Abstract
Cancer of unknown primary (CUP) is a well-recognized clinical disorder where the primary site cannot be identified after a standard diagnostic approach and it accounts for 3–5 % of all tumors. CUP is distinguished into two different clinicopathological entities, favorable or unfavorable. The subset of squamous cell carcinoma metastatic to cervical lymph nodes constitutes the 5 % of all head-and-neck cancers. For detection of the primary site, all patients need a detailed clinical examination and imaging investigation including PET scans, panendoscopy with directed biopsies, and possibly bilateral tonsillectomy. Lymph nodal stage, extracapsular spread, and HPV status are considered as the most prominent prognostic factors. Although, randomized trials are lacking concerning the optimal therapeutic management, combined-modality treatment is offering the most encouraging results. Surgery alone is indicated in N1 or N2a stages. Radiotherapy is used as a single modality for early-stage pN1 without extracapsular extensions or combined with neck dissection as postoperative therapy in more advanced disease. Chemoradiation can also be given in a neoadjuvant setting followed by surgery in certain cases as well in patients with comorbidities. Prognosis in general is encouraging with 5-year progression-free and overall survival rates of 85 % and 75 %, respectively.
Keywords
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Pavlidis N, Briasoulis E, Hainsworth J, Greco FA. Diagnostic and therapeutic management of cancer of an unknown primary. Eur J Cancer. 2003;39:1990–2005.
Pavlidis N, Fizazi K. Carcinoma of unknown primary (CUP). Crit Rev Oncol Hematol. 2005;54(3):243–50.
Pentheroudakis G, Golfinopoulos V, Pavlidis N. Switching benchmarks in Cancer of unknown primary: from autopsy to microarray. Eur J Cancer. 2007;43(14):2026–36.
Comess MS, Beahrs OH, Dockerty MB. Cervical metastasis from occult carcinoma. Surg Gynecol Obstet. 1957;104:607–17.
Jereczek-Fossa BA, Jassem J, Orecchia R. Cervical lymph node metastases of squamous cell carcinoma from an unknown primary. Cancer Treat Rev. 2004;30:153–64.
Grau C, Johansen LV, Jakobsen J, et al. 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;55:121–9.
Haas I, Hoffmann KT, Enger R, Ganzer U. Diagnostic strategies in cervical carcinoma of an unknown primary (CUP). Eur Arch Otorhinolaryngol. 2002;259:325–33.
de Braud F, Al-Sarraf M. Diagnosis and management of squamous cell carcinoma of unknown primary tumor site of the neck. Semin Oncol. 1993;20(3):273–8.
Molinari R, Cantu G, Ghiesa F, et al. A statistical approach to detection of the primary cancer based on the site of neck lymph node metastases. Tumori. 1997;63:267–82.
Mui S, Li T, Rasgon M, et al. Efficacy and cost effectiveness of multihole fine-needle aspiration of squamous cell carcinoma or head and neck masses. Laryngoscope. 1997;107(6):759–64.
Pisharodi LR. False negative diagnosis in fine needle aspiration of squamous cell carcinoma of head and neck. Diagn Cytopathol. 1997;17:70–3.
Mendenhall W, Mancuso A, Parsons J, et al. Diagnostic evaluation of squamous cell carcinoma metastatic to cervical lymph nodes from an unknown head and neck primary site. Head Neck. 1998;20:739–44.
Lee WY, Hsiao JR, Jin YT, et al. Epstein - Barr virus detection in neck metastases by in-situ hybridization in fine-needle aspiration cytologic studies: an aid differentiating the primary site. Head Neck. 2000;22:336–40.
Desai PC, Jaglal MV, Gopal P, et al. Human papilloma virus in metastatic squamous carcinoma from unknown primaries in the head and neck: a retrospective 7 years study. Exp Mol Pathol. 2009;87:94–8.
Adams JR, O’Brien CJ. Unknown primary squamous cell carcinoma of the head and neck: a review of diagnosis, treatment and outcomes. Asian J Surg. 2002;25(2):188–93.
Mancuso AA. Cervical lymph node metastases: oncologic imaging and diagnosis. Int J Radiat Oncol Biol Phys. 1984;10:411–23.
Muraki AS, Mancuso AA, Harnsberger HR. Metastatic cervical adenopathy from tumours of unknown origin: the role of CT. Radiology. 1984;152:749–53.
Tien RD, Hesselink JR, Chu PK, Jerzy S. Improved detection and delineation of head and neck lesions with fat suppression spin – echo MR imaging. AJNR Am J Neuroradiol. 1991;12:19–24.
Kassel EE, Keller MA, Kucharczyk W. MRI of the floor of the mouth, tongue and orohypopharynx. Radiol Clin North Am. 1989;2:331–51.
Kwee TC, Kwee RM. Combined FDG-PET/CT for the detection of unknown primary tumors: systematic review and meta-analysis. Eur Radiol. 2009;19:731–44.
Rudmik L, Lau HY, Matthews TW, et al. Clinical utility of PET/CT in the evaluation of head and neck squamous cell carcinoma with an unknown primary: a prospective clinical trial. Head Neck. 2011;33:935–40.
Keller F, Psychogios G, Linke R, et al. Carcinoma of unknown primary in the head and neck: comparison between position emission tomography (PET) and PET/CT. Head Neck. 2011;33(11):1569–75.
Wartski M, Le Stanc E, Gontier E, et al. In search of an unknown primary tumour presenting with cervical metastases: performance of hybrid FDG-PET-CT. Nucl Med Commun. 2007;28(5):365–71.
Masaki T, Katada C, Nakayama M, et al. Usefulness and pitfall of narrow band imaging combined with magnifying endoscopy for detecting an unknown head and neck primary site with cervical lymph node metastasis. Auris Nasus Larynx. 2012;39(5):502–6.
Ni XG, Cheng RR, Lai SQ, et al. Value of narrow band imaging endoscopy in the detection of unknown primary site with cervical lymph node metastasis of squamous cell carcinoma. Zhonghka Zhong Lin Za Zhi. 2013;35(9):698–702.
Coker DD, Casterline PF, Chamber RG, Jaques DA. Metastases to lymph nodes of the head and neck from an unknown primary site. Am J Surg. 1977;134:517–22.
Coster JR, Foote RL, Olsen KD, et al. Cervical nodal metastasis of squamous cell carcinoma of unknown origin: indications for withholding radiation therapy. Int J Radiat Oncol Biol Phys. 1992;23:743–9.
Wang RC, Goepfert H, Barber AE, et al. Unknown primary squamous cell carcinoma metastatic to the neck. Arch Otolaryngol Head Neck Surg. 1990;116:1388–93.
Iganej S, Kagan R, Anderson P, et al. Metastatic squamous cell carcinoma of the neck from an unknown primary: management options and patterns of relapse. Head Neck. 2002;24(3):236–46.
Koch WM, Bhatti N, Williams MF, Eisele D. Oncologic rationale for bilateral tonsillectomy in head and neck squamous cell carcinoma of unknown primary source. Otolaryngol Head Neck Surg. 2001;124:331–3.
Kothari P, Randhawa P, Farrell R. Role of tonsillectomy in the search for a squamous cell carcinoma from an unknown primary in the head and neck. Br J Oral Maxillofac Surg. 2008;46:283–7.
Lapeyre M, Malissard L, Peiffert D, et al. Cervical lymph node metastasis from an unknown primary: is a tonsillectomy necessary ? Int J Radiat Oncol Biol Phys. 1997;39(2):291–6.
Righi PD, Sofferman RA. Screening unilateral tonsillectomy in the unknown primary. Laryngoscope. 1995;105:548–50.
Randall DA, Johnstone PAS, Foss RD, et al. Tonsillectomy in diagnosis of the unknown primary of the head and neck. Otolaryngol Head Neck Surg. 2000;122:52–5.
Nieder C, Gregoire V, Ang K. Cervical lymph node metastases from occult squamous cell carcinoma: cut down a tree to get an apple? Int J Radiat Oncol Biol Phys. 2001;50:727–33.
Colletier PJ, Garden AS, Morrison WH, et al. Postoperative radiation for squamous cell carcinoma metastatic to cervical lymph nodes from an unknown primary site: outcomes and patterns of failure. Head Neck. 1998;20:674–81.
Erkal HS, Mendenhall WM, Amdur RJ, et al. 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;50:55–63.
Erkal HS, Mendenhall WM, Amdur RJ, et al. 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;59:319–21.
Beldi D, Jereczek-Fossa BA, D’Onofrio A, et al. 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(4):1051–8.
Strojan P, Ferlito A, Medina JE, et al. Contemporary management of lymph node metastases from an unknown primary to the neck: I. A review of diagnostic approaches. Head and Neck. 2013;35(1):123–32.
Million RR, Cassisi NJ, Mancuso AA. The unknown primary. In: Million RR, Cassisi NJ, editors. Management of head and neck cancer. A multidisciplinary approach. 2nd ed. Philadelphia: J.B Lippincott Company; 1994. p. 311–20.
Gregoire V, Scalliet P, Ang KK, editors. Clinical target volumes in conformal and intensity modulated radiation therapy. A clinical guide to cancer treatment. Berlin: Springer; 2004.
Frank SJ, Rosenthal DI, Petsuksiri J, et al. Intensity-modulated radiotherapy for cervical node squamous cell carcinoma metastases from unknown head-and-neck primary site: M.D. Anderson Cancer Center outcomes and patterns of failure. Int J Radiat Oncol Biol Phys. 2010;78:1005–10.
Ligey A, Gentil J, Crehange G, et al. Impact of target volumes and radiation technique on loco-regional control and survival for patients with unilateral cervical lymph node metastases from an unknown primary. Radiother Oncol. 2009;93:483–7.
Klem ML, Mechalakos JG, Wolden SL, et al. Intensity-modulated radiotherapy for head and neck cancer of unknown primary: toxicity and preliminary efficacy. Int J Radiat Oncol Biol Phys. 2008;70:1100–7.
Madani I, Vakaet L, Bonte K, Boterberg T, De Neve W. Intensity-modulated radiotherapy for cervical lymph node metastases from unknown primary cancer. Int J Radiat Oncol Biol Phys. 2008;71:1158–66.
Lu H, Yao M, Tan H. Unknown primary head and neck cancer treated with intensity-modulated radiation therapy: to what extent the volume should be irradiated. Oral Oncol. 2009;45:474–9.
Sher DJ, Balboni TA, Haddad RI, et al. Efficacy and toxicity of chemoradiotherapy using intensity-modulated radiotherapy for unknown primary of head and neck. Int J Radiat Oncol Biol Phys. 2011;80:1405–11.
Chen AM, Li BQ, Farwell DG, Marsano J, Vijayakumar S, Purdy JA. Improved dosimetric and clinical outcomes with intensity-modulated radiotherapy for head-and-neck cancer of unknown primary origin. Int J Radiat Oncol Biol Phys. 2011;79:756–62.
Villeneuve H, Despres P, Fortin BM, et al. Cervical lymph node metastasis from unknown primary cancer: a single institution experience with intensity modulated radiotherapy. Int J Radiat Oncol Biol Phys. 2012;82(5):1866–71.
Ragin CC, Taioli E. Survival of squamous cell carcinoma of the head and neck in relation to human papillomavirus infection: review and meta-analysis. Int J Cancer. 2007;121:1813–20.
Marur S, D’souza G, Westra WH, Forastiere AA. HPV-associated head and neck cancer: a virus-related cancer epidemic. Lancet Oncol. 2010;11:781–9.
Fakhry C, Westra WH, Li S, et al. Improved survival of patients with human papillomavirus-positive head and neck squamous cell carcinoma in a prospective clinical trial. J Natl Cancer Inst. 2008;100:261–9.
Ang KK, Harris J, Wheeler R, et al. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med. 2010;363:24–35.
Bernier J, Domenge C, Ozsahin M, et al. Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer. N Engl J Med. 2004;350(19):1945–52.
Cooper JS, Pajak TF, Forastiere AA, et al. Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck. N Engl J Med. 2004;350(19):1937–44.
Forastiere AA, Goepfert H, Maor M, et al. Concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancer. N Engl J Med. 2003;349(22):2091–8.
Vermorken JB, Mesia R, Rivera F, et al. Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med. 2008;359(11):1116–27.
de Braud F, Heilbrun LK, Ahmed K, et al. Metastatic squamous cell carcinoma of an unknown primary localized to the neck. Advantages of an aggressive treatment. Cancer. 1989;64(2):510–5.
Argiris A, Smith SM, Stenson K, et al. Concurrent chemoradiotherapy for N2 or N3 squamous cell carcinoma of the head and neck from an occult primary. Ann Oncol. 2003;14:1306–11.
Shehadeh NJ, Ensley JF, Kucuk O, et al. Benefit of postoperative chemoradiotherapy for patients with unknown primary squamous cell carcinoma of the head and neck. Head Neck. 2006;28:1090–8.
Mc Quone S, Eisele D, Lee D, et al. Occult tonsillar carcinoma in the unknown primary. Laryngoscope. 1998;108:1605–10.
Tong C, Luk M, Chow S, et al. Cervical nodal metastases from occult primary: undifferentiated carcinoma versus squamous cell carcinoma. Head Neck. 2002;24:361–9.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2016 Springer International Publishing Switzerland
About this chapter
Cite this chapter
Pavlidis, N., Plataniotis, G. (2016). Cervical Lymph Node Metastases of Squamous Cell Carcinoma from an Unknown Primary Site. In: Bernier, J. (eds) Head and Neck Cancer. Springer, Cham. https://doi.org/10.1007/978-3-319-27601-4_39
Download citation
DOI: https://doi.org/10.1007/978-3-319-27601-4_39
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-27599-4
Online ISBN: 978-3-319-27601-4
eBook Packages: MedicineMedicine (R0)