1.The genomic alterations for benign thyroid nodule, especially adenomatoid nodule, one of the most common types of hyperplasia lesion, are ill-studied.

2. Somatic mutation of BRAF (22/32) is only detected in PTC.

3. Mutations in SPOP (4/38), ZNF148 (6/38) and EZH1 (3/38) are found enriched in adenomatoid nodule.

4.In an expanded cohort of adenomatoid nodule (n=259)mutually exclusive SPOPP94REZH1Q571R and ZNF148

mutations are identified in 24.3% of them.

5.Adenomatoid nodules show very few overlapped mutations and distinct gene expression patterns with their coincidental PTC.

6.PTCs evolved independently from their matched benign nodules.

7. Benign nodules possess a unique molecular signature that differs from PTC.

8.Molecular marker evidence that Papillary thyroid cancer and benign nodules have independent origin.

9. This means that in the near future the molecular markers status of a given nodule can be used to assign a nodule to benign and result in no surgery and if there are symptoms or cosmetic reasons the use of ethanol and or radiofrequency ablation methods could be used.

10.The Cancer Genome Atlas (TCGA) project and other studies tumorigenesis related genetic events have been uncovered in 96.5% of PTC (for example, BRAF mutation, RAS mutation and so on)

11. Novel genetic alterations are associated with follicular adenoma, the benign neoplastic thyroid nodule.

12.While the genetic alterations for benign hyperplasia thyroid nodule, especially adenomatoid nodule, one of the most common hyperplasia lesions and undistinguished from follicular thyroid carcinoma in fine need aspiration.

13. Benign hyperplastic thyroid nodules have a distinct molecular pattern all their own. SPOPP94REZH1Q571R and ZNF148 mutations,

Figure 1: Overview of somatic mutations in thyroid tissues.
Figure 1

(a) Sampling schematic: Tissue samples were obtained from the thyroids of patients with or without PTC (>2 years follow-up). Sample Groups TB: benign nodule with concurrent PTC; SB: simple benign nodule without concurrent PTC. Normal tissues were at least 2 cm distant from the lesion foci. (b) Comparison of number of somatic mutations in PTCs, benign nodule and normal thyroid. Non-synonymous mutations included missense, stopgain SNV and indels. Mean±s.d., **P<0.01 Wilcoxon signed-rank test. (c) Comparison of number of somatic mutations in benign nodules from TB and SB patients, as well as normal thyroid from TB and SB patients. Mean±s.d., *P<0.05 by Wilcoxon signed-rank test.

14.The gene expression in benign nodules differs from PTC tumors.

15. Independent evolution of benign nodules and PTCs

16.Current DNA-based mutation testing of thyroid nodules only includes genes with defined roles in thyroid cancer formation, functioning as ‘rule in’ test.

17. The inclusion of SPOPZNF148 and EZH1 as benign nodule associated genes, has the potential to increase its diagnostic efficacy of DNA-based mutation testing by providing ‘rule out’ information.

18.Benign thyroid nodules have a genetic and transcriptome landscape that is distinct with PTC tumours.

19.These findings confirmed the conventional belief that benign nodule development is distinct from PTC tumour formation.

20.Benign associated mutations added in the current molecular diagnostic panel for thyroid cancer may increase its diagnostic efficacy by providing ‘rule out’ information.

Call me for details of the present state of marker testing on your thyroid nodule before you go to surgery.


You could be saved from that serious thyroidectomy in the hospital.



Richard Guttler MD,FACE,ECNU

Interventional thyroidologist