What are the differential diagnoses and appropriate work‑up for a soft‑tissue mass in the midline neck?

Differential Diagnosis and Work-Up for Midline Neck Soft Tissue Mass

A soft tissue mass in the central/midline neck in an adult must be considered malignant until proven otherwise, and requires immediate systematic evaluation with CT or MRI with contrast if any high-risk features are present. 1

Key Differential Diagnoses for Midline Neck Masses

Malignant Etiologies (Priority Consideration)

• Thyroid carcinoma (papillary, follicular, medullary, anaplastic) 1
• Metastatic squamous cell carcinoma from head and neck primary 1
• Lymphoma (especially if infiltrative, encasing vessels without invasion) 1
• Thyroglossal duct cyst carcinoma (1-7% of thyroglossal duct cysts, typically papillary carcinoma) 2, 3, 4
• Thymic malignancy (thymoma, thymic carcinoma) if prevascular/anterior mediastinal extension 1

Benign/Congenital Etiologies

• Thyroglossal duct cyst (most common congenital midline neck mass, 7% of population) 3, 5, 6
• Ectopic thyroid tissue 5
• Thymic hyperplasia (especially in younger patients or post-chemotherapy/stress) 1
• Dermoid/epidermoid cyst 5

Risk Stratification: High-Risk Features Requiring Urgent Work-Up

Clinical History Red Flags

• Mass present ≥2 weeks without significant fluctuation or uncertain duration 1
• No history of infectious etiology 1
• Age >40 years (higher malignancy risk) 1
• Rapid growth over weeks to months 2, 4
• Pain on swallowing or dysphagia 6

Physical Examination Red Flags

• Size >1.5 cm 1
• Firm consistency 1
• Fixation to adjacent tissues 1
• Ulceration of overlying skin 1
• Non-mobile mass (especially concerning for malignancy) 6

Diagnostic Algorithm

Step 1: Initial Evaluation

• Perform targeted history focusing on duration, growth rate, pain, dysphagia, voice changes, prior radiation exposure, family history of thyroid cancer 1
• Complete physical examination including visualization of larynx, base of tongue, and pharynx (requires laryngoscopy if high-risk features present) 1
• Palpate thyroid gland and cervical lymph nodes bilaterally 4

Step 2: Initial Imaging

• Plain radiographs are the fundamental first step for any neck mass to identify calcifications, bone involvement (hyoid destruction), or intrinsic fat 1, 7, 2
• Ultrasound is highly appropriate for superficial midline masses (sensitivity 94.1%, specificity 99.7%) to differentiate solid from cystic components and assess thyroid gland 7, 8, 4

Step 3: Advanced Imaging for High-Risk Masses

• CT neck with contrast OR MRI with contrast is strongly recommended for any mass with high-risk features 1
• CT provides superior evaluation of bone destruction (hyoid, thyroid cartilage), relationship to foramen cecum, and extent of disease 2, 5
• MRI is preferred when ultrasound is indeterminate or for superior soft tissue characterization 7
• Thyroid ultrasound should be performed to evaluate for concurrent thyroid pathology and cervical lymphadenopathy 4

Step 4: Tissue Diagnosis

• Fine-needle aspiration (FNA) is preferred over open biopsy for suspected malignancy 1
• Target solid components within cystic lesions on ultrasound guidance 4
• FNA has moderate sensitivity (62%) for thyroglossal duct cysts but higher accuracy for solid malignancies 6
• Core needle biopsy may be needed if FNA is non-diagnostic 7

Critical Pitfalls to Avoid

Common Diagnostic Errors

• Physical examination alone is insufficient (only 85% accurate for soft tissue masses) 7
• Assuming all midline cystic masses are benign thyroglossal duct cysts without imaging—7% harbor malignancy 4
• Performing open biopsy before imaging can compromise subsequent definitive surgery 1, 7
• Missing concurrent thyroid pathology—multifocal thyroid cancer found in 40% of thyroglossal duct cyst carcinoma cases 4

Specific Imaging Considerations

• Thyroglossal duct cysts typically located along embryologic path from foramen cecum, looping around hyoid bone anteriorly 5
• Solid nodule within cyst wall on ultrasound is highly suspicious for malignancy 4
• Destruction of hyoid bone or thyroid cartilage indicates aggressive behavior requiring urgent oncologic referral 2

Management Based on Findings

If Malignancy Confirmed or Highly Suspected

• Immediate referral to head and neck cancer specialist or surgical oncologist 1
• Total thyroidectomy should be considered for all thyroglossal duct cyst carcinomas due to multifocal disease risk 4
• Avoid empiric antibiotics for presumed infection without clear infectious etiology—this delays cancer diagnosis 1

If Low-Risk Benign Features

• Document clear follow-up plan with specific criteria triggering re-evaluation 1
• Advise patient of warning signs requiring immediate return (rapid growth, new symptoms) 1
• Surgical excision (Sistrunk procedure) remains standard for thyroglossal duct cysts even when benign 3