Field carcinogenesis

Slaughter et al. introduced the term field carcinogenesis in 1953 during their investigations of squamous cell carcinoma in the oral cavity. They observed histologically abnormal connective tissue in several areas, which was located in the immediate vicinity of the squamous cell carcinoma. They concluded that squamous cell carcinomas of the oral cavity can develop at different sites, especially in regions already pathologically altered by connective tissue. The persistence of such unphysiologically altered connective tissue regions could also explain why local recurrences occur after surgical resections.

The term field carcinogenesis has been described in several organ systems: neck, head, oropharynx, lung, esophagus, vulva, cervix, breast skin, colon and bladder. It plays a role in the assessment of MDE in work-related skin cancer (see BK 5103 below)

At present, there are several studies and ideas on how field carcinogenesis develops and what prognostic significance it has in terms of recurrence and healing rates. It is assumed, among other things, that there is at least one stem cell in an area ("field") that falls victim to mutations or genetic alterations in the course of its development. These mutated cells escape from the cycle of physiological growth and, in contrast to the unaltered cells, rapidly gain in size (so-called "growth advantage"). Due to the rapid expansion, the neighbouring, lateral areas are taken over, which leads to a local spread and the formation of conglomerates ("clusters") of the mutated cells. The expansion is at the expense of the physiologically existing tissue. In parallel to this process, genetic changes and mutations continue to occur in this area, for example due to UV radiation. It is therefore assumed that altered cells are in different stages and can eventually occupy an entire area like a minefield (so-called "ticking bomb"). The higher the number of altered cells, the higher the carcinogenic potency. This theoretical notion of carcinogenesis raises further questions in everyday clinical practice: If another tumour occurs in the same area after previous therapy, it remains unclear whether this is a recurrence or an independent, second tumour (so-called "second field tumour"). This discrimination implies important therapeutic consequences. Conclusion: The existence of pre-neoplastic cells in an area dramatically increases the risk of progression of carcinogenesis. Close clinical follow-up minimizes the risk.

Field carcinogenesis in actinic keratosis: Skin lesions occur preferentially in UV-exposed areas. A multiple occurrence is often registered. Histologically, actinic keratoses are characterized by an increase in basal keratinocytes ("crowding" phenomenon) and the detection of individual atypical keratinocytes in the basal zone. Such atypical cells can also be detected in higher epidermal layers. The existence of altered keratinocytes with different graduations in one area is also called field carcinogenesis. In a study in which more than 1000 squamous cell carcinomas from sun-exposed skin were histologically examined, histopathological changes in the sense of actinic keratoses were found in the periphery in almost 100% of the cases.

1. Braakhuis BJ et al (2003) A genetic explanation of Slaughter's concept of field cancerization: evidence and clinical implications. Cancer Res 63: 1727-1730
2. Diepgen TL et al. (2015) Reduction of earning capacity in BK 5103 " Squamous cell carcinomas or multiple actinic keratoses of the skin due to natural UV radiation " Dermatology at work and in the environment 63: 3-7
3. Slaughter DP et al (1953) Field cancerization in orally stratified squamous epithelium; clinical implications of multicentric origin. Cancer 6: 963-968