Volume 2, Issue 1 , Pages 40-42, March 2007
Primitive neuroectodermal tumor presenting as a neck mass
Article Outline
Summary
Primitive neuroectodermal tumors (PNET) comprise a family of the small blue round cell tumors. These neural crest origin tumors affect central nervous system (CNS) or peripheral tissues and are characterized by the set of unique chromosomal translocations and MIC-2 antigenic expression. PNET of the CNS are the most common malignant nervous system tumors of childhood. Reports of the peripheral PNET, which can present in the head and neck region are extremely limited. We present a case of the pediatric peripheral primitive neuroectodermal tumor manifested as an acute onset of neck swelling and ascending flaccid paralysis after routine first year immunizations.
Keywords: Primitive neuroectodermal tumor (PNET), CNS tumors, Small blue round cell tumors, Ewing's sarcoma, Ewing's sarcoma/PNET
1. Introduction
Primitive neuroectodermal tumors (PNET) are the most common malignant central nervous system (CNS) tumors of childhood. First recognized by Arthur Purdy Stout in 1918, they are the products of neoplastic transformation of primitive neuroepithelial cells [1]. Histologically PNET comprise a family of small blue round cell tumors, united by their neuroectodermal origin and unique antigenic expression of the MIC-2 gene. Peripherally located tumors carry a variable degree of the Ewing's sarcoma features and are called Ewing's sarcoma/PNET [1]. Intraspinal tumors can present as a neck mass. Although, reports of primary intraspinal PNET are very limited and head and neck manifestations are sparsely described in the literature, they may be the earliest manifestations of the tumor [2].
2. Patient synopsis
A thirteen month old boy was hospitalized with a 10 day history of intermittent fevers, left neck swelling, and generalized muscular weakness which started a day after routine 1 year immunizations, and did not improve after a week course of amoxicillin clavulanate potassium. Within 24
h of admission, the patient developed bilateral flaccid ascending paralysis and was intubated for respiratory distress. A diagnosis of Acute Inflammatory Demyelinating Polyneuropathy (Guilian-Barre Syndrome) with reactive neck lymphadenopathy was entertained and intravenous steroids and intravenous immune globulin were initiated.
The otolaryngology service was consulted and physical examination revealed a febrile patient with no active mobility below the neck and absent deep tendon reflexes. An isolated left Level II, 2cm firm, multinodular mass fixed to the deep structures was palpated in the neck. Fine needle aspiration revealed atypical lymphocytes and reactive hystiocytes.
Magnetic resonance imaging (MRI) with gadolinium demonstrated an extra-medullary anterior cervical spine mass with heterogeneous peripheral enhancement extending intraspinally from Level C2 to C6 compressing the spinal cord, and expanding bilaterally through the intervertebral foramina to the lateral neck (Fig. 1).
Fig. 1.
T1 coronal magnetic resonance image demonstrated intraspinal tumor extending into the soft tissue of the lateral neck.
Intraoperative incisional biopsy was performed after informed consent was obtained from the mother, and revealed a pale, rubbery mass with extension into the deep tissues. Frozen section depicted a small blue cell tumor. Final histopathologic examination demonstrated a malignant small cell neoplasm, consistent with primitive neuroectodermal tumor demonstrating strong membrane staining for CD99 and positive vimentin staining, but no reactivity for CD43, CD45, desmin, myogenin, synaptophysin, LCA, CD3, CD20, CD30, EMA, NSE, SFP, HHF 35, and S100. The staining profile strongly supported the diagnosis of Ewing's sarcoma/PNET (Fig. 2).
Fig. 2.
(A) Microscopic examination demonstrating a monomorphic sheet of undifferentiated small, blue, round cells with increased mitotic index and increased nuclear-cytoplasmic ratio. (B) Positive CD99 staining. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of the article.)
The child was treated with chemotherapy consisting of: doxorubicin hydrochloride, cyclophophomide, vincristine, mesna (sodium 2-mercaptoethane sulfonate), high dose intravenous steroids, and radiation therapy. Persistent bradycardia required continuous cardiodynamic support. Twelve weeks after initial presentation, the child developed right lung pneumonia complicated by Gram negative sepsis and experienced a cardiac arrest. Autopsy revealed a 4cm×2cm necrotic mass in the anterior cervical spine infiltrating the peripheral nerves, leptomeninges, and blood vessels. Postmorten histochemical evaluation confirmed the diagnosis of Ewing's sarcoma/PNET.
3. Discussion
Primitive neuroectodermal tumor describes a group of malignant embryonal neoplasms of neural crest origin with a variable degree of differentiation [3], [4]. PNET are subdivided into CNS and peripheral neoplasms. PNET of the CNS are the most common malignant brain tumors of childhood, comprising 20–25% of pediatric CNS tumors and include medulloblastoma, supratentorial PNET, ependymoblastoma, medulloepithelioblastoma, and atypical teratoid/rhabdoid tumor (ATRT) [3]. PNET of the periphery are represented by the tumors of Ewing's sarcoma/primitive neuroectodermal tumor family, previously known as peripheral neuroepithelioma. This tumor family demonstrates specific gene rearrangements between the EWS promotor gene on chromosome 22q12 and the ETS oncogene family on chromosome 11q24, as well as expression of the MIC2 gene products on the cellular membrane [3].
No pathognomonic signs or symptoms of the tumor exist. Intracranial PNET show signs and symptoms of increased intracranial pressure [3]. Spinal tumors can cause interruption of spinal impulse conduction and may present as a neck mass with occasional systemic findings, including fever, elevated erythrocyte sedimentation rate, anemia, and leukocytosis [5]. PNET are highly malignant both histologically and clinically, and frequently metastasize via direct dissemination. MRI is the preferential imaging technique. The typical tumor is a heterogeneously enhancing mass with ill-defined margins.
Definitive diagnosis relies on the histopathologic examination. The prevalent histologic pattern is a monomorphic sheet of undifferentiated small, blue, round cells with increased mitotic index and increased nuclear-cytoplasmic ratio. Ewing sarcoma and PNET are viewed as a spectrum of the same malignancy, differing in their degree of neural differentiation, where PNET are a more differentiated form [5]. Formation of Homer-Wright rosettes is an indication of neuronal differentiation but is not essential for diagnosis. Immunohistochemical detection of antigenic products of the MIC-2 gene, such as p30/32 cell surface glycoprotein-CD99, 12E7, E2, 013, and HBA71, suggests a PNET diagnosis. The reactivity to vimentin, NSE, and S100 may support the diagnosis but is not pathognomonic [4]. Ninety-five percent of Ewing sarcoma/PNET share the same chromosomal translocation (t[11;22][q24;q12]) which can be detected by the reverse transcriptase-polymerase chain reaction [4].
The optimal therapy for PNET is uncertain. Chemotherapy and surgical excision with or without radiation have been used. Immunotherapy specific for PNET is currently under investigation. Despite improvement in the chemotherapeutic modalities and investigational studies, prognosis is very poor with an average survival of less than 2 years [5].
PNET are common CNS tumors of childhood. They may present with otolaryngologic manifestations such as a neck mass. A high level of clinical suspicion, early identification, and prompt intervention are crucial in enhancing survival and preventing permanent neurologic damage.
References
- Primitive neuroectodermal tumor (PNET) of the kidney: a case report. BMC Cancer. 2004;4:3
- Primary intramedullary primitive neuroectodermal tumor of the cervical spinal cord. J. Neurosurg. Spine. 2006;4(6):497–502
- S. Ghosh, D. Jichici, Primitive neuroectodermal tumors of the central nervous system, eMedicine, 22 March 2005.
- . Primitive neuroectodermal tumor of the gallbladder. Arch. Pathol. Lab. Med. 2004;128:571–573
- . Primary intraspinal primitive neuroectodermal tumor (PNET): a rare occurrence. Neurol. India. 2002;50(1):75–80
PII: S1871-4048(06)00106-7
doi:10.1016/j.pedex.2006.12.002
© 2007 Elsevier Ireland Ltd. All rights reserved.
Volume 2, Issue 1 , Pages 40-42, March 2007
