Cytopathology of Chondromyxoid Fibroma: Report of 2 Cases with Immunocytochemical Expression of GRM1.

INTRODUCTION: Chondromyxoid fibroma (CMF) is a rare, benign bone tumor that occurs predominantly in the second and third decades of life, more frequently in males. Overexpression of GRM1 as a consequence of tumor-specific gene rearrangement of GRM1 has recently been reported as a useful immunohistochemical marker for histopathological diagnosis of CMF. However, the usefulness of GRM1 staining of cytology specimens has not yet been evaluated. In this report, the cytological findings and GRM1 immunocytochemistry of two cases of CMF are described. CASE PRESENTATIONS: Case 1 was a 15-year-old girl with a rib tumor. Imaging findings suggested a benign neurogenic tumor such as schwannoma. The tumor had increased in size over a 2-year period and was resected. Case 2 was a 14-year-old boy with a metatarsal tumor involving his left first toe. Imaging findings were suspicious of a benign neoplastic lesion. Biopsy findings suggested a benign tumor, and the patient underwent tumor resection. Cytologically, in both cases the tumor cells were predominantly spindle-shaped or stellate, with a myxoid to chondromyxoid background matrix and multinucleated giant cells, and these matrices were metachromatic with Giemsa staining. Cellular atypia was more accentuated in case 2 than in case 1. Immunocytochemical staining for GRM1 was positive in both cases. CONCLUSION: Due to the overlap in cytological findings, it is often difficult to differentiate CMF from chondroblastoma and chondrosarcoma grade 2. Immunocytochemical staining for GRM1 may support the diagnosis of CMF, and the reuse of Papanicolaou-stained specimens is applicable. The present cases further demonstrated the difficulty of differentiating CMF from other mimicking tumors such as chondroblastoma and chondrosarcoma grade 2. In such instances, immunocytochemistry for GRM1 is applicable to the diagnostic process, the value of which is strengthened by reusing Papanicolaou-stained specimens.

Chondroblastoma of proximal tibia diagnosed by arthroscopy-guided biopsy: a case report.

Chondroblastoma considered a rare form of osseous neoplasm contributes less than 1% of all bone tumours. It is typically found in young patients with chief complaints of moderate pain with joint stiffness. It develops as a lytic lesion in the epiphysis of long bones which might spread to the metaphysis. We report a case of an 18-year-old patient who presented with progressive right knee pain which aggravated with movements. Investigations included X-ray, magnetic resonance imaging (MRI), and biochemical assessment. A focal, well-defined, lesion in the upper end of the tibia with surrounding marrow oedema was observed and diagnostic arthroscopy was taken for management. Histopathology of specimen observed chondroblasts proliferation with areas of mature cartilage, and giant cells confirming intrasynovial chondroblastoma. Usually, surgery is the treatment of choice; however, possibilities of the secondary bone cyst, haemosiderin deposition on the joint, etc., make treatment approaches uncertain. Diagnostic arthroscopy is a rare but essential modality in such cases due to better visuals, complete tumour excision, and combination with adjuvant therapies. Chondroblastoma, if untreated, proves detrimental, hence, a thorough evaluation is critical for overall better outcomes.

DNA methylation profile discriminates sporadic giant cell granulomas of the jaws and cherubism from their giant cell-rich histological mimics.

Sporadic giant cell granulomas (GCGs) of the jaws and cherubism-associated giant cell lesions share histopathological features and microscopic diagnosis alone can be challenging. Additionally, GCG can morphologically closely resemble other giant cell-rich lesions, including non-ossifying fibroma (NOF), aneurysmal bone cyst (ABC), giant cell tumour of bone (GCTB), and chondroblastoma. The epigenetic basis of these giant cell-rich tumours is unclear and DNA methylation profiling has been shown to be clinically useful for the diagnosis of other tumour types. Therefore, we aimed to assess the DNA methylation profile of central and peripheral sporadic GCG and cherubism to test whether DNA methylation patterns can help to distinguish them. Additionally, we compared the DNA methylation profile of these lesions with those of other giant cell-rich mimics to investigate if the microscopic similarities extend to the epigenetic level. DNA methylation analysis was performed for central (n = 10) and peripheral (n = 10) GCG, cherubism (n = 6), NOF (n = 10), ABC (n = 16), GCTB (n = 9), and chondroblastoma (n = 10) using the Infinium Human Methylation EPIC Chip. Central and peripheral sporadic GCG and cherubism share a related DNA methylation pattern, with those of peripheral GCG and cherubism appearing slightly distinct, while central GCG shows overlap with both of the former. NOF, ABC, GCTB, and chondroblastoma, on the other hand, have distinct methylation patterns. The global and enhancer-associated CpG DNA methylation values showed a similar distribution pattern among central and peripheral GCG and cherubism, with cherubism showing the lowest and peripheral GCG having the highest median values. By contrast, promoter regions showed a different methylation distribution pattern, with cherubism showing the highest median values. In conclusion, DNA methylation profiling is currently not capable of clearly distinguishing sporadic and cherubism-associated giant cell lesions. Conversely, it could discriminate sporadic GCG of the jaws from their giant cell-rich mimics (NOF, ABC, GCTB, and chondroblastoma).

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.

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.

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.

Chondroblastoma: clinicopathological analyses of 307 cases from a single institution in China and the diagnostic value of the H3F3 K36M mutant antibody.

AIMS: To elucidate the clinicopathological features and the diagnostic value of mutation specific antibody H3F3 K36M of chondroblastoma (CB) in China. METHODS: Clinicopathological profiles were retrieved, and immunohistochemistry was performed on 185 CB specimens and the control group. RESULTS: Our series included 307 patients with a mean age of 22.1 years. Long tubular bones (63.8%, 196/307) were most commonly involved, followed by short bones of the hands and feet (22.1%, 68/307), sesamoid bones (8.1%, 25/307), flat bones and irregular bones (5.9%, 18/307). The most commonly involved site was the proximal femur, followed by distal femur, proximal humerus and calcaneus. The average age in the long bones group (20.3 years) was significantly younger than the short bones group (24.9 years) (p<0.001), sesamoid bones group (24.4 years) (p=0.02) and flat bones and irregular bones group (29.1 years) (p<0.001). Microscopically, aneurysmal bone cyst-like change (63.6%, 117/184), necrosis (43.5%, 80/184) and chicken-wire calcification (26.1%, 48/184) were variably noted. In rare cases, cortical destruction, soft tissue and lymphovascular invasion were identified. Positive immunoreaction with H3F3 K36M was examined in all non-decalcified, all EDTA decalcified, 87.1% hydrochloric acid (HCl) decalcified CB samples and the high-grade sarcoma secondary to CB, but not the control group. CONCLUSIONS: CB usually involves the long tubular bones in younger age group. H3F3 K36M can identify K36M mutation with 100% specificity and 100% sensitivity in non-decalcified and EDTA decalcified samples, more than 80% sensitivity in HCl decalcified samples. Virtually, all CBs harbour an H3K36M mutation.

Chondroblastoma: Cytomorphologic Analysis of 10 Cases with Review of the Literature.

INTRODUCTION: Chondroblastoma (CB) is a rare, benign cartilage-producing tumor, typically affecting the epiphysis of long bones in skeletally immature individuals. There have been only limited case reports describing the cytomorphologic features of this tumor, and thus the cytopathologic diagnostic criteria are controversial. Herein, we report the cytologic findings of 10 CB cases, discuss the diagnostic criteria and critical differential diagnosis, along with a comprehensive review of the literature. METHODS: We performed a retrospective search of our cytopathology and surgical pathology databases for cases diagnosed as CB that had corresponding cytology specimens from four large medical institutions. All available cytopathology specimens were retrieved and reviewed. Clinicopathologic and radiologic data were recorded. RESULTS: Ten cases were retrieved from 8 patients aged 15-42 years (mean, 24 years), five of whom were males. Eight cases represented primary tumors while 2 cases were recurrences. Three cases occurred in the femur, two cases occurred in the humerus, while 1 case occurred in each of the glenoid, talus, and proximal phalanx of the 3rd toe. The cytologic diagnosis of CB was achieved in 7 cases. The neoplastic mononuclear cells were present in all cases and their cytologic features were similar. These cells displayed round to oval eccentric nuclei, evenly distributed chromatin, and inconspicuous nucleoli; few of which had nuclear indentations. Multinucleated giant cells were present in 9 cases (90%). Fragments of chondromyxoid matrix were present in 4 cases on cytologic preparations (40%). Cell blocks were available in 8 cases. Mononuclear and multinucleated giant cells were present in all adequate cell blocks and their cytologic features were identical to those seen in the smears. The chondroid matrix was present in only three of the adequate cell blocks (43%). CONCLUSION: We concluded that with the appropriate clinical and radiologic setting, the diagnosis of CB can be achieved on cytology if characteristic chondroblasts are present. The presence of chondromyxoid matrix is a helpful clue but is not necessary for the diagnosis. As in surgical pathology, cytologic evaluation of bone tumors should be interpreted in conjunction with clinical and radiologic findings.

Anti-histone H3.3K36M Antibody is a Highly Sensitive and Specific Immunohistochemistry Marker for the Diagnosis of Chondroblastoma. A Validation Based on Study 136 Cases Comprising Chondroblastoma and its Mimics from Single a Centre in India.

Introduction. Chondroblastoma has a wide range of differential diagnosis encompassing various benign and malignant entities. The closest differential diagnosis is giant cell tumor of the bone due to overlapping radiological and histomorphological features. Extensive aneurysmal bone cyst like changes and lack of adequately sampled chondroid matrix often masquerades the primary bone lesion and amplifies the diagnostic difficulty in small biopsies with limited tissue. Immunohistochemistry is helpful in such instances to resolve the diagnostic dilemma. Objectives. To analyze the immunohistochemical expression of anti-histone H3F3K36M antibody inchondroblastoma and validate its utility in differentiating chondroblastoma from its histological mimics. Material and methods. Immunohistochemistry was performed using anti-histone antibody H3.3K36M in 44 histologically diagnosed chondroblastoma and 92 other histological mimickers. All chondroblastoma and giant cell tumor of the bone included in the study were also tested for anti-histone H3.3 G34W antibody. Of the 33 giant cell tumors of bone with classic morphology and imaging findings, 24 H3.3 G34W positive and 9 negative tumors were included intentionally to rule out the possibility of chondroblastoma. The sensitivity, specificity, positive and negative predictive value of marker with regard to chondroblastoma was calculated. Results. Immunohistochemistry revealed unequivocal nuclear positivity for H3.3K36M in the mononuclear cells in all the 44 chondroblastoma tested, denoting a sensitivity of 100% cases. Allthesetumors tested simultaneously for anti-histone H3.3G34W were negative. None of the histological mimickers were positive H3.3K36M indicating a specificity of 100%. The positive and negative predictive value was 100%. Conclusion. H3.3K36M mutant antibody is highly sensitive and specific IHC marker and can be used as a valuable adjunct to distinguish chondroblastoma from its histological mimics especially on small biopsies.

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.

Management of Primary Aggressive Tumors of the Knee.

Primary bone sarcomas and aggressive benign bone tumors are relatively rare. It is essential to recognize features that are concerning for these aggressive tumors based on a patient's history, physical exam, and radiographs. Physicians and other health care providers should have a high suspicion for these tumors and promptly refer these patients to orthopaedic oncologists. A multidisciplinary, team-based approach is required to obtain an accurate diagnosis and provide comprehensive care. This review discussed the appropriate work-up, biopsy principles, relevant peri-operative medical management, and surgical treatment options for patients with aggressive primary bone tumors around the knee. Primary bone sarcomas (osteosarcoma and chondrosarcoma) and aggressive benign bone tumors (giant cell tumor, chondroblastoma, and chondromyxoid fibroma) that have a predilection to the distal femur and proximal tibia are the focus of this review.

Clinical and Imaging Features of Tumors in the Scapula.

BACKGROUND: The scapula is a small irregular-shaped flat bone, which may suffer from a variety of tumors or tumor-like lesions. As the imaging manifestations are complex and changeable, correct imaging diagnosis is difficult. INTRODUCTION: At present, there are few related radiology literatures, and it is necessary to fully analyze the imaging signs of different types of benign and malignant tumors in scapula to guide clinical treatment. This study was to investigate clinical and imaging presentations of tumors and tumor- like lesions in the scapula so as to increase the diagnostic accuracy of diseases in the scapula. METHODS: Patients with scapular tumors confirmed by pathology were enrolled. The imaging and clinical data were analyzed. RESULTS: Among 108 patients, benign tumors were in 53 (49.1%) cases, intermediate in seven (6.5%), and malignant in 48 (44.4%) involving 16 diseases. Osteochondroma was the first benign tumors in 45 cases accounting for 84.9% of all benign scapular tumors, followed by chondroma in four cases (7.5%). The intermediate tumors were mainly eosinophilic granuloma in four cases. Metastatic tumors were the commonest malignant tumor (27 cases or 56.2% of all malignant tumors), followed by chondrosarcoma (in 13 cases). Except for the one case of chondroblastoma in which the lesion involved the glenoid cavity, all the other cartilaginous tumors were located in the scapular body and processes. The type of lesions in the bony processes is the same as in the scapular body, the common lesions in the central area of the body were malignant tumors, and the commonest lesions in the glenoid area were metastasis. Common imaging features of malignant scapular tumors were ill-defined margins, cortical destruction and soft tissue involvement. The imaging features of chondrosarcoma lack specificity except for calcification. Benign lesions usually had a clear boundary and marginal sclerosis. CONCLUSION: A wide variety of benign and malignant tumors may occur in the scapula with mostly cartilaginous and metastatic tumors, and the location and distribution of lesions are similar in the scapula to those in the long bones.

A Case of Arthroscopic Treatment of Chondroblastoma-Induced Chondropathy Situated at the Posterior Talus.

Chondroblastoma located in the talus is a rare incidence, and due to the weightbearing duty of the talus, the results of local excision may not be favorable. While the volume of the tumor increases, more sophisticated techniques may be undertaken. Cell-free matrix application for extensive osteochondral defects is gaining popularity for its structural support when it is used with microfracture and autograft application. In this case report, we present a patient with 13 × 20 × 8mm-sized chondroblastoma located in the talus. After evaluation of the mass, we performed curettage, iliac crest autograft application, and augmentation with cell-free matrix. After uneventful clinical follow up, we present our patient's postoperative second year magnetic resonance imaging and functional status.

Tumors and pseudotumors of foot and ankle: Bone lesions.

Bone tumors and tumor-like lesions (pseudotumors) are not uncommonly encountered as asymptomatic findings on imaging, or as symptomatic lesions clinically. Radiographic imaging is the first diagnostic tool for their management strategy, since the symptoms are commonly non-specific, such as pain, swelling, and redness. Image findings must be analyzed with attention to the specific features such as lesion location, margination, zone of transition, mineralization, size and multifocality, soft tissue component and/or loco-regional extent. Cross-sectional imaging including CT and MRI serve as complementary methods, providing additional information with respect to the lesion characterization, mineralization, extent and involvement of the adjoining soft tissues. Clinical and/or key imaging features aid in limiting the differential diagnostic possibilities and serve as a guide in determining the benignity or malignancy of the tumor as well as to exclude pseudotumors. This article reviews the key imaging features of foot and ankle lesions. Benign bone lesions include simple and aneurysmal bone cysts, lipoma, hemangioma, chondroblastoma, enchondroma, osteoid osteoma, osteoblastoma, and giant cell tumor. Locally aggressive intermediate category lesion includes hemangioendothelioma. Malignant lesions include osteosarcoma, Ewing's sarcoma, chondrosarcoma. Pseudotumors such as fibrous dysplasia, hemophilic pseudotumor, gout and Madura foot are also discussed with illustrative case examples.

Cytopathology of chondromyxoid fibroma: a case series and review of the literature.

INTRODUCTION: Chondromyxoid fibroma is a rare bone tumor characterized by immature myxoid mesenchymal tissue showing early primitive cartilaginous differentiation. There have been limited case reports describing the cytologic features of chondromyxoid fibroma. Herein, we reported cytologic features of chondromyxoid fibroma on fine-needle aspiration (FNA). MATERIALS AND METHODS: We performed a retrospective search in our cytopathology and surgical pathology database for cases diagnosed as chondromyxoid fibroma that had corresponding cytology specimens from three medical institutions. All available cytopathology specimens were reviewed. RESULTS: Eight cases were retrieved from patients aged 16-77 years (mean, 51 years), and M:F ratio of 1.7:1. Seven tumors (88%) were primary, and most (62%) occurred in flat bones. Cytologic diagnoses were made in 6 cases with cytologic slides not available to review in 1 case. All cases showed metachromatic matrix in the background, while hyaline cartilage fragments were absent. All cases had two cell populations comprising oval to round cells and stellate to spindle cells. The spindle to stellate cells were more commonly embedded in matrix material. Moderate atypia (hyperchromasia and moderate anisonucleosis) was present in 4 cases (80%), while no mitotic figure was present in all cases. CONCLUSIONS: Our study highlights common cytologic features of chondromyxoid fibroma, including the presence of the spindle or stellate cells embedded in matrix material. Hyaline cartilage is uncommon and, if present, diagnostic considerations should include enchondroma or low-grade chondrosarcoma. A specific cytologic diagnosis primarily using FNA samples can be challenging but possible when evaluated in conjunction with clinical and radiologic data.

Calcaneal Bone Tumors.

Bone tumors of the foot are an uncommon finding. Most tumors are found incidentally on imaging and are benign. Care must be taken although due to the aggressive nature of malignant bone tumors that can occur in the calcaneus. Malignant lesions will more commonly present with symptoms of pain and swelling. Often misdiagnosed as soft tissue injuries, it is critical to be able to diagnose and treat these lesions early. Imaging plays an important role with plain films and advanced imaging. Surgical treatments can range from curettage with grafting to amputation for more aggressive lesions.

H3.3 K36M Mutation as a Clinical Diagnosis Method of Suspected Chondroblastoma Cases.

OBJECTIVE: Whether H3.3 K36M mutation (H3K36M) could be an approach if the diagnosis of chondroblastoma (CB) patients was indistinct and it was suspected to be unclear clinically. METHODS: We reviewed and compared our clinical experiences of CB cases and some suspected cases, which were not diagnosed distinctly, between 2013 to 2019. A total of 15 male and four female cases included in this study were seperated into two groups, CB group and suspected case (SC) group. The CB group included 13 men and 3 women, with an age range from 9 to 54 (mean age, 22 years old). The SC group included two men and one woman, with the age range from 13 to 25 (mean age, 19 years old). In both groups the patients had been followed-up until December 2019 and none of the patients had prior treatment history. We evaluated the clinical complaints, radiological features, and clinical-histological features of the cases and performed an immunohistochemical (IHC) study to detect whether the H3K36M expression of cases was different, consistent with a gene-mutation analysis. RESULTS: In both groups, the radiologic features of both groups appeared as round low-density shadow with a clear edge, pathologic features showed diffuse proliferation of neoplastic cells with multinuclear giant cells. The radiological tumor size of CB group and SC group showed little difference, which was about 29.0*21.6 mm. Clinical-immunohistochemical features of both groups showed chondroid matrix inside with naïve tumor cells, multinucleated giant cells, and ground substance cells. Most of them showed chondro-related antibody positive (12 cases) but some of them showed S-100 negative (four cases). The clear difference of both groups was the result of H3K36M IHC study and gene analysis. In our cases, the CB group showed diffuse H3K36M positive and the SC group showed negative. The gene mutation analysis revealed that H3K36M-positive CB patients had K36M mutation, which were not found in the SC group. Sanger sequencing showed an A > T substitution at codon 36 of histone H3F3B. No other types of histone H3 mutation was detected in the CB group. Particularly, one of the suspected cases showed a G34W mutation was confirmed to be a giant cell tumor of bone (GCTB). CONCLUSIONS: Our study showed H3K36M immunohistochemistry and gene mutation analysis were specific clinical diagnostic tools to distinguish suspected CB from other giant cell-rich or cartilage matrix-diffuse bone tumors. The clinical-radiological and histomorphological features of patients gave suggestions on whether the H3K36M IHC and gene analysis should be required.