Background
Cystic lateral neck lesions provide a complex diagnostic problem. These lesions can represent a cystic metastasis of squamous cell carcinoma (SCC), usually from a primary in the tonsil or base of the tongue. However, on imaging, it can appear identical to branchial cysts, which are benign lesions also found in the neck. It is estimated that 20% of these lesions represent a cancer. Aspiration of the cyst fluid is almost universally acellular or non-diagnostic. A biopsy of the wall is technically challenging, often non-diagnostic and increases the risk of infection. It is common for patients to then receive a variety of investigations over a protracted time. A CT scan, MRI scan, PET scan, repeat US guided biopsy and occasionally a general anaesthetic, examination and then tonsillectomy.
It is common, therefore, to consider a cystic neck mass a malignancy until proven otherwise in all but the lowest-risk patient groups. Missing a diagnosis or a delayed diagnosis of cancer can have severe consequences for a patient’s outcome. Commonly the lesion will need surgical excision. However, without an accurate pre-operative diagnosis, performing an inappropriate operation in the setting of a cancer can occur, risking oncological outcomes. Over-treatment of a benign branchial cyst with a larger oncological neck dissection can also occur, with an increased risk of complications.
The majority of cancers in this setting of cystic neck lesions are HPV/p16-associated SCCs with small or undetected primaries. NHS Lothian has used circulating DNA analysis or a liquid biopsy, which is shown to correlate HPV-associated oropharyngeal SCC cancers, with a concordance of over 90% with standard-of-care tests.
We hypothesize that the same technique could be used in managing patients with cystic neck masses. This would lead to a more streamlined, efficient, and cost-effective patient pathway for these patients. This would allow industry engagement to provide additional utility to the liquid biopsy (circulating tumour DNA) testing platform.
Impact of ENT UK Foundation funding
The ENT UK funding will allow for the laboratory testing of the pre-operative blood samples and re-examination of the pathological specimens with any addition tests that are required.
Current Status
The study aimed to recruit patients and for a pre-operative blood sample to be taken in the specific cDNA blood tube. These patients would then progress to having their surgical treatment, and a final diagnosis could be made.
This will then be compared to the cDNA result, allowing the comparison of clinical, radiological and genomic variables.
We have currently recruited 12 patients with blood samples taken and stored. 10 of the 12 have had their formal surgery. The 2 outstanding patients will receive their surgery shortly.
Once the last 2 patients have completed their clinical pathway, the blood samples will be processed, and the results will be analysed.
Cystic lateral neck lesions can be challenging to diagnose, as they may be benign or indicate cancer. Diagnosis often involves multiple tests, including imaging and biopsies. Missing a cancer diagnosis can have severe consequences. Surgical excision is often necessary, but it's crucial to have an accurate pre-operative diagnosis to avoid inappropriate treatment. HPV/p16-associated SCCs are common, and liquid biopsy testing may offer a more streamlined and cost-effective diagnostic approach for these patients.
The diagnosis of cystic lateral neck lesions can be challenging as they can be mistaken for benign branchial cysts. However, 20% of these lesions may be cancerous, often stemming from squamous cell carcinoma (SCC) in the tonsil or base of the tongue. Diagnostic procedures such as aspiration of cyst fluid and biopsies of the wall can be inconclusive and pose risks. Consequently, patients may undergo multiple tests, including CT scans, MRI scans, PET scans, and biopsies. Given the possibility of malignancy, surgical excision is often necessary, but an accurate preoperative diagnosis is crucial to avoid inappropriate operations and over-treatment.
Most cancers found in cystic neck lesions are HPV/p16-associated SCCs, which can have small or undetected primaries. NHS Lothian has successfully used circulating DNA analysis, or liquid biopsy, to identify HPV-associated oropharyngeal SCC cancers with over 90% concordance with standard-of-care tests. This technique could potentially be applied to managing patients with cystic neck masses, offering a more efficient and cost-effective patient pathway.
The funding from ENT UK will support laboratory testing of preoperative blood samples and re-examination of pathological specimens, including any additional tests that may be necessary.
Update: We are conducting a study to recruit patients for pre-operative blood sample collection using a specific cDNA blood tube. After the collection, these patients will undergo surgical treatment, and a final diagnosis will be determined. We will then compare these results with the cDNA data to analyze clinical, radiological, and genomic variables. As of now, we have recruited 12 patients and collected their blood samples, and 10 out of the 12 have already undergone surgery. The remaining 2 patients will have their surgeries soon.