Carcinoma of Unknown Primary (CUP) versus CUP Turned to Primary Carcinoma of the Head and Neck—An Analysis of Diagnostic Methods and the Impact of Primary Tumor on Clinical Outcome

Abstract

Background. The purpose of this study was to analyze the value of different diagnostic methods in detecting the primary site and the impact of primary tumors on the clinical outcome of carcinoma of unknown primary (CUP). Methods. In this multicenter, retrospective study, 124 patients with true CUP (n = 94) and CUP turned to primary carcinoma (n = 30) were included. Patients with evidence of primary site during the clinical examination were excluded a priori. The diagnostic procedure was comprised of imaging and invasive methods (fine-needle-aspiration, tonsillectomy and panendoscopy). All patients were treated with curative intent. Results. Despite extensive diagnostic workup, the primary site remained unknown in 75.8%. Invasive diagnostic methods showed higher primary detection rates than imaging modalities (15.1% vs. 7.8%). Tonsillectomy and panendoscopy revealed the primary tumor in 14.9% and 15.2% of patients, whereas the detection rates of CT, MRI and FDG-PET-CT were 10.1%, 4.8% and 6.5%, respectively. The occurrence of primary tumors led to a significantly deteriorating 5-year overall survival (p = 0.002) and emerged as survival prognosticator (HR = 2.764, p = 0.003). Conclusion. Clinical examination in combination with tonsillectomy and panendoscopy was superior to imaging alone in detecting the primary tumor. When the CUP of patients turned to a primary tumor, clinical outcome was significantly worse than in CUP patients.

Diagnostic Approaches for Neuroendocrine Neoplasms of Unknown Primary (NEN-UPs) and Their Prognostic Relevance—A Retrospective, Long-Term Single-Center Experience

“…Subsequently, a primary tumor site could be identified in 13 out of these 113 patients (11%). The detection rate of a primary tumor site in patients originally being classified as having a CUP is known to vary between 10 and 40% according to the literature and could be increased more recently by means of newly available diagnostic tools, including NGS or molecular profiling [31][32][33][34][35]. Since targeted therapy approaches are available, an accurate characterization of the tumor is essential for the detection of potentially targetable molecular alterations.…”

Head and Neck Squamous Cell Carcinoma of Unknown Primary: A Diagnostic Work-Up

“…Faisal et al reported the results of a multicenter, retrospective study, analyzing the value of different diagnostic methods in detecting the primary tumor site in 124 patients of carcinoma of unknown primary, and the impact of primary tumors on their clinical outcome. 4 The diagnostic procedure comprised of nasopharyngoscopy, imaging, tonsillectomy, and panendoscopy. Despite extensive diagnostic work-up, the primary site remained unknown in 75.8%.…”

“…Furthermore, the PET/CT was not superior to the conventional imaging in the detection of the primary tumor site. 4 …”

“…An example of such a diagnostic algorithm includes a thorough clinical exam with in-office nasopharyngolaryngoscopy, imaging studies such as magnetic resonance imaging (MRI), computed tomography (CT) and 18-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT), and panendoscopy with biopsy of the abnormal findings seen on exam and/or imaging, or directed biopsies of the mucosal sites likely to harbor the hidden primary tumor sites (base of tongue, tonsil, nasopharynx and/or hypopharynx). 4 Despite this extensive workup, over 40% of primary tumors remain unidentified. 1 , 5 …”

A Systematic Review of Diagnostic and Prognostic Biomarkers for Head and Neck Cancer of Unknown Primary: An Unmet Clinical Need

“…The HNCUP diagnosis is made by exclusion, as it is represented in Figure 1 . The initial diagnostic workup consists of a thorough collection of anamnestic data, such as personal and familiar history of malignancies and the presence of risk factors (e.g., immunosuppressive factors), the clinical symptoms at the onset, diagnostic imaging, and complete H&N physical examination [ 4 , 5 , 6 ]. The age of onset of H&N cancer peaks at 60–70 years, and males are more affected than females.…”