Primitive neuroectodermal tumor after radiation therapy for craniopharyngioma

Case report

View More View Less
  • 1 Departments of Neurosurgery and
  • 2 Pathology, University of Illinois at Chicago, Illinois
Full access

The authors report a case of primitive neuroectodermal tumor induced by radiation therapy of craniopharyngioma. This African-American male patient originally presented with craniopharyngioma, for which he underwent resection and whole-brain radiation therapy. Eight years later, at the age of 20 years, he returned with a left facial droop and left hemiparesis. A right basal ganglia mass was identified and resected. Histopathological examination identified the lesion as primitive neuroectodermal tumor.

Although radiation therapy has shown to be beneficial in decreasing the recurrence rate in subtotally resected craniopharyngioma, the risks of radiation treatment should be clearly communicated to the patients, their families, and neurosurgeons before starting such treatment. This report expands the spectrum of reported radiation-induced neoplasms in the CNS.

Abbreviations used in this paper: GFAP = glial fibrillary acidic protein; PNET = primitive neuroectodermal tumor; WBRT = whole-brain radiation therapy.

The authors report a case of primitive neuroectodermal tumor induced by radiation therapy of craniopharyngioma. This African-American male patient originally presented with craniopharyngioma, for which he underwent resection and whole-brain radiation therapy. Eight years later, at the age of 20 years, he returned with a left facial droop and left hemiparesis. A right basal ganglia mass was identified and resected. Histopathological examination identified the lesion as primitive neuroectodermal tumor.

Although radiation therapy has shown to be beneficial in decreasing the recurrence rate in subtotally resected craniopharyngioma, the risks of radiation treatment should be clearly communicated to the patients, their families, and neurosurgeons before starting such treatment. This report expands the spectrum of reported radiation-induced neoplasms in the CNS.

Abbreviations used in this paper: GFAP = glial fibrillary acidic protein; PNET = primitive neuroectodermal tumor; WBRT = whole-brain radiation therapy.

Whole-brain radiation therapy is part of the treatment for craniopharyngioma. One of the rare side effects of radiation therapy is the evolvement of tumors, including malignancies such as sarcomas, gliomas, and benign neoplasms such as meningiomas and schwannomas. Few cases of postradiotherapy PNET have been described in the literature. The majority of these rare cases occurred in patients who undergone WBRT for the treatment of acute leukemia, lymphoma, or astrocytoma. This paper is the first description of the development of a postradiotherapy PNET after resection of craniopharyngioma.

Case Report

History and Presentation

This young African-American man was initially treated in our institution in 1994 (at the age of 12 years) for craniopharyngioma (Fig. 1). At that time, he presented with left hemiparesis and a history of similar, transient episodes during the previous few months with deterioration during the last week. The patient denied having headache, nausea, vomiting, ataxia, or seizures. He underwent resection of the mass and was treated with 6 weeks of WBRT. During that time, he suffered from panhypopituitarism and blindness.

Fig. 1.
Fig. 1.

Photomicrograph of an H & E–stained section of the initial pathological specimen demonstrating craniopharyngioma. Original magnification × 400.

He returned in 2002, at the age of 20 years, with new-onset left facial droop and left hemiparesis.

Neuroimaging

An MR imaging study of the brain demonstrated a 2.5-cm enhancing lesion that was hypointense on T1-weighted images and hyperintense on T2-weighted images. The lesion involved the right basal ganglia, the genu of the internal capsule, and the posterior internal capsule (Fig. 2 left). The mass was not noted to involve the sellar region (Fig. 2 right). The tumor was noted to exert mass effect on the right lateral ventricle.

Fig. 2.
Fig. 2.

Preoperative contrast-enhanced T1-weighted MR images. Left: Axial image showing a right enhancing lesion measuring 2.5 cm in diameter. Right: Coronal view demonstrating the lack of sellar involvement.

Operation and Postoperative Course

A brown-grayish necrotic tumor was subtotally resected via a right frontotemporopterional craniotomy.

The patient recovered from surgery with some improvement of motor strength. Histopathological examination of the tumor demonstrated a highly cellular neoplasm composed of cells with round-to-oval nuclei and scanty cytoplasm (Fig. 3A). Tumor cells showed widespread immunoreactivity for vimentin, neuron-specific enolase, and synaptophysin (Fig. 3B), and focal immunoreactivity for GFAP (Fig. 3C) and neurofilament protein. The results of immunohistochemical evaluation for keratin markers (AE1/AE3, CK7, CK20), carcinoembryonic antigen, Melan-A, epithelial membrane antigen, desmin, leukocyte common antigen, and smooth muscle–specific actin were negative. Mucicarmine staining was also negative. The Ki 67 proliferation marker stained over 30% of the tumor cells (Fig. 3D). The final diagnosis was a WHO Grade IV PNET. Postoperative imaging showed no residual mass (Fig. 4A).

Fig. 3.
Fig. 3.

Photomicrographs of sections of the second specimen (PNET) obtained 8 years after radiotherapy. A: An H & E–stained section demonstrating a highly cellular neoplasm composed of cells featuring round-to-oval nuclei and scanty cytoplasm, with significant pleomorphism. B: Synaptophysin immunoreactive staining of the PNET specimen demonstrating widespread immunoreactivity of tumor cells. C: Staining for GFAP showing focal immunoreactivity. D: Results of staining with Ki 67 proliferation marker showing staining in over 30% of tumor cells in the PNET specimen. Original magnifications × 400 (A–C) and × 200 (D).

Fig. 4.
Fig. 4.

Postoperative neuroimages. A: Noncontrast head CT obtained immediately after resection of the PNET, demonstrating no residual tumor. B: Axial contrast-enhanced T1-weighted MR image obtained 1 month postoperatively demonstrating a recurrent lesion measuring 3.5 cm in diameter. C: Axial contrast-enhanced T1-weighted MR image obtained 2 months postoperatively showing interval enlargement of the lesion, which is 5.8 cm in diameter in this image.

Two months later, follow-up MR imaging of the brain demonstrated that the mass in the right basal ganglia was now 3.5 cm (Fig. 4B). Another follow-up MR imaging study 3 weeks later revealed that the mass was larger still, at 5.2 × 4.4 × 5.8 cm (Fig. 4C).

The patient's records are incomplete, but the reports indicate that he received a full regimen of radiotherapy in 1994 for his craniopharyngioma; thus he was no longer a candidate for radiation therapy. A chemotherapy regimen consisting of vincristine, lomustine, and prednisone treatment was initiated. The patient was subsequently lost to follow-up.

Discussion

Primitive neuroectodermal tumor is a rare type of tumor in the adult population, and cases of radiation-induced PNET are especially rare.7,11 Possible risk factors for these tumors include young age at time of irradiation, genetic predisposition to malignancies, and genetic polymorphism in certain metabolic enzymes.12 The case presented here meets all the requirements for a radiation-induced neoplasm as described by Cahan et al. in 1948.3,5 These criteria are: 1) tumor originating from areas that were previously irradiated; 2) elapsed time between radiation treatment and the appearance of the radiation-induced lesion; 3) no other pathological conditions that will predispose to tumor development; and 4) the histological characteristics must be different from those of the primary lesion that prompted the radiation treatment.3,5 In our patient, the PNET was found in the field of irradiation almost 9 years after the initial treatment, and showed histopathological characteristics that were markedly different from those of the initial tumor. Eleven of the 12 reports of radiation-induced PNET involved pediatric patients who had undergone combination treatment with methotrexate and whole-neuraxis irradiation. A supratentorial PNET was reported 12 years after irradiation for a Grade II astrocytoma.4 Multiple cases of postradiotherapy PNET were reported following initial diagnoses of pilocystic astrocytoma, ependymoma, and low-grade astrocytoma.5,6,9 This is the first reported case of PNET after radiation therapy for the treatment of craniopharyngioma.

In the past, an association was found between mutation in the K-ras protooncogene and the development of PNET, implicating the combination of methotrexate and radiation therapy.1,2,6 The current case report indicates that acute lymphocytic leukemia, lymphoma, and the combination of methotrexate and radiation therapy are not necessary for PNET development, but rather radiation alone can induce PNET. Even though radiotherapy is clearly beneficial in decreasing the recurrence rate in cases of subtotally resected craniopharyngiomas, the risks should be clearly articulated to the families and neurosurgeons before starting such treatment.10,13 In the past, WBRT and proton beam therapy were used for the treatment of craniopharyngiomas.8 In the modern era, single- or multifraction stereotactic radiosurgery would probably be employed.14

Disclosure

The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

Author contributions to the study and manuscript preparation include the following. Conception and design: Chan. Drafting the article: Chan, Herrera, Wallace. Critically revising the article: Neckrysh, Valyi-Nagy, Charbel. Reviewed final version of the manuscript and approved it for submission: Valyi-Nagy, Charbel.

References

  • 1

    Barasch ES, , Altieri D, , Decker RE, , Ahmed S, & Lin J: Primitive neuroectodermal tumor presenting as a delayed sequela to cranial irradiation and intrathecal methotrexate. Pediatr Neurol 4:375378, 1988

    • Search Google Scholar
    • Export Citation
  • 2

    Brüstle O, , Ohgaki H, , Schmitt HP, , Walter GF, , Ostertag H, & Kleihues P: Primitive neuroectodermal tumors after prophylactic central nervous system irradiation in children. Association with an activated K-ras gene. Cancer 69:23852392, 1992

    • Search Google Scholar
    • Export Citation
  • 3

    Cahan WG, , Woodard HQ, , Higinbotham NL, , Stewart FW, & Coley BL: Sarcoma arising in irradiated bone: report of eleven cases. 1948. Cancer 82:834, 1998

    • Search Google Scholar
    • Export Citation
  • 4

    Chen AY, , Lee H, , Hartman J, , Greco C, , Ryu JK, & O'Donnell R, : Secondary supratentorial primitive neuroectodermal tumor following irradiation in a patient with low-grade astrocytoma. AJNR Am J Neuroradiol 26:160162, 2005

    • Search Google Scholar
    • Export Citation
  • 5

    Enchev Y, , Ferdinandov D, , Kounin G, , Encheva E, & Bussarsky V: Radiation-induced gliomas following radiotherapy for craniopharyngiomas: a case report and review of the literature. Clin Neurol Neurosurg 111:591596, 2009

    • Search Google Scholar
    • Export Citation
  • 6

    Hader WJ, , Drovini-Zis K, & Maguire JA: Primitive neuroectodermal tumors in the central nervous system following cranial irradiation: a report of four cases. Cancer 97:10721076, 2003

    • Search Google Scholar
    • Export Citation
  • 7

    Kim DG, , Lee DY, , Paek SH, , Chi JG, , Choe G, & Jung HW: Supratentorial primitive neuroectodermal tumors in adults. J Neurooncol 60:4352, 2002

    • Search Google Scholar
    • Export Citation
  • 8

    Miralbell R, , Lomax A, , Cella L, & Schneider U: Potential reduction of the incidence of radiation-induced second cancers by using proton beams in the treatment of pediatric tumors. Int J Radiat Oncol Biol Phys 54:824829, 2002

    • Search Google Scholar
    • Export Citation
  • 9

    Pal D, , Hall G, , Loughrey C, , Shivane A, , Chakrabarty A, & Chumas P: Primitive neuroectodermal tumour arising within low grade astrocytoma: transformation, de novo or radiation induced? Report of three cases and review of literature. Br J Neurosurg 22:402408, 2008

    • Search Google Scholar
    • Export Citation
  • 10

    Pereira P, , Cerejo A, , Cruz J, & Vaz R: Intracranial aneurysm and vasculopathy after surgery and radiation therapy for craniopharyngioma: case report. Neurosurgery 50:885888, 2002

    • Search Google Scholar
    • Export Citation
  • 11

    Reddy AT, , Janss AJ, , Phillips PC, , Weiss HL, & Packer RJ: Outcome for children with supratentorial primitive neuroectodermal tumors treated with surgery, radiation, and chemotherapy. Cancer 88:21892193, 2000

    • Search Google Scholar
    • Export Citation
  • 12

    Robison LL, & Bhatia S: Late-effects among survivors of leukaemia and lymphoma during childhood and adolescence. Br J Haematol 122:345359, 2003

    • Search Google Scholar
    • Export Citation
  • 13

    Strojan P, , Popović M, & Jereb B: Secondary intracranial meningiomas after high-dose cranial irradiation: report of five cases and review of the literature. Int J Radiat Oncol Biol Phys 48:6573, 2000

    • Search Google Scholar
    • Export Citation
  • 14

    Veeravagu A, , Lee M, , Jiang B, & Chang SD: The role of radiosurgery in the treatment of craniopharyngiomas. Neurosurg Focus 28:4 E11, 2010

If the inline PDF is not rendering correctly, you can download the PDF file here.

Contributor Notes

Address correspondence to: Michael Chan, M.D., University of Illinois at Chicago, Department of Neurosurgery, 912 South Wood Street, MC799, Chicago, Illinois 60612. email: mchan7@uic.edu.
  • View in gallery

    Photomicrograph of an H & E–stained section of the initial pathological specimen demonstrating craniopharyngioma. Original magnification × 400.

  • View in gallery

    Preoperative contrast-enhanced T1-weighted MR images. Left: Axial image showing a right enhancing lesion measuring 2.5 cm in diameter. Right: Coronal view demonstrating the lack of sellar involvement.

  • View in gallery

    Photomicrographs of sections of the second specimen (PNET) obtained 8 years after radiotherapy. A: An H & E–stained section demonstrating a highly cellular neoplasm composed of cells featuring round-to-oval nuclei and scanty cytoplasm, with significant pleomorphism. B: Synaptophysin immunoreactive staining of the PNET specimen demonstrating widespread immunoreactivity of tumor cells. C: Staining for GFAP showing focal immunoreactivity. D: Results of staining with Ki 67 proliferation marker showing staining in over 30% of tumor cells in the PNET specimen. Original magnifications × 400 (A–C) and × 200 (D).

  • View in gallery

    Postoperative neuroimages. A: Noncontrast head CT obtained immediately after resection of the PNET, demonstrating no residual tumor. B: Axial contrast-enhanced T1-weighted MR image obtained 1 month postoperatively demonstrating a recurrent lesion measuring 3.5 cm in diameter. C: Axial contrast-enhanced T1-weighted MR image obtained 2 months postoperatively showing interval enlargement of the lesion, which is 5.8 cm in diameter in this image.

  • 1

    Barasch ES, , Altieri D, , Decker RE, , Ahmed S, & Lin J: Primitive neuroectodermal tumor presenting as a delayed sequela to cranial irradiation and intrathecal methotrexate. Pediatr Neurol 4:375378, 1988

    • Search Google Scholar
    • Export Citation
  • 2

    Brüstle O, , Ohgaki H, , Schmitt HP, , Walter GF, , Ostertag H, & Kleihues P: Primitive neuroectodermal tumors after prophylactic central nervous system irradiation in children. Association with an activated K-ras gene. Cancer 69:23852392, 1992

    • Search Google Scholar
    • Export Citation
  • 3

    Cahan WG, , Woodard HQ, , Higinbotham NL, , Stewart FW, & Coley BL: Sarcoma arising in irradiated bone: report of eleven cases. 1948. Cancer 82:834, 1998

    • Search Google Scholar
    • Export Citation
  • 4

    Chen AY, , Lee H, , Hartman J, , Greco C, , Ryu JK, & O'Donnell R, : Secondary supratentorial primitive neuroectodermal tumor following irradiation in a patient with low-grade astrocytoma. AJNR Am J Neuroradiol 26:160162, 2005

    • Search Google Scholar
    • Export Citation
  • 5

    Enchev Y, , Ferdinandov D, , Kounin G, , Encheva E, & Bussarsky V: Radiation-induced gliomas following radiotherapy for craniopharyngiomas: a case report and review of the literature. Clin Neurol Neurosurg 111:591596, 2009

    • Search Google Scholar
    • Export Citation
  • 6

    Hader WJ, , Drovini-Zis K, & Maguire JA: Primitive neuroectodermal tumors in the central nervous system following cranial irradiation: a report of four cases. Cancer 97:10721076, 2003

    • Search Google Scholar
    • Export Citation
  • 7

    Kim DG, , Lee DY, , Paek SH, , Chi JG, , Choe G, & Jung HW: Supratentorial primitive neuroectodermal tumors in adults. J Neurooncol 60:4352, 2002

    • Search Google Scholar
    • Export Citation
  • 8

    Miralbell R, , Lomax A, , Cella L, & Schneider U: Potential reduction of the incidence of radiation-induced second cancers by using proton beams in the treatment of pediatric tumors. Int J Radiat Oncol Biol Phys 54:824829, 2002

    • Search Google Scholar
    • Export Citation
  • 9

    Pal D, , Hall G, , Loughrey C, , Shivane A, , Chakrabarty A, & Chumas P: Primitive neuroectodermal tumour arising within low grade astrocytoma: transformation, de novo or radiation induced? Report of three cases and review of literature. Br J Neurosurg 22:402408, 2008

    • Search Google Scholar
    • Export Citation
  • 10

    Pereira P, , Cerejo A, , Cruz J, & Vaz R: Intracranial aneurysm and vasculopathy after surgery and radiation therapy for craniopharyngioma: case report. Neurosurgery 50:885888, 2002

    • Search Google Scholar
    • Export Citation
  • 11

    Reddy AT, , Janss AJ, , Phillips PC, , Weiss HL, & Packer RJ: Outcome for children with supratentorial primitive neuroectodermal tumors treated with surgery, radiation, and chemotherapy. Cancer 88:21892193, 2000

    • Search Google Scholar
    • Export Citation
  • 12

    Robison LL, & Bhatia S: Late-effects among survivors of leukaemia and lymphoma during childhood and adolescence. Br J Haematol 122:345359, 2003

    • Search Google Scholar
    • Export Citation
  • 13

    Strojan P, , Popović M, & Jereb B: Secondary intracranial meningiomas after high-dose cranial irradiation: report of five cases and review of the literature. Int J Radiat Oncol Biol Phys 48:6573, 2000

    • Search Google Scholar
    • Export Citation
  • 14

    Veeravagu A, , Lee M, , Jiang B, & Chang SD: The role of radiosurgery in the treatment of craniopharyngiomas. Neurosurg Focus 28:4 E11, 2010

Metrics

All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 148 77 1
PDF Downloads 108 22 0
EPUB Downloads 0 0 0