Metastatic bone lesion type in gastric cancer patients: imaging findings of case reports

Introduction

Gastric cancer (GC) is the fifth most common cancer worldwide and the third leading cause of cancer death in 2020, after lung and colorectal cancer. There are significant geographic differences in GC. Although its highest incidence and mortality are in Asia, it is also a major cause of mortality in Europe, with over 130,000 cases and 95,000 deaths estimated in 2020 (1,2). According to Lauren’s classification, GC is divided into the intestinal type and the diffuse type (3). The diffuse type, with occasional presence of signet ring cells, is less frequent but has a worse prognosis than the intestinal type, both commonly spreading via hematogenous and lymphatic routes (40–60%) (4).

Approximately 40–50% of patients present with unresectable disease at the time of diagnosis due to locally advanced GC or metastatic spread (5). Following surgery or later during the clinical course, GC frequently spreads to regional lymph nodes, liver, peritoneum, and lungs (6). Forty percent of patients will experience relapse, and the long-term prognosis remains poor. Globally, the 5-year survival for GC is about 30% and has remained stable for many years (7).

Bone metastasis (BM) commonly occurs in advanced stages of cancer, more frequently during the clinical course of prostate, breast, and lung cancer. However, it is rare for GC, with an incidence ranging from 1.0% to 20.0% (8,9). The presence of BM in metastatic GC has been reported as an independent poor prognostic factor, and GC patients with BMs exhibit the poorest median survival time compared to patients with metastases to other organs, including the chest, liver, or peritoneum (5). There is no significant difference in the incidence of BM between men and women (10). The primary tumor location in patients with GC and BM is more likely to be found in the cardiac and gastric body regions rather than in the antrum and pylorus (11). Diffuse-type GC is the most common type to progress to GC-BM, while intestinal-type GC is relatively rare (12).

Typical sites of GC-BM are lumbar and thoracic vertebrae and costal bones, followed by the pelvis, ribs, sternum, and long bones of limbs (9). In addition, more than half of the lesions caused by GC-BM are osteolytic lesions, followed by mixed lesions, and osteogenic lesions are the least common (13). Once BM occur, osteolytic or osteogenic lesions can easily cause skeletal-related events (SREs), and approximately 31% of GC patients with BM will experience them. SREs include pathological fractures, spinal cord compression, and hypercalcemia, which may result in reduced physical function and quality of life, requiring treatment with radiotherapy or surgery (14).

The primary diagnosis of BM is mostly based on clinical manifestations such as bone pain and neuromuscular symptoms. Computed tomography (CT) is mainly used for the diagnosis and monitoring of primary lesions of GC and metastasis to other organs. Currently, it is not a routine examination method for BM and is only recommended when there are symptoms (15). This could lead to the asymptomatic BM of GC being neglected in CTs. Positron emission tomography/computed tomography (PET/CT) with 18F-fluorodeoxyglucose (18F-FDG) has become the most used method for staging, response evaluation, recurrence detection, and restaging of GC, as it has high specificity for detecting lymph nodes and occult metastasis (16). Bone scintigraphy is typically used to confirm the presence of BM (15). Finally, magnetic resonance imaging (MRI) is used only in the presence of neurological symptoms and in the assessment of spinal and pelvic metastasis. We present this article in accordance with the CARE reporting checklist (available at https://qims.amegroups.com/article/view/10.21037/qims-24-425/rc).

Case presentation

A ten-year retrospective analysis was conducted on a database of 118 GC patients treated at our institution between 2010 and 2020. Within this cohort, metastases were most frequently observed in the peritoneum, affecting 25 patients (21.2%), followed by the liver, where 16 patients (13.6%) exhibited metastatic involvement. Lung metastases were identified in 7 patients (5.9%), while the pancreas was affected in 4 patients (3.4%). Additionally, metastases were found in the pleura and adrenal glands in 2 patients each (1.7%). Less commonly, the gallbladder, uterus, and brain were sites of metastasis, each affecting 1 patient (0.8%). These findings highlight the peritoneum and liver as the predominant sites of metastasis in this population, consistent with patterns described in the literature (6). Notably, of the entire cohort, eight patients (6.8%) developed BM, with four of these cases being osteoblastic and the other four osteolytic. All four patients with osteoblastic BM were men, with a mean age of 72.25 years (range, 67–87 years). These four patients underwent fibrogastroscopy, enabling an endoscopic assessment of the tumor (Figure 1) and the collection of samples for pathological anatomy, revealing one case of intestinal type and three of diffuse type (Figures 2-5).

Figure 1 Initial presentation of each case (#1, #2, #3, #4). Fibrogastroscopy (A) revealing an ulcerated, irregular, friable, infiltrative lesion involving the prepyloric region of the antrum and deforming the pylorus in Patient #1 (arrow), an extensive ulcerated lesion on the anterior aspect and greater curvature of the gastric body in Patient #2 (arrow), a protruding lesion on the posterior aspect and lesser curvature of the distal antrum in Patient #3 (arrow) and a deep ulcer on the greater curvature at the mid-body level, characterized by irregular edges and retraction in Patient #4 (arrow). Thoracoabdominal CT in axial plane and soft tissue reconstruction (B) showing thickening of the stomach walls in the antropyloric region (arrow), with small locoregional lymph nodes (*) in Patient #1. Patient #2 exhibited parietal thickening of the greater gastric curvature (white arrow) and a lymph node in the gastrohepatic ligament (*). In patient #3, wall thickening was observed at the antrum (arrow), while Patient #4 showed no signs of local or distant extension. (C) Thoracoabdominal CT in coronal plane and bone reconstruction revealed no evidence of bone metastases in any of the patients. CT, computed tomography.

Figure 2 Pathological features of Patient #1 revealed features consistent with intestinal-type gastric adenocarcinoma. (A) Presence of gastric glands (circles) (hematoxylin-eosin, 10×). (B) Four mitoses observed within a very small area (dashed circle) and glands (circles) exhibiting nuclear atypia with low nuclear-to-cytoplasmic ratio (arrows) (hematoxylin-eosin, 40×).

Figure 3 Pathological features of Patient #2 revealed features indicative of poorly cohesive carcinoma (diffuse type) with lymph node involvement. (A) Normal gastric epithelium (circle) and significant cellular proliferation infiltrating into the submucosa (dashed circle) (hematoxylin-eosin, 10× magnification). (B) Staining of cytokeratin 7 (CK7, 10× magnification) demonstrates the presence of infiltrating epithelial cells (dashed circle). (C) The neoplastic cells are isolated or arranged in small aggregates without well-formed glands (arrows) (hematoxylin-eosin, 40× magnification). (D) Lymph node with metastasis (dashed circle) (hematoxylin-eosin, 40× magnification).

Figure 4 Pathological features of Patient #3 reveal features consistent with signet-ring cell gastric adenocarcinoma (diffuse type). (A) Normal gastric epithelium (circle) and significant cellular proliferation infiltrating into the submucosa (dashed circle) (hematoxylin-eosin, 4× magnification). (B) Staining of cytokeratin AE1AE3 (CK AE1A3, ×10) highlighting epithelial cells (dashed circle). (C) Tumor cells exhibiting nuclear atypia (arrows) and presence of signet ring cells (dashed arrows) (hematoxylin-eosin, 40× magnification).

Figure 5 Pathological features of Patient #4 reveal features consistent with poorly cohesive carcinoma (diffuse type) with signet ring cells. (A) Normal gastric epithelium (circle) and neoplastic cells (dashed circle) (hematoxylin-eosin, 10× magnification). (B) Staining of cytokeratin AE1AE3 (CK AE1AE3, ×10) demonstrates the presence of epithelial cells infiltrating into the submucosa (dashed circle). (C) Tumor cells exhibiting nuclear atypia (arrows) and presence of signet ring cells (dashed arrows) (hematoxylin-eosin, 40× magnification).

Initial thoracoabdominal CT scans were conducted for all patients to assess the presence of local or distant disease extension. Two of them had initial stages without lymph node involvement or distant metastasis, while the other two had advanced stages with lymph node and metastatic involvement (Figure 1). In all cases that presented metastases at the time of diagnosis, these manifested as peritoneal carcinomatosis. First-line chemotherapy was initiated, and patients underwent periodic thoracoabdominal CT scans to assess disease progression.

Regarding patients without metastases, one underwent total gastrectomy, while the other, due to advanced age, did not undergo aggressive treatment and instead received symptomatic treatment. All four patients, whether initially presenting with metastases or not, experienced bone disease progression, as confirmed by the emergence of osteoblastic BM through bone scintigraphy (Figure 6). The median time to the onset of BM since GC diagnosis was 27.5 months (range, 6–51 months).

Figure 6 The appearance of osteoblastic bone metastases was observed in all four patients, diagnosed through follow-up thoracoabdominal CT scans and confirmed via bone scintigraphy. Patient #1 has an osteoblastic lesion in L3. Patient #2 exhibits multiple metastases located in the skull, spine, rib cage, clavicle, left scapula, pelvis, sternum, and left femur. Patient #3 presents multiple lesions demonstrating uptake in the bone scintigraphy located in the spine, pelvis, and left humerus. Patient #4 showcases multiple bone metastases in the pelvis, vertebrae, ribs, sternum, and scapulae, confirmed through bone scintigraphy, indicating a pattern suggestive of medullary dissemination.

One patient exhibited osteoblastic lesions in the spine and pelvis. The remaining patients additionally showed BM in the sternum, scapulae, and ribs (Figure 7). Biopsy was not performed due to the late-stage appearance with palliative care activation.

Figure 7 Progression in the form of multiple osteoblastic BM was observed in periodic CT scans, involving the spine and pelvis in Patient #1 (arrows), and affecting the sternum, scapulae, and ribs in Patients #2 and #3. Patient #4 presents a pattern of endomedullary metastasis with diffuse involvement of the entire skeletal framework. BM, bone metastasis; CT, computed tomography.

One patient also progressed with leptomeningeal carcinomatosis, and other one with colonic metastases.

All patients were diagnosed with BM at advanced stages of GC, following several disease progressions despite treatment. The BM did not receive specific treatment; instead, the patients were enrolled in a comprehensive palliative care program. Finally, after the diagnosis of BM, all patients succumbed, with an average time of 8.5 months (range, 3–19 months) from the diagnosis of BM to death.

Clinical and radiological features of each patient are described in detail in Appendix 1.

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patients for publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Discussion

In this case series, we delineate an unusual pattern of disease progression in GC, characterized by the development of osteoblastic BM.

Concerning the diagnosis of GC, the symptoms manifested by our patients were nonspecific, aligning with observations in the existing literature. GC commonly exhibits asymptomatic features, with manifestations often becoming evident in advanced stages. Abdominal pain, though present in 60% of GC patients, is not highly sensitive or specific as an indicator for GC (17). Other symptoms such as nausea, loss of appetite, difficulty swallowing, and melena are more sensitive and specific, yet they occur in only 20% to 35% of cases (18).

The reported occurrence of BM as the initial presentation of GC falls within the range of 1% to 8% in clinical practice cases (15). Despite the rarity of BM in GC patients reported in the literature, we observed such lesions in eight patients. Therefore, GC should be considered in the diagnostic algorithm for BM of unknown origin. Interestingly, half of the cases in our series involved osteoblastic involvement, contrasting with the limited literature available, where osteoblastic BM are much less frequent. This observation may suggest a higher frequency of osteoblastic BM in GC than previously anticipated. One plausible explanation for the increased detection of osteoblastic BM could be the improved quality of radiological imaging tests and the prolonged survival of patients.

The patients in our series received a BM diagnosis subsequent to the identification of GC during periodic thoracoabdominal CT check-ups. The thoracoabdominal CT scan was performed according to the standard protocol used in our center, which includes intravenous contrast in the portal phase, with axial and coronal reconstructions, along with a lung filter for thorough evaluation of the pulmonary parenchyma. Based on our findings, we recommend that physicians pay close attention to any symptoms of pain or mobility deficits in patients, which may justify advancing the timing of CT scans during oncological follow-ups. In such cases, individualized radiological monitoring could facilitate the early detection or exclusion of BM. Radiologists, in turn, should pay special attention to bone structures during oncological follow-ups of GC patients. Systematic bone reconstruction could be helpful in achieving better bone resolution and detecting bone metastases of the smallest possible size.

MRI does not play a role in the routine radiological follow-up of GC. It is useful for detecting specific complications, such as leptomeningeal carcinomatosis or spinal cord compression. BM, if located in the spine, could potentially lead to spinal cord compression, which would necessitate an MRI. However, this MRI should not be performed routinely for the detection of BM and should only be conducted urgently in cases of clinical suspicion of spinal cord compression or in a scheduled manner to study metastatic involvement of the spine in more detail.

Typically, BM in GC tend to occur in younger individuals and show an association with histologically undifferentiated adenocarcinoma, particularly signet-ring cell carcinoma. Additionally, it is associated with high angioinvasiveness and with advanced-stage disease accompanied by lymph node metastasis (19). In three of our cases, the histological subtype of GC was diffuse, consistent with literature findings (19). It is exceptionally rare for the primary tumor type to be intestinal, as in one of our patients, with no reported cases in the literature to our knowledge.

Seto et al. documented that the spine was the most frequently affected site in cases of BM, and about 20% of patients with BM would exhibit widespread or diffuse bone involvement (20). Clinical characteristics are nonspecific, presenting with refractory pain, pathological fractures, hypercalcemia, and spinal syndromes (8). None of our patients exhibited symptoms suggestive of BM, emphasizing the crucial role of radiologists in the diagnostic process.

The overall prognosis for BM in GC tends to be unfavorable. According to Ohyama et al., survival rates at 3 and 6 months following the diagnosis of BM were notably low, at 33% and 11%, respectively (16). All our patients were under palliative care at the time of their BM diagnosis; however, none received specific treatments within palliative care to address their BM that would alleviate their pain. This underscores the importance of considering the possibility of BM in palliative patients with metastatic GC, akin to the considerations typically given to lung, prostate, or breast cancer. This awareness will enhance radiologists’ vigilance in detecting these metastases and increase oncologists’ attentiveness to any musculoskeletal pain symptoms that may necessitate further evaluation with thoracoabdominal CT scans to identify possible M1 lesions.

Additionally, given that BM typically occurs at very advanced stages, promoting collaborations between hospital centers and palliative care teams is essential to provide symptomatic treatment for pain management and improved mobility.

Finally, incorporating standardized quality of life or mobility metric scales into clinical practice, which were not previously implemented in the management of these patients, could provide a more systematic approach to monitoring treatment response. These tools would allow healthcare providers to more accurately assess the impact of interventions on patient well-being and mobility, thereby facilitating more tailored and effective palliative care strategies. Including such metrics in future guidelines would not only improve patient care but also contribute valuable data for ongoing research into the management of bone metastases in GC patients.

Building on our preliminary findings, a prospective study focusing on patients with progressive GC would be highly beneficial. Such research should examine the incidence of osteolytic and osteoblastic BM and systematically monitor pain and motor function. This would allow for the assessment of targeted therapies aimed at improving quality of life in advanced disease stages. Further research in this area is essential to enhance our understanding and optimize the management of BM in GC.

Acknowledgments

Funding: None.

Footnote

Provenance and Peer Review: With the arrangement by the Guest Editors and the editorial office, this article has been reviewed by external peers.

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://qims.amegroups.com/article/view/10.21037/qims-24-425/rc

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-24-425/coif). The special issue “Advances in Diagnostic Musculoskeletal Imaging and Image-guided Therapy” was commissioned by the editorial office without any funding or sponsorship. X.T. served as the unpaid Guest Editor of the issue. The authors have no other conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institution and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patients for the publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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