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Primitive neuroectodermal tumor of the mandible: Report of a rare case. (Original Article).


We describe what we believe is only the second reported case of primitive neuroectodermal tumor of the mandible. Our patient was successfully treated initially with surgery and adjuvant radiation and chemotherapy, but 18 months later she developed a fatal pulmonary metastasis. Although this tumor is aggressive and prone to recurrence and metastasis, early intervention might improve the prognosis in affected patients. In patients with unresectable disease, radiation and chemotherapy might have palliative value.


Peripheral primitive neuroectodermal tumors (PNETs) are rare. They presumably originate in the neural crest, and they occur primarily in the chest, pelvis, and retroperitoneum; in rare cases, they occur in the head and neck area. (1-7) In this article, we describe a rare case of PNET of the mandible. To the best of our knowledge, only one other report of a PNET involving the mandible has been published in the literature. (3)

Case report

A 38-year-old woman initially sought medical attention from her dentist for hypoesthesia and pain in the area of the mental nerve distribution. Despite the extraction of multiple teeth from the right posterior mandibular quadrant, she continued to experience pain and swelling. Her dentist diagnosed her symptoms as acute osteomyelitis, and she was placed on an antibiotic. Six months after the onset of her initial symptoms, the patient developed purulent drainage, and she was referred to an oral surgeon. At this point, she had right mandibular swelling with a limited incisal opening and numbness in the V3 distribution. Her medical history was remarkable for neurofibromatosis.

An x-ray revealed that the right mandible had a "moth-eaten" appearance that extended from the subcondylar area on the right to the symphyseal area on the left; obliteration of the right inferior alveolar canal was also evident (figure 1). Computed tomography (CT) demonstrated significant bone loss in the right mandible (figure 2).

A presumptive diagnosis of osteomyelitis was made, and the patient was taken to the operating room for debridement or resection of the involved bone. Intraoperatively, however, the surgeon discovered a mass that involved the masseter and the lateral pterygoid muscles; the surgeon also noted that the bone had an eroded appearance. Analysis of an intraoperatively obtained frozen section revealed that the mass was a poorly differentiated carcinoma. A segmental resection of the mandible was performed, and the mandible was stabilized with a titanium hollow-screw osseointegrating reconstruction plate. The final pathology findings were consistent with a PNET (figure 3), and the patient was referred to an otolaryngologist (J.M.B.).

Magnetic resonance imaging of the head and neck demonstrated obliteration of the tissue planes that separate the masseter muscle and the medial and lateral pterygoid muscles. The presence of artifact from the mandibular reconstruction plate made it difficult to assess the cranial extent of muscle involvement, but the floor of the middle cranial fossa appeared to be intact. No adenopathy was noted. CT of the chest did not detect any definitive evidence of metastatic disease.

The otolaryngology service performed a tracheostomy and en bloc resection of the right infratemporal fossa, the facial nerve, and the mandible from the right condyle to the left parasymphysis (figure 4). Selective neck dissection at levels I, H, and HI was also performed. Subsequently, a plastic and reconstructive surgeon (M.J.S.) created a free osteocutaneous fibula flap to reconstruct the mandible and grafted the great auricular nerve to the facial nerve branches (figure 5).

Postoperatively, the patient underwent chemotherapy with six cycles of etoposide (VP- 16) and ifosfamide. Palliative external-beam irradiation was directed to the L5 and S1 vertebral bodies. When the patient continued to complain of back pain, she underwent a bone scan, which detected an abnormal uptake in the left hip and in the T6 and L1-2 spine, suggesting skeletal metastases. A consultation with a radiation oncologist was obtained.

Frozen-section analyses of a lymph node specimen and a perimandibular soft-tissue specimen confirmed that the tumor was a poorly differentiated carcinoma. Immunohistochemical tests were positive for neuron-specific enolase, immunoreactive neurofilaments, CD57 (Leu-7), and synaptophysin. Conversely, tests were negative for AE1/AE3 monoclonal antibody, desmin, CD99 (MIC), chromogranin, CAM 5.2, S-100 protein, glial fibrillary acidic protein, immunoreactive calcitonin, immunoreactive parathyroid hormone, and epithelial membrane antigen.

Electron microscopy of the tumor identified clusters of three or four small, round to slightly elongated cells that were separated by collagen-rich connective tissue. The individual tumor cells possessed several primitive cell junctions. Basal lamina material was not noted. The nuclei were round and many were indented, and they featured both prominent nucleoli and small amounts of peripherally located heterochromatin. The cytoplasm was moderately scant and contained a normal complement of organelles. Neurosecretory granules and microtubules, however, were not observed. Many of the tumor cells had perinuclear bundles of intermediate filaments. Glycogen particles were observed infrequently. These electron microscopic findings were also consistent with a PNET.

At the 1-year follow-up, the patient had no evidence of local or regional recurrence. However, 6 months later she developed pulmonary metastatic disease and died; at the time of her death, she had not had a local or regional recurrence.


PNETs were initially described by Stout in 1918.8 At first, they were generally found to have arisen from major nerves. (9,10) Later reports described these tumors in other anatomic locations as well, including the chest wall, (11) retroperitoneum, extremities, bone, and paraspinal sites. (5) Today, this tumor is believed to be a neoplasm of nonneural soft tissue that primarily affects children and adolescents. (12)

The actual incidence of PNET is difficult to ascertain because diagnostic criteria have only recently been delineated. (3,13) These tumors can occur in any age group, but most occur in adolescents. There is no apparent predilection for either sex. These tumors are most often found (in decreasing order of frequency) in the chest, pelvis, abdomen, and extremities. (1,4,5) Most reports have shown that the lowest incidence is in the head and neck region. (1-3-5,7) In such cases, PNIETs have usually been reported in the craniofacial skeleton area, including the temporal area, (2) skull, (7) orbit, (14 15) masseter muscle, (16) and maxilla. (17) To the best of our knowledge, only one other report of a PNET of the mandible has been published. (3)

Among the cell lines that might be responsible for the development of PNETs, there are three likely candidates: the neural crest, primordial germ cells, and uncommitted mesenchymal cells. The initial enthusiasm for the neural crest as the origin has waned, and it is now believed that the likely progenitors of PNETs are mesenchymal stem cells. (9)

The exact classification of these rare neoplasms has been a source of continued controversy. (9,13,18-21) Dehner reviewed the contemporary medical literature and discovered a distinction between a central PNET and a peripheral PNET. (18) A central PNET originates in the brain or spinal cord; the classic medulloblastoma is a central PNET. A peripheral PNET includes adrenal and extraadrenal neuroblastomas of the soft tissues, nerves, and bones. Peripheral PNETs include peripheral neuroepitheliomas, peripheral medulloepitheliomas, Askin' s tumors, and (the recently added) Ewing's sarcomas. Peripheral PNETs share a common immunohistochemical staining profile and a unique chromosomal translocation t(11;22)(q24;q12). (9,19)

PNETs are typically grouped with other round, small-cell tumors, including Ewing's sarcoma, neuroblastoma, lymphoma, and rhabdomyosarcoma. Light microscopic examination generally reveals that PNETs contain sheets of small, round to oval cells with a scant amount of cytoplasm and coarse chromatin material. The presence of a rosette formation is generally believed to be necessary in order to make the diagnosis. (5,9,20,22,23) The presence of a cytoplasmic process, along with filaments, microtubules, and neurosecretory granules, can be seen on electron microscopy. (5,9,23) Immunohistochemical studies have improved the pathologist's ability to differentiate these small-cell tumors. PNETs are generally positive for neuron-specific enolase, neurofilament, HNK-l (Leu-7), S-100 protein, and MB2, (5,9,23,24) Molecular assays are also being used to diagnose Ewing's sarcoma and PNET, and the polymerase chain reaction can be used to identify the common chromosomal translocations found in various tumors. (13)

No large radiographic series of patients with PNET has been published. In a small series of eight patients with Askin's tumors of the chest wall, Sabate et al found a soft-tissue mass in all patients, but only two demonstrated bony erosion. (25) Radionuclide examination with technetium 99m detected bone involvement in six of these patients. CT showed intratumor calcification in two patients, and the tumor enhanced with intravenous contrast in all eight. Sabate et al concluded that the radiologic features of Askin's tumors are not pathognomonic and that these tumors cannot be diagnosed solely on the basis of radiographic techniques.

Peripheral PNETs are highly aggressive and have a propensity for local recurrence and metastasis to the lung, bone, and bone marrow. (3,4) After a tissue diagnosis has been made, the patient should undergo a full metastatic work-up, including a chest x-ray, CT of the lungs, a bone scan, and bone marrow aspiration to ascertain whether the tumor has metastasized. Bone erosion has been reported to be a common initial finding. (3,4) Similarly, many affected patients have metastatic disease; rates of metastasis in three large series ranged from 20 to 31%). (1,3,4) The prognosis for patients with peripheral PNET is poor. Jones and McGill reported that only 65% of patients they studied were still alive 2 years after diagnosis. (3) In patients who had metastatic disease, only 38% were alive at 2 years. (3)

In an interesting report, Cohn described a patient who had a mass in the arm and peripheral neuropathy of the median nerve. (26) Cohn noted the presence of von Recklinghausen's disease and an epithelial neoplasm of the median nerve. The patient underwent an initial resection and a subsequent resection for a recurrent lesion. Ultimately, the arm was amputated at the junction of the middle and distal thirds. There was no subsequent evidence of recurrence or metastasis.

Even though PNET is highly aggressive, it has been shown to be curable with multimodal therapy in some cases. In a large series, Kushner et al found that outcomes were more favorable among patients who underwent early surgical removal combined with radiation and doseintensive chemotherapy. (1) The recommended manner of treatment is similar to that for Ewing's sarcoma. (4,6,27) Surgical treatment of this lesion in the head and neck can be difficult in light of anatomic considerations. (6) Frequently used chemotherapeutic agents include cyclophosphamide, ifosfamide, vincristine, doxorubicin, and actinomycin D. Radiation is generally administered as an adjuvant therapy when surgical excision is incomplete, but it can also be used as a primary treatment for unresected lesions. Although PNETs are believed to be radiosensitive, radiation is not believed to be adequate to cure macroscopic disease. (1) Radiation therapy is usually given to doses of 55 to 60 Gy.

In conclusion, PNET is an aggressive tumor that is rarely encountered in the head and neck. It is characterized by rapid growth, cranial neuropathy, and manifestations of bone erosion. Involvement of the craniofacial skeleton can mimic osteomyelitis and cause a delay in diagnosis and treatment. Diagnosis depends on extensive histologic evaluation, including immunohistochemistry and electron microscopy. Treatment should include aggressive surgical resection combined with adjuvant radiation and chemotherapy. Because the rate of distant metastasis at the initial diagnosis approaches 30%, preoperative evaluation of the chest, bone, and bone marrow is warranted. (1,3,4) Radiation and chemotherapy have palliative value in unresectable cases. Heightened awareness and early intervention might result in a better chance for a good outcome in patients with this aggressive tumor.


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(19.) Grier HE. The Ewing family of tumors. Ewing's sarcoma and primitive neuroectodermal tumors. Pediatr Clin North Am 1997;44:991-1004.

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(23.) Llombart-Boseh A, Terrier-Lacombe MJ, Peydro-Olaya A, Contesso G. Peripheral neuroectodermal sarcoma of soft tissue (peripheral neuroepithelioma): A pathologic study of ten cases with differential diagnosis regarding other small, round-cell sarcomas. Hum Pathol 1989;20:273-80.

(24.) Kahn HJ, Thorner PS. Monoclonal antibody MB2: A potential marker for Ewing's sarcoma and primitive neuroectodermal tumor. Pediatr Pathol 1989;9:153-62.

(25.) Sabate JM, Franquet T, Parellada JA, et al. Malignant neuroectodermal tumour of the chest wall (Askin tumour): CT and MR findings in eight patients. Clin Radiol 1994;49:634-8.

(26.) Cohn I. Epithelial neoplasms of the peripheral and cranial nerves: Report of three cases, review of the literature. Arch Surg 1928;17:117-60.

(27.) von Schlippe M, Whelan JS. Primitive neuroectodermal tumour of the chest wall. Ann Oncol 1995;6:395-401.

From the Division of Plastic and Reconstructive Surgery (Dr. Sundine) and the Division of Otolaryngology (Dr. Bumpous), Department of Surgery, University of Louisville (Ky.) School of Medicine.

Reprint requests: Jeffrey M. Bumpous, MD, Department of Surgery, University of Louisville, Louisville, KY 40292. Phone: (502) 852-6994; fax: (502) 852-8915; e-mail:
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Author:Bumpous, Jeffrey M.
Publication:Ear, Nose and Throat Journal
Geographic Code:1USA
Date:Mar 1, 2003
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