Case Report
Primary intracranial peripheral PNET” A case report and review Kiranchand Velivela, Alugolu Rajesh, Megha Shantveer Uppin1, Anirrudh Kumar Purohit Departments of Neurosurgery and 1Pathology, Nizam’s Institute of Medical Sciences, Punjagutta, Hyderabad, Telangana, India
Abstract Address for correspondence: Dr. Alugolu Rajesh, Department of Neurosurgery, Nizam’s Institute of Medical Sciences, Punjagutta, Hyderabad-500 082, Telangana, India. E-mail:
[email protected] Received : 08‑09‑2014 Review completed : 03‑10‑2014 Accepted : 05‑12‑2014
The site of origin of primitive neuroectodermal tumors (PNETs) is quite varied and has significant influence on the prognosis. We report a case of intracranial peripheral PNET/ Ewing’s sarcoma arising from the superior tentorial surface in a 13‑year‑old girl. Gross total excision of the tumor was done. We have discussed the distinction between central nervous system PNET (CNS PNET) and Intracranial Peripheral PNET (pPNET/ES) as their treatment and prognosis varies radically. A review of literature shows that prognosis is better in intracranial pPNET/ES. Key words: CD 99, central nervous system PNET, intracranial, peripheral PNET (pPNET/
ES), tentorium
Introduction Primitive neuroectodermal tumors (PNET) of the central nervous system (CNS) are a heterogeneous group of embryonal tumors that occur predominantly in children and adolescents and show aggressive clinical behavior.[1,2] They may arise in the cerebral hemispheres, brain stem, or spinal cord.[1] PNETs arising outside the CNS are grouped into peripheral PNET/Ewing’s sarcoma family of tumors (pPNET/ES). They can occur in both osseous and extraosseous tissues, including intracranial (extraparenchymal), showing characteristic translocation t(11;22) (q24;q12).[3] A 13‑year‑old girl presented with occipital headache of 3 months duration, which increased with coughing and was associated with blurred vision. Neurologic examination revealed normal visual acuity, loss of color vision and bilateral papilledema. Magnetic resonance imaging (MRI) demonstrated a solid‑cystic lesion in
the left temporoparietal and occipital regions attached to tentorium. The solid component was isointense on both T1W and T2W and enhanced on Gd‑enhanced T1W images. There was mass effect over the midbrain and ipsilateral temporal and occipital horns with midline shift. Perilesional edema was minimal [Figure 1a‑f]. With the patient in prone position supported with horseshoe headrest, occipito‑temporo‑parietal
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Figure 1: MRI T2W imaging (a) axial, (b) sagittal and (c) coronal showing lesion in the left temporoparietal and occipital regions, attached to the tentorium which is heterogenous with cystic component and causing mass effect over the midbrain. MRI contrast scans (d) axial, (e) sagittal and (f) coronal show heterogenous enhancement of the lesion
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craniotomy was performed. The tumor was attached to the tentorium and was grayish white, firm and moderately vascular with well‑defined plane of cleavage from the surrounding brain parenchyma. Cysts were noted medially and laterally which were dissected along the plane of cleavage. Gross total excision of the tumor was done. The tumor was found to be attached to the tentorium. Postoperative period was uneventful. Postoperative MRI revealed no residual tumor [Figure 2a‑f]. Bone scan performed in the postoperative period was negative for any hotspots. Postoperatively the patient received local radiotherapy (50 Gy in 25 fractions over 30 days to the tumor bed) and was doing well with no evidence of disease after 24 months. Chemotherapy was not given as the parents did not give consent for chemotherapy. Microscopically the tumor showed small round blue cells with oval to elongated nuclei having vesicular chromatin [Figure 3a and b]. There was no evidence of neuroblastic differentiation with rosettes/necrosis/
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Figure 2: Postoperative MRI T2W imaging (a) axial, (b) sagittal and (c) coronal showing gliotic changes with enlargement of left occipital horn and no residual tumor. MRI contrast scan (d) axial, (e) sagittal and (f) coronal shows no tumor suggesting gross total excision of tumor
calcification. Immunohistochemical examination demonstrated CD99 and NSE positivity in tumor cells [Figure 3c]. Immunohistochemistry with CD34, GFAP, EMA, Synaptophysin was negative and INI‑1 expression was retained. Fluorescence in situ hybridization with a EWSR1 break apart probe (Vysis, Abbott diagnostics) showed > 15% of split signals confirming the diagnosis of pPNET [Figure 3d]. CNS and peripheral PNETs though cannot be distinguished on morphology have distinct genetic features [Table 1]. The MIC2 gene product (CD99), although expressed in nearly all pPNET,[7] is not specific and can also be detected in other small, blue round cell tumors like rhabdomyosarcoma, desmoplastic small round cell tumor, lymphoblastic lymphomas. However, the pattern of staining is often cytoplasmic, rather than the distinct membranous staining typical of pPNET. Central PNETs are reported to be negative for CD99 staining. Cytogenetic and molecular biologic characterization of ES/pPNET has revealed a consistent chromosomal
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Figure 3: (a) The cells lining the leptomeninges. (b) The cells are small round with vesicular nuclei H and E x400. (c) Immunohistochemical positivity for CD 99. HRP Polymer CD 99; 400. (d) FISH with EWS-FLI break apart probe showing the positive breakapart signals. (Arrowheads)
Table 1: Differences between cPNET and pPNET Location MR imaging
CD 99 Molecular abnormalities Radiotherapy Chemotherapy
CNS PNET
pPNET
Supratentorial Intra‑axial
Supra/infratentorial Extra‑axial (but larger lesions may obscure distinction between an intra‑axial or extra‑axial lesion) Lobulated, usually dura‑based, heterogeneous on T1 and T2 and heterogeneous intense enhancement.[4] Usually no dissemination Positive Chromosomal translocation‑t (11;22) (q24;q12) in most cases Variant translocations‑t(21;22), t(7;22), and t(17;22) Local radiotherapy Alternating cycles of cyclophosphamide, doxorubicin, vincristine and ifosfamide, etoposide[6]
T1 hypo, T2 heterogeneous lesions with calcification (50‑70%) and heterogeneous enhancement May have leptomeningeal dissemination Negative Non‑random cytogenetic gains and losses No 17q abnormalities Local and craniospinal irradiation Cisplatin, lomustine, and vincristine (or) alternating courses of cisplatin/etoposide and cyclophosphamide/vincristine[5]
CNS PNET - Central nervous system primitive neuroectodermal tumors, pPNET - Intracranial peripheral primitive neuroectodermal tumors
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translocation t(11;22) (q24;q12) found in up to 90‑95% of all cases, resulting in a chimeric fusion of the EWS gene on the long arm of chromosome 22 and the human homolog of the FLI1 gene on the long arm
of chromosome 11.[8,9] Variant translocations include t(21;22), t(7;22), and t(17;22), all of which involve the EWS gene on 22q12.[7] It is important to differentiate pPNET/ES from central PNETs because the treatment
Table 2: Reported cases of intracranial peripheral PNET
Case Author (year) no
Age/sex Symptoms and signs
Location
Molecular Treatment diagnosis
1
Jay et al., 1996
4/M
NA
Cerebellum
+
2
Papotti et al., 1998
30/F
Headache, vertigo
Rt frontal duramater
+
3
Katayama et al., 1999
5/M
Tentorium
ND
4
Antunes et al., 2001
6/M
Vomiting, left abducent nerve palsy Lethargy, vomiting
Lt frontal duramater
+
5
Kalmarides et al., 2001
34/F
Lt CP angle
ND
6
Niwa et al., 2001
Frontal duramater
ND
Gross total excision
Patient expired on 8th postoperative day
7
Simmons et al., 2001
Rt CP angle
ND
Biopsy done Radiotherapy
Expired 13 months after surgery
8
Elias et al., 2002
Cavernous sinus
NA
Transsphenoidal debulking Radiotherapy and chemotherapy
9
Dedeurwaerdere et al., 2002
Diagnosed to have Ewing’s sarcoma of distal left fibula 2 months later with multiple metastases involving spine, ribs and extremities No evidence of disease at 12 months No evidence of disease at 8 years
10
Vertigo, pulsatile tinnitus, gait disturbance, Rt nystagmus 5 months/F Exophthalmos, bloody nasal discharge 67/F Rt facial pain, Rt sided hearing loss, slurred speech 27/M Left retro orbital headache and 3rd nerve paresis
17/M
Headache
12/M
11
Utsunomiya et al., 2004
7/M
12
D’Antonio et al., 2004
50/F
13
Bunyaratavej et al., 2005
17/M
Headache, Lt neck, arm, chest paresthesias Headache, vomiting, Rt abducent nerve palsy Headache, vomiting, drowsiness Raised ICP
17/M
Raised ICP
46/M
Headache, nausea, vomiting, Right ophthalmoplegia, Rt ptosis and PL positive in Rt eye
14 15
Idrees et al., 2005
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Rt frontal duramater with delayed contralateral CP angle recurrence Rt frontal duramater Frontal duramater
Rt parieto‑ temporal duramater Rt fronto parietal region Lt temporal region Rt cavernous sinus
+
+
ND
Gross total excision Chemotherapy, Radiotherapy Gross total excision Radiation and chemotherapy given after local recurrence Gross total excision Radiotherapy and intrathecal chemotherapy Gross total excision Radiotherapy and chemotherapy Sub‑total excision Radiotherapy
Follow up
Gross total excision Local radiotherapy (Sub‑total excision of CP angle recurrence followed by chemotherapy and craniospinal radiation) Gross total excision Chemotherapy and craniospinal Radiotherapy Gross total excision Radiotherapy and chemotherapy
+
Gross total excision
ND
Gross total excision
ND
Gross total excision
_
Tumor biopsy Chemotherapy and radiotherapy
NA
Disease free for 7 years Died 10 years after diagnosis due to metastatic disease Disease free follow up of 7 years NA
Follow up after 1 year showed no recurrence
No evidence of disease at 27 months No evidence of disease 2 years after surgery
No evidence of disease 12 months after surgery No evidence of disease at 12 months No evidence of disease at 24 months NA
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Table 2: Contd....
Case Author (year) no
Age/sex Symptoms and signs
Location
Molecular Treatment diagnosis
16
Khusen et al., 2005
13/F
Orbital apex syndrome
Rt cavernous sinus
ND
17
Mazur et al., 2005
8/F
Headache, Rt tentorium nausea, vomiting
+
7/F
Headache, vomiting
Rt frontal lobe
+
Headache, Lt III, V1, V2 and VI cranial nerve involvement Headache, diplopia, Lt partial homonymous hemianopia
Lt cavernous sinus
+
Rt occipital parafalcine region
+
Partial resection Chemotherapy and radiotherapy
Bifrontal tumor extending on both sides of falx cerebri Rt tentorium extending into both supratentorial and infratentorial compartments Rt frontal falcine
+
Gross total excision Chemotherapy and radiotherapy
+
Incomplete excision Chemotherapy and radiotherapy
No evidence of disease 12 months after diagnosis
NA
Gross total excision Radiotherapy and chemotherapy Open biopsy Chemotherapy and radiotherapy
No evidence of disease after 20 years
18
19
Atabib et al., 2006
48/F
20
Mobley et al., 2006
21/M
21
Kazmi et al., 2007
7/F
Headache
22
Navarro et al., 2007
3/M
Acute onset headache, vomiting
23
Asano et al., 2007
24
Kobayashi et al., 2008
10/M
Rt lower cranial nerve palsies
Rt jugular foramen
25
Furuno et al., 2008
15/M
Headache
26
Bano S et al., 2009
11/F
Rt fronto temporal region Anterior falx
27
dos Santos Rubio et al., 2010
10/F
Midline frontal scalp swelling, headache, giddiness, epiphora, diplopia Headache, Lt CP angle vomiting, diplopia Lt V, VI, VII, VIII and XI cranial nerve involvement
21 months/ Raised ICP M
+
ND
+
+
Tumor biopsy Radiotherapy and chemotherapy
Follow up
Partial excision Radiation and chemotherapy Extent of resection not mentioned Radiotherapy and chemotherapy Tumor debulking Radiotherapy and chemotherapy
Metastatic workup detected mass at thyroid. Underwent total thyroidectomy and ERT to thyroid bed and mediastinum. Hip metastasis at 16 months. Died at 18 months No evidence of disease at 2 years NA
Residual tumor at 14 months postsurgery without neurological deficits Imaging at 18 months postsurgery detected intracranial disease and metastasis to multiple cervical and thoracic vertebrae 21 months‑ Chemotherapy and craniospinal radiation Received 48 weeks of systemic chemotherapy
Gross total excision Radiotherapy and chemotherapy Sub‑total excision
MRI showed complete remission of lesion 12 months after diagnosis No evidence of disease 6 months after diagnosis NA
Incomplete resection Chemotherapy and radiotherapy
Patient doing well 6 months after diagnosis
Contd.....
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Table 2: Contd....
Case Author (year) no
Age/sex Symptoms and signs
28
Antonelli et al., 2011
37/M
Presented in comatose state after 2 weeks of headache
29
Burkhardt et al., 2011
16/M
Rt brachiofacial hemisyndrome
30
Choudhury et al., 2011
11/F
31
Patibandla MR et al., 2011
32
Tanboon et al., 2012
Headache, vomiting, Lt temporal scalp swelling, 11 months/F Proptosis and Rt 6th nerve palsy 22/F
Rt frontal skull mass, Raised ICP
Location
Molecular Treatment diagnosis
Follow up
Rt fronto temporal dura with recurrence at temporal region after 1 year Lt frontoparietal bleed
+
Gross total excision Complete excision of recurrence Radiotherapy
Patient doing well 17 months after 1st surgery
_
No evidence of disease 3 months after surgery
Lt temporo‑ parietal
+
Gross total excision Radiotherapy and chemotherapy NA
Rt cavernous sinus
+
Rt frontal duramater
+
Debulking done One cycle of chemotherapy Gross total excision
NA
Patient died on postoperative day 37 Patient developed multiple intracranial metastases at 2 months and died 6 months after initial operation
NA - Not available, ND - Not done, + - Positive,− - Negative, CP angle - Cerebellopontine angle, PNET - Primitive neuroectodermal tumors, ICP – Intracranial pressure
and prognosis are radically different. The 5‑year progression‑free and overall survival in supratentorial PNETs is 37% and 53%.[10] In contrast, many patients with pPNETs as reported in literature achieved long‑term disease‑free survival [Table 2]. Long‑term disease‑free survival could be achieved with aggressive surgical resection, local radiotherapy and chemotherapy in primary intracranial pPNET/ES.
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5. Greenberg HS, Chamberlain MC, Glantz MJ, Wang S. Adult medulloblastoma: Multiagent chemotherapy. Neuro Oncol 2001;3:29‑34. 6. Womer RB, West DC, Krailo MD, Dickman PS, Pawel BR, Grier HE, et al. Randomized controlled trial of interval‑compressed chemotherapy for the treatment of localized Ewing sarcoma: A report from the Children’s Oncology Group. J Clin Oncol 2012;30:4148‑54. 7. Hasegawa SL, Davison JM, Rutten A, Fletcher JA, Fletcher CD. Primary cutaneous Ewing’s sarcoma: Immunophenotypicand molecular cytogenetic evaluation of five cases. Am J Surg Pathol 1998;22:310‑8. 8. Delattre O, Zucman J, Melot T, Garau XS, Zucker JM, Lenoir GM, et al. The Ewing family of tumors‑A subgroup of small‑round‑cell tumors defined by specific chimeric transcripts. N Engl J Med 1994;331:294‑9. 9. Sandberg AA, Bridge JA. Updates on cytogenetics and molecular genetics of bone and soft tissue tumors: Ewing sarcoma and peripheral primitive neuroectodermal tumors. Cancer Genet Cytogenet 2000;123:1‑26. 10. 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 2000;88:2189‑93. How to cite this article: Velivela K, Rajesh A, Uppin MS, Purohit AK. Primary intracranial peripheral PNET" - A case report and review. Neurol India 2014;62:669-73. Source of Support: Nil, Conflict of Interest: None declared.
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