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Background: Enterovirus is a well-known cause of infection in all age groups, with particular importance for neonates with both vertically and horizontally transmission. Neonatal clinical manifestations are highly variable and mostly is asymptomatic, but severe infections are described such as myocarditis, meningitis, encephalitis, hepatitis, coagulopathy, pneumonia and viral sepsis. Since 2022, The World Health Organization has recently reported an increasing number of severe neonatal infection associated with a new variant of Echovirus-11 (E-11). Many of the infants described with E-11 infections in a case reports series were preterm, male and twins. Despite the criticality of neonatal disease, the clinical management remains primarily supportive and therapeutic options are unfortunately few. Case presentation: We present the case of male dichorionic diamniotic late-preterm twins, born in December 2023 at Filippo del Ponte Hospital in Varese (Northen Italy) with early Echovirus-11 infection. They had two dramatically different clinical scenarios and one of them developed a severe and fatal hemorrhage-hepatitis syndrome. Conclusions: Our experience has the purpose to emphasize public health attention to Echovirus-11 neonatal infections and their rare dramatically neonatal clinical presentations. Prematurity, host genetic predisposition and vertical transmission seem to be strong risk factors for severe infections, but it still need to be elucidated. According to previous Italian report, a surveillance protocols in all cases with unexpected clinical presentations and sequencing complete genome in order to better understand typing and molecular characterization of emerging and re-emerging pathogenic variants and new strains are strongly recommend in Italy. [ABSTRACT FROM AUTHOR]

Objectives Sinonasal mucosal melanoma (SNMM) is an extremely rare and challenging sinonasal malignancy with a poor prognosis. Standard treatment involves complete surgical resection, but the role of adjuvant therapy remains unclear. Crucially, our understanding of its clinical presentation, course, and optimal treatment remains limited, and few advancements in improving its management have been made in the recent past. Methods We conducted an international multicenter retrospective analysis of 505 SNMM cases from 11 institutions across the United States, United Kingdom, Ireland, and continental Europe. Data on clinical presentation, diagnosis, treatment, and clinical outcomes were assessed. Results One-, three-, and five-year recurrence-free and overall survival were 61.4, 30.6, and 22.0%, and 77.6, 49.2, and 38.3%, respectively. Compared with disease confined to the nasal cavity, sinus involvement confers significantly worse survival; based on this, further stratifying the T3 stage was highly prognostic (p < 0.001) with implications for a potential modification to the current TNM staging system. There was a statistically significant survival benefit for patients who received adjuvant radiotherapy, compared with those who underwent surgery alone (hazard ratio [HR] = 0.74, 95% confidence interval [CI]: 0.57–0.96, p = 0.021). Immune checkpoint blockade for the management of recurrent or persistent disease, with or without distant metastasis, conferred longer survival (HR = 0.50, 95% CI: 0.25–1.00, p = 0.036). Conclusions We present findings from the largest cohort of SNMM reported to date. We demonstrate the potential utility of further stratifying the T3 stage by sinus involvement and present promising data on the benefit of immune checkpoint inhibitors for recurrent, persistent, or metastatic disease with implications for future clinical trials in this field. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study is to assess the association between clinical and radiological features as well as of isocitrate dehydrogenase 1 and 2 (IDH 1,2) mutations with outcome in head and neck chondrosarcomas.Study Design: Retrospective study.Setting: Tertiary referral center.Methods: Clinical, histological, and molecular data of patients with head and neck chondrosarcomas treated by surgery were collected.Results: Forty-six patients were included. The mean age at diagnosis was 56 years (range, 17-78). The tumor originated from the skull base (52.2%), facial bones (28.2%), or laryngotracheal area (19.6%). At last follow-up (median 52.5 months), 38 patients were alive, 30 of which were disease free, whereas 8 had died, 4 of disease progression and 4 of other causes. Fourteen (30.4%) had local recurrence and 2 (4.3%) had lung metastasis. All cases were negative for cytokeratin AE1/AE3, brachyury, and IDH1 at immunohistochemistry, while Sanger sequencing identified IDH1/2 point mutations, typically IDH1 R132C, in 9 (37.5%) tumors arising from the skull base. Margin infiltration on the surgical specimen negatively affected the outcome, whereas no correlation was identified with IDH mutation status.Conclusions: An adequate margin positively affects survival. IDH mutation status does not affect patient outcome. [ABSTRACT FROM AUTHOR]

Different risk factors are suspected to be involved in malignant transformation of sinonasal papillomas and include HPV infection, tobacco smoking, occupational exposure, EGFR/KRAS mutations and DNA methylation alterations. In our study, 25 inverted sinonasal papillomas (ISPs), 5 oncocytic sinonasal papillomas (OSP) and 35 squamous cell carcinomas (SCCs) from 54 patients were genotyped for 10 genes involved in EGFR signalling. HPV‐DNA detection was performed by in‐situ hybridisation and LINE‐1 methylation was quantitatively determined by bisulphite‐pyrosequencing. High‐risk HPV was observed only in 13% of ISP‐associated SCC and in 8% of de novo‐SCC patients. EGFR mutations occurred in 72% of ISPs, 30% of ISP‐associated SCCs and 17% of de novo‐SCCs. At 5‐year follow‐up, SCC arose in only 30% (6/20) of patients with EGFR‐mutated ISPs compared to 76% (13/17) of patients with EGFR‐wild‐type ISP (p = 0.0044). LINE‐1 hypomethylation significantly increased from papilloma/early stage SCC to advanced stage SCC (p = 0.03) and was associated with occupational exposure (p = 0.01) and worse prognosis (p = 0.09). In conclusion, our results suggest that a small subset of these tumours could be related to HPV infection; EGFR mutations characterise those ISPs with a lower risk of developing into SCC; LINE‐1 hypomethylation is associated with occupational exposure and could identify more aggressive nasal SCC. What's new? Cancer of the sinonasal tract is rare, and the contributions of different risk factors involved in transforming papillomas into carcinomas remain unclear. The authors report that infections with high‐risk human papilloma virus types play a minor role in this process while mutations in epidermal growth factor receptor signalling are frequent but ultimately protective of developing into cancer. In contrast, DNA hypomethylation was frequent among patients with a history of occupational exposure and might be useful in the future to identify aggressive sinonasal carcinomas. [ABSTRACT FROM AUTHOR]

Objective: Outcomes of locally advanced epithelial sinonasal cancers remain unsatisfactory; moreover, only limited and heterogeneous data exist on prognostic factors.Methods: We reviewed all consecutive patients with American Joint Committee Cancer stage III to IV epithelial sinonasal cancers treated with platinum-based induction chemotherapy (IC) followed by locoregional treatment between 1996 and 2015.Results: We identified 69 patients treated with a multimodal approach (IC, surgery, radiotherapy). Overall, 44 patients recurred (64%). Of those, 19 patients received salvage surgery, but only four remained disease-free. Median overall survival (OS) was 62.5 months. Sinonasal neuroendocrine and small cell histotypes (P = 0.0085), neuroendocrine differentiation (P = 0.006), and lack of response to IC (P = 0.03) were associated with worse OS. In patients who recurred, median OS was 13 months since recurrence. Survival was longer in patients submitted to salvage surgery (44%) than in those receiving chemotherapy alone at recurrence (29.5 vs. 4.6 months). Patients with a clinical benefit after palliative chemotherapy had a longer median OS than those with disease progression (29.2 vs. 4.4 months; P < 0.0001).Conclusion: Globally, the prognosis of locally advanced epithelial sinonasal cancers is dismal, with worse outcomes for neuroendocrine lesions. In the recurrent setting, feasibility of salvage surgery and clinical benefit from palliative chemotherapy are associated with longer OS. A multimodal treatment strategy with IC seems to offer improved OS when compared with other retrospective series not employing such a therapeutic tool.Level Of Evidence: 4 Laryngoscope, 130:857-865, 2020. [ABSTRACT FROM AUTHOR]

P53-abnormal endometrial carcinomas are high-grade and aggressive tumors which should be treated with chemo-/radiotherapy. In low-grade endometrioid carcinoma (LGEC), abnormal expression of p53 is an exceptional finding and is typically accompanied by patchy p16 positivity and diffuse hormone receptor expression., Herein, we report a case of LGEC exhibiting both p53 and p16 overexpression, highlighting the diagnostic pitfalls related to such phenotype., A 60-year-old woman underwent hysterectomy and bilateral salpingo-oophorectomy with pelvic lymphadenectomy due to a deeply myoinvasive endometrial mass. The tumor showed glandular architecture, low-grade nuclei and glandular differentiation. Focal lymphovascular space invasion and no lymph node metastases were observed. Immunohistochemically, the tumor showed p53 overexpression, p16 block-type positivity, diffuse hormone receptors positivity and retained mismatch repair proteins expression. No POLE mutations were identified. A diagnosis of p53-abnormal LGEC was eventually made., A glandular neoplasm with p53 and/or p16-overexpression on endometrial biopsy specimens may raise the concern of other entities such as serous carcinoma, HPV-related endocervical adenocarcinoma, and gastric-type adenocarcinoma. An immunohistochemical panel including hormone receptors, p53, p16 and mismatch repair proteins appears necessary for an accurate diagnosis of uterine adenocarcinomas., (Copyright © 2024 Società Italiana di Anatomia Patologica e Citopatologia Diagnostica, Divisione Italiana della International Academy of Pathology.)