Pancreas and adrenal pathology Flashcards
Pancreatic endocrine neoplasm
- 2% of pancreatic tumors
- Occur anywhere in pancreas, sometimes peripancreatic or duodenal
- Solitary or multiple
- Can secrete any pancreatic hormone or non-functional
- Gross: circumscribed, solid
- Look like neuroendocrine carcinomas (carcinoids) elsewhere
- –> Round nuclei
- –> Coarse “salt and pepper” chromatin
- Some features suggest the type of hormone produced, but no need to determine pathologically –> diagnosis based on clinical symptoms and blood levels
Insulinoma
Confined to the pancreas
- Amyloid deposition is characteristic
Clinical:
- Episodic hypoglycemia causing confusion, stupor, loss of consciousness
- Precipitated by fasting or exercise
- Alleviated by food
- Mild or asymptomatic in 80%
May also see with islet cell hyperplasia –> congenital secondary to maternal diabetes
Exclude other causes of hypoglycemia
- Abnormal insulin sensitivity, liver disease, inherited glycogenoses, ectopic insulin production (rare tumors), self-injection
Gastrinoma
Zollinger Ellison syndrome
- islet cell tumor
- hypersecretion of gastric acid
- severe peptic ulcers
- often presents with diarrhea
Tumors occur in pancreas or duodenal wall
- more than half are invasive or metastatic at presentation
- Glucagonoma
- Somatostatinoma
- VIPomas
Glucagonoma
- mild DB mellitus
- skin rash
- anemia
Somatostatinoma
- DB mellitus (inhibits insulin)
- cholelithiasis
- steatorrhea
- hypochlorhydria
VIPomas
- watery diarrhea
- hypokalemia
- achlorhydria
Pancreatic endocrine tumors - clinical
- behavior may be benign or malignant, but difficult to predict based on pathologic features
- features diagnostic for malignancy –> mets, vascular invasion, local infiltration
- insulinomas = 90% benign
- all others = 60-90% malignant
Adrenal cortical hyperplasia
- Always bilateral
- May be diffuse or nodular
- Usually secondary to external stimulus (e.g. pituitary adenoma) –> especially if diffuse
- May produce one or multiple hormones
- Microscopic: Hyperplasia of fasciculata and reticularis zones
Adrenal cortical adenoma
- Most clinically silent, discovered incidentally
- May produce glucocorticoids or aldosterone, or rarely androgens
- Well-circumscribed, yellow to brown, usually Foamy cells are lipid-rich
- –> Eosinophilic are lipid-poor
- Mitoses are rare
- Cortisol-secreting adenomas and (surprisingly) aldosterone-secreting adenomas both look like zona fasciculata
Adrenal cortical neoplasms
Spirinolactone bodies –> laminated eosinophilic cytoplasmic inclusions seen in aldo-secreting adenomas
- due to spironolactone treatment for htn
Adrenal cortical carcinoma
Clinical
- Occur at any age, even children
- More commonly functional than adenomas
- Virilization common
Gross:
- Larger than adenoma (usually >200 g and >20 cm)
- Unencapsulated, infiltrative, often obliterates rest of adrenal
- Necrosis, hemorrhage, cystic changes common
Histology
- range from bland to anaplastic nuclear features
- mitoses common
Prognosis
- often invades adrenal vein, IVC and lymphatics
- distant mets common –> regional lymph nodes, lungs, other organs
- median survival ~2 years
Adrenal adenoma vs. carcinoma
Gross:
- Large size, hemorrhage, necrosis favor malignant
Microscopic:
- Atypia
- Mitotic activity
- Atypical mitoses
- Absence of clear cells
- Diffuse archtitecture
- Necrosis
- Capsular invasion
- Vascular invasion
- 4 usually malignant
Myelolipoma
- Benign tumor composed of fat and hematopoietic elements
- looks like normal bone marrow
- may also see this feature within adenomas
Pheo - clinical
Clinical
- Paroxysmal hypertension
- Tachycardia, palpitations, headache, sweating, tremor, and sense of apprehesion
- Confirm diagnosis by measuring urine catecholamines : VMA and metanephrines
Associated with several syndromes: MEN-2, NF1, VHL
Rule of 10%: 10% bilateral (higher if familial) 10% extra-adrenal 10% malignant 10% asymptomatic (no hypertension) 10% familial (this one is wrong, actually more like 25%)
Pheo - gross and histologic
- malignancy
Gross
- variable size
- arise in medulla
- yellow-tan
- hemorrhage, necrosis and cysts common
Histology:
- polygonal to spindles cells arranged in nests = zellballen
- surrounded by small spindles = “sustentacular cells”
- cytoplasm is granular
- nuclei round with coarse salt and pepper chromatic
- tumor cells stain for neuroendocrine markers = synaptophysin + chromogranin
- sustentacular cells stain for S-100
Malignancy
- cannot be predicted by histologic features
- even local and vascular invasion not reliable
- only diagnosed as malignant if mets
- mets are to lymph nodes, liver, lung and bone
Paragangliomas
- same as pheo, but arise outside adrenal
- most common in neck (carotid body) and para-aortic (ganglia of sympathetic nervous system
Neuroblastoma
- Tumor of young children
- 80% >4 years
- Rarely see in adults
Presentation:
- Abdomninal mass
- Watery diarrhea – elaborate VIP
- Arise in adrenal, sometimes paraganglia
Gross: large, soft, gray; hemorrhage, necrosis common
- Solitary; <10% multifocal
Microscopic = small blue cell tumor
- homer wright rosettes seen in 25%
Prognosis
- overall 3 year survival = 30%
- recurrences within 2 years
- local extension to kidney and spinal cord; distant mets to liver, bone and lymph nodes
Ganglioneuroma
- Benign tumor
- Mostly adults
- Mostly paraganglia
- Gross: encapsulated, homogeneous, tan-white, firm
- Microscopic: Differentiated ganglion cells and spindled (Schwann-like) cells
- If any component of neuroblastoma, even minute = ganglioneuroblastoma
Ganglioneuroblastoma
- mainly in kids
- mainly in paraganglia
- microscopically intermediate between neuroblastoma and ganglioneuroma –> mix of both or features in between
- prognosis also intermediate
Secondary malignancy
- mets to adrenals relatively common - much more common than primary adrenal cortical carcinoma
- lung and breast most common sites of origin
MEN syndromes
Group of inherited disorders that cause neoplasia or hyperplasia in several endocrine organs
Occur at younger age than sporadic
Frequently multifocal within an organ
More aggressive than sporadic
MEN1
Wermer Syndrome
Three Ps:
- Parathyroid (80-95%) hyperplasia or adenoma – initial presentation in most
- Pancreas – endocrine tumors; usually aggressive and leading cause of death due to MEN-1
- Pituitary adenomas – most commonly prolactinoma
Also see duodenal gastrinomas, carcinoid tumors, thyroid adenomas, adrenal cortical adenomas, and lipomas more than normal
Prevalence 2 per 100,000
Mutation in MEN1 tumor supressor gene, abnormal menin protein
MEN2
Three distinct categories
Shared tumors
Medullary thyroid carcinoma
Pheochromocytoma (MEN-2A and 2B)
Think “medullary”
All due to mutations in RET proto-oncogene
Important to screen family members because medullary thyroid carcinoma is very aggressive; patients should have early prophylactic thyroidectomy
MEN2A
Sipple Syndrome
Tumors:
- Medullary thyroid carcinoma (100%), multifocal, with C-cell hyperplasia
- Pheochromocytomas (40-50%), often bilateral, and increased extra-adrenal paragangliomas
- Parathyroid hyperplasia (10-20%)
Mutation in RET proto-oncogene activates the tyrosine kinase it encodes
Familial medullary thyroid carcinoma –> considered a variant of MEN 2A, but only see medullary thyroid carcinomas
MEN2B
Tumors
- medullary thyroid carcinoma
- pheo
- mucosal neuromas
- marfanoid habitus
Different mutation in RET gene
