Thyroid Nodules: Clinical, Pathologic Flashcards

Question

Thyroid Nodules- Streamlined work-up

Answer 1

TSH Ultrasound Fine-needle aspiration biopsy

Answer 2

a. One approach used to determine whether the nodule is malignant is the fine needle biopsy (FNB), which some have described as the most cost-effective, sensitive and accurate test. b. FNB or ultrasound-guided FNA usually yields sufficient thyroid cells to assess the risk of malignancy, although in some cases, the suspected nodule may need to be removed surgically for pathological examination. c. The report may be done according to the Bethesda System for Reporting Thyroid Cytopathology.

Answer 3

a. Very accurate at finding malignant (98%) i. good for finding malignant b. Will find benign and suspicious DX at a lower rate c. We have a scan for suspicious tumors that we cannot determine if malignant or benign

Answer 4

1. Highly cellular aspirate 2. +/- colloid 3. Nuclear enlargement, elongation 4. Nuclear grooves, pseudoinclusions 5. Multiple small to large nucleoli 6. Psammoma bodies 7. Papillary cellular aggregates

Answer 5

a. The Bethesda system (TBS) is a system for reporting cervical or vaginal cytologic diagnoses, used for reporting Pap smear results b. Can be used for thyroid pathology, will be able to use this report to share info with pathology c. There are six categories: Non-Diagnostic, Benign, ACUS, suspicition for follow up neoplasm, Suspicious for Malignant, and Malignant

Answer 6

a. Proto-oncogene---> Normal gene which codes for a protein that promotes normal cell division b. Oncogene---> Mutated gene which codes for a protein that causes unregulated cell division c. Tumor Suppressor Gene--> Normal gene which codes for a protein that restrains cell division or that promotes cell differentiation, DNA repair or apoptosis

Answer 7

a, Tumors result from oncogene activation or tumor suppressor gene loss b. Cells transformed by genetic mutations are likely to develop more mutations c. Cancers result from multiple sequential genetic mutations

Answer 8

1. Papillary (85-90%) multifocal, LN 2. Follicular/Hurthle (5%) vascular spread 3. Anaplastic (<2%) very aggressive 4. Medullary (5%) familial Others malignant Lymphoma (rare) Sarcoma (rare) Metastatic (rare)

Answer 9

Thyroid Gland - Medullary Carcinoma a. Solid proliferation of cells with granular cytoplasm (C cells) b. Highly vascular stroma c. Hyalinized collagen and/or amyloid i. will see these deposited* d. May have Psammoma bodies (Ca2+ deposits) Immunostains: Thyroglobulin -, Calcitonin +, Chromogranin +

Answer 10

RET/PTC Rearrangement 20% a. Mutations associated with papillary thyroid cancer are mainly two forms of chromosomal translocation and one form of point mutation. i. These alterations lead to activation of a common carcinogenic pathway—the MAPK/ERK pathway. b. Chromosomal translocations involving the RET proto-oncogene (encoding a tyrosine kinase receptor that plays essential roles in the development of neuroendocrine cells) occur in approximately a fifth of papillary thyroid cancers. c. The fusion oncoproteins generated are termed RET/PTC proteins (ret/papillary thyroid carcinoma), and constitutively activate RET and the downstream MAPK/ERK pathway. d. The frequency of ret/PTC translocations is significantly higher in papillary cancers arising in children and after radiation exposure.[1] The gene NTRK1 (encoding the TrkA receptor e. Approximately a third to a half of papillary thyroid carcinomas harbor point mutations in the BRAF oncogene, also activating the MAPK/ERK pathway. i. In those cases the BRAF mutations found were V600E mutation

Answer 11

a. Oncogene gain of function is the most frequent molecular alteration described in thyroid cancer. i. It mainly includes the aberrant activation of the RAS/RAF/MEK/ERK pathway\ ii. These alterations regard the rearrangements of Ret/PTC and Trk tyrosine kinase receptors and point mutations of RAS or BRAF genes b. Loss of function of tumor suppressor proteins may also occur in thyroid cancer and includes PAX-8/PPARγ rearrangement, PTEN down-regulation, β-catenin, and p53 mutations c. While inactivating mutations of the p53 gene is very frequent in human cancers (50% of all human malignancies), they have been found in only 10% of thyroid carcinomasand mainly in poorly differentiated and aggressive histotypes. d. These observations and the indolent progression of most thyroid carcinomas have brought to the paradigm that p53 role is minor in thyroid cancer initiation and early stages, while it is important only in the rare case of progression to aggressive phenotypes i. However, the role of p53 functional inactivation in thyroid cancer has never been carefully studied and remains controversial.

Answer 12

* P53 mutation can lead to anaplastic carcinoma i. know this While inactivating mutations of the p53 gene is very frequent in human cancers (50% of all human malignancies), they have been found in only 10% of thyroid carcinomasand mainly in poorly differentiated and aggressive histotypes.