Normal and Diabetic Pancreas Histopathology
Normal Pancreas: Architecture and Islets of Langerhans
The pancreas is composed predominantly of the exocrine unit, while a small portion constitutes the endocrine unit, which is the focus of this topic. The exocrine unit is made up of the acini and the ductal system. The endocrine unit is called the Islet of Langerhans and is composed of neuroendocrine cells, some of which secrete insulin. Insulin is the key hormone whose deficiency underlies diabetes.
Islets of Langerhans: Cellular Composition
The islets are made up of neuroendocrine cells, with beta cells forming the majority. Beta cells make up of the islet cells and they produce insulin. Alpha cells compose about of the islets and they produce glucagon. Delta cells and pancreatic polypeptide (PP) cells are fewer in number and secrete somatostatin and pancreatic polypeptide, respectively.
Ultrastructure of Islet Cells
On electron microscopy, the neuroendocrine cells display dense-core neurosecretory granules, which are the characteristic ultrastructural feature of these cells. This ultrastructure supports the rapid and regulated secretion of peptide hormones like insulin and glucagon.
Diabetes: How the Islets Change
There are two prototypic forms of diabetes with characteristic islet histology: Type 1 diabetes and Type 2 diabetes. In Type 1 diabetes, the process is autoimmune, whereas Type 2 diabetes features amyloid deposition within the islets.
Type 1 Diabetes: Autoimmune Insulitis and Beta Cell Loss
In Type 1 diabetes, insulitis or inflammation targets the insulin-producing beta cells of the islets. The inflammatory infiltrate is composed of lymphocytes and plasma cells that progressively destroy the islets. Over time there is a reduction in the number of beta cells, with a spectrum of variation in the size and shape of the islets and a variable amount of inflammation; eventually beta cells become reduced or absent.
In contrast to Type 2 diabetes, Type 1 diabetes does not feature amyloid deposition within the islets.
Type 2 Diabetes: Islet Amyloid Deposition
In Type 2 diabetes, there is extracellular proteinaceous eosinophilic amorphous material within the islets, i.e., amyloid. The islet structure may be otherwise preserved, but the number of functional beta cells declines due to stress and metabolic demand.
Amyloid in Type 2 is composed of islet amyloid polypeptide (IAPP), also known as amylin. A notable consequence is the impairment of islet function and beta cell loss in the context of amyloid accumulation. The presence of amyloid distinguishes Type 2 histologically from Type 1, where amyloid deposition is absent.
Pathologists use Congo red staining to demonstrate amyloid deposition. Under polarized light, amyloid shows apple-green birefringence, a diagnostic feature of amyloid in tissue sections. .
Because of the amyloid deposition in Type 2, islet transplantation is not possible or effective in these patients; by contrast, patients with Type 1 diabetes may benefit from islet cell transplantation when clinically appropriate.
Pancreatogenic Diabetes (Type 3c): A Variant Caused by Loss of Exocrine Pancreas
There is a variant called pancreatogenic diabetes or Type 3c diabetes, which results from chronic pancreatitis or the loss of exocrine pancreatic tissue due to surgery, pancreatic cancer, or other conditions. Conditions such as cystic fibrosis and hemochromatosis can heavily affect the gland and cause ductal obstruction, secondary atrophy, and loss of large amounts of pancreatic parenchyma. These processes lead to loss of both exocrine and endocrine pancreatic units; consequently, exocrine damage inevitably affects endocrine function, contributing to diabetes.
Developmental Sequence and Pathophysiology of Type 1 Diabetes
The progression of Type 1 diabetes can be summarized as follows: a genetic predisposition exists, followed by an insult (such as an infection or precipitating event) that triggers immunologic abnormalities. This leads to progressive loss of beta cells, starting from normal glucose levels and advancing to insulin deficiency and overt diabetes over time.
Staining Techniques and Practical Notes
Pathologists employ various stains to highlight tissue components. For amyloid in Type 2 diabetes, Congo red staining is used, with apple-green birefringence on polarization—an important diagnostic hallmark. It is important to recognize that the amyloid in Type 2 diabetes is derived from islet amyloid polypeptide (IAPP) and that this deposition is not present in Type 1 diabetes.
Summary
In this session, we identified and described the features of normal and diabetic pancreas and delineated the main histopathological features observed in the pancreas of diabetics. We highlighted the distinct autoimmune beta-cell destruction in Type 1 diabetes, the amyloid-mediated beta-cell dysfunction in Type 2 diabetes, the diagnostic staining approach with Congo red, and the practical implications for treatment, including the differential viability of islet transplantation. We also discussed pancreatogenic diabetes as a form arising from loss of exocrine tissue and its impact on endocrine function.