Abstract
Objective:
This study aims to assess the histopathological and clinical characteristics of chondroblastomas (CBs), with particular emphasis on the correlation between local invasion and mitotic activity, cytological atypia, and recurrence.
Methods:
A retrospective analysis was performed on 26 cases of CB diagnosed between 2016 and 2024 and pathologically evaluated at a tertiary oncology center, with surgical procedures performed across 2 tertiary oncology referral centers. Clinical, radiological, and histopathological data were reviewed. For comparative analysis, tumors were grouped as non-infiltrative (confined to the bone) or infiltrative (showing invasion of the bone cortex and/or extracortical connective tissues). Tumors were assessed for cytological atypia, mitotic index, matrix production, calcification, aneurysmal bone cyst formation, and invasion pattern. Immunohistochemical staining for S100, DOG1, and Ki-67 was conducted. Statistical analyses included t-tests, Mann–Whitney U, chi-square, and correlation analyses.
Results:
The mean age at diagnosis was 17.7 years, with a male-to-female ratio of 1.36 : 1. The femur was identified as the most common site. Invasion beyond the bone cortex was observed in 16 patients (61.5%), including 4 instances of soft tissue involvement. Invasive tumors showed significant association with moderate cytological atypia (P = .022), higher mitotic index (P = .023), and lower extremity location (P = .02). A positive correlation was identified between mitotic index and both atypia (P = .001) and tumor invasiveness. Recurrence occurred in four patients (15.4%), all presenting invasive tumors. No metastases were reported during the mean follow-up period of 38.9 months.
Conclusion:
Although CB typically manifests benign behavior, a subset of these tumors demonstrates locally aggressive characteristics, such as cortical and soft tissue invasion. Elevated mitotic activity and moderate cytological atypia may serve as histopathological markers for local aggressiveness.
Level of Evidence:
Level IV, Prognostic Study.
Keywords: Bone tumors, Chondroblastoma, Cytological atypia, Histopathology, Local invasion, Mitotic index
Highlights
Chondroblastoma (CB) may exhibit locally aggressive behavior despite its benign nature.
Invasion beyond the cortex was observed in over 60% of cases.
Tumor invasiveness correlated with moderate atypia and higher mitotic activity.
All recurrent cases had histological evidence of local invasion.
Mitotic index and cytological atypia may serve as markers of aggressiveness.
Introduction
Chondroblastoma (CB) is a rare cartilage-producing bone tumor that typically arises in the epiphyseal region of long bones in young adults.1 They account for 1% of primary bone tumors and 4%-5% of benign primary bone tumors.3 Histologically, it is characterized by the proliferation of layers of small to medium-sized rounded polygonal chondroblasts with eosinophilic cytoplasm.1 Mitosis and cellular atypia are rare.1 A K36M mutation in the H3F3B gene, encoding the 3B protein of the histone 3 family, was found in 95% of cases.4,5 Although it was classified as a tumor of intermediate biological potential in the fourth edition of the WHO classification,6 CB is classified as a benign neoplasm in the fifth edition. While it was classified as a benign neoplasm, a significant challenge remains: the high rate of local recurrence, which can be as high as 31%.,3,7-9 This often necessitates repeat surgical procedures, leading to increased patient morbidity and potential complications, such as joint stiffness and growth plate abnormalities. Given these challenges, a better understanding of the factors contributing to recurrence is crucial for improving patient outcomes. Metastasis is rare and almost always to the lung.10,11 Surgery is the first-line treatment. Although complete curettage of the lesion is usually sufficient, local adjuvant treatments, such as chemical agents like phenol, hydrogen peroxide, or alcohol, may be added to prevent recurrence.,8 Chondroblastomas sometimes display local destructive growth with cortical breakthrough and soft tissue invasion.9,13 The study aimed to compare the histopathological features of CBs showing invasion with the tumors that are confined to the bone.
Material and methods
Patient cohort and study design
Twenty-six consecutive cases which had a diagnosis of CB between the years 2016-2024 at Prof. Dr. Cemil Tascioglu City Hospital oncology referral center were retrospectively reviewed by 2 pathologists. Pathological evaluation was performed at a single tertiary oncology center, while surgical procedures were conducted by several orthopedic oncologists across 2 tertiary oncology referral and teaching centers. All cases that met the diagnostic criteria were included. Patients with less than 12 months of follow-up from their initial surgery were excluded from the analysis. Patients presenting with recurrent disease were included regardless of the follow-up duration following reoperation. The cases were divided into 2 distinct groups to evaluate the impact of their local growth patterns on histopathological findings and recurrence rates.
Ethical standards compliance
The investigation was conducted in accordance with the Declaration of Helsinki of 1975. Patient consent forms were obtained. The analysis of the remnants of diagnostic tissues for research purposes has been approved by the local ethics committee of Prof. Dr. Cemil Tascioglu City Hospital (Approval No: E-48670771-514.99-226502169, Date: 09.10.2023).
Group definitions and data collection
The cases were categorized based on their local extension, a classification determined by microscopic findings. The first group, designated as non-infiltrative tumors, consisted of tumors confined to the bone. The second group, referred to as infiltrative tumors, included cases that showed invasion of the bone cortex and/or extracortical connective tissues. All hematoxylin/eosin-stained slides were evaluated for cytological atypia, necrosis, osteoid and chondroid matrix production, mitotic index, aneurysmal bone cyst formation, and invasion patterns. Cytologic atypia, which was graded based on the criteria established by Papke et al14 and Fritchie et al,15 focused on nuclear hyperchromasia, contour irregularity, nuclear shape and size difference, and nuclear enlargement. For both groups, detailed clinical and histopathological data were retrospectively collected and compared. The clinical variables included patient demographics (age and gender), tumor location, the specific surgical technique used (e.g., curettage alone, with a high-speed burr), the type of local adjuvant treatments applied (such as phenol, hydrogen peroxide), and the recurrence status during the follow-up period. Metastasis data was primarily obtained through radiological imaging, including computed tomography and magnetic resonance imaging.
Immunohistochemical (IHC) staining was performed on deparaffinized, rehydrated tissue sections obtained from representative formalin-fixed, paraffin-embedded blocks. Internal IHC staining protocols used with the avidin-biotin-peroxidase complex technique using the Ventana ULTRA automated platform and the following commercially available antibodies: DOG1 (sp31, prediluted; Ventana), S-100 (4c4.9, prediluted; Cell Marque), and Ki-67 (30-9, prediluted; Roche TD).
Statistical analysis
Statistical analyses were conducted using SPSS. Descriptive statistics (mean, SD, median, minimum, and maximum values) are used for quantitative variables, while frequencies and percentages are reported for categorical variables. The Shapiro–Wilk test was used to assess normality. The Student’s t-test was applied to compare normally distributed variables between 2 independent groups, while the Mann–Whitney U-test was used for non-normally distributed data. Categorical variables were analyzed using the chi-square test or Fisher’s exact test, as appropriate. Correlations between variables were examined using Point-Biserial, Spearman’s, and Pearson’s correlation analyses. A P-value of <.05 was considered statistically significant.
Results
A total of 26 patients were included in the study. The ratio of male to female patients was approximately 1.36 : 1 (15/11). At the time of diagnosis, the ages of the patients ranged from 10 to 24 years (average 17.7). In 19 patients, the tumor was located at the lower extremity, and the most frequently affected site was the femur (7 patients) and proximal tibia (5 patients) (Figure 1). The mean maximum dimension of the tumors was 34.4 mm (median, 30 mm; range 17 mm-80 mm). The clinical features of the patients are presented in Table 1.
Figure 1.

Magnetic resonance image of the knee joint from one of the patients. A chondroblastoma with lobulated contours, appearing hyperintense on the T2-weighted sequence, is located in the distal epiphysis of the tibia.
Table 1.
Clinical features of the chondroblastoma patients
| Clinical features | n (%) | ||
|---|---|---|---|
| Gender | Male | 15 (57.7) | |
| Female | 11 (42.3) | ||
| Diagnosis age of patient | Av ± Ss | 17.7± 3.7 | |
| Med (min-max) | 17 (10-24) | ||
| Location | Upper extremity | 5 (19.2) | |
| Pelvis | Ilium | 1 (3.8) | |
| Ischium | 1 (3.8) | ||
| Lower extremity | Femur | 7 (26.9) | |
| Tibia | 5 (19.2) | ||
| Patella | 1 (3.8) | ||
| Foot bones | Talus | 3 (11.5) | |
| Calcaneus | 3 (11.5) | ||
| Tumor diameter (mm) | Av ± Ss | 34.4 ± 14.94 | |
| Med (min-max) | 30 (17-80) | ||
| Surgical treatment status | Unknown | 1 (3.8) | |
| Curettage | 4 (15.4) | ||
| Curettage + grafting | 10 (38.5) | ||
| Curettage + cementation | 10 (38.5) | ||
| Marginal excision | 1 (3.8) | ||
| Resection | 0 (0) | ||
| Perioperative adjuvant therapy | Unknown | 3 (11.6) | |
| None | 2 (7.6) | ||
| Phenol | 1 (3.8) | ||
| Cauterization | 1 (3.8) | ||
| High speed burr | 1 (3.8) | ||
| Phenol + cauterization | 4 (15.4) | ||
| Phenol + high speed burr | 7 (26.9) | ||
| Phenol + cauterization + high speed burr | 6 (23.1) | ||
| Cauterization + high speed burr | 1 (3.8) | ||
Av, average; Med, median; Ss, standard deviation.
Histopathological findings are summarized in Table 2. Reviewing the slides of all tumors revealed characteristic findings of CB consisting of chondroblasts with eosinophilic cytoplasm (Figure 2a). In 18 tumors mild cytologic atypia and in 7 tumors moderate atypia were present (Figure 2b). In 26 tumors chondroid matrix and 13 tumors calcification were detected. Secondary aneurysmal bone cyst was present in 12 patients (M/F = 1.0) (46.2%) (Figure 3a). The mean mitotic index was 2 mm2 and ranged from 0 to 7 (Figure 3b). A total of 4 patients were found to have tumor infiltration into soft tissues. Specifically, 2 patients exhibited infiltration into the subcutaneous tissue, and 2 patients showed infiltration into the dermis (Figure 4). In addition, focal tumor infiltration through the bone cortex was observed in 12 patients (Figure 5). The average age of diagnosis was 17 in both infiltrative and non-infiltrative groups (Table 3). Tumors located in the lower extremities were found to show a statistically significant rate of invasion compared to tumors located in the upper extremities (P = .02). When patients were classified according to their invasion levels (no invasion, bone cortex invasion, and subcutaneous tissue and/or skin invasion), the tumor diameter was significantly greater in the group with subcutaneous and/or skin invasion compared to the other groups (P = .023) (Table 4).
Table 2.
Histopathological features of the chondroblastoma patients
| Histopathological features | n (%) | |
|---|---|---|
| Cytological atypia | None | 1 (3.8) |
| Mild | 18 (69.2) | |
| Moderate | 7 (26.9) | |
| Osteoid matrix | Absent | 5 (19.2) |
| Present | 21 (80.8) | |
| Chondroid matrix | Mature | 2 (7.6) |
| Immature | 20 (76.9) | |
| Mature + immature | 4 (15.4) | |
| Invasion | Absent | 10 (38.5) |
| Bone cortex | 12 (46.2) | |
| Subcutaneous tissue and/or skin | 4 (15.4) | |
| Secondary aneurysmal bone cyst | Absent | 14 (53.8) |
| Present | 12 (46.2) | |
| Calcification | Absent | 13 (50) |
| Present | 13 (50) | |
| Giant cells | Absent | 2 (7.7) |
| Present | 24 (92.3) | |
| Mitosis | Av ± Ss | 2 ± 2.02 |
| Med (min-max) | 1 (0-7) | |
| Ki-67 Index (%) | Av ± Ss | 7.04 ± 4.4 |
| Med (min-max) | 5.5 (1-15) | |
Figure 2.

(A) Tumor consisting of chondroblasts with eosinophilic cytoplasm within a chondroid matrix (×100; H-E). (B) Chondroblasts having moderate atypia (×400; H-E).
Figure 3.

(A) Aneurysmal bone cyst formation within the tumor (×20; H-E). (B) Mitotic activity of neoplastic cells (circle; ×400; H-E).
Figure 4.

Tumor infiltration through subcutaneous tissue (×5; H-E).
Figure 5.

Tumor infiltration through bone cortex (×100; H-E).
Table 3.
Relationships between invasion status and clinicopathological data
| Invasion (n) (%) | P | |||
|---|---|---|---|---|
| Present (n = 16) (61.5) | Absent (n = 10) (38.5) | |||
| Diagnosis age of patient | Av ± Ss | 17 ± 3.88 | 17.4 ± 3.56 | .37* |
| Med (min-max) | 16 (11-24) | 18 (10-22) | ||
| Gender | Male | 11 (64.7) | 4 (40) | .149** |
| Female | 5 (35.3) | 6 (60) | ||
| Location | Upper extremity | 1 (6.2) | 4 (40) | .020**** |
| Foot | 6 (37.5) | 0 (0) | ||
| Lower extremity | 7 (43.7) | 6 (60) | ||
| Pelvis | 2 (12.4) | 0 (0) | ||
| Tumor diameter (mm) | Av ± Ss | 33.6 ± 17.30 | 31.75 ± 9.73 | .423*** |
| Med (min-max) | 30 (17-80) | 30 (18-50) | ||
| Cytological atypia | None | 0 (0) | 1 (10) | .022**** |
| Mild | 9 (56.2) | 9 (90) | ||
| Moderate | 7 (43.8) | 0 (0) | ||
| Osteoid matrix | Absent | 4 (25) | 1 (10) | .345** |
| Present | 12 (75) | 9 (90) | ||
| Chondroid matrix | Mature | 1 (6.2) | 1 (10) | .803** |
| Immature | 12 (75) | 8 (80) | ||
| Mature + immature | 3 (18.8) | 1 (10) | ||
| Secondary aneurysmal bone cyst | Absent | 7 (43.8) | 7 (70) | .191** |
| Present | 9 (56.2) | 3 (30) | ||
| Calcification | Absent | 10 (62.5) | 3 (30) | .107** |
| Present | 6 (37.5) | 7 (70) | ||
| Mitosis | Av ± Ss | 2.5 ± 2 | 1 ± 1.79 | .023*** |
| Med (min-max) | 2 (0-7) | 0.5 (0-4) | ||
| Ki-67 Index (%) | Av ± Ss | 6.9 ± 3.56 | 6.6 ± 5.54 | .399*** |
| Med (min-max) | 6 (2-15) | 5 (1-15) | ||
Bold values indicate statistically significant results (P < .05).
*Student’s t-test.
**Pearson’s chi-square test.
***Mann–Whitney U-test.
****Fisher exact test.
Table 4.
Relationships between different invasion levels and clinicopathological data
|
|
Invasion Levels (n) (%) | ||||
|---|---|---|---|---|---|
| Absent (n = 10) (38.5) | Bone cortex (n = 12) (46.2) | Subcutaneous tissue and/or skin (n = 4) (15.4) | P | ||
| Diagnosis age of patient | Av ± Ss | 17.4 ± 3.565 | 17.38 ± 4.33 | 15.75 ± 1.7 | .684 |
| Med (min-max) | 18 (10-22) | 16 (11-24) | 15 (14-15) | ||
| Gender | Male | 4 (40) | 9 (75) | 2 (50) | .263 |
| Female | 6 (60) | 3 (25) | 2 (50) | ||
| Location | Upper extremity | 4 (40) | 1 (8.3) | 0 (0) | .501 |
| Foot | 0 (0) | 5 (41.6) | 1 (25) | ||
| Lower extremity | 6 (60) | 4 (33.3) | 3 (75) | ||
| Pelvis | 0 (0) | 2 (16.6) | 0 (0) | ||
| Tumor diameter (mm) | <34 | 6 (60) | 7 (58.4) | 1 (25) | .023 |
| ≥34 | 2 (20) | 5 (41.6) | 3 (75) | ||
| Cytological atypia | None | 1 (10) | 0 (0) | 0 (0) | .026 |
| Mild | 9 (90) | 7 (58.4) | 2 (50) | ||
| Moderate | 0 (0) | 5 (41.6) | 2 (50) | ||
| Osteoid matrix | Absent | 1 (10) | 3 (25) | 1 (25) | .67 |
| Present | 9 (90) | 9 (75) | 3 (75) | ||
| Chondroid matrix | Mature | 1 (10) | 1 (8.3) | 0 (0) | .699 |
| immature | 8 (80) | 9 (75) | 3 (75) | ||
| Mature + immature | 1 (10) | 2 (16.6) | 1 (25) | ||
| Secondary aneurysmal bone cyst | Absent | 7 (70) | 6(50) | 1 (25) | .319 |
| Present | 3 (30) | 6 (50) | 3 (75) | ||
| Calcification | Absent | 3 (30) | 9 (75) | 1 (25) | .061 |
| Present | 7 (70) | 3 (25) | 3 (75) | ||
| Mitosis | <2 | 8 (80) | 5 (41.6) | 1 (25) | .178 |
| ≥2 | 2 (20) | 7(58.4) | 3 (75) | ||
| Ki-67 Index (%) | <7 | 6 (60) | 7 (58.4) | 1 (25) | .471 |
| ≥7 | 3 (30) | 5 (41.6) | 3 (75) | ||
The cut-off values determined for tumor diameter, mitotic count, and Ki-67 proliferation index are based on average values.
One patient with missing Ki-67 data and 2 patients with missing tumor diameter data were excluded from the analysis.
Bold values indicate statistically significant results (P < .05).
The relationships between cytological atypia and clinicopathological parameters were examined, and cytological atypia was significantly correlated with mitotic activity (P = .001) (Table 5). The correlation between the mitotic index, invasion status, and histopathological features is presented in Table 6.
Table 5.
Relationships between cytological atypia and clinicopathological data
| Cytological atypia (n) (%) | P | |||
|---|---|---|---|---|
| Low (None + mild) (n = 19) (%) | High (moderate) (n = 7) (%) | |||
| Diagnosis age of patient | Av ± Ss | 16.8 ± 3.62 | 18.14 ± 4.05 | .21* |
| Med (min-max) | 16 (10-24) | 16.5 (15-24) | ||
| Gender | Male | 10 (52.6) | 5 (71.4) | .39** |
| Female | 9 (47.4) | 2 (28.6) | ||
| Location | Upper extremity | 4 (21) | 1 (14.3) | .379**** |
| Foot | 3 (15.8) | 3 (42.8) | ||
| Lower extremity | 11 (57.9) | 2 (28.6) | ||
| Pelvis | 1 (5.3) | 1 (14.3) | ||
| Tumor diameter (mm) | Av ± Ss | 32.5 ± 12.64 | 40.85 ± 19.52 | .162*** |
| Med (min-max) | 30 (17-67) | 40 (25-80) | ||
| Invasion | Absent | 10 (52.6) | 0 (0) | .028**** |
| Bone cortex | 7 (36.8) | 5 (71.4) | ||
| Subcutaneous tissue and/or skin | 2 (10.6) | 2 (28.6) | ||
| Osteoid matrix | Absent | 5 (26.3) | 0 (0) | .278**** |
| Present | 14 (73.7) | 7 (100) | ||
| Chondroid matrix | Mature | 2 (10.6) | 0 (0) | .110**** |
| Immature | 16 (84.2) | 4 (57.1) | ||
| Mature + immature | 1 (5.3) | 3 (42.8) | ||
| Secondary aneurysmal bone cyst | Absent | 10 (52.6) | 4 (57.1) | .838** |
| Present | 9 (47.4) | 3 (42.8) | ||
| Calcification | Absent | 9 (47.4) | 4 (57.1) | .658** |
| Present | 10 (52.6) | 3 (42.8) | ||
| Mitosis | Av ± Ss | 1.31 ± 1.52 | 4.14 ± 1.67 | .001*** |
| Med (min-max) | 1 (0-4) | 4.5 (2-7) | ||
| Ki-67 Index (%) | Av ± Ss | 7 ± 4.72 | 7.28 ± 3.09 | .243*** |
| Med (min-max) | 5 (1-15) | 9 (2-10) | ||
Bold values indicate statistically significant results (P < .05).
*Student’s t test.
**Pearson’s chi-square test.
***Mann–Whitney U-test.
****Fisher’s exact test.
Table 6.
Relationships between mitotic index, invasion status and histopathological parameters
| Mitotic index | Invasion status | |||
|---|---|---|---|---|
| r | P | r | P | |
| Cytological atypia | .669* | .001* | .5166* | .006* |
| Ki-67 Index | .1393*** | .506*** | −.051** | .809** |
| Tumor diameter | .2525*** | .245*** | .139** | .505** |
*Spearman’s.
**Point–Biserial correlation.
***Pearson.
Bold values indicate statistically significant results (P < .05).
In the immunohistochemical study, all tumors showed S100 immunopositivity varying in intensity and extent. The mean Ki-67 expression was slightly lower in the non-recurrent group (6.86) compared to the recurrent group (8.0), although this difference was not statistically significant (P = .35). Similarly, no significant difference in Ki-67 scores was found between the infiltrative and non-infiltrative groups (P = .39). DOG1 was mostly negative (positivity in eight tumors, 30.8%). Because of unavailability, H3K36 could not be performed.
The mean follow-up period was 38.9 months (range: 12-74 months). Ten patients were treated by curettage and grafting, 10 patients by curettage and cementing, 4 patients by curettage alone, and 1 patient by marginal excision. Treatment information for 1 patient could not be accessed. Recurrence was detected in 4 patients after a mean of 26 months (17-34 months) (Recurrence rate: 15.4%). All the recurrent tumors displayed invasion: 1 through the dermis, 2 subcutaneous tissue, and 1 bone cortex. Recurrent tumors were located at the proximal tibia in 2 patients, distal femur in 1 patient, and calcaneus in 1 patient. A patient with a tumor that had been previously treated by radiofrequency ablation, and that showed bone cortex invasion, underwent curettage. The patient is alive with no evidence of disease after 27 months. In the patient having invasion through the dermis, the recurrent tumor of the proximal tibia was treated by curettage and cementing. After 34 months of follow-up, she is well without evidence of the disease. One of the tumors located at the calcaneus, displaying soft tissue invasion, was treated by curettage and cementing. After 17 months of follow-up, the patient is well without evidence of the disease. The fourth recurrent tumor, which showed soft tissue invasion and represented a second recurrence in a previously operated patient, was treated by excision and grafting. After 10 months of follow-up from the second surgery, the patient is well without evidence of disease.
A total of 21 patients (80.8%) received perioperative adjuvant treatment. The most frequently employed regimen was the combination of phenol and a high-speed burr, used in 7 patients (26.9%). This was followed by a combination of phenol, cauterization, and a high-speed burr, which was applied in 6 cases (23.1%). None of the patients had metastasis.
Discussion
Chondroblastoma is a rare cartilage-producing tumor of bone.,13 In the series consisting of 26 patients, the male/female ratio was 1.36 : 1, slightly lower than the literature.13,16-19 Femur was the most common location. The local recurrence rate was 15.4% within the range reported in the literature.17,18,20,21 The possible causes of the recurrence have been investigated in several reports.21 Some of these were as follows: open growth plate, younger age, accompanying aneurysmal bone cyst formation. These factors did not appear to significantly affect the recurrence rate.17,18,21 A correlation between the recurrence rate and the aneurysmal bone cyst formation or the age of the patient could not be found. Lin et al claimed that inadequate surgery and biological aggressiveness played a role in local recurrence.21 They described biological aggressiveness as malignant transformation. Turcotte et al found a higher mitotic rate in recurrent tumors.16 However, in previous reports, it has been stated that mitotic activity did not correlate with the recurrence rate.22 In the series, moderate cytological atypia and a higher mitotic index were significantly more prevalent in invasive tumors compared to non-invasive tumors (P = .022 and P = .023, respectively) (Table 3).
The term “aggressive chondroblastoma” has been used for the tumors with local infiltrative growth.13 These tumors have been described to show invasion beyond the bone cortex into soft tissues. In their manuscript reviewing the tumors diagnosed as atypical CB, malignant CB, and CB-like osteosarcoma, Papke et al have tried to clarify this controversial entity.14 They have described malignant CB as tumors showing widespread invasion of soft tissues or metastasis, referring to Kyriakos et al23 They used permeative growth and/or significant cytologic atypia beyond that of conventional CB as criteria for malignant CB.14 In some case series, invasion of the bone cortex was frequently observed.16,20,22 Similarly, in the study, cortical invasion was present in 16 out of 26 cases (61.5%). Despite this relatively high incidence, only 4 tumors recurred, and none of the patients developed metastases. Notably, all 4 recurrent tumors exhibited local invasion, while none of the tumors confined to bone recurred. These findings suggest that local invasion may be a risk factor for recurrence, even in the absence of metastatic behavior. Some authors reported higher mitotic activity in tumors showing aggressive behavior.14 In the patients, it was found that tumors with higher cytological atypia and higher mitotic activity showed a significantly higher rate of invasion as a sign of local aggressiveness. Cytological atypia and mitotic activity were also correlated. Consistent with these findings, tumor diameter was found to be higher in the group with invasion into the subcutaneous tissue and/or skin.
Although H3K36 has been reported to be a sensitive and specific immunohistochemical marker for CB,19 DOG1 also has been claimed to be a useful marker for differential diagnosis.24 However, this suggestion was not supported because DOG1 positivity could be detected only in a subset of the tumors. The positivity was focal and low in intensity. It was considered difficult to obtain a standard staining procedure of DOG1 for CB.
Pulmonary metastasis of CB has been reported previously.23 Most of these metastatic diseases showed an indolent clinical course.10 However, in some patients, the outcome was fatal with widespread metastasis.14,23 Pulmonary metastasis was not observed in the patients; however, Kyriakos et al noted that there were no histopathological findings indicative of metastatic and fatal disease.23 Although the follow-up period was relatively limited, most recurrences tend to occur within the first three years.20 Still, given that late recurrences have been reported, long-term surveillance is advisable.16,21,23
The majority of the patients were treated with curettage followed by cement or bone grafting. A higher proportion of patients in the non-recurrent group received combined adjuvant therapy (18/19, 94.7%) compared to the recurrent group (2/4, 50%). However, no statistically significant difference was found between the recurrent and non-recurrent groups regarding the use of single vs. combined treatment modalities (P = .52). Specifically, in the recurrent group, 1 patient received no therapy, and one received a single modality, whereas in the non-recurrent group, 2 patients received no therapy and 2 received a single modality. Although the proportion of patients receiving combined treatment with phenol and high-speed burr was higher in the non-recurrent group (7/19, 36.9%) compared to the recurrent group (1/4, 25%), this difference was not statistically significant (P = .26). The lack of statistical significance may be attributed to the small number of recurrent patients in the series.
Regarding the surgical technique, no statistically significant difference in recurrence rates was observed between patients who underwent high-speed burr-assisted curettage and those who underwent manual curettage alone; however, the limited number of recurrent cases in the series restricts the interpretability of this finding. Larger prospective studies would be needed to definitively determine whether the use of a high-speed burr confers a protective benefit against local recurrence in CB.
About postoperative surveillance, it is suggested that patients harboring higher-risk features (local invasion, elevated mitotic activity, or moderate cytological atypia) warrant more frequent and prolonged follow-up. Although most recurrences in the cohort occurred within the first 3 years, late recurrences have been documented in the literature, and long-term surveillance remains advisable for all patients. A risk-stratified follow-up protocol, with shorter inter-visit intervals for patients demonstrating aggressive histopathological features, may facilitate earlier detection of recurrence and improve outcomes.
In conclusion, although the follow-up period in the study is limited, the findings suggest that CB generally behaves in a benign manner. Locally aggressive features, such as cortical or soft tissue invasion, were observed in several cases but did not lead to metastasis. High mitotic activity and moderate cytological atypia may serve as histopathologic indicators of local aggressiveness.
Funding Statement
The authors declared that this study has received no financial support.
Footnotes
Artificial Intelligence Usage Statement: The authors declared that no Artificial Intelligence tool was used in the preparation of the manuscript.
Ethics Committee Approval: Ethical committee approval was received from the Ethics Committee of Prof. Dr. Cemil Taşçıoğlu City Hospital (Approval no: 206, Date: 09.10.2023).
Informed Consent: Written informed consent was obtained from the patients/patient who agreed to take part in the study.
Peer-review: Externally peer-reviewed.
Author Contributions: Concept – M.İ.S.A., C.Ç.; Design – M.İ.S.A., C.Ç.; Supervision – C.Ç.; Resources – B.D., M.A.; Materials – B.D., M.A.; Data Collection and/or Processing – M.İ.S.A., C.Ç., R.T.; Analysis and/or Interpretation – M.İ.S.A., C.Ç.; Literature Search – M.İ.S.A., C.Ç.; Writing – M.İ.S.A, C.Ç.; Critical Review – C.Ç.
Declaration of Interests: The authors have no conflict of interest to declare.
Data Availability Statement:
The data that support the findings of this study are available on request from the corresponding author.
References
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The data that support the findings of this study are available on request from the corresponding author.

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