Pathology Iii Endocrine

Front 1

Hx of radiation exposure

Back 1

Think cancer, specifically Papillary carcinoma of thyroid

Front 2

cold, warm, hot thyroid nodules def.?

Back 2

Warm = functional, avidity for isotope in the lesion same as surrounding glands (normal)

Hot = hyperfunctional, traps more isotope than surrounding glands

Cold = hypofunctional, less isotope is trapped than in surrounding glands

Front 3

Hot vs Cold nodules

Back 3

“Hot” nodules are almost always benign.
80% of “cold” nodules are benign.

Front 4

solid thyroid lesions vs. cystic lesions

Back 4

Solid lesions are more worrisome than cystic lesions (which usually are adenomatous nodules umdergoing cystic degeneration).

Front 5

Papillary Carcinoma of thyroid

Back 5

Papillary carcinoma
a. Epidemiology
i. Account for 80% of malignant thyroid tumors
ii. Females> males; age 20-50
iii. Risk factor: radiation exposure
b. Micro
i. The tumor typically exhibits a papillary pattern
ii. Occasional psammoma bodies
iii. Characteristic nuclear features
. Clear "Orphan Annie eye" nuclei . Nuclear grooves
. Intranuclear cytoplasmic inclusions
c. Lymphatic spread to cervical nodes is common
d. Treatment
1. Resection is curative in most cases
11. Radiotherapy with iodine 131is effective for metastases
e. Prognosis: excellent; 20-year survival =90%

Front 6

Papillary Carcinoma of thyroid: histo

Back 6

Papillary structures w/ enlarged nuclei
Optically clear “Orphan Annie” nuclei (A)
Nuclear grooves (B)

Also, psamomma bodies

Front 7

What diseases have psammoma bodies?

Back 7

Dystrophic Calcification
Meningioma
Cysadenocarcinoma of the Ovary
Papillary Carcinoma of the Thyroid

Front 8

What are risk factors for papillary carcinoma of the thyroid?

Back 8

Irradiation of the head and neck areas during the first two decades of life
There is also a slightly increased risk of carcinoma in patients with Hashimoto thyroiditis

Front 9

What is an encapsulated tumor likely to be?

Back 9

The presence of a thick and irregular capsule tends to favor a follicular carcinoma over an adenoma on gross examination.

Front 10

Follicular carcinoma

Back 10

a. Accounts for 15% of malignant thyroid tumors
b. Females> males; age 40-60
c. Hematogenous metastasis to the bones or lungs is common

Front 11

Follicular carcinoma: Histology

Back 11

Small, closely packed neoplastic follicles containing colloid.
No well-formed papillae or psammoma bodies are present.

Front 12

Medullary carcinoma

Back 12

a. Accounts for 5% of malignant thyroid tumors
b. Arises from C cells(parafollicular cells) and secretes calcitonin
c. Micro: nests of polygonal cells in an amyloid stroma
d. Minority (25%) are associated with MEN II and MEN III syndromes (see Multiple
Endocrine Neoplasia Syndromes)

Front 13

Medullary carcinoma: gross and histo

Back 13

Round/polygonal tumor cells with abundant amphophilic granular cytoplasm; some cells have clear cytoplasm.
Stromal amyloid deposits, derived from calcitonin or its precursor molecules, is also present. //

The tumor is nodular and well circumscribed.

Front 14

Familial Medullary carcinoma

Back 14

May present with:

MENII (IIa or sipple): along with pheochromocytoma and parathyroid adenoma.//

MENIII (IIb): along with pheochromocytomas and neurofibromas.//

Front 15

What gene is involved in MEN II and MEN III?

Back 15

RET proto-onco gene

Front 16

Thyroid cancer frequency

Back 16

Papillary cancer ~70%
Follicular carcinoma ~20%
Medullary ~5%
Anaplastic ~5%.

ALSO SEE SLIDE 22 FOR COMPARISON

Front 17

Hashimoto thyroiditis

Back 17

a. Definition: chronic autoimmune disease characterized by immune destruction of
the thyroid gland and hypothyroidism
b. Most common noniatrogenic/nonidiopathic cause of hypothyroidism in the
United States
c. Clinical presentation
i. Females> males; age 40-65
ii. Painless goiter
iii. Hypothyroidism
iv. Initial inflammation may cause transient hyperthyroidism (hashitoxicosis)
d. Gross: pale enlarged thyroid gland .
e. Micro
i. Lymphocytic inflammation with germinal centers
ii. Epithelial "Hiirthle cell" changes
f. May be associated with other autoimmune diseases (SLE,RA, SS [Sjogren syndrome],
etc.)
g. Complication: increased risk of non-Hodgkin lymphoma (NHL) B-celllymphoma

Front 18

Hashimoto thyroiditis: Histo

Back 18

Histologic features:
Destruction and atrophy of thyroid follicles
Lymphocytic and plasmacytic infiltration of the thyroid stroma with lymphoid follicles; germinal centers can also be seen.

Front 19

Discuss the pathogenesis of Hashimoto disease.

Back 19

CD4+ T cells targeted at thyroid antigens are activated after an
infection or following exposure of sequestered thyroid antigens.
Activated CD4+ T cells stimulate B cells to produce antibodies
and CD8+ T cells to destroy the gland parenchyma.

Front 20

Hashimoto thyroiditis: More Histo features

Back 20

Oxyphilic cell metaplasia of follicular epithelium (Hürthle cells), with pink, slightly granular cytoplasm.

Front 21

Why does the cytoplasm of Hürthle cells looks granular?

Back 21

Increased number of mitochondria

Front 22

What autoantibodies are present Hashimoto thyroiditis?

Back 22

High titers of thyroid peroxidase, antithyroglobulin antibodies and TSH receptor antibodies
Iodine transporter antibodies may also be seen

Front 23

What is the effect of the anti-TSH receptor antibodies in
Hashimoto thyroiditis? …in Graves disease?

Back 23

In Hashimoto thyroiditis they block the action of TSH and contribute to hypothyroidism.
//
In Graves disease they mimic TSH and result in hyperthyroidism.

Front 24

In what population is Hashimoto thyroiditis most prevalent?

Back 24

Women, between 45 - 65 years old, often presenting with some degree of hypothyroidism.

Front 25

Patient with Hashimoto thyroiditis are at increased risk to develop what malignancy?

Back 25

B-cell lymphomas

Front 26

Cushing syndrome

Back 26

a. Definition: diseasecharacterized by increased levels of glucocorticoids
b. Etiology
i. Iatrogenic (exogenous corticosteroids)
ii. Pituitary corticotroph adenoma (Cushing disease) . Adenoma produces ACTH . ElevatedACTH
. Cortisol suppression with high-dose dexamethasone
iii. Adrenocortical adenoma
. Adenoma produces cortisol . DecreasedACTH . No cortisol suppression with dexamethasone
IV. Paraneoplastic syndrome . Small-cell lung cancer producing ACTH
ElevatedACTH
. No cortisol suppression with dexamethasone

Front 27

Cushing syndrome etiologies

Back 27

Adrenal adenomas account for 5-10% of cases of Cushing syndrome in adults and are the most common cause in children <8 years old.
Other etiologies include ectopic ACTH production and pituitary adenomas. Most common cause is exogenous glucocorticoids.

Front 28

dexamethasone suppression test

Back 28

High dose dexamethasone suppression test (suppression
would rule out pituitary cases) and plasma ACTH levels
(low in adrenal neoplasia, high in ACTH secreting tumors).

Front 29

Adrenal Cortical Adenoma

Back 29

Clear tumor cells adjacent to a rim of non-tumorous adrenal
Regular uniform large cells with ample clear cytoplasm, filled with lipid.
 Neoplastic cells form sheets, nests or cords.

Front 30

Conn Syndrome

Back 30

Primary hyperaldosteronism (Conn syndrome)
a. Definition: adrenocortical adenoma producing aldosterone
b. Clinical feature: hypertension
c. Lab:hypokalemia, elevated aldosterone, and decreased renin

Front 31

How does hypokalemia
manifest?

Back 31

Muscle weakness and
fatigue.

Front 32

This photograph suggests a cortical adenoma associated with Conn syndrome, not with Cushing syndrome. Why?

Back 32

The adjacent adrenal cortex is not atrophic, as would be expected in Cushing syndrome. Adenomas associated with hyperaldosteronism do not usually suppress ACTH secretion.

Front 33

What are some some causes of hypercalcemia?

Back 33

Parathyroid-related: adenomas, hyperplasias, lithium, MEN
Malignancy-related: SCC, bone metastases, leukemia,
Vitamin D-related: vitamin D intoxication
High bone turnover: hyperthyroidism, immobilization
Renal failure

Front 34

What would you expect the serum levels of PTH to be like if you suspected hypercalcemia from a squamous cell cancer?

Back 34

PTH should be very low or undetectable, PTHrP should be high.

Front 35

What are the clinical manifestations of primary hyperparathyroidism?

Back 35

Osteitis fibrosa cystica, kidney stones (“stone and bone” disease), mental status and mood changes, hyperactive reflexes, chronic pancreatitis and constipation are among the frequent manifestations.
Hypercalcemia and hypophosphatemia are the characteristic serum abnormalities.

Front 36

Parathyroid Adenoma

Back 36

 Parathyroid adenoma is typically an encapsulated, ovoid to round, soft tissue mass with homogeneous cut surface. About 10% occur in anomalous locations (mediastinum, pericardium, etc).

Front 37

What is the most common bone
disease associated with parathyroid
adenoma?

Back 37

Osteopenia

Front 38

Parathyroid Adenoma: Histo

Back 38

Chief cells (versus oxyphilic cells) are the dominant cell type in most adenomas and are often arranged in sheets, cords, nests, or glandular formations
Stromal fat cells are absent within an adenoma (in normal parathyroid glands, 50% of the gland is constituted by adipocytes)

Front 39

Early bone changes in hyperparathyroidism

Back 39

Abnormal cavities of osteoclastic resorption in the bone trabeculae accompanied by patchy marrow fibrosis.
Burrowing of an overzealous osteoclast into the bone matrix giving the lesion a tunneled (or “moth-eaten”) appearance

Front 40

Advance bone changes in hyperparathyroidism

Back 40

In advanced cases, multiple osteolytic lesions filled by giant cells, macrophages, plump fibroblasts and hemorrhage (called “brown tumors of hyperparathyroidism” on gross examination) are seen

Front 41

Discuss the etiology of primary hyperparathyroidism.

Back 41

Primary hyperparathyroidism is a syndrome caused by excessive secretion of PTH
Most commonly by a solitary parathyroid adenoma (80% of all cases),
or primary hyperplasia of all parathyroid glands (15% of all cases)
and rarely, a parathyroid carcinoma.

Front 42

Pheochromocytoma

Back 42

Pheochromocytoma
a. Definition: uncommon tumor of the adrenal medulla, which produces catecholamines
b. Clinical presentation
i. Severe headache
ii. Tachycardia and palpitations
iii. Diaphoresis and anxiety
iv. Hypertensive episodes
c. "Rule of 10's"
1. 10% occur in children
11. 10% are bilateral
iii. 10% occur outside the adrenal gland
iv. 10%are malignant
v. 10% are familial (MEN II and III)
d. Diagnosis: elevated urinary vanillylmandelic acid (VMA)

Front 43

In Pheochromocytoma, what operative complications should you anticipate and try to prevent?

Back 43

Hypertensive crisis, arrhythmias and lactic acidosis.

Front 44

Pheochromocytoma: gross

Back 44

Gross features
The tumor may acquire a brown color when exposed to dichromate fixatives (Zenker's solution) due to oxidation of stored catecholamines.

Front 45

Pheochromocytoma: Histo

Back 45

Low power view of the tumor showing tumor cells surrounded by fibrous septae (zellballen pattern)
Pleomorphism is also appreciated

Front 46

What laboratory tests can be used for the diagnosis of this tumor?

Back 46

24-hour urine can be assayed for vanillylmandelic acid (VMA),metanephrine (MN)
urinary free catecholamines (UFC) which are secreted by many pheochromocytomas.
The combined use of these tests is recommended.

Front 47

Pituitary Adenoma

Back 47

Can expand and erode the sella turcica, impinging on the optic chiasm to produce bitemporal hemianopsia.
May lead to increased intracranial pressure - manifests as headaches, nausea and vomiting.

Front 48

What are prolactinomas?

Back 48

The most common type of functional pituitary adenoma
In women of childbearing age, prolactinomas manifest clinically with amenorrhea or galactorrhea.
These tumors have been successfully treated with dopamine agonists such as bromocriptine, which inhibit prolactin secretion and produce tumor atrophy.

Front 49

What is the clinical presentations of a growth hormone (GH) adenoma.

Back 49

May produce gigantism in prepubertal children and acromegaly in the adults.
These patients also tend to have visual field defects because GH adenomas tend to be fairly large by the time they are discovered.