Image-based diagnosis of residual or recurrent nasopharyngeal carcinoma may be a phantom tumor phenomenon

Some nasopharyngeal carcinoma (NPC) patients may present convincing radiological evidence mimicking residual or recurrent tumor after radiotherapy. However, by means of biopsies and long term follow-up, the radiologically diagnosed residuals/recurrences are not always what they appear to be. We report our experience on this "phantom tumor" phenomenon. This may help to avoid the unnecessary and devastating re-irradiation subsequent to the incorrect diagnosis. In this longitudinal cohort study, we collected 19 patients of image-based diagnosis of residual/recurrent NPC during the period from Feb, 2010 to Nov. 2016, and then observed them until June, 2019. They were subsequently confirmed to have no residual/recurrent lesions by histological or clinical measures. Image findings and pathological features were analyzed. Six patients showed residual tumors after completion of radiotherapy and 13 were radiologically diagnosed to have recurrences based on magnetic resonance imaging (MRI) criteria 6 to 206 months after radiotherapy. There were 3 types of image patterns: extensive recurrent skull base lesions (10/19); a persistent or residual primary lesion (3/19); lesions both in the nasopharynx and skull base (6/19). Fourteen patients had biopsy of the lesions. The histological diagnoses included necrosis/ inflammation in 10 (52.7%), granulation tissue with inflammation in 2, and reactive epithelial cell in 1. Five patients had no pathological proof and were judged to have no real recurrence/residual tumor based on the absence of detectable plasma EB virus DNA and subjective judgment. These 5 patients have remained well after an interval of 38-121 months without anti-cancer treatments. Image-based diagnosis of residual or recurrent nasopharyngeal carcinoma may be unreliable. False positivity, the "phantom tumor phenomenon", is not uncommon in post-radiotherapy MRI. This is particularly true if the images show extensive skull base involvement at 5 years or more after completion of radiotherapy. MRI findings compatible with NPC features must be treated as a real threat until proved otherwise. However, the balance between under- and over-diagnosis must be carefully sought. Without a pathological confirmation, the diagnosis of residual or recurrent NPC must be made taking into account physical examination results, endoscopic findings and Epstein-Barr virus viral load. A subjective medical judgment is needed based on clinical and laboratory data and the unique anatomic complexities of the nasopharynx.