Researchers identify unique genetic signature in rare oral cancer

Cancer diagnosis can be challenging, and delayed diagnosis can allow cancer to progress, complicating treatment. Oral squamous cell carcinoma (OSCC), the most common type of oral cancer, can sometimes mimic benign conditions, such as gum disease or oral infections, making diagnosis difficult. Therefore, identifying new diagnostic methods for OSCC is crucial.

Now, researchers from The University of Osaka have identified a distinct genetic signature that sets carcinoma cuniculatum - a rare OSCC with a burrowing pattern - apart from the more aggressive, conventional forms of OSCC. These findings are set to be published in Head and Neck Pathology.

Carcinoma cuniculatum, a rare variant of OSCC, can behave very differently to conventional OSCC. This form grows slowly in burrow-like patterns, and while it rarely spreads and typically has a good prognosis, difficulties in diagnosis can delay treatment.

"Although carcinoma cuniculatum is a malignant tumor, its appearance can overlap with that of benign lesions that require very different treatments. In other words, it can be a 'wolf in sheep's clothing', meaning that diagnosing this rare condition can be difficult, even for specialists such as pathologists," explains corresponding author Katsutoshi Hirose. "This uncertainty highlights the need for better tools, including genetic testing, to help pathologists make clearer, faster diagnoses."

As part of their analysis, the researchers reviewed 2,002 cases of OSCC from the pathology archives of multiple institutions. They identified 23 cases of OSCC with a "burrowing" growth pattern. Based on their analysis of these 23 cases, they found that carcinoma cuniculatum has a distinct genetic fingerprint. Pathogenic genetic alterations were observed in 87.5% of the carcinoma cuniculatum cases examined.

The results have sparked great excitement, indicating that carcinoma cuniculatum shows fewer alterations in major oral cancer driver genes like TP53 and CDKN2A. However, alterations were more frequent in other genes, including FAT1, NOTCH1, PIK3CA, and CASP8, indicating the presence of a distinct genetic pattern. The involvement of these genes could potentially explain the slower growth and lower risk of spread of carcinoma cuniculatum compared with more aggressive forms of oral cancer.

Genetic testing has the potential to become a practical tool for accurate diagnosis and targeted treatment, helping clinicians identify certain conditions more reliably and improve patient care. Our findings suggest this diagnostic approach may also be useful for diagnosing carcinoma cuniculatum."

Sawako Ono, first author

This research offers a promising step toward making one of the most difficult-to-diagnose oral cancers easier to recognize and treat. By uncovering gene alterations, these insights could bring new hope for people facing this rare and overlooked form of oral cancer.