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Background: Molecular tumor boards (MTBs) match molecular alterations with targeted anticancer drugs upon failure of the available therapeutic options. Special and local needs are most likely to emerge through the comparative analysis of MTB networks, but these are rarely reported. This manuscript summarizes the state-of-art of 16 active Italian MTBs, as it emerges from an online survey curated by Alliance Against Cancer (ACC). Main text: Most MTBs (13/16) are exclusively supported through local Institutional grants and meet regularly. All but one adopts a fully virtual or a mixed face-to-face/virtual calling/attendance meeting model. It appears that the ACC MTB initiative is shaping a hub-and-spoke virtual MTB network reminiscent of non-redundant, cost-effective healthcare organization models. Unfortunately, public awareness of MTB opportunities presently remains insufficient. Only one center has a website. Dedicated e-mail addresses are for the exclusive use of the MTB staff. More than half of ACC members consider a miscellanea of most or all solid and hematological malignancies, and more than one-third consider neoplasms arising at any anatomical location. The average number of Staff Members in MTBs is 9. More than 10 staff members simultaneously attend MTB meetings in 13 MTBs. A medical oncologist is invariably present and is in charge of introducing the clinical case either with (45%) or without previous discussion in organ-specific multidisciplinary Boards. All but two MTBs take charge of not only patients with no standard-of-care (SoC) therapy option, but also cases receiving NGS profiling in SoC settings, implying a larger number of yearly cases. All MTBs run targeted NGS panels. Three run whole-exome and/or RNAseq approaches. ESCAT-ESMO and/or Onco-KB levels of evidence are similarly used for diagnostic reporting. Most MTBs (11) provide a written diagnostic report within 15 days. Conclusions are invariably communicated to the patient by the medical oncologist. Conclusions: MTB networking is crucial not only for molecular diagnosis and therapy assignment, but also for healthcare governance. Survey results show that MTBs review therapeutic opportunities at the crossover between standard-of-care with off-label, the former task being much beyond their scope. Societal and scientific implications of this beyond-the-scope MTB function may be relevant for healthcare in Italy and abroad. [ABSTRACT FROM AUTHOR]

Italy was the first European nation to be massively infected by SARS‐CoV‐2. Up to the end of May 2020, more than 33,000 deaths had been recorded in Italy, with a large prevalence among males, those over 75 years of age, and in association with co‐morbidities. We describe the lung pathological and immunohistochemical post‐mortem findings at the autopsy of nine patients who died of SARS‐CoV‐2‐associated disease. We found in the lung tissues of all patients histological changes consistent with diffuse alveolar damage in various evolution phases ranging from acute exudative to acute proliferative to fibrotic phase. Alveolar damage was associated with prominent involvement of the vascular component in both the interstitial capillaries and the mid‐size vessels, with capillary fibrin micro‐thrombi, as well as organized thrombi even in medium‐sized arteries, in most cases not related to sources of embolism. Eosinophilic infiltrate was also seen, probably reactive to pharmacological treatment. Viral RNA of SARS‐CoV‐2 was detected from the lung tissues of all the nine patients. Immunohistochemistry for the receptor of the SARS‐CoV‐2, ACE2, and its priming activator TMPRSS2 revealed that both proteins co‐localize in airway cells. In particular, the ACE2 protein was expressed in both endothelial cells and alveolar type I and II pneumocytes in the areas of histological diffuse alveolar damage (DAD). Pneumocytes, but not endothelial cells, also expressed TMPRSS2. There are no distinctive histological features of SARS‐CoV‐2 infection with respect to SARS‐CoV‐1 and other DAD with different aetiology. The identification of the cause of death in the course of SARS‐CoV‐2 infection is more likely multi‐factorial. © 2020 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background: In recent years, HER2 amplification has been evaluated as a potential prognostic biomarker and therapeutic target in urothelial carcinoma (UC). In this retrospective study, we aimed at exploring the prognostic role of HER2 amplification in UC, measured by chromogenic in situ hybridization (CISH)., Methods: We retrospectively evaluated the presence of HER2 amplification by using CISH in 31 UC patients followed at a single institution between 2018 and 2020. The primary objective was to assess the frequency of HER2 amplification and to compare clinical outcomes of HER2-amplified patients with non-amplified UCs., Results: HER2 amplification was identified in 4 out of 31 patients (12.9 %). After a median follow-up of 28.1 months (95 % Confidence Intervals [CI] 11.2-45.1), median overall survival (OS) in the whole population was 10.9 months (95 % CI 3.5-22.1). Despite not reaching statistical significance, median OS was shorter in HER2-amplified patients (6.8 months, 95 % CI 3.9-9.7) compared to HER2-negative UCs (15.4 months, 95 % CI 7.5-23.3) (p = 0.45)., Conclusions: Although limited by the small sample size, the results of our study suggest that HER2 amplifications by CISH could represent a prognostic factor for shorter survival in UC patients., (Copyright © 2021 Elsevier GmbH. All rights reserved.)

Vitamin A is a fat-soluble micronutrient involved in the regulation of several physiologic functions, such as visual acuity, epithelial tissue integrity, immune response, and gene expression, thus playing a crucial role in childhood growth and development. Although vitamin A deficiency (VAD) in resource-limited settings is still an actual issue and represents the leading cause of preventable childhood blindness, its occurrence in high-income countries is rare, although possibly underdiagnosed because of its nonspecific early manifestations. A good awareness of VAD symptoms and risk factors could aid its early diagnosis, which is fundamental to undertake a prompt treatment and to prevent ocular complications. Nevertheless, the role of restrictive dietary habits, increasingly common in developed countries, is often overlooked in infants and children. We present a case of VAD with permanent ocular sequelae in a 5-year-old girl from a high-income country. In the case described, VAD ensued from a highly restricted diet, mainly limited to oat milk, which had been followed for more than 2 years. This child presented with ocular symptoms, opportunistic infection, anemia, poor growth, and a diffuse squamous metaplasia of the bladder; after commencing retinol supplementation, a gradual healing of clinical VAD manifestations occurred, with the exception of the ocular sequelae, which resulted in irreversible visual loss., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2018 by the American Academy of Pediatrics.)

Aim: To define the histopathological features predictive of post-transplant hepatocellular carcinoma (HCC) recurrence after transarterial chemoembolization, applicable for recipient risk stratification., Methods: We retrospectively reviewed the specimens of all suspicious nodules (total 275) from 101 consecutive liver transplant recipients which came to our Pathology Unit over a 6-year period. All nodules were sampled and analyzed, and follow-up data were collected. We finally considered 11 histological variables for each patient: total number of nodules, number of viable nodules, size of the major nodule, size of the major viable nodule, occurrence of microscopic vascular invasion, maximum Edmondson's grade, clear cell/sarcomatous changes, and the residual neoplastic volume. Survival data were computed by means of the Kaplan-Meier procedure and analyzed by means of the Cox proportional hazards model. The multivariate linear regression and a k-means cluster analysis were also used in order to compute the standardized histological score., Results: The total number of nodules, the residual neoplastic volume (the total volume of all evaluated nodules minus the necrotic portion) and the microvascular invasion entered the Cox multivariate hazard model with HCC recurrence as dependent variable. The histological score was therefore computed and a cluster analysis sorted recipients into 3 risk groups, with 3.3%, 18.5% and 53.8% respectively of tumor recurrence rates and 1.6%, 11.1% and 38.5% of tumor-related mortality respectively at the end of follow-up., Conclusion: The histological score allows a reliable stratification of HCC recurrence risk, especially in those recipients found out to be beyond the Milan criteria after orthotopic liver transplantation (OLT).

Objectives: One-third of patients with positive surgical margins after radical prostatectomy develop recurrent disease. The distinction between pT2 with positive margins and pT3a can be difficult. Aim of the present study was to assess the impact of positive surgical margins on biochemical relapse after radical prostatectomy, adjusted for pathological stage and Gleason score., Methods: We retrospectively evaluated 837 consecutive patients who underwent radical prostatectomy for organ-confined or locally-advanced prostate cancer. Exclusion criteria were: presence of node or distant metastases, neo-adjuvant or adjuvant therapy, and unavailability of full data regarding pathological stage and margin status. A single dedicated genitourinary pathologist evaluated all the specimens. The Kaplan-Meier method and univariable and multivariable Cox regressions were applied for survival analyses., Results: The median follow up was 54.0 ± 35.0 months. Margin status, prostate-specific antigen and Gleason score significantly predicted biochemical relapse in the pT2 group at multivariable analysis, whereas only pathological stage and pathological Gleason score were significant predictors of recurrence in pT3a patients. There were no significant differences in biochemical disease-free survival among pT2 with positive margins patients and pT3a patients (with or without positive surgical margins). Pathological Gleason score was the only significant predictor of biochemical relapse in patients with negative and positive margins, regardless of the pathological stage., Conclusions: pT2 patients with positive surgical margins and pT3a (with or without positive margins) seem to have similar biochemical disease-free survival. Positive margins and pathological stage might be insufficient clinical predictors. Gleason score remains the most reliable prognostic factor., (© 2013 The Japanese Urological Association.)

Objectives: To evaluate the outcomes in patients with node-positive prostate cancer (PCa) after radical prostatectomy (RP) and pelvic lymph node dissection (PLND) according to the number of positive lymph nodes (LNs). To identify different risk groups among patients with node-positive PCa., Patients and Methods: We evaluated 98 consecutive patients with pN1M0 PCa who underwent RP between November 1995 and May 2011. Kaplan-Meier and Cox proportional univariable and multivariable regression models were used to analyse the survival rates. Patients were divided into two groups according to number of positive LNs using the most informative positive LN theshold for predicting survival, then into three different risk groups according to number of positive LNs and pathological Gleason score (GS)., Results: Mean (range) follow-up was 68.4 (10-192) months. Patients with 1-3 positive LNs (n = 75; 76.5%) had significantly better cancer-specific survival (CSS) and overall survival (OS) compared with those with >3 positive nodes (n = 23; 23.4%; P < 0.01). Patients with 1-3 positive LNs and pathological GS ≤7 (Group 1) had significantly better CSS than those with >3 positive LNs or GS 8-10 (Group 2 [P = 0.015]). Group 2 patients, moreover, had significantly better CSS (P = 0.019) and OS (P = 0.021) than those with >3 positive LNs and GS 8-10 (Group 3)., Conclusions: Patients with 1-3 positive LNs have higher CSS and OS rates than those with >3 metastatic LNs. Taking into account the pathological GS, as well as the number of positive nodes, three risk group categories with considerable differences in terms of survival can be found. Patients with LN-positive PCa should be stratified into different groups according to these two measures, to obtain a better prediction of oncological outcomes., (© 2013 BJU International.)

Background: We describe the results of the application of the Italian donor cancer screening protocol to all the 7608 candidate multiorgan donors presented in Italy in 2002-2005., Methods: All suspect findings raised in the two presurgical and surgical phases of the protocol were investigated by extemporary pathologic evaluation. Donors were classified as standard risk (no transmissible risk); nonstandard risk (low-risk of transmission, eligibility restricted to certified clinical emergencies pending informed consent); and unacceptable risk (unconditional exclusion because of high-risk pathologies)., Results: The protocol was successfully implemented for all 7608 candidates. In addition to 8 (0.1%) independent exclusions, clinical suspicion of cancer was raised for 337 (4.6%) donors. According to pathological examination 198 donors (2.6%) were judged at unacceptable risk of tumor transmission; 80 (1%) were included in the "standard risk". Used standard risk and nonstandard risk donors provided a total of 241 organs in 231 recipients. Although no suspect was raised after implementation of the protocol, a malignant tumor was discovered after organ transplantation in 14 (0.2%) donors. All the recipients transplanted with organs from ascertained nonstandard risk donors or from neoplastic donors who donated by accident have been carefully followed. At the time of most recent follow-up no donor/recipient tumor transmission has been reported., Conclusions: Implementation of the multiorgan cancer screening protocol is feasible at a national level in Italy. In view of the increasing demand for organs our protocol provides a useful tool for rationalization of the use of organs from neoplastic marginal donors.

Reduction of waiting-list length requires extension of the organ-donor pool to elderly males bearing an higher risk of prostate cancer incidence. Prostate-cancer screening in organ donors is currently based on prostate-specific antigen (PSA) assays (total PSA and free/total PSA). However, the specificity of these assays is restricted, limiting risk-benefit analysis. Since 2001, 33 multiorgan donor candidates presenting within Emilia-Romagna (Italy) with suspect ultrasonography or abnormal PSA values were submitted to a histopathologic screening method of the entire prostate based on extemporary frozen-section analysis (maximum 1 hour) of over 50% of the organ at 0.1 mm cutting levels. Extemporary diagnosis of adenocarcinoma was made in 12 (36%) cases, corresponding to 4.5% of the male candidates aged more than 50 years in the donor pool. In all cases, the final diagnosis confirmed the extemporary analysis. As well as maximizing safety, this novel approach should permit more refined risk-benefit analysis.

Background: We describe the Emilia-Romagna screening protocol for all multiorgan donors within this region of Italy and report on the first 2 years of implementation., Setting: Setting is a 24-hour multidisciplinary call service covering the 16 intensive care units in Emilia-Romagna (3,969,000 inhabitants) and a centralised pathology center, directed by a transplant coordination center. STUDY POPULATION AND PERIOD: All 271 effective donor candidates presenting in Emilia-Romagna in 2001-2002., Protocol: Anamnesis, external examination, and thorough laboratory and instrumental screening is followed by sampling of internal effusions and evaluation of all internal organs. All suspect findings are then investigated by extemporary pathologic evaluation. To fit national legal requirements, candidates are classified as standard risk (no transmissible risk); nonstandard risk (low-risk of transmission, eligibility restricted to certified clinical emergencies pending informed consent); and unacceptable risk (unconditional exclusion because of high-risk pathologies)., Results: The protocol was successfully implemented for all 271 candidates. In addition to 14 independent exclusions, clinical suspicion of cancer was raised for 61 donors presenting with 82 lesions or effusions. Along with one case of lymph-node tuberculosis (unacceptable risk), histocytologic screening revealed eight cases of malignancy (5 prostate, 1 papillary-thyroid, 1 follicular-thyroid, and 1 renal cell, all nonstandard risk); the remainder were benign (standard risk). Protocol implementation led to exclusion of 8 (3.0%) candidates (1 nonstandard risk transplantation was performed)., Conclusions: This stringent protocol-now adopted with some modifications at a national level-provides an initial example of a feasible intervention aimed at maximising donation safety while rationalizing use of marginal donors.