Background
Clinicians in Canada are currently faced with a lack of tools along the clinical care pathway that are needed to appropriately risk stratify patients who present with thyroid nodules. Following malignancy risk stratification by ultrasound, the current gold standard for the differential diagnosis of thyroid nodules is Fine Needle Aspiration Cytology (FNAC). However, in 20-30% of nodules FNAC is hampered by an inherent limitation that results in “indeterminate” categories that require a diagnostic lobectomy for diagnosis. Thus, every year thousands of Canadian patients are exposed to invasive and often unnecessary diagnostic surgery due to a lack of more elegant tools to address suspicion of thyroid cancer.
Modern molecular diagnostic tests offer an opportunity to overcome these limitations and reduce the patient burden, complications, and cost of managing thyroid nodules and thyroid cancer. Molecular diagnosis risk stratifies these indeterminate nodules for clinical decision making (follow up vs lobectomy vs total thyroidectomy).
ThyroSPEC™
ThyroSPEC™ is a proprietary, highly accurate, cost-efficient MALDI-TOF mass spectrometry-based mutation detection panel that detects the most prevalent 137 point mutations and gene fusions reported in thyroid cancer in the following genes:
| Genes (number of mutations) | Fusions (number of fusions) |
| AKT1 (1) | AGK::BRAF (1) |
| BRAF (7) | AKAP::BRAF (1) |
| CTNNB1 (11) | CRTC1::MAML2 (1) |
| DICER1 (3) | EML4::ALK (1) |
| EGFR (1) | ETV6::NTRK3 (1) |
| EIF1AX (4) | IGF2BP3::THADA (1) |
| EZH1 (1) | PAX8::PPARG (3) |
| HRAS (15) | RET::PTC (4) |
| IDH1 (1) | RPS2P32::THADA (1) |
| KRAS (17) | SND1::BRAF (1) |
| NRAS (15) | SQSTM1::NTRK3 (1) |
| PIK3CA (5) | STRN::ALK (1) |
| PTEN (1) | TFG::NTRK1 (1) |
| RET (19) | TMEM233::PRKAB1 (1) |
| SPOP (1) | TPM3::NTRK1 (1) |
| TERT (c.1-124C>T, c.1-146C>T) | TPR::NTRK1 (1) |
| TP53 (10) | |
| TSHR (2) |
ThyroSPEC™ inputs include DNA and RNA extracted from residual liquid FNAC material after preparation of slides, or air-dried FNAC smear, or FFPE of resected tissue. A separate pass is not required which means ThyroSPECTM does not necessitate changing the local aspiration practice.
Highly multiplexed genotyping on the MassARRAY MS platform (Agena Biosciences) is faster and has much lower cost per sample than next generation sequencing.
Ordering ThyroSPECTM
Alberta Precision Laboratories has implemented ThyroSPECTM as a reflex test for indeterminate thyroid FNACs in Alberta.
Alberta Precision Laboratories also offers ThyroSPECTM for out of province samples as a commercial test. To order the test the following is required:
– completion of the APL Molecular Pathology requisition,
– payment information,
– sample sent to APL for testing as per sample guidelines.
For more information: contact@thyrospec.com
Questions concerning the further clinical interpretation of ThyroSPEC™ results can be addressed to Dr. Ralf Paschke (ralf.paschke@albertahealthservices.ca)
Referral possibilities for patients with indeterminate FNA cytology and additional ThyroSPEC™ testing
Endocrinology and Metabolism – Calgary
Instructions: Please fax a referral to Endocrinology central triage. If a specific Endocrinologist is desired, please indicate this on the referral.
Endocrinologists:
Dr. Sana Ghaznavi, Dr. Peter Grundy, Dr. Susan Kinnear, Dr. Vicky Parkins, Dr. Ralf Paschke, Dr. Chris Symonds
Endocrinology central triage
Phone: 403-955-8103
Fax: 403-476-9626
Email: endo.cat@albertahealthservices.ca
Endocrine Surgery – Calgary
Instructions: Please fax a referral to Endocrine Surgery central triage. If a specific Endocrine surgeon is desired, please indicate this on the referral.
Endocrine surgeons:
Dr. Adrian Harvey, Dr. Caitlin Yeo, Dr. Samantha Wolfe
Endocrine Surgery central triage
Ph: 403-944-0966
Fax: 403-944-6008
ENT Surgery – Calgary
Instructions: Please fax a referral directly to the ENT surgeon of your choosing.
ENT surgeons:
Dr. Shamir Chandarana, Ph: 403-944-3954, Fax: 403-210-9828
Dr. Michael Deutschmann, Ph: 403-910-7971, Fax: 587-327-6135
Dr. Robert Douglas Hart, Ph: 403-944-3162, Fax: 403-991-7070
Dr. Ashley Hinther, Ph: 403-3253, Fax: 403-592-4836
Dr. Devon Livingstone, Ph: 403-453-7055, Fax: 587-387-7267
Dr. Wayne Matthews, Ph: 403-944-4501, Fax: 403-210-9752
Dr. Derrick Randall, Ph: 403-282-0054, Fax: 403-282-0059
ENT Surgery – Red Deer
Dr. Paul Douglas-Jones, Ph: 403-342-0494, Fax:
Dr. Arone Pabbies, Ph: 403-342-0494, Fax:
ENT Surgery – Lethbridge
Dr. Hendrik (Kendal) Uys, Ph: 403-524-3681, Fax: 403-381-7793
Dr. Gerrit Viljoen, Ph: 403-929-7545, Fax: 1-888-675-9960
General Surgery – Lethbridge
Dr. Aaron Banmann, Ph: 403-317-1890, Fax: 403-317-1893
Dr. Anthony Gomes, Ph: 403-380-4777, Fax:
ENT Surgery – Medicine Hat
Dr. Matthew Harris, Ph: 403-580-4600, Fax:
Referral possibilities for patients with indeterminate FNA cytology and additional ThyroSPEC™ testing in the AHS Calgary Health Care Region can also be found at the Alberta Health Services webpage: https://www.albertahealthservices.ca/assets/info/hp/cancer/if-hp-cancer-guide-molecular-fna-report.pdf
The Paschke & Eszlinger Lab 