Clinicopathological characteristics and prognostic factors in axial chondroblastomas: a retrospective analysis of 61 cases and comparison with extra-axial chondroblastomas.

BACKGROUND: A comprehensive understanding of the clinical characteristics and prognostic factors associated with axial chondroblastoma (ACB) is still lacking. This study aimed to understand the clinical characteristics and prognostic factors of axial chondroblastoma (ACB) and compare them with extra-axial chondroblastoma (EACB). METHODS: A retrospective review of our institution's local database was conducted, encompassing a total of 132 CB patients, of which 61 were diagnosed with ACB and 71 with EACB. Immunohistochemistry was employed to evaluate the expression levels of vimentin, S100, and cytokeratin. RESULTS: ACB and EACB shared similar characteristics, with the exception of advanced age, tumor size, elevated Vim expression, incidence of surrounding tissue invasion, and postoperative sensory or motor dysfunction. While wide resection and absence of surrounding tissue invasion consistently showed a favorable association with survival in both ACB and EACB cohorts during univariate analysis, most parameters exhibited differential prognostic significance between the two groups. Notably, the significant prognostic factors for local recurrence-free survival in the ACB cohort included the type of resection and the presence of chicken-wire calcification. In the multivariate analysis of overall survival, the type of resection emerged as a significant predictor in the ACB cohort, whereas in the EACB group, the type of resection and the occurrence of postoperative sensory or motor dysfunction were predictive of overall survival. CONCLUSION: There may exist distinct biological behaviors between ACB and EACB, thereby providing valuable insights into the prognostic characteristics of ACB patients and contributing to enhanced outcome prediction in this particular patient population.

Utility of immunohistochemical expression of H3.3K36M and DOG1 in the diagnosis of chondroblastomas: An experience from a tertiary cancer referral center.

Despite its characteristic clinicopathological features, chondroblastoma may pose a diagnostic challenge, given its morphological spectrum, potential for subdiagnostic appearances in limited biopsy specimens, and its potential mimicry of other entities. Recently, a characteristic H3F3B mutation underlying most chondroblastomas was described, which led to the identification of H3.3K36M as the corresponding diagnostic immunohistochemical marker. The present study is an evaluation of immunohistochemical features of 26 chondroblastomas, including DOG1 and H3.3K36M immunostaining. H3.3K36M immunostaining was graded as 1+, 2+ and 3+ in terms of staining intensity. There were 17 males and 9 females (M:F = 1.8:1) with ages ranging from 7 to 34 years (average = 16.7, median = 16). The most common location was proximal humerus (8, 30.7 %) followed by proximal tibia (5, 19.2 %), distal femur (3, 11.5 %), proximal femur (3, 11.5 %), pelvis (2,), followed by distal tibia, calcaneum, upper sternum, scapula, and D9 vertebra, in a single case, respectively. Eighteen (69.23 %) tumors displayed all the classic histopathological features. Immunohistochemically, the tumor cells were positive for S-100 P (19/22, 86.3 %), DOG1 (focal to patchy) (21/23 91.3 %), and H3.3K36M (26/26, 100 %). H3.3K36M tested in other tumors, constituting diagnostic mimics of a chondroblastoma, such as giant cell tumor of bone, chondromyxoid fibroma, and tenosynovial giant cell tumors, showed negative staining. Six tumors, initially diagnosed as chondroblastomas were reclassified into other entities with the help of negative H3.3K36M immunostaining. The present study reinforces H3.3K36M as a highly sensitive and specific marker for diagnosing chondroblastoma, including small biopsies, and in uncommon tumor sites with variable histopathological features. DOG1 is also useful in reinforcing a diagnosis of chondroblastoma in a clinicoradiological context, especially in laboratories lacking H3.3K36M immunostain. However, its staining pattern is variable.

Chondroblastoma of foot bones; a clinicopathological study of 29 cases confirming the diagnostic utility of H3K36M and H3G34W antibodies at an uncommon site.

OBJECTIVE: Chondroblastoma (CB) is a benign cartilaginous bone neoplasm which commonly occurs in long bones of adolescents. CB can uncommonly involve foot. Its mimics include both benign and malignant lesions. H3K36M immunohistochemical (IHC) stain is a helpful tool for establishing the diagnosis of CB in such challenging situations. In addition, H3G34W IHC stain helps to rule out giant cell tumor which is the closest differential of CB. Our objective was to describe the clinicopathological features and frequencies of H3K36M, H3G34W and SATB2 IHC stains in CB of foot. MATERIALS AND METHODS: We reviewed H&E slides and blocks of 29 cases diagnosed as "chondroblastoma" of foot at our institutions. RESULTS: Patient's age ranged from 6 to 69 (mean: 23.3 and median: 23) years. Males were almost 5 times more commonly affected than females. Talus and calcaneum were involved in 13 (44.8 %) cases each. Microscopically, tumors were composed of polygonal mononuclear cells and multinucleated giant cells and chondroid matrix. Other histological features included aneurysmal bone cyst-like (ABC-like) change (44.8 %), osteoid matrix (31 %), chicken-wire calcification (20.7 %), and necrosis (10.3 %). H3K36M was expressed in 100 % and SATB2 in 91.7 % cases. H3G34W was negative in all cases, where performed. One out of 11 patients with follow up information developed local recurrence after 48 months. CONCLUSION: CB in foot occur at an elder age and show more frequent ABC-like changes as compared to long bones. Males are affected ~5:1 as compared to 2:1 in long bones. H3K36M are H3G34W are extremely useful diagnostic markers for CB, especially elderly (aged or higher) patients and we report the largest series of foot CB cases confirmed by immunohistochemistry.

Distal Femoral Non-Epiphyseal Cortical Chondroblastoma Confirmed with H3F3B p. Lys36Met Mutation.

Background: Chondroblastoma is a primary bone tumor typically arising from the intramedullary space of the epiphysis or epimetaphysis. A non-epiphyseal chondroblastoma is uncommon. Case report: An 11-year-old girl presented with an eccentric cortical osteolytic lesion in the distal femur metaphysis. The typical morphology, diffuse H3.3 K36M immunohistochemical expression and H3F3B point mutation (c. 110A > T) unequivocally supported the diagnosis of chondroblastoma. Discussion: We described a non-epiphyseal cortical-based chondroblastoma involving the distal femur harboring the typical H3F3B mutation. Non-epiphyseal chondroblastoma may harbor the H3F3B mutation.

Chondroblastoma-like osteosarcoma: a clinicopathological and molecular study of a rare osteosarcoma variant.

OBJECTIVE: Chondroblastoma-like osteosarcoma (CBLOS) is a rare and poorly understood variant of OS. We examined the clinicopathological, immunohistochemical and molecular features of six CBLOSs to highlight the differences with conventional high-grade OS (CHGOS) and CB, including CB with aggressive features. METHODS: We performed histone 3.3 mutation analysis by gene sequencing and/or immunohistochemistry in all cases, while whole exome sequencing (WES) was performed on two CB-like osteosarcomas and 11 conventional high-grade OS. RESULTS: CBLOSs were predominantly localised at acral sites and involved mainly male subjects with a mean age of 29 years. One patient who had metastases at presentation died of disease, while another patient who developed multiple local recurrences and lung metastases was alive with no evidence of disease (ANED) at 294 months. The remaining patients were ANED after a mean interval of 70.8 months. Histologically, all CBLOS presented aggressive features, including nuclear atypia and infiltrative growth. Immunohistochemistry with H3F3 K36M mutant antibody was negative in all CBLOSs, and none of the five tumours tested by gene sequencing had H3F3B mutations. Conversely, all CBs presented the H3F3B K36M variant and were positive for immunostaining with the H3F3 K36M antibody. Two CBLOSs analysed by WES differed in amount and type of mutation from 11 cases of CHGOS. Moreover, CBLOSs showed lower copy number alteration (CNA) score values than CHGOSs. CONCLUSIONS: CBLOS presents a different genetic background and a less aggressive clinical behaviour in comparison with CHGOS. Search of the H3F3B K36M mutation is useful in the differential diagnosis with CB.

Total Calcanectomy and Bilateral Iliac Bone Autograft Reconstruction for the Treatment of Calcaneal Chondroblastoma Involving a Secondary Aneurysmal Bone Cyst: A Case Report and Literature Review.

Chondroblastoma is a rare, benign, cartilaginous-derived tumor accounting for ∼1% to 2% of all primary bone tumors and almost 9% of all benign bone tumors. In this case report, we describe a patient with chondroblastoma and a secondary aneurysmal bone cyst, with the adjacent talus being mildly affected. The initial diagnosis was giant cell tumor and was then confirmed after computed tomography-assisted biopsy. We performed a total calcanectomy via bilateral structural iliac bone autografting to relieve pain and reconstruct the loadbearing function because of the presence of extensive lesions. The patient was pain free and expressed satisfaction with postsurgical dorsiflexion and plantarflexion function at the 60-month follow-up visit. Radiographic images showed that the autografted iliac bone was completely healed, with no evidence of local recurrence.

Histone H3K36M mutation and trimethylation patterns in chondroblastoma.

AIMS: Histones are essential components of chromatin, and mutations in histones lead to alterations in methylation and acetylation, which play an important role in tumorigenesis. Most of the chondroblastomas harbour the H3K36M mutation. With the availability of a mutation-specific antibody, we sought to assess the sensitivity of this antibody and the alterations of histone methylation in a series of chondroblastoma cases. METHODS AND RESULTS: Immunohistochemical staining with antibodies against H3K36M, trimethylated histones (H3K27me3 and H3K36me3) and an osteoblastic marker (SATB2) was performed on 27 chondroblastomas from 27 patients. The clinical and radiological characteristics of each patient were reviewed. All 27 tumours showed typical radiological and histological features of chondroblastoma, with a subset of cases showing secondary aneurysmal bone cyst changes (11/27), giant-cell-rich foci (4/27), and matrix-rich areas mimicking chondromyxoid fibroma (1/27). All except one case (26/27, 96%) showed positive H3K36M immunostaining (nuclear). In the majority of cases, there was a diffuse staining pattern. Immunohistochemical staining for H3K27me3 and H3K36me3 showed a heterogeneous staining pattern in all cases, regardless of mutation status. None of the cases showed loss of positivity or diffuse positivity. Focal or diffuse SATB2 expression was seen in 21 of 26 tumours (81%). CONCLUSION: Our results demonstrate that the vast majority of chondroblastomas are positive for H3K36M by immunohistochemical analysis, confirming its diagnostic value. H3K27me3 expression and H3K36me3 expression are heterogeneous in these tumours.

Functional and Oncological Outcome After Treatment of Chondroblastoma With Intralesional Curettage.

BACKGROUND: Chondroblastoma is a rare cartilaginous benign bone tumor that commonly arises in long bones of young people. Surgical management is the primary treatment of choice for chondroblastoma and it entails adequate intralesional curettage alone or in combination with adjuvants. This study was performed to describe the epidemiological characteristics and clinical and radiologic results of intralesional curettage of chondroblastoma. METHODS: This was a retrospective study which included an analysis of 91 patients with chondroblastoma who were treated with intralesional curettage and were followed up between 1994 and 2014 for at least 3 years. Epidemiological data, clinical symptoms, radiologic and histologic investigations, surgery, functional outcomes, complications, and local recurrence rate were analyzed. RESULTS: There were 60 males (65.9%) and 31 females (34.1%) with a mean age of 16.4 years. The most commonly involved bone was the proximal tibia in 24 patients (26.4%), followed by distal femur in 20 patients (22%), proximal humerus in 17 patients (18.7%) and proximal femur in 15 patients (16.6%). All patients underwent intralesional curettage. High-speed burr was used in 66 patients (72.5%). The resultant cavity was filled with autogenous bone graft, bone substitute, bone cement or a combination of bone graft and cement. Four patients (4.4%) had complications. Three patients (3.3%) developed local recurrence. Age, site, history of previous intervention or pathologic fracture had no impact on the rate of recurrence. The mean Musculoskeletal Tumor Society (MSTS) score was 28.88 (range, 24 to 30) points. CONCLUSIONS: Thorough curettage using high-speed burr and bone-grafting or bone cement in the treatment of chondroblastoma has good local control, low recurrence rate and excellent functional long-term outcome. LEVEL OF EVIDENCE: Level IV, retrospective case series.

Chondroblastoma-like primary malignant giant cell tumor of the humerus - a case report.

35-year-old woman suffered prolonged pain in the left shoulder, where an aggressively growing tumor of the proximal humerus was revealed thereafter. The lesion caused massive osteolysis of the metaepiphysis with cortical disruption, but no soft tissue extension was evident. Given the unsatisfactory effect, the ongoing neoadjuvant chemotherapy was prematurely ceased and the resection 13 cm long segment of bone with modular prosthesis replacement followed. Histologically, clear-cut malignant tumor with both the presence of numerous reactive osteoclast-like giant cells and geographic structural deposition of chondroid matrix bore a close resemblance to chondroblastoma. Dominant cellular composition formed solid mosaic clusters of large, atypical, frequently binucleated cells with voluminous eosinophilic cytoplasm. Impressive nuclear pleomorphism was accentuated by both the grooving and atypical mitotic figures. Thorough sampling disclosed limited, but sharply contrasting parts, where biphasic arrangement of small uniform stromal elements together with regularly distributed, reactive osteoclasts suggested putative precursor giant cell lesion. Except the osteoclasts, all matrical and stromal cells were strongly SOX9 and D2-40 positive; in contrary desmin, SATB2, S100 and p63 yielded completely negative results. Detected H3F3A c.103G>T mutation in exon 2 finally established true nature of that peculiar neoplastic proliferation and lead to descriptive term of primary chondroblastoma-like malignant giant cell tumor. In the setting of all the microscopic variability, histogenesis and complex differential diagnosis of skeletal (malignant) giant cell lesions, there are discussed e.g. aggressive/malignant chondroblastoma, chondroblastoma-like osteosarcoma or giant cell-rich osteosarcoma and practical impact of specific mutational analysis results as well.

Cystic bone tumors of the foot and ankle.

Bone tumors are relatively rare in the foot and ankle region. Many of them present as cystic lesions on plain films. Due to the relative rarity of these lesions and the complex anatomy of the foot and ankle region, identification of such lesions is often delayed or they get misdiagnosed and mismanaged. This review discusses the most common cystic tumors of the foot and ankle including their radiographic features and principles of management.

Chondroblastoma of the Foot: 40 Cases From a Single Institution.

Chondroblastoma (CB) of the foot is a rare lesion. The purpose of this report was to report a large series from a single institution to analyze clinical, radiographic, and histologic characteristics; treatment; and local recurrence. We present 40 patients (30 males, 10 females; mean age 25 years) diagnosed and treated for CB of the foot from 1975 to 2012. The mean follow-up visit was 55 months (range 7 months to 11 years). Clinical presentation, histology, imaging, surgical treatment, and local recurrence were evaluated. Males were more affected than females. The main symptom was pain (100%) accompanied by swelling (35%), with median duration of 12 months. The talus (50%) and calcaneus (37.5%) were the most affected bones. All patients underwent surgery: curettage (10 cases), curettage and bone graft (15 cases), curettage and cement (13 cases), wide resection (1 case), and Chopart amputation (1 case). Ten patients (25%) had secondary aneurysmal bone cyst. One patient had local recurrence after surgery. In conclusion, patients with CB of the foot are usually older than 20 years, and males are most affected. The hindfoot is the most affected area. Surgical treatment is required, and intralesional curettage and packing with cement or graft is curative in most cases. Local recurrence in foot is lower than in other locations.

[Benign and malignant giant-cell rich lesions of bone: Pathological diagnosis with special emphasis on recent immunohistochemistry and molecular techniques]. / Diagnostic des lésions osseuses riches en cellules géantes : démarche diagnostique et intérêt des nouvelles techniques complémentaires immuno-histochimiques et moléculaires.

The infiltration by numerous osteoclastic giant cells is a frequent finding in bone tumors and pseudo-tumors. Pathologists must integrate clinical and radiological data to achieve a correct diagnosis in bone pathology. Benign giant-cell rich lesions of bone encompass giant cell tumor of bone, aneurysmal bone cyst, chondroblastoma, brown tumor and fibrous cortical defect/non-ossifying fibroma. Amongst malignant neoplasms, variants of conventional osteosarcoma, undifferentiated pleomorphic sarcoma, leiomyosarcoma and bone metastasis must be discussed. Recently, new diagnostic markers, antibodies for immuno-histochemistry and genetic markers, have been developed and are helpful to diagnose such lesions.

H3F3 mutation status of giant cell tumors of the bone, chondroblastomas and their mimics: a combined high resolution melting and pyrosequencing approach.

Behjati et al recently described recurrent mutations of H3F3 genes in giant cell tumors of the bone and chondroblastomas. Both these entities belong to the spectrum of giant cell-rich bone lesions, often presenting a diagnostic challenge for the pathologist. Our aim was to investigate the value of searching for H3F3 mutations in the diagnosis of giant cell tumors of the bone and giant cell-rich chondroblastomas. Two hundred eighty-one bone lesion samples, including 170 giant cell tumors of the bone, 26 chondroblastomas and 85 other giant cell-rich and/or epiphyseal tumors, were analyzed. Mutation status was determined using first high resolution melting screening and then mutation profiling pyrosequencing. Mutational status was compared with clinical data and, for giant cell tumors of the bone, with p63 immunostaining status. As histone methylation changes have been reported in association with H3F3 mutations, the methylation status of lysine 37 was investigated. H3F3A and H3F3B were found in 85% of giant cell tumors of the bone and 88% of chondroblastomas. In addition to the major G35W mutation, we found two rare H3F3A mutations: one G35R and one G35V. Among the other tumors studied, we only found H3F3A gene mutations in two cases of 'dedifferentiated chondrosarcoma mimicking giant cell tumor of the bone'. A H3F3B mutation was also observed in one case of dedifferentiated chondroblastoma. P63 expression in giant cell tumors of the bone seems to be associated with H3F3 gene mutations (P=0.004). H3F3 mutations did not correlate with clinical data, outcome or methylation changes in Lysin 37. In conclusion, H3F3 mutations are sensitive and specific markers of giant cell tumors of the bone and chondroblastomas. High resolution melting and pyrosequencing procedures are high-performance tools in this context. Determination of H3F3 mutation will allow reclassification of some entities belonging to the spectrum of giant cell-rich lesions.

Primary Orbital Chondromyxoid Fibroma: A Rare Case.

A 56-year-old male with history of chronic sinusitis was found to have a 3 cm left orbital lesion on CT. Subsequent MRI demonstrated a multilobulated enhancing soft tissue lesion at the superotemporal region of the left orbit. Initial biopsy was reported as a low-grade sarcoma. On further evaluation, a consensus was made that the lesion was likely a benign mixed mesenchymal type tumor but should nonetheless be surgically removed. Left lateral orbitotomy was performed which revealed a tumor originating in the lateral orbital bone with segments eroding through the wall of the orbit. Intraoperative frozen sections revealed myoepitheliod tissue with locally aggressive features and the tumor was completely removed. The final histopathologic analysis of the tissue was consistent with a chondromyxoid fibroma. Chondomyxoid fibroma is a rare entity in the orbital bones and is more commonly seen in long bones.

The H3F3 K36M mutant antibody is a sensitive and specific marker for the diagnosis of chondroblastoma.

AIMS: We recently reported that 95% of chondroblastomas harbour a p.K36M mutation in either H3F3A (chromosome 1) or H3F3B (chromosome 17), with the majority involving H3F3B. The aim of this study was to assess the expression of the K36M-mutated protein by immunohistochemistry in a large group of tumours. METHODS AND RESULTS: One thousand eight hundred and ninety-four tumours, including 85 chondroblastomas and 10 clear-cell chondrosarcomas, were studied; of these, 82 chondroblastomas and one clear-cell chondrosarcoma known to harbour the H3F3 p.K36M mutation expressed the mutated protein. Three chondroblastomas and nine clear-cell chondrosarcomas wild type for H3F3A/H3F3B were negative for p.K36M immunoexpression. The remaining 1799 cases tested, 545 of which were known to be wild type for the H3F3A and H3F3B p.K36M mutations, included 1047 primary bone tumours, and 507 soft tissue and joint tumours. Two hundred and forty-five other tumour types not expected to harbour the mutation were negative for p.K36M immunoexpression. CONCLUSIONS: Our data demonstrate the specificity and sensitivity of this immunomarker, and will be a useful adjunct for reaching a diagnosis of chondroblastoma.

Radiofrequency ablation of chondroblastoma: long-term clinical and imaging outcomes.

OBJECTIVES: To investigate the long-term clinical and imaging outcomes of patients with chondroblastoma treated by radiofrequency ablation (RFA). METHODS: Retrospective analysis of 25 consecutive patients treated with RFA from September 2006 to December 2013. Patients were reviewed within one month of the procedure, then every 3-6 months, and yearly for up to three years. Serial magnetic resonance imaging (MRI) was performed at follow-up to monitor recovery. Functional outcome was assessed using the Musculoskeletal Tumour Society Score (MSTS). RESULTS: Pre-procedure MRI confirmed osteolytic lesions (size range 1.0-3.3 cm; mean 2.0 cm). Patients reported continued symptomatic improvement at four months review. Serial MRI confirmed progressive resolution of inflammation with fatty consolidation of cavity. 88 % of patients became asymptomatic during the follow up period. Three patients' (12 %) symptoms returned at 16, 22 and 24 months respectively after RFA. MRI and biopsy confirmed recurrence in these patients. Functional assessment using MSTS score had an average score of 97.5 %. Mean follow up for the study group was 49 months. CONCLUSION: RFA is an effective alternative to surgery in the management of chondroblastoma. We recommend a multi-disciplinary approach and RFA should be considered as a first-line treatment. Long-term follow-up is required for timely detection of recurrences. KEY POINTS: • RFA is a safe and effective technique in the treatment of chondroblastoma. • Positive outcomes in 88 % patients at mean follow-up period of 49 months. • Local recurrences occurred in 12 % cases. • Long-term follow-up is required for timely detection of recurrences. • RFA should be considered as a first-line treatment for chondroblastoma.

Chondroblastoma-like osteosarcoma: a case report and review.

Chondroblastoma-like osteosarcomas are extremely rare malignancies having varying clinical, radiological and histological features. Their rarity causes challenges in both diagnosis and clinical management. They are often misdiagnosed as benign lesions. Their accurate diagnosis is important because they require adequate treatment. Misdiagnosed lesions or undertreatment may result in recurrences. We report a case of chondroblastoma-like osteosarcoma arising in the left first metatarsal bone with tarsometatarsal joint involvement in a 10-year-old boy for whom surgery with an original technique was planned after a multidisciplinary diagnostic review.

Surface-based chondroblastoma of the tibia: a unique presentation.

BACKGROUND: Chondroblastoma is a benign tumor classically located within the epiphysis of the long bones. The tumor is believed to arise from immature cells of the epiphyseal plate. Purely metaphyseal or diaphyseal chondroblastoma is exceedingly uncommon, occurring in approximately 2% of chondroblastoma cases. In all of these non-epiphyseal-based cases, the tumor has been intramedullary. METHODS: We describe the histologic and imaging features of the first detailed description of a surface-based chondroblastoma. RESULTS: The tumor was located in the anteromedial midshaft of the tibia in a 47-year-old male. CONCLUSION: We discuss the diagnostic considerations and possible etiology of chondroblastoma given this unusual location.