The use of ultrasound in the search for the primary site of unknown primary head and neck squamous cell cancers

Abstract

Background: Although human papillomavirus detection in cervical lymph nodes of head and neck squamous cell cancers (HNSCC) of unknown primary site (UP) is indicative of a primary tumor of the oropharynx (OP), localization can remain elusive. Therefore, we investigated ultrasonography (US) for the identification of the primary tumor.

Methods: Eligible cases had HNSCC of UP after evaluation by a head and neck surgical oncologist. Controls were healthy volunteers. Transcervical and intraoral ultrasonography was performed by a standard protocol using convex (3.75-6.0 MHz and 5-7.5 MHz) transducers. US findings were compared with operative examination (exam under anesthesia, direct laryngoscopy) and biopsies. The primary outcome of interest was the presence or absence of a lesion on US.

Results: 10 cases and 20 controls were enrolled. PET/CT scans were negative/nonspecific (9), or suspicious (1) for a primary lesion. On US, predominantly hypoechoic (9 of 10) lesions were visualized consistent with base of tongue (n=7) or tonsil (n=3) primary tumors. On operative examination, 5 of 10 were appreciated. Two additional primaries were confirmed with biopsies "directed" by preoperative US. This represents an overall diagnostic rate of 70%, which is 20% higher than our detection rate for 2008-2010. The three cases in which a suspicious lesion was visualized on US, yet remained UP despite further interventions, could represent false positives, misclassification or operator variability. No lesions were suspected among the controls.

Conclusion: Ultrasound has promise for detection of UPs of the OP and therefore warrants further investigation.

Keywords: Head and neck cancer; Human papillomavirus (HPV); Oropharynx neoplasm; Ultrasonography; Unknown primary.

Fig. 1

Transcervical ultrasound examination of oropharynx. Parasagittal view (A) demonstrates intact hyperechoic oral mucosa of oral and base of tongue (+). The hyoid (ψ) and mandibular (*) shadows are shown. The sonographic base of tongue is the posterior one third of the distance between the central portions of the mandible and hyoid annotated by (↓). The palatine tonsillar region is isoechoic (Φ). On coronal view (B) hyoid shadows are seen bilaterally (ψ). The oral mucosa is intact (+). The base of tongue musculature is noted to be symmetric. Panels C and D are images representative of a base of tongue lesion. On parasagittal view is a hypoechoic lesion, the majority of which is beneath the mucosal surface of the base of tongue, with a slight disruption of the mucosa (xx). The mass is also visualized in coronal view (D). Extent across midline is appreciated in coronal view.

Fig. 2

Clinical and radiographic images of a patient with head and neck squamous cell cancer of unknown primary. PET scan (A), MRI (B) and fiberoptic laryngoscopy (C) do not demonstrate any evidence of a primary lesion in the oropharynx. On transcervical ultrasound, right parasagittal view (D) posterior and anterior are labeled “post” and “ant”. Normal base of tongue (BOT) without evidence of a tonsillar mass is shown in panel D. The mucosa of the oral and base of tongue is intact. The myelohoid (MM) and geniohyoid (GH) muscles are visualized and intact. On left parasagittal view (E) a hypoechoic lesion, relative to the isoechoic normal tongue is appreciated and is consistent with a suspected base of tongue mass. This is confirmed on coronal view (F), whereby a small hypoechoic lesion is similarly appreciated.