Large Flat Bone Metastasis from Gastric Neuroendocrine Neoplasm Mimicking a Primary Bone Malignancy: A Rare and Unusual Presentation

Abstract

The presented case illustrates a rare presentation of a well-differentiated neuroendocrine tumor (NET) in the form of a large, infiltrative soft tissue flat bone mass which was ultimately diagnosed as an unusual skeletal metastasis from a gastric NET. While at initial diagnosis, a differential diagnosis of a primary bone tumor was considered based upon pelvic ultrasound and magnetic resonance imaging, the histopathological analysis confirmed a metastatic well-differentiated grade II NET with a MIB-1 labelling index of 5%. In summary, the case underscores the diagnostic and management challenges posed by NET metastases, particularly the potential for bone metastases to present as atypical, aggressive-appearing lesions. It also emphasizes the crucial role of advanced imaging in guiding accurate diagnosis and therapeutic decision-making.

 

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Keywords

neuroendocrine tumors (NETs) - ¹⁸F-AlF-NOTA-octreotide - ¹⁸FDG PET/CT - SSTR - bone metastasis

Introduction

Neuroendocrine neoplasms (NENs) form a heterogenous group of tumors, which are broadly divided into well-differentiated grade I to III neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine carcinoma, based on tumor morphology, mitotic count, and the Ki67 proliferation index. The skeletal system is a frequent site of metastasis from solid tumors, including NETs. Approximately half of the patients with NET at initial staging are metastatic, with bone metastases (BMs) affecting around 20% of patients, the most common primary sites being the pancreas, small bowel, and lungs.[1] [2] Of the skeletal sites, the vertebral bodies are most commonly involved, followed by pelvic bones and ribs. Metastasis to the appendicular skeleton is relatively rare.[3]

Herein, we report a teaching case study of a rare case of skeletal metastasis from gastric NET, mimicking a primary pelvic bone tumor at presentation. A 48-year-old woman with persistent left hip pain was found to have a metastatic grade II well-differentiated NET in the left iliac bone. Somatostatin receptor (SSTR)-based positron emission tomography/computed tomography (PET/CT) scans identified the likely primary tumor in the stomach, with additional metastases in the liver, spine, and humerus. Low grade 18F-fluorodeoxyglucose (18 F-FDG) uptake indicated moderate proliferative activity, consistent with the tumor grade. The case highlights the diagnostic challenges posed by BMs from NETs, which can on instances mimic primary bone neoplasms.

The noteworthy learning points were a large and atypical bone lesion in the setting of NET, the significance of a thorough differential diagnosis, the role of advanced imaging modalities like SSTR-based PET/ CT and ¹⁸F-FDG PET/CT in the evaluation of NEN metastases, and the management of such patients. It provided insights into the heterogeneous behavior of NETs, which can lead to varied presentations, thereby helping clinicians recognize and treat these metastases effectively.

 

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Case Report

A 48-year-old woman with no known comorbidities presented with left hip pain radiating to the left lower limb, which was attributed to a minor fall she had experienced a year previously. She was further evaluated using regional ultrasound for persistent pain, which revealed a large infiltrative soft tissue mass in the left iliac bone. A contrast-enhanced magnetic resonance imaging showed a large, lobulated mass in the left iliac bone infiltrating the left sacroiliac joint. A differential diagnosis of a primary bone tumor was considered, and a biopsy was performed. Histopathological analysis confirmed a metastatic grade II well-differentiated NET with a MIB-1 labelling index of 5% and serum chromogranin A level of 3,368 ng/mL ([Fig. 1]).

Fig. 1 (A) Histopathologic evaluation revealed a uniform population of neoplastic cells arranged in anastomosing cords and trabeculae and composed of plasmacytoid cells with stippled chromatin (hematoxylin and eosin, 100× original magnification). (B) Tumor cells are strongly positive for cytoplasmic chromogranin (immunoperoxidase, 200× original magnification). (C) Ki-67 labelling index by MIB-1 immunohistochemistry shows reactivity in 5% tumor nuclei (immunoperoxidase, 400× original magnification).

To localize the primary tumor and assess other metastatic sites, a SSTR-based ¹⁸F- 1,4,7-triazacyclononane-1,4,7-triacetate (NOTA)-octreotide PET/CT scan was performed. A subtle SSTR-expressing nodule was identified along the lesser curvature of the stomach, suggesting a gastric primary tumor. Additionally, SSTR-expressing hypodense lesions in the liver and three skeletal lesions were detected: two in the spine and one in the right humerus. To further assess tumor biology and prognosis, an ¹⁸F-FDG PET/CT scan was performed, showing low-grade ¹⁸F-FDG uptake similar to the liver background in all the lesions identified on SSTR PET/CT ([Figs. 2] and [3]). The high SSTR expression and low FDG avidity were consistent with the typical molecular imaging characteristics of a grade II well-differentiated NET.

Fig. 2 Maximum-intensity projection (MIP) image of ¹⁸F-NOTA-octreotide PET/CT (A) showing an intensely SSTR-expressing large mass in the left iliac bone and sacrum (Krenning score 3, SUV_max: 16.0), SSTR-expressing gastric nodule-primary tumor site (red arrow), and other skeletal metastatic sites (blue arrows). ¹⁸F-FDG PET/CT MIP (G) shows low-grade ¹⁸F-FDG uptake similar to the liver background in all the lesions identified on SSTR PET/CT. Fused trans-axial PET/CT slice of ¹⁸F-AlF-NOTA-octreotide PET/CT (B), ¹⁸F-FDG PET/CT (C), and the corresponding CT slice (D) in soft tissue window showing intense SSTR expression and low-grade FDG concentration in a large osteolytic mass in the left iliac bone infiltrating the left sacroiliac joint and S1 and S2 vertebra along the left lateral aspect. Post-contrast T1-weighted MRI trans-axial image (E) shows heterogeneous arterial enhancement in the same lesion. CT, computed tomography; MRI, magnetic resonance imaging; PET, positron emission tomography; SSTR, somatostatin receptor.

Fig. 3 Fused ¹⁸F-NOTA-octreotide PET/CT axial images (A and B) with corresponding CT slices (B and C) demonstrating the primary gastric nodule (Krenning's score 3, SUV_max: 10.2) in soft tissue window (long white arrow) and lytic lesion in left lamina of D12 vertebral body (Krenning score 3, SUV_max: 11.5) in bone window (short bold white arrow). CT, computed tomography; PET, positron emission tomography.

 

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Discussion

NETs originate from neuroendocrine cells, which are distributed throughout the body and typically exhibit indolent growth. Although approximately 60 to 70% of NETs arise in the gastroenteropancreatic system, gastric NETs are particularly rare, with an incidence of just 0.2 cases per 100,000 people. The prognosis of NETs depends on multiple factors, including primary tumor site, tumor grade and stage, functional status (hormone secretion), and receptor status (e.g., SSTR expression). Notably, small intestine NETs often have a higher malignant potential but may still progress slowly, even when metastatic. In contrast, gastric and rectal NETs usually have a lower tendency to metastasize; however, if they do spread, their progression can become aggressive.[4] [5]

The skeletal system, particularly the axial skeleton, is a common site for BMs due to the rich vascular supply of red marrow.[6] Adhesion molecules produced by cancer cells allow them to bind to marrow cells, leading to proliferation through the release of growth factors. BMs in NET can be challenging to diagnose, as patients are often asymptomatic, and small lesions may not be detected on conventional imaging. Typically, BMs are incidentally detected during the initial staging workup because only about half of the patients show skeletal-related symptoms. The BM characteristics of NET are small osteoblastic lesions. Osteolytic and mixed blastic-lytic lesions are relatively infrequent. Synchronous BMs are considered negative prognostic markers of overall survival in patients with NET.[3] [7] [8]

Well-differentiated NETs exhibit high SSTR expression, making them ideal targets for diagnosis, staging, and radionuclide therapy using radiolabeled somatostatin analogs (SSAs). For diagnostic imaging, ⁶⁸Ga-DOTA-SSA PET/CT—including ⁶⁸Ga-DOTATATE, ⁶⁸Ga-DOTATOC, and ⁶⁸Ga-DOTANOC—is currently the gold standard. However, ⁶⁸Ga has several limitations, such as a short half-life (requiring an on-site generator), high production costs, and low activity yield. These challenges are addressed by ¹⁸F-labeled tracers, such as ¹⁸F-AlF-NOTA-octreotide (¹⁸F-AlF-OC), which offer distinct advantages like longer half-life, enabling centralized production and wider distribution to PET centers without on-site radiopharmacy facilities, as well as a higher activity yield and superior spatial resolution due to a shorter positron range.

Prospective studies comparing ⁶⁸Ga-DOTA-SSAs and ¹⁸F-AlF-OC have demonstrated comparable diagnostic accuracy, with ¹⁸F-AlF-OC showing noninferiority in detection rate, a higher tumor-to-background ratio, and improved detection of liver metastases. However, ⁶⁸Ga-DOTATATE may still outperform ¹⁸F-AlF-OC in identifying BMs in some cases.[9] [10] Given its cost-effectiveness and logistical advantages, ¹⁸F-AlF-OC serves as an excellent alternative to ⁶⁸Ga-DOTA-SSAs, as illustrated in this case where the patient underwent 18F-AlF-OC PET/CT at an external diagnostic center prior to referral to our hospital.

To our knowledge, few cases of such large infiltrative BM from NET have been reported in the literature. Despite the aggressive nature of this lesion, as seen by its infiltrative growth on CT, ¹⁸F-FDG PET/CT reveals low avidity, consistent with the well-differentiated nature of typical NET. In our case, as the patient was symptomatic, she received local radiotherapy for her large inoperable skeletal lesion, following which her pain dramatically reduced and was then planned for lutetium-177 (¹⁷⁷Lu)-DOTATATE-based peptide receptor radionuclide therapy for metastatic site targeting.

 

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Conclusion

In summary, this case illustrates a rare presentation of a large, infiltrative soft tissue flat bone mass mimicking a primary bone neoplasm, which was ultimately diagnosed as an unusual skeletal metastasis from a likely gastric NET. It underscores the heterogeneous nature of NET and highlights the promising role of advanced imaging techniques, such as SSTR-based PET/CT and ¹⁸F-FDG PET/CT, in staging, managing, and prognosticating these tumors.

 

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Conflict of Interest

None declared.

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Publication History

Article published online:
07 July 2025