The GIST of It

As Head of Surgical Pathology at the National Cancer Institute, what does your job entail?

I lead a group of three surgical pathologists and participate in clinical activities that include handling surgical pathology cases of all kinds, as well as internal and external cases of soft tissue and bone pathology. I also have a research group that studies the improvement of diagnostic methods, especially immunohistochemistry. Our research also includes the study of gastrointestinal stromal (GIST) and related tumors, including genomic studies. Today, we analyze not only stromal tumors and sarcomas, but also common tumors, such as colon cancer. Lately, we have been focusing on fusion tumors; for example, I recently examined a series of colonic adenocarcinomas with NTRK gene fusions. Last, but not least, we have an anatomic pathology residency at NCI, so I also participate in resident education.

Our pathology unit is called the Laboratory of Pathology. It supports both the National Cancer Institute and the diagnostic needs of all branches of the National Institutes of Health. Its clinical units – for instance, surgical pathology, cytopathology, flow cytometry, and molecular pathology – support numerous clinical trials ongoing in our clinical center, which has a hospital solely devoted to such trials. The department also has investigators who perform basic research in pathology and cell biology and to whom I provide specialized pathology support.

How does your current work compare with your previous position?

Before coming to the National Institutes of Health, I was at the Armed Forces Institute of Pathology, which has now closed. The AFIP was a unique research institute devoted to studying the pathology of disease – especially, but not exclusively, tumors of various organs. It had a large collection of specimens, which gave me the opportunity to study rare tumors. Although it provided consultations for federal government entities and hospital pathologists, its staff did not work directly with clinicians.

In contrast, the NIH is a complex of institutes devoted to basic and clinical research. Our laboratory practices pathology in close contact with clinicians developing new treatments for cancer and other diseases. I am grateful for my time here, because I have learned so much from my colleagues on such a great variety of topics, including immunotherapy, immune deficiencies, genomic and epigenetic pathology, and even some clinical and therapeutic thinking.

After the closure of the AFIP, the Joint Pathology Center (JPC) of the Armed Forces took over AFIP’s clinical activities, such as consultation support to military and Veterans Administration hospitals. The NIH’s Laboratory of Pathology remains, in many ways, connected with the JPC. For example, both institutions mutually support specialty pathology consultation and research collaboration on diagnostic pathology, especially with respect to advanced modalities, such as molecular diagnostics.

When I moved to the NIH, my study of cancer took priority – especially colon carcinoma, which is common, important, and easily available as a native specimen. Patients with less common rectal and gastroesophageal cancers usually receive neoadjuvant treatment so effective that no apparent tumor remains for study – so I opted for a disease that both needed and facilitated ongoing research.

What do you consider your most important contribution to surgical pathology?

Perhaps our studies on pathology and clinical correlation of GIST, including the generation of a prognostication system. It is well known that the availability of KIT/PDGFRA kinase inhibitor drugs made clinical study of GIST very popular – a  fact reflected in the citation numbers of articles on GIST pathology. Some large surveys on the diagnostic utility of immunohistochemical markers may also fall into this category.

Books on soft tissue pathology are my main educational products; I have written several. And I have learned that writing a book teaches many lessons – not only to its readers, but also to its authors!

Naturally, there are always unfinished projects. I try to give priority to those that are significant, feasible, and personally interesting. It is impossible to predict what may happen in research even just five years from now, and therefore too difficult to determine what research will happen still further in the future. I hope that we will gain access to new methods that simplify now-complex diagnostic modalities. For example, I would like to see extensive genomic analysis with virtually whole-genome sequencing… with the results and analysis available after only a few days.

What do you see in pathology’s future?

I think histopathology will remain valuable even as molecular tools become increasingly available. Although molecular diagnosis is essential in some cases (and important for finding treatment targets), most diagnoses can still be made using histology and immunohistochemistry. We know that many unrelated tumors have similar mutations and gene fusions, so a precise non-histologic diagnosis requires comprehensive expression profiling on top of genomic analysis. In comparison, classic histopathology is much faster and more cost-efficient.

The other big advance on the horizon is digital pathology. However, at least for now, I feel its time has not come – it remains more costly and time-consuming than traditional methods. However, digital diagnosis has major advantages in the creation of numeric precision, sharing histologic images, and allowing for telework, so I believe it will one day become a major, possibly dominant, diagnostic tool.

What advice would you give young doctors considering a career in pathology?

Pathology is an enormously satisfying specialty with unlimited intellectual challenges. To get the best of surgical pathology, one has to integrate new tools into the morphologic diagnosis: immunohistochemistry, molecular analysis, and epigenetics. Although pioneered by hematopathologists and neuropathologists, these are now becoming important in many subspecialties. It pays to become familiar with them, regardless of your field of focus. And, above all, entering pathology at this time of rapid change is an incredibly fun opportunity!