Clinical features and prognostic factors of spinal fibroblastic/myofibroblastic tumors: a long-term, single-center, retrospective study

Data collection

Fifty-one patients with spinal FMTs received consecutive surgical treatments and adjuvant therapies at our center between April 2006 and September 2018. We collected demographic and relevant clinical data of the patients from their medical records in a retrospective review. The data included baseline information, clinical symptoms, blood biochemical indices, and tumor locations and involved the scope, pathological classification, and details of the therapeutic regimen. The Changzheng Hospital Ethics Committee approved our study protocol (No. D3108N0525), and written informed consent was obtained from all patients or their legal guardians.

Contrast-enhanced computed tomography (CT) and magnetic resonance imaging (MRI) with gadolinium enhancement were used to detect bony destruction and soft tissue involvement. The Eastern Cooperative Oncology Group (ECOG) scoring system and Frankel score were used to evaluate the preoperative performance and neurological status, respectively. The individualized surgical protocol, including en bloc resection (marginal or wide excision) and piecemeal excision, was designed for all the patients according to the Tomita classification (Tomita et al., 2001) and Weinstein-Boriani-Biagini (WBB) surgical staging system (Boriani, Weinstein & Biagini, 1997). Radiotherapy and chemotherapy were administered based on the surgical outcome and tumor pathology. The use of bisphosphonate was introduced to the patients with osteolytic lesions. Histopathology and immunochemical staining were reviewed postoperatively. The scoring of Ki-67 staining depended on the definite immunochemical results, and was expressed as a percentage of positivity. Other immunochemical indicators were provided in the form of positivity or negativity.

Follow-up strategy

The follow-up period started from the date of surgery and ended on December 20th, 2018. DFS was the primary endpoint in our study and OS was the secondary endpoint. DFS was defined as the duration from the date of surgery to the date of the first evidence of recurrence/metastasis on the basis of the clinical manifestations and imaging changes, death caused by relevant diseases, or the end of follow-up care. OS was defined as the duration from the date of surgery to death or the end of follow-up care. Follow-up care was routinely performed either by outpatient visits or telephone interviews every 3 months for the first 6 months, every 6 months for the next 2 years, and then annually until care was discontinued.

Statistical analysis

Quantitative data are described by mean/median (standard deviation, SD), and qualitative data are reported by counts (percentages, 95% confidential interval [CI]). The chi-square test or Fisher exact method was used for categorical data, and student t-test was used for quantitative data when appropriate.

Univariate and multivariate analyses were performed to investigate the factors affecting DFS and OS for patients with spinal FMTs. The log-rank test was used in univariate analysis, and variables with a p < 0.05 in a univariate analysis were subjected to the Cox proportional hazards regression model to identify independent prognostic factors. DFS and OS rates were estimated using the Kaplan–Meier method. A two-sided p < 0.05 were considered statistically significant. All statistical analyses were conducted using SPSS statistics, version 21.0 (IBM, Armonk, New York).

Demographic data

A total of 51 patients (24 male and 27 female) with FMTs in the axial skeleton were surgically treated with adjuvant therapies at our institution. Detailed patient information is found in Table 1.

The patients ranged in age from 15 to 70 years with a mean of 31.6 ± 16.1 years, including 28 (54.9%) patients younger than 25 years of age. The most common symptom was chronic endurable pain with or without radiating pain. Attendant symptoms included numbness of the extremities, progressive dyskinesia, segmental limitation of motion, varying degrees of sphincter disturbances, and weight loss. Weight loss was defined as a > 5% reduction in body weight (BW) within 6 months. The duration of preoperative symptoms ranged from 0.25 to 144 months (9.0 ± 21.2 m).

Thirty-eight (74.5%) patients had previously received treatments in other hospitals and were referred to our hospital because of recurrence and the remaining 13 patients were initially identified with primary FMTs in our hospital. The preoperative neurologic and performance status of the patients was assessed using the Frankel score 19 and ECOG 20, respectively.

The tumor location and involved segments were recorded for further analysis.

Solitary lesions were detected in 47 cases (92.2%) and multiple lesions were detected in four cases (7.8%). The lesions were evaluated by the WBB and Tomita classification systems. The vertebral body was affected in 18 cases (35.3%) (sector 5-9 or 4-8 by WBB system, sector 1 by Tomita classification), and included involvement of the posterior aspect in 16 cases (31.4%) (sector 3-10 by WBB system, sector 2 or 3 by Tomita classification). Deep vertebral involvement was detected in more than 34 cases (66.7%) (layer C by WBB system and I-III by Tomita classification). However, only three lesions (5.9%) were defined in the vertebrae (layer B-C by WBB system). There were 19 confirmed cases in which the tumor extended into the epidural space (39.6%) (layer D by WBB system and IV by Tomita classification). Soft tissue involvement was observed in 40 cases (83.3%).

Radiographical findings

CT scan findings included a heterogeneously or homogeneously asymmetric mass with adjacent vertebral marginal osteogenic changes, and intense but inhomogeneous enhancement following the administration of contrast agent. Some lesions appeared as radiolucent, shuttle-shaped expansile osteolysis with thinning of the bone cortex. MRI T1-weighted imaging showed hypo- to iso-intensity signals, with T2-weighted imaging hyperintensity or mixed intensity. A peripheral enhancement effect was occasionally observed after the administration of contrast agent (Figs. 1C, 1D).

Treatment and outcomes

The SINS (spinal instability neoplastic score) system was used to evaluate the spinal stability and assist with the surgical protocol. This score was less than seven in 10 cases (21.4%), 7–12 in 29 cases (63.0%), and more than 12 in 7 cases (15.2%). Fifteen patients (29.4%) were treated surgically by en bloc method (marginal and wide), and 36 tumors were removed piecemeal because of the large tumor size, adjacent neurovascular structure, and/or multiple vertebral extensions. Fourteen patients (27.4%) underwent surgical removal using a combined anterior and posterior approach, while vertebrectomies and sagittal resections were applied to tumor removal through a single posterior or anterior approach in 37 patients (72.5%). The representative patient who underwent en bloc resection is depicted in Figs. 1G–1I.

Thirty-six tumors (70.5%) were removed in a piecemeal fashion. 15 patients (29.4%) with an appropriate tumor location received en bloc surgical treatment. Three patients experienced a local recurrence after a marginal resection, and metastasis occurred in one patient after a wide resection. Of the patients receiving a piecemeal resection, seven patients (13.7%) underwent extra postoperative radiotherapy, while chemotherapy was administered to 15 patients (29.4%). The chemotherapy regimen was determined by the pathological subtype of spinal FMTs. Nine patients (15.7%) with inflammatory myofibroblastic tumors received ALK tyrosine kinase inhibitors. The sarcoma-like regimen of isosfamide (12–15 mg/m²) and doxorubicin (75 mg/m²) was used in 10 patients (adult fibrosarcoma, low grade fibromyxoid sarcoma, low grade myofibroblastic sarcoma). Chemotherapy produced varied results in spinal FMTs. Six patients with inflammatory myofibroblastic tumors developed local recurrence after the administration of ALK tyrosine kinase inhibitors. Follow-up imaging showed relapse in three patients with adult fibrosarcoma, one patient with low grade fibromyxoid sarcoma, and two patients with low grade myofibroblastic sarcoma after chemotherapy. The chemotherapy regimen was restarted until the next surgery or tumor regression. Zoledronic acid was used to prevent osteolytic bone destruction in 23 patients (45.1%). Bone-related events were not observed in patients with the use of bisphosphonate.

Pathology

The histologic diagnoses were as follows: fibromatosis colli (two cases), desmoplastic fibroblastoma (five cases), calcifying fibrous tumor (one case), desmoid-type fibromatoses (three cases), lipofibromatosis (three cases), solitary fibrous tumor (12 cases), low grade myofibroblastic sarcoma (four cases), inflammatory myofibroblastic tumor (14 cases), hyalinizing spindle cell tumor (one case), low grade fibromyxoid sarcoma (two cases), and adult fibrosarcoma (four cases). The histological images are shown in Fig. 1J.

In our study, the positive immunohistochemistry showed the following: vimentin (12/14, 85.7%), SMA (33/36, 91.7%), CD34 (7/11, 63.6%), Bcl-2 (14/18, 77.8%), β-catenin (12/18, 66.7%), CK (5/10, 50%), ALK (+) (10/14, 71.4%), and EMA (1/12, 8.3%), respectively. The Ki-67 range was tested in all cases (9.71 ±  7.81%, 9%). Our immunochemical findings revealed that the tumor cells were positive for the different scoring of Ki-67 (Fig. 2).

Complications and recurrence

Wound complications and urinary tract infections were observed in two patients who recovered fully after intensive treatment and meticulous nursing care. One patient (1.9%) suffered incisional disunion, and debridement was subsequently performed. Another patient (1.9%) developed a urinary tract infection on the 5th postoperative day and was treated with oral antibiotics and irrigation of the urinary tract.

During the mean follow-up period of 46.2 months, 25 patients (49.0%) were still alive without any evidence of recurrence or metastasis. All of the surviving patients recovered well postoperatively and had no neurological deficit. Fourteen patients died of tumor-related disease within a mean period of 53.6 ±  20.0 months (25.6–81.7 m). One patient died of surgery-related causes and eleven patients died of other diseases within a mean interval of 61.3 ±  48.1 m (19.7 m-154.6 m, 39.8 m).

Twenty-eight of the 38 patients (74.5%) patients treated at other hospitals developed local recurrences, within a mean follow-up of 30.0 months (11.2–60.8), and 2 patients developed metastasis within an average period of 20.4 months (17.5–23.2). The other 8 recurring cases were patients with a primary tumor who received initial treatment at our institute (seven for piecemeal resection, one for en bloc resection). Two patients developed distant metastasis 30.2 and 39.7 months after surgery, respectively.

Prognostic analysis of DFS and OS

The results of univariate analysis of the prognostic factors affecting both DFS and OS are listed in Table 2. As the table shows, patients with age ≤25 (p = 0.03), initial admission (p = 0.003), Ki-67 ≥5% (p = 0.007), multicentricity (p = 0.015), metastatic pathology (p = 0.008) and piecemeal surgical treatment (p = 0.001) had lower DFS. Tumor location (p = 0.014), surgical resection style (p = 0.013), recurrence on admission (p = 0.04), weight loss (p = 0.04), and combined radiotherapy (p = 0.029) were unfavorably associated with OS.

Multivariate analysis using the Cox proportional hazards regression model identified that recurrence on admission (p = 0.008), Ki-67 ≥5% (p = 0.029) and surgical protocol (p = 0.011) were independent predictors of DFS. En bloc resection (p = 0.020) was correlated with better OS but radiotherapy affected OS negatively. The details of independent prognostic factors are illustrated in Table 3. The Kaplan–Meier survival curves of DFS and OS for their independent predictors are shown in Figs. 3 and 4. The 5-year DFS and OS were 10% and 53%, respectively.