Detection of Nasopharyngeal Carcinoma by MR Imaging: Diagnostic Accuracy of MRI Compared with Endoscopy and Endoscopic Biopsy Based on Long-Term Follow-Up

Discussion

The results from this long-term follow-up study show that MR imaging is a highly sensitive tool for NPC detection because all biopsy-proven NPCs in the initial and 3-year follow-up study had been detected on the initial evaluation by MR imaging. By comparison, tumors in 12% and 6% of patients with NPC confirmed at histology were missed by initial endoscopy and by endoscopic biopsy, respectively. In our opinion, these findings demonstrate the necessity of greater use of MR imaging for the diagnostic work-up of patients with suspected NPC because neither endoscopy nor endoscopy plus biopsy can exclude NPC.

A particular strength of MR imaging is that it can assess the nasopharyngeal recess, which is where most NPCs originate. This site is often difficult to inspect endoscopically due to its lateral projection and apposition of its anterior and posterior walls. In 1 patient in the study, both initial and repeat MR imaging examinations detected an NPC within the pharyngeal recess that was missed on initial endoscopy and biopsy and on a repeat biopsy that was targeted to the MR imaging–detected abnormality, and it was only finally confirmed after a repeat biopsy several years later. In this regard, blind biopsies of this site can be hazardous due to the close proximity of the internal carotid artery to the lateral aspect of the recess; and as in our case, deeply sited small tumors may be missed even with targeted biopsies. These findings highlight the importance of maintaining a high index of suspicion for NPC even if initial biopsies are negative for it.

The optimal management of patients with a suspected but unproved small deeply sited tumor on MR imaging is unclear, though it probably should entail a combination of close imaging surveillance with MR imaging to document whether abnormalities persist or regress, serology, and endoscopy with repeat biopsies as appropriate. In this respect, the optimum timing, frequency, and duration of follow-up MR imaging examinations are unknown. Our example demonstrated only a small increase in tumor size during >3 years, suggesting that early NPCs may have slow growth initially. In fact, there is a paucity of data on growth rates of early NPCs, though published reports¹¹ of long latency periods between finding an abnormal serology test result and the eventual proof of NPC could be explained by small tumors that remain endoscopically occult for several years. The role of FDG-PET in early NPC detection is unclear because although NPCs are typically metabolically active, small tumors may have insufficient metabolic load to be detectable and may be obscured by metabolic activity due to normal lymphatic tissue and/or concomitant inflammatory changes in the nasopharynx. In those regions of the world where NPC is endemic, there are major resource implications for further imaging of these patients; therefore, follow-up is usually based on endoscopy plus or minus serology testing. However, the results of this long-term study suggest that further imaging, by FDG-PET/CT or serial MR imaging, would be best used for those patients with a grade 4 tumor on MR imaging because all of these patients had proved NPC.

The present study confirmed that MR imaging had a 100% negative predictive value for NPC, which supports the previous conclusion that invasive biopsies are not required when MR imaging findings are negative, especially when the endoscopic examination findings are also negative.¹⁰ These findings also suggest that a negative MR imaging finding could potentially override a positive endoscopy result, in which a suspicious midline nasopharyngeal mass is seen on endoscopy that is characteristic of adenoidal hyperplasia on MR imaging, based on the presence of a mass with a symmetric striped or striated appearance.¹²

All patients with a tumor identified by MR imaging (grade 4) had NPC, but MR imaging had an imperfect specificity (92%), which was attributable to false-positive cases in patients with asymmetry in an otherwise generalized lymphoid hyperplasia MR imaging pattern (grade 3). Clearly, it would be beneficial to improve the positive predictive value of MR imaging to avoid unnecessary biopsies in healthy subjects, especially if MR imaging is to be used more widely to support NPC serology screening programs in areas with endemic NPC. In this respect, of those patients with a grade 3 positive MR imaging finding, only those who also had an accompanying positive endoscopy examination finding had NPC. Therefore, we speculate that a grade 3 pattern should undergo biopsy only if the endoscopic examination also shows a suspected tumor, though caution would still be advised for those patients with asymmetry in a striped pattern of the adenoid because the internal structure of the adenoid cannot be visualized endoscopically.

The only method that currently can reliably exclude NPC in this patient population is follow-up to ensure that patients did not have a subclinical tumor at initial presentation. Follow-up was performed by re-examination of the nasopharynx at a minimum of 3 years, with a mean of almost 5 years, but 1 remaining limitation of the study is that patients with small slow-growing cancers may not have been identified.