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Small cell neuroendocrine carcinoma of the parotid gland
Small cell neuroendocrine carcinoma of the parotid gland CETIN VURAL, MD, ONER DOGAN, MD, ERTUGRUL YAVUZ, MD, HAKKI SUHA OZCELIK, MD, and ARAS SENVAR, MD,
Istanbul, Turkey
Small cell carcinoma is most frequently found in the lung. Extrapulmonary sites of this neoplasm account for only 4% of all small cell carcinomas. Small cell carcinomas arising in the salivary glands are extremely rare, accounting for less than 1% of all parotid gland carcinomas and 3.5% of all malignant minor salivary gland tumors. These tumors are classified into 2 groups: small cell neuroendocrine carcinomas and small cell ductal carcinomas. In 1972 Koss et al1 reported 14 cases with anaplastic small cell carcinoma arising from the minor salivary glands. They indicated that, morphologically, these tumors resembled pulmonary small cell carcinoma; however, patients with the salivary gland tumors appeared to have a better prognosis. Their conclusion is such that this tumor should have a salivary gland ductal origin. CASE REPORT A 52-year-old man was admitted to Sisli Etfal Hospital for evaluation of a rapidly growing 6-cm mass in the right parotid gland. There was no evidence of lymphadenopathy in the neck, and the results of the remainder of the physical examination were normal. Chest radiographs demonstrated no pulmonary disease. The patient underwent a total parotidectomy with preservation of the facial nerve. Histopathologic examination revealed a small cell malignant neoplasm in which a diffuse or irregularly organoid pattern was seen (Fig 1). Positive cytoplasmic pancytokeratin, epithelial membrane antigen, chromogranin A, and neuronspecific antigen immunostaining was observed in the tumor cells. Histopathologic diagnosis was small cell cancer with neuroendocrine features. The patient was referred for radiotherapy, but he refused. Two months after parotidectomy, he was seen again with a 4cm mass behind the angle of the mandible. A radical neck dissection was performed, including the superior aspect of the trapezius muscle. The result of the histopathologic examina-
From the Clinic of Otolaryngology–Head and Neck Surgery, Sisli Etfal Hospital (Drs Vural, Yavuz, Ozcelik, and Senvar); and the Department of Pathology, Istanbul University, Istanbul School of Medicine (Dr Dogan). Reprint requests: Cetin Vural, MD, Halaskargazi Caddesi, No: 323325, Kat 3 Sisli, Istanbul, 80260, Turkey. Otolaryngol Head Neck Surg 2000;122:151-2. Copyright © 2000 by the American Academy of Otolaryngology– Head and Neck Surgery Foundation, Inc. 0194-5998/2000/$12.00 + 0 23/78/98757
tion of the neck specimen was small cell tumor metastasis in the upper jugular lymph nodes. After neck dissection the patient received radiotherapy, including 50 Gy to the neck and parotid region. He died 12 months after diagnosis because of recurrence in the primary site. DISCUSSION Undifferentiated carcinomas are composed of either small cells (which are about 30 µm or less in diameter) with scant cytoplasm and uniform nuclei or larger, more pleomorphic cells that are 3 or more times the size of small cells. This difference in cell size and morphology permits segregation of undifferentiated carcinomas into a small cell type and a large cell type.2 Small cell carcinoma of the salivary glands is a rare, primary malignant tumor that with conventional light microscopy is described as undifferentiated cells and with ultrastructural or immunohistochemical studies demonstrates neuroendocrine differentiation. This tumor has also been referred to as extrapulmonary oat cell carcinoma.2 Small cell cancers have been classified by several investigators into 2 groups, based on the ultrastructural presence or absence of intracytoplasmic neuroendocrine granules: small cell neuroendocrine carcinoma and small cell ductal carcinoma.3,4 A recent study by Gnepp and Wick5 of some of the same tumors that in a previous study lacked dense core granules ultrastructurally, showed neuroendocrine characteristics when studied immunohistochemically. For this reason, they concluded that dividing small cell carcinomas of the salivary glands into 2 histologic subtypes is not justified. In immunohistochemical studies of these tumors, most cells are immunoreactive for keratin, although focal areas are nonreactive. The paranuclear, globular staining pattern seen in many of these tumors is not evident in other types of salivary gland carcinoma. In addition to the staining with anticytokeratin, other determinants that indicate neuroendocrine differentiation include immunoreactivity of tumor cells with anti-Leu-7, synaptophysin, chromogranin, and neuron-specific enolase.2 In our case the immunohistochemical findings of the specimen were positive staining with epithelial membrane antigen and cytokeratin and weak staining with chromogranin. Electron microscopy shows small, closely apposed, primitive but uniform cells with scant cytoplasm and pyknotic nuclei.3,4 Small cell carcinoma is a common neoplasm that accounts for 25% to 36% of all lung carcinomas. Four percent of small cell carcinomas arise in extrapulmonary sites.3 In the head and neck region, small cell carcinomas arise most commonly in 151
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VURAL et al
the larynx but have also been reported in the nose, paranasal sinuses, pharynx, oral cavity, and cervical esophagus. Small cell carcinoma of the parotid gland is very rare. Although the prognosis for patients with small cell carcinoma of the salivary glands is better than for those with small cell carcinoma of the lung or larynx, it is a high-grade malignancy that is treated aggressively.2 Gnepp et al3 found that the 2-year and 5-year survival rates for major salivary gland tumors were 70% and 46%, respectively. Chemoradiation is the standard treatment for patients with small cell cancer of the lung. Many authors treated their patients who had small cell cancer of the salivary glands with radiation therapy and/or chemotherapy after surgery.3,4 We think this case shows the necessity for aggressive treatment of salivary gland small cell tumor. REFERENCES
Fig 1. Neoplastic infiltration of salivary gland tissue. (Hematoxylin-eosin stain; original magnification ×310.)
1. Koss LG, Spiro RH, Hajdu S. Small cell (oat cell) carcinoma of minor salivary gland origin. Cancer 1972;30:737-41. 2. Ellis GL, Auclair PL. Tumors of the salivary glands. In: Ellis GL, Auclair PL, editors. Atlas of tumor pathology. 3rd ed. Washington (DC): Armed Forces Institute of Pathology; 1996. p. 296-306. 3. Gnepp DR, Corio RL, Brannon RB. Small cell carcinoma of the major salivary glands. Cancer 1986;58:705-14. 4. Kraemer BB, Mackay B, Batsakis JG. Small cell carcinomas of the parotid gland. A clinicopathologic study of three cases. Cancer 1983;52:2115-21. 5. Gnepp DR, Wick MR. Small cell carcinoma of the major salivary glands. An immunohistochemical study. Cancer 1990;66:185-92.
Laser Voice Surgery and Voice Care
The 5th International Workshop on Laser Voice Surgery and Voice Care will be held April 14-15, 2000, in Paris, France. This year’s topic will be “Bilateral Lesions of the Vocal Folds.” For further information, contact Jean Abitbol, MD, 1, Rue Largillière, 75016 Paris, France; phone, 33-1-46-47-91-89; fax, 33-1-45-27-72-30; e-mail, [email protected].
Istanbul, Turkey
Small cell carcinoma is most frequently found in the lung. Extrapulmonary sites of this neoplasm account for only 4% of all small cell carcinomas. Small cell carcinomas arising in the salivary glands are extremely rare, accounting for less than 1% of all parotid gland carcinomas and 3.5% of all malignant minor salivary gland tumors. These tumors are classified into 2 groups: small cell neuroendocrine carcinomas and small cell ductal carcinomas. In 1972 Koss et al1 reported 14 cases with anaplastic small cell carcinoma arising from the minor salivary glands. They indicated that, morphologically, these tumors resembled pulmonary small cell carcinoma; however, patients with the salivary gland tumors appeared to have a better prognosis. Their conclusion is such that this tumor should have a salivary gland ductal origin. CASE REPORT A 52-year-old man was admitted to Sisli Etfal Hospital for evaluation of a rapidly growing 6-cm mass in the right parotid gland. There was no evidence of lymphadenopathy in the neck, and the results of the remainder of the physical examination were normal. Chest radiographs demonstrated no pulmonary disease. The patient underwent a total parotidectomy with preservation of the facial nerve. Histopathologic examination revealed a small cell malignant neoplasm in which a diffuse or irregularly organoid pattern was seen (Fig 1). Positive cytoplasmic pancytokeratin, epithelial membrane antigen, chromogranin A, and neuronspecific antigen immunostaining was observed in the tumor cells. Histopathologic diagnosis was small cell cancer with neuroendocrine features. The patient was referred for radiotherapy, but he refused. Two months after parotidectomy, he was seen again with a 4cm mass behind the angle of the mandible. A radical neck dissection was performed, including the superior aspect of the trapezius muscle. The result of the histopathologic examina-
From the Clinic of Otolaryngology–Head and Neck Surgery, Sisli Etfal Hospital (Drs Vural, Yavuz, Ozcelik, and Senvar); and the Department of Pathology, Istanbul University, Istanbul School of Medicine (Dr Dogan). Reprint requests: Cetin Vural, MD, Halaskargazi Caddesi, No: 323325, Kat 3 Sisli, Istanbul, 80260, Turkey. Otolaryngol Head Neck Surg 2000;122:151-2. Copyright © 2000 by the American Academy of Otolaryngology– Head and Neck Surgery Foundation, Inc. 0194-5998/2000/$12.00 + 0 23/78/98757
tion of the neck specimen was small cell tumor metastasis in the upper jugular lymph nodes. After neck dissection the patient received radiotherapy, including 50 Gy to the neck and parotid region. He died 12 months after diagnosis because of recurrence in the primary site. DISCUSSION Undifferentiated carcinomas are composed of either small cells (which are about 30 µm or less in diameter) with scant cytoplasm and uniform nuclei or larger, more pleomorphic cells that are 3 or more times the size of small cells. This difference in cell size and morphology permits segregation of undifferentiated carcinomas into a small cell type and a large cell type.2 Small cell carcinoma of the salivary glands is a rare, primary malignant tumor that with conventional light microscopy is described as undifferentiated cells and with ultrastructural or immunohistochemical studies demonstrates neuroendocrine differentiation. This tumor has also been referred to as extrapulmonary oat cell carcinoma.2 Small cell cancers have been classified by several investigators into 2 groups, based on the ultrastructural presence or absence of intracytoplasmic neuroendocrine granules: small cell neuroendocrine carcinoma and small cell ductal carcinoma.3,4 A recent study by Gnepp and Wick5 of some of the same tumors that in a previous study lacked dense core granules ultrastructurally, showed neuroendocrine characteristics when studied immunohistochemically. For this reason, they concluded that dividing small cell carcinomas of the salivary glands into 2 histologic subtypes is not justified. In immunohistochemical studies of these tumors, most cells are immunoreactive for keratin, although focal areas are nonreactive. The paranuclear, globular staining pattern seen in many of these tumors is not evident in other types of salivary gland carcinoma. In addition to the staining with anticytokeratin, other determinants that indicate neuroendocrine differentiation include immunoreactivity of tumor cells with anti-Leu-7, synaptophysin, chromogranin, and neuron-specific enolase.2 In our case the immunohistochemical findings of the specimen were positive staining with epithelial membrane antigen and cytokeratin and weak staining with chromogranin. Electron microscopy shows small, closely apposed, primitive but uniform cells with scant cytoplasm and pyknotic nuclei.3,4 Small cell carcinoma is a common neoplasm that accounts for 25% to 36% of all lung carcinomas. Four percent of small cell carcinomas arise in extrapulmonary sites.3 In the head and neck region, small cell carcinomas arise most commonly in 151
152
Otolaryngology– Head and Neck Surgery January 2000
VURAL et al
the larynx but have also been reported in the nose, paranasal sinuses, pharynx, oral cavity, and cervical esophagus. Small cell carcinoma of the parotid gland is very rare. Although the prognosis for patients with small cell carcinoma of the salivary glands is better than for those with small cell carcinoma of the lung or larynx, it is a high-grade malignancy that is treated aggressively.2 Gnepp et al3 found that the 2-year and 5-year survival rates for major salivary gland tumors were 70% and 46%, respectively. Chemoradiation is the standard treatment for patients with small cell cancer of the lung. Many authors treated their patients who had small cell cancer of the salivary glands with radiation therapy and/or chemotherapy after surgery.3,4 We think this case shows the necessity for aggressive treatment of salivary gland small cell tumor. REFERENCES
Fig 1. Neoplastic infiltration of salivary gland tissue. (Hematoxylin-eosin stain; original magnification ×310.)
1. Koss LG, Spiro RH, Hajdu S. Small cell (oat cell) carcinoma of minor salivary gland origin. Cancer 1972;30:737-41. 2. Ellis GL, Auclair PL. Tumors of the salivary glands. In: Ellis GL, Auclair PL, editors. Atlas of tumor pathology. 3rd ed. Washington (DC): Armed Forces Institute of Pathology; 1996. p. 296-306. 3. Gnepp DR, Corio RL, Brannon RB. Small cell carcinoma of the major salivary glands. Cancer 1986;58:705-14. 4. Kraemer BB, Mackay B, Batsakis JG. Small cell carcinomas of the parotid gland. A clinicopathologic study of three cases. Cancer 1983;52:2115-21. 5. Gnepp DR, Wick MR. Small cell carcinoma of the major salivary glands. An immunohistochemical study. Cancer 1990;66:185-92.
Laser Voice Surgery and Voice Care
The 5th International Workshop on Laser Voice Surgery and Voice Care will be held April 14-15, 2000, in Paris, France. This year’s topic will be “Bilateral Lesions of the Vocal Folds.” For further information, contact Jean Abitbol, MD, 1, Rue Largillière, 75016 Paris, France; phone, 33-1-46-47-91-89; fax, 33-1-45-27-72-30; e-mail, [email protected].