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Giant cell lesions of bone share similar clinical, radiological, and histological features. The most challenging differential diagnosis is between giant cell tumor (GCT) and brown tumor (BT) secondary to hyperparathyroidism. Differential diagnosis is based on determining serum calcium concentration and other markers of calcium metabolism. The authors present the unusual case of a 37-year-old Caucasian woman affected by a GCT of the proximal left tibia and concomitant asymptomatic primary hyperparathyroidism (PHPT) due to a parathyroid adenoma. The presence of two concurrent diseases complicated diagnosis and relative treatment. The patient was first treated for the adenoma, then after 9 months, she underwent curettage of tibial GCT. Denosumab treatment was administered for 12 months to control a relapse occurring at 15 months post-curettage. At 32-month follow-up from primary tibial surgery, the patient was free from tumor disease. To our knowledge, this is the first case in the literature reporting the concomitant presence of asymptomatic PHPT and GCT. The possibility of concomitant finding these two diseases has to be considered during the decision-making process.

Background:Limited information is available on the applicative value of liquid biopsy (LB) in rare tumors, including Ewing’s sarcoma (ES). The accepted precision diagnostics standards would greatly benefit from a non-invasive LB test monitoring pathognomonic gene rearrangements in the bloodstream.Methods:Tissue and blood samples were collected from six and four ES patients, respectively. Plasma was cleared by two successive rounds of centrifugation and stored frozen until RNA extraction by the QIAmp CNA kit. RNA was retro-transcribed and subjected to real-time quantitative polymerase chain reaction (RT-qPCR) and digital polymerase chain reaction (dPCR). Reactions were set up using two custom primer sets identifying types 1 and 2 EWS-FLI1 fusion transcripts.Results:The two prevalent types of EWS-FLI1 rearrangements could be identified using only two sets of polymerase chain reaction primers, regardless of patient-specific EWS-FLI1 DNA breakpoints. RT-qPCR and dPCR discriminated the two variants in five tumor tissue RNAs and in four circulating tumor RNAs (ctRNAs). Of note, EWS-FLI1 molecular diagnosis was possible using blood samples even when tumor tissue was not available. ctRNA levels correlated (p < 0.05) with volume-based positron emission tomography (PET) parameters (metabolic tumor volume and total lesion glycolysis), and allowed the fine tracking of disease course after surgery, during adjuvant as well as neoadjuvant chemotherapy, and at follow up in one patient.Conclusions:To our knowledge, this is one of the few single-marker LB assays in solid tumors specifically designed to detect rearranged RNAs in blood, and the first study describing EWS circulating tumor RNAs in ES patients. Altogether, our results support the idea that LB may have a considerable impact on ES patient monitoring and management.

Although the medical treatments of sarcoma have evolved in the last years, a significant portion of patients develops recurrence after therapies suggesting the need to identify novel targets to improve the treatments. By the use of patient-derived and established cell lines from liposarcoma, as well as specimens from patient biopsies, we found that HMGA1 is involved in the progression of dedifferentiated and myxoid liposarcoma. The immunohistochemical and RT-PCR analyses of 68 liposarcoma specimens revealed a significant high expression of HMGA1, at the protein and RNA levels, both in myxoid and dedifferentiated liposarcoma subtypes compared with differentiated ones. Loss- and gain-of-function experiments by HMGA1-specific depletion and overexpression in dedifferentiated and myxoid liposarcoma cells showed the contribution of this oncogenic factor in cell proliferation, motility, invasion, and drug resistance. The in vitro and in vivo treatment of myxoid liposarcoma with trabectedin, a drug with a potent anti-tumor activity, revealed downregulation of HMGA1, E2F1, and its-downstream targets, vimentin and ZEB1, indicating a critical role of trabectedin in inhibiting the mesenchymal markers of these tumors through the HMGA1/E2F1 axis. These data were also confirmed in patients’ tumor biopsies being HMGA1, E2F1, and vimentin expression significantly reduced upon trabectedin therapy, administered as neo-adjuvant chemotherapy. Furthermore, trabectedin treatment inhibits in vitro NFkB pathway in mixoyd liposarcoma sensitive but not in resistant counterparts, and the inhibition of NFkB pathway re-sensitizes the resistant cells to trabectedin treatment. These data support the rational for combining NFkB inhibitors with trabectedin in liposarcoma patients, who have become resistant to the drug.

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BackgroundPrimary heart sarcomas are exceedingly rare tumors. Among primary cardiac sarcomas, synovial sarcoma is one of the rarest, involving cardiac cavities or pericardium.Case presentationTwo cases of synovial sarcoma are presented with the clinical course and therapy. Both cases were treated with surgery and chemo/radiotherapy. Interestingly, one of the patient, a 52-year-old male with an intracardiac synovial sarcoma, undergone a SynCardia total artificial heart implantation, but died for multiple pulmonary metastases waiting for transplantation.ConclusionComplete surgical resection of cardiac synovial sarcoma is the gold standard of therapy, though rarely possible. Although guidelines for the treatment are not well established, due to limited number of cases reported, chemotherapy and radiotherapy are frequently administered and seem to prolong mean patient’s survival. Cardiac transplantation could be considered in selected cases.

Loss of histone H3 trimethylation on lysine 27 and nuclear expression of transducin-like enhancer 1 in primary intracranial sarcoma, DICER1-mutant Aims: Primary intracranial sarcoma, DICER1-mutant is a recently described central nervous system tumour with specific genomic and DNA-methylation profiles. Although some of its histological features (focal spindle-cell morphology, intracytoplasmic eosinophilic granules, and focal heterologous differentiation) are common across most reported cases, the presence of significant histological variability and the lack of differentiation pose diagnostic challenges. We aim to further define the immunoprofile of this tumor. Methods and results: We reviewed the clinical history and performed immunohistochemistry for glial fibrillary acidic protein, oligodendrocyte transcription factor 2, SOX2, SOX10, S100, histone H3 trimethylated on lysine 27 (H3K27me3), desmin, myogenin, CD99, epithelial membrane antigen (EMA) and transducin-like enhancer of split 1 (TLE1) on six primary intracranial sarcomas, DICER1-mutant, with appropriate controls. Targeted exome sequencing was performed on all cases. The sarcomas showed diffuse (n = 4), mosaic (n = 1) or minimal (≤5%, n = 1) loss of H3K27 trimethylation and nuclear TLE1 expression (n = 6). Four had immunohistochemical evidence of myogenic differentiation. SOX2, SOX10, S100 and EMA were negative; CD99 expression ranged from focal cytoplasmic (n = 4) to crisp diffuse membranous (n = 2). One tumour had focal cartilaginous differentiation. Similar immunohistochemical findings were observed in a pleuropulmonary blastoma (albeit with focal TLE1 expression), a DICER1-related pineoblastoma, and an embryonal tumour with a multilayered rosette-like DICER1-related cerebellar tumour. Targeted exome sequencing confirmed the presence of pathogenic biallelic DICER1 mutations in all tumours included in this study. Conclusion: We conclude that H3K27me3 and TLE1 immunostains, when utilised in combination, can be helpful diagnostic markers for primary intracranial sarcoma, DICER1-mutant.