Search

Upper aerodigestive squamous cell carcinoma (UASCC) is an aggressive and lethal neoplasm, with its early neoplastic transformation mechanisms remaining poorly understood. Here, we characterize over 25 genetically-defined organoid models derived from murine and human oral/esophageal tissues harboring key driver mutations. Double knockout of TP53 and CDKN2A induced morphological dysplasia, hyperproliferation, loss of squamous differentiation, and tumorigenicity, which were further exacerbated by additional driver mutations (e.g., PIK3CA , NOTCH1 , KMT2C ). Single-cell analysis revealed an expansion of quiescent basal cells and proliferative squamous cells, alongside a loss of differentiated squamous cells during malignant transformation. A distinct senescence program, regulated by ANXA1, was markedly diminished during early neoplastic evolution. Mechanistically, the ANXA1-SMAD3-p27 KIP1 pathway was identified as a critical regulator of this senescence program, acting to suppress neoplastic features in organoid models. Lastly, our high-throughput, single-organoid-resolution drug screens unexpectedly revealed PIK3CA -driven organoids exhibited sensitivity to Mitomycin C and Onalespib. This study provides novel mechanistic insights into early neoplastic evolution and underscores the value of genetically-defined organoid models for investigating cancer biology and identifying targeted therapies.

Dens evaginatus (DE) presents a clinical conundrum due to its fragility and propensity to cause pulpal and periapical complications. Clinicians should heed the presence of DE during clinical examinations and avoid unnecessary intervention., Competing Interests: No conflict of interests to disclose., (© 2024 The Authors. Clinical Case Reports published by John Wiley & Sons Ltd.)

Subcutaneous tumors of the head and neck resembling cutaneous mixed tumors may be misdiagnosed pleomorphic adenomas of salivary gland origin. Physicians should consider salivary mixed tumors in the differential diagnosis for suspected cutaneous tumors., Competing Interests: No conflict of interests to disclose., (© 2024 The Authors. Clinical Case Reports published by John Wiley & Sons Ltd.)

The presence and reactivation of oral lesions such as herpetic gingivostomatitis, erythema multiforme, and candidiasis in a COVID-19 recovered patient could be related to COVID-19s profound role in immune dysregulation or related therapies., Competing Interests: There are no conflicts of interest., (© 2023 The Authors. Clinical Case Reports published by John Wiley & Sons Ltd.)