Rare bone metastasis of neuroendocrine tumors of unknown origin: A case report and literature review

Background:
Neuroendocrine tumors (NETs) are rare neoplasms, accounting for approximately 0.5% of all tumors, and are characterized by their potential to metastasize to the liver, lymph nodes, and bones. Bone metastases from NETs are uncommon, and cases with unknown primary origin are even rarer. In this study, we report a unique case of a 30-year-old male presenting with diffuse osteosclerotic lesions secondary to bone metastases of a neuroendocrine tumor with no identifiable primary site, and we summarize relevant literature on diagnosis, differential diagnosis, and treatment.

Methods:
The patient presented with chronic lower back and leg pain. Imaging, including X-ray, CT, MRI, and bone scintigraphy, revealed multiple osteosclerotic lesions. Laboratory tests ruled out metabolic and hematologic disorders. Tumor markers were largely normal except for elevated NSE. Iliac crest and cervical lymph node biopsies confirmed a diagnosis of G2-grade metastatic neuroendocrine tumor with positive markers including Synaptophysin and Chromogranin A. PET/CT and pathological evaluation failed to locate the primary site. A detailed differential diagnosis was performed, comparing imaging and clinical features with osteopetrosis, skeletal fluorosis, and Paget disease.

Results:
The case demonstrated rare radiologic findings of diffuse osteosclerosis without typical osteolytic destruction, highlighting the diagnostic challenge. Pathology confirmed a well-differentiated neuroendocrine tumor with a Ki-67 index of 10%, consistent with G2 grade. Despite comprehensive imaging, the primary tumor remained unidentified. Symptomatic support and pain management were administered. A review of the literature revealed similar cases, with varying sites of metastasis and treatment responses including peptide receptor radionuclide therapy (PRRT), chemotherapy, and surgical interventions.

Conclusion:
We present a rare case of bone metastasis from a neuroendocrine tumor of unknown primary origin, featuring diffuse osteosclerotic changes. The unusual imaging findings and diagnostic complexity underscore the need for comprehensive evaluation using multimodal imaging and pathology. This case contributes to the growing body of literature on metastatic NETs and emphasizes the importance of considering NETs in the differential diagnosis of unexplained osteosclerosis.
 

Dr. Qing Pan is a PhD candidate in Orthopaedics at Union Hospital, Tongji Medical College, Huazhong University of Science and Technology. His research focuses on bone tumors, particularly the molecular mechanisms underlying osteosarcoma progression and drug resistance. He has published three SCI Q1 and three Q2 papers in the field. Dr. Pan’s recent work centers on gene fusion and autophagy-related pathways in sarcoma. With a strong background in translational research and experimental therapeutics, he aims to advance precision medicine approaches for bone cancer. He is actively engaged in both clinical and laboratory-based orthopedic oncology research.