thyroid neoplasms

Question 1

goiter

Answer 1

Enlargement of the thyroid, or goiter is caused by impaired synthesis of thyroid hormone, which is most often the result of dietary iodine deficiency

Question 2

Diffuse Nontoxic (Simple) Goiter

Answer 2

enlargement of the entire gland without producing nodularity.

Endemic- where low iodine
- eating cabbage, cauliflower, Brussels sprouts, turnips, and cassava), has been documented to be goitrogenic

Sporadic goiter occurs less frequently than does endemic goiter. There is a striking female preponderance and a peak incidence at puberty or in young adult life.

Question 3

Impairment of thyroid hormone synthesis leads to

Answer 3

a compensatory rise in the serum TSH level, which, in turn, causes hypertrophy and hyperplasia of thyroid follicular cells and, ultimately, gross enlargement of the thyroid gland.

Question 4

Clinical Course of a simple goiter

Answer 4

most are clinically euthyroid
mass effects major issue (push on trachea, suppress SVC, etc)

serum T3 and T4 levels are normal, the serum TSH is usually elevated or at the upper range of normal, as is expected in marginally euthyroid individuals.

Question 5

Multinodular Goiter

Answer 5

recurrent episodes of hyperplasia and involution combine to produce a more irregular enlargement of the thyroid, termed multinodular goiter.

Multinodular goiters produce the most extreme thyroid enlargements and are more frequently mistaken for neoplasms than any other form of thyroid disease

Question 6

Clinical course of a multinodular goiter.

Answer 6

mostly mass effects
. In addition to the obvious cosmetic effects, goiters may cause airway obstruction, dysphagia, and compression of large vessels in the neck and upper thorax (superior vena cava syndrome).

most patients are euthyroid

sometimes, an autonomous nodule may develop within a long-standing goiter and produce hyperthyroidism (toxic multinodular goiter). This condition, known as Plummer syndrome, is not accompanied by the infiltrative ophthalmopathy and dermopathy of Graves disease.

Question 7

Dominant nodules in a multinodular goiter can present as

Answer 7

a “solitary thyroid nodule”, mimicking a thyroid neoplasm. A radioiodine scan demonstrates uneven iodine uptake (including the occasional “hot” autonomous nodule)

Question 8

solitary thyroid nodule

Answer 8

is a palpably discrete swelling within an otherwise apparently normal thyroid gland

4x more in women

major concern: possible malignant neoplasm

most are localized, nonneoplastic lesions or benign neoplasms such as follicular adenoma.

benign neoplasms outnumber thyroid carcinomas by a ratio of nearly 10 : 1.

Question 9

likelihood of a thyroid nodule to be neoplastic

Answer 9

More likely to be neoplastic:

• Solitary nodules
• younger patients
• males
• A history of radiation treatment to the head and neck region
• Cold nodules

(Functional nodules that take up radioactive iodine in imaging studies (hot nodules) are much more likely to be benign than malignant.)

Question 10

Thyroid adenomas

Answer 10

typically discrete, solitary masses, derived from follicular epithelium, and hence they are also known as follicular adenomas.

a small subset produces thyroid hormones and causes clinically apparent thyrotoxicosis. Hormone production in functional adenomas (“toxic adenomas”) is independent of TSH stimulation.

Question 11

thyroid adenoma morphology

Answer 11

solitary, spherical, encapsulated. (distinguishes from multinodular)

Question 12

what does hurthle cell change mean?

Answer 12

lots of eosinophilic cytoplasm

metaplastic change in thyroid

unpredictable

Question 13

follicular adenomas

Answer 13

tend to be cold nodules, unilateral painless masses

Careful evaluation of the integrity of the capsule is therefore critical in distinguishing follicular adenomas from follicular carcinomas

definitive dx can only be made after histologic exam of the resected specimen

Question 14

major subtypes of thyroid carcinoma

Answer 14

Papillary carcinoma (>85% of cases)
Follicular carcinoma (5% to 15% of cases)
Anaplastic (undifferentiated) carcinoma (<5% of cases)
Medullary carcinoma (5% of cases)

Question 15

Pathogenesis of thyroid carcinoma

Answer 15

Genetic alterations in the three follicular cell–derived malignancies are in growth factor receptor signaling pathways

Question 16

environmental factors in thyroid carcinomas

Answer 16

The major risk factor predisposing to thyroid cancer is exposure to ionizing radiation, particularly during the first 2 decades of life.

In keeping with this, there was a marked increase in the incidence of papillary carcinomas among children exposed to ionizing radiation after the Chernobyl nuclear disaster in 1986.

Deficiency of dietary iodine (and by extension, an association with goiter) is linked with a higher frequency of follicular carcinomas.

Question 17

papillary carcinoma histology

Answer 17

eyeballs of orphan annie

“optically clear nuclei”

Question 18

psammoma bodies

Answer 18

concentric lamellated calcified structures, observed most commonly in papillary thyroid carcinoma (PTC), meningioma, and papillary serous cystadenocarcinoma of ovary

Question 19

papillary carcinoma staining

Answer 19

RET immunostaining

Question 20

Clinical course for papillary carcinoma

Answer 20

Most conventional papillary carcinomas present as asymptomatic thyroid nodules, but the first manifestation may be a mass in a cervical lymph node. Interestingly, the presence of isolated cervical nodal metastases does not have a significant influence on prognosis, which is generally good

Papillary carcinomas are cold masses on scintiscans

Excellent prognosis

youngest presentation

Question 21

Follicular Carcinoma

Answer 21

more frequent in areas with dietary iodine deficiency
3:1 women

between 40-60 years of age

Question 22

Clinical Course of follicular carcinoma

Answer 22

present as slowly enlarging painless nodules.

Most frequently they are cold nodules on scintigrams, although rare, better-differentiated lesions may be hyperfunctional, take up radioactive iodine and appear warm on scintiscan.

little propensity for invading llymphatics, but vascular dissemination is common with metastases to bone, lungs, liver, and elsewhere

prognosis depends on invasion and stage at presentation.

Question 23

treatment of follicular carcinoma

Answer 23

total thyroidectomy followed by the administration of radioactive iodine, which can be used to identify metastases and to ablate such lesions.

In addition, because any residual follicular carcinoma may respond to TSH stimulation, patients are usually treated with thyroid hormone after surgery to suppress endogenous TSH levels. Serum thyroglobulin levels are used for monitoring tumor recurrence, because this thyroid protein should be barely detectable in a patient who is free of disease.

Question 24

Molecular diagnosis - follicular carcinomas

Answer 24

associated with acquired mutations that activate RAS or the PI-3K/AKT arm of the receptor tyrosine kinase signaling pathway

Question 25

Anaplastic (Undifferentiated) Carcinoma

Answer 25

undifferentiated tumors
mortality rate approaching 100%
older people- mean age 65 yrs

Approximately a quarter of patients with anaplastic thyroid carcinomas have a past history of a well-differentiated thyroid carcinoma

Question 26

Clinical Course of anaplastic carcinoma

Answer 26

rapidly enlarging bulky neck mass
In most cases, the disease has already spread beyond the thyroid capsule into adjacent neck structures or has metastasized to the lungs at the time of presentation.

Symptoms related to compression and invasion, such as dyspnea, dysphagia, hoarseness, and cough, are common.

no effective therapies
usually death in less than a year

Question 27

Medullary Carcinoma

Answer 27

neuroendocrine neoplasms derived from the parafollicular cells, or C cells.

secrete calcitonin, the measurement of which plays an important role in the diagnosis and postoperative follow-up of patients.

(classically find amyloid)

Question 28

Clinical Course of medullary carcinoma- sporadic

Answer 28

Sporadic cases- most often a mass in the neck, sometimes associated with dysphagia or hoarseness.

In some instances, the initial manifestations are those of a paraneoplastic syndrome caused by the secretion of a peptide hormone (e.g., diarrhea due to the secretion of VIP, or Cushing syndrome due to ACTH).

Notably, hypocalcemia is not a prominent feature, despite the presence of raised calcitonin levels. In addition to circulating calcitonin, secretion of carcinoembryonic antigen by the neoplastic cells is a useful biomarker, especially for presurgical assessment of tumor load and in calcitonin-negative tumors.

Question 29

Clinical Course of medullary carcinoma- familial

Answer 29

may come to attention because of symptoms localized to the thyroid or as a result of endocrine neoplasms in other organs (e.g., adrenal or parathyroid glands). Medullary carcinomas arising in the context of MEN-2B are generally more aggressive and metastasize more frequently than those occurring in patients with sporadic tumors, MEN-2A, or FMTC.

Question 30

what do we do with asymptomatic MEN-2 patients carrying germline RET mutations?

Answer 30

they are offered prophylactic thyroidectomy as early as possible to prevent the otherwise inevitable development of medullary carcinomas

Question 31

thyroid neoplasms- key concepts

Answer 31

most are solitary and non-neoplaastic

follicula adenoma- most common benign neoplasm

papillary carcinoma- most common malignancy

RAS/ Pl-3K gene- follicularcarcinoma
RET/ BRAF- in papillary
RET- in medullary

follicular adenomas and carcinomas- well-differentiated; latter has capsular and/or vascular invasion

papillary carcinomas– ground-glass nuclei, pseudoinclusions, etc. Psamoma bodies

anaplastic- dedifferentiation, highly aggressive, lethal

medullary- arise from parafollicular C cells. Sporadic or familial. amyloid deposits

Question 32

plummer syndrome

Answer 32

sometimes, an autonomous nodule may develop within a long-standing goiter and produce hyperthyroidism (toxic multinodular goiter). This condition, known as Plummer syndrome, is not accompanied by the infiltrative ophthalmopathy and dermopathy of Graves disease.