Chondroblastoma: A Sharing of Therapeutic Experiences

doi:10.21203/rs.3.rs-4695183/v1

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Chondroblastoma: A Sharing of Therapeutic Experiences

https://doi.org/10.21203/rs.3.rs-4695183/v1

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Background

Chondroblastoma (CBL) is a rare benign bone tumor with potentially local recurrence and metastases. At present, the local recurrence risk factors are controversial. The purpose of this study is to analysis local recurrence factors in our medical centre. Sharing Our Therapeutic Experience.

Methods

In a retrospective study, we identified 28 patients who were diagnosed pathologically and an analysis that included age at diagnosis, gender, side, tumor location, tumor volume, epiphyseal plate status, affected epiphyseal plate, aneurysmal bone cyst, surgical therapy was performed. Kaplan-Meier estimators were used to analyze the local recurrence-free survival (LRFS). Intraclass Correlation Coefficient (ICC) and Kappa coefficient were utilized for the analysis of inter-rater variability in medical evaluations.

Results

All relapsed patients were over the 11 years old. There was a statistically significant difference in tumor volume between patients with recurrence and those without recurrence, as determined by the unpaired t-test. Furthermore, the Kaplan-Meier curve revealed a statistically significant association between local recurrence-free survival and tumor volume, with a distinct separation observed between patients with tumor volumes greater than 25 cm³ and those with volumes less than 25 cm³.

Conclusion

Curettage, combined with alcohol as an adjuvant and bone grafting, has demonstrated promising outcomes. However, it is noteworthy that a larger tumor size correlates with an increased likelihood of recurrence.

Chondroblastoma (CBL) is defined as a benign bone tumor with potentially aggressive local growth and pulmonary metastases. Kolodny was the first person to recognized it ^[1] and Codman used the term “epiphyseal chondromatous giant cell tumour” to described it ^[2]. Jaffe and Lichtenstein found that it originated from chondroblasts ^[3]. Thus, it was termed benign chondroblastic neoplasm. CBL often occurs in the second decade of male life, and the metaphysis of long bones is its common site.

At present, the gold standard treatment for chondroblasts has not been put forward. Curettage, either alone or in combination with bone grafting or packing the cavity with polymethylmethacrylate, or coupled with cryosurgery ^[4], radiofrequency ablation ^[5–7] have been reported. However, the treatment of chondroblastoma is decided by the patient.

The purpose of this report was to report a large series from a single institution to analyze clinical and radiographic characteristics, treatment, complications and local recurrence.

Inclusion criteria

A retrospective search from the institute database was performed to identify all patients with histologically verified CBL treated between 2012 and 2023. All patients underwent curettage for the first time. The surgical methods were curettage with or without bone grafting.

Exclusion criteria

Patients who were not followed up regularly or lost follow-up were excluded. The patients who were not the first received treatment was not involved. Patients with incomplete clinical progress note were unaccepted. Patients with other orthopedic diseases in the past were also excluded.

Clinical data

There were 28 CBL patients who were included. The diagnoses were based on the histological criteria. All the operations were performed by senior pediatric orthopedic surgeons in a single institution. This study has been approved by the Ethics committee of a Children's Hospital affiliated to Chongqing Medical University.

All patients underwent radiography of the chest and lesion and CT scan of the lesion. Through X-ray, the status of adjacent epiphyseal plate was classified as open, closing and closed. If the wide and clear epiphyseal plate was displayed on the X-ray, it was considered open; Narrow and curved was considered closing; epiphyseal scar was closed ^[8–10].

We measured the tumor size on the preoperative CT. The maximum size of the lesion was measured according to CT in coronal, sagittal and axial view. The volume of the lesion was expressed by the product of three maximum values divided by 2.

By reviewing the hospital medical records, we were able to define the age at diagnosis, gender (male/female), side (left/right), location (proximal humerus/Ischium/femoral head/femoral neck/ distal femur/proximal tibia/distal end of fibula/Ankle), tumor volume, epiphyseal plate status (closing/closed), affect epiphyseal plate (yes/no), aneurysmal bone cyst (with/without), surgical therapy (curettage alone/curettage with artificial bone grafting/ curettage with mixed bone grafting/curettage with autogenous bone grafting). Recurrence was defined as an increase in the low-density shadow in the postoperative follow-up X-ray film compared with the previous one, and the result of reoperation biopsy confirmed it as CBL. The MSTS was used to evaluate the postoperative function.

Statistical analysis

Local recurrence-free survival (LRFS) was presented using Kaplan-Meier method. Differences of LRFS was determined using the log-rank test. Differences between means and proportions were tested with the Fisher’s exact test for categorical variables and the unpaired t-test for continuous variables. Intraclass Correlation Coefficient (ICC) and Kappa coefficients are utilized to assess inter-rater differences in continuous and categorical variables among various researchers. A probability value of P ≤ 0.05 was considered statistically significant.

There were 28 patients in our retrospective study, 18 males and 10 females. The ratio of males to females was close to 1.8 : 1. The commonly affected sites were distal femur (32.1%), followed by the proximal tibia and femoral head (25.0%), femoral neck (7.1%), proximal humerus (3.6%), Ischium (3.6%) and distal fibula (3.6%). The mean for follow-up time was 33 months (range 8 to 91). The epiphyseal plate status was presented as closing in eleven, closed in seventeen (Table 1). The main symptom was pain (85.7%) accompanied by limping (33.3%), with median duration of 6 months (range 0.2–48 months). All patients underwent curettage procedures, with the adjunctive use of anhydrous alcohol. Specifically, seventeen patients (60.7%) received artificial bone grafting to fill the curettage defects, while five patients (17.9%) were treated with allograft bone grafts. Additionally, four patients (14.3%) did not receive any bone grafting, and one patient (3.6%) underwent mixed bone grafting. One patient (3.6%) specifically received autogenous bone grafting. Postoperatively, patients were encouraged to initiate movement on the second day, with gradual partial weight-bearing commencing six weeks postoperatively, followed by full weight-bearing three months after the surgical procedure.

Table 1

Baseline Characteristics of chondroblastoma patients
	Chondroblastoma patients
Age at diagnosis
9 years	1
10 years	2
11 years	2
12 years	4
13 years	4
14 years	8
15 years	5
16 years	2
Gender
Male	18
Female	10
Side
Left	15
Right	13
Location
Proximal femur	1
Ischium	1
Femoral head	7
Femoral neck	2
Distal femur	9
Proximal tibia	7
Distal fibula	1
Lower than 25mm³	22
Epiphyseal plate status
Closing	11
Closed	17
Affected the epiphyseal plate
Yes	23
No	5
With aneurysmal bone cyst
Yes	2
No	26
Total	28

There were three patients who developed the local recurrence (LR), the mean time to local recurrence was 9 months (range 3 to 12 months). An 11-year-old boy with distal femur chondroblastoma relapsed 3 months post operation, and he accepted a second aggressive curettage. A 14-year-old boy developed the sinus and local recurrence in the proximal humerus after 6 weeks and 11 months primary procedure respectively. A 15-year-old boy had local recurrence in the distal femur 12 months later. Epiphyseal plates of relapsed patients were influenced by the tumors and status of them were closing, closed, closed respectively. Primary tumors were without ABC in all local recurrence case. The LR rate was 10.3%. Of note, all recurrence patients relapsed in 2 years postsurgery. The mean volume of LR chondroblastoma was 42.00cm³ (range 24.76–65.38), which was much greater than no recurrence patients of 10.37cm³ (range 0.69–88.19) (P < 0.05). Only 3 patients without recurrence had CBL lesions larger than 25cm³, which were 26.23cm³, 26.93cm3, 88.19cm3 respectively. In the updated analysis, we categorized all patients into two distinct groups based on their volume: one group with volumes less than 25cm³ and another group with volumes greater than or equal to 25cm³. This categorization allowed for a more nuanced exploration of CBL characteristics and treatment outcomes across different volume ranges. There were significant statistical difference between recurrence and both bulk (< 25cm³/≧25cm³) and volume (P < 0.05). Kaplan-Meier estimated local recurrence survival rates were 96.4% at 7 months, 92.4% at 11 months and 83.2% at 20 months for curettage patients (Fig. 1) The Kaplan-Meier showed that tumor size larger than 25cm³ was associated with local recurrence chondroblastoma (log-rank P < 0.05).

Figure 1. aplan-Meier survival curve showing the risk of local recurrence for chondroblastoma. All local recurrences arose within 48 months of initial treatment

One patient presented with a pathological fracture in the femoral neck at the three months after surgery, and the lesion volume of him was 26.23cm³. Two boys had the sinus of the primary lesion at the six weeks and eight weeks post operation respectively. The mean of MSTS score was 27(range 14 to 30), which was considered as the good result for postoperative person. There was only one person whose MSTS score was less than 25, which was 14 points. He had poor walking ability and developed LLD and knee varus after proximal tibia CBL curettage and artificial bone grafting. The kappa coefficient for observer agreement on epiphyseal plate status was 0.85 (P < 0.05), indicating strong reliability. Similarly, the intraclass correlation coefficient (ICC) for focus volume was high at 0.92. These results suggested a good correlation between different observers.

Chondroblastoma was defined as a benign tumor, but it could develop local recurrence and metastasis. The local recurrence rate of lesion curettage was 0 ~ 39% ^[4,11–19]. The risk factors of tumor recurrence have been controversial. There are several risk factors that were considered to be related to tumor recurrence such as age, gender, tumor with aneurysmal bone cyst (ABC), the biologic aggressiveness of tumor, location, epiphyseal plate status, affected epiphyseal plate, therapy method.

The age at diagnosis of CBL was considered as a risk factor for local recurrence, and the most previous studies believed that the younger the patient the greater was the risk for local recurrence. Cong Huang et al. observed that all the patients whose tumors recurred were less than 12 years old. All of their patients were less than 14 years old and were similar to our patients’ age ^[17]. Meanwhile, R. Suneja et al. mentioned that there were seven local recurrence patients and six of seven were lower than 14 years old. They thought that the local recurrence was associated with younger patients ^[4]. According to Francesco Muratori et al., at the age of 7 to 42, the age less than 11 was the only significant factor that influenced local recurrence risk. According to our results, all cases with local recurrence were over 11 years old and were less than 6 months from onset to diagnosis. The misdiagnosis of CBL is common, although case with classical features could be diagnosed quickly, but there is few confused cases with giant cell bone tumor (GCT) or ABC may give an overlap clinical presentation ^[20]. Local pain was the most common symptom and could last more than 1 years and there were a few of patients without any symptom, which will delay the diagnosis ^{[4, 15, 20]}. It is not easy to explain our result that all of recurrent patients were more than 11 years old. It may be the bias caused by only three patients less than 11 years old in our group and we were unable to determine the duration of the asymptomatic incubation period prior to the onset of clinical symptoms. There was only one article whose results is similar to ours, that is, advanced age is a risk factor for recurrence ^[15] and we tended to believe that younger age serves as a risk factor for the recurrence of CBL.

In this study, we also explored the relationship between tumor volume and local recurrence and we found that the larger the tumor volume the greater was the risk for local recurrence (P < 0.05). In the updated analyses, volume over 25cm³ was associated with a statistically significant increase in local recurrence. In the context of other tumors, a larger tumor volume was generally regarded as being associated with a higher likelihood of recurrence ^{[21, 22]}. As we all know, there were few studies that mentioned this relationship in CBL. On the one hand, when surgeons tackled large tumors, they were worried that, in comparison to smaller tumors, patients were at a heightened risk of developing limb-length discrepancy (LLD) following extensive curettage of the epiphyseal plate ^{[4, 17, 23]}. Notably, 82.1% of our patients' epiphyseal plates were affected, with only a single case of a patient with a closing plate experiencing postoperative LLD and knee varus. It was postulated that with meticulous care, the epiphyseal plate could potentially undergo repair ^[16]. Prior investigations have established a correlation between the extent of the injured epiphyseal plate and the resistance of long bones to normal growth and development ^{[24, 25]}. Meanwhile, several animal experiments have proved that the epiphyseal plate has extremely limited plasticity, when the injured percentage of eccentric lesion is more than 9%, it could cause obvious restriction ^{[24, 26]}. Otherwise, according to the Dales and Harris classification, the epiphyseal plates of the distal femur and the proximal tibia were both type B, the blood supply primarily originated from the blood vessels of the adjacent soft tissues, which would sustain minimal damage during the operation. This minimized damage was advantageous for the subsequent repair of the epiphyseal plates ^[27]. On the contrary, The damage to the epiphyseal plate was considered to be irreversible in a few studies ^[28]. However, we held the belief that there existed a potential for spontaneous repair of the epiphyseal plate, because most epiphyseal plate were hurt by tumors but only one patient who developed LLD.

On the other hand, the tissue of chondroblastoma was soft and poorly interconnected, leading to the leakage of numerous granular-like tumor tissues during the scraping of larger tumor masses. This leakage prevented complete removal and subsequently resulted in recurrence. To address this issue, we employed alcohol immersion for 3–5 minutes to enhance the brittleness of the tumor tissue, facilitating both inactivation and scraping. Anhydrous ethanol can cause protein denaturation in tumor cells, cytoplasm denaturation in cells, and embolization of small blood vessels supplying the tumor. Additionally, anhydrous alcohol has been proven to have a few adverse effects on surrounding tissues ^[29]. Concurrently, the application of alcohol to the sclerosed zone surrounding the tumor was advantageous in facilitating the infiltration of progenitor cells into the cavity, thus contributing to the repair of the cavity.

CBL has been proved to be common in distal femur, proximal tibia and proximal humerus, although our results only partially concurred with this observation. In this study, CBL mainly occurred in proximal humerus, distal humerus and proximal tibia. There was few researches that reported that special anatomic site, such as pelvis ^[30]. The reason why CBL in pelvis was easy to recur was believed that its anatomical position made it difficult to completely expose the tumor and incomplete curettage leaded to recurrence. In this study, there was a patient whose CBL was located in the pelvis. After adequate curettage, the patient has no signs of recurrence at present. Frédéric Sailhan et al. found that CBL far away from the active epiphysis (close to the elbow or far from the knee) has a higher recurrence rate among their patients, which was completely contrary to our results. The CBL of our recurrent patients were located in the proximal humerus, distal femur and proximal tibia respectively. Our study found no significant correlation between the location of CBL and local recurrence.

In our center, the main treatment methods of CBL were curettage, assisted by anhydrous alcohol as adjuvant and bone grafting. Alcohol as adjuvant was considered had a good effect of inhibiting tumor recurrence. Tumors located in the proximal femur and pelvis were reported to be susceptible to recurrence because they were difficult to achieve complete surgical resection ^{[4, 30–32]}. Therefore, it is necessary to use adjuvants. High-speed burring and it has been proved that it could obviously reduce local recurrence in CBL curettage ^{[33, 34]}. However, Cong Huang et al. expressed concerns that the epiphyseal plate might sustain damage from the heat generated by the burr during the procedure ^[17]. Cement was also deemed potentially harmful to the epiphyseal plate due to the heat released during its solidification process ^[20]. Furthermore, the use of other adjuvants, such as phenol or liquid nitrogen, could potentially lead to necrosis ^[13]. Alcohol has been proved to have a good effect on inactivating tumor cells and has little effect on surrounding tissues ^[29]. But there were few researches using alcohol alone as the adjuvant to treat the CBL.

Previous studies have suggested that ABC is a risk factor for CBL local recurrence ^{[11, 35, 36]}. Whether ABC was the recurrence factor of CBL has always been controversial, and there were also a large number of documents showing that ABC is not related to the recurrence of CBL ^{[19, 37]}. According to our results, there was no significant difference between ABC and local recurrence and only 2 patients CBL with ABC, which located in ischium and distal femur respectively and both of them were not developed local recurrence.

Among patients who underwent curettage and artificial bone grafting, three patients developed femoral neck fracture, gluteal sinus tract, and upper limb sinus tract. The bone graft substitutes that were used included calcium phosphate (CaP) and calcium sulfate (CaS) compounds. Generally, the main benefit of CaP ceramics stemmed from their osteoconductive properties, and they could provide some structural support in the form of compression strength. However, they were brittle and their low tensile strength may have contributed to increased postoperative fracture risks ^[38]. Additionally, CaS compounds were believed to be associated with persistent serous wound drainage, which resulted from the inflammatory response to their resorption. In most cases, this was a sterile drainage that persisted until the calcium sulfate was radiologically absorbed ^[39]. With proper local wound care, the wounds of two patients with sinus tracts recovered smoothly.

The primary limitation of this study lies in the rarity of the tumor and the relatively small sample size. Additionally, the average follow-up duration was insufficient to adequately assess complications such as secondary osteoarthritis. Furthermore, the retrospective nature of this study may undermine the robustness of our findings. Moreover, this study did not incorporate comparisons with other surgical interventions, such as radiofrequency ablation, to evaluate their impact on recurrence rates.

In conclusion, although CBL is classified as benign tumor, there is still the risk of local recurrence. Larger tumors will increase the possibility of local recurrence of CBL in patients. The complete curettage, combined with alcohol as an adjuvant and followed by bone grafting, has achieved good results in the treatment of this disease.

ABC	Aneurysmal bone cyst
CaP	Calcium phosphate
CaS	Calcium sulfate
CBL	Chondroblastoma
ICC	Intraclass Correlation Coefficient
LLD	Leg Length Discrepancy
LRFS	Local recurrence-free survival
LR	Local recurrence

Ethics approval and consent to participate

The research had been approved by the Ethics Committee of Children's Hospital affiliated to Chongqing Medical University.

Consent for publication

Not applicable

Availability of data and materials

The datasets generated and analysed during the current study are not publicly available due personal privacy but are available from the corresponding author on reasonable request.

Competing interests

The authors declare that they have no competing interests.

Funding

Not applicable

Authers’ Contributions

DY and ZLW designed the study; DY, ZYZ collected the data; ZLW and DY analyzed the data; DY drafted the initial manuscript; DY and ZLW revised the article critically; HO repeated measurement data; DY, ZLW and HO reviewed and edited the article; All authors read and approved the final manuscript.

Acknowledgements

Not applicable

Statement for use of human tissue samples

Informed consent was obtained from all of their legal guardians.

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No competing interests reported.

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Chondroblastoma: A Sharing of Therapeutic Experiences

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