NEXT-GENERATION SEQUENCING  MOLECULAR GENETICS TESTING
Clarifying Indeterminate Thyroid Nodules The most common application of molecular testing in thyroid nodule assessment is to guide care for patients with indeterminate nodules. Ultrasound-guided FNAC is the gold standard preoperative tests in obtaining cells for cytology i.e studies of cells to understand the nature of the swelling whether cancerous or not. However in about 15-30% of nodule aspirates, the results are indeterminate.
Molecular Genetics   Thyroid Nodule
“Ruling In” Cancerous Tissue The above chart shows the common known specific genes mutation/alterations associated with cancer. It often includes testing BRAF, and three RAS genes for specific point mutations and testing for three gene fusions: RET/PTC 1, RET/PTC3, and PAX8/PPARG. This type of molecular testing has been considered primarily as a “rule in” test for cancer due to its typically higher specificity for cancer, yet lower sensitivity. And this affects even the type/extent of surgery done: While mutational testing alone may not be enough to help the physician determine whether a patient requires surgery, it may help inform what type of surgery to perform. For example, because the BRAF V600E mutation has been shown to have a high positive predictive value for cancer, some surgeons may choose to perform a full total thyroidectomy, rather than a lobectomy/hemithyroidectomy, on patients in whom this mutation is found. The same is true in cases of RET/PTC1 and RET/PTC3.
Additionally, several molecular tests have demonstrated the ability to identify medullary thyroid cancer (MTC), an aggressive, but rare form of cancer that is often difficult to detect with cytopathology. Knowing that a patient has MTC before surgery can enable the surgeon to more appropriately plan. Further testing include the necessary germline genetic counseling and testing, and tumor marker tests that inform the need for additional tests, such as imaging studies to evaluate for metastases. Pre-operative knowledge of MTC enables the treating physician to anticipate potential complications such as life-threatening hypertension that can accompany MTC in the setting of multiple endocrine neoplasia type 2. Differentiating thyroid from non-thyroid tissue Some molecular tests have also demonstrated the ability to distinguish parathyroid tissue from thyroid nodules. Because parathyroid cells often appear similar to atypical thyroid cells under the microscope, cytopathologists often designate them as indeterminate – typically, as Bethesda III or IV. This can lead to unnecessary thyroid surgery for these patients. Therapeutic Targets Selection Genetic testing allows the right and effective anti-cancer (tyrosine kinase inhibitor TKI) agent to be chosen based on the genetic make-up of the thyroid cancer.
“Ruling Out” Presence of Cancer Certain genetic alteration eg. BRAF V600E, TERT genetic alteration has been shown to have a high positive predictive value for cancer. So if certain gene mutations are absent, the nodule is most likely benign.
Indeterminate nodules have a high enough risk of cancer to warrant additional evaluation. Very commonly in the past, most patients with cytologically indeterminate nodules have been referred for diagnostic surgery ie. Remove first the thyroid and let the pathologist in the lab know if you have cancer from the study of the already-resected thyroid specimen, be it 1 lobe (half the entire gland) or the entire thyroid gland. Though eventually 70-80% of these nodules ultimately prove to be benign by surgical postoperative histopathology examination (HPE) meaning the surgery was unnecessary. A bigger misery for those who may have sustained complication(s) from the surgery. Yet for patients who didn’t agree to the surgery, they would probably harbour the actual real thyroid cancer disease and may have missed out on the actual surgical treatment. These limitations in cytopathology have led to the emergence of molecular testing to provide cytopathologists and treating physicians with previously undetectable diagnostic information about patients’ thyroid nodules. Genetic molecular testing therefore enables specialist to better determine which patients can safely avoid surgery as part of their diagnostic work-up and make better surgical decisions for those patients who require it.
Molecular testing is increasingly becoming the new standard of care in evaluating thyroid nodules for the presence of cancer. This methodology is now included in recommendations of leading clinical guidelines, including those from the American Thyroid Association (ATA), National Comprehensive Cancer Network (NCCN). So how does molecular genetic testing benefit the patient ?
DOWNLOAD OUR CONTACT DETAILS:
ENTdrvincenttan@gmail.com
+603-3377 7864 +6012-3760 728
Vincent Ear, Nose, Throat, Head and Neck Surgery Specialist Clinic, Clinic Suite 210, Level 2, KPJ Klang Specialist Hospital No.102, Persiaran Rajawali/KU 1, Bandar Baru Klang, 41150 Klang, Selangor
Mon-Fri: 930am-5pm Sat: 9am-1230pm
vincentENTHNS
3.062578,101.46332 (Google Maps, Waze: KPJ Klang, Vincent ENT)
CONTACT US
CLINIC HOURS:
Vincent ENT Clinic
vincententhns
VINCENT
Ear, Nose and Throat (ENT), Thyroid, Head and Neck
Biopsy & Surgery Specialist Clinic
Committed to YOUR Well-being
Copyright Dr.Vincent Tan 2023
NEURON - the building blocks of the brain
NEXT-GENERATION SEQUENCING  MOLECULAR GENETICS TESTING Molecular Genetics   Thyroid Nodule
“Ruling In” Cancerous Tissue The above chart shows the common known specific genes mutation/alterations associated with cancer. It often includes testing BRAF, and three RAS genes for specific point mutations and testing for three gene fusions: RET/PTC 1, RET/PTC3, and PAX8/PPARG. This type of molecular testing has been considered primarily as a “rule in” test for cancer due to its typically higher specificity for cancer, yet lower sensitivity. And this affects even the type/extent of surgery done : While mutational testing alone may not be enough to help the physician determine whether a patient requires surgery, it may help inform what type of surgery to perform. For example, because the BRAF V600E mutation has been shown to have a high positive predictive value for cancer, some surgeons may choose to perform a full total thyroidectomy, rather than a lobectomy/hemithyroidectomy, on patients in whom this mutation is found. The same is true in cases of RET/PTC1 and RET/PTC3.
“Ruling Out” Presence of Cancer Certain genetic alteration eg. BRAF V600E, TERT genetic alteration has been shown to have a high positive predictive value for cancer. So if certain gene mutations are absent, the nodule is most likely benign.
Indeterminate nodules have a high enough risk of cancer to warrant additional evaluation. Very commonly in the past, most patients with cytologically indeterminate nodules have been referred for diagnostic surgery ie. Remove first the thyroid and let the pathologist in the lab know if you have cancer from the study of the already-resected thyroid specimen, be it 1 lobe (half the entire gland) or the entire thyroid gland. Though eventually 70-80% of these nodules ultimately prove to be benign by surgical postoperative histopathology examination (HPE) meaning the surgery was unnecessary. A bigger misery for those who may have sustained complication(s) from the surgery. Yet for patients who didn’t agree to the surgery, they would probably harbour the actual real thyroid cancer disease and may have missed out on the actual surgical treatment. These limitations in cytopathology have led to the emergence of molecular testing to provide cytopathologists and treating physicians with previously undetectable diagnostic information about patients’ thyroid nodules. Genetic molecular testing therefore enables specialist to better determine which patients can safely avoid surgery as part of their diagnostic work-up and make better surgical decisions for those patients who require it.
Molecular testing is increasingly becoming the new standard of care in evaluating thyroid nodules for the presence of cancer. This methodology is now included in recommendations of leading clinical guidelines, including those from the American Thyroid Association (ATA), National Comprehensive Cancer Network (NCCN). So how does molecular genetic testing benefit the patient ?
Clarifying Indeterminate Thyroid Nodules The most common application of molecular testing in thyroid nodule assessment is to guide care for patients with indeterminate nodules. Ultrasound-guided FNAC is the gold standard preoperative tests in obtaining cells for cytology i.e studies of cells to understand the nature of the swelling whether cancerous or not. However in about 15-30% of nodule aspirates, the results are indeterminate.
Additionally, several molecular tests have demonstrated the ability to identify medullary thyroid cancer (MTC), an aggressive, but rare form of cancer that is often difficult to detect with cytopathology. Knowing that a patient has MTC before surgery can enable the surgeon to more appropriately plan. Further testing include the necessary germline genetic counseling and testing, and tumor marker tests that inform the need for additional tests, such as imaging studies to evaluate for metastases. Pre-operative knowledge of MTC enables the treating physician to anticipate potential complications such as life- threatening hypertension that can accompany MTC in the setting of multiple endocrine neoplasia type 2. Differentiating thyroid from non-thyroid tissue Some molecular tests have also demonstrated the ability to distinguish parathyroid tissue from thyroid nodules. Because parathyroid cells often appear similar to atypical thyroid cells under the microscope, cytopathologists often designate them as indeterminate typically, as Bethesda III or IV. This can lead to unnecessary thyroid surgery for these patients. Therapeutic Targets Selection Genetic testing allows the right and effective anti-cancer agent to be chosen based on the genetic make-up of the thyroid cancer.
ENTdrvincenttan@gmail.com
+603-3377 7864 +6012-3760 728
Vincent Ear, Nose, Throat, Head and Neck Surgery Specialist Clinic, Clinic Suite 210, Level 2, KPJ Klang Specialist Hospital No.102, Persiaran Rajawali/KU 1, Bandar Baru Klang, 41150 Klang, Selangor
vincentENTHNS
3.062578,101.46332 (Google Maps, Waze: KPJ Klang, Vincent ENT)
Mon-Fri: 930am-5pm Sat: 9am-1230pm
CONTACT US
CLINIC HOURS:
vincententhns
Vincent ENT Clinic
DOWNLOAD OUR CONTACT DETAILS:
APPOINTMENT:  +603-3377 7864 +6012-3760 728 VINCENT EAR, NOSE & THROAT, THYROID , HEAD AND NECK SURGERY SPECIALIST CLINIC  VINCENT
Ear, Nose and Throat (ENT), Thyroid, Head and Neck
Biopsy & Surgery Specialist Clinic
Committed to YOUR Well-being
Copyright Dr.Vincent Tan 2023