Chapter 46: Insulinoma

INTRODUCTION

Insulinomas are relatively rare tumors of the endocrine pancreas that cause debilitating and even life-threatening symptoms. Although insulinomas are rare, with an incidence of approximately 4 cases per 1 million person years, these tumors are the most common functional islet cell tumors of the pancreas.^1,2 Increased awareness of this condition and advances in technology over the last several decades have improved the diagnostic accuracy and facilitated treatment planning. Given the rare incidence of insulinomas and the potentially misleading clinical presentation, it is vital for the physician to have a thorough understanding of the diagnosis and management of this condition.

EPIDEMIOLOGY

In general, patients with insulinoma are divided into two major categories: those who have sporadic insulinomas and those who have insulinomas secondary to a genetic syndrome such as multiple endocrine neoplasia type 1 (MEN-1). This distinction is key as it determines the diagnostic workup and surgical approach.³ The majority of patients with insulinoma (up to 90%) are in the former category and have a solitary, benign tumor in the pancreas.^1,4,5 For these patients, insulinomas may occur at any age but they are most frequently diagnosed in the fourth and fifth decades of life. Additionally, there is a slight female predominance of up to 50% to 60%.^1,4,6

However, up to 10% of patients with insulinoma have an inherited form of the disease that is typically associated with MEN-1 syndrome and these patients usually have multiple pancreatic tumors.^5-7 These patients tend to be diagnosed at a younger age (usually the mid-20s), and there is no gender predominance.⁸ They often have between 2 and 16 insulinomas, with an average of 6 to 7,^8,9 and their risk of tumor recurrence after surgical treatment is three- to fourfold higher as compared to patients without MEN-1.¹ This higher incidence of recurrence can be due to the lack of intraoperative detection of smaller tumors or incomplete removal of tumors.¹⁰

Of all insulinomas, 4% to 14% are malignant. The incidence of malignancy in patients with sporadic insulinomas ranges from 3.8% to 4.9%, whereas the incidence of malignancy in patients with MEN-1 associated insulinomas ranges from 0.42% to 0.89%.^1,6 The staging of insulinomas follows the TNM (tumor/node/metastases) staging guidelines for all neuroendocrine tumors. One of the most important predictors of survival for all neuroendocrine cancers lies in the grade of the tumor, which depends on the rate of proliferation. The proliferative index is defined by the percentage of tumor cells that are immune positive for the Ki-67 antigen (Ki-67 index) or by the mitotic rate (the number of mitoses per 10 high-power microscopic fields) with less aggressive, low-grade tumors having a lower mitotic rate and a lower proliferative index.^11,12 Overall, malignant insulinoma is associated with decreased survival ...