Thứ Năm, 15 tháng 9, 2011

http://jco.ascopubs.org Journal clinical oncology


Salivary Gland Tumors: Mouth-watering Neoplasms With Tough-to-Chew Prognoses

Blog. 2008 May 12, Edwina Baskin-Bey


A 77-year-old man with a left facial mass presented to the surgical suites for consultation. He had been followed previously by his local ear, nose, and throat surgeon. Over the last 6 years, he had undergone 4 fine-needle aspirations (FNAs) to rule out malignancy. Each time, cytologic analysis showed inflammatory cells involving the parotid salivary gland. His last FNA demonstrated adenocarcinoma. 
On examination, the patient was a stout man with a wide face. His lips and chin on the left side drooped. He mentioned that his partial facial paralysis started approximately 3 months ago, but he otherwise felt well. Computed tomographic (CT) scan showed a large mass within the left parotid gland that compressed but did not appear to invade branches of the facial nerve. On CT, the mass appeared to involve several lymph nodes. 
Just 3 days after his office visit, the patient underwent an uncomplicated parotidectomy with excision of the cervicofacial branches of the facial nerve. Pathology revealed a 3- x 3.5-cm high-grade adenoid cystic carcinoma with perineural invasion of the facial nerve and lymph node spread. Postoperatively, the patient developed a surgical site infection and Frey syndrome. He was offered radiation and chemotherapy after surgery but refused to undergo any further therapy. 
Parotid gland tumors: The most common SGTs 
Oral/pharyngeal cancer is the sixth most common malignancy reported worldwide. The global number of new cases was estimated at 405,318. In the United States, 30,000 people are diagnosed with oral or pharyngeal cancer each year. Salivary gland tumors (SGTs) represent 2% to 4% of head and neck neoplasms. Tumors of the salivary glands comprise those of the major glands (parotid, submandibular, and sublingual) or the minor glands (oral mucosa, palate, uvula, floor of mouth, posterior tongue, retromolar area and peritonsillar area, pharynx, larynx, and paranasal sinuses). 
Most SGTs (70%) originate in the parotid gland. The remaining tumors arise in the submandibular gland (8%) and minor salivary glands (22%). Although 75% of parotid gland tumors are benign, slightly more than 50% of tumors of the submandibular gland and 80% of minor SGTs are found to be malignant. SGTs are more common in women than in men, with the peak incidence in the third and fourth decades of life. 
The parotid gland is situated in the musculoskeletal recess formed by portions of the temporal bone, atlas, and mandible and their related muscles. The gland has a superficial and a deep lobe, between which runs the extratemporal portion of the facial nerve. The main trunk then becomes embedded in parotid tissue and divides into temporofacial and cervicofacial branches just superficial to the retromandibular vein and the external carotid artery. Our patient’s tumor involved the cervicofacial branches, which therefore had to be sacrificed. The submandibular gland encompasses most of the submandibular or digastric triangle. The sublingual gland occupies the same anatomical space as does the submandibular gland, located between the mylohyoid and hyoglossus muscles. The minor salivary glands are widely dispersed throughout the upper respiratory tract, including the palate, lip, pharynx, nasopharynx, larynx, and parapharyngeal space. The greatest number of minor glands is found in the hard and soft palates (250 and 150 glands, respectively). 
Etiology and classification 
Although the etiology of SGTs is unknown, the involvement of environmental or genetic factors has been suggested. Radiation exposure has been linked to the development of the benign Warthin tumor and to the malignant mucoepidermoid carcinoma. Epstein-Barr virus may be a factor in the development of lymphoepithelial tumors of the salivary glands. Genetic alterations, such as allelic loss, monosomy and polysomy, and structural rearrangement, have all been implicated in the development of SGTs. Another reported risk factor is an association between wood dust inhalation and adenocarcinoma of the minor salivary glands of the nose and paranasal sinuses. Other factors linked to SGTs include alcohol use, exposure to sunlight (ultraviolet radiation), and hair dye use. There is evidence that people infected with herpes viruses and human immunodeficiency virus may be at greater risk for SGTs. 
Tumors of the salivary glands are classified based on their cytologic, architectural, and biologic characteristics. The World Health Organization classification groups both benign and malignant tumors into epithelial and nonepithelial categories. Benign epithelial tumors include pleomorphic adenoma, Warthin tumor, monomorphic adenoma, intraductal papilloma, oncocytoma, and sebaceous neoplasms. Benign nonepithelial tumors (mesenchymal origin) include hemangioma, angioma, lymphangioma (cystic hygroma), lipoma, and neural sheath tumors. An additional category of tumor-like lesions includes necrotizing sialometaplasia, benign lymphoepithelial lesions, cystic lymphoid hyperplasia (in persons with acquired immune deficiency syndrome), and salivary gland cysts. Tumors originating in other sites can also metastasize to the salivary glands. Of these metastatic tumors, 46% are melanomas, 37% are squamous cell carcinomas, and 17% are various other tumor types. 
There are 6 main types of salivary gland carcinomas. The most common parotid malignancy is mucoepidermoid carcinoma. Adenoid cystic carcinoma is the most common malignant tumor of all minor salivary glands and, specifically, the submandibular gland. Adenoid cystic carcinoma usually is slow growing and often is a low-grade tumor. These tumors tend to invade nearby nerves, rarely involve the lymph nodes, and have a propensity for hematogenous spread. Acinic cell carcinomas are slow-growing, low-grade tumors with a low likelihood of recurring or metastasizing. Polymorphous low-grade adenocarcinomas have a tendency for the minor salivary gland sites and are low grade and are mostly curable. Rare adenocarcinomas include basal cell adenocarcinoma, clear cell carcinoma, cystadenocarcinoma, sebaceous adenocarcinoma, oncocytic carcinoma, salivary duct carcinoma, and mucinous adenocarcinoma. 
Diagnosis and treatment 
Imaging studies are most helpful in the diagnostic evaluation. Magnetic resonance imaging (MRI) is the most sensitive test for establishing the borders of soft tissue tumor extension. In most circumstances, CT scan and MRI findings cannot be used to differentiate benign from malignant disease reliably. FNA results may help to differentiate between benign and malignant SGTs. The final pathologic diagnosis is based mainly on findings from surgical excision. 
Complete surgical excision of the tumor is the most common treatment of SGTs. Because many nerves and blood vessels lie near the 3 major pairs of salivary glands, particularly the parotids, the surgery can be quite complicated. A promising form of treatment for patients at high risk of tumor recurrence in the salivary glands near the base of the skull is gamma knife surgery. Tumor recurrence after surgery is usually caused by inadequate excision, spillage, or inoculation. The recurrence rate, as reported after a mean follow-up period of 11.8 years, can be as high as 25%. Complications after surgical excision include transient facial nerve paralysis, Frey syndrome, and salivary fistulae with wound healing. Frey syndrome ranges from erythema related to eating to copious gustatory sweating and is believed to be caused by an aberrant connection between the parasympathetic fibers to the sweat gland and the overlying flap of skin. In historical studies, radiation therapy has been shown to reduce the risk of recurrence after surgery, and its use is thus considered in most patients after surgical resection. Chemotherapy is reserved for palliative treatment of metastatic disease but has had disappointing results. In a recent study, only the use of platinum-based chemotherapy was identified as an independent predictor of increased survival. Median survival was increased from 2.5 to 4.9 months for patients treated with platinum chemotherapy (P = .007). 
Several agents that target molecular signaling and cancer cell biology are currently being tested, in order to improve patient survival. Novel treatments under evaluation include tyrosine kinase inhibitors, antibodies, angiogenesis inhibitors, demethylating agents, and proteasome inhibitors. In a recent trial, patients with progressive, recurrent, or metastatic adenoid cystic carcinoma immunohistochemically expressing epidermal growth factor receptor were treated with lapatinib (1500 mg daily). The antitumor effects observed were mainly cytostatic. 
What’s the BITE? 
The BITE (Bey’s indispensable tip at the end) for SGTs: Most SGTs originate in the parotid gland. FNA is helpful to differentiate between benign and malignant tumors. Full surgical excision and consideration of adjuvant radiation therapy offer the best chance for cure. More research on chemotherapeutic agents and targeted therapies is necessary to help improve the survival of patients with metastatic disease. 
References used for this blog: 
Agulnik M, Cohen EW, Cohen RB, et al. Phase II study of lapatinib in recurrent or metastatic epidermal growth factor receptor and/or erbB2 expressing adenoid cystic carcinoma and non adenoid cystic carcinoma malignant tumors of the salivary glands. J Clin Oncol. 2007 Sep 1;25(25):3978-84. 
Cannon DM, Lee NY. Recurrence in region of spared parotid gland after definitive intensity-modulated radiotherapy for head and neck cancer. Int J Radiat Oncol Biol Phys. 2008 Mar 1;70(3):660-5. 
Chandana SR, Conley BA. Salivary gland cancers: current treatments, molecular characteristics and new therapies. Expert Rev Anticancer Ther. 2008 Apr;8(4):645-52. 
Rizk S, Robert A, Vandenhooft A, Airoldi M, Kornek G, Machiels J-P. Activity of chemotherapy in the palliative treatment of salivary gland tumors: review of the literature. Eur Arch Otorhinolaryngol. 2007 Jun;264(6):587-94. 
Vattemi E, Graiff C, Sava T, Pedersini R, Caldara A, Mandarà M. Systemic therapies for recurrent and/or metastatic salivary gland cancers. Expert Rev Anticancer Ther. 2008 Mar;8(3):393-402. 

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