Practice question III answers Pathology of thyroid

Practice question III answers

Pathology of thyroid

©Jun Wang, MD, PhD

 

1. B. This lesion is characterized by capsulated nodular growth of packed small follicles with normal appearing follicular cells. This can be either follicular adenoma, if no invasion can be seen, or follicular carcinoma, if vascular or capsular invasion is seen. Capsular invasion is seen in this case, characterized by capsule disconnected due to follicular tissue. Hashimoto thyroiditis is characterized by follicular destruction in a background of diffuse polyclonal lymphoid infiltrate, with or without lymphoid follicle formation. Multinodular goiter is characterized by unevenly benign enlargement of thyroid with nodular growth pattern and follicles markedly various in size. Papillary thyroid carcinoma, including follicular variant, is diagnosed based on typical nuclear features, such as enlarged nuclei, washed out chromatin, nuclear grooves or inclusion.

2. B. PAX8, PTEN and RAS/PI3KCA mutation can be seen in various tumors, including follicular carcinoma of thyroid. TSH receptor mutation may be seen in toxic follicular adenoma. BRAF and Ret-PTC mutation is seen in papillary thyroid carcinoma. p53 mutation is usually seen high grade malignancies, including anaplastic thyroid carcinoma.

3. C. Thyroid carcinoma may invade surrounding tissue and cause damage of nerves. Recurrent laryngeal nerve may be involved and result in abnormal vocal cord function. It is very rare for a tumor to invade cartilage or joint. Superior laryngeal nerve has two branches. Its external branch innervates cricothyroid muscle, and its injury due to surgery or tumor invasion may result in loss of voice. However, its internal branch contains sensory component only. Thyroid cancer extending to vocal cord mucosa, while possible, is rare and if occurs, usually happens at a very late stage.

4. E. This lesion is characterized by the presence of nuclear inclusion and grooves. These features are diagnostic for papillary thyroid carcinoma. Follicular adenoma is usually capsulated nodule with packed small follicles, usually similar sizes, without vascular or capsular invasion, or nuclear feature for papillary thyroid carcinoma. Graves disease is characterized by proliferation of follicular cells, thin pale colloid with vacuoles adjacent to follicular cells, with intact follicular structure.  Hashimoto thyroiditis is characterized by follicular destruction in a background of diffuse polyclonal lymphoid infiltrate, with or without lymphoid follicle formation. Multinodular goiter is characterized by unevenly benign enlargement of thyroid with nodular growth pattern and follicles markedly various in size.

5. D. Multifocality is characteristic for papillary thyroid carcinoma. Capsular invasion or vascular invasion is needed when diagnose follicular carcinoma of thyroid, but does not have to be present for papillary thyroid carcinoma. Large follicles lined by flat cells can be seen in multinodular goiter. Marked lymphocytic infiltrate can be seen in Hashimoto thyroiditis or subacute lymphocytic thyroiditis. Pale colloid is suggestive of hyperfunctioning follicles, can be seen in various disorders, including Graves disease.

6. E. See discussion of question 2.

7. E. Total thyroidectomy is the preferred management for papillary thyroid carcinoma, since it is commonly bilateral and multifocal. Although granulomatous thyroiditis may be associated with viral infection, it tends to be self-limited and anti-viral treatment is not needed. Anti-viral treatment is irrelevant to treatment of any of the thyroid neoplasm. Inhibitors of thyroid hormone synthesis, such as propylthiouracil, can be used to treat hyperthyroidism, including Graves disease. Iodine supplementation can be used for iodine deficiency and thyroxine replacement can be used for hypothyroidism. 

8. A. This thyroid lesion is characterized by poorly differentiated epithelial cords or nests that is positive for cytokeratin and p53, but negative for thyroglobulin and PSA. This is consistent with anaplastic thyroid carcinoma. Diffuse large B cell lymphoma has diffuse growth of large atypical lymphocytes that are negative for cytokeratin, but are usually positive for CD45, and B cell markers, including CD19, CD20, and CD79a. Medullary thyroid carcinoma has eccentric nuclei, punctuate chromatin, and amyloid deposit, without marked pleomorphism, and are positive for calcitonin. Metastatic prostate adenocarcinoma is positive for PSA. Papillary thyroid carcinoma, including follicular variant, is diagnosed based on typical nuclear features, such as enlarged nuclei, washed out chromatin, nuclear grooves or inclusion.

9. B. This lesion is characterized by solid growth of cells with eccentric nuclei. There are amorphous deposits that is likely amyloid, and likely to be positive for Congo red stain. Acid fast bacilli and fungal infections usually have granulomatous changes. Serum anti-TSH receptor and anti-peroxidase can be detected in Graves disease and Hashimoto thyroiditis. 

10. A. Green birefringence under polarized light suggest positive Congo red stain. This lesion is medullary thyroid carcinoma that express calcitonin. CD3 is a T cell marker. Light chain is expressed by B-cells and plasma cells. Parathyroid hormone is positive for parathyroid cells, either normal, hyperplastic, or neoplastic, such as parathyroid adenoma, or parathyroid carcinoma. Parathyroid growth usually do not have amyloid. Thyroglobulin is expressed by normal thyroid follicular cells, and tumors derived from follicular cells, including papillary thyroid carcinoma and follicular carcinoma of thyroid.

11. E. Positive calcitonin reactivity confirmed the diagnosis of medullary thyroid carcinoma. RET mutation is commonly seen in medullary thyroid carcinoma, either sporadic or those associated with multiple endocrine neoplasm type 2. MEN1 mutation is associated multiple endocrine neoplasm type 1, that is characterized by tumors of parathyroid gland, enteropancreatic endocrine cells, the anterior pituitary gland. Also see discussion of question 2.

12. C. See discussion of question 8. follicular carcinoma is characterized by capsulated nodular growth of packed small follicles with normal appearing follicular cells, with the presence of vascular or capsular invasion. Plasmacytoma has aggregates of plasma cells that will be positive for Cd38, CD138 and negative for calcitonin and cytokeratin.

13. B. See discussion of questions 1 and 8.

14. B. This lesion is characterized by follicular destruction in a background of diffuse lymphoid infiltrate, with lymphoid follicle formation, features consistent with Hashimoto thyroiditis. Anti-thyroid peroxidase and anti-thyroglobulin are most commonly seen in patients with Hashimoto thyroiditis. Activating TSH receptor antibodies are seen in patients with Graves disease. Calcitonin and chromogranin are elevated in patients with medullary thyroid carcinoma. Monoclonal immunoglobulin are commonly seen in patient with B cell neoplasia, especially plasma cell neoplasms.

15. C. This lesion is characterized by follicular destruction in a background of diffuse lymphoid infiltrate, with lymphoid follicle formation, features consistent with Hashimoto thyroiditis. Follicular lymphoma has packed lymphoid follicles with similar size and abnormal follicular architecture. Graves disease is characterized by proliferation of follicular cells, thin pale colloid with vacuoles adjacent to follicular cells, with intact follicular structure, without prominent lymphocytic infiltrate. Multinodular goiter is characterized by unevenly benign enlargement of thyroid with nodular growth pattern and follicles markedly various in size. Subacute lymphocytic thyroiditis has variable lymphocytic infiltrate without follicular destruction. 

16. A. This patient has hypothyroidism, as suggested by elevated TSH and low T3. The elevated TSH is a result of low levels of thyroid hormones. Hypothyroidism seen in Hashimoto thyroiditis is caused by destruction of follicles and lack of thyroid hormone production. Iodine deficiency may cause hypothyroidism and result in goiter, a hyperplastic change of thyroid without lymphocytic infiltrate. Systemic viral infection is associated with granulomatous thyroiditis, a condition may rarely associated with hypothyroidism. TRH overproduction and TSH secreting tumor may cause elevated TSH, as well as elevated T3 and T4.

17. A. This patient has features of thyrotoxicosis, as suggested by her suppressed TSH and elevated T4. The enlarged thyroid with tall follicular cells, pale colloid and many vacuoles in colloid are consistent with Graves disease. Activating TSH receptor antibodies are the most commonly seen autoantibodies in patients with Graves disease. Anti-thyroid peroxidase, anti-thyroglobulin and inhibitory TSH receptor antibodies are seen in patients with Hashimoto thyroiditis. Calcitonin and chromogranin are elevated in patients with medullary thyroid carcinoma. 

18. B. The enlarged thyroid with tall follicular cells, pale colloid and many vacuoles in colloid are consistent with Graves disease. Also see discussion of question 1.

19. C. Bulging eyes in Graves disease is associated with increased volume of retro-orbital stroma tissue, resulted from a cross-reaction of activated lymphocytes to the stromal cells that express TSH receptor. 

20. E. See discussion of questions 1 and 8.

 

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