Neoplastic and non-neoplastic lesions occur commonly in the bones of the knee. For certain tumours, it is the most frequent location, and it is also a common site for neoplasms and non-neoplastic tumour mimics that do not demonstrate a particular anatomic preference. Lesions may arise at the end of the bone (subarticular) or in the metaphysis and extend towards the joint. Tumours and tumour mimics occurring in subarticular locations or extending from the metaphysis are considered separately in this review. We have included lesions that we expect will be identifiable on routine knee MRI examinations.

Fibrocartilaginous mesenchymoma is a locally aggressive intraosseous lesion first described in 1984, which most commonly presents in the long bones of children and young adults. It is rare-less than 40 cases have been reported to date. The typical radiological features are those of an expansile lytic lesion with chondroid calcification, cortical destruction and frequent extraosseous extension, suggesting an aggressive benign or low-grade malignant tumour. On MRI the lesion returns low T1 and high T2 signal and usually shows intense contrast enhancement. Histologically the lesion is characterised by a spindle cell proliferation, areas of ossification and benign cartilage nodules resembling the epiphyseal plate, the latter considered the hallmark of this tumour. We present a case of fibrocartilaginous mesenchymoma in the rib of a 28-year-old female, a very uncommon location for this tumour. The case is also exceptional because of the age of the patient and its unusual imaging appearances: the lesion showed no evidence of chondral-type matrix mineralisation, displayed profound T2 hypointensity and only minimal enhancement following intravenous Gadolinium administration.

We report two bone-forming tumors driven by a newly recognized fusion. The first is a lesion in the distal radius of a 59-year-old female subject, which had been present for 10 years. Imaging showed an intramedullary tumor with an exophytic dorsal component and marked sclerosis, histologically best classified as low-grade osteosarcoma. The second was a destructive lesion in the left ulna of a 13-year-old female with a short history of elbow pain. Imaging showed a lytic lesion with subtle tumor ossification, histologically best classified as an atypical osteoblastoma-like tumor. A NIPBL::BEND2 fusion was found in both cases on whole genome sequencing. This fusion has been previously reported in three bone lesions, two of which were reported as phosphaturic mesenchymal tumors and the other exhibited features of a high-grade osteosarcoma. These newly reported cases were bone-forming, but histologically indolent, with no features of high-grade osteosarcoma, and did not demonstrate the typical features of a phosphaturic mesenchymal tumor nor evidence of tumor-induced osteomalacia. The World Health Organization has not established a specific name for tumors associated with a NIPBL::BEND2 fusion, and their biological potential cannot currently be predicted. These cases add to the expanding clinical and histological knowledge of this entity and illustrate that, in addition to the other rarely reported phenotypes, low-grade bone-forming tumors may also be caused by this exceptionally rare fusion.

Fusions involving the PLAG1 gene are associated with multiple cancers and benign tumors, including lipoblastoma and the more recently described pediatric fibromyxoid soft tissue tumor. We report two PLAG1-rearranged mesenchymal tumors arising in adults which, although largely similar histologically to the fibromyxoid tumors reported in infants, display limited adipocytic differentiation. In both cases, the novel fusion partner was DLEU2. Whole genome sequencing of one of the tumors also showed loss of 13p including the RB1 locus. Expression of PLAG1 was demonstrated by extensive immunoreactivity in both cases. We discuss the similarities of our cases to the previously described fibroblastic variants of lipoblastomas and the recently reported cases of PLAG1-rearranged fibromyxoid soft tissue tumors, highlighting the overlapping morphological and molecular features. We consider that there is growing evidence that these histological entities are related to conventional lipoblastoma and represent tumors of adipocytic lineage exhibiting different stages of cellular maturation.

Recognition of unusual histological features can augment and hasten a diagnosis but also stimulate ideas about physiological and pathological cellular interactions. Osteoclasts resorb mineralised tissue and therefore can be found at sites of heterotopic bone formation. However, multinucleated giant cells with morphological features of osteoclasts, so called ‘osteoclast-like cells’ can also be encountered in a variety of soft tissue tumours unrelated to ossification and calcification. Prompted by the presence of osteoclast-like cells in undifferentiated pleomorphic sarcoma while undertaking our Artificial Intelligence project for classifying sarcoma, we reviewed the English literature for these cells in soft tissue tumours and we found that this was poorly documented, and much was published before the release of the WHO essential diagnostic criteria in 2020. There were numerous single case reports and small series of a broad range of soft tissue tumours with osteoclast-like cells but only a limited number of diagnoses in which these cells were reported recurrently. We provide a comprehensive update of osteoclast-like cells and mineralisation in soft tissue tumours from the literature. We also present real-world incidence of osteoclast-like cells from selected tumour types in our Whole Slide Image (WSI) library of soft tissue tumours. Assessment of WSI from 1100 different patients showed that osteoclast-like cells were relatively common and under-recognised in nodular fasciitis (18.5 of 200), angiomatoid fibrous histiocytoma (17.5% of 40), undifferentiated pleomorphic sarcoma (15% of 261) and epithelioid sarcoma (9% of 68) while they were never encountered in myxofibrosarcoma (0/250) and clear cell sarcoma of soft tissue (0/80). Awareness of this phenomenon not only helps shape the differential diagnosis but also can be used to stimulate pathobiological questions and to enhance the performance of AI models for classifying disease.

The aim of this research was to investigate the pathogenesis of the bone cancer chordoma and the role of the germline rs2305089 SNP in TBXT. Using medical imaging and genotyping studies, we observed that benign notochordal cell tumours (BNCTs) were associated with chordomas and with the variant rs2305089 A-allele with enrichment of the AA genotype compared to controls. We engineered in vitro mesoderm models, representing notochord, which showed higher expression of TBXT and activation of its regulatory network in the presence of the variant A allele. Heterozygotes (GA) displayed enrichment of Wnt/β-catenin and epithelial mesenchymal transition pathways, faster cell migratory capacity, and altered expression of endoplasmic reticulum and intracellular transport mediators. WT lines (GG) were enriched for metabolic pathways and MTORC1 signalling, suggesting that rs2305089 genotype regulates notochord vacuoles during notochord regression. By leveraging patient-derived data and functional studies, we show that the variant rs2305089 A-allele predisposes to BNCTs and ultimately to chordomas. © 2025 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Achilles tendinopathy is a disabling condition that affects more than 50% of runners. Pre-clinical studies in a large animal model of naturally-occurring tendinopathy similar to human Achilles tendinopathy has shown benefits of autologous bone marrow-derived mesenchymal stem cell (MSC) implantation. However, MSCs are advanced therapies medicinal products (ATMPs), with strict regulatory requirements. Guided by the regulator we carried out a first in man study to assess the safety and efficacy of autologous MSC injection in human patients with non-insertional Achilles tendinopathy. Ten patients, mean age 47 with mid-portion Achilles tendon pain and swelling for more than 6 months, underwent autologous cultured cell injections (median 12.2 × 106, range 5–19 × 106 cells) into their Achilles tendon. At 24 weeks follow-up, no serious adverse reactions or important medical events were observed. MOXFQ, EQ-5D-5L, and VISA-A scores improved clinically at 12 and 24 weeks. VAS pain improved increasingly at 6, 12 and 24 weeks. MOXFQ Pain and VISA-A Scores improved > 12 points from baseline to 24 weeks in 8 patients. Maximum anteroposterior tendon thickness as measured by greyscale US decreased by mean 0.8 mm at 24 weeks. This phase IIa study demonstrated the safety of autologous MSC injection for non-insertional Achilles tendinopathy and provides proof-of-concept of the technique in patients, all of whom had previously failed conservative treatments for chronic disease and leads the way for a larger randomised controlled trial.

is diffuse enlargement of the right 3rd rib with expansion of the medullary canal and cortical thickening.There is circumferential surrounding lipomatous tissue, showing

The revised European Society of Musculoskeletal Radiology (ESSR) consensus guidelines on soft tissue tumor imaging represent an update of 2015 after technical advancements, further insights into specific entities, and revised World Health Organization (2020) and AJCC (2017) classifications. This second of three papers covers algorithms once histology is confirmed: (1) standardized whole-body staging, (2) special algorithms for non-malignant entities, and (3) multiplicity, genetic tumor syndromes, and pitfalls. A validated Delphi method based on peer-reviewed literature was used to derive consensus among a panel of 46 specialized musculoskeletal radiologists from 12 European countries. Statements that had undergone interdisciplinary revision were scored online by the level of agreement (0 to 10) during two iterative rounds, that could result in ‘group consensus’, ‘group agreement’, or ‘lack of agreement’. The three sections contain 24 statements with comments. Group consensus was reached in 95.8

An update of the first European Society of Musculoskeletal Radiology (ESSR) consensus on soft tissue tumor imaging in 2015 became necessary due to technical advancements, further insights into specific entities, and the revised WHO classification (2020) and AJCC staging system (2017). The third part of the revised guidelines covers algorithms and techniques beyond initial imaging: (1) Imaging after neoadjuvant therapy in soft tissue sarcoma, (2) sarcoma surveillance, and (3) special aspects, including surveillance of non-malignant entities and the role of interventional radiology. A validated Delphi method based on peer-reviewed literature was used to derive consensus among a panel of 46 specialized musculoskeletal radiologists from 12 European countries. Statements that had undergone interdisciplinary revision were scored online by level of agreement (0 to 10) during two iterative rounds that could result in either ‘group consensus,’ ‘group agreement,’ or ‘lack of agreement.’ The three sections contain 47 statements with comments. Group consensus was reached in 91.5

Paget disease of bone is a metabolic disorder with a strong genetic component, characterised by pronounced disorganised bone remodelling. Complications of this disease include an increased risk of developing bone neoplasms. Here, we describe the case of a 60-year-old Italian patient with Paget disease of bone, presenting with an osteoclast-rich tumour. Our analysis of this entity, based on the clinical, morphological and genetic data (whole exome sequencing), suggests that osteoclast-rich lesions in Paget disease of bone are genetically distinct from classical giant cell tumour of bone. We discuss the importance of differentiating these osteoclast-rich lesions.

Purpose or Learning Objective: To review trunk and extremity myxofibrosarcoma with emphasis on magnetic resonance imaging (MRI).

Extra-skeletal osteosarcoma is a rare malignant soft tissue sarcoma which can cause a diagnostic challenge due to its non-specific presentation and soft tissue mineralisation, thus potentially mimicking conditions such as myositis ossificans. This review will outline the demographics, clinical presentation, key imaging features, differential diagnosis, management and outcomes of extra-skeletal osteosarcoma and serve as a reference to radiologists and other clinicians involved in the care of patients with soft tissue tumours and tumour-like lesions.

OBJECTIVE:To determine the differential diagnosis of bone lesions causing hip pain in children and the association between radiographic features of aggression and MRI appearances with final diagnosis.METHODS:Retrospective review of children with hip pain referred to a specialist musculoskeletal oncology service between September 2018 and December 2020. Patient demographics, lesion location, the radiographic and MRI features, and the final diagnosis, which was made either by image-guided biopsy, surgical curettage or based on typical imaging features were recorded. Statistical analysis examined the association between the Lodwick-Madewell score (determined from available radiographs) and MRI findings with final diagnosis.RESULTS:Fifty-nine patients were included, 40 males and 19 females with mean age 10.9 years, (range 3-16 years). Final diagnoses were based on histology in 24 (40.7%) cases and imaging in 35 (59.3%) cases. Eighteen lesions (30.5%) were classed as non-neoplastic, 31 (52.5%) as benign and 10 (16.9%) as malignant, of which four were primary bone sarcomas. There was a significant association between the Lodwick-Madewell score and final diagnosis (p < 0.001). On MRI, bone marrow oedema, presence of a focal lesion, bone expansion and the presence of an extraosseous mass were all significantly associated with final diagnostic classification.CONCLUSION:The differential diagnosis of hip pain in children presenting to a bone tumour service is wide. Most cases are due to benign or non-neoplastic conditions, with only 10 out of 59 children having a malignant lesion. Radiography complemented by MRI plays a major role in differentiating non-neoplastic, benign neoplastic and malignant lesions and in determining the requirement for needle biopsy.ADVANCES IN KNOWLEDGE:This is the first study to consider how imaging features relate to diagnosis in suspected paediatric hip tumours. Use of this information can help in determining which cases should undergo needle biopsy.

Objective: To determine the additional benefit of MRI for children with flatfoot deformity assessed with weight bearing radiographs in a specialist paediatric orthopaedic unit. Methods and materials: Patient cohort was obtained by searching the Radiology Information System for children referred for investigation of flatfoot. All patients with flatfoot on weight-bearing radiographs who had undergone MRI were included. Radiographs were classified by a consultant musculoskeletal radiologist as showing no underlying abnormality, talo-calcaneal coalition, calcaneonavicular coalition, accessory navicular or other abnormality. MRI studies were classified similarly by a different consultant musculoskeletal radiologist blinded to the radiographic findings. Results: 33 males and 24 females were included (mean age 12.5 years; range 3-18 years). 24 had bilateral abnormality, so 81 feet were assessed. Radiographs showed no specific abnormality (n = 51), talocalcaneal coalition (n = 6), calcaneonavicular coalition (n = 3), os naviculare (n = 12) or other abnormality (n = 9). MRI showed no specific abnormality (n = 40), talocalcaneal coalition (n = 10), calcaneonavicular coalition (n = 5), os naviculare (n = 12) or other abnormality (n = 14). Assuming MRI as the diagnostic gold-standard, additional relevant diagnostic information was identified in 19 (23.5%) cases, while in the 51 cases for which radiographs provided no specific diagnosis MRI confirmed no underlying abnormality in 31 (60.8%). Conclusion: MRI is a valuable adjunct to weight bearing radiography for investigating paediatric flatfoot deformity. Advances in knowledge: MRI is of value in the assessment of paediatric flatfoot, additional diagnostic information to radiography being identified in 23.5% cases, while in 60.8% of cases for which radiographs provided no specific diagnosis MRI confirmed no underlying abnormality.

Oncohistones represent compelling evidence for a causative role of epigenetic perturbations in cancer. Giant cell tumours of bone (GCTs) are characterised by a mutated histone H3.3 as the sole genetic driver present in bone-forming osteoprogenitor cells but absent from abnormally large bone-resorbing osteoclasts which represent the hallmark of these neoplasms. While these striking features imply a pathogenic interaction between mesenchymal and myelomonocytic lineages during GCT development, the underlying mechanisms remain unknown. We show that the changes in the transcriptome and epigenome in the mesenchymal cells caused by the H3.3-G34W mutation contribute to increase osteoclast recruitment in part via reduced expression of the TGFβ-like soluble factor, SCUBE3. Transcriptional changes in SCUBE3 are associated with altered histone marks and H3.3 G34W enrichment at its enhancer regions. In turn, osteoclasts secrete unregulated amounts of SEMA4D which enhances proliferation of mutated osteoprogenitors arresting their maturation. These findings provide a mechanism by which GCTs undergo differentiation in response to denosumab, a drug that depletes the tumour of osteoclasts. In contrast, hTERT alterations, commonly found in malignant GCT, result in the histone-mutated neoplastic cells being independent of osteoclasts for their proliferation, predicting unresponsiveness to denosumab. We provide a mechanism for the initiation of GCT, the basis of which is dysfunctional cross-talk between bone-forming and bone-resorbing cells. The findings highlight the role of tumour/microenvironment bidirectional interactions in tumorigenesis and how this is exploited in the treatment of GCT.

This review provides an overview of the spectrum of tumors showing notochordal differentiation. This spectrum encompasses benign entities that are mostly discovered incidentally on imaging, reported as benign notochordal cell tumor, usually not requiring surgical intervention; slowly growing and histologically low-grade tumors referred to as conventional chordoma but associated with a significant metastatic potential and mortality; and more aggressive disease represented by histologically higher-grade tumors including dedifferentiated chordoma, a high-grade biphasic tumor characterized by a conventional chordoma juxtaposed to a high-grade sarcoma, usually with a spindle or pleomorphic cell morphology, and associated with a poor prognosis and poorly differentiated chordoma.