What is the appropriate diagnostic approach for a lesion in the supraclavicular region?

Diagnostic Approach for Supraclavicular Lesions

For any supraclavicular mass, obtain tissue diagnosis via ultrasound-guided fine needle aspiration (FNA) with core biopsy, as this location carries a 78-79% probability of malignancy and requires histologic confirmation to guide treatment. 1, 2

Initial Clinical Assessment

Key Physical Examination Elements

• Assess for primary malignancy sites systematically: 3
  • Head and neck examination: Complete visualization and palpation of nasopharynx, base of tongue, hypopharynx, supraglottic larynx, tonsils (bimanual palpation), and floor of mouth 3
  • Skin examination: Evaluate entire integument for melanoma or squamous cell carcinoma 3
  • Thyroid and salivary gland palpation 3
  • Breast examination (in women) 3
  • Abdominal examination: Assess for hepatomegaly or masses 3
  • Testicular examination (in men over 40) 3
  • Gynecologic examination (in women) for ovarian primary 3

Laterality Significance

• Left supraclavicular nodes (Virchow's node): Strongly suggest infradiaphragmatic primary malignancies including gastric, pancreatic, genitourinary (16 of 17 cases), or ovarian cancers 3, 4, 1
• Right supraclavicular nodes: More commonly associated with lung, breast, or esophageal primaries 1, 2
• Either side: Can represent metastases from head/neck squamous cell carcinoma, lymphoma, or breast cancer 3

Mandatory Diagnostic Workup

Tissue Acquisition (First Priority)

• Ultrasound-guided FNA with core biopsy is the primary diagnostic modality for all supraclavicular masses ≥0.5 cm 5, 6, 2
• Rapid on-site evaluation (ROSE) by cytologist improves diagnostic yield 2
• Tissue adequacy is critical for both diagnosis and molecular profiling 2

Laboratory Studies Based on Histology Type

For Adenocarcinoma or Carcinoma NOS: 3

• PSA (men >40 years or any age with bone metastases) 3
• CA-125 (women with mediastinal, peritoneal, or retroperitoneal involvement) 3
• CA 19-9 and AFP (if cholangiocarcinoma suspected) 4
• HER2 testing (for advanced disease treatment planning) 3

For Squamous Cell Carcinoma: 3

• Follow NCCN Head and Neck Cancer occult primary guidelines 3
• Consider anal endoscopy if inguinal nodes also involved 3

For Neuroendocrine Tumors: 3

• Follow NCCN Neuroendocrine Unknown Primary guidelines 3

Cross-Sectional Imaging (Mandatory)

• CT chest/abdomen/pelvis with contrast (or MRI if contrast contraindicated) 3
• PET/CT scan to identify occult primary and assess extent of disease 3, 6
• Brain MRI only if neurologic symptoms present 3

Endoscopic Evaluation Based on Histology

For Adenocarcinoma: 3

• Upper endoscopy with narrow-band imaging or Lugol's solution 3
• Colonoscopy (if liver involvement or positive fecal occult blood) 3
• Bronchoscopy (if lung lesion identified) 3

For Squamous Cell Carcinoma: 3

• Fiberoptic examination of nasopharynx, base of tongue, hypopharynx, larynx 3
• Consider direct laryngoscopy with biopsies under anesthesia 3

Ancillary Studies for Treatment Planning

Immunohistochemistry Panel (71.6% of cases require) 2

• Adenocarcinoma: CK7/CK20, TTF-1, GATA3 (for urothelial), CDX2 (for GI primary) 4, 2
• Squamous cell carcinoma: CK5/6, p63, p40 3
• Neuroendocrine markers: Synaptophysin, chromogranin 3

Molecular Testing (When Indicated) 2

• PD-L1 testing (23.9% of cases) for immunotherapy eligibility 2
• Next-generation sequencing (9.1% of cases) for targetable mutations 2
• FISH testing (8.0% of cases) for specific translocations 2
• Flow cytometry (22.7% of cases) if lymphoma suspected 2

Common Pitfalls to Avoid

• Do not rely on palpation alone: 40% of supraclavicular abnormalities are nonpalpable but detectable on imaging 6
• Do not skip tissue diagnosis: Clinical and radiologic assessment cannot reliably distinguish benign from malignant lesions (21.6% are benign) 5, 1
• Do not assume head/neck primary: 50% of level IV and supraclavicular masses originate below the clavicle 3
• Do not perform inadequate biopsy: Ensure sufficient tissue for both diagnosis and molecular profiling in the era of precision medicine 2
• Do not overlook tuberculosis: This accounts for 38% (11/29) of benign supraclavicular masses in some series 1

Staging Implications

• Breast cancer: Ipsilateral supraclavicular node involvement is N3c disease (Stage IIIC), no longer M1 3
• Lung cancer: Supraclavicular involvement requires invasive mediastinal staging regardless of CT/PET findings 3
• Esophageal cancer: Supraclavicular nodes indicate metastatic disease requiring systemic therapy rather than curative resection 3