Paul T. Nghiem, MD, PhD
Seattle Cancer Care Alliance
University of Washington School of Medicine
Fred Hutchinson Cancer Research Center
Dermatology, Merkel cell carcinoma, melanoma, graft versus host disease, complex skin cancer management in a multidisciplinary team
I like to provide patients with as much information as they are comfortable with and engage them in the decision making process regarding management options in caring for complex skin cancers.”
Why do you practice oncology?
A Sleuth Takes on the Case of the Mysterious Skin Cancer Sometimes we do what the higher-ups want only because we’re in no position to refuse. But our acquiescence occasionally leads to fortuitous discoveries. When Paul Nghiem, MD, PhD, was a new attending physician at Dana-Farber Cancer Institute in Boston in 1998, a mentor recruited him to help write a textbook chapter on Merkel cell carcinoma (MCC). But Dr. Nghiem had seen only one case of MCC and knew very little about it. “I was very unenthusiastic about this assignment,” recalls Dr. Nghiem. His disinterest faded as he dug into the existing studies on MCC. “When I actually sat down and read the literature, I found out Merkel cell carcinoma is a very interesting and unique cancer that is poorly understood,” he says. Since then, unraveling the mysteries of MCC has been a major focus of Dr. Nghiem’s clinical work and increasingly his lab research. Several aspects of MCC piqued Dr. Nghiem’s curiosity. For one thing, MCC strikes more aggressively than any other type of skin cancer, such as the more common melanoma and basal cell carcinoma. “It’s the most lethal of all skin cancers, killing upwards of a third of all patients diagnosed with it,” says Dr. Nghiem, a dermatologist specializing in skin malignancies. There are also some important differences in risk factors for MCC and how the disease develops, and it is managed differently than other skin cancers. Read more about MCC. Expanding Skin Cancer Services After the textbook project, Dr. Nghiem’s interest grew. At the time, there was no one who specialized in treating MCC in the greater Boston and New England area, says Dr. Nghiem, so he quickly developed into the region’s go-to man on the subject. In January 2006, Dr. Nghiem brought his experience to the Seattle Cancer Care Alliance, joining the skin cancer experts already on staff here. He is working primarily with several other SCCA doctors, David R. Byrd, MD, Shailander Bhatia, MD, and John A. Thompson, MD, to expand the SCCA multidisciplinary skin oncology clinic to serve people with more types of skin disease. “The melanoma clinic is well established,” said Dr. Nghiem right after his move. “I am looking forward to joining the team and expanding the clinic’s focus to include a greater breadth of skin cancers and dermatology. I am also interested in enhancing integration of teaching and research into the clinic,” says Dr. Nghiem, also a professor of Medicine in Dermatology at the University of Washington. Working with Patients and in the Lab As of 2015, approximately 2,000 people annually in the United States are diagnosed with MCC, says Nghiem. In Boston, he saw about one new patient per week, and that has now doubled at SCCA. About 20 percent of his time is spent with skin cancer patients, overseeing their medical care and coordinating with surgeons and medical and radiation oncologists to make sure they get all the treatment options that are appropriate. The other 80 percent of Dr. Nghiem’s time is spent in his laboratory at the new South Lake Union campus of UW Medicine. A researcher affiliated with SCCA partner Fred Hutchinson Cancer Research Center, Dr. Nghiem moved not only himself and his family but also his lab from Boston to Seattle. He studies the checkpoints in the cell cycle that relate to damage from ultraviolet radiation. In the process, he’s trying to find small molecules that selectively damage P53-negative cells. P53 is a very important tumor suppressor. In cells that are deficient in P53, cancer has an advantage instead of being suppressed. Dr. Nghiem is trying to find ways to intervene and reverse that advantage so that cancer cells are more effectively killed by chemotherapy and radiation. Read more about Dr. Nghiem’s lab. “The science and clinical opportunities here are outstanding,” says Dr. Nghiem about his move to SCCA. Understanding the Mysteries of MCC MCC stands out from other skin cancers in several ways that have important implications for treatment. “The most important therapies for melanoma,” says Dr. Nghiem, “are early detection and complete surgical excision [removing all the cancerous area]. For Merkel cell carcinoma, early detection is, of course, important, and surgery can be effective,” he says. “But unlike in melanoma, surgery alone has very high local recurrence rates for this disease.” MCC is a cancer that spreads discontinuously, Dr. Nghiem explains. So when doctors remove a cancerous area, it may appear they got it all. For instance, the margins around the excised tissue may be free of cancer cells when examined under the microscope. But there are often cancer cells left in the adjacent tissue that will grow and make their presence known over time. “The other important thing about this cancer is that it’s very sensitive to radiation,” says Dr. Nghiem. There is some evidence that in some people radiation alone may be a viable treatment option, he says. It is only a hypothesis at this point, and it needs further study, he adds. But in any case, he says, “radiation plays a uniquely important role in this skin cancer.” Minimizing immunosuppression is very important in this disease, too—“unusually important compared to other skin cancers,” says Dr. Nghiem. People whose immune system isn’t functioning at a normal level are at increased risk for MCC. For instance, people whose immune systems are suppressed because of human immunodeficiency virus (HIV), a solid organ transplant, or chronic lymphocytic leukemia or another cancer are 10 to 20 times more likely to get MCC and much more likely to die of it once they’ve got it. Minimizing patients’ immunosuppression can become part of the therapy for MCC. If there’s any way to decrease the immunosuppression, this may help the body control MCC. Making Treatment Choices People with MCC can get diagnostic services at SCCA as well as a full range of treatment options here in Seattle. Dr. Nghiem also consults with patients from other parts of the country and their doctors, who want expert guidance on how to proceed. Important issues include whether a sentinel lymph node biopsy needs to be done to check for cancer spread, whether more surgery needs to be done after the initial excision, whether the primary site needs irradiation, whether the bed of lymph nodes that drains the area needs irradiation, whether chemotherapy should be given, and whether immunosuppressive therapy could be modulated to improve the body’s defenses. “Those decisions need to be really customized,” says Dr. Nghiem. “You need one really extensive consultation early on,” he says, to look at the whole picture and consider all the options. Then patients who live elsewhere in the country can be managed by their local doctors. “I see a lot of people who come from across the country, and I can then work with their local physicians,” says Dr. Nghiem. As of 2015, several clinical trials are ongoing to test the ability of immune stimulating drugs to treat this cancer. Besides seeing people with MCC, Dr. Nghiem sees many patients with melanoma, and he has a special interest in graft-vs.-host-disease (GVHD). GVHD can occur in people who receive transplanted tissue from a donor, such as in an allogeneic bone marrow or stem cell transplant. The disease occurs when the transplanted cells recognize the recipient’s body as foreign and attack the tissues. GVHD can affect many body systems and organs, including the skin. Coming back the Northwest Dr. Nghiem grew up in Olympia, Wash., and his wife grew up in Redmond, just across Lake Washington from Seattle. Both of their immediate and extended families are here, so they were happy to make the move, says Dr. Nghiem, when the job opportunity arose at the SCCA and UW. Nghiem’s wife, Dr. Stephanie Lee, researches the outcomes of stem cell transplants and cancers that affect the blood, such as leukemia and multiple myeloma. She is the director for the Long Term Follow-Up Clinic and a researcher at the Hutchinson Center and also an attending physician at SCCA, where she works with transplant recipients. After 13 years in the Boston area, the transition to Seattle has been time consuming—especially the complex process of moving his research laboratory, says Dr. Nghiem. But the family is glad to have made the move. In January, shortly after their arrival, Drs. Nghiem, Lee, and their two young children were enjoying the proximity to family and looking forward to hiking and camping in the Northwest. Dr. Nghiem earned his medical degree from Stanford University School of Medicine in 1994 along with a PhD from Stanford’s Program in Cancer Biology. He was an intern at Brigham & Women's Hospital from 1994 to 1995 and a resident in dermatology at Massachusetts General Hospital from 1995 to 1998. From 1998 to 2002, he was a Howard Hughes Physician Postdoctoral Fellow in the Department of Chemistry and Chemical Biology at Harvard University with Stuart Schreiber. Among his many involvements in professional organizations and publications, Dr. Nghiem has served on the editorial board of the Journal of the American Academy of Dermatology for several years. In 2014, he was also elected as a member of the American Society for Clinical Investigation (the ASCI organization) that recognizes physicians whose research has had an impact on the understanding and treatment of disease.
Massachusetts General Hospital
Dermatology, 1998, American Board of Dermatology
PhD, Cancer Biology, Stanford University; Internship, Medicine, Brigham & Women's Hospital