UPS, previously termed malignant fibrous histiocytomas (MFH), is a common subtype of soft tissue sarcoma. UPS is an aggressive tumor type and is associated with a high risk of local recurrence and distant metastasis[5–10]. UPS of the bones predominantly affects males and has a peak incidence between the ages of 50 and 70 years old[11, 12]. The prognosis of UPS is poor, with five-year survival rates ranging between 30–50%[1, 2]. UPS can appear throughout the body, but 60% of cases occur in the extremities[5, 13]. Primary UPS arising from the bone is relatively rare. The statistics have shown that skeletal involvement of UPS represents less than 2% of primary malignant bone tumors. In most cases, UPS of the bone develops around knee joints and in proximal femurs and humerus[3, 14]. Only a small number of UPS cases involving the spine have been reported since its first description in 1975.
Currently, surgical resection is still the mainstay of treatment for spinal UPS, and complete resection with a negative margin can improve the survival of patients. Ozkurt et al reported that patients with wide surgical margins had a five-year survival probability of 81.9%, while for patients with marginal surgical margins this was 33.3%. Goertz et al retrospectively studied 192 UPS patients and found that those with negative margins had better overall survival. In the treatment of UPS, surgery alone is not sufficient and the rate of local recurrence (LR) and distant metastasis is high. LR occurs in between 25–75% of cases[3, 15], especially for patients with inadequate margins. Radiotherapy should be considered as an adjuvant therapy, especially for patients with non-wide margins. Dahlin et al  used radiotherapy to treat two cases of unresectable pelvic tumors, neither patient suffered distant metastasis or local recurrence during follow-up. In one large study, patients with high-grade MFH of the extremities who underwent excisional surgery, followed by postoperative radiotherapy, experienced a 10-year relapse-free survival of 62% and an overall survival rate of 80%[15, 17]. Ole Goertz et al found that adjuvant radiotherapy could decrease the risk of local failure and significantly improve overall survival (OS). The use of chemotherapy in spinal UPS treatment is controversial. UPS is also less sensitive to the first-line chemotherapeutics Doxorubicin and Ifosfamide. Lehnhardt et al analyzed 140 patients with UPS in their extremities and found adjuvant chemotherapy to have no effect on prognosis[3, 8]. Nevertheless, Weiner et al treated three patients who suffered MFH of the bone with radical resection and adjuvant chemotherapy. All three patients remained disease-free with no complications over a follow-up period of 42–48 months. Bacci et al reported that 70% of patients who received neoadjuvant chemotherapy combined with surgery survived 6.5 years during the follow-up period, which was significantly higher compared to the 20 patients who underwent surgical resection only.
It is notable that in our case the patient’s condition was unique. He suffered from two primary malignancies and had a strong family history of cancer. We suspected that the patient had LFS and recommended him for further genetic testing. The result showed mutation of the TP53 gene. These characteristics met the diagnostic criteria of LFS. Patients with LFS have an increased risk of malignancy and mutations in TP53. The lifetime risk of cancer has been previously reported to be nearly 100% by the age of 60 years in women and 73% in men[19, 20]. Breast cancer, bone, soft tissue sarcomas, brain tumors, and adrenocortical carcinoma are ‘core’ LFS cancers. Radiation exposure should be avoided in patients with LFS because it may induce secondary cancers. In terms of chemotherapy, patients with LFS should not be treated with alkylating agents because of their DNA-damaging properties. In patients with LFS, whether to give adjuvant therapy for the treatment of spinal UPS is a conundrum. For tumors with a high degree of malignancy and poor prognosis, we believe that the prognostic benefits of postoperative adjuvant therapy outweigh the risks of long-term secondary cancer. Potapov et al reported that surgery combined with chemotherapy has a good prognosis in the treatment of anaplastic oligodendroglioma. Klein JD et al used surgery and adjuvant radiotherapy to treat mucosal melanoma with LFS, and there was no recurrence, metastasis, or second primary tumor at a 30-month follow-up. While Hosoya T et al used both postoperative radiotherapy and chemotherapy to treat a 7-year-old boy who suffered anaplastic ependymoma with LFS, but the prognosis was poor, and recurrence could not be prevented. In these studies, postoperative adjuvant therapy did not result in a secondary primary tumor. The difference in the effects of the treatments was mainly related to whether the primary tumor was sensitive to chemoradiotherapy. Spinal UPS is an aggressive malignant tumor, and some studies have shown that chemoradiotherapy is effective in reducing local recurrence and metastasis rates. In our case, the patient undertook postoperative adjuvant radiotherapy, and there was no local recurrence, metastasis and secondary cancer during the 31-month follow-up. So, we believe that for these patients, the benefits of postoperative adjuvant chemoradiotherapy outweigh the risks of secondary primary cancer.
It is rare for a patient to have two primary malignancies at the same time. In our case, the patient already had confirmed ACC before coming to our hospital. PET/CT indicated increased uptake in many parts of the body. The lesion in the L4 VB was suspected to be derived from the ACC. ACC is a rare malignancy with poor prognosis and high rates of metastasis. However, postoperative pathological findings indicated UPS. How to differentiate between spinal UPS and metastatic carcinoma of the spine is very important to determine the treatment regimen. For spinal UPS, computed tomographic scans revealed osteolytic destruction without periosteal reaction or new bone formation. Moreover, magnetic resonance imaging showed a rapidly enlarged paraspinal soft tissue mass at the contiguous level, with a tendency to extensively invade surrounding structures around the vertebrae. As for osteolytic metastatic cancers of the spine like ACC, osteolytic destructions are visible on a plain radiograph. The cancellous bone was resorbed and cortical bone disappeared. In the sagittal position, double margin shadows could be observed at the upper margin of the vertebral body caused by pathological vertebral collapse. CT revealed moth-eaten changes, vertebral bodies, and pedicles which disappeared and were replaced by soft-tissue masses. MRI revealed an epidural soft-tissue mass or convex posterior vertebral body border. On T1-weighted images, the lesion showed a low signal change, while on T2-weighted images, this was a high signal change. These differences in imaging findings may help to differentiate spinal UPS from other metastatic carcinomas. Of course, the final diagnosis still depends on the pathological findings.
Many studies have shown that advanced age is an independent risk factor for poor prognosis[26, 27]. Lou et al revealed that an age ≥ 55 years were independently associated with poor overall survival in spinal UPS. Therefore, early diagnosis is quite important. While the early diagnosis of spinal UPS is difficult and often not made until an advanced stage has been reached, when the lesion is large or nerve compression has been presented. For asymptomatic patients with a family history of malignancy, genetic testing can be valuable. If LFS is apparent, monitoring for the occurrence of spinal UPS should be conducted vigilantly. An annual spine MRI can help to detect microscopic lesions early. Individuals who undergo cancer surveillance have significantly lower cancer-related mortality and higher overall survival compared with those who do not, suggesting that a comprehensive surveillance strategy is feasible and clinically relevant.