B97 Tumors of the thyroid gland

Question 1

What are the tumors of the thyroid gland.

Answer 1

Diffuse multinodular goiter

Adenomas

• nonfunctional adenoma <– the vast majority of thyroid tumors.
• secretory, toxic adenomas

Carcinomas, less than 1% of solitary nodules.

• Papillary
• Follicular
• Medullary
• Anaplastic

Metastatic lymphoma. 1%

Question 2

What are some basic principles of neoplasias in the thyroid gland.?

Answer 2

Both benign and malignant neoplastic tumors of the thyroid generally present as solitary nodules.

The vast majority are benign

• follicular adenomas
• non-neoplastic conditions
  
  • simple cysts, nodular hyperplasia, or a foci of thyroiditis.

Only about 1% are malignant.

There are characteristics strongly associated with benign or malignant types, but the final determination can only be decided by histology.

1. Solitary nodules - Are more likely to be neoplastic than are multiple nodules.
2. Nodules in younger patients - Are more likely to be neoplastic than are those in older patients.
3. Nodules in males - Are more likely to be neoplastic than are those in females.
4. A history of radiation treatment to the head and neck region - Is associated with an increased incidence of thyroid malignancy.
5. Nodules that take up radioactive iodine in imaging studies - Are less likely to be malignant.

Question 3

What is the main radiologic method of distinguishing benign or malignant nodule?

What are other examination techniques to dteremine what kind of nodule it is?

Answer 3

Radioactive Iodine uptake and scintiography is a major tool.

• High uptake = a Hot nodule, highly physiologically active, indicates Graves disease or Nodular Goiter. Hot nodules are virtually never malignant.
• Low uptake = Cold nodule, indicates Carcinoma or adenoma and must be biopsied.

Other techniques: Ultrasound, fine needle aspiration or core biopsy.

Determination of malignant vs. benign nodules requires examination of the capsule, and thus can only be conclusively determined after surgical resection and examination.

Question 4

Describe the gross morphology and histology of Follicular Adenomas

Answer 4

• Benign neoplasia of the follicular epithelium
• Usually solitary and nonfunctional.
• They are solitary, spherical, and encapsulated, and cause compression of the surrounding thyroid tissue.
  
  • Encapsulation is the critical feature. A well formed and fully in-tact capsule is the distinguishing feature for follicular adenoma from multinodular goiter, and from follicular carcinoma.
• Histologically, the cells within the capsulated adenoma look like normal thyroid tissue. With circular, normal sized follicles, and cuboidal epithelial cells.
• The epithelial cells may or may not undergo Hurthle cell change, and would be called a hurthle cell adenoma, but it has the exact same clinical behavior as a normal follicular adenoma.
• The epithelial cells may also have focal areas of noticeable aplasia or pelomorphism. but as long as the tumor has a very clear, non-penetrated capsule, it is a benign adenoma.

Question 5

What is a toxic adenoma and what are important mutations involved in their development?

Answer 5

A Small percentage of follicular adenomas that produce thyroid hormone

They cause thryotoxicosis, thus are called toxic adenomas.

Toxic adenomas are not precancerous lesions and do not transform, but their occurence indicates increased risk for a separate development of thyroid follicular carcinoma.

Development:

Activating mutations to the TSH receptor or in the gene coding for the alpha subunit of Gs protein. Cause clonal expansion of the epithelial cells, and the autonomous TSH receptor produces thyroid hormone secretion.

About 20% of follicular adenomas have point mutations in the RAS family of oncogenes, whic are also seen in 50% of follicular carcinomas

This finding has raised the possibility that some adenomas may progress to
carcinomas.

Question 6

Describe the clinical presentation and prognosis of a follicular adenoma

Answer 6

Presentation:

• Presents as a painless nodule on the thyroid, usually discovered during routine physical exams.
• Very large adenomas may produce difficulty in swallowing
• Follicular adenomas are cold nodules.
• Toxic adenomas are hot nodules.

Progression:

• Excellent prognosis, do not recur, and do not metastasize
• the exception is the toxic adenomas, which have in increased risk for future development of follicular carcinoma.

Question 7

What is the etiology of Thyroid carcinoma?

What are the most and least frequent types?

Answer 7

Are about 1% of all cancers

Most occur in the elderly, but papillary thyroid carcinoma has a prediliction for childhood.

Question 8

Describe papillary carcinoma, etiology, and presentation

treatment

Answer 8

Most common form, 60%, occurs in young and old patients.

Related to prior radiation therapy or exposure to the neck.

• Forms papillary structures with neoplasitc epithelium and stroma.
• Orphan annie eyes and nuclear grooves of psuedoinclusions are the defning feature, not papillary formation.
• Psamomma bodies are present
• RET tyrosine kinase mutation

treatment: node excision, I131, total thyroidectomy.

Metastasizes via lymph, and in rare bad cases via blood to the lung.

Has best prognosis of the types of thyroid cancer, 95% 10 year survival, prognosis better if young and female.

Question 9

Describe follicular carcinoma, morphology, epidemiology, prognosis, treatment

Answer 9

5-15% of thyroid cancers, with a 3:1 ratio more common in female. Present between ages 40 and 60. Related to dietary iodine deficiency.

morphology

• can look very similar to follicular adenoma, with normal looking follicles, and stroma. Can have hurthle cells
• or can be less differentiated with few glands and mostly solid sells.
• Important part is that it has a capsule, but it invades through the capsule.

They present most often as cold nodules but in rare cases may be hot, hyperfunctional.

These types have hematogenous spread, and thus the blood vessels should be checked.

If there has been spread 10 year surv is 50%, and it has not, it is above 90%.

Treatment, surgical excision I131. Post surgical inhibition of TSH somatostatin like drugs.

Question 10

Describe anaplastic carcinoma of thyroid, epidemiology, morph, prog, treatment

Answer 10

Bulky, highly invasive, beyond the thyroid capsule into surrounding neck structures.

Cords of large, pleomorphic, highly dysplastic/anaplastic cells.

These have very bad prognosis, and aggressive local growth compromises vital neck strucutres, esophagus, trachea, vagus/phrenic nerves.

Death usually occurs within 1 year.

Occurs in elderly, again 3:1 female male.

Question 11

Medullary carcinoma, epidem, mroph, treat, prog

Answer 11

5% of thyroid cancers,

Originating form the parafolicular C-cells (calcitonin).

Secrete calcitonin which is used as a tumor marker after excision to see if it has been albated or is reappearing. It also produces amyloid deposits within the thyroid gland.

Some cases can secrete other hormones like VIP, or serotonin causing symptoms like diarrhea or flushing.

70% are sporadic, 30% are associated with MEN 2a and 2b

Both familial and sporadic cases have RET activating mutations.

Occurs in the 50s and 60s if it is sporadically, but familial cases of MEN 2a/2b can occur in children or young adults.

Multicentric C cell hyperplasia is present in the surrounding areas of the tumor, though to represent a pre-neoplastic lesion.

Treatment is surgery.

Question 12

Tumor summary notes

Answer 12

• Most thyroid neoplasms manifest as solitary thyroid nodules,
but only 1% of all thyroid nodules are neoplastic.
• Follicular adenomas are the most common benign neoplasms,
while papillary carcinoma is the most common
malignancy.
• Multiple genetic pathways are involved in thyroid carcinogenesis.
Some of the genetic abnormalities that are fairly
unique to thyroid cancers include PAX8/PPARG fusion
(in follicular carcinoma), chromosomal rearrangements
involving the RET oncogene (in papillary cancers), and
mutations of RET (in medullary carcinomas).
• Follicular adenomas and carcinomas both are composed of
well-differentiated follicular epithelial cells; the latter are
distinguished by evidence of capsular and/or vascular
invasion.
• Papillary carcinomas are recognized based on nuclear features
(ground glass nuclei, pseudoinclusions) even in the
absence of papillae. These neoplasms typically metastasize
by way of lymphatics, but the prognosis is excellent.
• Anaplastic carcinomas are thought to arise by dedifferentiation
of more differentiated neoplasms. They are highly
aggressive, uniformly lethal cancers.
• Medullary cancers are nonepithelial neoplasms arising from
the parafollicular C cells and can occur in either sporadic
(70%) or familial (30%) settings. Multicentricity and C cell
hyperplasia are features of familial cases.Amyloid deposits
are a characteristic histologic finding.

Also, Metastatic Lymphoma

Question 13

Thyroid lymphoma epidem, morph, treatment, progn

Answer 13

Appears in old patients, 60s.

1% of all thyroid cancers

Grows rapidly, more rapidly than th other kinds (except anaplastic)

has a good prognosis if diagnosed quickly

non-hodkins T cell lymphomas,

• MALT lymphoma,
• diffuse large B cell lymphoma,
• follicular lymphoma.

Hashimoto thyroiditis is a risk factor for future thyroid lymphoma.

combined chemotherapy is treatment. 95% complete response for MALT lymphoma.