Expanding the spectrum of tyrosine kinase fusions in calcified chondroid mesenchymal neoplasms: Identification of a novel PDGFRA::USP8 gene fusion.

Calcified chondroid mesenchymal neoplasms represent a distinct, and recently recognized, spectrum of tumors. To date most cases have been reported to be characterized by FN1 gene fusions involving multiple potential tyrosine kinase partners. Following incidental identification of a tumor morphologically corresponding to calcified chondroid mesenchymal neoplasm, but with a PDGFRA::USP8 gene fusion, we undertook a retrospective review to identify and characterize additional such cases. A total of four tumors were identified. Each was multilobulated and composed of polygonal-epithelioid-stellate cells with a background of chondroid matrix containing distinctive patterns of calcification. Targeted RNA sequencing revealed an identical PDGFRA (exon 22)::USP8 (exon 5) gene fusion in each case. Subsequent immunohistochemical staining confirmed the presence of PDGFRα overexpression. In summary, we report a series of four tumors within the morphologic spectrum of calcified chondroid mesenchymal neoplasms. In contrast to prior reports, these tumors harbored a novel PDGFRA::USP8 gene fusion, rather than FN1 rearrangement. Our findings expand the molecular diversity of these neoplasms, and suggest they are united through activation of protein kinases.

A retrospective external validation study of the Birmingham Atypical Cartilage Tumour Imaging Protocol (BACTIP) for the management of solitary central cartilage tumours of the proximal humerus and around the knee.

OBJECTIVES: This study aimed to externally validate the Birmingham Atypical Cartilage Tumour Imaging Protocol (BACTIP) recommendations for differentiation/follow-up of central cartilage tumours (CCTs) of the proximal humerus, distal femur, and proximal tibia and to propose BACTIP adaptations if the results provide new insights. METHODS: MRIs of 123 patients (45 ± 11 years, 37 men) with an untreated CCT with MRI follow-up (n = 62) or histopathological confirmation (n = 61) were retrospectively/consecutively included and categorised following the BACTIP (2003-2020 / Ghent University Hospital/Belgium). Tumour length and endosteal scalloping differences between enchondroma, atypical cartilaginous tumour (ACT), and high-grade chondrosarcoma (CS II/III/dedifferentiated) were evaluated. ROC-curve analysis for differentiating benign from malignant CCTs and for evaluating the BACTIP was performed. RESULTS: For lesion length and endosteal scalloping, ROC-AUCs were poor and fair-excellent, respectively, for differentiating different CCT groups (0.59-0.69 versus 0.73-0.91). The diagnostic performance of endosteal scalloping and the BACTIP was higher than that of lesion length. A 1° endosteal scalloping cut-off differentiated enchondroma from ACT + high-grade chondrosarcoma with a sensitivity of 90%, reducing the potential diagnostic delay. However, the specificity was 29%, inducing overmedicalisation (excessive follow-up). ROC-AUC of the BACTIP was poor for differentiating enchondroma from ACT (ROC-AUC = 0.69; 95%CI = 0.51-0.87; p = 0.041) and fair-good for differentiation between other CCT groups (ROC-AUC = 0.72-0.81). BACTIP recommendations were incorrect/unsafe in five ACTs and one CSII, potentially inducing diagnostic delay. Eleven enchondromas received unnecessary referrals/follow-up. CONCLUSION: Although promising as a useful tool for management/follow-up of CCTs of the proximal humerus, distal femur, and proximal tibia, five ACTs and one chondrosarcoma grade II were discharged, potentially inducing diagnostic delay, which could be reduced by adapting BACTIP cut-off values. CLINICAL RELEVANCE STATEMENT: Mostly, Birmingham Atypical Cartilage Tumour Imaging Protocol (BACTIP) assesses central cartilage tumours of the proximal humerus and the knee correctly. Both when using the BACTIP and when adapting cut-offs, caution should be taken for the trade-off between underdiagnosis/potential diagnostic delay in chondrosarcomas and overmedicalisation in enchondromas. KEY POINTS: • This retrospective external validation confirms the Birmingham Atypical Cartilage Tumour Imaging Protocol as a useful tool for initial assessment and follow-up recommendation of central cartilage tumours in the proximal humerus and around the knee in the majority of cases. • Using only the Birmingham Atypical Cartilage Tumour Imaging Protocol, both atypical cartilaginous tumours and high-grade chondrosarcomas (grade II, grade III, and dedifferentiated chondrosarcomas) can be misdiagnosed, excluding them from specialist referral and further follow-up, thus creating a potential risk of delayed diagnosis and worse prognosis. • Adapted cut-offs to maximise detection of atypical cartilaginous tumours and high-grade chondrosarcomas, minimise underdiagnosis and reduce potential diagnostic delay in malignant tumours but increase unnecessary referral and follow-up of benign tumours.

Periosteal chondrosarcoma: an unusual juxtacortical sarcoma.

Periosteal chondrosarcoma is a rare tumor. It can be difficult to diagnose radiographically and pathologically and can be confused with periosteal osteosarcoma; however, the treatment of these two lesions is quite different. Increased awareness of imaging features of this lesion, particularly those that can help differentiate it from other surface-based tumors, can help one recognize this entity. We report the case of a periosteal chondrosarcoma in a young woman, highlighting the diagnostic imaging features of this disease, and her treatment with a joint-sparing geometric resection of the distal femur, using patient-specific 3D-printed cutting guides and matched allograft reconstruction.

Chondroma Arising from the Temporomandibular Joint: A Case Report.

Periarticular chondromas are common in the humerus and femur but rarely occur in the temporomandibular joint. We report a case of a chondroma in the anterior part of the ear. One year prior to his visit, a 53-year-old man became aware of swelling in the right cheek region which gradually increased in size. In the anterior part of the right ear, there was a palpable 25 mm tumor, elastic and hard, with poor mobility and without tenderness. A contrast-enhanced computed tomography CT showed a mass lesion with diffuse calcification or ossification in the upper pole of the parotid gland and areas of poor contrast within. A magnetic resonance imaging showed a low-signal mass lesion at the parotid gland with some high signals in both T1 and T2. Fine-needle aspiration cytology did not lead to diagnosis. Using a nerve monitoring system, the tumor was resected with normal tissue of the upper pole of the parotid gland in the same way as for a benign parotid tumor. Distinguishing between pleomorphic adenoma, including diffuse microcalcification of the parotid gland and cartilaginous tumors of the temporomandibular joint, may be sometimes difficult. In such cases, surgical resection may be a beneficial treatment option.

[Soft tissue tumours with FN1 (Fibronectin 1) fusion gene]. / Tumeurs des tissus mous avec fusion du gène FN1 (Fibronectine 1).

Translocations involving FN1 gene have been described in several tumours, which share the presence of a cartilaginous matrix with or without calcifications and a good prognosis. They encompass: soft tissue chondroma, synovial chondromatosis, calcifying aponeurotic fibroma, phosphaturic mesenchymal tumour and a new spectrum of tumours: "the calcified chondroid mesenchymal neoplasms". We review all the clinical, histopathological and molecular data of these tumours and discuss the differential diagnoses.

"Slipped capital femoral epiphysis in a 25-year-old hypogonadic man with a large cranial chondroma: causality or coincidence? ".

BACKGROUND: Slipped capital femoral epiphysis (SCFE) is a hip disorder frequently occurring in adolescence. In adults it is rare and so far very few cases have been documented. CASE PRESENTATION: This report presents a 25-year-old patient diagnosed with an anterior fossa giant chondroma, hypogonadotropic hypogonadism, and SCFE. The patient underwent surgical and hormonal therapy. His symptoms revealed, and he became a father. CONCLUSIONS: Every patient diagnosed with SCFE in adulthood should undergo endocrinological assessment based on physical examination and laboratory tests.

Effects of Interobserver Variability on 2D and 3D CT- and MRI-Based Texture Feature Reproducibility of Cartilaginous Bone Tumors.

This study aims to investigate the influence of interobserver manual segmentation variability on the reproducibility of 2D and 3D unenhanced computed tomography (CT)- and magnetic resonance imaging (MRI)-based texture analysis. Thirty patients with cartilaginous bone tumors (10 enchondromas, 10 atypical cartilaginous tumors, 10 chondrosarcomas) were retrospectively included. Three radiologists independently performed manual contour-focused segmentation on unenhanced CT and T1-weighted and T2-weighted MRI by drawing both a 2D region of interest (ROI) on the slice showing the largest tumor area and a 3D ROI including the whole tumor volume. Additionally, a marginal erosion was applied to both 2D and 3D segmentations to evaluate the influence of segmentation margins. A total of 783 and 1132 features were extracted from original and filtered 2D and 3D images, respectively. Intraclass correlation coefficient ≥ 0.75 defined feature stability. In 2D vs. 3D contour-focused segmentation, the rates of stable features were 74.71% vs. 86.57% (p < 0.001), 77.14% vs. 80.04% (p = 0.142), and 95.66% vs. 94.97% (p = 0.554) for CT and T1-weighted and T2-weighted images, respectively. Margin shrinkage did not improve 2D (p = 0.343) and performed worse than 3D (p < 0.001) contour-focused segmentation in terms of feature stability. In 2D vs. 3D contour-focused segmentation, matching stable features derived from CT and MRI were 65.8% vs. 68.7% (p = 0.191), and those derived from T1-weighted and T2-weighted images were 76.0% vs. 78.2% (p = 0.285). 2D and 3D radiomic features of cartilaginous bone tumors extracted from unenhanced CT and MRI are reproducible, although some degree of interobserver segmentation variability highlights the need for reliability analysis in future studies.

[CT and Magnetic Resonance Imaging Findings of the Intracranial Extra-cerebral Chondroma:A Case Report].

Intracranial intradural chondroma is a rare disorder,the imaging findings of which have been rarely reported.The current study reported a case of intracranial extra-cerebral chondroma and described the detailed CT and magnetic resonance imaging findings,which would provide valuable imaging evidence for the diagnosis of intracranial extra-cerebral chondroma.

Solitary enchondromas-diagnosis and surveillance : Danish guidelines.

Enchondromas (EC) are frequent incidental findings on magnetic resonance imaging (MRI) performed for the diagnosis of joint pathology, especially observed on MRI examinations of the knee and shoulder. Enchondroma has potential for malignant transformation to chondrosarcoma (CS), and it may be difficult to distinguish EC from low-malignant CS on the basis of imaging or histopathology studies. Therefore, EC is mostly followed up to monitor any growth and/or changes indicating aggressive tumor.There is no consensual evidence on when and how to follow up patients with EC with regard to potential malignant transformation. Therefore, the Danish Multidisciplinary Cancer Groups initiated and supported the elaboration of Danish guidelines in 2020 based on a literature review. The guidelines are presented here, in addition to a summary of the background literature.

[Cartilage tumors: morphology, genetics, and current aspects of target therapy]. / Knorpeltumoren: Morphologie, Genetik und Basisaspekte der Targettherapie.

Cartilage tumors are a heterogeneous group of mesenchymal tumors whose common characteristic is the formation of a chondroblastic differentiated groundsubstance by the tumor cells. The basic features of their histological classification were already developed in the 1940s and supplemented by further entities in the following decades. Only in the past 10-15 years have fundamental new insights been gained through molecular genetic analysis. So, osteochondromas are characterized by alterations in the EXT1 and EXT2 genes. The description of mutations of isocitrate dehydrogenase 1 and 2 (IDH 1 and 2) in chondromas and chondrosarcomas is particularly important. The mesenchymal chondrosarcoma is characterized by a fusion of the HEY1-NCOA2 genes. The molecular genetic alterations characteristic for the individual tumor entities are first of all an essential supplement for the differential diagnosis of radiologically and histologically difficult cases. They also provide the basis for the establishment of molecular target therapies for malignant chondrogenic tumors. This applies in particular to conventional chondrosarcoma, for which all approaches to chemo- and radiotherapy have proven to be ineffective. However, the use of target therapies is still in its beginnings.

Loss of succinate dehydrogenase B immunohistochemical expression distinguishes pulmonary chondromas from hamartomas.

AIMS: Pulmonary chondromas, which are rare cartilaginous neoplasms that often arise in the setting of Carney triad, are morphologically similar to pulmonary hamartomas, which are much more common. There is evidence that succinate dehydrogenase (SDH) deficiency drives neoplasia in patients with Carney triad, and SDHB immunohistochemistry can be used as a surrogate marker to detect SDH deficiency. The aim of this study was to investigate the utility of SDHB immunohistochemistry in distinguishing pulmonary chondromas from hamartomas. METHODS AND RESULTS: Immunohistochemistry for SDHB (clone 21A11AE7) was performed on histological sections from six cases of pulmonary chondroma and 33 cases of pulmonary hamartoma. SDHB expression was retained in all 33 pulmonary hamartomas, and lost in the majority of evaluable chondromas (five of six). Of the five patients with chondromas showing SDHB loss, four had definitive Carney triad. Most patients with pulmonary hamartomas were older males with small solitary masses, whereas chondromas often presented as multiple masses in young females. CONCLUSION: Loss of SDHB immunohistochemical expression can be useful for differentiating pulmonary chondromas from hamartomas, and potentially identifying patients with Carney triad.

Chondroma of the falx cerebri: A case report and review of literature.

Chondroma is a benign cartilage-forming tumor which usually occurs in small bones of extremities but occasionally occurs in the brain. Usually, intracranial chondromas originate from skull base; however, chondroma of the falx cerebri is a very rare condition. We here report a rare case of falcine chondroma in a 19-year-old man who had normal physical examination without signs of any syndromic disorder. The neuroimaging findings were inconclusive, and the diagnosis was based on histopathological examination. The purpose of this paper is to raise attention about intracranial chondromas and suggest that chondroma must be ruled out in any patient presenting with masses arising from the falx.

Benign bone tumours of tibial tuberosity clinically mimicking Osgood-Schlatter disease: a case series.

INTRODUCTION: Osgood-Schlatter disease (OSD) is a traction apophysitis of the tibial tubercle and a common cause of anterior knee pain in growing adolescents. A variety of benign neoplasms can also cause bony prominence over the tibial tubercle in adolescents that might clinically imitate OSD. Therefore, the differential diagnosis of tumours mimicking OSD is critical and considered the primary goal of this study. METHODS: Eleven patients who were referred to our orthopaedic oncology department with clinical suspicions of OSD and obscure radiographic presentation were identified. The final diagnosis was OSD in three cases. The demographic, clinical, and radiologic characteristics of the remaining eight patients in whom a tumour mimicked OSD were evaluated. The diagnosis was confirmed by pathologic examination. RESULTS: The final diagnosis was periosteal chondroma in four cases, osteochondroma in three cases, and dysplasia epiphysealis hemimelica (DEH) in one case. The average age of the patients was 10.5 ± 3.1 years. In the majority of patients (62.5%), the lesion was painless. The mean size of the bump was 6.5 ± 1.2 cm2. In patients with a painful knee, the pain was constant and activity-independent. At history taking, the pain and bump size were progressive. CONCLUSION: Lack of pain, progressive pain and bump, activity-independent pain, a bump size larger than 5 cm2 at presentation, and age fewer than ten years could be considered in favour of tumours and against OSD.

Primary chondroma of posterior mediastinum with Horner's syndrome: a case report.

BACKGROUND: Chondroma is a slowly growing, benign cartilaginous tumor which predominantly occurs in long bones of the hands and feet. Primary mediastinal chondroma is rare, especially with Horner's syndrome. CASE PRESENTATION: We reported the case of a 31-year-old woman with a posterior mediastinum mass associated with Horner's syndrome. After complete dissection of the mass, a pathological diagnosis of the primary mediastinal chondroma was rendered. The patient has shown no local recurrence or distal disease in a 3.5-year follow-up period. CONCLUSIONS: The preoperative diagnosis of chondroma should combine various examinations for comprehensive evaluation. Complete surgical resection should be the first choice of the treatment due to the risk of malignancy.

Periosteal chondroma of the cuboid with secondary aneurysmal bone cyst in a setting of secondary hyperparathyroidism.

We report the case of a 35-year-old woman with painful, nontender mass at the right lateral hindfoot. Computed tomography (CT) and magnetic resonance imaging (MRI) indicated the suspect of a chondroid tumour in the cuboid. The tumour was resected en bloc and histology revealed the presence of a periosteal (juxtacortical) chondroma with secondary aneurysmal bone cyst. Secondary hyperparathyroidism was detected in laboratory tests and put into context with the histopathologic findings. In conclusion, a rare case of periosteal chondroma of the cuboid with secondary aneurysmal bone cyst in a setting of secondary hyperparathyroidism due to vitamin D deficiency is presented. LEVEL OF CLINICAL EVIDENCE: 4.

Large enchondroma of the thoracic spine: a rare case report and review of the literature.

BACKGROUND: Enchondroma, a subtype of chondroma, originates from the medullary cavity of the bone and produces an expansile growth pattern. Enchondroma located in the spine is rare and a few cases of large thoracic enchondroma have been reported. The authors document a rare case of large enchondroma in the thoracic spine of a 49-year-old woman, and discuss its clinical, radiological and histopathological characteristics. CASE PRESENTATION: The patient presented with rapidly progressive and severe pain on her upper back. Magnetic resonance imaging revealed an expansile lesion at the posterior elements of T3 that was hypointense on T1-weighted images and mixed iso- to hyperintense on T2-weighted images. Administration of gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) resulted in heterogeneous enhancement. During surgery, a large tumor of 4.2cm × 4.7cm × 2.1cm was resected along with the lamina and spinous process. Histological examination revealed that the tumor consisted of mature hyaline cartilage with typical chondrocytes, indicating that it was an enchondroma. CONCLUSIONS: Despite its benign-growing nature, enchondroma should be examined closely for signs of enchondromatosis and enchondrosarcoma. Complete surgical resection is the treatment of choice for immediate relief of symptoms and avoidance of recurrence.

Trigger Finger Caused by Extraskeletal Chondroma.

Chondroma is a relatively rare, but well-reported benign neoplasm. This lesion normally occurs attached to bone; however, they may be rarely found without association to bone and embedded in soft tissue. The authors describe the case of a 76-year-old man in whom flexor tendon triggering was associated with an extraskeletal chondroma between the annular ligament and the flexor tendon.

[A clinical observation of an extensive chondroma of oro- and laryngopharynx]. / Klinicheskoe nabliudenie obshirnoi khondromy roto- i gortanoglotki.

This article was designed to report a rare case of oropharyngeal chondroma in a 31 year-old male patient. Computed tomography revealed an encapsulated cystic-solid tissue mass having the clear-cut contours with multiple diffuse foci of calcification in the tissue thickness. The neoplasm was morphologically characterized as a chondroma. The tumour was removed with the use of the modified Lauers-Balon procedure with the dissection of the lower jaw.

Radiologic follow-up of untreated enchondroma and atypical cartilaginous tumors in the long bones.

BACKGROUND AND OBJECTIVES: Both enchondroma and atypical cartilaginous tumors (ACT) are not considered malignant, so inactive and asymptomatic tumors might not need surgery. To the best of our knowledge, this is the first study that has been done to evaluate the natural course of conservative-treated enchondroma and ACT in the long bones. METHODS: For this retrospective study, we analyzed the results of patients in whom we refrained from surgery and only regularly performed radiological follow-up of the tumor. Minimal follow-up after initial diagnosis was 24 months. RESULTS: Forty-nine patients were included in this study. Eight out of forty-nine cases received surgical treatment during follow-up of the tumor. The reasons for this surgery were radiologic growth of the tumor in two cases, pain in one case, patient request in three cases, another indication for surgery in the same limb in two cases. CONCLUSION: In this small series of conservatively treated enchondroma and ACT, only 6% of the patients had a medical indication for surgery. This study shows that indication for surgery should be discussed more thoroughly. Based on our results, we would recommend annual radiologic follow-up for asymptomatic enchondroma or ACT in the long bones, irrespective of tumor size. J. Surg. Oncol. 2016;114:987-991. © 2016 Wiley Periodicals, Inc.