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Bilateral Orbital Peripheral Primitive Neuroectodermal Tumor: A Case Report
Ahmad Razif Omar1*, Khairy Shamel Sonny Teo1, Ariffin Nasir2, Nur Asyilla Che Jalil3, Chandran Nadarajan4 and Mohtar Ibrahim1
1Department of Ophthalmology, Universiti Sains Malaysia, Malaysia
2Department of Paediatric, Universiti Sains Malaysia, Malaysia
3 Department of Pathology, Universiti Sains Malaysia, Malaysia
4 Department of Radiology, Universiti Sains Malaysia, Malaysia
Submission: July 13, 2018; Published: August 08, 2018
*Corresponding author: Ahmad Razif Omar, Department of Ophthalmology, School of Medical Sciences, Health Campus, Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan, Malaysia.
How to cite this article: Ahmad Razif O, Khairy S S T, Ariffin N, Nur Asyilla C J, Chandran N, et al. Bilateral Orbital Peripheral Primitive Neuroectodermal
Tumor: A Case Report. JOJ Ophthal. 2018; 6(5): 555700. DOI: 10.19080/JOJO.2018.06.555700
Peripheral primitive neuroectodermal tumors (pPNETs) are a group of small round-cell, neuroectodermal origin soft tissue tumors that arises outside the central or sympathetic nervous system. The definite diagnosis of pPNET is based on immunohistochemical examination. pPNET arising from the orbital region is very rare. To date, only unilateral cases of orbital pPNET have been reported. Herein, we present a unique case of bilateral orbital pPNET in 2-year old boy as an additional report to this rare disease.
Keywords: Peripheral primitive neuroectodermal tumour; Orbital pPNET; Childhood proptosis
Primitive neuroectodermal tumor (PNET) is a highly malignant tumor arising from cells that are believed to be retained from fetal brain development . Therefore, most PNETs occur in the central nervous system (CNS). However, PNETs that occur outside of CNS are recognized as peripheral primitive neuroectodermal tumors [1,2]. Imaging and histopathological examination (HPE) such as light microscopy, immunohistochemistry (IHC) and cytogenetic features are helpful in recognizing pPNET [3,4]. Histologically, PNET is a small round blue cells tumor with highly cellular pattern, hyperchromatic nuclei and scanty cytoplasm [1,4,5]. IHC analyses has been helpful in distinguishing PNETs
from other small, round, poorly differentiated tumors, such as rhabdomyosarcoma, neuroblastoma, and lymphoma [2,4,5]. pPNET has no gender predilection. It can occur in any age group but most commonly affects adolescents and young adults [1,3,6]. To the best of our knowledge, so far only 19 cases of orbital pPNET have been reported in literature worldwide. All the 19 reported cases have been unilateral presentation of the disease [1,7-10]. Apart from extremely rare disease, our case is unique because the pPNET arises from bilateral orbit with involvement of extradural site in the bilateral fronto-parietal region and extra-axial calvarial soft tissue.
A previously healthy 2-year-old boy was admitted for 3-week
history of persistent high-grade fever, poor oral intake and
lethargy. He also had bilateral lid swelling and redness. There
was no other ocular symptom, chills, rigors, limb weakness
and seizures. Systemic review was unremarkable. Initial
eye assessment showed bilateral swollen and erythematous
eyelids. Extraocular muscle movement was normal with no eye
deviations, proptosis or ptosis.
Within a week of hospitalisation, he rapidly developed severe
proptosis in both eyes with lagophthalmos, conjunctival chemosis
and prolapse (Figure 1). Extraocular muscle movement was
almost completely restricted at this time. RAPD was equivocal
and both pupils were mid-dilated with sluggish pupillary light
response. There was presence of exposure keratopathy in both
eyes and intraocular pressures were above 30mmHg bilaterally.
Posterior segment examination bilaterally revealed choroidal
folds and hyperaemic discs. Prompt treatment was initiated to
reduce the IOP and control the exposure keratopathy.
Urgent magnetic resonance imaging (MRI) of brain and
orbit was performed (Figure 2). The MRI showed multiple
lobulated soft tissue masses in both orbits causing displacement
of the extraocular muscles and optic nerves. The lesions caused
expansion of the orbital cavity, significant periorbital swelling
and marked proptosis. It was also associated with bifrontoparietal
extradural collection, multifocal lobulated extra-axial
calvarial soft tissue lesions as well as erosions of the orbital and
calvarial bones adjacent to the masses.
He underwent urgent bilateral craniotomy and orbitotomy
for tissue biopsy. Intraoperatively, there was extradural
hemorrhagic fluid in multiple pockets, extensive tissue
granulation with sclerosis, caseous material and erosion of the
overlying bone. Subdural region and the brain parenchymal
were found to be normal. HPE results from a tissue biopsy
demonstrated the tumour cells as undifferentiated small round
blue cells arranged in diffuse pattern. The cells had oval to
round, deeply basophilic nuclei and inconspicuous nucleoli.
The cytoplasm was scanty and indistinct with nuclear molding.
Mitoses were abundant and clearly seen. The cells were positive
for Synaptophysin, Chromogranin, CD99 and negative for
Leucocyte Common Antigen (LCA), Desmin, CKAE1&AE3 and
GFAP. The diagnosis of pPNET was made based on these IHC
findings and cytogenic analysis (Figure 3).
He was treated using modified Memorial Sloan Kettering
Cancer Centre (MSKCC) chemotherapy protocol for PNET
consisting of Cyclophosphamide, Adriamycin and Vincristine
and Ifosphamide and Etoposide. There was significant clinical
improvement after 3 cycles of chemotherapy. Exposure
keratopathy resolved and IOPs were normal. Repeated
radiological studies showed good response to chemotherapy.
Bilateral intraorbital masses were no longer visualized and their
contents showed normal signal intensities with no proptosis
(Figure 2). He received another 3 cycles of chemotherapy
and went into remission after the 6 cycles were completed.
He was followed up regularly for another 10 months during
which time there was no evidence of recurrence clinically and
radiographically. Unfortunately, he defaulted subsequent imaging
and oncology appointments due to social and logistic reasons.
He succumbed to his illness as a result of intracranial extension
and lung metastasis 5 months after his last appointment.
Primitive neuroectodermal tumors (PNETs) are a highly
malignant tumors arising from neuroepithelial stem cell that
have not differentiated in a similar manner as a normal neuron
and they appear as primitive cell. PNETs are believed to be
retained from fetal brain development [1,7]. It is classified into
two types based on its location; PNET and pPNET. Most PNETs
occur in the brain and central nervous system (CNS) due to its
embryological origin. However, PNETs that occur outside of CNS
are recognized as peripheral primitive neuroectodermal tumors
PNETs usually affect adolescents and young adults and
represent approximately 4% of all pediatric soft tissue tumors
and have no sex predilection [1,2,5]. An orbital pPNETs tend to
occur in younger patients when compared with other pPNETs.
Only 4 out of the 19 published cases were older than 13 years
at the time of diagnosis [1,7,8,10]. To the best of the authors’
knowledge there were only 19 cases of orbital pPNET reported
in the literature to date. None of the previous reported cases had
bilateral eye involvement.
We report the only case of bilateral orbital pPNET with an
extensive involvement of adjacent sites including extradural site
in bifronto-parietal region and extra-axial calvarial soft tissue
because of the highly metastatic feature and rapid growth of
the pPNET tissue. There was also evidence of erosions in the
orbital and calvarial bones adjacent to the soft tissue masses on
radiological imaging. Besides that, an expansion of intraorbital
pPNET mass retro-orbitally leads to displacement or proptosis
of the globe [6,11].
Histopathologically, PNET demonstrates small round cells
which have a highly cellular pattern with hyperchromatic
nuclei and scanty cytoplasm [1,3-5]. PNET is also capable of
demonstrating varying grades of neural differentiation. Homer-
Wright rosettes can be seen in certain cases . Differential
diagnoses of small round blue cells tumor in children include
lymphoma, rhabdomyosarcoma, extra-adrenal neuroblastoma
and metastatic nephroblastoma . Immunohistochemical
and cytogenetic studies help in the diagnosis confirmation of
PNET. In this case, the diagnosis of pPNET was establised in
view of IHC staining showed positivity towards synaptophysin,
chromogranin, CD99 and negativity towards LCA, Desmin,
S100 and GFAP [1,3-5,12]. PNET staging is done by radiological
imaging of the brain and spinal column as well as spinal fluid
Therapeutic strategy in PNET could be surgery,
chemotherapy, chemoradiotherapy or combination [1,3,5]. The
modality of treatment depends on the staging, type, site and size
of tumour, extent of metastasis as well as the age and general
health status of the patient [5,8]. Surgery was performed as the
initial treatment for orbital pPNET in most reported cases [1,5,8].
However, complete surgical removal of the tumor is difficult.
Treatment option for young children is chemotherapy alone, as
radiation may interfere with their development . The patient was treated well with MSKCC chemotherapy protocol for PNET
using Cyclophosphamide, Adriamycin, Vincristine, Ifosfamide,
Etoposide regime. This chemotherapy protocol had been used in
latest orbital pPNET cases published and showed a good result
Orbital pPNET is extremely rare entity and this is the only
case of bilateral orbital pPNET to have been reported thus far
in medical literature [1,7-9]. Clinical diagnosis in this case was
challenging due to vague presentation. The definitive diagnosis
was reached with the IHC studies supported by the modalities of
imaging and HPE . Chemotherapy modality is considered as
the best treatment option with the good result in this case.
Written informed consent was obtained from the patient for
publication of this case report and any accompanying images. A
copy of the written consent is available for review by the Editorin-
Chief of this journal.