대한비과학회

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－ 57 －

KISEP Case Reports J Rhinol 4((((1)))), 1997

Primitive Neuroectodermal Tumor of Nasal Cavity：：：：Case Report

Heung Man Lee, M.D.

¹

, Seung Hoon Han, M.D.

¹

, Jeong Su Woo, M.D.

¹

, Seong Jin Cho, M.D.

²

, Han Kyeom Kim, M.D.

²

and Sang Hag Lee, M.D.

¹ ABSTRACT

The primitive neuroectodermal tumor is a highly malignant small round cell tumor characterized by neuroectodermal origin and poor prognosis. The thoracopulmonary region is known to be the most common site of the disease, with peak incidence during adolescence. Primitive neuroectodermal tumors are very rarely reported in the head and neck area, and there have been only a few involving the nasal cavity. We treated a 60 year-old female patient who had nasal obstruction over a three-month period with radical surgery and postoperative radiation therapy. This paper presents our diagnostic workup and approach in treating this unique tumor, and the immunohistochemical findings. A guideline for the treatment of this aggressive neoplasm is reviewed with our experiences in treating this primitive neuroectodermal tumor of the nasal cavity by combined treatment modalities.

KEY WORDS：Primitive neuroectodermal tumor·Nasal cavity.

INTRODUCTION

The primitive neuroectodermal tumor (PNET) is rarely found in the nasal cavity. Since the initial description of PNET made in 1918 by Stout,¹⁾ who described a malignant tumor of the forearm, there have been only a few reported cases of this tumor arising in the head and neck. The most common form of PNET was first reported in 1979. The malignant small round cell tumor which was found in the thoracopulmonary region was neuroectodermal in origin, and is known today as Askin’s tumor.²⁾ Since then, there have been debates and controversies on the terminology and classification of this very rare disease.

Since there has been no single clinical or laboratory test to aid in eliminating its often questionable diagnosis, PNET has been difficult to differentiate from other small round cell tumors, especially Ewing’s sarcoma.³⁾ Although there are relat- ively few cases reported in existing literature, several studies have shown PNET to have a clinically aggressive behavior with significantly worse survival rates than other small round cell tumors.⁴⁾⁵⁾⁶⁾

CASE REPORT

A previously healthy 60 year-old female patient was re- ferred to the Otolaryngology - Head and Neck Surgery Depa- rtment at the Korea University Hospital with a three-month history of left nasal obstruction. The patient had found the mass in the left nasal cavity two months earlier. The patient also complained of both fronto-temporal headache, however, she denied symptoms of rhinorrhea, postnasal dripping and nasal bleeding. Physical examination with a nasal endoscope revealed a smooth-surfaced, polypoid mass filled the left nasal cavity (Fig. 1). There was subcutaneous or contralateral nasal cavity mass, nor any palpable cervical lymph nodes. No cranial nerve deficits were found either.

Radiological investigations including paranasal sinus X-rays, chest X-rays, and a high-resolution contrast-enhanced com- puted tomography (CT) of paranasal sinsuses (PNS) were performed. An axial view of PNS CT revealed a soft tissue density mass filling the left nasal cavity. There was no bony destruction and the paranasal sinus appeared unaffected (Fig. 2).

A diagnostic biopsy was performed as an out-patient proc- edure. With the initial diagnosis of malignant PNET, further studies were carried out for the purpose of a metastatic workup which would include an ultrasonogram of the abdomen, brain magnetic resonance imaging, and a bone scan. The results of these studies revealed little. Other routine laboratory test yi- elded normal results. A maxillectomy via lateral rhinotomy incision was performed for initial treatment. The mass sized 3×2 cm was attached superior to the inferior turbinate (Fig.

Department of ¹Otorhinolaryngology- Head and Neck Surgery,

2Surgical Pathology, Korea University College of Medicine, Se- oul, Korea

Address correspondence and reprint requests to Heung Man Lee, M.D., Department of Otorhinolaryngology-Head and Neck Surgery, Korea University College of Medicine, 80, Gurodong, Gurogu, Seoul 152-050, Korea

Tel：82-2-818-6157, Fax：82-2-868-0475 Accepted for publication March 12, 1997

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58 / J Rhinol 4(1), 1997

3). There was no invasion of the left maxillary sinus and no evidence of bone destruction.

The patient was discharged without any event on the 10th postoperative day. Postoperatively, she received a total of 61 Grey of external beam radiation for six weeks. She was con- tinually and closely followed up with nasal endoscopic exa- minations, and PNS CT for seven with no evidence of rec- urrence. The patient is alive and well.

On examing a gross section, the cut surface showed a poorly demarcated pale-gray tumor measuring 3×2 cm cross-secti- onally. Light microscopic evaluation revealed no specific ar- chitectural pattern, and the tumor was composed of small primitive cells with scant cytoplasm, and round or oval nucleoli.

No definite rosettes or pseudorosettes could be identified

(Fig. 4). In immunohistochemical staining, there were positive findings for neuron-specific enolase (NSE)(Fig. 5) and synaptophysin (Fig. 6). However, negative findings were observed for the antibodies of neuroblastoma, MIC2, leukocyte common antigen, and HMB45.

Fig. 2. Preoperative axial CT scan of paranasal sinuses showing inhomogenous soft tissue density (*) filling the left nasal cavity.

Fig. 1. Preoperative endoscopic finding showing smooth surfa- ced, polypoid mass filling the left nasal cavity.

Fig. 4. Microscopic finding showing patterless growth of primitive cells and the high frequency of mitotic cells (H & E stain, ×400).

Fig. 3. Surgical specimen appearing irregular surfaced mass sized 3.5×3×1 cm.

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DISCUSSION

There have been several reports of tumors which are si- milar to PNET, but with controversiesy about their proper terminology or classification. It was not until 1973, when Hart and Earle⁷⁾ applied the term‘primitive neuroectodermal tumor’that the controversies subsided. They described a group of small round cell tumors of the central and peripheral nervous system, and identified them as being derived from fetal neuroectodermal precursor cells. PNETs have their origins ou- tside the autonomic nervous system, hence they are often called peripheral neuroectodermal tumors along with other terms such as peripheral neuroepithelioma and peripheral neuroblastoma.⁵⁾

Incidence of these tumors is very rare, and it can occur at any age, with peak incidence during adolescence. Two cases of PNET were reported in the maxillary/ethmoid sinus of a 13 year-old patient and the nasal cavity of a 17 year-old patient.⁸⁾ The predominent location of PNET is the chest

wall.^2)4)5)8)9) Here we encountered a rare case of PNET arising in the nasal cavity.

Because of its aggressive nature it is important to make a correct diagnosis of PNET. However, even today, there are arguments among pathologists and oncologists in its diagnosis. Increasingly, ultrastructural, immunohistochemical, and cytogenetic findings have been necessary to confirm the diagnosis of PNET.⁴⁾⁶⁾⁹⁾ Differential diagnosis is imperative for PNET since even today many pathologists argue that these putative soft tissue tumors are nothing more than a metastasis from an unrecognized neuroblastoma or a carcinoma. The diagnosis of PNET can only be made by exclusion, following an extensive search for a primary neuroblastoma.¹⁰⁾ Differen- tial diagnosis includes taking Ewing’s sarcoma, neuroblastoma, lymphoma, and embryonic variants of rhabdomyosarcoma into account.^3)6)11)12)

Microscopically, PNETs appear as small round cell sheets or lobules with the presence of Homer-Wright rossettes.⁴⁾ Our case did not show any definite rosette formations, however, small round cells were detected. Ultrastructural characteristics include sheets of primitive tumor cells with large, round, oval or irregular shaped nuclei with prominent nucleoli and scant cytoplasm. The most distinguishing findings were the presence of interdigitating, long cytoplasmic processes containing glial filaments with glial differentiation, and the presence of dense core granules and microtubules with neuronal differentiation.⁵⁾⁸⁾

These tumors are immunoreactive for NSE, Synaptophysin, S-100 protein, and MB2 monoclonal antibodies.⁶⁾ Our case showed positive immunoreaction for NSE and synaptophysin, strongly suggesting neurogenic origin, but showed negative immunoreaction for leukocyte common antigen, UCHL-1, L26, CD68, and cytokeratin. Although previous reports have shown that MIC2 expression is detected in PNET between 82%

to 97% of the time,¹³⁾ our case did not.

Diagnosis of neuroblastoma could be excluded for our case even with the negative MIC2 findings due to the fact that our case did not demonstrate any neurofibrillary backgr- ound which should be presented to make a diagnosis of neuroblastoma. Cytogenetic evaluation of the patient with PNET showed specific translocation of chromosomes 11 and 22 [＋

(11：22) (q24：q12)], which can also be seen in Ewing’s sarcoma.^4)5)8)11) However, our case did not show specific translocation of chromosomes 11 and 22 (data not shown). Ev- entually the confirmation of diagnosis is made by combination of all of these diagnostic modalities.

Because of its aggressiveness and poor prognosis the mu- ltimodality approach in the treatment of PNET is currently being advocated.⁸⁾¹¹⁾ Even with radical surgical therapy combined with chemotherapy and radiation therapy, the prognosis

Fig. 5. Immunohistochemical staining of NSE (×400).

Fig. 6. Immunohistochemical staining of synaptophysin (×400).

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is still very poor.

There is a marked difference between the outcomes of patients undergoing radical and non-radical surgical proced- ures. Early initial treatment also seems to be important factor in increasing the survival rate.⁹⁾ External beam radiation therapy using 50 to 65 Grey at the primary site and regional nodes is advocated. No studies have shown an effective single-agent regimen, therfore, multidrug therapy using drugs such as doxorubicin, vincristine, and cyclophosphamide is recommended.⁴⁾ Our patient underwent resection of the tumor followed by radiation therapy using 61 Grey for six weeks.

Clinically, the tumor is a highly aggressive malignant tumor with a significantly worse survival rate than other small round cell tumors.⁶⁾ Metastasis at presentation is fairly common with up to 31%.⁸⁾ The most common metastatic sites are the lung, bone, and brain.⁴⁾ It is important to carry out an intensive metastatic workup at the initial diagnosis of PNET. Our case showed no definite metastatic lesion on chest X-rays, abdominal ultrasonogram, brain MRI, and whole bone scan. Unlike other studies we did not note any bone erosion due to local extension of the tumor. Some studies have emphasized routine use of bone marrow biopsy and aspiration along with chest CT and chest radiography for determination of metatstasis.⁸⁾

Complete remission following treatment is common, however, long-term disease-free survival has been less encouraging.

Two year-survival rate is less than 65%⁸⁾ and is dramatically reduced to 25% when the tumor size is greater than 5 cm⁹⁾. Furthermore, the three-year survival rate is below 50%.⁵⁾ Alt- hough our patient showed complete remission of the disease following surgery and radiation therapy, a much longer follow- up period is needed to accurately predict the prognosis of PNET in the nasal cavity.

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