Endo Path, Lecture 2: Pathology Of The Thyroid

Front 1

Thyroid “vocabulary words”

Hot Scan:

Cold Scan:

Hurthle:

Follicular:

Goiter:

Back 1

Scan: radionuclide scan
“hot”: actively take up iodine
“cold”: inactive (relative to normal thyroid)

Hurthle: used as synonym for oxyphyl or eosinophilic change; due to accumulation of acidic mitochondria in cytoplasm

Follicular: refers to things that make follicles, as well as tumors that are derived from follicular cells

Goiter: enlargement of thyroid for any reason

Front 2

Thyroglossal duct cyst:

Back 2

a developmental/congential abnormality

Can present at any age, but most often in kids or young adults

Remnant of descent: midline in the neck; if only partially obliterated, can form cyst

Variable lining: squamous, respiratory, or thyroid epithlium

Can be intensely inflamed or infected, may form abscesses, sinuses, or fistula tracts

May involve the hyoid bone; resected with bone to prevent recurrence
Rarely the site of thyroid tumors

Front 3

Other Thyroiditis variants

Back 3

Subacute granulomatous thyroiditis, or “deQuervain’s thyroiditis”

Riedel’s thyroiditis

Front 4

Other Thyroiditis variants

Subacute granulomatous thyroiditis, or “deQuervain’s thyroiditis”

Back 4

Classic presentation includes pain, unlike Hashimoto’s

Also, self-limited process

Front 5

Other Thyroiditis variants

Riedel’s thyroiditis

Back 5

A fibrosing process, can extend to surrounding neck structures, to simulate tumors

Part of a family of fibrosing diseases: retroperitoneal fibrosis, sclerosing mediastinitis, sclerosing cholangitis of liver

Front 6

Diffuse hyperplasia, toxic“Grave’s disease”

Clinical triad of:

Back 6

- Thyrotoxicosis with diffuse hyperplasia

- Ophthalmopathy: proptosis, upper lid retraction, lid lag,diplopia, and increased intraocular pressure

- Dermopathy: edemetaous skin change, usually in the lower extremities

Individual cases may have any combination of three, and at different times

Front 7

Diffuse hyperplasia, toxic“Grave’s disease”

Epidemiology:

Back 7

Common: 0.4% of population
F:M ratio 5:1, peaks in third, fourth decades
Associated with HLA DR3, also other autoimmune diseases

Front 8

Pathogenesis of Grave’s disease

Back 8

There is a postulated defect in antigen-specific T-cell suppressor function

Leads to production of auto-antibodies against the TSH receptor, that are directly causative of the disease

Antibody stimulation of the TSH receptor leads to both thyroid growth, and hyperfunction

There may also be anti-microsomal antibodies, that can cross react with the ocular muscles to produce the ophthalmopathy

Front 9

Nodular hyperplasia:“multinodular goiter”

General Features:

Clinical Presentation:

Back 9

Very common

This may be a late phase of diffuse non-toxic goiter, but may arise de novo

Can be extreme enlargement: 2 kgs or more

Most patients euthyroid, rarely mild hyperthyroid

Similar demographics as non-toxic goiter, but occurs in older individuals

Various clinical presentations:
- Symmetric enlargement: pressure symptoms

- Asymmetric: may simulate a neoplasm

Front 10

Nodular hyperplasia:“multinodular goiter”

Pathogenesis:

Back 10

Subclinical iodine deficiency

Dietary goitrogens

Low levels of stimulating antibodies

Front 11

Benign neoplasm: Follicular adenoma

Features and Morphologic Criteria:

Back 11

Usually presents as a solitary cold nodule

Most are small (< 4.0 cm)

Morphologic criteria:
Completely surrounded by a fibrous capsule

Difference in architecture inside and outside of nodule

Lack of other nodules in the thyroid

Nuclear atypia and mitotic figures can be seen in adenomas

There can be varying amounts of degenerative changes in ________: cystic change, hemorrhage, fibrosis, calcifications, and Hurthle cell change

Front 12

Thyroid

Malignant neoplasms:

Generalities (Epidemiology)

Back 12

2-3:1 female:male ratio

4-7% of adults in U.S. have thyroid nodules, many fewer cancers (esp. clinically relevant ones).

So which nodules are most suspect?
- More suspicious in men, the young, and when solitary

- Most cancers are “cold” on scan

- Most cancers are solid

Nodules often evaluated first with needle aspiration cytology

Front 13

Papillary carcinoma

Papillary - definition:

Back 13

papillae: [derived from Latin for nipple, from diminutive of papula] noun: protuberance, small projecting part or bud; nipple-like

papillary: adjective form

Front 14

Papillary carcinoma

General Features (Epidemiology)

Back 14

Accounts for about 80% of thyroid carcinomas, even greater percentage of cases under age 40

Common, up to 10% in some detailed autopsy studies (subclinical cases)

Most common in the 3rd to 5th decades of life

2-4:1 F:M ratio

Associated with childhood neck irradiation; also linked to iodine excess, and some suggestion of increased cases with thyroiditis

Derived from follicular epithelial cells

Ret-PTC mutations

Can present as an incidental finding, painless lump, or as neck lymphadenopathy; only rare cases have local invasion signs at presentation

Front 15

Papillary carcinoma

Histological Presentation:

Look for _______ body and ________

Back 15

“psammoma body”

and

Intranuclear cytoplasmic inclusions and grooves in cytology prep

Front 16

Papillary carcinoma

Behavior:

Bad prognostic signs may include:

Back 16

Behavior:
- Indolent in most cases: >90% 20 year survival

- Up to 40% of patients have lymph node metastases, with no prognostic importance

- 5-7% may develop bone or lung metastases; can still be treated with radioactive iodine

- death in rare cases is usually due to local invasion

Bad prognostic signs may include:
- Age: patients> 45 or 50 years old do worse

- Extra-thryroidal invasion

- Abnormal DNA content: aneuploidy

- De-differentiated variant

Front 17

Follicular thyroid carcinoma

Histological Presentation:

Look for _______ and _________

Back 17

vascular invasion

and

capsular invasion

Front 18

Follicular thyroid carcinoma

Back 18

5-10% of thyroid carcinoma; higher in areas of iodine deficiency

Older age than papillary; 5th and 6th decades; F>M

Many cases: PAXX8-ppar gamma fusion

Clinically presents as a solitary nodule, an enlarging mass, or with metastases, such as a pathologic fracture

Lymph node metastases essentially do not occur.

Metastases are blood-borne, to lungs, liver, and bones

Front 19

Medullary thyroid carcinoma

Back 19

5-10% of thyroid carcinoma

Derived from C-cells; in the family of neuroendocrine carcinomas

80% are sporadic, 5th to 6th decades, solitary

10-20% are familial: young (2nd to 3rd decade), multiple, preceded by C-cell hyperplasia

- MEN IIA or “Sipple syndrome:” medullary thyroid carcinoma, adrenal pheochromocytomas, parathyroid carcinomas

- MEN IIB or MENIII: medullary carcinoma, pheochromocytoma, mucosal neuromas

- Both autosomal dominant, chromosome 10 defects in RET gene

Front 20

T/F

Medullary thyroid carcinoma

Most secrete calcitonin (may excrete others)

Back 20

True

Front 21

Medullary thyroid carcinoma:

Histology:

Look for ______ and _______ (with a certain stain) and _________ (on EM)

Back 21

Amyloid

and Calcitonin (via calcitonin immunostain)

Neurosecretory granules by EM

Front 22

Prognosis of medullary carcinoma

Sporadic:

Familial:

Back 22

Sporadic: usually discovered later, larger, and may have metastases; mean survival of about 5 years

Familial: with screening, should be found earlier, and so in some studies, up to 85% 10 year survival. In contrast, some studies suggest that MEN IIB cases do worse

For patients develop both regional node metastases, and visceral organ spread, death occurs over several years

Front 23

Histological Features for Papillary thyroid carcinoma:

Back 23

Fibrovascular cores
Nuclear clearing
Inclusions
Grooves

Front 24

Autoimmune thyroiditis:

Hashimotos thyroiditis

Key Features:

Back 24

Middle age (30-50); rarely occurs in children as well

Female:male - 10:1

Associated with other autoimmune disease: lupus, rheumatoid arthritis, Sjogren’s syndrome, Schmidt’s syndrome (autoimmune attack of pancreas, pituitary, adrenal and thyroid gland

Linked to HLA DR5

Front 25

Autoimmune thyroiditis: Hashimoto’s thyroiditis

Classic Presentation:

Back 25

Classic presentation: painless goiter with hypothyroidism

Rarely: transient hyperthyroidism, called “Hashitoxicosis;” reflects release of thyroid hormones due to destruction of follicles

Front 26

Pathogenesis of Hashimoto’s thyroiditis

Back 26

Postulated deficiency in antigen-specific T-suppressor cell clone, leading to:

- Unregulated cytotoxic T-cell attack on follicular epithelium

- Unregulated T-cell support for B-cell production of autoantibodies

- Variety of autoantibodies; pathogenic? Versus secondary to damage:
-- Anti-TSH receptor (thyroid growth)
-- Anti-microsome
-- Anti-thyroglobulin
-- Antibodies against follicular cell membranes

Front 27

Pathogenesis of Hashimotos thyroiditis:

Role for Follicular cell HLA-DR expression?

Back 27

Viral infection of thyroid leads to lymphocytes in the thyroid

-->

Lymphocytes produce gamma interferon

-->

Gamma interferon causes follicular cells to express HLA-DR

-->

Follicular cells expressing HLA-DR can present self antigens, and become a target for cell-mediated immunity

Front 28

Classic Hashimoto Histological Presentation:

Back 28

- Diffuse lymphocytic invasion
- Extensive fibrous tissue replacement of normal thyroid