We met on social media after a Twitter chat on lung cancer. It was an unlikely connection — an artist on a long journey with cancer (Linnea) and a pathologist (Michael). But it is one we hope can be a model for others down the road. We believe that closer, more personal connections between physicians, including pathologists, and their patients can create a better understanding of cancer, from both scientific and humanistic perspectives.
Misialek: I am interested in learning more about the patients behind my slides. I invited Linnea to the lab, where I showed her different lung cancers under the microscope, including her specific cancer type.
Olson: After I was diagnosed with non-small cell lung cancer in April of 2005, I wrote a letter of thanks to the pathologist. I was so very grateful that I now had a credible explanation for the cough, shortness of breath, and general malaise that my general practitioner had misattributed to adult onset asthma. As an information-based individual, even though a diagnosis of lung cancer was devastating, knowing the actual cause of my symptoms was a huge relief.
Misialek: I’ve been a pathologist for 17 years. Most of my work is with microscope slides that bear small smears of stained tissue. I scrutinize them to find an answer for a patient’s symptoms, to make a diagnosis, or to assess the response to treatment. The first time a patient’s cells are illuminated under the microscope represents to me a new challenge that must be answered.
Although I rarely have the opportunity to interact directly with patients, I am often the physician that first makes the diagnosis, an important first step in caring for a patient. But my involvement doesn’t end there. Additional information is often needed to tailor treatment or gauge effectiveness. Pathology is essential not just for diagnosis but also in health and the prevention of disease. The role of the pathologist has taken on greater meaning in this era of precision medicine.
Olson: I am an artist and once studied to become a medical illustrator. When I was young, I had my own microscope and a dissecting kit. Over the years I have collected a wide variety of natural specimens for use in my art.
When I visited Michael in the lab, it was the most extensive view I’ve ever had of lung cancer slides under the microscope. I had never held a lung before, and seeing what a tumor actually looked like was mind-blowing. It is so different than how it appears on CT or MRI scans. Seeing one in real life gave me a greater appreciation for how a tumor invades healthy tissue.
I was already working on some pieces that were more autobiographical, so it was cool to see more intimately what is going on inside the body. Tissue freshly removed from the body (like the lung Michael showed me) is so very different than what we usually see in photos or how it is represented in models or drawings. It is so obviously alive — like the difference between a living tree and a piece of wood. The microscope slides were another window into the complex processes going on inside each of us that we are often oblivious to. I find it all fascinating and inspiring and it has informed both my painting and some multimedia pieces I am working on.
Misialek: Pathology is both an art and a science. There is art in making a diagnosis. On another level, there is art to the colors and patterns of cells under the microscope, just like Linnea’s pigments on canvas. Lung cancer appears as masses of foreign cells, recognizable at low magnification. The delicate sponge-like lattice of normal lung tissue is violated by infiltrating cancer cells, breaking up the harmonious pattern, wreaking havoc on the body.
Olson: My cancer was classified as bronchial alveolar carcinoma mucinous — now referred to as invasive mucinous adenocarcinoma. It came as a surprise, because I was young at the time (45) and wasn’t a smoker.
Misialek: Mucinous adenocarcinoma cells spill the mucus they accumulate. Under the microscope, they look like oil tankers with breached hulls.
Olson: My tumor was relatively large (5 centimeters) but all of the nearby lymph nodes that were removed were clear of cancer. A sample of my tissue was submitted for genetic screening.
Misialek: Perhaps no greater example of the power of precision medicine is the way that it has transformed our approach to lung cancer. In 1987, scientists found that the epidermal growth factor receptor (EGFR), which sits on the surface of lung cancer cells, could be a target for treatment. This receptor acts as an important regulator of cellular functions, ultimately controlling cell survival, tumor growth, invasion, and spread. In 2003, the FDA approved gefitinib (Iressa), the first drug that homes in on EGFR, beginning an era of targeted therapy. Others have been approved since then. Pathologists at Massachusetts General Hospital studied Linnea’s tumor, unraveling and reading its unique genetic code, searching for an Achilles heel. Unfortunately, Linnea’s tumor did not carry an EGFR mutation.
Olson: My initial treatment was a lobectomy — an operation to remove the lower lobe of my left lung. That was followed by four rounds of chemotherapy. I had hoped this would cure my cancer, but it returned almost immediately. With no further viable treatments, we began a period of watching and waiting. Each subsequent scan of my lungs showed additional cancerous nodules.
By the summer of 2008, I had more than 33 tumors in my lungs, and a biopsy confirmed that it was spreading beyond the lung. Given three to five months to live, I tried a last ditch therapy with a drug called erlotinib (Tarceva). Not only did my cancer get worse, but I experienced all of the side effects. However, my oncologist had an encouraging bit of news. Genetic screening of tissue removed at my latest biopsy had come back positive for what’s known as an EML4-ALK translocation. This mutation supports the unregulated growth of non-small cell lung cancer cells. That mutation let me enroll in a clinical trial and, on Oct. 1, 2008, I became the fourth person in the world with non-small cell lung cancer to take an experimental drug called crizotinib (now marketed as Xalkori).
Misialek: An international team that included Linnea’s oncologist, Dr. Alice Shaw of Massachusetts General Hospital, described ALK mutated lung cancers in the New England Journal of Medicine. This unique mutation is found in about 4 percent of patients with non-small cell lung cancer. In them, crizotinib can yield dramatic improvements.
Olson: I am acutely aware of how close I came to dying, but also of how being in the right place at the right time saved my life. My tissue was submitted for ALK testing just after it was identified as a driver in non-small cell lung cancer.
Misialek: Targeted therapy comes with a price. Tumors inevitably mutate and develop resistance to the drug. This happened with Linnea’s tumor. It becomes a cat and mouse game. Researchers have found ways around this for both EGFR and ALK mutations. Dr. Shaw and her team reported on how a new drug can circumvent ALK resistance.
Olson: Crizotinib brought me back from the brink but it didn’t cure me. I am now enrolled in my third phase I clinical trial for an ALK inhibitor. I entered it with low expectations, but have had a significant and a sustained response. I am grateful for every single day — at this point they all feel like a bonus. In April 2016, I marked 11 years since my diagnosis. However, I can’t help but think about my next treatment options (such a beautiful word — options!) and the fact that I need medical science to stay one step ahead of my cancer.
Misialek: Great strides have been made over the years in fighting lung cancer. One new approach is immunotherapy. It uses medications that boost the immune system so it can kill cancer cells. Many advances in treating lung and other cancers have begun with the work of pathologists. Not only is the information from pathology important for diagnosis, prognosis, and treatment, but it is essential for enrolling patients in clinical trials.
Olson: I am so fortunate to be witnessing a new era in cancer treatment. Cure is a lovely notion but next best is living with cancer — something that more and more people such as myself are now doing.
Misialek: Even though we have made much progress in our understanding of lung cancer, there is still a long way to go. We still don’t know what causes the vast majority of lung cancers. As new driver mutations are discovered, companion drugs that target these mutations must be developed. Unfortunately, most patients currently don’t have the opportunity to get targeted therapy.
Olson: What still makes me sad and angry about my disease is how most people instinctively link lung cancer with smoking, and there is a not-so-subtle premise that people with lung cancer have somehow brought this disease upon themselves. How do I know this? Because upon hearing that I have lung cancer, virtually everyone eventually gets around to asking me if I smoked.
Misialek: Cancer knows no boundaries. Anyone can get it. Precision medicine with targeted therapy and immunotherapy forming the mainstays of treatment will help many of them live longer.
Olson: It was a privilege to go the lab with Michael and look at lung cancer cells under the microscope and hold an actual lung. I’m a strong advocate for patients as partners in their own care. I feel that the more we know about our disease, the better we are able to make good choices.
Misialek: Working directly with Linnea has given me a new perspective on my work. I better understand the impact of my diagnoses, and the faces behind the slides. Pathologists should all have the opportunity to meet with their patients.
Linnea Olson is an artist, mother, activist, and author of the “Life and breath: outliving lung cancer” blog. Michael J. Misialek, MD, is associate chair of pathology at Newton-Wellesley Hospital in Newton, Mass., and clinical assistant professor of anatomic and clinical pathology at Tufts University School of Medicine.