11. Thyroid nodules and cancer Flashcards
What are the types of thyroid tumors?
- Benign (Follicular adenoma, Harthle cell adenoma)
- Malignant (Papillary cc., Follicular cc., Medullary cc., Anaplastic cc.,
- Others : Fibrosarcoma, lymphoma, teratoma, mets
What is the incidence of thyroid nodules in the population?
4-7% of the population has palpable nodules.
What is the likelihood of solitary cold nodules being malignant?
5-10% of solitary cold nodules are malignant.
What factors are considered in determining the likelihood of a thyroid nodule becoming malignant?
- Patient’s history,
- characteristics of the nodule,
- other symptoms (hyperthyroid/hypothyroid, compression),
- family history,
- neck irradiation
What is the probability of cancer in the presence of microcalcification in a thyroid nodule?
The probability of cancer is 70% in the presence of microcalcification.
What is the gold standard for thyroid nodule evaluation?
Fine needle aspiration biopsy (FNAB).
What is the diagnostic approach for thyroid nodule evaluation?
History and physical exam, ultrasound, cytology, and genetic tests.
What is the most common histological type of thyroid malignancy?
Papillary thyroid carcinoma (PTC).
What percentage of all thyroid malignancies does PTC comprise?
60-80%.
What percentage of PTC cases have somatic mutations?
More than 40-70%.
What is the second most common histological type of thyroid malignancy?
Follicular thyroid carcinoma (FTC).
What percentage of all thyroid malignancies does FTC comprise?
10-15%.
What percentage of FTC cases have mutations?
30-50%.
What is the main genetic alteration found in PTC?
BRAF
What is the correlation between BRAF mutation and tumor aggressivity in PTC?
BRAF mutation is thought to correlate with extrathyroidal growth, lymph node involvement, radioiodine resistance, and tumor recurrence.
What is the main genetic alteration found in FTC?
RAS
What is the risk of cancer in nodules positive for RAS mutations?
79% of RAS mutation-positive “benign” nodules have evidence for clonal neoplasm and early transformation to cancer.
What are the three signaling pathways involved in thyroid cancer?
MAP-kinase, PIP3-kinase/protein-kinase-B (PI3K/AKT), and adhesion and migration.
What is the effect of mutated RAS protein in thyroid cancer?
Mutated RAS protein elicits GTP-ase effect and, consequently, activation of follicular cell proliferation, leading to genomic instability, increased growth potential, and tumor development.
What is the RET proto-oncogene?
The RET proto-oncogene encodes a tyrosine-kinase transmembrane receptor.
What is the effect of RET/PTC1 fusion protein in thyroid cancer?
RET/PTC1 fusion protein results in reduced malignancy.
What is the effect of RET/PTC3 fusion protein in thyroid cancer?
RET/PTC3 fusion protein results in enhanced malignancy.
What is the PAX8 gene?
The PAX8 gene encodes a transcriptional factor that has a role in tissue differentiation.
What is the PAX8/PPAR-gamma-1 gene rearrangement?
The PAX8/PPAR-gamma-1 gene rearrangement has been observed in follicular thyroid cancer (FTC).
What are TERT point mutations in thyroid cancer?
TERT point mutations are genetic alterations observed in thyroid cancer.
What is the genomic landscape of anaplastic thyroid cancer?
The genomic landscape of anaplastic thyroid cancer involves multiple driver mutations, such as BRAF and PIK3CA.
What is the driving gene fusion in medullary thyroid cancer?
The driving gene fusion in medullary thyroid cancer is ALK fusion genes.
What is the significance of BRAF and PIK3CA mutations in thyroid cancer?
They are multiple driver mutations.
What are some of the genes associated with thyroid cancer?
TP53, TERT, ALK fusions, NTRK1 fusions, NTRK3 fusions, BRAF V600E, RET/PTC, RAS, PTEN, BRAF K601E, PAX8/PPARG.
What is the ThyroSeq v2?
It is a 56-gene panel used for molecular testing of thyroid nodules.
What is the ThyroSeq v3?
It is a 112-gene panel used for molecular testing of thyroid nodules.
What is the platform used for ThyroCanTM?
IonTorrent PGM.
What is the purpose of the Afirma Veracyte test?
It is used for molecular testing of thyroid nodules.
What is the NGS-based method used in ThyroCanTM?
It is a method that uses 23 cancer genes and 2 tissue control genes to detect 568 mutations and 2 expressions.
What is the platform used for the analysis of +2 tissue control genes?
IonTorrent PGM.
What is the target gene analysis method used in this study?
Targeted NGS, mutation analysis.
What are the genes targeted for mutation analysis in this study?
BRAF, KRAS, NRAS, HRAS, TERT, RET, TP53, AXIN1, APC, IDH1, SMAD4, MET, CTNNB1, PIK3CA, DICER1, VHL, PTEN, LPAR4, EIF1AX, GAS8-AS1, TSHR, AKT1, GNAS.
What is the purpose of scintigraphy in the diagnosis of thyroid nodules?
To detect hyperfunctioning nodules.
What are the treatment options for hyperfunctioning thyroid nodules?
Radioiodine treatment or surgery.
What imaging technique is used to suspect thyroid nodules?
Ultrasound.
What is the purpose of a TSH assay in the management of thyroid nodules?
To determine if the patient has suppressed, normal, or elevated levels of TSH.
What is the next step in the management of a hyperfunctioning thyroid nodule?
Radioiodine treatment or surgery.
What is the purpose of an ultrasound in the management of thyroid nodules?
To determine if the nodule is suspect or not suspect for malignancy.
What is the purpose of a fine-needle aspiration biopsy in the management of thyroid nodules?
To obtain cytology and determine if the nodule is malignant or benign.
What is the next step in the management of a thyroid nodule with uncertain cytology?
Repeated biopsy or observation.
What are some molecular markers that can be used in the treatment of thyroid tumors?
Positive markers.
What characteristics need to be checked in thyroid nodules?
- size,
- consistency,
- multiple/solitary,
- fixed/mobile,
- cervical lymph nodes,
- hypodensity,
- microcalcification,
- hypervascularisation,
- solid nodule,
- irregular borders,
- lack of halo sign
