Profiling clonality and progression in multiple premalignant and malignantoral lesions identifies a subgroup of cases with a distinct presentation of squamous cell carcinoma

A cohort of head and neck cancer patients, without exposure to tobacco and alcohol, presented with multiple preneoplastic and neoplastic lesions, the natural history of which may span several decades. Examination of these cas es provides an opportunity to study the relationship between genetic, morph ological, and clonal progression in these fields and establish whether they represent a unique presentation of squamous cell carcinoma, The presence o f a common novel microsatellite allele, a common breakpoint or concordant a llelic imbalance at multiple loci, reveals that a high proportion of these serial lesions arise due to spread of a precursor, The tumors arising in th ese patients were typically nonaggressive, although metastases developed at a late stage, supporting the notion that the genotype results in a phenoty pe with a propensity for lateral spread, rather than invasion. Different ge netic aberrations were detected in morphologically similar phenotypes such that no consistent early or late events were associated with development of premalignant lesions. Combining information about the clinicopathological features and histological examination of the margins with that derived from clonality analysis reveals that a subgroup of patients, without exposure t o the traditional risk factors associated with this disease, developed mult iple clonally related oral lesions and represents a unique presentation of head and neck squamous cell carcinoma, We suggest the term clonal canceriza tion to describe multiple premalignant and malignant lesions when there is conclusive evidence that they arise due to lateral spread from a common pre cursor.