A Novel Technology for 3D‐Printing Artificial Vertebral Bodies for Treating Lumbar Spine Adrenal Pheochromocytoma Metastases: A Case Report and Review of the Literature

Abstract

Background

Pheochromocytoma is an adrenal medullary neuroendocrine tumor that rarely metastasizes to the spine. Currently, its specific treatment methods still present challenges.

Case Description

A 41‐year‐old male patient who underwent left total adrenalectomy due to pheochromocytoma 3 years ago presented with lower back pain, accompanied by numbness and decreased muscle strength in both legs, as well as decreased sensation. Abnormal transmittance of the L3 vertebral body could be seen on anterior–posterior and lateral lumbar X‐rays, irregular bone destruction of the L3 vertebral body was found on CT, and an MRI scan showed that the tumor was located within the L3 vertebral body, protruding into the spinal canal and compressing the epidural sac. No recurrence was found in the abdomen. Preoperatively, perform local embolization of the blood vessels supplying the tumor. First, the L2‐3 intervertebral disc, L3‐4 intervertebral disc and L3 vertebral body were removed using an anterior approach, the whole tumor was removed, and some of the vertebrae were taken for pathological examination and replaced with a 3D‐printed prosthesis. Then, four pedicle screws were placed in the bilateral pedicles of L2 and L4 using the posterior approach, pre‐bent connecting rods were installed to replace the bone cortex of the lamina and articular process followed by bone graft fusion of the interlaminar and facet joints. The postoperative results were satisfactory, and there were no perioperative complications.

Conclusion

Lumbar pheochromocytoma metastasis is rare, difficult to treat, and should be considered in spinal metastases' differential diagnoses so early diagnosis can be made based on medical history and imaging. Preoperative local vascular imaging and embolization of the blood supply vessels were performed. After total en‐bloc spondylectomy of the tumor during surgery, a prosthesis was implanted and combined with pedicle screw fixation to reconstruct spinal biomechanical stability, achieving satisfactory results. Therefore, 3D printed artificial vertebral bodies are a good choice for treating adrenal pheochromocytoma lumbar metastasis. The key to successful treatment is close interdisciplinary collaboration in formulating rigorous comprehensive perioperative plans.

Lumbar pheochromocytoma metastasis is rare, difficult to treat, and should be considered in spinal metastases' differential diagnoses so early diagnosis can be made based on medical history and imaging. Preoperative local vascular imaging and embolization of the blood supply vessels were performed. After total en‐bloc spondylectomy of the tumor during surgery, a prosthesis was implanted and combined with pedicle screw fixation to reconstruct spinal biomechanical stability, achieving satisfactory results.

Introduction

Pheochromocytoma is a catecholamine‐secreting adrenal medullary neuroendocrine tumor with an estimated incidence of 0.2–0.9 cases per 0.1 million person‐years; of which the incidence of malignant pheochromocytoma accounts for approximately 10%. Histology alone is not enough to distinguish benign and malignant pheochromocytomas. Tumor metastasis is one of the criteria for malignancy. ¹ , ² , ³ , ⁴ , ⁵ , ⁶ Although bone is the most common site of metastasis, spinal involvement is rare. Metastatic pheochromocytoma often has a poor prognosis and limited long‐term survival rate. ⁷ , ⁸ In this case report, we describe a case of left adrenal pheochromocytoma with subsequent lumbar vertebral metastasis after surgery, and review the literature to explore its clinical characteristics and treatment methods.

Case Description

A 41‐year‐old male patient underwent a left adrenalectomy and total tumor resection for pheochromocytoma 3 years ago. Three years after the operation, the patient began to develop low back pain, and numbness of both lower limbs, but without a headache, palpitations, sweating or other symptoms. Physical examination revealed numbness in both lower limbs, more pronounced in the left lower limb. There is reduced sensation accompanied by pain in the anterior and lateral aspects of the thighs, particularly evident in the lower one‐third of the anterior aspect of the left thigh in an oblique belt‐like pattern. Weakness is observed during hip joint flexion, abduction, and adduction movements. Slight atrophy of the quadriceps femoris muscle is present, along with weakness in knee extension and diminished patellar reflex. Plasma epinephrine and norepinephrine and 24‐hour urinary vanillylmandelic acid were all at normal levels, abnormal transmittance of the L3 vertebral body could be seen on anterior and lateral lumbar X‐ray, and irregular bone destruction of the L3 vertebral body and local interruption of the bone cortex were found on lumbar CT examination. Lumbar MRI examination showed an abnormal signal of the L3 vertebral body, the lesion protruded back into the spinal canal, and the corresponding level of the dural sac was compressed. On the cross‐sectional MRI scan, there were signal voids in multiple areas of the tumor (Figures 1 and 2).

FIGURE 1.

(A, B): Anterior and lateral X‐rays of lumbar vertebrae showed abnormal transmittance of the L3 vertebral body and disorder of bone trabeculae. (C–E) CT of lumbar vertebrae showed irregular bone destruction of the L3 vertebral body with multiple septal shadows and local interruption of the bone cortex.

FIGURE 2.

(A–D) Lumbar MRI showed an abnormal signal for the L3 vertebral body, a low signal intensity on T1WI and T2WI for lesions, and a slightly high signal intensity on STIR for lesions, protruding into the posterior spinal canal and compressing the dural sac.

Based on the patient's previous history of adrenal pheochromocytoma and absence of other tumor‐related medical records, coupled with imaging findings displaying typical vertebral body osteolysis and intruding mass compressing the dura mater within the vertebral canal, a preliminary diagnosis of adrenal pheochromocytoma metastasis to the lumbar vertebrae is established. The conclusive pathological examination of the specimen further corroborated the initial diagnosis. A multi‐disciplinary treatment (MDT) consultation was conducted, involving the oncology, surgical oncology, spinal tumor, and interventional radiology departments. Following extensive team discussions, considering the patient's overall physical condition, tumor vasculature, and endocrine characteristics, the final decision was to proceed with localized tumor embolization under the guidance of the interventional radiology team. This was aimed at reducing tumor blood supply, thereby minimizing intraoperative bleeding during the subsequent surgical intervention. The approach involved an anterolateral entry for total en‐bloc spondylectomy of the tumor mass, followed by implantation of a patient‐individual 3D‐printed artificial vertebral body, crafted using preoperative imaging data. The artificial vertebral body was secured, and subsequently, a posterior entry approach was adopted to stabilize the adjacent vertebrae using pedicle screws, thereby restoring spinal biomechanical stability and physiological equilibrium. Post‐surgery, a consolidation therapy was administered in accordance with the radiation and chemotherapy protocols formulated by the oncology department.

The right femoral artery was punctured under local anesthesia, and abdominal aortography was performed before the operation. The results showed that the trunk of the bilateral L2 vertebral artery and right L3 and 4 vertebral arteries were enlarged, the terminal vessels were disorderly, and a patchy tumor shadow could be seen in the parenchymal phase. Three slender tortuous vessels were seen at the beginning of the inferior mesenteric artery were visualized, and the tumor blood vessels were embolized. After that, the patient was placed in the right lying position under general anesthesia. The patient received intraoperative somatosensory evoked potential (SEP) monitoring throughout the surgery. The operation was performed from a lumbar lateral anterior approach and layer‐by‐layer incision and blunt dissection were used to expose the L2, 3 and 4 vertebrae. The L2‐3 and L3‐4 intervertebral discs were excised and all tumors were removed. Some of the tissue was sent for pathological examination. Total resection of L3 vertebra and exposure of L3 segment dura mater was followed by 3D printing prosthesis implantation and tightening of the screws. C‐arm fluoroscopy showed that the prostheses were in a good position. The drainage tube was placed in the low position, and the wound was sutured layer by layer and bandaged with an aseptic dressing. After turning the patient over, the spinous process, articular process and lamina of L2‐4 were cut and exposed layer by layer with the L2‐4 spinous process at the center, and four screws were placed in the bilateral pedicles of L2 and L4. Pre‐curved connecting rods were installed and C‐arm fluoroscopy showed that the position of internal fixation was good. The bone cortex of the vertebral lamina and facet joint was treated, bone graft fusion between the lamina and facet joint was performed, and a drainage tube was placed in a low position. The wound was sutured layer by layer and dressed with aseptic dressing. The SEP monitoring was normal, the patient had no symptoms (such as palpitations or sweating), and the hemodynamics remained stable during the operation. Three days after the surgery, the lumbar spine anteroposterior and lateral X‐ray showed that the 3D printed artificial vertebral body and internal fixation were in good position, and the intervertebral height was satisfactory. During the final follow‐up 1 year after the surgery, X‐ray and CT scan showed that the position of the artificial vertebral body was good, without loosening, fractures or subsidence. The internal fixation remained intact without detachment or breakage and the spinal canal walls were intact (Figure 3). The patient's lower limbs exhibited good mobility and sensation, with normal muscle strength.

FIGURE 3.

(A) Preoperative angiography reveals a significantly enhanced shadow of the L3 vertebral body compared to a normal vertebral body, suggesting a highly abundant blood supply to the tumor. (B) After embolization of the blood vessels supplying the tumor, the shadow of the vertebral body appears similar to a normal vertebral body, indicating a significant reduction in tumor blood supply. (C, D): three days after the surgery, the lumbar spine anteroposterior and lateral X‐ray showed that the 3D printed artificial vertebral body and internal fixation were in good position, and the intervertebral height was satisfactory. (E, H) During the final follow‐up 1 year after the surgery, X‐ray and CT scan showed that the position of the artificial vertebral body was good, without loosening, fractures or subsidence. The internal fixation remained intact without detachment or breakage and the spinal canal walls were intact.

Bone metastatic pheochromocytoma was diagnosed by histopathology during the operation. Hematoxylin–eosin staining showed that a large number of chromaffin cells were separated into lobules or nests, showing the characteristic Zellballen nest shape of uniform pheochromocytoma (Figure 4). The cells were granular eosinophilic cytoplasm, and basophilic nuclei were pleomorphic. Immunohistochemistry showed that synaptophysin and chromogranin A were positive, while cytokeratin, epithelial membrane antigen and other markers were negative (Figure 5). Blood pressure was normal after the operation, and the levels of epinephrine and norepinephrine in blood and urine were in the normal range. No obvious tumor residues were found on MRI examination. The results of gene detection for von Hippel–Lindau disease and multiple endocrine tumor syndrome were also negative.

FIGURE 4.

(A, B) Pathological hematoxylin–eosin staining showed that the tumor cells were composed of round or oval cells, some of the nuclei were large, the cytoplasm was rich and eosinophilic, and some of the nuclei were pleomorphic. (Bar = 100μm; magnification 100×).

FIGURE 5.

(A, B): Pathological immunohistochemical staining showed strong positivity for chromogranin A and synaptophysin. (Bar = 100μm; magnification 100×).

Discussion

Pheochromocytoma is characterized by persistent or intermittent hypertension, often accompanied by paroxysmal symptoms, most of which are unilateral and benign, but approximately 10% bilateral malignant. ² After the first operation of benign pheochromocytoma, 13% of the cases will relapse into benign or malignant tumors. Some studies have claimed that the 5‐year survival rate of malignant pheochromocytomas is 40%. ² , ⁹ , ¹⁰ In the Remine et al. study, one group of patients with metastatic pheochromocytoma had a relatively high mortality rate within 5 years of metastasis, while another group had a maximum survival time of up to 20 years after being diagnosed with metastatic tumors. ¹¹ Lumbar metastasis of adrenal pheochromocytoma is very rare, and less than 10 cases have been reported as far as we know. It has been reported that for those patients, only surgical resection of metastatic lesions without any adjuvant therapy can increase survival for up to 26 years. ² In the cases of lumbar metastasis in these studies, the average interval between the diagnosis of pheochromocytoma and spinal metastasis was 5 years, which was longer than that for our patient; our interval was only 3 years. For patients with lumbar metastasis, especially those with a history of pheochromocytoma, the metastasis of pheochromocytoma should be considered in the differential diagnosis.

Adrenal pheochromocytoma is different from paraganglioma; most of them are functional, and the malignant degree of adrenal pheochromocytoma (10%–15%) is lower than that of paraganglioma (29%–40%). ¹² The diagnosis of pheochromocytoma or functional paraganglioma is based on the measurement of plasma or urine levels of catecholamines and their metabolites. According to reports, screening with 24‐h urine catecholamines has a sensitivity of 87% to 90% and specificity of 99%. It can also detect catecholamines in plasma, with a sensitivity and specificity of 96% and 85%, respectively. ¹³ , ¹⁴ Our patient's preoperative blood catecholamine levels were within the normal range, which also confirmed that this metastatic pheochromocytoma was likely nonfunctional. In addition, the location of the tumor can usually be determined using abdominal CT or MRI. ¹⁵ Iodine‐131 metaiodobenzylguanidine (131I‐MIBG) whole‐body scans with a sensitivity of nearly 81% can be used as a screening method, which depends on radionucleotide uptake by tumor cells and is very important for locating extra‐adrenal tumors. ¹⁶

Pheochromocytoma has obvious histological features, with a large cluster of principal cells arranged in a nest (Zellballen) pattern surrounded by a delicate layer of fibrovascular matrix. The tumor cells had granular and eosinophilic cytoplasm, round or oval nuclei, and demonstrated a positive immunohistochemical staining for synaptophysin, chromogranin, Smur100 and tumor specific antigen. Malignant tumors are not necessarily determined by histological evaluation but can be confirmed by metastasis and invasion. ¹⁷

The treatment of metastatic pheochromocytoma includes tumor resection combined with internal fixation, tumor reduction surgery combined with cyclophosphamide and vincristine chemotherapy, supplemented with high‐dose and repeated‐dose ¹³¹I‐MIBG. ¹⁶ Studies have shown that radiotherapy is effective in relieving pain in patients with bone metastases. ¹⁸ However, the rarity of this condition and the lack of long‐term follow‐up are clearly not in line with the premise of treatment guidelines. If the patient shows symptoms such as paroxysmal hypertension, palpitations and sweating before the operation, alpha receptor blockers should be used for 2–4 weeks before the operation to prevent catecholamine‐related symptoms and prevent a perioperative hypertensive crisis. ¹⁹ Cai et al. ²⁰ successfully cured one case of pheochromocytoma with vertebral and pelvic metastases using minimally invasive bone cement osteoplasty technology, tumor resection, and a screw and rod system. They also performed sacral bone cement augmentation surgery followed by decompression and sacroiliac screw fixation for a patient with adrenal pheochromocytoma and sacrum metastases. For patients with metastatic pheochromocytoma who are not suitable for or refuse surgery, osteoplasty by cement augmentation may be a therapeutic option. It can provide sustained pain relief and stabilize the vertebral body affected by metastatic malignant pheochromocytoma. However, spinal canal decompression is essential for patients experiencing neurological symptoms. Liu et al. ²¹ reported a case of malignant pheochromocytoma with sacrum metastases. After performing embolization of the internal iliac artery, tissue biopsy, and sacral osteoplasty, exploratory surgery was conducted, followed by circumferential spinal cord decompression and posterior stabilization procedure. Postoperatively, the patient's neurological symptoms were markedly alleviated (Table 1). Liu et al., ²² in a retrospective study of nine patients with spinal metastatic pheochromocytoma, suggested that, for solitary spinal metastases, complete resection is preferred, including total resection and total resection, to remove the metastatic lesions, reconstruct the stability of the spine as much as possible, and obtain satisfactory results through tumor resection and decompression combined with radiotherapy and chemotherapy. Kheir et al. ²³ reported a patient with C6‐7 intervertebral disc pheochromocytoma metastasis that was treated with C6 and C7 vertebral body resection and decompression with anterior titanium cage plate internal fixation combined with posterior C3‐T4 nail‐rod system fixation and fusion. Because of the abundant tumor blood vessels, there was considerable bleeding during the operation, which was not conducive to the patient's postoperative recovery. Simpson et al. ²⁴ suggested routine preoperative blood preparation and angiography embolization 24–48 h before the operation to reduce tumor blood supply to reduce the risk of accidental bleeding during the operation. Our patient underwent angiography combined with local tumor vascular embolization before the operation to reduce intraoperative blood loss and to model the 3D‐printed artificial vertebral body according to the imaging data. The titanium alloy artificial vertebral body is more in line with an individualized and accurate design, and its greatest advantage is that its elastic properties are very close to those of vertebral bone with good mechanical strength, corrosion resistance and biocompatibility. Han et al. ²⁵ compared the clinical efficacy of 3D‐printed artificial vertebral bodies with traditional titanium cages and found that 3D‐printed artificial vertebral bodies can slow the settlement of postoperative supporting prostheses and maintain the height of decompressed vertebral bodies. We performed total en‐bloc spondylectomy of the tumor, prosthesis implantation, posterior interlaminar and facet joint fusion and a pedicle screw rod internal fixation to maximize the biomechanical stability and physiological curvature of the spine during the operation and to further reduce the incidence of long‐term internal fixation failure and prevent further deterioration of the spinal nerves. At the final follow‐up, satisfactory effectiveness and good fusion were achieved. In addition, careful treatment of the tumor and reasonable anesthesia are needed during the operation to minimize the intraoperative hypertension caused by the treatment of the tumor; which requires close cooperation between surgeons and anesthesiologists during the operation. The patient's hemodynamic state was monitored until the end of the operation.

TABLE 1.

Surgical methods for the previous study of adrenal pheochromocytoma metastases.

Study	Site of lesion	Surgical methods
Cai et al. 20	Lumbar spine	Lumbar pheochromocytoma was resected and reconstructed with a screw and rod system.
	Pelvis	Osteoplasty procedure by cement was done in the right posterior ilium.
	Sacrum	Surgical decompression combined with sacroiliac screw fixation after the bone cement sacroplasty procedure.
Liu et al. 21	Sacrum	Bone cement augmentation, exploratory surgery, circumferential spinal cord decompression, and a stabilization procedure via a posterior approach after embolization of the internal iliac artery.
Kheir et al. 23	Cervical spine	Vertebrectomy vertebra was performed and stabilized with titanium cage and plate fixation anteriorly. This was supplemented with posterior instrumented fusion.

At present, there are no standard guidelines for the treatment of spinal pheochromocytoma metastasis. The authors recommend prioritizing early diagnosis based on many factors including the function of the tumor, the characteristics of imaging invasion, the physical condition of patients, and postoperative expectations. Multidisciplinary diagnosis, treatment, perioperative planning should be further explored in the future for this field.

Conclusions

Lumbar pheochromocytoma metastasis is rare, difficult to treat, and should be considered in spinal metastases' differential diagnoses so early diagnosis can be made based on medical history and imaging. Preoperative local vascular imaging and embolization of the blood supply vessels were performed. After total en‐bloc spondylectomy of the tumor during surgery, a prosthesis was implanted and combined with pedicle screw fixation to reconstruct spinal biomechanical stability, achieving satisfactory results. Therefore, 3D printed artificial vertebral bodies are a good choice for treating adrenal pheochromocytoma lumbar metastasis. The key to successful treatment is close interdisciplinary collaboration in formulating rigorous comprehensive perioperative plans.

Author Contributions

Dingjun Hao and Lequn Shan designed the study and critically revised the manuscript. Yadong Zhang carried out drafted the manuscript. Houkun Li contributed in designing the study, and in drafting and critically revising the manuscript. Yadong Zhang and Wentao Wang were responsible for the data collection and measurement of radiographic data. Dingjun Hao and Lequn Shan read and approved the final manuscript. Yadong Zhang, Houkun Li and Wentao Wang are co‐first authors for this study.

Conflict of Interest Statement

The authors declare no conflicts of interest.

Ethics Statement

This case report was approved by the ethics committee of Xi'an Honghui Hospital, and written informed consent was obtained from the patient to publish the details of his case. We confirm that all methods were performed in accordance with the relevant guidelines and regulations.