What symptoms warrant a thyroid cancer workup for a check2 (check 2) individual?

Symptoms Warranting Thyroid Cancer Workup in CHECK2 Individuals

For CHECK2 (CHEK2) mutation carriers, a thyroid cancer workup should be initiated when presenting with a rapidly growing neck mass, vocal cord paralysis, dysphagia, dyspnea, or cervical lymphadenopathy, as these symptoms significantly increase the likelihood of thyroid malignancy. 1

Clinical Symptoms Requiring Evaluation

High-Risk Clinical Presentations

• A rapidly growing thyroid nodule or neck mass warrants immediate evaluation as it significantly increases the probability of malignancy 1
• Vocal cord paralysis, which may present as hoarseness, is a concerning symptom that increases cancer likelihood approximately 7-fold 1
• Dysphagia (difficulty swallowing) suggests possible invasion of surrounding structures 1
• Dyspnea (breathing difficulty) may indicate compression of the trachea by a malignant growth 1
• Presence of enlarged regional lymph nodes, particularly in the central or lateral neck compartments 1, 2
• Neck pain, especially when associated with a firm nodule 1
• Horner's syndrome (ptosis, miosis, anhidrosis) may indicate invasion of sympathetic chain 1

Physical Examination Findings

• Firm nodule fixed to adjacent structures (increases likelihood of malignancy by approximately 7-fold) 1
• Hard mass invading the neck structures 1
• Palpable cervical lymphadenopathy (present in approximately 40% of thyroid cancer patients) 1
• Evidence of local invasion with symptoms such as hemoptysis 3

Risk Factors Warranting Lower Threshold for Workup

For CHECK2 mutation carriers, certain risk factors should lower the threshold for initiating a thyroid cancer workup:

• Male gender (thyroid cancer is less common but more aggressive in men) 1
• Age less than 15 years or advanced age (>70 years) 1, 2
• Family history of thyroid cancer 1, 2
• History of head and neck radiation exposure 1, 2
• History of diseases associated with thyroid carcinoma (familial adenomatous polyposis, Carney complex, Cowden's syndrome, MEN 2A or 2B) 1

Diagnostic Algorithm for CHECK2 Individuals

1. Initial Assessment: For any suspicious thyroid nodule, perform ultrasound-guided fine needle aspiration (FNA) as the first diagnostic test 2

2. Laboratory Testing: Measure serum TSH levels (higher levels associated with increased cancer risk) 1, 2

3. Imaging Studies:

   • Ultrasound of the thyroid and central neck (essential for all thyroid nodules) 2
   • CT/MRI with contrast for fixed, bulky, or substernal lesions 1, 3
   • Consider evaluation of vocal cord mobility (ultrasound, mirror indirect laryngoscopy, or fiberoptic laryngoscopy) 1

4. FNA Criteria: Perform FNA for:

   • Any nodule >1 cm 2
   • Nodules <1 cm with suspicious ultrasound features (microcalcifications, central hypervascularity, irregular borders) 1, 2
   • Any size nodule with suspicious clinical features in CHECK2 carriers 1

Important Considerations and Pitfalls

• False Negatives: A reassuring FNA should not override worrisome clinical findings, as false-negative results can occur 2
• Multiple Nodules: When multiple nodules are present, prioritize those with suspicious ultrasound features for FNA 2
• Voice Changes: Even in patients with preserved recurrent laryngeal nerves, voice quality can be temporarily affected after thyroid surgery, so baseline voice assessment is valuable 4
• Overdiagnosis Concern: Be aware that increased imaging has led to detection of many small, indolent thyroid cancers that may not require aggressive treatment 5, 6

Follow-up Recommendations

• For benign FNA results in CHECK2 carriers with suspicious clinical features, consider repeat FNA in 3-6 months due to higher baseline risk 2
• If FNA is inadequate or nondiagnostic, it should be repeated 2
• For indeterminate cytology, consider molecular testing to further stratify risk 2

Remember that CHECK2 mutation carriers may have an increased baseline risk for certain cancers, so maintaining a higher level of suspicion for malignancy is prudent when evaluating thyroid nodules in these individuals.