Management des T1a Stimmlippenkarzinoms

R. Reiter; S. Brosch; E. Smith; A. Pickhard

doi:10.1055/s-0033-1349085

Laryngo-Rhino-Otologie, Table of Contents

Laryngorhinootologie 2013; 92(12): 797-807
DOI: 10.1055/s-0033-1349085

Übersicht

Management des T1a Stimmlippenkarzinoms

Management of T1a Vocal Fold Carcinoma

R. Reiter

¹Sektion für Phoniatrie & Pädaudiologie, der Universitäts-HNO-Klinik, Ulm

,

S. Brosch

¹Sektion für Phoniatrie & Pädaudiologie, der Universitäts-HNO-Klinik, Ulm

,

E. Smith

¹Sektion für Phoniatrie & Pädaudiologie, der Universitäts-HNO-Klinik, Ulm

,

A. Pickhard

²Hals-Nasen-Ohrenklinik, Technischen Universität München, München

› Author Affiliations

Abstract

Zusammenfassung

Etwa 2/3 der Larynxkarzinome befallen die Stimmlippen. Der Hauptrisikofaktor hierfür ist Nikotingenuss. Meist gehen sie aus Leukoplakien hervor, die Dysplasien enthalten. Sie werden aufgrund einer Dysphonie in der Regel frühzeitig entdeckt. Mikrostroboskopisch ist ein phonatorischer Stillstand nahezu pathognomonisch für ein Stimmlippenkarzinom. Die Therapie des einseitigen glottischen (T1a) Stimmlippenkarzinoms besteht in der transoralen Laserresektion, die aus onkologischer und funktioneller Sicht gleichwertig wie die primäre Bestrahlung ist. Da lokoregionäre und Fernmetastasen eine Rarität bei einseitigen Stimmlippekarzinomen darstellen, wird bei der Nachsorge laryngostroboskopisch auf den Lokalbefund besonderer Wert gelegt. Bei suspekten Befunden muss eine bioptische Sicherung erfolgen, um dann ggf. zügig eine Therapie einleiten zu können. Insgesamt hat das T1a Stimmlippenkarzinom eine sehr gute Prognose mit einer 5 Jahres Überlebensrate von nahezu 100%.

Abstract

Management of T1a Vocal Fold Carcinoma

About 2/3 of the larynxcarcinomas affect the vocal chords. The main risk factor is smoking. Carcinomas in this localisation often arise from leukoplakias with dysplasia. A typical symptom is dysphonia. Arrest of vibration in microlaryngostroboscopy is a hint that a carcinoma could be present. Transoral lasercordectomy or radiotherapy show equivalent oncological results and results in quality of voice in the treatment of vocal fold carcinoma (T1a). As lymph node and distant metastasis are very rare, follow-up can concentrate on microlaryngoscopy. In case of a suspicious area on the vocal fold, biopsy of the affected tissue is needed to plan correct treatment. The prognosis of the T1 vocal chord carcinoma is quite good with a 5-year survival rate of almost 100%.

Schlüsselwörter

Karzinom - Larynx - T1a - Stimmlippe - Stimme

Key words

carcinoma - larynx - T1a - vocal fold - voice

Full Text

References

Literatur
1 Robert Koch Institut. Zentrum für Krebsregisterdaten, Krebs in Deutschland 2007/2008. 8. Ausgabe 2012: 12-13 und 52–55
2 Globocan: Estimated cancer incidence worldwide. 2008 http://globocan.iarc.fr/factsheet.asp letzter Zugriff 17.04.2013
3 Lang S, Wollenberg B, Dellian M, Steuer-Vogt MK, Schwenzer K, Sautier W, Chucholowski M, Eckel R, Faas I, Wilms E, Ehrenfeld M, Arnold W, Kastenbauer E, Hölzel D. Clinical and epidemiological data of patients with malignomas of the head and neck. Laryngo-Rhino-Otolo 2002; 81: 499-508
4 Probst R, Grevers G, Iro H. Hals-Nasen-Ohrenheilkunde. 3. Auflage Stutgart: Thieme; 2008: 1-470
5 Wittekind C, Meyer HJ. TNM Klassifikation maligner Tumore. 7. Auflage UICC (International Union against cancer); 2010: 37-42
6 Waldfahrer F, Hauptmann B, Iro H. Lymph node metastasis of glottic laryngeal carcinoma. Laryngorhinootologie 2005; 84: 96-100
7 Garavello W, Ciardo A, Spreafico R, Gaini RM. Risk factors for distant metastases in head and neck squamous cell carcinoma. Arch Otolaryngol Head Neck Surg 2006; 132: 762-766
8 Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin 2012; 62: 10-29
9 Leemans CR, Braakhuis BJ, Brakenhoff RH. The molecular biology of head and neck cancer. Nat Rev Cancer 2011; 11: 9-22
10 Agrawal N, Ha PK. Management of early-stage laryngeal cancer. Otolaryngol Clin North Am 2008; 41: 757-769
11 Arens C. Transoral treatment strategies in head and neck tumors. Laryngo-Rhino-Otolo 2012; 91 (Suppl. 01) 86-101
12 Chera BS, Amdur RJ, Morris CG, Kirwan JM, Mendenhall WM. T1N0 to T2N0 squamous cell carcinoma of the glottic larynx treated with definitive radiotherapy. Int J Radiat Oncol Biol Phys 2010; 78: 461-466
13 Vaezi MF, Qadeer MA, Lopez R, Colabianchi N. Laryngeal cancer and gastroesophageal reflux disease: a case-control study. Am J Med 2006; 119: 768-776
14 Talamini R, Bosetti C, La Vecchia C, Dal Maso L, Levi F, Bidoli E, Negri E, Pasche C, Vaccarella S, Barzan L, Franceschi S. Combined effect of tobacco and alcohol on laryngeal cancer risk: a case-control study. Cancer Causes Control 2002; 13: 957-964
15 Huebbers CU, Preuss SF, Kolligs J, Vent J, Stenner M, Wieland U, Silling S, Drebber U, Speel EJ, Klussmann JP. Integration of HPV6 and downregulation of AKR1C3 expression mark malignant transformation in a patient with juvenile-onset laryngeal papillomatosis. PLoS One 2013; 8: e57207
16 Reidy PM, Dedo HH, Rabah R, Field JB, Mathog RH, Gregoire L, Lancaster WD. Integration of human papillomavirus type 11 in recurrent respiratory papilloma-associated cancer. Laryngoscope 2004; 114: 1906-1909
17 Jo VY, Mills SE, Stoler MH, Stelow EB. Papillary squamous cell carcinoma of the head and neck: frequent association with human papillomavirus infection and invasive carcinoma. Am J Surg Pathol 2009; 33: 1720-1724
18 Baumann JL, Cohen S, Evjen AN, Law JH, Vadivelu S, Attia A, Schindler JS, Chung CH, Wirth PS, Meijer CJ, Snijders PJ, Yarbrough WG, Slebos RJ. Human papillomavirus in early laryngeal carcinoma. Laryngoscope 2009; 119: 1531-1537
19 Kreimer AR, Clifford GM, Boyle P, Franceschi S. Human papillomavirus types in head and neck squamous cell carcinomas worldwide: a systematic review. Cancer Epidemiol Biomarkers Prev 2005; 14: 467-475
20 Dietz A, Wichmann G. Head and neck cancer: effective prevention in youth and predictive diagnostics for personalised treatment strategies according to biological differences. EPMA J 2011; 2: 241-249
21 Deitmer T. Legal cases on the correlation between exposure to asbestos fiber dust and laryngeal cancer. Laryngo-Rhino-Otol 1992; 71: 491-494
22 Marchand JL, Luce D, Leclerc A, Goldberg P, Orlowski E, Bugel I, Brugère J. Laryngeal and hypopharyngeal cancer and occupational exposure to asbestos and man-made vitreous fibers: results of a case-control study. Am J Ind Med 2000; 37: 581-589
23 Straif K, Benbrahim-Tallaa L, Baan R, Grosse Y, Secretan B, El Ghissassi F, Bouvard V, Guha N, Freeman C, Galichet L, Cogliano V. WHO International Agency for Research on Cancer Monograph Working Group . A review of human carcinogens – part C: metals, arsenic, dusts, and fibres. Lancet Oncol 2009; 10: 453-454
24 Schultz P. Vocal fold cancer. Eur Ann Otorhinolaryngol Head Neck Dis 2011; 128: 301-308
25 Baan R, Grosse Y, Straif K, Secretan B, El Ghissassi F, Bouvard V, Benbrahim-Tallaa L, Guha N, Freeman C, Galichet L, Cogliano V. WHO International Agency for Research on Cancer Monograph Working Group . A review of human carcinogens – Part F: chemical agents and related occupations. Lancet Oncol 2009; 10: 1143-1144
26 Jayaprakash V, Natarajan KK, Moysich KB, Rigual NR, Ramnath N, Natarajan N, Reid ME. Wood dust exposure and the risk of upper aero-digestive and respiratory cancers in males. Occup Environ Med 2008; 65: 647-654
27 León X, Quer M, Diez S, Orús C, López-Pousa A, Burgués J. Second neoplasm in patients with head and neck cancer. Head Neck 1999; 21: 204-210
28 Lee CH, Lee KW, Fang FM, Wu DC, Shieh TY, Huang HL, Chen CH, Chen PH, Chen MK, Kuo SJ, Chang CH, Tsai YS, Chiang SL, Tu HP, Chen BH, Ko YC. The use of tobacco-free betel-quid in conjunction with alcohol/tobacco impacts early-onset age and carcinoma distribution for upper aerodigestive tract cancer. J Oral Pathol Med 2011; 40: 684-692
29 Amemiya K, Shibuya H, Yoshimura R, Okada N. The risk of radiation-induced cancer in patients with squamous cell carcinoma of the head and neck and its results of treatment. Br J Radiol 2005; 78: 1028-1033
30 Malard O, Toquet C, Gayet-Delacroix M, Bordure P, Beauvillain de Montreuil C, Bardet E. Radiation-induced cancers of the pharynx and larynx: a study of five clinical cases. Clin Otolaryngol Allied Sci 2002; 27: 68-74
31 Ulusan M, Yilmazer R, Ozluk Y, Enoz M, Suoglu Y. Radiation-induced osteosarcoma of the larynx: case report and literature review. Ear Nose Throat J 2012; 91: 22-25
32 Freije JE, Beatty TW, Campbell BH, Woodson BT, Schultz CJ, Toohill RJ. Carcinoma of the larynx in patients with gastroesophageal reflux. Am J Otolaryngol 1996; 17: 386-390
33 Cammarota G, Galli J, Cianci R, De Corso E, Pasceri V, Palli D, Masala G, Buffon A, Gasbarrini A, Almadori G, Paludetti G, Gasbarrini G, Maurizi M. Association of laryngeal cancer with previous gastric resection. Ann Surg 2004; 240: 817-824
34 Bacciu A, Mercante G, Ingegnoli A, Bacciu S, Ferri T. Reflux esophagitis as a possible risk factor in the development of pharyngolaryngeal squamous cell carcinoma. Tumori 2003; 89: 485-487
35 Pickhard A, Smith E, Rottscholl R, Brosch S, Reiter R. Disorders of the larynx and chronic inflammatory diseases. Laryngo-Rhino-Otol 2012; 91: 758-766
36 Gong H, Shi Y, Zhou L, Tao L, Shi Y, Cao W, Cheng L. Helicobacter pylori infection of the larynx may be an emerging risk factor for laryngeal squamous cell carcinoma. Clin Transl Oncol 2012; 14: 905-910
37 Kutler DI, Auerbach AD, Satagopan J, Giampietro PF, Batish SD, Huvos AG, Goberdhan A, Shah JP, Singh B. High incidence of head and neck squamous cell carcinoma in patients with Fanconi anemia. Arch Otolaryngol Head Neck Surg 2003; 129: 106-112
38 Rutt AL, Hawkshaw MJ, Sataloff RT. Laryngeal cancer in patients younger than 30 years: a review of 99 cases. Ear Nose Throat J 2010; 89: 189-192
39 Rinaldo A, Ferlito A, Healy GB. Cancer of the larynx in children and adolescents: a neoplastic lesion with a different etiology. Acta Otolaryngol 2004; 124: 992-994
40 Macfarlane TV, Macfarlane GJ, Oliver RJ, Benhamou S, Bouchardy C, Ahrens W, Pohlabeln H, Lagiou P, Lagiou A, Castellsague X, Agudo A, Merletti F, Richiardi L, Kjaerheim K, Slamova A, Schejbalova M, Canova C, Simonato L, Talamini R, Barzan L, Conway DI, McKinney PA, Znaor A, Lowry RJ, Thomson P, Healy CM, McCartan BE, Marron M, Hashibe M, Brennan P. The etiology of upper aerodigestive tract cancers among young adults in Europe: the ARCAGE study. Cancer Causes Control 2010; 21: 2213-2221
41 Dietz A. Kopf-Hals-Tumoren – Therapie des Larynx-/Hypopharynxkarzinoms unter besonderer Berücksichtigung des Larynxorganerhalts. 2. Auflage UNI-MED Verlag AG; Bremen-London-Boston: 2010: 1-199
42 Perez-Ordoñez B, Beauchemin M, Jordan RC. Molecular biology of squamous cell carcinoma of the head and neck. J Clin Pathol 2006; 59: 445-453
43 Hunter KD, Parkinson EK, Harrison PR. Profiling early head and neck cancer. Nat Rev Cancer 2005; 5: 127-135
44 Isenberg JS, Crozier DL, Dailey SH. Institutional and comprehensive review of laryngeal leukoplakia. Ann Otol Rhinol Laryngol 2008; 117: 74-79
45 Barnes L, Eveson JW, Reichart P, Sidransky D. Pathology and Genetics of Head and Neck Tumours. World Health Organization Classification of Tumours. IARC Press; Lyon: 2005: 1-112
46 Eckel HE, Raunik W, Rogatsch H. Laryngeal intraepithelial neoplasia. Laryngorhinootologie 2008; 87: 425-438, 439–443
47 Reiter R, Rettinger G, Veit J, Pilcher C, Brosch S. Chondrosarcoma of the larynx in patient with vocal fold augmentation with teflon. Laryngo-Rhino-Otol 2012; 91: 644-645
48 Smith E, Rottscholl R, Brosch S, Reiter R. Malignant lymphoma in the larynx. Laryngo-Rhino-Otol angenommen 03.2013
49 Montgomery J, White A. A decade of laryngeal dysplasia in Paisley, Scotland. Eur Arch Otorhinolaryngol 2012; 269: 947-951
50 Weller MD, Nankivell PC, McConkey C, Paleri V, Mehanna HM. The risk and interval to malignancy of patients with laryngeal dysplasia; a systematic review of case series and meta-analysis. Clin Otolaryngol 2010; 35: 364-372
51 Sllamniku B, Bauer W, Painter C, Sessions D. The transformation of laryngeal keratosis into invasive carcinoma. Am J Otolaryngol 1989; 10: 42-54
52 Sadri M, McMahon J, Parker A. Management of laryngeal dysplasia: a review. Eur Arch Otorhinolaryngol 2006; 263: 843-852
53 Hirano M. Clinical examination of voice. Wien, New York: Springer Verlag; 1981: 100
54 Hirano M. Structure and vibratory patterns of the vocal folds. In: Swashima N, Cooper PS. (eds.). Dynamic aspects of speech production. Tokyo: University of Tokyo Press; 1977: 13-27
55 Seidner W, Wendler J, Halbedel G. Mikrostroboskopie. Folia phoniat 1972; 24: 1-8
56 Chu EA, Kim YJ. Laryngeal cancer: diagnosis and preoperative work-up. Otolaryngol Clin North Am 2008; 41: 673-695
57 Zhao R, Hirano M, Tanaka S, Sato K. Vocal fold epithelial hyperplasia: Vibratory behaviour versus extent of lesion. Arch Otolaryngol Head Neck Surg 1991; 117: 1015-1018
58 Reiter R, Brosch S. Chronic laryngitis – associated factors and voice assessment. Laryngo-Rhino-Otol 2009; 88: 181-185
59 Vukasinović M, Djukić V, Stanković P, Krejović-Trivić S, Milovanović J, Mikić A, Ugrinović A, Dragisić M. Nonvibrating segment predicting glottis carcinoma. Acta Chir Iugosl 2009; 56: 61-64
60 Gamboa J, Echeverría L, Molina B, Cobeta I. Stroboscopic assessment of chronic laryngitis. Acta Otorrinolaringol Esp 2006; 57: 266-269
61 Pentenero M, Carrozzo M, Pagano M, Galliano D, Broccoletti R, Scully C, Gandolfo S. Oral mucosal dysplastic lesions and early squamous cell carcinomas: underdiagnosis from incisional biopsy. Oral Dis 2003; 9: 68-72
62 AWMF. S2 k-Leitlinie: Diagnostik und Management von Vorläuferläsionen des oralen Plattenepithelkarzinoms in der Zahn-, Mund- und Kieferheilkunde. Stand 01.03. 2010
63 Schwartz LH, Ozsahin M, Zhang GN, Touboul E, De Vataire F, Andolenko P, Lacau-Saint-Guily J, Laugier A, Schlienger M. Synchronous and metachronous head and neck carcinomas. Cancer 1994; 74: 1933-1938
64 Lin K, Patel SG, Chu PY, Matsuo JM, Singh B, Wong RJ, Kraus DH, Shaha AR, Shah JP, Boyle JO. Second primary malignancy of the aerodigestive tract in patients treated for cancer of the oral cavity and larynx. Head Neck 2005; 27: 1042-1048
65 Laccourreye O, Veivers FD, Hans S, Brasnu FD, Garcia D, Laccourreye FL. Metachronous second primary cancers after successful partial laryngectomy for invasive squamous cell carcinoma of the true vocal cord. Ann Otol Rhinol Laryngol 2002; 111: 204-209
66 Gao X, Fisher SG, Mohideen N, Emami B. Second primary cancers in patients with laryngeal cancer: a population-based study. Int J Radiat Oncol Biol Phys 2003; 56: 427-435
67 Shvero J, Shvili I, Mizrachi A, Shpitzer T, Nageris B, Koren R, Hadar T. T1 glottic carcinoma involving the posterior commissure. Laryngoscope 2009; 119: 1116-1119
68 Shvero J, Hadar T, Segal K, Yaniv E, Marshak G, Feinmesser R. T1 glottic carcinoma involving the anterior commissure. Eur J Surg Oncol 1994; 20: 557-560
69 Steiner W, Ambrosch P. Endoscopic laser surgery of the upper aerodigestive tract. Stuttgart: Thieme; 2000: 1-98
70 Peretti G, Piazza C, Bolzoni A. Endoscopic treatment for early glottic cancer: indications and oncologic outcome. Otolaryngol Clin North Am 2006; 39: 173-189
71 Rucci L, Romagnoli P, Scala J. CO(2) laser therapy in Tis and T1 glottic cancer: indications and results. Head Neck 2010; 32: 392-398
72 Sigston E, de Mones E, Babin E, Hans S, Hartl DM, Clement P, Brasnu DF. Early-stage glottic cancer: oncological results and margins in laser cordectomy. Arch Otolaryngol Head Neck Surg 2006; 132: 147-152
73 Ambrosch P. The role of laser microsurgery in the treatment of laryngeal cancer. Curr Opin Otolaryngol Head Neck Surg 2007; 15: 82-88
74 Rödel RM, Steiner W, Müller RM, Kron M, Matthias C. Endoscopic laser surgery of early glottic cancer: involvement of the anterior commissure. Head Neck 2009; 31: 583-592
75 Grant DG, Repanos C, Malpas G, Salassa JR, Hinni ML. Transoral laser microsurgery for early laryngeal cancer. Expert Rev Anticancer Ther 2010; 10: 331-338
76 Eckel HE, Thumfart W, Jungehülsing M, Sittel C, Stennert E. Transoral laser surgery for early glottic carcinoma. Eur Arch Otorhinolaryngol 2000; 257: 221-226
77 Eckel HE. Lasers in the larynx, hypopharynx and trachea in benign diseases. Laryngo-Rhino-Otol 2003; 82 (Suppl. 01) 89-113
78 Remacle M, Eckel HE, Antonelli A, Brasnu D, Chevalier D, Friedrich G, Olofsson J, Rudert HH, Thumfart W, de Vincentiis M, Wustrow TP. Endoscopic cordectomy. A proposal for a classification by the Working Committee, European Laryngological Society. Eur Arch Otorhinolaryngol 2000; 257: 227-231
79 Spielmann PM, Majumdar S, Morton RP. Quality of life and functional outcomes in the management of early glottic carcinoma: a systematic review of studies comparing radiotherapy and transoral laser microsurgery. Clin Otolaryngol 2010; 35: 373-382
80 Medini E, Medini I, Lee CK, Gapany M, Levitt SH. The role of radiotherapy in the management of carcinoma in situ of the glottic larynx. Am J Clin Oncol 1998; 21: 298-301
81 Hristov B, Bajaj GK. Radiotherapeutic management of laryngeal carcinoma. Otolaryngol Clin North Am 2008; 41: 715-740
82 Núñez Batalla F, Caminero Cueva MJ, Señaris González B, Llorente Pendás JL, Gorriz Gil C, López Llames A, Alonso Pantiga R, Suárez Nieto C. Voice quality after endoscopic laser surgery and radiotherapy for early glottic cancer: objective measurements emphasizing the Voice Handicap Index. Eur Arch Otorhinolaryngol 2008; 265: 543-548
83 Han YJ, Lee HS, Kim SW, Hong JC, Kim ST, Park HS, Lee KD. Transoral laser microsurgery of recurrent early glottic cancer after radiation therapy: clinical feasibility and limitations. Ann Otol Rhinol Laryngol 2012; 121: 375-382
84 Feng Y, Wang B, Wen S. Laser surgery versus radiotherapy for T1-T2N0 glottic cancer: a meta-analysis. ORL J Otorhinolaryngol Relat Spec 2011; 73: 336-342
85 Bae JS, Roh JL, Lee SW, Kim SB, Kim JS, Lee JH, Choi SH, Nam SY, Kim SY. Laryngeal edema after radiotherapy in patients with squamous cell carcinomas of the larynx and hypopharynx. Oral Oncol 2012; 48: 853-858
86 Osborn HA, Hu A, Venkatesan V, Nichols A, Franklin JH, Yoo JH, Ceron M, Whelan F, Fung K. Comparison of endoscopic laser resection versus radiation therapy for the treatment of early glottic carcinoma. J Otolaryngol Head Neck Surg 2011; 40: 200-204
87 Sittel C, Eckel HE, Eschenburg C. Phonatory results after laser surgery for glottic carcinoma. Otolaryngol Head Neck Surg 1998; 119: 418-424
88 Le QT, Takamiya R, Shu HK, Smitt M, Singer M, Terris DJ, Fee WE, Goffinet DR, Fu KK. Treatment results of carcinoma in situ of the glottis: an analysis of 82 cases. Arch Otolaryngol Head Neck Surg 2000; 126: 1305-1312
89 Sengupta N, Morris CG, Kirwan J, Amdur RJ, Mendenhall WM. Definitive radiotherapy for carcinoma in situ of the true vocal cords. Am J Clin Oncol 2010; 33: 94-95
90 Garcia-Serra A, Hinerman RW, Amdur RJ, Morris CG, Mendenhall WM. Radiotherapy for carcinoma in situ of the true vocal cords. Head Neck 2002; 24: 390-394
91 Zhang SY, Lu ZM, Luo XN, Chen LS, Ge PJ, Song XH, Chen SH, Wu YL. Retrospective analysis of prognostic factors in 205 patients with laryngeal squamous cell carcinoma who underwent surgical treatment. PLoS One 2013; 8: e60157
92 Delsupehe KG, Zink I, Lejaegere M, Bastian RW. Voice quality after narrow-margin laser cordectomy compared with laryngeal irradiation. Otolaryngol Head Neck Surg 1999; 121: 528-533
93 Dietz A, Meyer A, Singer S. Measuring quality of life in head and neck cancer. Current status and future needs. HNO 2009; 57: 857-865
94 Wallesch B, Sieron J, Johannsen HS. The value of indirect microlaryngo-stroboscopy in the follow-up care of patients with vocal cord carcinoma treated with primary irradiation. Laryngo-Rhino-Otol 1991; 70: 559-561
95 Tsunoda K, Soda Y, Tojima H, Shinogami M, Ohta Y, Nibu K, Tayama N, Niimi S, Hirose H. Stroboscopic observation of the larynx after radiation in patients with T1 glottic carcinoma. Acta Otolaryngol Suppl 1997; 527: 165-166
96 Tabor MP, Brakenhoff RH, Ruijter-Schippers HJ, Van Der Wal JE, Snow GB, Leemans CR, Braakhuis BJ. Multiple head and neck tumors frequently originate from a single preneoplastic lesion. Multiple head and neck tumors frequently originate from a single preneoplastic lesion. Am J Pathol 2002; 161: 1051-1060
97 van der Waal I. Potentially malignant disorders of the oral and oropharyngeal mucosa; terminology, classification and present concepts of management. Oral Oncol 2009; 45: 317-323
98 Esser D, Anke S, Roessner A, Freigang B. Second carcinomas in cancers of the mouth cavity, pharynx and larynx. Clinical, histopathologic and cell kinetic findings. Laryngo-Rhino-Otol 2000; 79: 478-482
99 Colasanto JM, Haffty BG, Wilson LD. Evaluation of local recurrence and second malignancy in patients with T1 and T2 squamous cell carcinoma of the larynx. Cancer J 2004; 10: 61-66
100 Leitlinienprogramm Onkologie . S3 Leitlinie Mundhöhlenkarzinom, Kurzversion: Mundhöhlen Karzinom „Diagnostik und Therapie des Mundhöhlenkarzinoms“. AWMF 2012; 1-38