Apple's Apudoma

Copyright (C) 2009 Robert S. Rosson. All rights reserved.

The current and highly-publicized medical situation of the well-known CEO and founder of Apple Computer suggests to me the possibility of a metastatic apudoma or neuroendocrine tumor. He is said to be a four year survivor of “pancreatic cancer” who now has a “hormonal imbalance.” I have no knowledge of his actual medical diagnosis, but I am reminded of some of the most memorable patients I cared for in my career. Let me illustrate with a few anecdotes from memory.

A woman in her fifties presented with severe diarrhea, weight loss, and extreme loss of body potassium. When an extensive workup failed to reveal a cause, we resorted to diagnostic laporotomy. I went to the OR in time to see the surgeon holding up an orange-sized tumor from the tail of the pancreas. The resected specimen showed an islet cell tumor of the pancreas, possibly malignant. At about that time, in the 1960s, reports began to appear of vasoactive intestinal peptide (VIP) secreting tumors which produced this clinical syndrome. She recovered dramatically and, in spite of later spread to the liver, she lived for another twenty-five years. I stored the tumor in a freezer in the hope of a future assay for VIP or other hormones. It disappeared, however, mysteriously from the freezer (perhaps it became part of someone’s lunch), and we could never do the assay. Nevertheless it is clear that the tumor was a VIPoma, as it is now known.

A forty year-old man developed an ulcer in his lower esophagus. That unusual location led to our finding a markedly elevated serum gastrin. CT scan showed no abnormality in the pancreas. He was explored and a tiny tumor was found in the first portion of the duodenum. When it was resected the profuse drainage of acid from his stomach tube stopped immediately, as if a spigot had been turned off. He recovered uneventfully and suffered no recurrence. The pathology sections showed a typical neuroendocrine tumor which stained for gastrin -- a classic case of Zollinger-Ellison Syndrome due to a solitary benign gastrinoma.

A 55-year-old man was seen for right upper abdominal pain and abnormal liver blood tests. CT scan revealed multiple liver lesions which, upon biopsy, showed metastatic islet cell cancer. The tumor did not stain for peptide hormones, nor were there clinical symptoms of hormone secretion. The primary tumor was never located. Two years later, when he developed signs of liver failure, he underwent liver transplantation over the strenuous objections of his health insurance company. In spite of later recurrences in liver and bone, he lived productively and relatively comfortably for fifteen years after transplant. Although this was initially a non-secreting, malignant neuroendocrine tumor, the subsequent metastases secreted gastrin and caused a gastric ulcer. Liver transplantation was offered because these tumors grow slowly and do not seem to be accelerated by anti-rejection therapy. His response to liver transplantation was gratifying and provided outstanding palliation.

These cases illustrate the dramatic clinical syndromes the various hormones secreted by these tumors can produce. In addition these tumors, even when malignant, are indolent and can be compatible with long survival. They are among the most interesting, challenging, and rewarding diseases confronting the clinician. Even when the primary tumor cannot be found or removed, treatment of the hormonal syndrome, for example using proton pump inhibitors for gastrinoma, can bring about dramatic relief. Modern diagnostic tools such as CT scan, MRI, nuclear scan, and serum hormone assays are effective in making the diagnosis.

There are reports that the aforementioned CEO is being considered for liver transplantation. If true, this lends credence to my diagnostic speculation.

Published originally in YJHM January 25, 2009