Multifocal Laryngeal Carcinoma: A Clinical And Molecular Biology Study

Part Ⅰ Synchronous Multifocal Laryngeal Carcinoma:A Clinical and Pathological AnalysisObjective: To evaluate the carcinogenesis and the possible risk factors of synchronousmultifocal laryngeal carcinomas.Methods: The histological type, pathological grading, T staging, tumor size, tumor locationand history of 12 cases of synchronous multifocal laryngeal carcinomas operated between1991 and 1999 were retrospectively reviewed and analyzed.Results: The incidence of synchronous multifocal laryngeal carcinomas was 1.4%(12/861).All of them were squamous cell carcinomas. The histological type and pathological gradingof different focuses in each patient were the same. The rate of two-focus cancer was91.7%(11/12), and only one case was a three-focus tumor. The lesions of 66.7% (8/12)cases were located in vocal cords. Three patients (25.0%) had a history of radiotherapy, andone had two biopsies for dysplasia of vocal cords. All the cases hadn't been diagnosedaccurately before surgery.Conclusions: The incidence of synchronous multifocal laryngeal carcinoma is low. Most ofthe lesions are located in glottis. The different focuses located in vocal cords might arisefrom one tumor cell clone and the intralaryngeal implantation by vibration and contact oftwo vocal cords might be the cause. Irradiation might be the induced factors. Thesynchronous multifocal possibility of laryngeal cancer should be emphasized so that the lowdiagnosis rate is improved.Part Ⅱ Synchronous Multifocal Laryngeal Carcinoma: Microsatellite Analysis for CarcinogenesisObjective: To define the carcinogenesis of synchronous multifocal laryngeal carcinoma and then to supply the instruments for diagnosis and treatment of laryngeal cancer. Methods: To analyze the clinical features and compare the different allele pattern in main and second tumors of synchronous multifocal laryngeal cancers between 1991 and 1999 in our hospital by microsatelite analysis using 10 microsatellite markers at chromosome arms 3p, 6q, 8p, 9q and 14q.Results: One of 3 cases has two separate masses just in the opposed parts of vocal cords and had two biopsies for moderate to severe dysplasia before surgery. The ratio of different and same allele pattern in both main and second tumor DNA is 2/8, therefore this case may be monocentric origin. The lesions of the other 2 cases can't contact each other and the ratio of different and same allele pattern in both main and second tumor DNA are 9/1 and 6/4, so the cases are considered to be multicentricity.Conclusions: ① Synchronous multifocal laryngeal cancers may have two possible carcinogeneses: one is monocentric meaning that second lesion has the same genesis with main lesion; the other is multicentric which has the different clone origin between the main and the second tumors. ②The possible reason for monocentric carcinogenesis of synchronous multifocal laryngeal cancer may be intralaryngeal implantation of cancer cells from one vocal cord to the other during vibrating. Therefore, early treatments to early glottic cancers would decrease the risk of intralaryngeal implantation. ③ Multifocal laryngeal cancers whose separate lesions failed to touch might be multicentric. ④The technique of microsatellite analysis is valuable to judge the carcinogenesis of synchronous multifocal laryngeal cancer, and might be used in clinic in the future.Part Ⅲ Metachronous Multifocal Laryngeal Carcinoma:A Clinical and Pathological AnalysisObjective: To define the relevant factors of local recurrence and analyze the possible carcinogenesis of laryngeal cancers.Methods: The clinical features and the relationship between local recurrence and clinicopathological factors of 36 cases of laryngeal carcinoma operated between 1991 and 1999 were retrospectively reviewed and analyzed statistically.Results: Of 160 cases of laryngeal carcinoma, local recurrences were occurred in 36 cases (22.5%). Local recurrence occured between 1 and 78 months with medium month 22.3 and it's limited in 1 year in 24 cases (66.7%). The shortest surgical margin were located in inferior margin accounting for 41%. Local recurrence was statistically significantly related to the surgical margin, T staging, anatomical type and size of the tumor. The histological type and pathological grading of primary lesion and recurrent lesion in 10 patients who had secondary laryngectomy were the same. The place of recurrent tumors were associated with the shortest surgical margin in 5 cases with surgical margin less than 3 mm. In the other cases with surgical margin ≥3 mm, there is no anatomical relevance between primary tumor and recurrent tumor, 2 of which the local recurrence was found more than 5 years from first laryngectomy.Conclusions: The reason why most of the shortest surgical margin was located in inferior margin might be the lack of extent evaluation of subglottic lesions. 5mm as a surgical margin is relatively safe for the glottic carcinoma, but it is not the case for the surpraglottic carcinoma. Therefore, the surgical margin more than 5 mm is proposed for surpraglottic carcinoma. For the patients with surgical margin less than 3 mm, postoperative irradiation can effectively reduce the rate of local recurrence, but this does not mean that we can reduce the standard surgical margin during the laryngectomy. Local recurrence was related to the surgical margin, T staging, anatomical type and size of the tumor, but might not be associated with pathological grading and surgical methods. Inadequate surgical margin may be the main reason for local recurrence. The recurrent rate elevated significantly for cases with surgical margin ≤3 mm, so we should perform further treatment. For the patients with surgical margin less than 3 mm, postoperative irradiation can effectively reduce the rate of local recurrence, but this does not mean that we can reduce the standard surgical margin during the laryngectomy. For cases with surgical margin <3mm the recurrent tumor may have the same clone origin with primary tumor. And for those with resection margin ≥ 3 mm and recurrent time more than 5 years, they may be multicentric genesis.