Primary carcinoma of the Eustachian tube (ET) is exceptionally rare, accounting for only a minute fraction of head and neck cancers. A systematic review identified 78 reported cases of primary ET tumors and tumor-like lesions, including malignant lesions, of which 18 were carcinomas [1],[2],[3],[4]. Because of its deep anatomical location and nonspecific symptoms such as ear fullness or hearing loss, early diagnosis is often difficult. In addition, standard temporal bone CT may not adequately visualize the ET, making radiological evaluation challenging.

We report a rare case of ET squamous cell carcinoma (SCC), emphasizing the diagnostic difficulties and the importance of meticulous radiological and pathological evaluation.

A 53-year-old Sri Lankan male presented with a two-year history of left ear fullness and progressive hearing loss, without otorrhea, otalgia, or ear bleeding. He initially visited a local ear, nose, and throat (ENT) clinic and was diagnosed with left otitis media with effusion (OME). Despite tympanostomy tube placement, his symptoms did not improve and his hearing gradually worsened. He was therefore referred from the local ENT clinic to a tertiary care hospital, where cholesteatoma was suspected based on temporal bone CT, and surgical treatment was planned.

Medical history: Lumbar disc herniation (surgically treated at age 40)

Alcohol consumption: Beer 350 mL/day (positive alcohol flush reaction)

Smoking: None

Examination Findings at the Referring Hospital

Tympanic membrane findings: A tympanostomy tube was observed in the left tympanic membrane, with serous effusion discharge.

Temporal bone CT: Figure 1A, Figure 1B, Figure 1C, Figure 1D, Figure 1E, Figure 1F.

Pure-tone audiometry showed severe conductive hearing loss on the left (four-frequency average 66.3 dB) and normal hearing on the right (18.8 dB) (Figure 1G).

Based on these findings, the patient underwent tympanoplasty with canal wall-up mastoidectomy at the referring hospital. Intraoperatively, extensive, friable granulation tissue extended from the entire tympanic cavity to the mastoid antrum, with erosion of the incus long process. A remnant tympanostomy tube was found in the anterior mesotympanum, likely contributing to the granulation tissue proliferation. The facial nerve was not exposed intraoperatively. Initial pathological examination revealed inverted papilloma (IP); however, the diagnosis was revised to SCC at our hospital, and the patient was referred to our institution for further management.

At the initial visit to our hospital, a tumor was observed at the pharyngeal orifice of the ET (Figure 2A and Figure 2B). Magnetic resonance imaging (MRI) revealed a 34 mm enhancing lesion along the ET (Figure 2C and Figure 2D), with corresponding FDG uptake on PET-CT (Figure 2E and Figure 2F). Biopsy from the tumor at the pharyngeal opening also confirmed SCC (Figure 3). Radical chemoradiotherapy (CDDP 100 mg/m² × three times, RT S60 Gy) led to complete remission without grade 3 or higher toxicity. The patient remains disease-free at five years, and tympanoplasty was later performed for residual perforation.

This case represents an exceedingly rare malignancy originating from the ET, a site that is seldom involved in head and neck cancers. The clinical challenges of accurately diagnosing the tumor and identifying its site of origin, as well as the suspected malignant transformation from IP, are notable features.

Tumor Origin and Diagnostic Considerations

Most reported ET carcinomas are histologically SCC or non-keratinizing carcinoma (formerly called transitional cell carcinoma) [1],[2],[3],[4]. The ET, approximately 3.5 cm in length, connects the nasopharynx to the middle ear and is lined with ciliated columnar epithelium. The nasopharyngeal mucosa comprises stratified squamous, ciliated columnar, and transitional epithelium, whereas the middle ear is predominantly lined by columnar epithelium. Ciliated columnar epithelium is known to undergo squamous metaplasia under chronic inflammatory conditions, which may contribute to carcinogenesis.

In this case, SCC was identified at both the pharyngeal and tympanic orifices of the ET, and EBER-ISH was negative (Figure 3C), unlike nasopharyngeal carcinoma where EBV association is frequent [5]. Imaging demonstrated a lesion following the ET course without clear predominance toward either the nasopharynx or middle ear (Figure 2C), making the primary site indeterminate. Future molecular analyses may help elucidate the epithelial origin of such tumors.

Malignant Transformation of Inverted Papilloma

Primary IP of the middle ear is extremely rare, with recurrence and malignant transformation rates (53.8% and 38.5%) exceeding those of sinonasal IPs (5–27%) [6],[7],[8]. Because many cases of middle ear IP coexist with sinonasal IP, a nasopharyngeal origin was also considered in the present case.

Immunohistochemically, p16 expression has been reported in 18–55% of IPs [8],[9], although its correlation with human papillomavirus (HPV) DNA remains relatively low [10]. Diffuse p16 positivity was observed in this case; however, p16 overexpression is not specific for HPV-driven carcinogenesis and may also reflect reactive changes associated with chronic inflammation or non-HPV-related pathways [11]. As HPV DNA testing was not performed, the role of HPV in the present tumor cannot be determined.

Challenges in Radiological Diagnosis

In standard temporal bone CT protocols, the imaging field usually spans from approximately 1 cm superior to the petrous apex to the mastoid tip, generally including the ET. However, some institutions limit the scanning range or upload only bone-window images, reducing diagnostic accuracy.

In the present case, a subtle bony destruction anterior to the petrous apex was identifiable only in retrospect on the pre-treatment CT; however, recognizing this as indicative of ET carcinoma would have been extremely difficult at the time. Even in candidates for otologic surgery, evaluation should extend beyond the temporal bone to include the petrous apex and the entire ET. In addition to high-resolution CT—carefully inspected for subtle bony destruction—contrastenhanced MRI and, when indicated, nasopharyngoscopy may help detect lesions at the pharyngeal orifice of the ET that can be overlooked when the clinical focus is primarily on middle ear disease. The lack of nasopharyngoscopic evaluation before ear surgery may also have contributed to delayed detection of this lesion.

Primary SCC of the ET is rare and may present with nonspecific otologic symptoms, leading to delayed diagnosis. In this case, the tumor extended along the course of the ET and was difficult to detect on routine preoperative imaging focused on the middle ear. When unilateral OME is prolonged and even subtle abnormal findings are present preoperatively, disease involvement beyond the middle ear, including ET and nasopharynx, should be considered. Careful review of temporal bone CT, together with contrast-enhanced MRI and nasopharyngoscopy when appropriate, may help avoid missing this rare entity.