Staging in patients with multiple tumours: integrating morphology and molecular profiling

With improvements in lung cancer diagnosis and management, the phenomenon of patients having more than one lung cancer is becoming increasingly frequent. Whether a second cancer is considered a separate primary lung cancer or an intrapulmonary metastasis fundamentally changes the staging and can have critical importance for treatment decisions. Histological comparison of cancers is often an effective tool in discriminating between separate primary lung cancer and intrapulmonary metastasis. The advent of genomic profiling has brought another powerful tool to our arsenal. While there is compelling evidence that both approaches accurately resolve the majority of cases, neither is without limitations and it is easy to succumb to pitfalls from both histological and genomic assessment. A combined approach by a pathologist who is skilled in recognizing discriminating histological features, and who has a good grounding in the molecular evolution of cancers and in the limitations of molecular techniques, is required to optimize these judgements. In this review, we discuss the tools which can be brought to bear on the dilemma of classifying multiple lung cancers. We begin by reviewing the clinical and radiological clues, before discussing the value of histological comparison, and finally the value which molecular profiling can bring.