, the current case may not be described as fully neuronally differentiated. The differential diagnosis of pPNET of the orbit includes the other small blue round cell tumours: lymphoma neuroblastoma, Ewing’s sarcoma, rhabdomyosarcoma, small cell osteogenic sarcoma, and mesenchymal chondrosarcoma. Although no rosettes were identified on light microscopy, establishing the neural differentiation immunohistochemically led to the diagnosis of pPNET. This recently recognized rare tumour of the orbit should be considered in the differential diagnosis of hypercellular small round cell tumours of the orbit and, because of its close relation with Ewing’s sarcoma, treatment is recommended to be aggressive. REFERENCES
Fig. 3—The tumour cells demonstrate neuronspecific enolase positivity (streptavidin–biotin stain; original magnification ×400).
1. Dehner LP. Primitive neuroectodermal tumor and Ewing’s sarcoma. Am J Surg Pathol 1993;17:1–13. 2. Shah N, Roychoudhury A, Sarkar C. Primitive neuroectodermal tumor of maxilla in an adult. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1995;80:683–6. 3. Charney DA, Charney JM, Ghali VS, Teplitz C. Primitive neuroectodermal tumor of the myocardium: a case report, review of the literature, immunohistochemical, and ultrastructural study. Hum Pathol 1996;27:1365–9. 4. Jurgens H, Bier V, Harms D, et al. Malignant peripheral neuroectodermal tumors. A retrospective analysis of 42 patients. Cancer 1988;61:349–57. 5. Sangueza OP, Sangueza P, Valda LR, Meshul CK, Requena L.
CAN J OPHTHALMOL—VOL. 42, NO. 1, 2007
139
Neuroectodermal tumour of the orbit—Tamer et al
6.
7.
8.
9.
10.
11.
12.
Multiple primitive neuroectodermal tumors. J Am Acad Dermatol 1994;31(2 Pt 2):356–61. Danner DB, Hruban RH, Pitt HA, Hayashi R, Griffin CA, Perlman EJ. Primitive neuroectodermal tumor arising in the pancreas. Mod Pathol 1994;7:200–4. Jones JE, McGill T. Peripheral primitive neuroectodermal tumors of the head and neck. Arch Otolaryngol Head Neck Surg 1995;121:1392–5. Miller JA, Tomkovich K, Romberger C. Primitive neuroectodermal tumour of the chest wall (Askin tumour): CT and roentgenographic findings in a 51-year-old male. Respir Med 1995;89:705–8. Kiratli H, Bilgic S, Gedikoglu G, Ruacan S, Ozmert E. Primitive neuroectodermal tumor of the orbit in an adult. A case report and literature review. Ophthalmology 1999;106: 98–102. Singh AD, Husson M, Shields CL, De Potter P, Shields JA. Primitive neuroectodermal tumor of the orbit. Arch Ophthalmol 1994;112:217–21. Wilson WB, Roloff J, Wilson HL. Primary peripheral neuroepithelioma of the orbit with intracranial extension. Cancer 1988;62:2595–601. Sen S, Kashyap S, Thanikachalam S, Betharia SM. Primary primitive neuroectodermal tumor of the orbit. J Pediatr Ophthalmol Strabismus 2002;39:242–4.
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13. Howard GM. Neuroepithelioma of the orbit. Am J Ophthalmol 1965;59:934–7. 14. Shuangshoti S, Menakanit W, Changwaivit W, Suwanwela N. Primary intraorbital extraocular primitive neuroectodermal (neuroepithelial) tumour. Br J Ophthalmol 1986;70:543–8. 15. Alyahya GA, Heegaard S, Fledelius HC, Rechnitzer C, Prause JU. Primitive neuroectodermal tumor of the orbit in a 5-yearold girl with microphthalmia. Graefes Arch Clin Exp Ophthalmol 2000;238:801–6. 16. Bansal RK, Gupta A. Primitive neuroectodermal tumour of the orbit: a case report. Indian J Ophthalmol 1995;43:29–31. 17. Fletcher JA, Kozakewich HP, Hoffer FA, et al. Diagnostic relevance of clonal cytogenetic aberrations in malignant softtissue tumors. N Engl J Med 1991;324:436–42. 18. Fletcher CDM, ed. Diagnostic Histopathology of Tumors. Vol 27. Edinburgh: Churchill Livingstone; 1995:1239–50. 19. Kleinert R. Immunohistochemical characterization of primitive neuroectodermal tumors and their possible relationship to the stepwise ontogenetic development of the central nervous system. 2. Tumor studies. Acta Neuropathol (Berl) 1991;82:508–15. Key words: orbita, primary primitive neuroectodermal tumor, immunohistochemical stains