Leukaemias are malignant neoplasms that affect the bone marrow, compromising the production of functional blood cells. In Brazil, leukaemia is the 13th most frequent cancer and the most common among individuals up to 20 years old. This study analysed the incidence and mortality of acute and chronic myeloid and lymphoid leukaemias in Brazil from 1990 to 2021, using adjusted and estimated data from the Global Burden of Diseases Study 2021. This is an ecological time-series study with age-standardised rates, expressed per 100,000 inhabitants. Trends were assessed using Joinpoint regression, considering the average annual percentage change. The results indicated an increase in the incidence of chronic lymphocytic leukaemia (CLL) and Acute Myeloid Leukaemia in males, as well as an increase in AML-related mortality in both sexes. On the other hand, a reduction in the incidence and mortality of acute lymphocytic leukaemia (ALL) and chronic myeloid leukaemia (CML) was observed in both sexes. ALL-related mortality also decreased in females, whereas CLL-related mortality increased in males. According to age group and sex, varied trends were observed for these neoplasms. These findings highlight the need for further studies on haematologic neoplasms to inform public health policies, foster research on targeted therapies and promote advancements in the management of these diseases in Brazil.

Primary lymphoma of bone (PLB) is an uncommon malignancy, representing ~4-5% of primary malignant bone tumors and 1% of all malignant lymphomas. Diffuse large B-cell lymphoma (DLBCL) is the most common subtype, accounting for ~80% of cases, and is highly curable with appropriate treatment. Therefore, accurate and timely diagnosis is crucial for favorable outcomes. The current study presents a 42-year-old male with primary DLBCL of the proximal humerus. The initial diagnosis was challenging due to overlapping morphological features with other small round cell tumors like Ewing's sarcoma and small cell osteosarcoma, particularly on small, decalcified biopsy samples. However, a definitive diagnosis was achieved through specific immunohistochemical markers. Following standard chemo-radiotherapy, the patient suffered a persistent, non-healing pathological fracture, resulting in severe functional shoulder impairment. This report details successful surgical management using a novel technique: A reverse shoulder megaprosthesis combined with a liquid nitrogen-treated autologous bone graft. This case report underscores PLB's diagnostic challenges and highlights a significant treatment-related complication. It presents a novel and effective surgical solution for managing pathological fractures in this context, emphasizing the necessity of a multidisciplinary, individualized approach to cure the disease, restore function and preserve the limb.

Salivary duct carcinoma (SDC) is one of the most aggressive salivary gland carcinomas. Heterotopic ossification (HO) is the formation of mature bone in non-skeletal tissues. HO can occur in a number of neoplastic lesions. However, its occurrence is markedly rare in salivary gland neoplasms and to the best of our knowledge, SDC with HO has not yet been reported. Therefore, the present report describes the first reported case of SDC with HO in the parotid gland and reviews the clinicopathological features of salivary gland neoplasms with HO. A 38-year-old Japanese male presented with a mass in the left parotid region. Physical examination revealed a poorly mobile mass, measuring 2 cm, in the left parotid gland. Total left parotidectomy was performed. A number of metastases were observed in the bone and brain, despite postoperative anti-HER2 combination chemotherapy. Histopathological examination of the resected parotid gland tumour revealed invasive neoplastic growth comprising cribriform and papillary proliferations. These neoplastic cells exhibited a rich eosinophilic cytoplasm and large nuclei containing conspicuous nucleoli. In addition, the present report outlines peculiar finding in the presence of mature bone tissue within the tumour. Accordingly, a diagnosis of SDC with HO was made. Despite the detailed mechanisms underlying the occurrence of HO in salivary gland neoplasms remaining unclear, neoplastic myoepithelial cells may serve a role in the development of HO in pleomorphic adenoma and carcinoma ex pleomorphic adenoma. However, SDC exhibited no myoepithelial cell components, therefore the mechanism of HO in SDC may differ from that in PA.

Targeted immunotherapies have revolutionized outcomes for lymphoid malignancies, but success in myeloid neoplasms is limited by the lack of amenable targets and immunologically hostile tumor microenvironment (TME). Myeloproliferative neoplasms (MPNs) are chronic myeloid blood cancers, a third of which are driven by mutations in calreticulin. Calreticulin mutant protein (mutCALR) binds and activates thrombopoietin receptor (TpoR) and results in the display of the mutCALR-TpoR complex on the extracellular membrane of disease-driving cells, thus exposing a therapeutic vulnerability. Here, we present a chimeric antigen receptor T cell (CAR T cell) therapy that specifically targets mutCALR+ cells, both in vitro and in vivo. The CAR T cell therapy selectively depleted mutCALR+ stem cells in samples from patients with myelofibrosis without affecting healthy stem cells and improved survival in mutCALR leukemia xenograft models. To mimic myelofibrotic marrow, we developed a human "chimeroid" model and showed no decrease in the potency of CAR T cell-mediated target cell killing even in a fibrotic TME. We also devised a method to boost the cell surface expression of mutCALR in CD34+ cells isolated from patients with accelerated/blast phase MPNs (defined as >10% blasts in the peripheral blood or bone marrow), enhancing CAR T cell targeting. This study presents a therapeutic strategy with potential to eradicate mutCALR-driven malignancies and highlights an innovative strategy to evaluate blood cancer-targeting immunotherapies in a relevant TME.

We present a rare case of a chondroid tenosynovial giant cell tumor (TGCT) involving the temporomandibular joint (TMJ) in a 46-year-old man with an asymptomatic but progressively enlarging lesion centered within the zygomatic air cell tract superior to the TMJ. A computed tomography (CT) scan performed for sinusitis symptoms revealed an expansile lesion near the zygomatic air cell tract above the TMJ, which had grown undetected over 16 years, eroding the squamous temporal bone and extending to the middle fossa dura. Magnetic resonance imaging (MRI) showed T1- and T2-hypointense, heterogeneously enhancing nodules in the TMJ, with susceptibility artifacts on diffusion-weighted sequences indicating hemosiderin staining, suggestive of a chondroid TGCT originating from the synovial disc in the glenoid fossa. A preauricular infratemporal approach enabled complete resection of the tumor, synovial disc, and adjacent affected bone. The mandibular condyle was unaffected and preserved. Reconstruction was performed using a pedicled temporoparietal fascia flap. One-year follow-up MRI showed no recurrence, and the patient experienced successful mastication without pain. This case illustrates the diagnosis and surgical management of chondroid TGCT of the TMJ, emphasizing its potential for slow, asymptomatic growth and its CT appearance of a primary temporal bone lesion. The characteristic MRI features assist in diagnosis, and chondroid TGCT should be considered when evaluating erosive lesions near the glenoid fossa.

Disruptions in bone tissue metabolic balance can lead to osteoporosis, osteoarthritis, rheumatoid arthritis, and bone tumors. This disruption typically manifests as reduced or abnormal bone mass, accompanied by pathological changes such as inflammation, fractures, and pain. Recent studies have revealed that mitochondrial dysfunction is prevalent in the aforementioned pathological processes, participating in the regulation of bone tissue cell function and intracellular immune function. Mitochondrial transfer, a newly discovered physiological phenomenon in recent years, can regulate mitochondrial function within recipient cells, thereby influencing metabolic activities, proliferation, differentiation, apoptosis, and immune function of various bone tissue cells. This article primarily reviews the regulatory effects of mitochondrial transfer associated with MSCs on various cells in bone and joint tissues. Given the role of mitochondrial transfer in regulating bone metabolism, we elucidate the application of mitochondrial transfer therapy in the treatment of osteoporosis, osteoarthritis, rheumatoid arthritis, and other bone tissue diseases. The Translational Potential of this Article: This review elaborates in detail on the therapeutic strategies provided by mitochondrial transplantation technology or targeted mitochondrial delivery systems for the treatment of bone tissue diseases, based on the occurrence of mitochondrial transfer in bone tissue tips and its therapeutic effects on related diseases such as OA, RA, osteoporosis.

Myelodysplastic neoplasms (MDS) disrupt bone marrow hematopoiesis, yet clinical assessment relies largely on blast enumeration and qualitative morphology, which incompletely capture marrow architecture and disease state. We applied whole-slide multiplex immunofluorescence imaging with single-cell phenotyping to map bone marrow microarchitecture in MDS. Diagnostic biopsies (n = 36), longitudinal treatment samples (n = 29), precursor states (n = 13), and normal controls (n = 21) were analyzed, comprising >5 million spatially resolved cells. MDS marrow exhibited coordinated, genotype-imprinted architectural remodeling, including altered progenitor composition and spatial patterning, disrupted erythroid island organization, and displacement of hematopoietic stem and progenitor cells from perivascular niches. Interrogation of 82 cellular and spatial features yielded a composite Microarchitectural Perturbation Score (MDS-MAPS), derived from diagnostic samples and fixed prior to longitudinal analyses. In leave-one-patient-out cross-validation, MDS-MAPS discriminated remission from active disease more accurately than blast percentage (AUC 0.883 vs 0.660) and distinguished low-blast MDS from clonal cytopenia of undetermined significance (CCUS) (AUC 0.815). Mixed-effects modeling showed MAPS decreased in remission statistically independent of blast burden, with architectural normalization during remission and re-emergence at relapse. These findings define quantitative bone marrow architecture as a dynamic tissue-state biomarker that complements molecular and blast-based assessment in MDS.