Summary Brown tumors (BTs) are expansile osteolytic lesions complicating severe primary hyperparathyroidism (PHPT). Clinical, radiological and histological features of BTs share many similarities with other giant cell-containing lesions of the bone, which can make their diagnosis challenging. We report the case of a 32-year-old man in whom an aggressive osteolytic lesion of the iliac crest was initially diagnosed as a giant cell tumor by biopsy. The patient was scheduled for surgical curettage, with a course of neoadjuvant denosumab. Routine biochemical workup prior to denosumab administration incidentally revealed high serum calcium levels. The patient was diagnosed with PHPT and a parathyroid adenoma was identified. In light of these findings, histological slices of the iliac lesion were reviewed and diagnosis of a BT was confirmed. Follow-up CT-scans performed 2 and 7 months after parathyroidectomy showed regression and re-ossification of the bone lesion. The aim of this case report is to underline the importance of distinguishing BTs from other giant cell-containing lesions of the bone and to highlight the relevance of measuring serum calcium as part of the initial evaluation of osteolytic bone lesions. This can have a major impact on patients’ management and can prevent unnecessary invasive surgical interventions. Learning points: Although rare, brown tumors should always be considered in the differential diagnosis of osteolytic giant cell-containing bone lesions. Among giant cell-containing lesions of the bone, the main differential diagnoses of brown tumors are giant cell tumors and aneurysmal bone cysts. Clinical, radiological and histological characteristics can be non-discriminating between brown tumors and giant cell tumors. One of the best ways to distinguish these two diagnoses appears to be through biochemical workup. Differentiating brown tumors from giant cell tumors and aneurysmal bone cysts is crucial in order to ensure better patient care and prevent unnecessary morbid surgical interventions.

Background The SELECT trial led to the approval of Lenvatinib for the treatment of advanced radioiodine-refractory differentiated thyroid carcinomas (DTCs) but also revealed an important adverse events’ (AEs) profile which may limit its use in clinical practice. We aim to describe the efficacy and toxicity profiles of Lenvatinib in real life. Methods We included all patients who received lenvatinib for an advanced DTC at our institution, enrolling 27 patients. We reviewed retrospectively electronic medical records to assess efficacy and AEs. Results Among the 24 patients with evaluation of tumor response during treatment, overall response rate (ORR) was 37.0% [95% confidence interval (CI), 19.4 to 57.6], and disease control rate was 85.2% [95% CI, 66.3 to 95.8]. The median progression free survival (PFS) was 12 months [95% CI, 7.5 to 16.5]. The most prevalent AEs were hypertension (77.8%), fatigue (55.6%), and weight loss (51.9%). 25/27 patients (92.6%) experienced at least one grade ≥ 3 AE, mostly hypertension (59.3%). Lenvatinib was discontinued due to AEs in 13/27 patients (48.1%). Interestingly, one patient experienced a grade 4 posterior reversible encephalopathy syndrome, and another developed a Takotsubo cardiomyopathy. Conclusions Safety profile of lenvatinib in our cohort was similar to that reported in the literature, with a predominance of hypertension. Rigorous blood pressure control is therefore essential to avoid discontinuing therapy. We also report two severe and rarely described AEs that physicians should lookout for. As for efficacy, although less than in the SELECT trial, ORR and PFS were similar to other real-life studies.

The treatment of advanced, radioiodine refractory, differentiated thyroid cancers (RR-DTCs) has undergone major advancements in the last decade, causing a paradigm shift in the management and prognosis of these patients. Better understanding of the molecular drivers of tumorigenesis and access to next generation sequencing of tumors have led to the development and Food and Drug Administration (FDA)-approval of numerous targeted therapies for RR-DTCs, including antiangiogenic multikinase inhibitors, and more recently, fusion-specific kinase inhibitors such as RET inhibitors and NTRK inhibitors. BRAF + MEK inhibitors have also been approved for BRAF-mutated solid tumors and are routinely used in RR-DTCs in many centers. However, none of the currently available treatments are curative, and most patients will ultimately show progression. Current research efforts are therefore focused on identifying resistance mechanisms to tyrosine kinase inhibitors and ways to overcome them. Various novel treatment strategies are under investigation, including immunotherapy, redifferentiation therapy, and second-generation kinase inhibitors. In this review, we will discuss currently available drugs for advanced RR-DTCs, potential mechanisms of drug resistance and future therapeutic avenues.

Purpose of review To summarize recent developments in the diagnosis and management of patients with anaplastic thyroid cancer (ATC). Recent findings An updated edition of the Classification of Endocrine and Neuroendocrine Tumors was released by the World Health Organization (WHO), in which squamous cell carcinoma of the thyroid are now a subtype of ATC. Broader access to next generation sequencing has allowed better understanding of the molecular mechanisms driving ATC and improved prognostication. BRAF-targeted therapies revolutionized the treatment of advanced/metastatic BRAFV600E-mutated ATC, offering significant clinical benefit and allowing better locoregional control of disease through the neoadjuvant approach. However, inevitable development of resistance mechanisms represents a major challenge. Addition of immunotherapy to BRAF/MEK inhibition has shown very promising results and significant improvement in survival outcomes. Summary Major advancements took place in the characterization and management of ATC in recent years, especially in patients with a BRAF V600E mutation. Still, no curative treatment is available, and options are limited once resistance to currently available BRAF-targeted therapies develops. Additionally, there is still a need for more effective treatments for patients without a BRAF mutation.