Islet cell tumors of the pancreas

Tumors of the islets of Langerhans were known to morphologists as early as the beginning of the 20th century.

The description of endocrine syndromes became possible only with the discovery of hormones of the pancreas and gastrointestinal tract.

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Epidemiology

There are no precise data to judge the prevalence of islet cell tumors. Pathologists find one adenoma for every 1000-1500 autopsies. In general-purpose institutions, the ratio of patients with a functioning tumor of the islets of Langerhans to those hospitalized is 1/50 thousand. About 60% of all endocrine tumors of the pancreas are insulin-secreting.

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Pathogenesis

Islet cell tumors are much less common than other pancreatic tumors. They are classified based on the clinical manifestations they cause and the cell type and hormones identified in them, especially immunohistochemically. A significant proportion of these tumors produce multiple hormones that are found in different tumor cells, but the clinical symptoms are usually due to one hormone that is biologically active and produced in the greatest quantity. Moreover, metastases in the case of a malignant tumor may consist of only one cell type, even in the case of a primarily polyclonal tumor. In addition, there are tumors of a single cell type that produce a variety of peptides. In some cases, the clinical and hormonal picture is due to multiple endocrine tumors of the pancreas and/or hyperplasia of islet cells of one or different types.

There are two possible sources of endocrine tumors: insular, which is where their name, insuloma, comes from, and ductal, from multipotent stem cells in the ductal epithelium (nesidoblasts), which can proliferate and differentiate into cells producing various peptides. These tumors are often a source of ectopic hormone production. They most often occur in adults in any part of the pancreas, and rarely have their own capsule (especially small ones). Unencapsulated tumors have a so-called zigzag growth pattern, similar to infiltrative tumors. They may resemble an accessory spleen in color and appearance due to unusually rich vascularization; the cut surface is homogeneous, grayish-pink or cherry-colored, and hemorrhages and cystic areas are occasionally detected. With severe stromal fibrosis with deposition of lime salts, insulomas acquire a cartilaginous density. The sizes of autonomous tumors vary from 700 microns to several centimeters in diameter. Tumors with a diameter of 2 cm are usually benign, and more than 6 cm are malignant.

Solitary or even multiple tumors are often accompanied by the development of hyperplasia and/or hypertrophy of the islet apparatus in the surrounding pancreatic tissue, primarily due to beta cells (in insulinomas).

Insular tumors are primarily adenomas and, less commonly, adenocarcinomas. The tumor cells are similar in size and shape to the corresponding cells of normal islets: polygonal or prismatic, rarely spindle-shaped. In some cells, the cytoplasm is eosinophilic, in others, basophilic, and in others, light, and its volume varies from scanty to abundant. Nuclear polymorphism is a fairly common phenomenon. In more than half of the tumors, the stroma is fibrotic, hyalinized, and calcified to varying degrees. In approximately 30%, amyloid deposition in the stroma is observed. In 15% of cases, psammoma bodies are detected, the number of which varies. In 2/3 of the total number of tumors, ductal structures and transitional structures from ductal to tumor are found. The latter form anastomosing cords, nests, rosettes, alveoli, papillary structures separated by numerous thin-walled vessels. Depending on the predominant structure, three types of tumors are distinguished:

• I - solid, also called diffuse;
• II - medullary, often called trabecular (this type of structure is more common in insulinomas and glucagonomas);
• III - glandular (alveolar or pseudoacinar). This type is more common in gastrinomas and Werner's syndrome. All types of structure can be in one tumor in its different areas.

Beta-cell tumors (insulinomas) are the most common islet tumors, 90% of which are benign. About 80% of them are solitary. In 10% of cases, hypoglycemia is caused by multiple tumors, 5% of which are malignant, and 5% are nesidioblastosis, which is characterized by islet hyperplasia due to their neoplasm from ductal cells, islet hypertrophy caused by hyperplasia and/or hypertrophy of the cells that form it, mainly beta cells. The term nesidioblastosis was introduced by GF Laidlaw in 1938. It is also characterized by the phenomena of acinus-insular transformation. There is a certain relationship between the clinical manifestations of insulinomas and their sizes. Immunohistochemically, A- and/or D-cells, rarely EC-cells can be detected in insulinomas.

One of the significant achievements of the last two decades in the field of histochemistry and endocrinology is the development of APUD (Amine Precursor Uptake and Decarboxylation) - a concept that made it possible to explain the secretion, in particular by islet cell neoplasms of the pancreas, of many hormones that are not characteristic of its physiological function, so it is not surprising that recent years have reported the ability of these tumors to secrete, in addition to the hormones already mentioned, such as chorionic gonadotropin, calcitonin, various prostaglandins, growth hormone, antidiuretic hormone, the independent role of which in the formation of any endocrine syndromes has not been definitively proven, but it is possible that further research in this direction will allow us to establish a causal relationship between some even known diseases of the gastrointestinal tract and tumors of the pancreas.

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Forms

Currently, functioning tumors of the pancreas are divided into two groups: orthoendocrine, secreting hormones characteristic of the physiological function of the islets, and paraendocrine, secreting hormones not characteristic of them. The first group includes neoplasms of alpha-, beta-, sigma- and F-cells, which secrete glucagon, insulin, somatostatin and pancreatic peptide, respectively, which is reflected in their name: hence glucagonoma, insulinoma, somatostatinoma and PPoma. The cellular origin of paraendocrine tumors has not yet been definitively established, it is only known that they are not of the P-cell type. These include neoplasms secreting gastrin - gastrinoma, vasoactive intestinal peptide - vipoma, ACTH-like activity - corticotropinoma, as well as tumors with a clinical picture of carcinoid syndrome. Paraendocrine tumors also include some rare tumors that secrete other peptides and prostaglandins.

As a rule, neoplasms of the islets of Langerhans, especially malignant ones, are characterized by polyhormonal secretion; “pure” tumors are rare; however, the prevalence of secretion of one or another hormone leads to the development of a certain clinical endocrine syndrome.

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