Molecular developments in parasellar tumors and potential therapeutic implications.

The parasellar region is the anatomical area around the sella turcica that represents a crucial crossroad for important adjacent structures. Several distinct tumors can primarily originate from this area, the most common being meningiomas, gliomas, embryonal cell tumors, germ cell tumors and craniopharyngiomas. In addition, a number of systemic and inflammatory disorders can also affect the parasellar region most commonly involving the pituitary. These lesions have different pathology characteristics and malignant potential according to the new WHO CNS5 2021 classification. Signs and symptoms may be non-specific and are mostly related to a mass effect on the surrounding anatomical structures and/or impairment of endocrine function whereas the vast majority lack a secretory component. The mutational signature analysis based on advances in molecular techniques, has recently enabled the identification of specific gene mutations or signalling pathway aberrations. These developments may serve as a powerful mean to delineate the pathophysiology of these lesions and serve as a diagnostic, prognostic and therapeutic tool, particularly for high-risk populations. Treatment options include surgery alone or in combination with radiotherapy, chemotherapy and disease-specific medical therapy in order to prevent recurrence or further tumor growth along with replacement of coexistent pituitary hormonal deficiencies. In this comprehensive review, we present current state-of-the-art developments in the histopathology and molecular biology of these lesions that may be utilized by a dedicated multidisciplinary team of relevant specialties for the diagnosis, monitoring and treatment of the parasellar lesions that often represent a diagnostic and therapeutic challenge.

Mönckeberg sclerosis in patients with thyroid papillary carcinoma.

Background: Mönckeberg sclerosis is a form of calcification of the tunica media of small and medium size arteries. It occurs more often in the peripheral arteries of the lower limbs and it has been associated with diabetes and renal disease. Although there are a few reports of Mönckeberg sclerosis in thyroid vessels, there are no data regarding its significance in thyroid disease. Objective: The aim was to investigate the possible prognostic value of Mönckeberg sclerosis in thyroid vessels of patients with diagnosed thyroid cancer. Methods: We retrospectively studied patients with papillary thyroid cancer treated at the Theagenio Hospital of Thessaloniki from 2005 to 2021. The patients were divided into two groups based on the presence, or absence, of histopathological findings of Mönckeberg sclerosis in the thyroid vessels along with papillary thyroid cancer. Patient characteristics, histopathological details, personal history of thyroid disease, and metabolic parameters were compared between the two groups. Results: Thirty-three patients with papillary thyroid carcinoma and Mönckeberg sclerosis were identified and matched to 33 controls with papillary thyroid cancer, without evidence of Mönckeberg sclerosis. The metabolic profile of patients with Mönckeberg sclerosis was not significantly different from those who did not have Mönckeberg sclerosis. Moreover, the comparison between the two groups did not reveal any remarkable differences in terms of the aggressiveness of the disease. Conclusion: The presence of Mönckeberg sclerosis does not seem to impact on histological characteristics of patients with papillary thyroid cancer.

Intrathyroidal parathyroid adenoma mimicking thyroid cancer.

Primary hyperparathyroidism (PHPT) is the most common cause of hypercalcemia; patients are usually asymptomatic and the cause in 80-85% of cases is a single parathyroid adenoma (PA). Parathyroid adenomas arise from clonal expansion of tumor cells and may be located either posteriorly to the thyroid lobes or in ectopic sites. The incidence of intrathyroidal PAs varies from 1% to 6% and although uncommon, they pose certain diagnostic difficulties which may complicate treatment. The identification of the adenoma requires a combination of clinical evidence, imaging information and cytological findings due to the challenging distinction between thyroid and parathyroid lesions. We present the case of a patient with a large, partially cystic intrathyroidal parathyroid adenoma which was initially identified as a malignant thyroid nodule. We discuss the caveats that present in these rare cases and the important clinical and histological features that aid in the final diagnosis. In the case of our patient the cytological similarities between thyroid malignant cells and parathyroid cells, in combination with the negative sestamibi scan, resulted in a more invasive surgery than that a single parathyroid adenoma would require. Clinicians need to be vigilant in terms of the similarities between parathyroid and thyroid cytology in order to provide optimal patient care in these rare cases.

Farnesoid X nuclear receptor agonists for the treatment of nonalcoholic steatohepatitis.

Nonalcoholic fatty liver disease (NAFLD) affects 20-40% of the general population. Despite significant disease burden and mortality associated with advanced disease, i.e., nonalcoholic steatohepatitis (NASH), there is currently no approved medication for NASH. Farnesoid X receptor agonists have been investigated as candidates for the treatment of NASH. Obeticholic acid, approved for the treatment of primary biliary cholangitis, has gained significant attention after showing promising results in patients with NASH and fibrosis. Three trials investigating the effect of obeticholic acid in patients with NASH have been completed and the preliminary results of an ongoing one have also been made public. Generally, treatment with obeticholic acid improved hepatic histology, including inflammation and fibrosis, the latter being the main histological predictor of advanced disease. Nonetheless, there were adverse effects, the most common being pruritus and unfavorable changes in the lipid profile. Pruritus led to discontinuation of treatment in some patients. Obeticholic acid, however, is not the only farnesoid X receptor agonist currently investigated for the treatment of NASH. Another farnesoid X receptor agonist, cilofexor, in combination with firsocostat, an acetyl-CoA carboxylase inhibitor, improved hepatic steatosis, liver stiffness, liver function tests and serum fibrosis markers, without causing pruritus after 12 weeks of treatment. In conclusion, current evidence regarding the effect of farnesoid X receptor agonists on hepatic histology in patients with NASH is promising, but several safety issues need further evaluation.

Menopause and Non-Alcoholic Fatty Liver Disease: A Review Focusing on Therapeutic Perspectives.

There is increasing evidence that menopause is associated with the progression and severity of non-alcoholic fatty liver disease (NAFLD). Estrogen deficiency worsens non-alcoholic steatohepatitis (NASH) in mice models with fatty liver. The prevalence of NAFLD seems to be higher in postmenopausal compared with premenopausal women. Although more data are needed, lower serum estradiol levels are associated with NASH in postmenopausal women. Apart from estrogen deficiency, relative androgen excess and decrease in sex hormone-binding protein are observed in postmenopausal women. These hormonal changes seem to interplay with an increase in abdominal adipose mass, also observed in postmenopausal women, and aging, which are both closely related to the severity and progressive forms of NAFLD. NAFLD adds extra morbidity to postmenopausal women, possibly increasing the risk of type 2 diabetes mellitus and cardiovascular disease. Improving parameters of the metabolic syndrome via modifications in diet and physical exercise may reduce the risk of NAFLD and its related morbidity. Limited studies have shown a beneficial effect of hormone replacement therapy (HRT) on NAFLD, although adverse hepatic effects have been attributed to progesterone in one study. Phytoestrogens may be alternatives to HRT, but their long-term efficacy and safety remain to be shown. The aim of this review was to summarize evidence linking menopause with NAFLD with a special focus on potential therapeutic perspectives.