Islet Cell Tumors of the Pancreas

Clinical, Radiologic, and Pathologic Correlation in Diagnosis and Localization

Abstract Introduction and Historical Perspective Clinical Features

Pathologic and Histologic Features Radiologic Features Differential Diagnosis Treatment and Prognosis

Summary Source Information References

Introduction and Historical Perspective

Islet cell tumors include a broad group of endocrine neoplasms. Some believe that these tumors originate from amine precursor uptake and decarboxylation (APUD) cells and broadly refer to such tumors, along with carcinoids, pheochromocytomas, and medullary thyroid cancer, as apudomas (1). Alternatively, there is evidence that these tumors may arise from multipotential cells in the pancreatic ductal epithelium (2). Whatever the case, islet cell tumors share a number of common features in their clinical manifestation, imaging features, treatment, and prognosis.

Islet cell tumors are divided on clinical grounds into those that produce a recognizable, clinically evident endocrine syndrome (functioning islet cell tumors) and those that are clinically silent (the so-called nonfunctioning islet cell tumors). Islet cell tumors may be clinically silent for a number of reasons: They may not produce sufficient hormone, hormone may be produced but not released, the hormone may be in an inactive form, or the hormone may not produce symptoms even when secreted in large amounts (eg, pancreatic polypeptide).

Functioning islet cell tumors are named according to the active hormone that they produce, for example, insulinoma or gastrinoma. They may also be divided into insulin-producing and non-insulin-producing types. There is a definite association between the size, consistency, behavior, and function of islet cell tumors (gastrinomas are an exception). The smaller tumors tend to be homogeneous masses without local invasion or distant metastases and typically are insulinomas. Larger tumors more commonly demonstrate cystic changes, necrosis, calcification, local invasion, vascular invasion, and distant metastases, and they are either clinically silent lesions or are associated with less clinically evident endocrine syndromes than are insulinomas (3).

The initial descriptions of islet cell tumors parallel the historical discovery and identification of the various hormones that they elaborate. The first pancreatic islet cell tumor, an insulinoma, was discovered in 1902, but Banting and Best did not isolate insulin until 1922 (4). The Whipple triad of symptoms in patients with insulinoma was described in 1935. It was not until 1955 that Zollinger and Ellison (5) described a syndrome of recurrent peptic ulcer disease. Gastrin was identified as the active polypeptide responsible for this syndrome in 1964. This discovery was followed by the eventual discovery and identification of other active hormones related to islet cell tumors, including vasoactive intestinal polypeptide, glucagon, somatostatin, adrenocorticotropic hormone (ACTH), and others. Historical perspective supports the notion that insulinomas have a much more dramatic clinical manifestation than the other functioning islet cell tumors. That is, the more obvious the syndrome, the earlier in its course the tumor comes to medical attention, and the smaller the tumor is when it is identified. Conversely, the less apparent the clinical syndrome, the longer the delay to diagnose the neoplasm, which may then be quite large and have greater opportunity to metastasize. This situation is particularly true for clinically silent islet cell tumors, which come to attention because of mass effect, local invasion, or metastatic disease.

Islet cell tumors are rare, with an incidence of about one case per million population per year. Small (less than 1 cm in diameter), clinically silent tumors were present in up to 1.5% of individuals in an autopsy series, but the tumors were incidental findings and of no clinical consequence (6). Insulinomas are the most common of the functioning islet cell tumors, followed by gastrinomas, and then the remainder of the less common functioning tumors. Clinically silent islet cell tumors are about as common as insulinomas (3,7,8).

This report is based on a review of the literature and of over 150 cases of islet cell tumors with cross-sectional imaging studies accessioned to the archives of the Armed Forces Institute of Pathology (AFIP) from January 1980 through June 1996. Both functioning and clinically silent tumors are reviewed. Clinical syndromes discussed include those associated with insulinoma, gastrinoma, glucagonoma, somatostatinoma, vipoma, and ACTH- producing tumors. Representative examples of these cases are illustrated in this article, which examines the clinical, pathologic, and radiologic features of islet cell tumors. Differential diagnosis, treatment, and prognosis are also discussed.

Abstract Introduction and Historical Perspective Clinical Features

Pathologic and Histologic Features Radiologic Features Differential Diagnosis Treatment and Prognosis

Summary Source Information References