Diagnosis of branchial cyst carcinoma: Role of stem cells and dormancy

Abstract

Branchial cleft cysts are among the commonest causes for a congenital neck mass. Branchial cleft cyst carcinoma (BCCC) is a type of cancer that arises from cells within these cysts. Congenital branchial cysts and BCCC tumours may result from progenitor cell rests of the embryological branchial development. In the stem-cell carcinogenesis model, a niche of stem-cells, maintains a distinct cellular population. Based on this model, one could anticipate that an explicit stem cell population, remnants of the branchial embryogenesis, would be required to generate any branchial cleft cyst. These cells (TSCs) would need to survive in dormancy for some time before their awakening could be trailed by the clinical presentation of the brachial cleft cyst. For the brachial cleft cyst to continue existing rather than involute, the progenitor stem cells would need to proliferate. With time and while the cyst remains unresected, stem cells could acquire mutations due to genomic instability. During the following years, this population of stem cells would proliferate, maintain and enlarge the cyst and acquire further mutations. With accumulation of further mutations in the stem cells, dysplasia and malignant transformation to TSCs might occur. These mutations might by the driving force for malignant transformation of some progenitor cell clone to TSCs. Such clone TSC populations could beresponsible for BCCC tumours. Inadvertent microbial, viral or traumatic infl ammation of the region, could result in amplifi cation of neck lump signs described above. From the stem-cell perspective, host monocytes and macrophages approaching the area, along with regional fi broblasts and mesenchymal normal stem cells would modify the cyst microenvironment. This might result in advanced proliferation, possible new mutations and further novel epigenetic changes. Such a process would augment the machinery available to TSCs to overcome the hurdles proposed by Hanahan and Weinberg.