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Cervical lymph node metastases of squamous cell carcinoma from an unknown primary site: a favourable prognosis subset of patients with CUP

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  • Molecular and Cellular Biology of Cancer
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Abstract

Squamous cervical cancer of unknown primary site (SQCCUP) presents in patients as neck lymph nodes involved by squamous carcinoma in the absence of identifiable primary in the head, neck or lung. This CUP subset affects male patients previously exposed to alcohol and tobacco, though a proportion of cases may be related to chronic infection of the oropharynx by human papilloma virus. A standardised diagnostic work-up consisting of panendoscopy of the upper aerodigestive tract, CT of the chest/abdomen and histology supplemented by immunohistochemistry is warranted for the diagnosis. The scant available evidence on the molecular biology of the disease is reviewed. The cornerstones of management are excisional biopsy or surgical extirpation of the disease followed by bilateral neck external beam radiotherapy and chemotherapy. The necessity for complete surgical resection of involved neck nodes, irradiation of all head/neck mucosal sites and administration of concurrent chemotherapy is currently being debated. Aggressive multimodal therapy results in long-term disease control in 50–60% of patients, though data are mainly based on retrospective cohorts. Factors predicting for superior patient outcome are radical management with surgery or radiotherapy, low stage and volume of disease, absence of extracapsular spread and good performance status. Recently introduced molecular profiling platforms may provide biological classification to a primary tissue of origin as well as insights into the pathophysiology of this clinical entity.

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References

  1. Pavlidis N, Briasoulis E, Hainsworth J, Greco FA (2003) Diagnostic and therapeutic management of cancer of unknown primary. Eur J Cancer 39:1990–2005

    Article  PubMed  CAS  Google Scholar 

  2. Comess MS, Beahrs OH, Dockerty MB (1957) Cervical metastasis from occult carcinoma. Surg Gynecol Obstet 104:607–617

    PubMed  CAS  Google Scholar 

  3. Jereczek-Fossa BA, Jassem J, Orecchia R (2004) Cervical lymph node metastases of squamous cell carcinoma from an unknown primary. Cancer Treat Rev 30: 153–164

    Article  PubMed  Google Scholar 

  4. Grau C, Johansen LV, Jakobsen J et al (2000) Cervical lymph node metastases from unknown primary tumours. Results from a national survey by the Danish Society for Head and Neck Oncology. Radiother Oncol 55:121–129

    Article  PubMed  CAS  Google Scholar 

  5. Psyrri A, Di Maio D (2008) Human papillomavirus in cervical and head neck cancer. Nat Clin Pract Oncol 5:24–31

    Article  PubMed  CAS  Google Scholar 

  6. Haas I, Hoffmann KT, Enger R, Ganzer U (2002) Diagnostic strategies in cervical carcinoma of an unknown primary (CUP). Eur Arch Otorhinolaryngol 259:325–333

    Article  PubMed  Google Scholar 

  7. Califano J, Westra W, Koch W et al (1999) Unknown primary head and neck squamous cell carcinoma: molecular identification of the site of origin. J Natl Cancer Inst 91:599–603

    Article  PubMed  CAS  Google Scholar 

  8. Deshpande AM, Wong DT (2008) Molecular mechanisms of head and neck cancer. Expert Rev Anticancer Ther 8:799–809

    Article  PubMed  CAS  Google Scholar 

  9. Seiwert T, Cohen E (2008) Targeting angiogenesis in head and neck cancer. Semin Oncol 35:274–285

    Article  PubMed  Google Scholar 

  10. Pentheroudakis G, Briasoulis E, Pavlidis N (2007) Cancer of unknown primary site: missing primary or missing biology? Oncologist 12:418–425

    Article  PubMed  CAS  Google Scholar 

  11. Pentheroudakis G, Pavlidis N (2006) Perspectives for targeted therapies in cancer of unknown primary site. Cancer Treat Rev 32:637–644

    Article  PubMed  CAS  Google Scholar 

  12. de Braud F, Al-Sarraf M (1993) Diagnosis and management of squamous cell carcinoma of unknown primary tumor site of the neck. Semin Oncol 20:273–278

    PubMed  Google Scholar 

  13. Molinari R, Cantu G, Ghiesa F et al (1997) A statistical approach to detection of the primary cancer based on the site of neck lymph node metastases. Tumori 63:267–282

    Google Scholar 

  14. Mui S, Li T, Rasgon M et al (1997) Efficacy and cost effectiveness of multihole fine-needle aspiration of squamous cell carcinoma or head and neck masses. Laryngoscope 107:759–764

    Article  PubMed  CAS  Google Scholar 

  15. Pisharodi LR (1997) False negative diagnosis in fine needle aspiration of squamous cell carcinoma of head and neck. Diagn Cytopathol 17:70–73

    Article  PubMed  CAS  Google Scholar 

  16. Mendenhall W, Mancuso A, Parsons J et al (1998) Diagnostic evaluation of squamous cell carcinoma metastatic to cervical lymph nodes from an unknown head and neck primary site. Head Neck 20:739–744

    Article  PubMed  CAS  Google Scholar 

  17. Lee WY, Hsiao JR, Jin YT et al (2000) Epstein-Barr virus detection in neck metastases by in situ hybridization in fine-needle aspiration cytologic studies: an aid diffentiating the primary site. Head Neck 22:336–340

    Article  PubMed  CAS  Google Scholar 

  18. Gillison ML, Koch WM, Capone RB et al (2000) Evidence for a casual association between human papillomavirus and a subset of head and neck cancers. J Natl Cancer Inst 92:709–720

    Article  PubMed  CAS  Google Scholar 

  19. Adams JR, O’Brien CJ (2002) Unknown primary squamous cell carcinoma of the head and neck: a review of diagnosis, treatment and outcomes. Asian J Surg 25:188–193

    PubMed  Google Scholar 

  20. Mancuso AA (1984) Cervical lymph node metastases: oncologic imaging and diagnosis. Int J Rad Onc Biol Phys 10:411–423

    CAS  Google Scholar 

  21. Muraki AS, Mancuso AA, Harnsberger HR (1984) Metastatic cervical adenopathy from tumours of unknown origin: the role of CT. Radiology 152:749–753

    PubMed  CAS  Google Scholar 

  22. Tien RD, Hesselink JR, Chu PK, Jerzy S (1991) Improved detection and delineation of head and neck lesions with fat suppression spin-echo MR imaging. AJNR Am J Neuroradiol 12:19–24

    PubMed  CAS  Google Scholar 

  23. Kassel EE, Keller MA, Kucharczyk W (1989) MRI of the floor of the mouth, tongue and orohypopharynx. Radiol Clin North Am 2:331–351

    Google Scholar 

  24. Rusthoven KE, Koshy M, Paulino AC (2004) The role of fluorodeoxyglucose positron emission tomography in cervical lymph node metastases from an unknown primary tumor. Cancer 101:2641–2649

    Article  PubMed  Google Scholar 

  25. Johansen J, Eigtved A, Buchwald C et al (2002) Implication of 18F-fluoro-2-deoxy-D-glucose position emission tomography on management of carcinoma of un-known primary in the head and neck: a Danish cohort study. Laryngoscope 112:2009–2014

    Article  PubMed  Google Scholar 

  26. Fleming AJ Jr, Smith SP Jr, Paul CM et al (2007) Impact of [18F]-2-fluorodeoxyglucose-positron emission tomography/computed tomography on previously untreated head and neck cancer patients. Laryngoscope 117:1173–1179

    Article  PubMed  Google Scholar 

  27. Delgado-Bolton R, Fernandez-Perez C, Gonzalez-Matez A, Carreras JL (2003) Metaanalysis of the performance of FDG-PET in primary tumour detection in un-known primary tumours. J Nucl Med 44:1301–1314

    PubMed  Google Scholar 

  28. Wartski M, Le Stanc E, Gontier E et al (2007) In search of an unknown primary tumour presenting with cervical metastases: performance of hybrid FDG-PET-CT. Nucl Med Common 28:365–371

    Article  Google Scholar 

  29. Kwee TC, Kwee RM (2009) Combined FDGPET/CT for the detection of un-known primary tumors: systematic review and metaanalysis. Eur Radiol 19:731–744

    Article  PubMed  Google Scholar 

  30. Beldi D, Jereczek-Fossa BA, D’Onofrio A et al. (2007) 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 69:1051–1058

    PubMed  Google Scholar 

  31. Huang CC, Tseng FY, Yeh TH et al (2008) Prognostic factors of unknown primary head and neck squamous cell carcinoma. Otolaryngol Head Neck Surg 139:429–435

    Article  PubMed  Google Scholar 

  32. Coster JR, Foote RL, Olsen KD et al (1992) Cervical nodal metastasis of squamous cell carcinoma of unknown origin: indications for withholding radiation therapy. Int J Radiat Oncol Biol Phys 23:743–749

    PubMed  CAS  Google Scholar 

  33. Iganej S, Kagan R, Anderson P et al (2002) Metastatic squamous cell carcinoma of the neck from an unknown primary: management options and patterns of relapse. Head Neck 24:236–246

    Article  PubMed  Google Scholar 

  34. Nieder C, Gregoire V, Ang K (2001) Cervical lymph node metastases from occult squamous cell carcinoma: cut down a tree to get an apple? Int J Radiat Oncol Biol Phys 50:727–733

    PubMed  CAS  Google Scholar 

  35. Colletier PJ, Garden AS, Morrison WH et al (1998) Postoperative radiation for squamous cell carcinoma metastatic to cervical lymph nodes from an unknown primary site: outcomes and patterns of failure. Head Neck 20:674–681

    Article  PubMed  CAS  Google Scholar 

  36. Erkal HS, Mendenhall WM, Amdur RJ et al (2001) Squamous cell carcinomas metastatic to cervical lymph nodes from an unknown head-andneck mucosal site treated with radiation therapy alone or in combination with neck dissection. Int J Radiat Oncol Biol Phys 50:55–63

    Article  PubMed  CAS  Google Scholar 

  37. Erkal HS, Mendenhall WM, Amdur RJ et al (2001) Squamous cell carcinomas metastatic to cervical lymph nodes from an unknown head-andneck mucosal site treated with radiation therapy with palliative intent. Radiother Oncol 59:319–321

    Article  PubMed  CAS  Google Scholar 

  38. Klop WM, Balm AJ, Keus RB et al (2000) Diagnosis and treatment of 39 patients with cervical lymph node metastases of squamous cell carcinoma of unknown origin referred to Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, 1979–1998. Ned Tijdschr Geneeskd 144:1355–1360

    PubMed  CAS  Google Scholar 

  39. Jesse RH, Perez CA, Fletcher GH (1973) Cervical lymph node metastasis: unknown primary cancer. Cancer 31:854–859

    Article  PubMed  CAS  Google Scholar 

  40. Bataini JP, Rodriguez J, Jaulerry C et al (1987) Treatment of metastatic neck nodes secondary to an occult epidermoid carcinoma of the head-and-neck. Laryngoscope 97:1080–1084

    Article  PubMed  CAS  Google Scholar 

  41. Maulard C, Housset M, Brunel P et al (1992) Postoperative radiation therapy for cervical lymph node metastases from an occult squamous cell carcinoma. Laryngoscope 102:884–890

    Article  PubMed  CAS  Google Scholar 

  42. Lefebvre JL, Coche-Dequeant B, Van JT et al (1990) Cervical lymph nodes from an unknown primary tumour in 190 patients. Am J Surg 160:443–446

    Article  PubMed  CAS  Google Scholar 

  43. Koch WM, Bhatti N, Williams MF, Eisele D (2001) Oncologic rationale for bilateral tonsillectomy in head and neck squamous cell carcinoma of unknown primary source. Otolaryngol Head Neck Surg 124:331–333

    Article  PubMed  CAS  Google Scholar 

  44. Kothari P, Randhawa P, Farrell R (2008) Role of tonsillectomy in the search for a squamous cell carcinoma from an unknown primary in the head and neck. Br J Oral Maxillof Surg 46:283–287

    Article  Google Scholar 

  45. Adelstein DJ, Li Y, Adams GI et al (2003) An intergroup phase III comparison of standard radiation therapy and two schedules of concurrent chemoradiotherapy in patients with unresectable squamous cell head and neck cancer. J Clin Oncol 21:92–98

    Article  PubMed  Google Scholar 

  46. Bernier J, Domenge C, Ozsahin M et al (2004) Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer. N Engl J Med 350:1945–1952

    Article  PubMed  CAS  Google Scholar 

  47. Cooper JS, Pajak TF, Forastiere AA et al (2004) Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck. N Engl J Med 350:1937–1944

    Article  PubMed  Google Scholar 

  48. Forastiere AA, Goepfert H, Maor M et al (2003) Concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancer. N Engl J Med 349:2091–2098

    Article  PubMed  CAS  Google Scholar 

  49. Vermorken JB, Mesia R, Rivera F et al (2008) Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med 359:1116–1127

    Article  PubMed  CAS  Google Scholar 

  50. de Braud F, Heilbrun LK, Ahmed K et al (1989) Metastatic squamous cell carcinoma of an unknown primary localized to the neck. Advantages of an aggressive treatment. Cancer 64:510–515

    Article  PubMed  Google Scholar 

  51. Argiris A, Smith SM, Stenson K et al (2003) Concurrent chemoradiotherapy for N2 or N3 squamous cell carcinoma of the head and neck from an occult primary. Ann Oncol 14:1306–1311

    Article  PubMed  CAS  Google Scholar 

  52. Shehadeh NJ, Ensley JF, Kucuk O et al (2006) Benefit of postoperative chemoradiotherapy for patients with unknown primary squamous cell carcinoma of the head and neck. Head Neck 28:1090–1098

    Article  PubMed  Google Scholar 

  53. Ganly I, Kaye SB (2000) Recurrent squamous cell carcinoma of the head and neck: overview of current therapy and future prospects. Ann Oncol 11:11–16

    Article  PubMed  CAS  Google Scholar 

  54. Wong SJ, Machtay M, Li Y (2006) Locally recurrent, previously irradiated head and neck cancer: concurrent reirradiation and chemotherapy or chemotherapy alone? J Clin Oncol 24:2653–2658

    Article  PubMed  Google Scholar 

  55. Mc Quone S, Eisele D, Lee D et al (1998) Occult tonsillar carcinoma in the unknown primary. Laryngoscope 108:1605–1610

    Article  CAS  Google Scholar 

  56. Tong C, Luk M, Chow S et al (2002) Cervical nodal metastases from occult primary: undifferentiated carcinoma versus squamous cell carcinoma. Head Neck 24:361–369

    Article  PubMed  Google Scholar 

  57. Pentheroudakis G, Golfinopoulos V, Pavlidis N (2007) Switching benchmarks in cancer of unknown primary: from autopsy to microarray. Eur J Cancer 43:2026–2036

    Article  PubMed  Google Scholar 

  58. Pentheroudakis G, Greco FA, Pavlidis N (2009) Molecular assignment of tissue of origin in cancer of unknown primary may not predict response to therapy or outcome: A systematic literature review. Cancer Treat Rev 35:221–227

    Article  PubMed  CAS  Google Scholar 

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Pavlidis, N., Pentheroudakis, G. & Plataniotis, G. Cervical lymph node metastases of squamous cell carcinoma from an unknown primary site: a favourable prognosis subset of patients with CUP. Clin Transl Oncol 11, 340–348 (2009). https://doi.org/10.1007/s12094-009-0367-1

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