Gupta - Pathology Flashcards
1
Q
What do you see here?
A
- Segmental demyelination: earliest histopathologic change in diabetic neuropathy -> this nerve has lost around 75% of its myelin
- Luxol fast blue stain: stains myelin blue (normal attached)
2
Q
What are the clinical manifestations of the 3 MEN syndromes (image?
A
3
Q
How does excess IC glucose affect bacterial killing?
A
It hinders it by impairing oxidative burst
4
Q
What is this?
A
- Posterior pituitary
- Vasopressin (ADH) and oxytocin made in the hypothalamus (supraoptic and paraventricular nuclei) are transported into the intra-axonal neurosecretory granules where they are released
5
Q
What are some diabetic ocular complications?
A
- Diabetes-induced hyperglycemia leads to CATARACTS: acquired opacification of the lens
- Long standing diabetes is also associated with increased intraocular pressure (GLAUCOMA), and resulting damage to the optic nerve
- Most profound histopathologic changes of diabetes are seen in the retina
6
Q
MEN-2A
A
- Mutation in RET oncogene
- Autosomal dominant with high penetrance:
1. 100% have medullary thyroid carcinoma
2. 30-50% have pheochromocytoma
3. 10-15% have parathyroid hyperplasia
7
Q
What do you see here?
A
- Adrenal nodules: often vacuolated, lipid-rich, fasciculata-like (yellow color grossly)
8
Q
What is the most important stimulus for insulin synthesis and release? How does this work?
A
- GLUCOSE
- Influx of glucose into β cells through the GLUT-2 receptors initiates a cascade of signaling events that culminates in Ca 2+ -induced release of stored insulin (see attached image)
9
Q
Epi and prognosis for papillary carcinoma?
A
- MOST COMMON form of thyroid cancer: nearly 85% of primary thyroid malignancies in the US
- Occur throughout life, but most often between the ages of 25 and 50
- Diagnosis of papillary carcinoma has INC markedly in last 30 years, partly because of the recognition of follicular variants that were misclassified in the past (not really that incidence has INC, but rather we are getting better at diagnosis)
- Excellent prognosis, with a 10-year survival rate in excess of 95%
10
Q
MEN-1
A
- Gene: MEN1 tumor suppressor gene (encodes menin)
- PITUITARY: most often a prolactin-secreting microadenoma
- PARATHYROID: 1o hyperparathyroidism (hyperplasia or adenoma)
1. May be the first clinical manifestation
2. Most common manifestation - PANCREAS: endocrine tumors are what kill them
1. Often multiple, aggressive and functional
11
Q
What happened to these guys? How can you help them?
A
- Children w/meningococcal sepsis, DIC, diffuse purpura, and Waterhouse-Friderichsen syndrome
- Overwhelming sepsis, typically due to Neisseria meningitidis, leading to shock, hemorrhagic obliteration of adrenals, extreme acute adrenal insufficiency, and DIC
1. Other causal bacteria: Staphylococcus aureus and Streptococcus pneumoniae - Earliest possible dx and aggressive management are KEYS TO SURVIVAL of these pts
12
Q
What is this? Describe the histology.
A
- Anterior pituitary
- Pink ACIDOPHILS secrete growth hormone (GH) and prolactin (PRL)
- Dark purple BASOPHILS secrete corticotrophin (ACTH), thyroid stimulating hormone (TSH), and the gonadotrophins, follicle stimulating hormone and luteinizing hormone (FSH and LH)
- Pale staining CHROMOPHOBES have few cytoplasmic granules, but may have secretory activity
13
Q
What is this?
A
-
Adrenocortical carcinoma: larger than adenomas (200-300g) -> RARE
1. Encapsulated
2. Anaplastic characteristics (can be difficult if not present to call carcinoma) until it metastasizes
3. 2-yr. survival - Irregular external surface w/yellow-tan color; hemorrhagic with minor cystic change (necrosis)
14
Q
Pituitary carcinoma
A
- RARE -> less than 1% of pituitary tumors
- Good example of something that we know is malignant bc it METASTASIZES
1. Metastases usually appear late in the course, following multiple local recurrences - Most are functional, w/prolactin and ACTH being the most common secreted products
15
Q
What are the 3 most common forms of primary hyperaldosteronism? Features?
A
- See attached image for most common causes
1. Bilateral nodular hyperplasia: less severe HTN than those with adrenal neoplasms (cause unknown -> idiopathic hyperaldosteronism) - Overproduction of aldosterone that suppresses renin-angiotensin system
- Most common manifestation is BLOOD PRESSURE ELEVATION
16
Q
What is going on here? Arrowhead?
A
- Diabetic retinopathy: extensive hard exudates (arrowhead)
- DM microangiopathy is assoc w/edema and retinal exudates that are “soft” microinfarcts or “hard” yellowish waxy exudates, which are deposits of plasma proteins and lipids
1. Hard exudates are more a feature of older individuals with T2DM - Additional findings with background retinopathy include capillary microaneurysms, dot and blot hemorrhages, flame-shaped hemorrhages, and cotton-wool spots (soft exudates)
17
Q
What is this?
A
- Normal thyroid histo
- Interstitium, which may contain C cells, not prominent
18
Q
How is neuroblastoma dx’d? Tx’d? Prognosis?
A
- Diagnosis:
1. Urine collections for VMA and HVA
2. Imaging studies
a. Body scan with 131 I-MIBG (metaiodo-benzylguanidine): malignant cells pick up the radioactive material
b. Bone scans to detect lytic lesions -
Treatment: depends on age, stage of disease
1. Surgery, irradiation, multiagent chemotherapy - Prognosis: overall survival is 40%
1. Children <1 year old have a 90% cure rate
19
Q
What are the primary and secondary causes of hypothyroidism?
A
- PRIMARY:
1. Genetic defects in thyroid development: PAX8, FOXE1, TSH receptor mutations (rare)
2. Thyroid hormone resistance syndrome: THRB mutations (rare)
3. Postablative: surgery, radioiodine therapy, or external irradiation
5. Autoimmune hypothyroidism: Hashimoto thyroiditis
7. Iodine deficiency
8. Drugs: lithium, iodides, p -aminosalicylic acid
9. Congenital biosynthetic defect: dyshormono-genetic goiter (rare) - SECONDARY:
1. Pituitary failure (rare)
2. Hypothalamic failure (rare)
20
Q
What is this? How do you know?
A
- Insulinoma: syndrome with characteristic hypoglycemia
- Histologically, may reveal abundant amyloid
21
Q
What are the 2 cardinal metabolic defects that characterize T2D?
A
- DEC response of peripheral tissues, especially skeletal muscle, adipose tissue, and liver, to insulin
1. INSULIN RESISTANCE - Inadequate insulin secretion in the face of insulin resistance and hyperglycemia
1. β-CELL DYSFUNCTION
22
Q
What is chronic lymphocytic thyroidits?
A
- Variants of Hashimoto’s autoimmune thyroiditis
- PAINLESS
- May evolve to hypothyroidism, and look like Hashimotos under the scope –> can’t really distinguish them histologically
23
Q
In patient taking exogenous corticosteroids, what would you expect adrenals to look like?
A
- Bilateral atrophy
- ACTH is suppressed and lack of stimulation of the fasciculata and reticularis
- Glomerulosa is independent of ACTH
24
Q
What is this?
A
- Nodular glomerulosclerosis: aka, Kimmelstiel-Wilson disease
- Ovoid or spherical, often laminated, nodules of matrix in the periphery -> PAS-positive
1. Can be surrounded by patent peripheral capillary loops - Not all lobules in individual glomeruli are usually involved, but even uninvolved lobules and glomeruli show striking diffuse mesangial sclerosis
- 15-30% develop nodular glomerulosclerosis, and in most instances it is associated with RENAL FAILURE
25
Q
What are the clinical manifestations of acute adrenal insufficiency?
A
- Predominant manifestation of adrenal crisis SHOCK, but pts often have non-specific symptoms:
1. Anorexia, weakness, fatigue, lethargy
2. N/V, abdominal pain
3. Fever, confusion or coma - Hypoglycemia is a RARE manifestation of primary acute adrenal insufficiency
26
Q
What is this?
A
-
Charcot joint (neuropathic arthropathy): PROGRESSIVE (slow or rapid), DESTRUCTIVE variant with large amounts of dead bone and cartilage particles embedded in synovium
1. Severe subluxation or dislocation of joint with extreme deformity
2. Fibroblastic proliferation, reactive new bone formation
27
Q
How can you prevent the mental retardation associated with cretinism?
A
Give tx within few days of birth
28
Q
What happened here?
A
- Hypothyroidism (Hashimoto’s)
- Facial/preorbital myxedema -> resolved with successful treatment
29
Q
What do you see here?
A
- Anterior pituitary: basophils, acidophils, and chromophobes
- Epithelial cells derived from developing oral cavity
- Release is controlled by the hypothalamus
30
Q
VHL
A
- von Hippel Lindau: 10-20% of patients
- Cysts of kidney, liver and epididymis
- Renal cell carcinoma (clear cell type)
- Pheochromocytoma
- Angiomas
- Cerebellar hemangioblastoma
31
Q
Pretibial/localized myxedema/thyroid dermopathy
A
- Autoimmune manifestation of Graves’ disease (also occurs in Hashimoto’s thyroiditis)
- Lesions are usually asymptomatic and have only cosmetic importance, but are associated with relatively severe opthalmopathy
1. Usually ophthalmopathy appears first and dermopathy much later. - High serum concentrations of TSH-receptor Abs, indicating the severity of the autoimmune condition
- Occurrence in areas other than pretibial skin indicates a systemic process -> TSH-receptors in CT may be the Ag responsible for the immune process.
1. Humoral + cellular immune mechs involved in stimulation of fibroblasts and production of large amounts of glycosaminoglycans
2. Localization in the pretibial area relates to mechanical factors and dependent position - Diagnosis based on signs and typical pretibial skin lesions in association with a history of Graves’ hyperthyroidism and ophthalmopathy
32
Q
Why is there increased deposition of GAGs in Graves disease?
A
- TSH has receptors on more cells than just those in the thyroid; they may bind with fibroblasts of tissue in various locations and cause receptor increases the deposition of glycosaminoglycan
- TSH receptor protein expression by normal dermal fibroblasts raises possibility that TSH-receptor antibodies and/or antigen specific T cells initiate the inflammatory response, which stimulates the production of glycosaminoglycans by these cells as seen in the accompanying Graves’ orbitopathy
- Cytokines like TNF-alpha and gamma interferon induce GAG release from fibroblasts, and may be secreted by Th1 type T cells activated by TSH receptor antigen
33
Q
Plurihormonal pituitary adenomas
A
- Elaborate more than one hormone, i.e., mammo-somatotroph adenomas (5% incidence; GH and PRL release, and effects)
- These tumors are usually aggressive
34
Q
What are the most common benign/malignant thyroid tumors?
A
- BENIGN: follicular adenomas
- MALIGNANT: papillary carcinomas
35
Q
What is a neuroblastoma? Clinical and lab findings? Sites?
A
- Malignant neoplasm of postganglionic sympathetic neurons that is most common in kids <5 years old
1. 3rd most common cancer in children, and mean age of onset: 18 months - Primarily in adrenal medulla; commonly metastasize to skin and bones (70% have mets at time of dx -> hematogenous)
1. Skin mets and <1-y/o = GOOD PROGNOSIS - Amplification of N-MYC oncogene: indicator of a POOR PROGNOSIS
- Clinical and laboratory findings:
(1) Palpable abdominal mass
(2) Diastolic HTN
(3) INC urine VMA and HVA (90-95% sensitivity)
36
Q
What is the most common cause of hypercortisolism?
A
- Exogenous administration of steroids
- Followed by:
1. Pituitary adenoma
2. Primary adrenal neoplasm
3. Paraneoplastic, ACTH-producing tumors
37
Q
What are the 3 characteristic lesion types in diabetic nephropathy?
A
- Three lesions:
(1) glomerular lesions: most important of these are cap BM thickening, diffuse mesangial sclerosis, and nodular glomerulosclerosis
(2) renal vascular lesions, principally arteriolosclerosis; and
(3) pyelonephritis, including necrotizing papillitis - NOTE: renal failure 2nd only to MI as a COD from this disease
38
Q
What happened here? Lab values? Most common cause of death?
A
- ACROMEGALY due to INC GH secretion
- Lab values: ↑GH, IGF-1, glucose (secondary DM)
- Most common COD: cardiomyopathy
39
Q
What are the clinical features of Cushing syndrome?
A
- INC glucocorticoids
- Flushed face, acne
- Buffalo hump, bruisability
- Immunosuppression, mental changes, insomnia
- Hunger, truncal and facial obesity, “diabetes,” gastric ulcers
- HTN, edema, hypokalemia
- Osteoporosis, muscle wasting, thinning skin
40
Q
What is this?
A
Papillary thyroid cancer: orphan-annie eyed nuclei
41
Q
Primary vs. secondary hyperaldosteronism? Causes?
A
- PRIMARY: autonomous overproduction of aldosterone; DEC plasma renin activity
1. Bilateral idiopathic hyperaldosteronism
2. Adrenocortical neoplasm (Conn syndrome)
3. Rarely: familial hyperaldosteronism - SECONDARY: aldosterone release due to activation of renin-aldosterone system -> WAY MORE COMMON
1. DEC renal perfusion
2. Arterial hypovolemia
3. Pregnancy
42
Q
What do these arrows show? Why is this important?
A
- Solid arrow: optic nerve and its proximity to the sella turcica (dotted white arrow)
- While pituitary adenomas are BENIGN, they can produce problems either from mass effect (usually visual problems from pressing on the optic chiasm and/or headaches) or from production of hormones like prolactin or ACTH
43
Q
What are 4 causes of hyperthyroid signs/symptoms that are not associated w/hyperthryoidism?
A
- Granulomatous (de Quervain) thyroiditis (PAINFUL)
- Subacute lymphocytic thyroidits (PAINLESS)
- Struma ovarii: ovarian teratoma w/ectopic thyroid
- Factitious thyrotoxicosis: exogenous thyroxine intake
44
Q
What is going on in the adrenals on the bottom? What could have caused this?
A
- Bilateral cortical hyperplasia (can be nodular)
- This could be due to:
1. Pituitary adenoma secreting ACTH (Cushing’s disease), or
2. Cushing’s syndrome from ectopic ACTH production, or
3. Idiopathic adrenal hyperplasia - Normal adrenals on top (medulla is brown center)
45
Q
What is this?
A
- ANAPLASTIC CARCINOMA
- Large, pleomorphic giant cells, including occasional osteoclast-like multinucleate giant cells
- Spindle cells with a sarcomatous appearance
46
Q
What are these?
A
- Pheochromocytomas: commonly gray, pink, or red (hemorrhage)
47
Q
What are the 3 blood tests for dx of diabetes and pre-diabetes (what levels are diagnostic)?
A
- For all 3 tests, w/in the prediabetes range, the higher the test result, the greater the risk of diabetes
48
Q
What is the most common cause of hyperparathyroidism? Clinical symptoms?
A
- Parathyroid adenomas
- Typically associated with: hypercalcemia and a # of clinical symptoms involving neuromuscular, skeletal, renal, and CV
49
Q
What do you see here?
A
- Multinodular goiter: note the ABSENCE OF A PROMINENT CAPSULE, a distinguishing feature from follicular neoplasms
- GROSS: coarsely nodular gland with areas of fibrosis and cystic change
- MICRO: hyperplastic nodule with compressed residual thyroid parenchyma on the left
50
Q
What is this? Describe the disease.
A
- Subacute granulomatous (de Quervain) thyroiditis
- Uncommon; diffuse pain; 40-60 F
- Thought to be viral-induced -> activation of CTLs
- Marked ACUTE INFLAM: lymphos, macros, giant cells
- Follicle destruction
- Most pts fully recover in 6-8 wks (don’t see many biopsies for these people)
51
Q
What happened here? Arrows?
A
- Metastatic tumor: leading to chronic adrenal insufficiency
- Blue arrow: tumor
- Purple arrow: residual cortex
- NOTE: TB and HIV are also important causes of chronic adrenal insufficiency
52
Q
What is this?
A
Hashimoto thyroiditis
53
Q
What are the pitfalls in dx diabetes blood tests?
A
- People w/hemoglobin variants like SICKLE CELL (hemoglobin S) will have DEC amt of hemoglobin A, which may limit usefulness of A1c test in dx and/or monitoring this pt’s diabetes, depending on method
- Anemia, hemolysis, or heavy bleeding: A1c test results may be falsely low
- Iron-deficient: A1c level may be increased
- Recent blood transfusion: A1c may be inaccurate and may not accurately reflect glucose control for 2 to 3 months
54
Q
What are some of the causes of hypopituitarism?
A
- TUMORS: pituitary, adenoma, craniopharyngioma, cerebral tumor
- HYPOTHALAMIC DISORDERS: tumor, functional disturbance (e.g., anorexia), isolated GH, GnH secretion due to impaired secretion of hypothal releasing hormones
- MISCELLANEOUS: sarcoidosis
- VASCULAR DS: necrosis (Sheehan’s), infarction, severe hypotension, cranial arteries
- TRAUMA
- INFECTION: meningitis, esp. TB, syphilis
- IATROGENIC: sx, irradiation, prolonged Rx with glucocorticoid or thyroid hormones -> isolated TSH or ACTH suppression
55
Q
What are the key features of the 5 pancreatic neuroendocrine tumors?
A
- Insulinoma: hypoglycemia
- Glucagonoma: necrolytic migratory erythema
- Gastrinoma: peptic ulcers, diarrhea
- Somatostatinoma: diabetes, cholelithiasis, steatorrhea
- VIPoma: watery diarrhea, achlorhydria (no HCl production in stomach)
56
Q
What do you see here? Describe the histologic features.
A
-
Adrenocortical adenoma: distinguished from nodular hyperplasia by solitary, circumscribed nature
1. Atrophy of normal adrenal tissue, if functional, but can’t really tell from gross image
2. Many incidental, and weigh <30g
3. 10% secrete cortisol, 2% secrete aldosterone -
Histologic features: neoplastic cells are vacuolated because of the presence of intracytoplasmic lipid
1. Mild nuclear pleomorphism
2. Mitotic activity and necrosis are NOT seen
3. Cells similar to those in normal zona fasciculata (see attached image) - Note: func status of adrenocortical adenoma can NOT be predicted from gross or micro appearance
57
Q
Insulinoma
A
- Pancreatic beta-cell tumors: most common type of pancreatic neuroendocrine tumor (1,200/yr)
- Generally INDOLENT: 87% single benign, 7% multiple benign, <10% malignant (most likely to metastasize bc most common, but most often indolent)
- 8% part of MEN1 syndrome: more likely to be synchronous (multiple occurring at same time) and metachronous (coming up at different times)
- Patients will come in with episodic hypoglycemia
58
Q
What do you see here?
A
- Necrolytic migratory erythema: NOT specific to glucagonomas
- Erythematous, painful, pruritic rash that begins as macules that coalesce and develop central bullae, then erode, leaving hyperpigmentation and crusting of the periphery
- Usually begins in perirectal area with subsequent spread to the perineum, thighs, buttocks and legs
59
Q
What is the difference between these 2 adrenal glands?
A
-
Diffuse hyperplasia: of the adrenal on the bottom vs. normal adrenal on the top
1. Cortex yellow and thickened, with a subtle nodularity - This abnormal gland was from a patient with ACTH-dependent Cushing syndrome, in whom both adrenals were diffusely hyperplastic
60
Q
Why is hypoglycemia so dangerous?
A
- Can cause seizures or cardiac arrhythmias, both of which can kill
- Thought to account for 3-4% of deaths in insulin-treated diabetics
61
Q
What is going on here? Epi of this disease?
A
- Follicular carcinoma: 5-15% of 1o thyroid cancers; more frequent in areas w/dietary iodine deficiency (25-40% of thyroid cancers)
- More common in WOMEN (3 : 1)
- Present more often in OLDER PTS (40-60) than do papillary carcinomas
- Follicular adenoma vs. carcinoma = capsular invasion or vascular invasion (and this invasion must be capsular or outside of the lesion)
1. One of few carcinomas that spreads hematogenously -> important bc even if you don’t see capsule being breached, this could be from how you cut/sectioned the tumor (but, if you have vessel invasion outside of the tumor, you can still call it follicular carcinoma)
62
Q
What is auto-immune adrenalitis?
A
- Most comm cause of chronic adrenal insufficiency in the Western world
- Part of 2 autoimmune polyendocrine syndromes:
1. APS1 (AIRE gene): chronic mucocutaneous candidiasis + abnormalities of skin, dental enamel, and nails (ectodermal dystrophy) in assoc w/combo of organ-specific autoimmune disorders (autoimmune adrenalitis, autoimmune hypoparathyroidism, idiopathic hypogonadism, pernicious anemia)
2. APS2: combination of adrenal insufficiency and autoimmune thyroiditis or type 1 diabetes - NOTE: we do NOT need to know the specifics of these two mutations
63
Q
ACTH-producing adenomas
A
- Usually small; stain w/PAS due to accumulation of glycosylated ACTH (incidence: 10-15%)
- Can be clinically silent or cause hypercortisolism, this manifests as CUSHING DISEASE (the syndrome will be discussed with the adrenal)
1. ACTH stimulates the adrenal - Because ACTH is part of the larger prohormone that includes melanocyte-stimulating hormone (MSH), patients may have hyperpigmentation
64
Q
What are the 6 adenomas and their associated hormones/syndromes (table)?
A
65
Q
Glucagonomas
A
-
α -cell tumors associated with INC serum levels of glucagon and a syndrome consisting of:
1. Mild diabetes mellitus,
2. Characteristic skin rash (necrolytic migratory erythema -> smaller lesions that coalesce), and
3. Anemia - Occur most frequently in perimenopausal and postmenopausal women and are characterized by extremely high plasma glucagon levels
66
Q
What hereditary endocrinopathies are associated with pancreatic NETs?
A
- 85% in patients with MEN-1
- Can also occur in:
1. Von-Hippel Lindau
2. Neurofibromatosis-1
3. Tuberous sclerosis
67
Q
Pancreatic neuroendocrine tumor basics
A
- Rare (3,000/year in the US)
- Most sporadic, and in middle-aged patients
- Most (up to 75%) non-functioning, i.e., no assoc hormonal syndrome
- All MALIGNANT unless microadenoma (
- Liver is the most common site of metastases
- Serum chromogranin A elevated in about 70% of pts with pancreatic NETs (functioning and non-functioning), but specificity is poor
68
Q
What do you see here? Black, blue, green arrows?
A
- PAPILLARY CARCINOMA
- Black: intranuclear grooves
- Blue: pseudoinclusions (invaginations of the cytoplasm that cover up parts of the nucleus)
- Green: optically clear
- This is an FNA: cells in a fluid, not tissue
69
Q
What is this? How do you know?
A
- Papillae having a fibrovascular stalk covered by a single to multiple layers of cuboidal epithelial cells.
-
Nuclear features: 1) optically clear or empty, 2) intranuclear grooves, and 3) pseudoinculsions
1. Dx can be made based on nuclear features, even in absence of papillary architecture - PSAMMOMA BODIES (can happen in multiple contexts; not always an indicator for malignancy)
- Foci of lymphatic invasion by tumor often present
- Metastases to adjacent cervical lymph nodes occur in up to 50% of cases
70
Q
What is the most common cause of hypoparathyroidism?
A
Typically due to surgical interventions (but less common then hyperparathyroidism)
71
Q
What are the 4 primary adrenal neoplasms?
A
- Cortex:
1. Adrenal cortical adenoma
2. Adrenal cortical carcinoma - Medulla:
1. Pheochromocytoma
2. Neuroblastoma
72
Q
Somatotroph cell adenomas
A
- 2nd most common functional pituitary adenoma; effects can be subtle (incidence: 10-15%)
- Persistent GH secretion stimulates hepatic release of IGF-1 (somatostatin C), stimulating bone, cartilage, soft tissue growth (clinical manifestations)
1. Gigantism (children), acromegaly (adults) - Prolactin can be produced in sufficient quantities to produce signs and symptoms
- GH excess can also be associated with a variety of other disturbances, including: gonadal dysfunction, DM, generalized muscle weakness, HTN, arthritis, CHF, and INC risk of GI cancers
-
Hyperglycemia (diabetes): GH INH of peripheral glucose uptake and INC hepatic glucose production
1. Compensatory hyperinsulinism -> insulin resistance -> DM
73
Q
These tumor cells are arranged in:
A. Glands
B. Nests
C. Sheets
D. Strands
E. Trabeculae
A
- TRABECULAE
- Non-neoplastic pancreas on the left
- Tumor on the right (these don’t all have capsules, but this one has a little one)
74
Q
What do you see here?
A
- Auto-immune adrenalitis: extensive mononuclear infiltrate
- Most common cause of primary adrenocortical insufficiency in Western world
- Autoantibodies to key steroidogenic enzymes APS1 and APS2
- Irregular shrunken glands, but medulla preserved
- Scant residual cortical cells in a collapsed network of connective tissue
75
Q
What should this make you suspicious of?
A
CAH: suspect in neonates with ambiguous genitals
76
Q
What do you think is going on here? Why?
A
- Metastatic adrenal neoplasms: bilateral and multi-focal tumors almost always metastatic
- Common sites of the primary tumors: LUNG, BREAST, KIDNEY
- Most common malignancies in the adrenals, BY FAR = metastases
77
Q
Describe the pathogenesis of anterior adenomas.
A
- Guanine nucleotide-binding protein (G-protein) mutations encoded by the GNAS1 gene
- Lead to unchecked CELLULAR PROLIFERATION
- 40% of GH-secreting somatotroph cell adenomas and a minority of ACTH-secreting adenomas bear GNAS1 mutations
78
Q
What is the difference between these two tissues?
A
- Left: pituitary ADENOMA -> cellular monomorphism and absence of a reticulin network (reticulin stain highlights this)
- Right: normal pituitary
79
Q
What happened here?
A
- Nephrosclerosis: in a pt w/long-standing diabetes
- Kidney has been bisected to show:
1. Diffuse granular transformation of the surface (left), and
2. Marked thinning of the cortical tissue (right) - Also some irregular depressions, the result of pyelonephritis, and an incidental cortical cyst (far right)
80
Q
What is the pathogenesis of follicular adenomas?
A
- Somatic muts of TSH receptor signaling pathway in toxic adenomas and toxic multinodular goiter; most often:
1. Gene encoding TSH receptor (TSHR) or α-subunit of Gs (GNAS) —> cause follicular cells to secrete thyroid hormone independent of TSH stimulation (“thyroid autonomy”)
a. Rare in follicular carcinomas - Leads to symptoms of hyperthyroidism and produces a functional “hot” nodule on imaging
- Minority (<20%) of nonfunctioning follicular adenomas have RAS or PIK3CA muts, genetic alterations that are shared with follicular carcinomas
81
Q
What is the most common cause of hypoPTH?
A
Accidental removal of PTHs in surgery
82
Q
Briefly describe the anatomy of the pituitary.
A
- Small, bean-shaped structure at base of brain, in the confines of the sella turcica
- Intimately related to hypothalamus -> connected by a stalk
- Two morphologic and func distinct components:
1. Anterior
2. Posterior
83
Q
MEN-2A
A
- Thyroid – medullary carcinoma in the first two decades of life
1. Stain with calcitonin (C cells) - Adrenal medulla – 50% get pheochromocytomas
- Parathyroid – 10-20% get hyperplasia and manifestations of primary hyperparathyroidism
- NOTE: also familial medullary thyroid cancer (variant of 2A medullary cancer w/o clinical manifestations)
84
Q
What is this?
A
Normal adrenal histo
85
Q
What is myxedema?
A
- Hypothyroidism in older children/adults
- General apathy and mental sluggishness –> can mimic depression
-
Mucopolysaccaride-rich edematous fluid builds up broad, coarse facial fxs -> large tongue, deep voice
1. GAGs build up in the tissue (more like a clay than a watery texture, unlike fluid edema) - Bowel slowing, causing constipation and pericardial effusions are common
- Cold intolerant and often overweight
- Measurement of serum TSH level is most sensitive screening test for this disorder
86
Q
What is this?
A
Hurthle cell adenoma: enlarged epi cells w/abundant eosinophilic, granular cytoplasm as a result of altered mito (follicular in origin)
87
Q
What 3 distinctive clinical syndromes are caused by excess androgens?
A
- Cushing syndrome
- Hyperaldosteronism
- Adrenogenital or virilizing syndromes
88
Q
What are the key features of the multiple endocrine neoplasia (MEN) syndromes? Manifestations of each (image)?
A
- Inherited diseases of multiple endocrine organs
- Typically occur in younger patients (i.e., 30s)
- Multifocal -> can be synchronous or metachronous
- Typically have hyperplasia of cell before neoplasm
- Typically more aggressive and recur (vs. sporadic)
89
Q
What are the 3 types of negative feedback INH?
A
- Long-loop: 3rd hormone going back up
- Short-loop: 2nd hormone
- Ultra-short loop: auto-INH
90
Q
What is this?
A
-
Craniopharyngioma: thought to arise from vestigial remnants of Rathke pouch
1. Slow-growing tumors that account for 1 - 5% of intracranial tumors
2. Bimodal age distribution: children and adults in 50s-60s - Pts come to attention due to headaches and visual disturbances (bitemporal hemianopsia); children sometimes present with growth retardation due to pituitary hypofunction and GH deficiency
- Abnormalities of WNT signaling pathway, incl. activating muts of gene encoding β-catenin, have been reported in craniopharyngiomas in children
- Note the wet keratin (NOT squamous cell carcinoma) and stellate reticulum (edema)
91
Q
Sturge-Weber
A
- Cavernous hemangiomas (port-wine spots) of trigeminal nerve (cranial nerve V)
- Pheochromocytoma
92
Q
What is this? Bottom right vessel too?
A
- PAS stain of nodular glomerulosclerosis (Kimmelstiel-Wilson disease) in a pt with long-standing diabetes mellitus
- Note also the markedly thickened arteriole at the lower right which is typical for the hyaline arteriolosclerosis that is seen in diabetic kidneys as well
93
Q
What is congenital adrenal hyperplasia? Most common form?
A
- Autosomal recessive; F may have masculinization, and M have precocious puberty
- Enzyme deficiencies, so no cortisol synthesis, and precursors shunted into excess androgen production
- Most common form: 21-hydroxylase deficiency (wastes sodium -> hypotension)
- 11-hydroxylase deficiency: retains sodium (HTN) bc DOC is a potent mineralocorticoid
94
Q
What is this?
A
- ACTH-independent hyperplasia (primary cortical hyperplasia) -> very uncommon
- Micronodular hyperplasia: 1-3mm
- Darkly pigmented (lipofusion) nodules with intervening atrophy
95
Q
How common is diabetic neuropathy?
A
- Diabetic neuropathy: varies, depending on the duration of the disease
- Up to 50% of diabetics overall have peripheral neuropathy clinically, and up to 80% of those who have had the disease for more than 15 years
96
Q
What is empty sella syndrome?
A
- Any condition or treatment that destroys part or all of the pituitary gland
-
PRIMARY TYPE: anatomic defect in child
1. Subarachnoid space herniates into sella turcica and fills w/CSF -> pressure compresses gland
2. INC in pressure on pituitary gland causes it to flatten out and undergo atrophy
3. Questions often include obese patients with HTN and a history of multiple pregnancies - SECONDARY TYPE: mass, i.e., pituitary adenoma, enlarges sella and is then either surgically removed or undergoes infarction -> loss of pituitary function
97
Q
What are the 3 layers of the adrenal cortex? Origin? Hormones?
A
- Mesodermal origin
- Glomerulosa: mineralocorticoids
- Fasciculata: glucocorticoids
- Reticularis: estrogens and androgens
98
Q
What is this?
A
- Pancreatic histo in T1D: leukocytic infiltrates in islets (insulitis) are principally composed of T-lymphos
- Also seen in animal models of autoimmune diabetes
- Reduction in the # and size of islets
99
Q
What happens in loss of anterior pituitary? Posterior?
A
- Ant pituitary loss: panhypopituitarism
- Post pituitary loss: deficiency of ADH -> diabetes insipidus
100
Q
What do you see here?
A
- Subacute lymphocytic thyroiditis (aka, painless thyroiditis -> variant of Hashimoto)
- Fine needle aspiration biopsy NOT typically part of the evaluation of painless thyroiditis
- Lymphos and macros, normal thyroid epithelial cells, a few damaged thyroid follicles, and masses of colloid
- During recovery, lymphocytic infiltration persists, may be mild fibrosis, but the thyroid follicles are normal
- These findings differ from those of chronic auto-immune thyroiditis in that there is:
1. More follicular disruption, but
2. Fewer lymphocytes,
3. Fewer germinal centers, and
4. Less fibrosis in painless thyroiditis
101
Q
What is cretinism?
A
- Hypothyroidism that develops in infancy or early childhood
- RARE now that iodine is supplemented in food
-
Clinical features: severe mental retardation
1. Short stature
2. Coarse facial features
3. Protruding tongue (and abdomen)
4. Umbilical hernia
102
Q
What are the basic features of adrenal cortical tumors?
A
- Typically incidental, discovered on imaging
-
Non-functioning adenomas, with 2 exceptions:
1. 10% secrete cortisol (Cushing syndrome)
2. 2% secrete aldosterone (HTN + hypokalemia, aka, Conn syndrome) - Usually a yellow (or gold) color, like butter, bc lots of CHOLESTEROL
103
Q
What is the most common type of neuroendocrine tumor to produce an endocrine syndrome? Clinical manifestation?
A
- Insulinoma
- Hypoglycemia
- Note: pancreatic neuroendocrine tumors are RARE
104
Q
What is a pheochromocytoma?
A
- Catecholamine-secreting tumor of adrenal medulla
- Rare: 2,400/year in US (most comm in middle age)
- SYNDROMES: up to 20% in pts with MEN-2, von Hippel-Lindau (VHL) syndrome, or Li-Fraumeni
- CLASSIC TRIAD: 1) Episodic headache, 2) Sweating, 3) Tachycardia
- Hypertension (+/- paroxysmal)
105
Q
VIPoma
A
- Release of vasoactive intestinal peptide (VIP)
1. Watery diarrhea
2. Hypokalemia, hypovolemia, and acidosis
3. Achlorhydria (absent or reduced production of HCl in stomach)
4. Severe diarrhea -> VIP assay should be done on all pts w/severe, secretory diarrhea - Some are locally invasive and metastatic
- Neural crest tumors, such as neuroblastomas, ganglioneuroblastoma, and ganglioneuromas and pheochromocytomas can also be associated with the VIPoma syndrome
106
Q
What do you see? HInt: there are 2 different types of tissue here.
A
- Pheochromocytoma: typically composed of cells in clusters (“Zellballen”)
- Tumor cells often have abundant BASOPHILIC cytoplasm -> compare the pheo cells to the adrenal cortical cells in the lower right (in the right-hand image)
107
Q
What do you see here?
A
- Electron micrograph of a β cell shows the characteristic membrane-bound granules, each containing a dense, often rectangular core and distinct halo
- Portions of an α cell (left: dense, round center) and a δ cell (right) also show granules, but with closely apportioned membranes
108
Q
What is Hashimoto thyroiditis?
A
- Chronic lymphocytic thyroiditis: breakdown in self-tolerance -> AUTO-IMMUNE disease
1. Auto-Abs against thyroglobulin and thyroid peroxidase (lympho-mediated destruction) - 45-65 F; HLA-DR3, HLA-DR5
- Strong genetic component: most significant CTLA-4
- Progressive depletion of thyroid epi cells, with replacement by inflam and fibrosis
- Risk of developing B-cell lymphoma
109
Q
What is this?
A
- Adrenal cortical adenoma: looks a lot like normal zona glomerulosa, with mild pleomorphism
- Abundant lipid
- Really need to have the gross nodule to be able to tell that this is not normal
110
Q
What do you see here?
A
-
Diffuse mesangial sclerosis: diffuse INC in mesangial matrix
1. INC in mesangial matrix, a slight INC in mesangial cellularity, and capillary BM thickening -> will eventually become sclerotic - As disease progresses, expansion of mesangial areas can extend to nodular configurations
1. Progression correlates with measures of deteriorating renal function -> INC proteinuria
111
Q
Why do you need your adrenals for things like surgery?
A
- Stress = bodily response to disturbances of homeostasis
- Mediated by CATECHOLAMINES (acute) or CORTICOSTEROID hormones (chronic)
- Causes tachycardia, HTN, hyperventilation and hyperglycemia
115
Q
This is a caseating granuloma of tuberculosis in the adrenal gland. Tuberculosis used to be the most common cause of chronic adrenal insufficiency. Now, idiopathic (presumably autoimmune) Addison’s disease is much more often the cause for chronic adrenal insufficiency. What would glucose, sodium, and potassium look like in this patient?
A
Low glucose, low sodium, high potassium
- Tuberculosis used to be the most common cause of chronic adrenal insufficiency; now, idiopathic (presumably autoimmune) Addison’s disease is much more often the cause for chronic adrenal insufficiency
- Lack of cortisol leads to hypoglycemia, hyponatremia, and hyperkalemia
116
Q
What is the difference b/t the 2 images on the left and that on the right?
A
- Normal parathyroid on the right
-
Parathyroid adenoma on the left -> major cause of 1o hyperparathyroidism (the most common cause of asymptomatic hypercalcemia)
1. Most important distinction is the LACK OF FAT in the adenoma
117
Q
What is this?
A
- Renal atherosclerosis/arteriolosclerosis in diabetes
- Thickening of renal arteriolar wall -> “onion skin” appearance to the media
- The thickening has left a tiny lumen
119
Q
What do you see here? Arrows? Circle?
A
- Biopsy in pt w/chronic renal failure -> yields little useful information
- TOP ARROW: atherosclerosis & arteriolosclerosis severely affect the kidney in DM
- NEXT ARROW: cortex is fibrotic, glomeruli are sclerotic, the arteries are thickened, and there are scattered chronic inflammatory cell infiltrates
- BOTTOM ARROW: sclerotic glomeruli
- CIRCLE: tubules often dilated and filled with pink casts -> “thyroidization”
120
Q
What happened to this top set of adrenals?
A
- Patient with adrenal atrophy due to:
1. Long-standing Addison’s, or
2. Long-term corticosteroid therapy
126
Q
What do you see here?
A
- ANAPLASTIC CARCINOMA
- Large, pleomorphic giant cells, including occasional osteoclast-like multinucleate giant cells
- Spindle cells with a sarcomatous appearance
129
Q
What is going on here?
A
- Nelson syndrome: large, destructive pituitary adenomas that devo after sx removal of the adrenal glands (to tx Cushing’s)
- Loss of INH effect of adrenal corticosteroids on a preexisting corticotroph (ACTH) microadenoma
1. Because adrenals are absent in persons with this disorder, hypercortisolism does NOT devo - Hyperpigmentation possible bc stimulatory effect of MSH on melanocytes (o/product of ACTH precursor)
131
Q
How can parathyroid devo go wrong?
A
- Normally, there are 4 parathyroids, but up to 8 can occur
- Normally located posterior to thyroid at upper and lower poles, but sometimes reside in the thyroid, or below it, even as low as in the mediastinum
- NOTE: these anatomic variations are very important for SURGEONS
132
Q
What do you see here?
A
- HASHIMOTO THYROIDITIS
- Chronic inflam of T-lymphos, incl follicle formation
1. Germinal center in top right
2. Hyper -> Eu -> Hypothyroid - Remaining tissue can become atrophic, and undergo Hurthle cell change (follicular cells get more abundant pink cytoplasm)
- Risk of developing B-cell lymphoma
133
Q
What is subacute lymphocytic thyroiditis?
A
- 5% of cases of hyperthyroidism (2o to thyroid tissue damage)
- Middle-aged F
- Mild goiter or hyperthyroidism -> most recover, but some progress to hypothyroidism
- AUTO-IMMUNE: anti-thyroid peroxidase Abs
1. Thyroid peroxidase oxidizes iodide ions to form iodine atoms for addition onto tyrosine residues on thyroglobulin for the production of thyroxine (T4) or triiodothyronine (T3) -> image attached - Excludes women who have a painless thyroiditis syndrome w/in 1 yr of delivery, abortion, or miscarriage (silent can be associated w/pregnancy, per Dr. Steinberg)
136
Q
What is this? Name the layers.
A
- Normal adrenal gland histology:
1. Capsule
2. Zona glomerulosa
3. Zona fasciculata
4. Zona reticularis
5. Medulla - Lot of fat is going to clue you in this is the adrenal
137
Q
What is chronic adrenal insufficiency? Clinical features? Dx?
A
- Addison disease: 90% caused by auto-immune disease, AIDS, infection, or cancer
- 90% of tissue has to be destroyed for clinical manifestations, which include:
1. Fatigue, weakness, GI disturbances
2. 1o adrenocortical insufficiency also has high ACTH levels and skin pigmentation - ACTH stimulation test: improvement w/ACTH admin suggests secondary (pituitary/hypothalamic) disease
140
Q
What is this?
A
Congenital Adrenal Hyperplasia
141
Q
What happened here?
A
- Pyelonephritis: acute or chronic inflammation of the kidneys (more common in diabetics, and tends to be more severe involvement)
- Usually begins in interstitial tissue, then spreads to affect the tubules
- One special pattern of acute pyelonephritis, necrotizing papillitis (or papillary necrosis), is much more prevalent in diabetics than in nondiabetics
144
Q
What do you see here?
A
- Subacute (de Quervain) granulomatous thyroiditis
- Self limited; symptomatic treatment
- Often after flu-like symptoms
- Acute phase may be associated with mild hyperthyroidism, which is usually followed by a period of hypothyroidism
- GRANULOMAS and lymphoplasmacytic (chronic) inflitrate
- Note: memory tool -> vain = pain
145
Q
What are the clinical manifestations of diabetes (image)?
A
147
Q
How does hyperglycemia affect neutrophils?
A
- Upregulates CD11b on neutrophils
- Also upregulates ICAM-1, VCAM-1, and E-selectin on endothelial cells
- Creates an “ADHESIVE PHENOTYPE”
- This all impairs neutrophil exodus from blood vessels to sites of infection
148
Q
This tumor has an immunostain for insulin. What is its significance?
A
- This tumor is an INSULINOMA
- However, stains often do NOT correlate with secretion
- NOT helpful when really needed
151
Q
What could this thyroid tissue be stained for?
A
- IHC calcitonin stain
- Identifies the C (parafollicular) cells, which secrete CALCITONIN
153
Q
What is going on in these two images?
A
- Renal cortex showing thickening of tubular basement membranes in a diabetic patient (left image; PAS stain)
- Microangiopathy
156
Q
What is this? Arrows?
A
- Neuroblastoma: small cell tumor composed of malignant neuroblasts; well-circumscribed
- Arrows: Homer-Wright rosettes -> neural appearing center with cells wrapped around it
- See attached image for gross appearance
157
Q
What is this?
A
- Expanded zona reticularis in adrenal hyperplasia
159
Q
What do you see here?
A
- Spironolactone bodies in aldosterone-producing adenoma: eosinophilic, laminated cytoplasmic inclusions (characteristic feature)
- Found after treatment with the antihypertensive agent spironolactone, which is the drug of choice in primary hyperaldosteronism
- NOTE: in contrast to cortical adenomas associated with Cushing syndrome, those associated with hyperaldosteronism do NOT usually suppress ACTH secretion -> adjacent adrenal cortex and that of the contralateral gland are NOT atrophic
161
Q
What type of pts did these 3 pairs of adrenals come from?
A
- Top row: pt w/adrenal atrophy -> either Addison’s disease or long-term corticosteroid therapy
- Middle: NORMAL
- Bottom row: bilateral cortical hyperplasia; could be due to pituitary adenoma secreting ACTH (Cushing’s disease), Cushing’s syndrome from ectopic ACTH production, or idiopathic adrenal hyperplasia
162
Q
What could this be?
A
Adrenal cortical adenoma (lipid-rich, like normal zona glomerulosa)
164
Q
What do you see here?
A
- Amyloid deposition in islets in T2D: begins in and around capillaries, and between cells
- May be a subtle reduction in islet cell mass
- At advanced stages, the islets may be virtually obliterated; fibrosis may also be observed
- Similar lesions may be found in older nondiabetics, as part of normal aging
165
Q
What is Sheehan Syndrome?
A
- Physiologic expansion of pituitary gland during pregnancy -> NOT accompanied by INC in blood supply from low-pressure venous system, so there is relative hypoxia
- Posterior pituitary usually NOT affected: receives blood directly from arterial branches, so it is much less susceptible to ischemic injury
- Can get empty sella from this -> first thing mom will notice is that she cannot lactate
- Can get some GENITAL HAIR LOSS as well
166
Q
What is this?
A
- Aldosterone-producing adenoma: almost always solitary, small (<2 cm diameter), well-circumscribed lesions
- Characteristic feature is presence of eosinophilic, laminated cytoplasmic inclusions -> spironolactone bodies
1. Found AFTER tx w/antihypertensive agent spironolactone, the drug of choice in primary hyperaldosteronism
167
Q
What is bilateral idiopathic hyperplasia of the adrenals?
A
- Most common cause of primary hyperaldosteronism
- Diffuse and focal hyperplasia of cells resembling normal glomerulosa
- Often wedge shaped
168
Q
What do you see here?
A
-
Necrotizing papillitis, complicating acute pyelonephritis
1. Much more prevalent in diabetics than in non-diabetics - Infarct-like papillary necrosis (blue arrow) with surrounding cellular exudate (red arrow)
171
Q
What happened here?
A
- Acute adrenal insufficiency
- Typical “bag of blood” appearance of hemorrhagic adrenals
172
Q
What is endemic goiter?
A
- Occurs in areas where the environment is low in naturally occurring iodine (Albania, Bangladesh, Ethiopia examples provided in class)
- “Endemic” if >10% of the population has goiter
- Other causative factors (diet, genetics) contribute
- Starts as diffuse thyroid enlargement, but generally progresses (through multiple episodes of regression and enlargement) to multinodular state
174
Q
Describe the WHO grading system for neuroendocrine tumors of the digestive tract.
A
- Based on mitotic figures and Ki-67 staining:
1. LOW grade (G1): <2 mitoses / 10 hpf AND <3% Ki67 index
2. INTERMEDIATE grade (G2): 2-20 mitoses / 10 HPF OR 3%-20% Ki67 index
3. HIGH grade (G3): >20 mitoses / 10 hpf OR >20% Ki67 index - High grade = higher propensity to metastasize, but this does not mean that it has, or will (can’t really tell based on histology many times)
- BONA FIDE CARCINOMAS DX’D ON BASIS OF LOCAL INVASION AND DISTANT METASTASES
- Don’t need to memorize these numbers, but know there is a grading system
177
Q
What types of cells do you see in these two images?
A
- THYROID GLAND
- Left image:
1. Hurthle cells: enlarged epi cells with abundant eosinophilic, granular cytoplasm as a result of altered mito (follicular in origin)
2. Lymphocytes - Right Image: follicular cells in a follicular adenoma
178
Q
What is this? Associated lab findings?
A
- Graves disease: tall, columnar appearance with small clear vacuoles that create SCALLOPED EDGE
- Lab:
1. TSH decreased in the serum
2. Free T3 and T4 are elevated
179
Q
What are the symptoms of hypoglycemia?
A
- Shakiness
- Sweatiness
- Nervousness
- Hunger
- Weakness
- Visual disturbances
- Palpitations
- Pallor
- Mental status changes (patient may not remember)
180
Q
How does insulin affect adipose tissue?
A
- SUPPORTS lipogenesis (glucose storage as lipid in adipose)
- PREVENTS lipolysis
- Does the same with protein
181
Q
What do you see here?
A
- Graves
- Pretibial myxedema
182
Q
What are some of the clinical manifestations of anterior pituitary hypopituitarism?
A
- GH: pituitary dwarfism
- Gonadotropin: amenorrhea, infertility in F; DEC libido, impotence, loss of pubic/axillary hair in M
- TSH: hypothyroidsim
- ACTH: hypoadrenalism and pallor
- Prolactin: postpartum lactation failure
184
Q
List the 5 pancreatic neuroendocrine tumor syndromes and their features.
A
- Glucagonoma: anemia, diabetes, necrolytic migratory erythema
- Insulinoma: hypoglycemia, confusion, blurred vision, muscle weakness, sweating, palpitations
- Gastrinoma: Zollinger-Ellison syndrome -> parietal cell hyperplasia, peptic ulcers
- VIPoma: vasoactive intestinal peptide -> achlorhydria (no HCl production), severe diarrhea, hypokalemia, acidosis, hypovolemia
- Somatostatinoma: achlorhydria, cholelithiasis, diabetes, steatorrhea
187
Q
What is this? Describe the characteristic histo.
A
- Pancreatic NET: small, bland, uniform, monotonous, benign-looking cells
- Arranged in nests or cords
- Round-to-oval nuclei and inconspicuous nucleoli
- Stippled chromatin pattern sometimes called “salt and pepper,” and scant pink eosinophilic granular cytoplasm
1. Note: salt and pepper chromatin does NOT make these cells malignant
188
Q
What is this? Describe the typical histo.
A
- Pancreatic NET: small, bland, uniform, monotonous, benign-looking cells
- Arranged in nests or cords
- Round-to-oval nuclei and inconspicuous nucleoli
- Stippled chromatin pattern sometimes called “salt and pepper,” and scant pink eosinophilic granular cytoplasm
- These all look the same, regardless of the organ
190
Q
What is going on here?
A
- Adrenal cortical carcinoma: INVASION (into vein here) and METASTASES are most reliable indicators of malignancy
- Closely resembles normal adrenal cortex; difficult to determine malignancy in endocrine neoplasms based on cytology alone
- Most endocrine neoplasms are benign adenomas
191
Q
What is the pathogenesis of diabetic neuropathy (flow chart)?
A
192
Q
Gastrinomas
A
- 2nd most comm pancreatic neuroendocrine tumor
-
Zollinger-Ellison syndrome:
1. Unrelenting peptic ulcer disease,
2. Hypersecretion of acid, and
3. Pancreatic islet cell lesion - Just as likely to arise in the duodenum and peri-pancreatic soft tissues as in the pancreas (so-called gastrinoma triangle)
- 25% are in pts with MEN-1
- Treatment-resistant -> do not go away (definitive tx is removal of the tumor)
- Cells still really monotonous, w/trabecular pattern
194
Q
How are insulin/glucagon oppositional (image)?
A
195
Q
What do you see here?
A
- Follicular adenoma
- Follicular growth pattern usually quite distinct from the adjacent nonneoplastic thyroid
- Neoplastic cells show little variation in cell size, cell shape, or nuclear morphology
199
Q
What do you see here?
A
- Transverse CT and MR images in a 35-year-old woman with VHL syndrome and pancreatic NET
- Left: contrast-enhanced CT scan shows a 2.0 x 1.8-cm mass in the pancreatic head (arrows) that is homogeneously enhancing
- Right: T1-weighted spoiled gradient-echo MR image of same mass (arrows) 7 months later -> well defined, low in signal intensity, and has increased slightly in size (2.2 x 2.0 cm)
200
Q
What is this?
A
- Tall cell variant of papillary carcinoma: cells twice as tall as wide comprise 50% of tumor
- Abundant eosinophilic cytoplasm and papillary nuclear features
- Aggressive behavior
202
Q
What are the four forms of Cushing syndrome?
A
- Pituitary/hypothalamus: e.g., a tumor, aka, Cushing disease
- Adrenal: nodular hyperplasia, adenoma, or carcinoma
- Paraneoplastic: lung (most often small cell) or other neuroendocrine cancer that makes ACTH
- Iatrogenic: via corticosteroids
- MNEMONIC: Adrenal, Cushing disease, Tumor secreting ACTH, Hormone therapy
203
Q
Somatostatinoma
A
- δ -cell tumors: high plasma somatostatin levels are required for diagnosis
- Somatostatinoma syndrome (only 10% of pts with the tumor have this syndrome):
1. Diabetes mellitus: INH insulin release from beta cells
2. Cholelithiasis: gall stones bc INH release of cholecystokinin, delaying gallbladder emptying
3. Steatorrhea: INH pancreatic secretion and lipid absorption - Smelly, greasy diarrhea due to fat malabsorption
204
Q
What is this?
A
-
Reidel thyroiditis: rare, unknown etiology
1. Young women; will describe as “woody” - Extensive fibrosis that may be associated with idiopathic fibrosis in other parts of the body
- HISTO: 1) Fibrosis, 2) Lymphocytes, 3) Hyperplastic germinal centers
- Infiltrative: surgeon goes in, and has a really hard time getting everything out
- Main thing is to be able to distinguish this from a carcinoma, in which you would be able to see the cells, not just this kind of diffuse fibrosis
205
Q
What are goitrogens?
A
- Substances that interfere with thyroid hormone syn at some level when they are ingested
- Examples: vegetables belonging to the Brassicaceae (Cruciferae) family (e.g., cabbage, cauliflower, brussel sprouts, turnips)
206
Q
What are the potential site of paragangliomas?
A
- Sites of paraganglia in which neoplasms may form:
1. Branchiomeric
2. Intra-vagal
3. Aortico-sympathetic - Paragangliomas can be thought of as extra-adrenal pheochromocytomas
- Looks the same as pheo histologically
208
Q
What are the clinical manifestations of Graves disease?
A
- Diffuse enlargement of thyroid gland
- Infiltrative opthalmopathy: inflam cells + accumulated extracellular matrix components + fatty infiltration
- Infiltrative dermatopathy (sometimes caller pretibial myxedema): if present is from glycosaminoglycans and lymphocytes
210
Q
What do you see here?
A
- Diabetic ocular complications:
1. Flame-shaped and dot-blot hemorrhages
2. Cotton-wool spots: soft exudates, e.g., microinfarcts
3. Microaneurysms
213
Q
What do you see here? Describe the histo.
A
- MEDULLARY CARCINOMA
- Polygonal to spindle-shaped cells, which may form nests, trabeculae, and even follicles
- Calcitonin is readily demonstrable in cytoplasm of the tumor cells
- Acellular amyloid deposits derived from calcitonin polypeptides present in the stroma in many cases
1. Amyloid is the pink, amorphous, anuclear part
214
Q
What is going on in these images?
A
- Electron micrograph of a renal glomerulus showing markedly thickened glomerular basement membrane (left) in a diabetic (MICROANGIOPATHY)
215
Q
What is this?
A
Caseating TB granuloma in the adrenal gland
- Note: histoplasma, coccidioides, and HIV can also cause chronic adrenal insufficiency
217
Q
What is this?
A
- MEDULLARY CARCINOMA
- Polygonal to spindle-shaped cells, which may form nests, trabeculae, and even follicles
- Calcitonin is readily demonstrable in cytoplasm of the tumor cells
- Acellular amyloid deposits derived from calcitonin polypeptides present in the stroma in many cases
1. Amyloid is the pink, amorphous, anuclear part
218
Q
What is going on here?
A
- Thyroglossal duct cyst
- Usually MIDLINE, between isthmus of thyroid and hyoid bone
- Usually apparent at birth or in childhood
- Tend to get repeated INFECTIONS
- NOT hormonally active
219
Q
How are the MEN syndromes different/similar (table)?
A
221
Q
What are 3 of the important cell types/hormones in the Islets of Langerhans? How is insulin made/stored?
A
- BETA CELLS: insulin -> proteolytically cleaved in the Golgi complex to gen the mature hormone and the byproduct, C-peptide
1. Both are then stored in secretory granules, and secreted in equimolar quantities after physiologic stimulation - ALPHA CELLS: glucagon
- DELTA CELLS: somatostatin
- See attached image for relative distribution of these 3 types of cells and their contents (immunoperoxidase stains w/dark rxn products)
224
Q
What hormones are released by the anterior/posterior pituitary? What do they do (image) and where?
A
227
Q
Describe the anatomic devo of the parathyroid.
A
- 4 parathyroid glands (2 superior, 2 inferior) devo from the 3rd and 4th branchial pouches
- Inferior -> 3rd branchial pouch; also gives rise to the thymus (DiGeorge)
- Superior -> 4th branchial pouch
231
Q
What is this? Describe it.
A
- Diabetic macrovascular disease: takes the form of an amorphous, hyaline thickening of the wall of the arterioles, which causes narrowing of the lumen
- HYALINE ARTERIOSCLEROSIS, the vascular lesion associated with HTN is both more prevalent and more severe in diabetics than in nondiabetics
232
Q
What is the difference b/t these 2 images?
A
- Left: pancreatic NET -> sheets of uniform cells with “salt and pepper” chromatin
- Right: normal pancreatic islet
234
Q
What happened here? Potential causes?
A
- Acute adrenal insufficiency
- Causes include:
1. Waterhouse-Friderichson syndrome
2. Sudden withdrawal of exogenous steroids
3. Sudden stress in a patient w/chronic adrenal insufficiency
235
Q
What are these?
A
-
Lateral aberrant thyroid: embryonic rests in lateral neck, sometimes in lymph nodes
1. Lymph node with ectopic thyroid: metastatic until proven otherwise - Beware, especially in adults: what seems to be lateral aberrant thyroid is most likely metastatic follicular thyroid carcinoma
- NOTE: in paratracheal musculature (left-hand image) and outer cervical musculature (right-hand)
236
Q
What is this?
A
- ADENOMA: derived from FOLLICULAR epithelium, so called follicular adenoma
- Typically SOLITARY and ENCAPSULATED
- Not considered a forerunner to carcinoma, but there are shared genetic alterations
- Most are NONFUNCTIONAL; a small minority are toxic adenomas
- REMEMBER: only difference b/t follicular adenoma and carcinoma is that the carcinoma will breach the capsule (have to take it out and look at it)
237
Q
What is this? Arrow?
A
- Neovascularization with diabetic proliferative retinopathy -> note the proliferation (arrow) of small vessels near the optic disc
- These are prone to bleed, producing vitreal hemorrhages that obscure vision
- Always perform fundoscopy (opthalmoscopy) on these patients (refer to opthalmologist, if necessary)
238
Q
What are the gross and histologic features of Congenital Adrenal Hyperplasia?
A
- GROSS: marked thickening of adrenal w/enlarged, cerebriform appearance (see attached image)
1. Cut surface would be more brown than yellow - HISTOLOGY: diffuse cortical hyperplasia, esp. involving the zona reticularis; cortical cells are lipid depleted
- ADDITIONAL FXS: many also have hyperplasia of corticotrophs (ACTH secreting cells) in the pituitary
1. May have tumors in testes hilus due to increase ACTH
243
Q
What do you see here?
A
Graves disease: thyroid hyperplasia characterized by papillary infoldings (this is a pathognomonic histo slide for Graves)
245
Q
What is this?
A
- Hashimoto’s thyroiditis: NONTENDER
- Can be hyperthyroid due to early attack, and follicle rupture
- HYPOTHYROID in long-term
- Follicles, lymphocytes, and Hurthle cell change
246
Q
What do you see in A? B?
A
- A: duodenal peptic ulcer in pt with Zollinger-Ellison Syndrome -> punched-out lesion
- B: pancreatic gastrinoma that caused it
1. White/tan color to the tumor (can get hemorrhage if they get big enough)
248
Q
What is the “buffalo hump” mnemonic for Cushing syndrome?
A
- Buffalo hump
- Unusual behavior (depression, personality changes, and fatigability)
- Facial features (moon face, hirsutism in women)
- Fat accumulation (obesity)
- ACTH (and cortisol) in blood ↑; ACTH and dexamethasone test abnormalities
- Loss of muscle mass (thin legs and arms; protruding abdomen due to weak abdominal muscles)
- Overextended skin (striae with easy bruisability due to weak vessels)
- Hypertension
- Urinary cortisol ↑ and 17-hydroxycorticosteroids ↑
- Menstrual irregularities
- Porosity of bones (osteoporosis)
249
Q
What is secondary adrenal insufficiency?
A
- ACTH reduced due to hypothalamus or pituitary insult
- Hyperpigmentation is absent because melanotropic hormone levels are low
- LOW ACTH with prompt rise in cortisol with ACTH administration
250
Q
What are the two subgroups of Cushing Syndrome?
A
-
ACTH-dependent: bilateral diffuse or nodular hyperplasia of the adrenals
1. Cushing disease (anterior pituitary): 70%; young adult F w/microadenoma (bc functioning)
2. Ectopic corticotropin syndrome: non-pituitary tumors (i.e., small cell carcinoma of lung with crush artifacts -> see attached image) -
ACTH-independent: adrenal adenoma (10%) or adrenal carcinoma (5%)
1. Cortisol high, ACTH low
252
Q
What could this be?
A
-
Adrenal cortical adenoma: mid-size cells arranged in nests and cords
1. Tumor cells have mid-size, round-oval nuclei, and abundant granular eosinophilic cytoplasm - 29-y/o female with VIRILIZING (masculinization) symptoms, in this case
253
Q
What is this?
A
- Struma ovarii = monodermal TERATOMA of ovary, composed mainly (>50%) of adult thyroid tissue (see histo image on the right)
- May functionally cause thyrotoxicosis
- Adenomas are COMMON; 5% are malignant
- All different parts look different, so all different types of tissue
254
Q
28 year old female presented with a history of hypokalemia and hypertension. CT of the abdomen showed a 2.4 cm mass of the left adrenal and normal right adrenal. The patient underwent left adrenalectomy. Grossly the adrenal appeared normal sized, with a 2.0 cm nodule seen compressing adjacent normal adrenal. The cut surface of the lesion was golden yellow. Microscopically, the nodule appeared to arise from the cortex, with compression of a rim of normal adrenal tissue. The cells of the nodule were large, clear cells with characteristic microvesicular cytoplasm, mimicking the zona fasciculata of the normal adrenal. What is the diagnosis?
A
Conn Syndrome
257
Q
What is this?
A
- ACTH-independent hyperplasia (primary cortical hyperplasia) -> very uncommon
- Macronodular: typically >3mm -> almost entirely replaced by prominent nodules of various sizes
- Typically sporadic, but association with McCune-Albright (GNAS mutations)
- Cortisol is regulated by non-ACTH hormones
- Mix of lipid poor and lipid rich cells b/t nodules have microscopic nodularity (vs diffuse hyperplasia which does not)
258
Q
What do you see here?
A
-
Pituitary infarct: high power view of coagulative necrosis of all the pituitary parenchymal cells
1. Only viable cells are erythrocytes, leukocytes and a few endothelial cells - Really really pink celss are RBCs
- Inflam cells are there to help clean up the mess
259
Q
What 2 layers of the adrenal do you see here? What hormones do they produce?
A
- RETICULARIS (top): estrogens and androgens
- MEDULLA (bottom): epinephrine and NE
1. Neuroectodermal origin
262
Q
How does insulin affect the liver?
A
- REDUCES the production of glucose in the liver
264
Q
What do you see here?
A
- Adamantinomatous craniopharyngioma
- Squamous epithelium
- Compact, lamellar “WET KERATIN”
- Dystrophic calcification
- Cholesterol-rich, thick brownish-yellow fluid (“MACHINE OIL”) in cysts
265
Q
What do you see here?
A
- Nodular glomerulosclerosis: Kimmelstiel-Wilson lesion
- Nodules of pink, hyaline material form in regions of glomerular capillary loops in the glomerulus
- Due to a marked INC in mesangial matrix from damage as a result of non-enzymatic glycosylation of proteins
266
Q
MEN-2B
A
- Thyroid – medullary carcinoma in the first two decades of life
- Adrenal medulla – get pheochromocytomas
- Difference from MEN-2A: NO HYPER-PTH
1. Extra-endocrine manifestations: ganglioneuromas, marfanoid habitus (long axial skeleton, and hyperflexible joints) - Histo of ganglioneuroma attached: ganglion cells and schwann cells
