Distinguishing de Novo Second Cancer Formation from Tumor Recurrence : Mutational Fingerprinting by Microdissection Genotyping

Abstract

Patients with one form of cancer are known to possess a higher risk for development of a second tumor, presenting synchronously or metachronously over time. Distinguishing whether the second tumor represents a de novo cancer or a recurrence/metastasis of the first cancer has important implications for treatment and prognosis and specific clinical and pathological evidence is sought to resolve this issue. De novo cancer formation is favored by long latency interval (usually exceeding five years), better differentiation in the subsequent tumor, solitary second tumor formation and occurrence of the later tumor in a site not typical of metastatic spread. Conversely, recurrent metastatic disease is favored by short interval to second cancer formation, similar histology with increased anaplasia in the second tumor and lack of in situ malignancy and multifocal tumor deposits. While these criteria are sufficient in most instances to distinguish between the two, varying degrees of uncertainty can persist with a minority of cases remaining unresolved.