Metastases of squamous cell carcinoma in the lymph nodes of the neck without the revealed primary focus

Objective is to identify regularity of metastases distribution of the squamous cell carcinoma (SCC) in the lymph nodes of the neck without revealed primary focus, as well as to evaluate the effectiveness of various methods of treatment.

Materials and methods. Performed the retrospective 45 patients data analysis with metastases of SCC in cervical lymph nodes without  the revealed primary focus treated in different departments of N.N. Blokhin National Medical Research Center of Oncology from 2005  to 2012. The source of information were outpatient studies and medical histories, histological preparations and paraffin blocks.

Results. Metastases of SCC without revealed primary focus are most typical for nodes of a neck and upper part of the body, there are among the patients mostly males aged 50–59 years. To establish the localization of the primary focus, traditional diagnostic procedures are not always effective: in morphological analysis, the primary focus can be hidden behind inflammatory changes, in addition, the tumor lesion can be of a primary focus. Tumors, similar to lymphoepithelioma-like carcinoma, could also simulate metastasis in the lymph node. Tonsil cancer is very often not detected even with repeated biopsies, therefore diagnostic tonsillectomy is justified. Survival depends slightly  on the identification of the source of metastasis. The range of treatment methods for SCC is limited, combined and complex methods demonstrate greater efficiency, chemotherapy is less reasonable. The leading prognostic factor is the degree of distribution of metastatic lesion. Virologic analysis allows only to assume localization of the tumor process in the nasopharynx in patients with human papillomavirus and predict their greater survival, and the number of patients with Epstein–Barr virus is too small for reasonable hypotheses.

Conclusion. With metastases of SCC in the lymph nodes of the neck without the revealed primary focus, the hidden distributing tumor is most often appears in the pharyngeal tonsils and in the root region of the tongue. In some cases, the metastatic node can be the primary focus.  The most effective complex therapy is surgical intervention with followed radiation therapy in combination with chemotherapy. The spectrum (range) of diagnostic procedures can include bilateral tonsillectomy and mucosectomy of the root region of the tongue. 

1. Рак без выявленного первичного очага. В кн.: Минимальные клинические рекомендации Европейского общества медицинской онкологии (ESMO). М.: Изд. группа РОНЦ им. Н.Н. Блохина РАМН, 2010. С. 348–353. [Cancer without detected primary focus. In: Minimal clinical recommendations of the European Society for Medical Oncology (ESMO). Moscow: Publ. group of the N.N. Blokhin ROSC, 2010. Pр. 348–353. (In Russ.)].

2. Pavlidis N., Fizazi K. Carcinoma of unknown primary (CUP). Crit Rev Oncol Hematol 2009;69(3):271–8. DOI: 10.1016/j.critrevonc.2008.09.005.

3. Pavlidis N., Pentheroudakis G. Cancer of unknown primary site: 20 questions to be answered. Ann Oncol 2010;21 Suppl 7: vii303–7. DOI: 10.1093/annonc/mdq278.

4. Комаров И.Г., Слетина С.Ю. Метастазы злокачественных опухолей без выявленного первичного очага. Онкогинекология 2015;(2):50–8. [Komarov I.G., Sleti- na S.Yu. Metastases of malignant tumor of unknown primary. Onkoginekologiya = Gynecologic Oncology 2015;(2):50–8. (In Russ.)].

5. Nystrom J.S., Weiner J.M., Heffelfin- ger-Juttner J. et al. Metastatic and histologic presentation in unknown primary cancer. Semin Oncol 1977;4(1):53–8. PMID: 841350.

6. Гончарова Е.В., Сенюта Н.Б., Смирнова К.В. и др. Вирус Эпштейна–Барр (ВЭБ) в России: инфицированность населения и анализ вариантов гена LMP1 у больных ВЭБассоциированными патологиями и здоровых лиц. Вопросы вирусологии 2015;60(2):11–7. [Goncharova E.V., Senyuta N.B., Smirnova K.V. et al. Epstein–Barr virus (EBV) in Russia: infection of the population and analysis of the LMP1 gene variants in patients with EBV-associated pathologies and healthy individuals. Voprosy virusologii = Problems of Virology 2015;60(2):11–7. (In Russ.)].

7. Chauhan A., Tiwari S., Pathak N. Primary branchiogenic carcinoma: report of a case and a review of the literature. J Cancer Res Ther 2013;9(1):135–7. DOI: 10.4103/09731482.110380.

8. Choi J., Nahm J.H., Kim S.K. Prognostic clinicopathologic factors in carcinoma of unknown primary origin: a study of 106 consecutive cases. Oncotarget 2017;8(37):62630–40. DOI: 10.18632/ oncotarget.16021.

9. Mackenzie K., Watson M., Jankowska P. et al. Investigation and management of the unknown primary with metastatic neck disease: United Kingdom National Multidisciplinary Guidelines. J Laryngol Otol 2016;130(Suppl 2):170–5. DOI: 10.1017/S0022215116000591.

10. Al Kadah B., Papaspyrou G., Linxweiler M. et al. Cancer of unknown primary (CUP) of the head and neck: retrospective analysis of 81 patients. Eur Arch Otorhinolaryngol 2017;274(6):2557–66.

11. Martell K., Mackenzie J., Kerney W., Lau H.Y. Management delays in patients with squamous cell cancer of neck node(s) and unknown primary site: a retrospective cohort study. J Otolaryngol Head Neck Surg 2017;46(1):39. DOI: 10.1186/s40463017-0217-z.

12. Du C., Ying H., Zhang Y. et al. Treatment for retropharyngeal metastatic undifferentiated squamous cell carcinoma from an unknown primary site: results of a prospective study with irradiation to nasopharyngeal mucosa plus bilateral neck. Oncotarget 2017;8(26):42372–81. DOI: 10.18632/ oncotarget.16344.

13. Axelsson L., Nyman J., Haugen-Cange H. et al. Prognostic factors for head and neck cancer of unknown primary including the impact of human papilloma virus infection. J Otolaryngol Head Neck Surg 2017;46(1):45. DOI: 10.1186/s40463-017-0223-1.

14. Schroeder L., Boscolo-Rizzo P., Dal Cin E. et al. Human papillomavirus as prognostic marker with rising prevalence in neck squamous cell carcinoma of unknown primary: A retrospective multicentre study. Eur J Cancer 2017;74:73–81. DOI: 10.1016/j.ejca.2016.12.020. PMID: 28335889.