Pathology of the Endocrine Pancreas

Islet Cell Hypoplasia

Type 1 Diabetes Mellitus – the only significant cause of Islet cell hypoplasia

Morphology – total weight of pancreas can decrease 60% or more – total islet mass is also significantly decreased

insulitis

acute (never see it) Þ inflammation (PMNs) around b cells in recent onset type 1 diabetes mellitus

chronic Þ lymphocytic infiltration and fibrosis; seen in 2/3 of young diabetics Þ loss of b cells

hyalinization – fibrosis and amyloid deposition in long-standing type 1 diabetes mellitus

islet amyloid peptide (amylin): is of unknown function; secreted by b , d , and insulinoma cells; accumulates in islets and possibly contributes to their destruction; more common in type II DM

this process is not specific to diabetes mellitus, and is actually more common in non-diabetic atherosclerosis

overall, histology is not a diagnostic tool for diabetes mellitus (diagnosis must be made via glucose test)

Extrapancreatic Complications

Causes:

Excessive Non-enzymatic Glycosylation – glucose monomer added to various biological molecules (reversible), but can become Advanced Glycated Endproduct (AGE) (irreversible) – alters vessel wall permeability, accelerated atherogenesis, Ý protein deposition

Polyol Pathway – Ý intracellular glucose Þ Ý sorbitol Þ damage to pericytes and Schwann cells

Effects:

Cardiovascular – accelerated atherosclerosis of small vessels (microangiopathy) and large vessels (macroangiopathy)

presents at a younger age and more severe, but otherwise lesions are indistinguishable from non-diabetics

macroangiopathy – MI (leading cause of death in diabetics), peripheral vascular disease leading to peripheral insufficiency, chronic skin ulcers, poor wound healing, Ý risk of gangrene/infections, limb amputations

microangiopathy – diffuse thickening and widening of basement membranes in small vessels and capillaries by a homogeneous material; manifests clinically at retinal and renal glomerular vessels (retinopathy,nephropathy)

Peripheral vascular disease – periph vascular insufficiency; chronic skin ulcers; poor wound healing; gangrene/infections

Cerebrovascular accidents – strokes

Nephropathy – takes several years to develop; affects 50% type I, 10% type II; Changes include:

Arteriosclerosis and arteriolonephrosclerosis

Capillary basement thickening Þ very permeable

Glomerulosclerosis (diffuse and nodular) Þ proteinuria, renal insufficiency

Exudative lesions (fibrin caps, capsular drops – protein excess)

Retinopathy – changes include:

Retinal micro-aneurysms
Cataracts – opacity of lens

Neuropathy – presents as polyneuropathy, mononeuropathy, dysautonomia (dysfunction of autonomic NS)

Mechanisms: Schwann cell injury, myelin degeneration, axonal damage (from sorbitol accumulation)

Type 2 diabetes mellitus – probably does not involve any pathological pancreatic changes due to the disease.

b cells may actually be reactively hyperplastic, while later amyloid deposits are probably due to atherosclerosis.

Islet Cell Hyperplasia

Nesidioblastosis – diffuse disseminated proliferation of islet cells from duct epithelium

associated with persistent hyperinsulinemic hypoglycemia in newborns

Clinical Manifestations – somnolence, seizures, loss of consciousness, persistant neonatal hypoglycemia

Islet Cell Tumors

Islet cell tumors are relatively uncommon (10% of pancreatic tumors) –can be benign (adenoma) or malignant (carcinoma)

Most tumors (60-85%) are functional, and produce hormone: insulin, gastrin, somatostatin, VIP, glucagon, PTH, ADH, ACTH, and PP

clinical manifestation is dependent upon type of hormone produced

Types:

Islet b cell tumor (insulinoma) – most common; 85-90 % solitary, benign; 5-10% malignant – usually male, 40-60 years old, type 1 diabetes, hypeglycemia

Gastinoma (G-cells) – 2^nd most common; Zollinger-Ellison Syndrome; usually male, 30-50 years old, type 1 diabetes; 90% in pancreas, 10% in gut; genetics plays a role

Glucagonoma (A-cells) – rare tumor; 50% malignant; clinical

Somatostatinoma (D cells) – rare tumor; found also in duodenum

VIPoma – extremely rare; 3-5% of islet tumors; Vernor-Morrison (WDHA) syndrome

Pancreatic Polypeptide (PP) Producing Tumor – extremely rare, benign; pancreatic mass with high PP levels