Is it time for pathologists to take a more active role in lung cancer?

Noted for his contributions to numerous guidelines and to the World Health Organization lung cancer classifications, Keith Kerr, Professor of Pathology from the Aberdeen University School of Medicine and Dentistry, Aberdeen, UK, received the Heine H. Hansen Award at the European Lung Cancer Congress 2025 (Paris, 26–29 March). In his keynote lecture, Kerr discusses ‘history, histopathology and hyperbole’ as lung cancer pathology continues to evolve.

How do you think your work as a pathologist has influenced lung cancer management?

Over 25 years ago, I was involved in research looking into the relationship between lung cancer and the immune system (Histopathology. 1998;33:55–63). Some patients undergoing tumour resection showed evidence that the immune system had partially induced tumour regression. This, albeit rare, phenomenon – which had previously been reported in other tumour types, such as melanoma – was associated with a better-than-expected prognosis. The observation, years later, that similar pathology is seen in lung cancers resected after neoadjuvant immunotherapy, confirms the power of manipulating the immune system to extend innate benefits to a wider group of patients. In another work, I helped to establish an association between the precursor lesions, atypical adenomatous hyperplasia and lung adenocarcinoma in Western Caucasians (Br J Cancer. 2000;83:632–636), a link which had previously only been shown in Japanese populations.

Diagnostically, I was part of the team recommending the classification of non-small cell lung carcinoma-not otherwise specified (NSCLC-NOS) in cases of uncertainty. This led to the publication of the first paper demonstrating the value of immunohistochemistry (IHC) to predict the likely cell type in small biopsy samples from patients with a diagnosis of NSCLC-NOS (J Clin Pathol. 2000;53:537–540). The inclusion of NSCLC-NOS in management guidelines, together with this IHC work, has resulted in a more accurate classification of the disease, which in turn, has helped to guide appropriate treatment.

How has lung cancer pathology evolved over the years?

Forty years ago, medical oncology as a specialty was really still in its infancy. Surgery was the mainstay of treatment, but there was little interplay of ideas between surgeons and pathologists. Today, the situation has been completely transformed, mainly due to therapeutic requirements, and pathologists have very much secured their place in the multidisciplinary team.

One of the early drivers of change was the introduction of different types of chemotherapy for patients with lung carcinomas not categorised as ‘small cell’. Originally, all these patients received more or less the same treatment. The advent of new chemotherapy options led to the requirement for pathologists to confirm whether the disease was squamous cell or an adenocarcinoma, in order to enable treatment to be directed effectively. Later, the concept of molecularly targeted therapies raised awareness of different driver mutations and other alterations, which pathologists have been closely involved in identifying. More recently, when immunotherapy emerged, pathologists quickly recognised that its efficacy was influenced by particular characteristics, such as the expression of PD-L1, which then became a focus of the oncology and pathology communities.

Identifying pathological characteristics as biomarkers to define which patients are likely to benefit from a particular therapy is now firmly established and is an area that will continue to develop. Exploring global DNA and RNA sequencing and understanding how best to use the complex genomic information generated is also a priority. Other new technologies, including artificial intelligence, will undoubtedly help to advance the field, but they come with their own challenges – pathologists need to learn how best to leverage novel tools without being distracted by the hype.

How can today’s lung cancer pathologists help facilitate further progress?

There is still a disconnect between clinicians treating lung cancer patients and the science behind the treatments. The pathologist is the medium through which the different elements can link up and greater understanding can be forged. It is vital, therefore, that the pathology community replaces its often reactive approach with a more proactive standpoint, running towards change and not away from it.