PANCREATIC DISEASE (INCLUDING DIABETES)
Ed Friedlander, M.D., Pathologist
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STUDY OBJECTIVES

Distinguish acute pancreatitis and "chronic pancreatitis", and recognize the terms that describe the severity of the former illness.

Describe the typical clinical settings for acute pancreatitis, its presentation, and what is known of its etiology.

Distinguish the two histologic types of "chronic pancreatitis", and their differing etiologies. Describe and recognize the histopathology of both.

Cite the known and possible risk factors for cancer of the pancreas. Describe its typical presentation, anatomic pathology, and course. Name the mutation most strongly linked to this disease, and the operation which is occasionally curative.

Define "diabetes mellitus", "impaired glucose tolerance", "gestational diabetes mellitus", and "previous/potential abnormality of glucose tolerance". Mention some archaic synonyms for each one. Tell when hyperglycemia simply isn't diabetic.

Describe the essential lesion in, and typical clinical course of, type I diabetes. Outline current thinking about its etiology, cite the risk to siblings and twins, and describe the HLA association.

Describe the essential lesion in, and typical course of, type II diabetes. Describe current thinking about the pathophysiology of this illness. Mention its genetics. Identify MODY, its most familiar genetic locus, and its pattern of inheritance.

Explain the pathophysiology of diabetic ketoacidosis and hyperosmolar nonketotic coma.

Define "secondary diabetes mellitus". Recognize the important causes. Compare the effects of hyperglycemia on the rest of the body in secondary diabetes and primary diabetes. Briefly describe amylin.

Tell why diabetics have increased polyols, and relate this to complications.

Distinguish diabetic large and small vessel disease. Suggest why diabetics so often lose legs. Outline the common renal lesions in diabetes.

Identify the causes of blindness in diabetes. Give the anatomic pathology of the various forms of diabetic retinal disease.

Describe the things that happen to the peripheral nerves of diabetics, and what problems these cause.

Explain what is meant by "nonenzymatic glycosylation". Tell how this relates to thinking about diabetic complications, and to the HgbA1c blood test for diabetic control.

Describe insulin shock, fasting hypoglycemia, and postprandial hypoglycemia. Give a simple differential diagnosis for the last two. Tell what really causes the "idiopathic postprandial syndrome".

Comment on the following, heard at a party: "Diabetes is caused by eating refined sugar. If there were no white sugar, there would be no diabetes. There should be a law!"

Recognize the following histopathologic lesions of diabetes: diabetic nodular glomerulosclerosis, diabetic arteriolar sclerosis, hepatic nuclear glycogenosis, and hyalinization (amyloid/collagen) of islets.

KCUMB Students
"Big Robbins" -- Exocrine Pancreas
Lectures follow Textbook

KCUMB Students
"Big Robbins" -- Endocrine
Lectures follow Textbook

QUIZBANK Metabolic #'s 42-81; Pancreas (all except #'s 1-8)

Liver / Pancreas
Taiwanese pathology site
Good place to go to practice

Pancreas
Photo Library of Pathology
U. of Tokushima

Pancreas Images
University of Washington
Pictures and comments

Pancreas
From Chile
In Spanish

Diseases of the Pancreas

Chaing Mi, Thailand

Pancreas Exhibit
Virtual Pathology Museum Interactive Pathology Museum


University of Connecticut

Pancreas Transplant Pictures
Great site
Transplant Pathology Internet Services

Pancreas
"Pathology Outlines"
Nat Pernick MD

Gastrointestinal
Brown Digital Pathology
Some nice cases

NORMAL PANCREAS

{25019} normal pancreas, the white hamburger
{14887} normal pancreas, trichrome; no blue, so no dense fibrous tissue in the healthy pancreas.
{12463} islets of Langerhans (no, IZZ-lett is not really an acceptable pronunciation); H&E stain

{49140} annular pancreas; sideways, liver on left, pancreas extends across duodenum and gall bladder

THE PANCREAS IN SYSTEMIC DISEASE

{00044} cystic fibrosis; trichrome stain, showing dilated ducts plugged with good, and absent acini
{20204} hemochromatosis; Prussian Blue stain
{24505} hemochromatosis, gross, one's a Prussian blue
{24506} hemochromatosis, rusty color
{38848} hemochromatosis, rusty color. Scar tissue is white.

ACUTE PANCREATITIS ("soapsuds"; "chicken soup"; the classic term "rum belly" seems no longer in use; NEJM 330: 1998, 1994; Lancet 361: 1446, 2003 also describes chronic cases; update Lancet 371: 143, 2008; inflammatory mediation Surg. Clin. N.A. 87: 1325, 2007)

{39802} acute pancreatitis. Feels as bad as it looks.
{49232} ditto. Black area is a big hematoma.

Hemorrhagic pancreatitis
Autopsy specimen
KU Collection

Hemorrhagic pancreatitis
Urbana Atlas of Pathology

Enzymatic fat necrosis
White flecks
WebPath Photo

CMV pancreatitis

Yutaka Tsutsumi MD

{08339} enzymatic fat necrosis, gross; it is the chalky granular stuff. The background is hemorrhagic pancreatitis.
{08342} enzymatic fat necrosis, microscopic; left upper corner
{08348} enzymatic fat necrosis, microscopic

{49233} pseudocyst; spleen at right. Hollow and filled with fluid.

{49234} chronic pancreatitis; pale white is scar
{08853} chronic pancreatitis; extensive scarring
{20279} chronic pancreatitis in an alcoholic, nice protein plug
{46283} chronic pancreatitis with calculi
{49230} burned out alcoholic chronic pancreatitis, with calculi; the tube along the bottom is the splenic artery, twisting in and out

Chronic alcoholic Chronic obstructive
Lobules unevenly scarred All lobules in an area involved equally
Protein plugs in small ducts Few or no protein plugs
Perineural chronic inflammation Normal nerves

NON-MALIGNANT MASSES

{49238} cystadenoma of the pancreas; has been cut in half and opened; spleen at right

CANCER OF THE PANCREAS ("cank of the pank", "the dismal disease", etc.; Lancet 378:607, 2011; BMJ 344: e2476, 2012)

{08851} adenocarcinoma of pancreas; no normal pancreas on the slide; some glands are more anaplastic than others;
{26003} adenocarcinoma of pancreas; mucin-producer (pale apical cytoplasm, sharp borders)

Cancer of the pancreas
Primary and liver metastases
KU Collection

Pancreatic cancers
Histopathology
Wikimedia Commons

Nice guide to the differential diagnosis of a pancreatic tumor, for pathologists: Arch. Path. Lab. Med. 133: 454, 2009.

Eurytremiasis, the pancreatic fluke
Advanced students
Yutaka Tsutsumi MD

CLASSIFYING DIABETES MELLITUS AND RELATED CONDITIONS

Pathology of Diabetes
WebPath Tutorial

Diabetes Mellitus, pancreas
Text and photomicrographs. Nice.
Human Pathology Digital Image Gallery

Insulitis
Type I diabetes
WebPath photo

PRIMARY DIABETES TYPE I ("juvenile onset", "labile", "ketoacidosis-prone", "insulin-dependent"): 10% of diabetics (review Lancet 383: 69, 2014)

PRIMARY DIABETES TYPE II ("adult onset", "stable", "ketosis-resistant", "non-insulin-dependent"): 90% of diabetics.

SECONDARY DIABETES has many etiologies

ANATOMIC PATHOLOGY OF DIABETES MELLITUS: These are usually the effects, rather than the causes, of hyperglycemia.

{09378} diabetic gangrene
{48076} diabetic gangrene
{48022} diabetic ulcer
{48023} diabetic ulcer
{48150} diabetic ulcer

{08892} KW disease; note balls of hyaline, and thick GBM (i.e., you can actually tell where it is)
{17159} diabetes with hyalinized arteriole
{16789} diabetic glomerulosclerosis, electron micrograph (thick GBM)
{16790} diabetic glomerulosclerosis, electron micrograph (thick GBM)
{16791} diabetic glomerulosclerosis, H&E
{16792} diabetic glomerulosclerosis, PAS; nice capsular drop too
{16793} diabetic glomerulosclerosis, H&E
{08893} Kimmelstiel-Wilson diabetic nodular glomerulosclerosis; H&E
{08895} Kimmelstiel-Wilson diabetic nodular glomerulosclerosis, PAS
{09877} Kimmelstiel-Wilson diabetic nodular glomerulosclerosis
{17158} Kimmelstiel-Wilson diabetic nodular glomerulosclerosis
{17171} end-stage diabetic glomerulosclerosis

Diabetes in the Kidney
Text and photomicrographs. Nice.
Human Pathology Digital Image Gallery

Nodular diabetic glomerulosclerosis
Slide from Andrea McCollum MD
Cuyahoga County Coroner's Office

Nodular glomerulosclerosis
PAS stain
KU Collection

Nodular glomerulosclerosis

KU Collection

Great fibrin cap (hyalinosis in diabetes)
Slide from Andrea McCollum MD
Cuyahoga County Coroner's Office

{46306} Armanni-Ebstein; lots of glycogen in the tubular cells

{49306} pyelonephritis and papillary necrosis in a diabetic

{09365} diabetic retinopathy; hemorrhages and exudates
{22036} diabetic retinopathy; microaneurysms
{22039} diabetic retinopathy
{22042} diabetic retinopathy, notice the hemorrhages
{22045} diabetic retinopathy -- bleed
{22904} microaneurysm
{23156} cotton wool patches
{23180} diabetic retinopathy
{23183} diabetic retinopathy

{09366} proliferative retinopathy
{22895} proliferative retinopathy
{22901} proliferative retinopathy -- "scar contracts" and tears off the retina

{48174} Charcot's neuropathic joint changes

Amyloid islet
Type II diabetes
WebPath photo

{08084} hyalinized pancreatic islets, type II diabetes

OTHER PROBLEMS FOR DIABETICS

{48090} diabetic abscess
{48091} diabetic abscess

{12214} necrobiosis lipoidica diabeticorum

* ADDITIONAL INFORMATION ABOUT DIABETES

Student Doctor
Alex Yartsev
"Pathology Outlines"
on diabetes MD

HYPOGLYCEMIA -- worth mentioning concurrently with diabetes mellitus

Normal islet
WebPath photo

Normal islet
Immunostain
WebPath photo

PANCREATIC ISLET CELL TUMORS: Not-to-be-overlooked causes of striking clinical syndromes. Complex diagnostic and surgical problems. Update for pathologists: Arch. Path. Lab. Med. 130: 963, 2006; surgeons Br. J. Surg. 99: 88, 2012. A synonym is "pancreatic neuroendocrine tumors" ("PanNET's"), another is "pancreatic endocrine tumors". They are being found much more often thanks to lots of people getting of abdominal scans (Gastroenterology 139: 742, 2010).

Pancreatic islet cell tumor
Great photos
Pittsburgh Pathology Cases

Islet cell adenoma
WebPath photo

Islet cell adenoma
WebPath photo

Islet cell adenoma
Stains for insulin
WebPath photo

{24576} islet cell adenoma
{49239} islet cell adenoma -- top center

{09279} gastrinoma (to prove it, we'd need to do an immunoperoxidase stain that stains gastrin brown and everything else white)
{09282} gastrinoma

* SLICE OF LIFE REVIEW


08093 islet, normal
11748 pancreas, normal
14886 pancreas, normal
14886 pancreas, normal
14887 pancreas, normal
14888 pancreas, duct & islets
14889 pancreas, duct & islets
14890 pancreas, serous acini & islet
14891 pancreas, serous acini & islet
14892 pancreas, exocrine and endocrine
14893 zymogen cells, normal pancreas
14894 islet of Langerhans
14895 islet of Langerhans
14896 pancreas, zymogen granules
14897 pancreas, zymogen granules
14898 pancreas, central acinar cells
14899 pancreas, central acinar cells
15274 pancreas, normal
15275 pancreas, normal
15276 islet of Langerhans, #65
15277 pancreas, intercalated duct
15278 pancreas, centroacinar cell and duct
15279 islet of Langerhans, #65
15280 ?pancreas, ct in duct??
15793 pancreas, normal
20879 pancreas
20880 intercalated duct, pancreas
20881 acinar cell, pancreas
20882 islets of Langerhans, pancreas
20883 pancreas, centroacinar cell
20884 pancreas
20885 islet of Langerhans
20886 pancreas, interlobar duct
20887 pancreas, interlobar duct
25019 pancreas, normal
25020 pancreas, normal
25021 pancreas, normal
25794 columnar cells, pancreatic epithelium - norma
25973 pancreas, normal
25988 pancreas, normal
25991 acinar cells, normal pancreas


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