Objective
Parathyroid Carcinoma is a rare malignant neoplasm, accounting for less than 1% of primary hyperparathyroidism cases. Parathyroid carcinomas are characterized by markedly elevated levels of PTH, severe hypercalcemia and established target organ damage. The authors report the experience of a single centre regarding the management and outcome of patients with parathyroid carcinomas and revise relevant literature.
Design
Retrospective review of all patients with parathyroid carcinoma evaluated at a tertiary oncologic centre from 1991 until 2021.
Results
Seventeen patients were identified (10 males), with a mean age at diagnosis of 53 ± 16 years and a median follow‐up of 16.5 years. Most patients presented with hypercalcemia (n = 15), with a mean serum calcium concentration of 13.5 mg/dl (9.6–16.5) and mean PTH of 1173 pg/ml (276–2500). Hyperparathyroidism‐mediated organ damage was observed in most patients (n = 16), with predominant renal (n = 12) and skeletal (n = 9) complications. En bloc surgical resection was performed in nine patients. Three patients underwent adjuvant radiotherapy. Recurrence was observed in 8 cases (47.1%) after a median of 24 months following surgery and no independent predictors of recurrence were identified. The overall survival and disease specific survival at 5‐year was 88% and 94%, respectively. CDC73 mutations were present in 38.5% of analysed patients and one patient was diagnosed with MEN1.
Conclusion
Parathyroid carcinoma is associated with a significant rate of recurrence and limited effective treatment beyond initial complete surgical resection. Therefore, preoperatively high index of suspicion is paramount to optimize patient care. This is, to our knowledge, the largest Portuguese cohort published so far.
Osteosarcomas of the jaws (OSJ) are difficult to diagnose, rare malignant lesions, with uncharacteristic radiographic and clinical presentation. Early diagnosis and treatment are essential to improve long-term prognosis. The current report presents a rare case of a primary conventional osteoblastic osteosarcoma of the anterior maxilla in a 25-year-old female. She presented to a private dental clinic after developing pain, facial oedema and palpation tenderness of a mass associated with the upper right lateral incisor. The signs and symptoms mimicked very closely a regular radiolucent and symptomatic periapical pathology, and the definitive diagnosis was only possible through a combination of clinical, radiographic and histopathological findings. The patient was referred to an oncology facility, where she was submitted to radical excision surgery through a hemi-maxillectomy. Although other pathologies are uncommon, the differential diagnosis of lesions compatible with odontogenic periapical pathology should not be neglected.
Background
Despite current improvements in systemic cancer treatment, brain metastases (BM) remain incurable, and there is an unmet clinical need for effective targeted therapies.
Methods
Here, we sought common molecular events in brain metastatic disease. RNA sequencing of thirty human BM identified the upregulation of UBE2C, a gene that ensures the correct transition from metaphase to anaphase, across different primary tumor origins.
Results
Tissue microarray analysis of an independent BM patient cohort revealed that high expression of UBE2C was associated with decreased survival. UBE2C-driven orthotopic mouse models developed extensive leptomeningeal dissemination, likely due to increased migration and invasion. Early cancer treatment with dactolisib (dual PI3K/mTOR inhibitor) prevented the development of UBE2C-induced leptomeningeal metastases.
Conclusions
Our findings reveal UBE2C as a key player in the development of metastatic brain disease and highlight PI3K/mTOR inhibition as a promising anticancer therapy to prevent late-stage metastatic brain cancer.
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