Adeno Ca
Adeno Ca
Adeno Ca
Background: Salivary gland carcinomas of the larynx are rare, and account for <1% of laryngeal malignancy. The purpose of this study is to review our management experience of salivary gland carcinomas of the larynx in Taipei Veterans General Hospital and to compare it with other major existing series. Methods: From 1981 to 2000, 11 patients with laryngeal salivary gland carcinomas treated in Taipei Veterans General Hospital were included in this study. Their demographic data, treatment modalities, survival, and failure pattern, obtained by review of medical records, were analyzed. Results: All 11 patients were male. Median follow-up period was 95 months (range, 18181 months). The 5-year overall survival rate of all patients was 71%, and the 5-year disease-specific survival rate was 83%. Conclusion: The mainstay treatment of laryngeal salivary gland carcinomas in these cases was surgery or surgery with postoperative radiotherapy. The survival rate was satisfactory and similar to that of squamous cell carcinoma of the larynx. [J Chin Med Assoc 2006;69(7):322325] Key Words: carcinoma, larynx, salivary gland carcinoma
Introduction
Squamous cell carcinoma accounts for about 99% of laryngeal malignancies. Non-epidermoid malignancies of the larynx include sarcoma, lymphoma, and salivary gland carcinoma. Salivary gland carcinomas of the larynx are rare tumors, which account for <1% of laryngeal malignancy.1 Few major series report on a detailed MEDLINE search. The purpose of this study is to review our experiences in diagnosis and therapy of patients with salivary gland carcinoma in Taipei Veterans General Hospital and to compare our treatment results with those of other major existing series.
Methods
From 1981 to 2000, 1,564 patients with laryngeal malignancy treated in Taipei Veterans General Hospital were found from the computer database of the Cancer Treatment Center. Twelve patients from among them were diagnosed with salivary gland carcinoma of the
larynx. One of the 12 patients was excluded from our study due to distant metastasis at the time of diagnosis. The remaining 11 patients were included in this study. Demographic data, clinical staging of tumors, pathologic classifications, treatment modalities, failure patterns, and survival were obtained by reviewing the medical records. Tumors were staged according to the 2002 American Joint Committee on Cancer (AJCC) staging system for laryngeal tumors. All the pathologic slides were re-examined by a single pathologist for histologic study. Clinical and pathologic data were entered into a computer database (Microsoft Access 2000) and statistical analysis of data was performed by using a commercially available computer software package (JMP 4.0, SAS Institute Inc., Cary, NC, USA). The follow-up interval was calculated in months from the date of initial surgery or radiotherapy (RT) to the date of the last follow-up or death, and disease-free interval was calculated from the date of initial surgery or RT to the date of the first recurrence. For disease-specific survival, patients who died of causes unrelated to laryngeal cancer were censored.
*Correspondence to: Dr Pen-Yuan Chu, Department of Otolaryngology, Taipei Veterans General Hospital, 201, Section 2, Shih-Pai Road, Taipei 112, Taiwan, R.O.C. E-mail: pychu@vghtpe.gov.tw Received: October 13, 2005 Accepted: March 21, 2006
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Overall survival rates and disease-specific survival rates were calculated using the KaplanMeier product-limit method.
Results
All the 11 patients were male, aged from 48 to 84 years with a median of 65. The demographic data, subsites of primary tumor, and TNM staging system are shown in Table 1. Three patients were at an early stage, Stage I and II. Others were at the advanced Stage III or IV. The treatment modalities included surgery, surgery with postoperative RT or RT alone (Table 1). A total of 9 patients (82%) underwent surgery. Surgery alone was performed in 5 patients and surgery combined with postoperative RT was used in 4 patients. Seven patients underwent total laryngectomy. Only 2 patients had conservation surgery, including 1 supraglottic partial laryngectomy and 1 vertical partial laryngectomy. Neck dissections were performed in 4 patients (2 unilateral and 2 bilateral). Two patients received RT alone as their mainstay treatment. Therefore, laryngeal preservation rate was 36% (4/11) under surgery or RT. All the pathologic slides were re-examined by a single pathologist. Four patients were classified as having adenoid cystic carcinoma (Table 1). Three patients were classified with mucoepidermoid carcinoma and
3 patients with adenocarcinoma (Table 1). For surgical margins, 2 were positive and the remaining were negative. Perineural invasion was noted in 2 patients and both of them were adenoid cystic carcinoma. For cell differentiation, intermediate grade predominated. Only 1 case was high grade and 2 cases were low grade. The median follow-up period was 95 months (range, 18181 months). One patient developed local recurrence and 1 developed distant metastasis to the lung. No patient had second primary tumor during the follow-up period. The overall survival rate was 71% in 5 years, and 57% in 10 years. Disease-specific survival was 83% in 5 years, and 63% in 10 years.
Discussion
Salivary gland carcinomas of the larynx are rare and account for <1% of laryngeal malignancies.1 It was about 0.76% in our series. Tumors of minor salivary gland origin arise from subepithelial glands. Spiro et al reviewed 492 cases of tumors of minor salivary gland origin in the head and neck in Memorial Hospital during a 25-year period, and the most common origin of minor salivary gland tumor was the palate (36.8%).2 Adenoid cystic carcinoma was the leading pathologic diagnosis (35.4%). Only 3% of salivary gland tumors were in the larynx. In the database of our cancer center, salivary gland carcinomas of the larynx accounted for
Table 1. Epidemiologic characteristics of patients, histology, details of treatment, and outcome Case 1 2 3 4 5 6 7 Age 48 60 65 63 69 74 61 Sex M M M M M M M Primary site Glottic Glottic Subglottic Glottic Supraglottic Glottic Glottic Stage T3N0M0 T3N0M0 T4N0M0 T3N2bM0 T2N0M0 T4N0M0 T1N0M0 Histology ACC ACC AdenoCa AdenoCa ACC AdenoCa Mucoepi Treatment S RT RT S S S + RT S + RT Type of surgery TL Laryngeal preservation No Yes Yes No Yes No Yes Outcome DNED at 239 mo DNED at 120 mo ANED at 123 mo ANED at 91 mo ANED at 94 mo DNED at 31 mo Local recurrence at 8 mo; ANED at 48 mo ANED at 9 mo ANED at 122 mo Died of lung metastasis at 22 mo
TL + ND SGL TL + ND VPL
8 9 10
79 73 58
M M M
TL TL + ND TL + ND
No No No
11
84
T3N0M0
AdenosquaCa
TL
No
ACC = adenoid cystic carcinoma; AdenoCa = adenocarcinoma; Mucoepi = mucoepidermoid carcinoma; AdenosquaCa = adenosquamous carcinoma; S = surgery; RT = radiotherapy; C/T = chemotherapy; TL = total laryngectomy; ND = neck dissection; SGL = supraglottic laryngectomy; VPL = vertical partial laryngectomy; DNED = died with no evidence of disease; ANED = alive with no evidence of disease.
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M.C. Wang, et al
1.4% (12/856) of all head and neck salivary gland carcinomas. We reviewed 5 major series of a similar topic in the literature37 and compared them with our data (Table 2). There were many more male than female patients in most series except 1 (UCLA series) where males and females were equal in number. The fact that all the cases in our series were male may partly be due to the fact that veterans were the major patient population in our hospital. Salivary gland carcinomas of the larynx account for a similar percentage of all laryngeal malignancies, ranging from 0.6 to 0.87% in these major series. Most tumors had supraglottic or subglottic involvement,3,8 possibly because the distribution density of subepithelial glands is higher in the supraglottic and subglottic areas than in the glottic area. Tumors arising from subepithelial glands1,2,9 begin as submucosal lesions, and are difficult to detect earlier. This explains why most patients were diagnosed late at the advanced stage in all series. Toomey3 reported 8 cases of adenocarcinoma of the larynx and reviewed 29 reported cases in the literature.4 In these 37 cases, male gender and old age were predominant. Ninety-five percent of them had supraglottic or subglottic involvement. The most frequent site of distant metastasis was the lung. In our series, 63% of patients had supraglottic or subglottic involvement, and the site of distant metastasis was also the lung. The symptoms and signs of laryngeal salivary gland carcinoma are related to location and size.9 Patients will suffer from dysphagia if the tumor is located in the supraglottic area. Hoarseness or even dyspnea is indicative of glottic involvement. Stridor and airway obstruction might imply a subglottic tumor. The definite diagnosis of laryngeal salivary gland carcinoma is
made by biopsy of the laryngeal tumor under laryngoscope and histopathologic examination of the specimen. Surgery with or without postoperative RT6,7,10,11 is the widely accepted major treatment modality of laryngeal salivary gland carcinomas. Ipsilateral neck dissection should be performed in cases with cervical adenopathy, adenocarcinoma, and high-grade mucoepidermoid carcinoma. Elective neck dissection is not recommended for those who present with adenoid cystic carcinoma and low-grade mucoepidermoid carcinoma.6,7,10,11 Surgery remains the mainstay treatment for salivary gland carcinoma of the larynx. Although aggressive treatment is recommended, the role of RT is unclear, but it may be valuable as an adjuvant modality for adenoid cystic carcinoma with perineural spread, high-grade tumors, or positive surgical margin. Chemotherapy may be useful as an adjuvant therapy of high-grade lesions, either in conjunction with surgery to prevent distant metastases or with RT as palliation for patients with distant metastases at initial presentation.10 The 5-year overall survival in our series was 71%, and the 5-year disease-specific survival was 83%. Although we did not find any statistically significant factors of better prognosis due to the small sample size, high-grade tumor cell type, positive surgical margin, or perineural invasion still tend to be indicative of poor prognosis. When compared with the treatment results of squamous cell carcinoma of the larynx in our institute between 1981 and 1991,12 we found the 5-year survival rate to be 67% in squamous cell carcinoma of the larynx and 71% in this study. These survival rates are similar. In conclusion, laryngeal salivary gland carcinomas are rare. They account for <1% of laryngeal
Table 2. Data from different centers Institute Barnes hospital, 1967 Memorial hospital, 1968 Mayo Clinic, 1974 MD Anderson, 1985 UCLA, 1999 VGH, 2003 *Patient no. (%) 8/NA 17/2,500 (0.68) 27/3,100 (0.87) 18/2,967 (0.6) 12/1,547 (0.78) 12/1,564 (0.76) Subsites of tumor (%) SG (37), SubG (13), TG (50) NA SG (19), G (7), SubG (37), HY (4) SG (78), SubG (22) SG (42), G (33), SubG (25) SG (27), G (37), SubG (9), TG (27) TNM stage I + II: 1 III + IV: 7 NA NA I + II: 6 III + IV: 12 I + II: 2 III + IV: 10 I + II: 2 III + IV: 9 Treatment (%) S (75), RT (25) S (82), RT (18) S (67), RT (33) S (61), RT (11), S + RT (28) S (30), RT (0), S + RT (70) S (55), RT (18), S + RT (27) Survival (5 yr) 3 ANED/8 2 ANED/17 2 AWD/17 Average survival 69 mo DSS: 42.8% OS: 45.2% OS: 71% DSS: 83%
*Number of patients with salivary gland carcinoma of the larynx over number of patients with laryngeal malignancy. SG = supraglottis; SubG = subglottis; TG = transglottis; G = glottis; HY = hypopharynx; S = surgery; RT = radiotherapy; ANED = alive with no evidence of disease; AWD = alive with disease; DSS = disease-specific survival; OS = overall survival; NA = not available.
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malignancies, and only 13% of head and neck salivary gland carcinomas. They usually originate in the supraglottic or subglottic area with a predominance of male gender and old age. Most patients were diagnosed late at an advanced stage. Surgery alone or in combination with postoperative RT is the main treatment modality. The overall 5-year survival rate of laryngeal salivary gland carcinoma is similar to that of laryngeal squamous cell carcinoma in our institution.
References
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4. Cady B, Rippey JH, Frazell EL. Non-epidermoid cancer of the larynx. Ann Surg 1968;167:11620. 5. Wicker JH, Neel HB III, Weiland LH, Devine KD. Adenocarcinoma of the larynx. Ann Otol Rhinol Laryngol 1974;83: 48790. 6. Cohen J, Guillamondegiu OM, Batasakis JG, Medina JE. Cancer of the minor salivary glands of the larynx. Am J Surg 1985; 150:5138. 7. Alavi S, Calcaterra TC, Namazie A, Blackwell KE. Glandular carcinoma of the larynx: the UCLA experience. Ann Otol Rhinol Laryngol 1999;108:4859. 8. Olofsson J, Van Norstrand AWP. Adenoid cystic carcinoma of the larynx: a report of four cases and a review of the literature. Cancer 1977;40:130713. 9. Levine HL, Tubbs R. Nonsquamous neoplasms of the larynx. Otolaryngol Clin North Am 1986;19:47588. 10. Browne JD. Management of the nonepidermoid cancer of the larynx. Otolaryngol Clin North Am 1997;30:21529. 11. Veivers D, Vito AD, Luna-Ortiz K, Brasnu D, Laccourreye O. Supracricoid partial laryngectomy for non-squamous cell carcinoma of the larynx. J Laryngol Otol 2001;115:38892. 12. Chu PY, Chang SY, Chang P. Treatment of laryngeal cancer: analysis of ten years cases in VGH, Taipei. J Otolaryngol Society ROC 1994;29:37683.
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