p16 Examination Is not Sufficient
The explanation of diagnostics required for CUP syndrome, for neck metastases without detectable primary tumor, is incomplete (1). Immunohistochemical examination using the p16 protein is inadequate. The confirmation of p16 is used exclusively to detect oropharyngeal carcinomas and not—and the article does not make this clear—to generally confirm squamous cell carcinomas of the head and neck. The authors did not mention nasopharyngeal carcinoma as an important location of the primary tumor. The current 8th edition of the TNM classification requires for the purpose of diagnosing cervical CUP syndrome to test for the Epstein-Barr virus (EBV), typically by using in-situ hybridization (2). In this way, CUP syndrome with a primary tumor in the nasopharynx can be confirmed or ruled out. Furthermore, the sensitivity for finding the primary tumor by combining p16 confirmation and testing for EBV in the neck metastasis seems superior to positron emission tomography combined with computed tomography (18F-FDG-PET/CT) (3).
Prof. Dr. med. Orlando Guntinas-Lichius
HNO-Klinik, Universitätsklinikum Jena
|1.||Zaun G, Schuler M, Herrmann K, Tannapfel A: CUP syndrome—metastatic malignancy with unknown primary tumor. Dtsch Arztebl Int 2018; 115: 157–62 VOLLTEXT|
|2.||Wittekind C (ed.): TNM-Klassifikation maligner Tumoren. 8. edition Weinheim Wiley-VCH, 2017.|
|3.||Cheol Park G, Roh JL, Cho KJ, et al.: 18 F-FDG PET/CT vs. human papillomavirus, p16 and Epstein-Barr virus detection in cervical metastatic lymph nodes for identifying primary tumors. Int J Cancer 2017; 140: 1405–12 CrossRef MEDLINE|