Benign thyroid nodules mimicking malignancy:

Mummified nodules^2,3

• Mummification occurs spontaneously or after aspiration for symptomatic relief:Blood supply interruption(from extracting large tissue amounts, traumatic venous thrombosis, rough needle use, and multiple passes/vigorous aspiration)→Centronodular thyrocyte hypoxia→nodule haemorrhage→intracystic modification→scarring.
• Key sonographic features:
  -Marked volume shrinkage(necrosis)
  -Echogenic foci(dystrophic calcifications)
  -Desiccation
  -Ill-defined margins(collapse of initially well-defined nodule)
  -Taller-than-wide shape(asymmetric fibrous healing with transverse shrinking)
  -Hypoechogenicity and high elastographic stiffness(necrotic changes→cystic component shrinkage→progressive dense fibrosis)
  -Absent vascularity(cystic/necrotic nodules)
  -Posterior accoustic shadowing and peripheral hypoechoic halo.
  -Eggshell macrocalcification (benign calcified granulation tissue) with regular complete linear features. Irregular/interrupted eggshell calcification with nodular tissue outside calcification line favours malignancy.

• Pitfall:‘Mummified’ nodules can show 'suspicious' sonographic features thus scored higher on TIRADS. 
• Proposed approach:
  -Conservative management
  -Sonographic follow-up, regardless of TR score. 

As benign thyroid nodules 'mummify', sonographic features resembling malignancy can appear³:

• Echogenic foci resembling malignant microcalcifications corresponding to psammoma bodies.
• Considerable tumour shrinkage may rarely occur in micropapillary thyroid carcinoma.
• Non-visualized internal vascularity does not definitively rule out malignancy, as strong stromal desmoid reaction can preclude tumour neoangiogenesis.

Proposed approach:

• Chronological analysis of sonographic changes of 'suspicious-appearing' nodules. If no prior comparison studies or doubtful findings, consider FNAC.
• Knowledge of prior imaging and intervention would prevent misinterpretation of sonographic features of mummification as suspicious.
• Assess for intranodular vascularity on colour Doppler. If present, the likelihood of solid component is higher. Conversely, mummified cyst contents is more likely in absence of internal vascularity.

Case1:14-year-old patient underwent FNAC(Histology:Acellular/haemorrhagic yield) for a left thyroid nodule which was followed up over 2 years and recently showed interval 'suspicious' features. Retrospective review of prior imaging revealed progressive mummification over time(Fig. 1).

Case2:60-year-old patient underwent FNAC for a left thyroid nodule demonstrating internal punctate echogenic foci and ‘solid’ component, misinterpreted as suspicious. Internal vascularity was however absent and features of mummification were present over several ultrasound studies(Fig. 2). Histology:Inspissated/’mummified’ cyst contents. 

Nodules subjected to prior intervention (e.g.ethanol/radiofrequency ablation or image-guided sampling)

• After FNAC or ethanol injection, thyroid nodules can desiccate or haemorrhage over time³.
• As with mummified nodules, review prior imaging and interventions to avoid misinterpreting suspicious features.

Case3:52-year-old patient presents with a bulky left neck lump. Sonographic evaluation revealed a mildly suspicious left thyroid nodule. Subsequent FNAC (Histology:MNG) and radiofrequency ablation(RFA) were done. Over time, the nodule mummified(Fig. 3). If prior imaging was not reviewed, further FNAC could be inappropriately recommended for mummification features mistaken to be suspicious.

Densely calcified benign thyroid nodules⁴

• Microcalcifications(punctate echogenic foci≤1mm) within a thyroid nodule are generally considered suspicious, but is not a reliable isolated finding as benign nodules can also demonstrate calcifications.
• Pitfall:Densely calcified nodules are usually classified a minimum level of TR3 from indeterminate composition/echogencity due to calcification. Depending on interobserver variability in intepretation, additional points may be assigned for macrocalcifications or peripheral rim calcifications casting posterior shadowing, raising the TR level and thus lowering the threshold for FNAC.
• Based on our local experience, FNAC of densely calcified thyroid nodules often turn out to be non-diagnostic/benign. 

Proposed approach:

• Close-interval CT or sonographic follow-up.
• In doubtful cases, consider PET-CT to determine any suspicious metabolic activity.
• FNAC if interval suspicious features seen.

Case4:50-year-old patient underwent FNAC of several densely calcified left thyroid lobe nodules deemed TR4(Fig. 4). Histology:Insufficient yield(despite several attempts and cytotechnologist’s guidance).

Autoimmune diseases(e.g. Graves or Hashimoto’s Thyroiditis)

• Autoimmune thyroiditis may cause focal or diffuse involvement.
• Uniformly hyperechoic (“white-knight”) appearance and variegated pattern of hyperechoic areas separated by hypoechoic bands reminiscent of giraffe hide in the setting of Hashimoto’s thyroiditis has been described as a reliable benign feature¹.
• Pitfalls:Focal types may appear highly vascular, and diffuse types can appear heterogenous, giving false impressions of irregular hypoechoic nodules. Higher TIRADS scores may be assigned inappropriately.

Proposed approach:

• Clinical and biochemical correlation to avoid unnecessary FNAC.
• Report differential considerations.
• TIRADS may not be appropriate in such cases. 

Case5:60-year-old patient with a highly vascular TR3 focal left thyroid nodule underwent FNAC in view of marked internal vascularity(Fig. 5). Histology:Focal lymphocytic thyroiditis.

Case6:63-year-old patient underwent FNAC for several bilateral indistinct thyroid nodules deemed as TR4(Fig. 6). Histology:Diffuse lymphocytic thyroiditis.

Avascular cystic nodule with internal debris/sludge

• Pitfalls:Intranodular vascularity or mobility of internal contents are not considered on TIRADS as features for scoring. Such nodules, if large in size or containing large echogenic debris, could be misintepreted as suspicious and upgraded to higher TR levels and subjected to unnecessary FNAC.

Proposed approach:

• Evaluate on doppler or elastography to assess for features of a solid component.
• If the apparent internal solid component is mobile, present at the dependant aspect and shows no convincing internal vascularity, a cyst with internal debris is more likely→Consider routine sonographic follow-up.

Case7:40-year-old patient with a TR4 right thyroid nodule that was initially considered suspicious due to its large size and internal echogenic component, deemed as 'solid'. FNAC showed cyst with debris(Fig. 7). Unecessary FNAC could be avoided with sonographic surveillance.

Malignant clinical entities mimicking benignity:

Cystic variant of Papillary Thyroid Carcinoma (PTC)

• PTC undergoes cystic changes more frequently than other thyroid neoplasms, although rare. It may mimic sonographic features of non-neoplastic thyroid nodules, the most common being adenomatoid (nodular) colloid goitre⁵.
• Pitfall:Cystic PTC may be scored lower on TIRADS, especially in the presence of eccentric solid component associated with other adjacent mobile components, collectively deemed as debris.

Proposed approach:

• In solid-cystic lesions, the eccentric/pedunculated non-dependant echogenic internal components should be considered for FNAC, even if their size is disproportionately smaller compared to the cystic component or overall lesion size. 
• Doppler assessment for internal vascularity to determine if the echogenic component could be solid.
• If clinical doubt remains, consider FNAC and/or PET-CT.

Case8:60-year-old patient underwent sonographic evaluation of a large right thyroid cystic lesion containing a disproportionately small solid component(Fig. 8). FNAC of the internal echogenic component was performed due to presence of internal vascularity. Histology:PTC.

Cystic thyroid metastases

• Malignant melanoma and lung,breast,kidney,GI tract,head/neck malignancies may secondarily involve the thyroid gland.
• Pitfall:Cystic thyroid metastases may appear benign and falsely awarded a lower TIRADS score. 

Proposed approach:

• Close-interval sonographic follow-up or further evaluation with PET-CT.
• FNAC if persistent clinical doubt.

Case9:45-year-old patient with known lung adenocarcinoma presents with a left neck lump, sonographically evaulated to be a TR2 left thyroid nodule with overall benign appearances. However, FNAC was performed due to presence of internal vascularity and persistent clinical doubt (Fig. 9). Histology:Metastasis.

Other miscellaneous thyroid lesions:

Multiple thyroid nodules qualifying for FNAC

Pitfall:No clear recommended management approach for multinodular goitres (MNG) containing discrete suspicious nodules in both lobes or remnant lobe (post-thyroidectomy patients for MNG) meeting the criteria for FNAC.

Proposed approach:

• Multiple similar-appearing 'suspicious' nodules in remnant lobe (MNG):
  -Two nodules with highest TR levels meeting FNAC criteria should be sampled as per ACR-TIRADS recommendations.
• Bilateral suspicious thyroid nodules, with top two TR level and largest sized nodules in the same lobe (Case2), consider:
  -Additional FNAC of the highest TR level nodule(s) in contralateral lobe or FNAC of the highest TR level nodule in each lobe, to complete bilateral lobe evaluation, as this aids in surgical management decision(e.g. total versus hemithyroidectomy).
• Referring physician’s preference and patient’s risk factors for thyroid cancer, anxiety, comorbidities, life-expectancy, and bleeding risk should be considered.

Case10:51-year-old patient underwent total right thyroidectomy for MNG. Six TR4-classified nodules were present in the remnant left lobe,all recommended for FNAC(Fig. 10).

Case11:50-year-old patient with known MNG had multiple TR4 and TR5 nodules in both lobes, all recommended for FNAC(Fig. 11).

Spongiform nodules

• Typically benign, comprising predominantly (>50%) small cystic spaces¹(Fig. 12).
• Pitfall:No recommended management approach for symptomatic/large nodules.

Proposed approach:

• Asymptomatic/non-bothersome spongiform nodules can be managed like TR3 nodules.
• Consider alcohol ablation or surgical excision for large lesions.

Subcentimetre thyroid lesions closely related to vital structures

• Pitfall: No recommended management. These nodules may complicate surgery due to local invasion in the context of PTC.
• Critical locations:common carotid artery,tracheoesophageal groove (along recurrent laryngeal nerve),trachea,oesophagus(Fig. 13).

Proposed approach:

• Early FNAC, especially if additional suspicious features are present.
• Close-interval imaging follow up.