What is the appropriate work‑up and management for a patient with a 2.3 cm lesion, several weeks of unexplained weight loss, episodes of syncope, and no relevant family history?

Evaluation and Management of a 2.3 cm Lesion with Weight Loss and Syncope

This patient requires urgent comprehensive evaluation with imaging, endocrine workup, and cardiac assessment, as the combination of a 2.3 cm lesion, unexplained weight loss, and syncope raises concern for either a functional neuroendocrine tumor or malignancy with systemic effects.

Immediate Diagnostic Priorities

Determine Lesion Location and Characteristics

The 2.3 cm size is critical because it crosses key thresholds for malignancy risk depending on anatomic location:

• If adrenal: Lesions >3 cm have higher malignancy risk, but at 2.3 cm with constitutional symptoms, immediate imaging with non-enhanced CT or chemical shift MRI is indicated to characterize the lesion 1
• If gastric/gastrointestinal: A 2.3 cm gastric lesion warrants presumption of GIST until proven otherwise, requiring EUS-guided biopsy for tissue diagnosis and risk stratification 2, 3
• If hepatic: In the context of weight loss, a 2.3 cm liver lesion requires dynamic contrast imaging (CT or MRI) to assess vascular characteristics, as hypervascular lesions with washout suggest hepatocellular carcinoma or metastasis 1

Syncope Evaluation Takes Precedence

The syncope must be evaluated urgently as it may represent life-threatening cardiac arrhythmia or carcinoid crisis 1:

• Obtain 12-lead ECG immediately to exclude long QT syndrome, Brugada pattern, or AV block 1
• Echocardiography is indicated for structural heart disease assessment and risk stratification, particularly if the lesion could be a cardiac tumor or if carcinoid heart disease is suspected 1
• Exercise stress testing should be performed if syncope occurred during or shortly after exertion, as this suggests cardiac etiology 1

Endocrine Workup for Functional Tumors

Given the triad of a discrete lesion, weight loss, and syncope, functional neuroendocrine tumors must be excluded 1:

• 24-hour urine 5-HIAA and serum chromogranin A to screen for carcinoid syndrome
• Plasma or urine metanephrines to exclude pheochromocytoma before any biopsy attempt, as undiagnosed pheochromocytoma can cause life-threatening hypertensive crisis during procedures 1
• Fasting glucose and insulin levels if hypoglycemic episodes could explain syncope (insulinoma)
• Serum gastrin if peptic symptoms present (gastrinoma)

Imaging Algorithm Based on Initial Findings

For Adrenal Lesions (2.3 cm)

• Non-enhanced CT is the first-line test: attenuation <10 HU indicates benign adenoma 1
• If attenuation >10 HU, proceed to chemical shift MRI or delayed contrast-enhanced CT 1
• FDG-PET should be considered if CT/MRI are indeterminate, as SUV >4 suggests malignancy 1
• Biopsy only after pheochromocytoma is biochemically excluded 1

For Gastric/GI Lesions (2.3 cm)

• EUS with assessment of cortical thickness, echogenicity, and margins 2
• EUS-guided core needle biopsy (not FNA) for tissue architecture and immunohistochemistry 2
• KIT (CD117) and DOG1 immunostaining to confirm GIST 2
• Contrast-enhanced CT abdomen/pelvis to assess for metastatic disease 2

For Hepatic Lesions (2.3 cm)

• Dynamic contrast CT or MRI: hypervascular in arterial phase with washout in portal/venous phase is diagnostic of HCC in cirrhotic patients 1
• If vascular profile is atypical, biopsy is required 1
• AFP level >200 ng/mL eliminates need for biopsy in appropriate clinical context 1

Management of Constitutional Symptoms

Weight Loss Investigation

• Comprehensive metabolic panel, CBC, TSH to exclude metabolic causes
• If neuroendocrine tumor confirmed, octreotide 50 mcg/hour IV infusion should be initiated before any surgical intervention to prevent carcinoid crisis 1

Syncope-Specific Interventions

• If cardiac cause identified (structural disease, arrhythmia), cardiology consultation for potential pacemaker or ICD 1
• If neurocardiogenic syncope suspected after cardiac causes excluded, tilt-table testing may be considered, though this is less urgent than ruling out life-threatening etiologies 1

Critical Pitfalls to Avoid

• Never biopsy a suspected pheochromocytoma without biochemical exclusion first - this can precipitate hypertensive crisis 1
• Do not assume syncope is benign vasovagal - in the context of a mass lesion and weight loss, cardiac and endocrine causes must be excluded first 1
• Avoid FNA when core biopsy is feasible - tissue architecture is essential for accurate diagnosis of GISTs and other tumors 2
• Do not delay imaging based on clinical impression - a 2.3 cm lesion with constitutional symptoms warrants urgent imaging regardless of physical exam findings 1

Multidisciplinary Coordination

This patient requires coordinated evaluation by:

• Cardiology for syncope workup and risk stratification 1
• Endocrinology for functional tumor assessment 1
• Surgical oncology if malignancy confirmed or high-risk features present 1, 2
• Gastroenterology if GI primary suspected for EUS and potential endoscopic resection 2, 3