Evaluation and Management of the Unknown Primary Carcinoma of the Head and Neck

View More View Less
  • a From the Departments of Thoracic/Head and Neck Surgery and Thoracic/Head and Neck Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas.

Squamous cell carcinoma of unknown primary origin in the head and neck is encountered as a recurring clinical problem in head and neck cancer clinics, affecting 3% to 25% of patients. This article describes the clinical presentation, appropriate evaluation, and treatment strategies for this important subgroup. Treatment—best carried out with multidisciplinary teams of specialists experienced in the care of head and neck cancer patients—is curative for most of these patients.

If the inline PDF is not rendering correctly, you can download the PDF file here.

Correspondence: Merrill S. Kies, MD, University of Texas M. D. Anderson Cancer Center, Department of Thoracic/Head and Neck Medical Oncology, Unit 432, P.O. Box 301402, Houston, TX 77230-1402. E-mail: mkies@mdanderson.org
  • 1.

    Miller FR, Hussey D, Beeram M. Positron emission tomography in the management of unknown primary head and neck carcinoma. Arch Otolaryngol Head Neck Surg 2005;131:626629.

    • Search Google Scholar
    • Export Citation
  • 2.

    Califano J, Leong PL, Koch WM. Second esophageal tumors in patients with head and neck squamous cell carcinoma: an assessment of clonal relationships. Clin Cancer Res 1999;5:18621867.

    • Search Google Scholar
    • Export Citation
  • 3.

    Jesse RH, Neff LE. Metastatic carcinoma in cervical nodes with an unknown primary lesion. Am J Surg 1966;112:547553.

  • 4.

    Harwick RD. Cervical metastases from an occult primary site. Semin Surg Oncol 1991;7:28.

  • 5.

    Issing WJ, Taleban B, Tauber S. Diagnosis and management of carcinoma of unknown primary in the head and neck. Eur Arch Otorhinolaryngol 2003;260:436443.

    • Search Google Scholar
    • Export Citation
  • 6.

    Kirschner MJ, Fietkau R, Waldfahrer F. [Therapy pf cervical lymph node metastases of unknown primary tumor]. Strahlenther Onkol 1997;173:362368 [in German].

    • Search Google Scholar
    • Export Citation
  • 7.

    Grau C, Johansen LV, Jakobsen J. Cervical lymph node metastases from unknown primary tumours. Results from a national survey by the Danish Society for Head and Neck Oncology. Radiother Oncol 2000;55:121129.

    • Search Google Scholar
    • Export Citation
  • 8.

    Schmalbach CE, Miller FR. Occult primary head and neck carcinoma. Curr Oncol Rep 2007;9:139146.

  • 9.

    Mendenhall WM, Mancuso AA, Parsons JT. Diagnostic evaluation of squamous cell carcinoma metastatic to cervical lymph nodes from an unknown head and neck primary site. Head Neck 1998;20:739744.

    • Search Google Scholar
    • Export Citation
  • 10.

    Martin H, Morfit HM. Cervical lymph node metastasis as the first symptom of cancer. Surg Gynecol Obstet 1944;78:133159.

  • 11.

    Jones AS, Cook JA, Phillips DE, Roland NR. Squamous carcinoma presenting as an enlarged cervical lymph node. Cancer 1993;72:17561761.

  • 12.

    Erkal HS, Mendenhall WM, Amdur RJ. Squamous cell carcinomas metastatic to cervical lymph nodes from an unknown head-and-neck mucosal site treated with radiation therapy alone or in combination with neck dissection. Int J Radiat Oncol Biol Phys 2001;50:5563.

    • Search Google Scholar
    • Export Citation
  • 13.

    Colletier PJ, Garden AS, Morrison WH. Postoperative radiation for squamous cell carcinoma metastatic to cervical lymph nodes from an unknown primary site: outcomes and patterns of failure. Head Neck 1998;20:674681.

    • Search Google Scholar
    • Export Citation
  • 14.

    Erkal HS, Mendenhall WM, Amdur RJ. Squamous cell carcinomas metastatic to cervical lymph nodes from an unknown head and neck mucosal site treated with radiation therapy with palliative intent. Radiother Oncol 2001;59:319321.

    • Search Google Scholar
    • Export Citation
  • 15.

    Amedee RG, Dhurandhar NR. Fine-needle aspiration biopsy. Laryngoscope 2001;111:15511557.

  • 16.

    Layfield LJ. Fine-needle aspiration of the head and neck. Pathology (Phila) 1996;4:409438.

  • 17.

    McGuirt WF, McCabe BF. Significance of node biopsy before definitive treatment of cervical metastatic carcinoma. Laryngoscope 1978;88:594597.

    • Search Google Scholar
    • Export Citation
  • 18.

    Robbins KT, Cole R, Marvel J. The violated neck: cervical node biopsy prior to definitive treatment. Otolaryngol Head Neck Surg 1986;94:605610.

    • Search Google Scholar
    • Export Citation
  • 19.

    Ellis ER, Mendenhall WM, Rao PV. Incisional or excisional neck-node biopsy before definitive radiotherapy, alone or followed by neck dissection. Head Neck 1991;13:177183.

    • Search Google Scholar
    • Export Citation
  • 20.

    Mack Y, Parsons JT, Mendenhall WM. Squamous cell carcinoma of the head and neck: management after excisional biopsy of a solitary metastatic neck node. Int J Radiat Oncol Biol Phys 1993;25:619622.

    • Search Google Scholar
    • Export Citation
  • 21.

    Muraki AS, Mancuso AA, Harnsberger HR. Metastatic cervical adenopathy from tumors of unknown origin: the role of CT. Radiology 1984;152:749753.

    • Search Google Scholar
    • Export Citation
  • 22.

    Regelink G, Brouwer J, de Bree R. Detection of unknown primary tumours and distant metastases in patients with cervical metastases: value of FDG-PET versus conventional modalities. Eur J Nucl Med Mol Imaging 2002;29:10241030.

    • Search Google Scholar
    • Export Citation
  • 23.

    Greven KM, Keyes JW Jr, Williams DW III. Occult primary tumors of the head and neck: lack of benefit from positron emission tomography imaging with 2-[F-18]fluoro-2-deoxy-D-glucose. Cancer 1999;86:114118.

    • Search Google Scholar
    • Export Citation
  • 24.

    Johansen J, Buus S, Loft A. Prospective study of 18FDG-PET in the detection and management of patients with lymph node metastases to the neck from an unknown primary tumor. Results from the DAHANCA-13 study. Head Neck 2008;30:471478.

    • Search Google Scholar
    • Export Citation
  • 25.

    Nieder C, Gregoire V, Ang KK. Cervical lymph node metastases from occult squamous cell carcinoma: cut down a tree to get an apple? Int J Radiat Oncol Biol Phys 2001;50:727733.

    • Search Google Scholar
    • Export Citation
  • 26.

    Rusthoven KE, Koshy M, Paulino AC. The role of fluorodeoxyglucose positron emission tomography in cervical lymph node metastases from an unknown primary tumor. Cancer 2004;101:26412649.

    • Search Google Scholar
    • Export Citation
  • 27.

    Nabili V, Zaia B, Blackwell KE. Positron emission tomography: poor sensitivity for occult tonsillar cancer. Am J Otolaryngol 2007;28:153157.

    • Search Google Scholar
    • Export Citation
  • 28.

    Silva P, Hulse P, Sykes AJ. Should FDG-PET scanning be routinely used for patients with an unknown head and neck squamous primary? J Laryngol Otol 2007;121:149153.

    • Search Google Scholar
    • Export Citation
  • 29.

    Pfister DG, Ang K, Brockstein B. NCCN Practice Guidelines for Head and Neck Cancers. Oncology (Williston Park) 2000;14:163194.

  • 30.

    Wartski M, Le Stanc E, Gontier E. In search of an unknown primary tumour presenting with cervical metastases: performance of hybrid FDG-PET-CT. Nucl Med Commun 2007;28:365371.

    • Search Google Scholar
    • Export Citation
  • 31.

    Freudenberg LS, Fischer M, Antoch G. Dual modality of 18F-fluorodeoxyglucose-positron emission tomography/computed tomography in patients with cervical carcinoma of unknown primary. Med Princ Pract 2005;14:155160.

    • Search Google Scholar
    • Export Citation
  • 32.

    Gluckman JL, Robbins KT, Fried MP. Cervical metastatic squamous carcinoma of unknown or occult primary source. Head Neck 1990;12:440443.

  • 33.

    Chepeha D, Koch W, Pitman K. Management of unknown primary tumor. Head Neck 2003;25:499504.

  • 34.

    Lee DJ, Rostock RA, Harris A. Clinical evaluation of patients with metastatic squamous carcinoma of the neck with occult primary tumor. South Med J 1986;79:979983.

    • Search Google Scholar
    • Export Citation
  • 35.

    Righi PD, Sofferman RA. Screening unilateral tonsillectomy in the unknown primary. Laryngoscope 1995;105(5 Pt 1):548550.

  • 36.

    Randall DA, Johnstone PA, Foss RD, Martin PJ. Tonsillectomy in diagnosis of the unknown primary tumor of the head and neck. Otolaryngol Head Neck Surg 2000;122:5255.

    • Search Google Scholar
    • Export Citation
  • 37.

    Haas I, Hoffmann TK, Engers R, Ganzer U. Diagnostic strategies in cervical carcinoma of an unknown primary (CUP). Eur Arch Otorhinolaryngol 2002;259:325333.

    • Search Google Scholar
    • Export Citation
  • 38.

    McQuone SJ, Eisele DW, Lee DJ. Occult tonsillar carcinoma in the unknown primary. Laryngoscope 1998;108(11 Pt 1):16051610.

  • 39.

    Koch WM, Bhatti N, Williams MF, Eisele DW. Oncologic rationale for bilateral tonsillectomy in head and neck squamous cell carcinoma of unknown primary source. Otolaryngol Head Neck Surg 2001;124:331333.

    • Search Google Scholar
    • Export Citation
  • 40.

    Slaughter DP, Southwick HW, Smejkal W. Field cancerization in oral stratified squamous epithelium; clinical implications of multicentric origin. Cancer 1953;6:963968.

    • Search Google Scholar
    • Export Citation
  • 41.

    Lydiatt WM, Anderson PE, Bazzana T. Molecular support for field cancerization in the head and neck. Cancer 1998;82:13761380.

  • 42.

    Califano J, van der Riet P, Westra W. Genetic progression model for head and neck cancer: implications for field cancerization. Cancer Res 1996;56:24882492.

    • Search Google Scholar
    • Export Citation
  • 43.

    Papadimitrakopoulou VA, Shin DM, Hong WK. Molecular and cellular biomarkers for field cancerization and multistep process in head and neck tumorigenesis. Cancer Metastasis Rev 1996;15:5376.

    • Search Google Scholar
    • Export Citation
  • 44.

    Califano J, Westra WH, Koch W. Unknown primary head and neck squamous cell carcinoma: molecular identification of the site of origin. J Natl Cancer Inst 1999;91:599604.

    • Search Google Scholar
    • Export Citation
  • 45.

    Feinmesser R, Miyazaki I, Cheung R. Diagnosis of nasopharyngeal carcinoma by DNA amplification of tissue obtained by fine-needle aspiration. N Engl J Med 1992;326:1721.

    • Search Google Scholar
    • Export Citation
  • 46.

    Yap YY, Hassan S, Chan M. Epstein-Barr virus DNA detection in the diagnosis of nasopharyngeal carcinoma. Otolaryngol Head Neck Surg 2007;136:986991.

    • Search Google Scholar
    • Export Citation
  • 47.

    Gillison ML, Koch WM, Capone RB. Evidence for a causal association between human papillomavirus and a subset of head and neck cancers. J Natl Cancer Inst 2000;92:709720.

    • Search Google Scholar
    • Export Citation
  • 48.

    Paz IB, Cook N, Odom-Mayon T. Human papillomavirus (HPV) in head and neck cancer. An association of HPV 16 with squamous cell carcinoma of Waldeyer's tonsillar ring. Cancer 1997;79:595604.

    • Search Google Scholar
    • Export Citation
  • 49.

    Venuti A, Badaracco G, Rizzo C. Presence of HPV in head and neck tumours: high prevalence in tonsillar localization. J Exp Clin Cancer Res 2004;23:561566.

    • Search Google Scholar
    • Export Citation
  • 50.

    Hoffmann M, Gottschlich S, Gorogh T. Human papillomaviruses in lymph node neck metastases of head and neck cancers. Acta Otolaryngol 2005;125:415421.

    • Search Google Scholar
    • Export Citation
  • 51.

    Reimers N, Kasper HU, Weissenborn SJ. Combined analysis of HPV-DNA, p16 and EGFR expression to predict prognosis in oropharyngeal cancer. Int J Cancer 2007;120:17311738.

    • Search Google Scholar
    • Export Citation
  • 52.

    Begum S, Gillison ML, Nicol TL, Westra WH. Detection of human papillomavirus-16 in fine-needle aspirates to determine tumor origin in patients with metastatic squamous cell carcinoma of the head and neck. Clin Cancer Res 2007;13:11861191.

    • Search Google Scholar
    • Export Citation
  • 53.

    Harper CS, Mendenhall WM, Parsons JT. Cancer in neck nodes with unknown primary site: role of mucosal radiotherapy. Head Neck 1990;12:463469.

    • Search Google Scholar
    • Export Citation
  • 54.

    Maulard C, Housset M, Brunel P. Postoperative radiation therapy for cervical lymph node metastases from an occult squamous cell carcinoma. Laryngoscope 1992;102:884890.

    • Search Google Scholar
    • Export Citation
  • 55.

    Coster JR, Foote RL, Olsen KD. Cervical nodal metastasis of squamous cell carcinoma of unknown origin: indications for withholding radiation therapy. Int J Radiat Oncol Biol Phys 1992;23:743749.

    • Search Google Scholar
    • Export Citation
  • 56.

    Nieder C, Ang KK. Cervical lymph node metastases from occult squamous cell carcinoma. Curr Treat Options Oncol 2002;3:3340.

  • 57.

    Glynne-Jones RG, Anand AK, Young TE, Berry RJ. Metastatic carcinoma in the cervical lymph nodes from an occult primary: a conservative approach to the role of radiotherapy. Int J Radiat Oncol Biol Phys 1990;18:289294.

    • Search Google Scholar
    • Export Citation
  • 58.

    Sinnathamby K, Peters LJ, Laidlaw C, Hughes PG. The occult head and neck primary: to treat or not to treat? Clin Oncol (R Coll Radiol) 1997;9:322329.

    • Search Google Scholar
    • Export Citation
  • 59.

    Beldi D, Jereczek-Fossa BA, D'Onofrio A. Role of radiotherapy in the treatment of cervical lymph node metastases from an unknown primary site: retrospective analysis of 113 patients. Int J Radiat Oncol Biol Phys 2007;69:10511058.

    • Search Google Scholar
    • Export Citation
  • 60.

    Weir L, Keane T, Cummings B. Radiation treatment of cervical lymph node metastases from an unknown primary: an analysis of outcome by treatment volume and other prognostic factors. Radiother Oncol 1995;35:206211.

    • Search Google Scholar
    • Export Citation
  • 61.

    Strojan P, Anicin A. Combined surgery and postoperative radiotherapy for cervical lymph node metastases from an unknown primary tumour. Radiother Oncol 1998;49:3340.

    • Search Google Scholar
    • Export Citation
  • 62.

    Aslani M, Sultanem K, Voung T. Metastatic carcinoma to the cervical nodes from an unknown head and neck primary site: is there a need for neck dissection? Head Neck 2007;29:585590.

    • Search Google Scholar
    • Export Citation
  • 63.

    Greenberg JS, Fowler R, Gomez J. Extent of extracapsular spread: a critical prognosticator in oral tongue cancer. Cancer 2003;97:14641470.

  • 64.

    Davidson BJ, Spiro RH, Patel S. Cervical metastases of occult origin: the impact of combined modality therapy. Am J Surg 1994;168:395399.

  • 65.

    Iganej S, Kagan R, Anderson P. Metastatic squamous cell carcinoma of the neck from an unknown primary: management options and patterns of relapse. Head Neck 2002;24:236246.

    • Search Google Scholar
    • Export Citation
  • 66.

    Reddy SP, Marks JE. Metastatic carcinoma in the cervical lymph nodes from an unknown primary site: results of bilateral neck plus mucosal irradiation vs. ipsilateral neck irradiation. Int J Radiat Oncol Biol Phys 1997;37:797802.

    • Search Google Scholar
    • Export Citation
  • 67.

    Friesland S, Lind MG, Lundgren J. Outcome of ipsilateral treatment for patients with metastases to neck nodes of unknown origin. Acta Oncol 2001;40:2428.

    • Search Google Scholar
    • Export Citation
  • 68.

    Bhide S, Clark C, Harrington K, Nutting CM. Intensity modulated radiotherapy improves target coverage and parotid gland sparing when delivering total mucosal irradiation in patients with squamous cell carcinoma of head and neck of unknown primary site. Med Dosim 2007;32:188195.

    • Search Google Scholar
    • Export Citation
  • 69.

    Klem ML, Mechalakos JG, Wolden SL. Intensity-modulated radiotherapy for head and neck cancer of unknown primary: toxicity and preliminary efficacy. Int J Radiat Oncol Biol Phys 2008;70:11001107.

    • Search Google Scholar
    • Export Citation
  • 70.

    de Braud F, Heilbrun LK, Ahmed K. Metastatic squamous cell carcinoma of an unknown primary localized to the neck. Advantages of an aggressive treatment. Cancer 1989;64:510515.

    • Search Google Scholar
    • Export Citation
  • 71.

    Argiris A, Smith SM, Stenson K. Concurrent chemoradiotherapy for N2 or N3 squamous cell carcinoma of the head and neck from an occult primary. Ann Oncol 2003;14:13061311.

    • Search Google Scholar
    • Export Citation
  • 72.

    Shehadeh NJ, Ensley JF, Kucuk O. Benefit of postoperative chemoradiotherapy for patients with unknown primary squamous cell carcinoma of the head and neck. Head Neck 2006;28:10901098.

    • Search Google Scholar
    • Export Citation
  • 73.

    Miller FR, Karnad AB, Eng T. Management of the unknown primary carcinoma: long-term follow-up on a negative PET scan and negative panendoscopy. Head Neck 2008;30:2834.

    • Search Google Scholar
    • Export Citation
  • 74.

    Stoeckli SJ, Mosna-Firlejczyk K, Goerres GW. Lymph node metastasis of squamous cell carcinoma from an unknown primary: impact of positron emission tomography. Eur J Nucl Med Mol Imaging 2003;30:411416.

    • Search Google Scholar
    • Export Citation
  • 75.

    Fleming AJ Jr, Johansen ME. The clinician's expectations from the use of positron emission tomography/computed tomography scanning in untreated and treated head and neck cancer patients. Curr Opin Otolaryngol Head Neck Surg 2008;16:127134.

    • Search Google Scholar
    • Export Citation
  • 76.

    Zanation AM, Sutton DK, Couch ME. Use, accuracy, and implications for patient management of [18F]-2-fluorodeoxyglucose-positron emission/computerized tomography for head and neck tumors. Laryngoscope 2005;115:11861190.

    • Search Google Scholar
    • Export Citation
All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 81 27 5
PDF Downloads 44 22 5
EPUB Downloads 0 0 0