Unraveling Neuroendocrine Tumors: Clinician Reflects on 60 Years of Discovery

Richard R.P. Warner, MD
Published: Wednesday, Mar 01, 2017
Richard R.P. Warner, MD

Richard R.P. Warner, MD

At age 89, I could probably earn the Guinness World Record for the oldest neuroendocrine cancer clinician in the United States, and perhaps even the world. I retired from clinical practice at The Mount Sinai Hospital in New York City in November 2016 to focus on research, lecturing, and patient advocacy. At this interesting point in my career, I am taking time to reflect on the more than 60 years I’ve spent studying, diagnosing, and treating patients with neuroendocrine tumors and carcinoid syndrome. I think it would be valuable to share the key learnings and insights that have built my legacy within this important field.

The Early Years: Piecing Together Evidence

During my internal medicine internship and residency in the early 1950s, a subspecialty in oncology was not yet recognized by a certifying board. Therefore, despite my interest in the eld, I chose to pursue a gastroenterology fellowship in 1954 and read everything in the literature that had any bearing on gastroenterology. I was impressed by an article in the American Heart Journal that mentioned a new syndrome marked by diarrhea and facial flushing, which was associated with little tumors (carcinoids) in the small intestine that had spread to the liver and with prominent right-sided heart valve lesions. This became known as "carcinoid syndrome."

Having completed 1 year of gastroenterology training, I was named chief of gastroenterology for a major hospital while serving in the Air Force Medical Corps during the Korean War in 1955. It was during this time that I encountered a patient with undiagnosed debilitating diarrhea and flushing, and I remembered the article that established carcinoid syndrome as an entity. The case appeared similar, but did not present with a small bowel carcinoid.

My first instinct was to investigate it further, so I went to Oklahoma City to request that this patient’s previous healthcare providers retrieve a lung specimen that had been resected 8 years prior. Keep in mind that at this time, long-term survival of lung cancer was particularly uncommon. After much persuasion, the archived resected lung specimen was retrieved, and I sent it to my pathologist at Mount Sinai for reevaluation. It turns out that it was not adenocarcinoma of the lung, but rather what was designated at that time to be a “bronchial adenoma,” carcinoid type. Hence, I was able to con rm my diagnosis of carcinoid syndrome, interestingly occurring from a lung carcinoid instead of an intestinal carcinoid.

I wrote up the case when I returned to Mount Sinai in 1956 and presented it to my chief, who was also editor of the American Journal of Medicine. He told me about another case that was puzzling other physicians in the hospital and asked me to examine that patient. I performed the examination, and it appeared the patient also had carcinoid syndrome. I requested a 5-HIAA urine test to con rm the diagnosis. When serotonin is metabolized in the body, it becomes 5-HIAA, and when a patient has carcinoid syndrome, he or she tends to have high levels of 5-HIAA in the blood and in the urine, which is a key signal for diagnosis.

At that time, there was no commercial 5-HIAA test available, so I took matters into my own hands, and went directly to the National Institutes of Health to receive a quick tutelage on how to conduct the assay myself. When I returned and tested the patient, his levels were very high, which confirmed a carcinoid syndrome diagnosis.

While trying to treat these patients, my intrigue and interest continued to grow and I knew wholeheartedly I wanted to continue to focus more time on learning the intricacies of this disease. I wrote up these 2 carcinoid syndrome cases, and they were published in the American Journal of Medicine in 1958. The article represented the first cases of carcinoid syndrome reported as occurring from lung carcinoids. At present, 28% to 30% of all carcinoids arise in the lung; however, not all of these tumors develop into carcinoid syndrome since the majority of all carcinoids are endocrinologically nonfunctioning.

I continued to take a strong interest in this rare disease and collected more cases over the years, progressively becoming an expert in this field. Zollinger-Ellison syndrome was recognized clinically around the same time as carcinoid syndrome, and the similarity between these conditions led clinicians to believe both diseases were part of the same family.

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Online CME Activities
TitleExpiration DateCME Credits
Community Practice Connections™: 14th Annual International Symposium on Melanoma and Other Cutaneous Malignancies®Apr 30, 20192.0
Oncology Consultations®: The Advancing Role of CAR T-Cell Therapies in Hematologic MalignanciesApr 30, 20191.5
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