Transcription Factor Expression in Sinonasal Neuroendocrine Neoplasms and Olfactory Neuroblastoma (ONB): Hyams' Grades 1-3 ONBs Expand the Spectrum of SATB2 and GATA3-Positive Neoplasms.

Sinonasal neuroendocrine neoplasms (SN-NENs) are rare and mostly include neuroendocrine carcinoma (NEC), whereas neuroendocrine tumor (NET) is exceptional in this site. Olfactory neuroblastoma (ONB) is a malignant neuroectodermal neoplasm arising in the nasal cavity. Albeit crucial for correct patients' management, the distinction of high grade ONB from NEC is challenging and requires additional diagnostic markers. The transcription factor SATB2 has been recently introduced in routine diagnostics as an immunohistochemical marker of distal intestine differentiation. No specific data are available about SATB2 and GATA3 expression in SN-NENs. GATA3, SATB2, and, for comparison, CDX2 expression were investigated in a series of epithelial and non-epithelial SN-NENs. We collected 26 cases of ONB and 7 cases of epithelial SN-NENs diagnosed and treated in our Institution. ONBs were graded according to Hyams' system and epithelial NENs were reclassified into 5 NECs, 1 MiNEN, and 1 amphicrine carcinoma. Immunohistochemistry was performed using standard automated protocols. Hyams' grades 1-3 ONBs stained diffusely and intensely for SATB2, whereas grade 4 ONBs and NECs were globally negative. The non-neuroendocrine component of MiNEN and the amphicrine carcinoma were strongly positive. GATA3 was heterogeneously and unpredictably expressed in Hyams' grades 1-3 ONBs, whereas grade 4 ONBs and NECs were completely negative. CDX2 was negative in all cases. Our study identifies, for the first time, SATB2 and GATA3 expression as features of Hyams' grades 1-3 ONBs, expands the spectrum of SATB2 and GATA3-positive neoplasms, and suggests that Hyams' grade 4 ONBs are not only clinically but also biologically different from low graded ONBs.

Surgical management of tracheal chondrosarcoma.

Background: Tracheal chondrosarcoma is an extremely rare, slow-growing, malignant tumour. This study aims to analyze the cases of tracheal chondrosarcoma published in the literature and our case report, in order to better define tracheal chondrosarcoma management.Methods: A systematic review of the English literature was carried out for fully described tracheal chondrosarcoma cases. Additionally, we reported a new case of a 58-year-old man undergoing tracheal resection and reconstruction for tracheal chondrosarcoma.Results: To date, 30 cases were published. This tumour predominantly involved male patients (93%; median age: 65 years), generally conditioning dyspnoea and cough. Most of the patients underwent tracheal resection with end-to-end anastomosis, without recurrence (median follow-up: 2 years). Tumours endoscopically treated recurred in half cases.Conclusion: Tracheal resection is the treatment of choice for chondrosarcoma, with an excellent prognosis. Endoscopic treatment and/or radiotherapy should be indicated for patients unfit for surgery.

Methylation Drivers and Prognostic Implications in Sinonasal Poorly Differentiated Carcinomas.

BACKGROUND: Poorly differentiated sinonasal carcinomas (PDSNCs) are rare and aggressive malignancies, which include squamous cell carcinoma (SCC), sinonasal undifferentiated carcinoma (SNUC), and neuroendocrine carcinomas (NEC). Several epigenetic markers have been suggested to support the histopathological classification, predict prognosis, and guide therapeutic decision. Indeed, molecularly distinct subtypes of sinonasal carcinomas, including SMARCB1-INI1 or SMARCA4 deficient sinonasal carcinoma, isocitrate dehydrogenase (IDH)-mutant SNUC, ARID1A mutant PDSNCs, and NUT carcinomas, have recently been proposed as separate entities. Identification of aberrant DNA methylation levels associated with these specific epigenetic driver genes could be useful for prognostic and therapeutic purpose. METHODS: Histopathological review and immunohistochemical study was performed on 53 PDSNCs. Molecular analysis included mutational profile by NGS, Sanger sequencing, and MLPA analyses, and global DNA methylation profile using LINE-1 bisulfite-PCR and pyrosequencing analysis. RESULTS: Nine SWI/SNF complex defective cases and five IDH2 p.Arg172x cases were identified. A significant correlation between INI-1 or IDH2 defects and LINE-1 hypermethylation was observed (p = 0.002 and p = 0.032, respectively), which were associated with a worse prognosis (p = 0.007). CONCLUSIONS: Genetic and epigenetic characterization of PDSNCs should be performed to identify distinct prognostic entities, which deserved a tailored clinical treatment.

Paroxetine versus Vortioxetine for Depressive Symptoms in Postmenopausal Transition: A Preliminary Study.

Background: The impact of menopause is a consequence of social, physical and mental changes; hormonal changes play an important role in inducing an increased risk of developing depressive symptoms. It is essential to treat mood and vasomotor symptoms and to prevent their onset to promote an improvement in the quality of life, both in terms of clinical and psychological conditions. Objective: This observational study aims to compare paroxetine and vortioxetine in a sample of patients affected by postmenopausal depression attending the Anxiety and Depression Clinic in terms of: efficacy in determining clinical remission (HDRS ≤ 7) and tolerability; improvement of autonomic and cognitive symptoms. Methods: 39 female outpatients with a diagnosis of Postmenopausal Depression (according to DSM-5 criteria) were evaluated as the routine clinical practice through the following scales: Hamilton Depression Rating Scale (HDRS); Menopause Rating Scale (MRS); Montreal Cognitive Assessment (MoCA); Antidepressant Side-Effect Checklist (ASEC); data from/of baseline, after 8 weeks and 12 weeks were recorded. Results: Both antidepressants resulted to be effective in clinical remission (HDRS ≤ 7) without statistical differences between the two groups (p = 0.3), although paroxetine showed a faster remission than vortioxetine (p = 0.01). Autonomic symptoms showed a higher improvement in the vortioxetine group (p = 0.002). Paroxetine group referred insomnia and sexual problems while patients taking vortioxetine referred diarrhoea and palpitations. Data show a superiority of cognitive performance in the Paroxetine group (p = 0.005), contrary to what stated in literature. Conclusions: Data are related to a small sample retrospectively assessed trough a 6-month observation period. Thus, the preliminary results need further research to be confirmed.