中國醫藥大學機構典藏 China Medical University Repository, Taiwan:Item 310903500/23806

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(1)CASE REPORT. 41. Poorly Differentiated Neuroendocrine Carcinoma of the Nasal Cavity Tzu-Chieh Lin, Ming-Hsui Tsai Department of Otorhinolaryngology, Head and Neck Surgery, China Medical University Hospital, Taichung, Taiwan.. Poorly differentiated neuroendocrine carcinoma of the nasal cavity is a rare and aggressive neoplasm. We report a 47-year-old woman with poorly differentiated neuroendocrine carcinoma of the nasal cavity. Despite treatment with radical surgery, adjuvant radiotherapy and palliative chemotherapy, the patient died due to multiple distant metastases to lungs, bone and liver. ( Mid Taiwan J Med 2009;14:41-5 ). Key words head and neck, nasal cavity, neuroendocrine carcinoma, sinus, small cell carcinoma. INTRODUCTION. Patients with sinonasal malignancies of neuroendocrine origin usually present with locally advanced disease. These neoplasms cannot generally be distinguished based on clinical or radiologic criteria and hence require expert pathologic diagnosis [1]. The most common site of head and neck neuroendorcine carcinoma is the larynx. Carcinoid tumors are commonly considered to be well-differentiated neuroendocrine carcinoma, whereas atypical carcinoid tumors are regarded as moderately differentiated neuroendocrine carcinoma. Small cell neuroendocrine carcinomas are classified as poorly differentiated neuroendocrine carcinoma, small cell carcinoma or small cell undifferentiated (neuroendocrine) carcinoma [1,2]. Primary poorly differentiated neuroendocrine carcinoma of the nasal cavity is a rare and aggressive neoplasm. It has a high recurrence rate, and a tendency to metastasize to other sites via the lymphatic system and blood stream [3]. The 5-year survival Received : 19 November 2007. Revised : 11 June 2008. Accepted : 25 November 2008. Correspondence to : Ming-Hsui Tsai, Department of Otorhinolaryngology, Head and Neck Surgery, China Medical University, 2 Yuh-Der Road, Taichung 404, Taiwan.. rate is only 13% [3]. Treatment includes surgery, radiation and chemotherapy. Progress in understanding and improving outcomes in this uncommon sinonasal malignancy has been hampered by difficulties in pathologic diagnosis and the rarity of this malignancy. The poor outcome of poorly differentiated neuroendocrine carcinoma of the sinonasal tract is consistent with the expected outcome of small cell carcinoma arising at other sites [1]. We report a rare case of primary neuroendocrine carcinoma of the nasal cavity. CASE REPORT. A 47-year-old women presented to our outpatient clinic at the China Medical University Hospital on 1 June, 2005 with a one-month history of left-sided nasal obstruction and yellowish bloody discharge from the left nostril. The patient was a non-smoker and had not been exposed to radiation or environmental irritants. The patient’s medical history was noncontributory. Physical examination revealed an erosive tumor arising from the left inferior turbinate. Computed tomography (CT) revealed a homogeneous tumor in the left inferior turbinate (Fig. 1)..

(2) 42. The patient underwent incision biopsy of the tumor on 2 June, 2005. Histologic examination revealed a highly cellular tumor exhibiting a trabecular growth pattern and a focal rosette formation of undifferentiated cells with a high mitotic rate and extensive necrosis (Fig. 2). The tumor had invaded the underlying minor salivary glands and bone. The section margin was free of tumor. There was no definite lymphovascular or perineural permeation. Immunohistochemical staining was positive for. Fig. 1. CT scan with contrast of the head and neck reveals disproportionate hypertrophy of the left inferior nasal turbinate (axial view).. Fig. 2. Photomicrograph shows undifferentiated tumor cells arranged in a trabecular pattern with focal rosette formation. (H & E, original magnification 200). Neuroendocrine Carcinoma of Nasal Cavity. cytokeratin, chromogranin A and synaptophysin (Fig. 3), and negative for protein S-100 and neurofibriliar protein (NFP). Based on these findings, poorly differentiated neuroendocrine carcinoma was diagnosed. Systemic workup, including abdominal sonography and bone scan, showed no evidence of distant metastasis. The clinical stage of this tumor was T1N0M0, stage I. After consulting with a medical oncologist and a radiation oncologist, surgical resection of the tumor and post-operative radiotherapy were planned. We approached the tumor via a transoral partial left medial maxillectomy. The neoplasm was a granular cell tumor extending from the left inferior pole of the left inferior turbinate to the lateral wall of the inferior meatus. There was no involvement of the left maxillary sinus mucosa or left middle turbinate. The left inferior turbinate and the left medial maxillary wall were completely excised. The patient then underwent local radiotherapy. A total of 54.9 Gy were fractionated into 36 sessions and radiotherapy was completed on 2 August, 2005. No local or regional recurrence was found during routine follow-up from August 2005 to October 2005. On 22 November, 2005, however, the patient presented to the outpatient clinic with a mass on the left side of her neck. T1- and T2-weighted magnetic resonance images showed an enhanced mass in the left carotid space with a greatest diameter of 1.3 cm. Pathological. Fig. 3. Immunohistochemical staining reveals positive staining for cytokeratin, chromogranin A and synaptophysin. (original magnification 400).

(3) Tzu-Chieh Lin, et al.. study confirmed regional recurrence. An 18Ffluorodeoxyglucose (FDG) positron emission tomographic scan revealed multiple foci of increased FDG uptake in the left side of the neck, the right lateral chest wall, both lungs, and liver. Abdominal sonography revealed 4 tumors in both lobes of the liver. The patient received 5 courses of salvage chemotherapy (Etoposide 26.32 mg/m2 qd 3 days Cisplatin 105.28 mg/m 2 qd 3 days). As the disease progressed, the regimen was changed to Doxorubicin (52.64 mg/m 2 qd 1 day), Vincristine (1.32 mg/m 2 qd 1 day), Filgrastim (0.20 mg/m 2 qd 3 days), and 2 Topotecan (2.63 mg/m qd 5 days) in May 2006. On 2 October 2006, she was sent to our emergency department because of a 2-day history of progressive dyspnea. She died on 4 October, 2006 due to progressive disease, lung metastasis and respiratory failure induced by the enlarging neck mass. DISCUSSION. Primary neuroendocrine carcinoma of the nasal cavity is rare. The most common site for this tumor in the head and neck region is the larynx. The presentation of neuroendocrine carcionoma depends on the site of origin. Most patients with neuroendocrine carcinomas of the head and neck present with epistaxis and facial pain. Other symptoms can include facial swelling, nasal obstruction, proptosis, paresthesia, and anosmia. The most frequent sites for distant metastases are the lungs, liver, and bone. Neuroendocrine carcinomas may produce ectopic hormones, but clinical manifestations of hormone production are uncommon in these tumors when arising in the head and neck. Microscopically, poorly differentiated neuroendocrine carcinomas arising in the head and neck are indistinguishable from those of bronchogenic origin. Typically there are sheets, cords, and ribbons of small cells with little or no cytoplasm that appear undifferentiated under light microscopy. The nuclei have a uniformly stippled chromatin pattern. Mitotic figures are frequent. Necrosis varies from scattered, individual cell. 43. death to irregular zones of infarct-like change. Intravascular and perineural invasion are common. Conventional microscopy is generally insufficient for the diagnosis of neuroendocrine carcinoma, as it shares histological features with other neoplasms, such as lymphomas, sinonasal undifferentiated carcinoma, and olfactory neuroblastoma [3]. Immunohistochemical findings are generally useful in differentiating between small cell tumors of different histogenetic origins. The pattern of immunostaining in paranasal poorly differentiated neuroendocrine carcinoma is similar to that in pulmonary small cell carcinoma. Typically there is reactivity for cytokeratins, often with a punctuate perinuclear pattern, a feature noted in small cell carcinoma. Neuroendocrine markers such as chromogranin, synaptophysin, and neuron-specific enolase are also frequently expressed. Microscopically, the differential diagnosis includes olfactory neuroblastoma and malignant lymphoma. In these cases, olfactory neruoblastoma is excluded by negative staining for S100 and the presence of extensive necrosis, which is usually absent or minimal in olfactory neuroblastoma. Negative staining for leukocyte common antigen can exclude malignant lymphoma [4]. The treatment of poorly differentiated neuroendocrine carcinoma has not been clearly defined. Depending on clinical condition and tumor staging, surgical excision of localized disease, radiation therapy to the primary site, multiple-drug chemotherapy, or a combination of these modalities may be appropriate [5]. Treatment of poorly differentiated neuroendocrine carcinoma has varied over time [2]. In the 1980s, surgery followed by radiotherapy was favored [6]. In the late 1990s, neoadjuvant chemotherapy and high-dose proton-photon radiotherapy, with or without surgery, produced encouraging results at 45 months for poorly differentiated neuroendocrine carcinoma of the nasal and paranasal cavities [7]. Commonly used adjuvant agents include cyclophosphamide, cisplatin, doxorubicin, vincristine, and methotrexate [8]..

(4) Neuroendocrine Carcinoma of Nasal Cavity. 44. Extrapulmonary poorly differentiated neuroendocrine carcinoma is a highly aggressive neoplasm with a poor prognosis. The reported 5year overall survival rate is 13% [9]. Duration of survival from onset of symptoms to death for patients with poorly differentiated neuroendocrine carcinoma of the head and neck is only about 13 months [2]. The causes of death include failure to control local disease and distant tumor metastasis. REFERENCES 1. Danny Rischin, Andrew Coleman. Sinonasal Malignancies of Neuroendocrine Origin. Hematol Oncol Clin N Am 2008;22:1297-316. 2. Babin E, Rouleau V, Vedrine PO, et al. Small cell neuroendocrine carcinoma of the nasal cavity and paranasal sinuses. J Laryngol Otol 2006;120:289-97. 3. Marco Tarozzi, Federica Demarosi, Giovanni Lodi, et al. Primary small cell carcinoma of the nasal cavity with an unusual oral manifestation. J Oral Pathol Med 2007;36:252-4.. 4. Galera-Ruiz H, Villar-Rodriguez JL, Sanchez-Chlazdo JA, et al. Sinonasal neuroendocrine carcinoma presenting as a nasopharyngeal mass. Otolaryngol Head Neck Surg 2001;124:475-6. 5. Kin SG, Jang HS. Small cell carcinoma of the oral cavity: report of a case. J Oral Maxillofac Surg 2001; 59:680-4. 6. Smith SR, Som P, Fahmy A, et al. A clinicopathological study of sinonasal neuroendocrine carcinoma and sinonasal undifferentiated carcinoma. Laryngoscope 2000;110:1617-22. 7. Fitzek MM, Thornton AF, Varvares M, et al. Neuroendocrine tumor of the sinonasal tract. R e su lt s of pr os pec ti ve s tud y inc or por at ing chemotherapy, surgery, and combined protonproton radiotherapy. Cancer 2002;94:2623-34. 8. Perez-Ordonez B, Caruana SM, Huvos AG, et al. Small cell neuroendocrine carcinoma of the nasal cavity and paranasal sinuses. Hum Pathol 1996;28: 826-32. 9. Galanis E, Frytak S, Lloyd RV. Extrapulmonary small cell carcinoma. Cancer 1997;79:1729-36..

(5) 45. 2005. 5. 47. 2006 2006. 10. 2. 5 2006. 13% 2009;14:41-5. 404. 2. 2007. 11. 19. 2008. 11. 25. 2008. 6. 11. 10. 4.

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