Tubarial glands and their cryptic role in mimicking symptoms of rare Plummer–Vinson syndrome variants in the nasopharynx

To the Editor, The tubarial glands (TGs) represent previously overlooked pairs of macroscopic salivary glands (SGs) located in the posterolateral aspect of nasopharyngeal submucosa, primarily within the region of torus tubarius. Visualization and subsequent identification of these salivary structures were accomplished by PET/CT imaging with prostate-specific membrane antigen targeting ligand[1]. Furthermore, histological analysis demonstrated the composition, that is, primarily of mucinous acini, similar to minor SGs, which are responsible for secreting mucin-rich fluid essential for maintaining local moisture balance and preserving epithelial integrity of nasopharyngeal submucosa[2]. This article aligns with the TITAN Guidelines on the need for transparency in artificial intelligence use in health care[3]. Clinically, radiation therapy to the nasopharyngeal region, as observed in the cancers of the head and neck, can cause damage to the mucinous acini of TGs, lowering their secretory output. This leads to the loss of local lubrication, resulting in xerostomia and dysphagia[1]. These symptoms closely mimic the clinical signs of Plummer–Vinson syndrome (PVS), in which iron-deficiency-induced mucosal atrophy causes dysphagia. Therefore, in patients with a history of head and neck radiotherapy along with the complaints of dysphagia, the assessment of the TGs is essential as it is a significant differential diagnosis[4]. TG’s histology resembles that of minor SGs[1]. Suppose TG secretions include lactoferrin, transferrin, or ferritin, like other minor SGs, impaired function due to inflammation, radiation, or atrophy could disturb local iron homeostasis at the nasopharyngeal/esophageal junction[5]. Similarly, evidence of dysphagia and xerostomia was found in patients receiving radiotherapy in these areas. The study found a link between the Radiation Therapy (RT) dose to the TGs and the side effects (P < 0.05)[1]. PVS is a rare condition characterized by the triad of dysphagia, iron-deficiency anemia, and upper esophageal webs, also known as Paterson-Brown-Kelly syndrome or sideropenic dysphagia[6]. Keeping in mind these similar clinical features, such as iron imbalance and dysphagia, could lead to a possible misdiagnosis in clinical practice due to mistakenly attributing symptoms of one disease while overlooking the other. With due consideration of current limitations, endoscopic biopsies targeting the TGs may serve as a more effective diagnostic tool by confirming involvement and differentiating it from other conditions with overlapping symptoms. Current knowledge of the underlying cause in such cases is limited. It is speculated that disturbances in iron homeostasis are a prominent factor[6]. Therefore, iron-chelating agents may offer potential benefits in regulating systemic iron levels. However, the extent of iron involvement in TGs remains unclear. More research is needed to precisely link iron metabolism and TGs. Despite being identified as a potential organ at risk for radiotherapy[1], a multi-layered gap prevents the TGs integration into routine clinical practice. Owing to limited data about their pathological and physiological importance, these glands remain neglected in radiotherapy planning protocols, resulting in their overexposure. This causes symptoms such as dysphagia, which may overlap with other conditions, including PVS[6]. To address this, further studies and randomized controlled trials are required. Moreover, it is crucial for radiation oncologists to consider TGs while planning radiotherapy protocols and guidelines to mitigate post-treatment morbidity. Finally, we suggest clinicians include TG dysfunction in the differential diagnosis of nasopharyngeal pathologies. Ultimately, this critique underscores the necessity for clear differentiation between TG pathology and PVS variants in the nasopharynx. Further studies are essential to establish definitive diagnostic criteria and illuminate the precise cryptic role of these glands. To address this gap further, well-structured studies are required not only to establish diagnostic criteria but also to unravel the cryptic role of these newly discovered glands.