Ressenyes

Index de les obres ressenyades: Carlo GINZBURG, El queso y los gusanos. El cosmos según un molinero del siglo XV

Cristo si è fermato a Eboli Gagliano e il parco letterario di Aliano : metamorfosi di una memoria

La relazione fra Carlo Levi, la sua opera Cristo si é fermato a Eboli ed il paese di Aliano ha subito dei cambiamenti dal momento della pubblicazione del libro (1945) fino all'istituzione del Parco Letterario Carlo Levi (2001). L'esperienza e il ricordo del confino influenzarono molto la formazione dell'intellettuale antifascista e marcarono profondamente le sue successive scelte letterarie e politiche. Di pari intensità fu la reazione che il libro suscitò nel piccolo centro lucano. Passati ormai più di cinquanta anni, l'iniziale posizione critica e distante degli alianesi si é via via modificata fino a permettere, grazie al patrimonio letterario lasciato da Levi, una valorizzione culturale del territorio.The relationship between Carlo Levi, his work Christ Stopped at Eboli and the village of Aliano, has changed a great deal between the first publication of the book in 1945 and the establishment of the Parco Letterario Carlo Levi in 2001. The experience and the memory of Levi's exile in Aliano profoundly affected his intellectual development and deeply influenced both his subsequent literary and political choices. When the book first appeared, it provoked an intense reaction, but fifty years later the initial response from the critics had changed to the extent that an easier and more constructive relationship between people from Aliano, the author and his masterpiece was possible. This process culminated in a cultural endowment called the Parco Letterario Carlo Levi, which aims to improve links between the region territory and its literary heritage

Consumptive hypothyroidism in a patient with malignant rhabdoid tumor of the kidney: case report on a newly found association

Introduction: Consumptive hypothyroidism is a rare paraneoplastic condition most commonly associated with infantile hemangiomas. It is caused by overexpression of deiodinase type 3 (D3), which leads to preferential conversion of thyroxine to the metabolically inactive reverse triiodothyronine (rT3), paralleled by a decrease of the biologically active T3. Case presentation: A 46-year-old male patient with previously normal thyroid function was diagnosed with a renal carcinoma with rhabdoid differentiation. He was treated with sunitinib, followed by the immune checkpoint inhibitors ipilimumab and nivolumab, and he developed primary hypothyroidism secondary to thyroiditis. Substitution with unusually high doses of levothyroxine as high as 4.3 mu g/kg/day did not normalize his thyroid function. Poor compliance was refuted because there was no improvement after observed administration. He had no malabsorption. Although tyrosine kinase inhibitors can increase the expression of D3, this effect tends to be modest. Therefore, the suspicion of tumor-related consumptive hypothyroidism was raised and supported by low free T3 and elevated rT3 levels. The therapy could not be further modified because the patient opted for palliative care and passed away 12 days later.Immunohistochemistry of the tumor from a sample obtained prior to systemic therapy documented abundant expression of D3, corroborating the diagnosis of consumptive hypothyroidism. Conclusions: This observation extends the spectrum of malignancies overexpressing D3. Although rare, increased awareness of this paraneoplastic syndrome is key, if persistent hypothyroidism cannot be explained by compliance issues or malabsorption. Substitution with high doses of levothyroxine, and combination therapy with liothyronine, can correct hypothyroidism in these patients

Microallelotyping defines the monoclonal or the polyclonal origin of mixed and collision endocrine-exocrine tumors of the gut

Mixed endocrine-exocrine tumors of the gut are a heterogeneous group of neoplasms with uncertain histogenesis showing different morphologic and clinical features. The aim of this work is to clarify the histogenesis of these tumors by studying the genetic profile of both the endocrine and exocrine components. We performed an allelotyping analysis of five mixed endocrine-exocrine tumors (two gastric and three colonic) and one rectal collision tumor, using 35 polymorphic microsatellite markers covering a total of six chromosomes, including 3, 5q, 6, 11, 17, and 18. The loss of heterozygosity (LOH) analysis showed concurrent losses of the same allele in both the endocrine and exocrine components in all of the five mixed tumors composed by a poorly differentiated endocrine carcinoma or a well differentiated endocrine carcinoma associated with adenocarcinoma or adenoma. Among these tumors an identical LOH pattern was frequently found on chromosomes 17p, 18q, and 5q. Additional allelic losses restricted to the poorly differentiated endocrine carcinoma were often observed. On the contrary, in the only collision tumor composed by a well differentiated endocrine carcinoma associated with adenocarcinoma, completely different allelotypes between the two components were detected. These findings confirm a close genetic relationship between the two distinct histologic components within mixed endocrine-exocrine tumors, supporting the hypothesis that a monoclonal mechanism of tumorigenesis is the most frequent genetic event in mixed exocrine-endocrine tumors. The clonal divergence observed in the only collision tumor, composed by a well differentiated endocrine carcinoma associated with an adenocarcinoma, confirms the existence of double tumors growing next to each other coincidentally but showing different histogenesis and different tumorigenetic pathway

Exploring the Prognostic Role of Ki67 Proliferative Index in Merkel Cell Carcinoma of the Skin: Clinico-Pathologic Analysis of 84 Cases and Review of the Literature.

The exact prediction of outcome of patients with Merkel cell carcinoma (MCC) of the skin is difficult to determine, although several attempts have been made to identify clinico-pathologic prognostic factors. The Ki67 proliferative index is a well-known marker routinely used to define the prognosis of patients with neuroendocrine neoplasms. However, its prognostic value has been poorly investigated in MCC, and available published results are often contradictory mainly because restricted to small series in the absence of standardized methods for Ki67 evaluation. For this reason, we explored the potential prognostic role of Ki67 proliferative index in a large series of MCCs using the WHO standardized method of counting positive cells in at least 500 tumor cells in hot spot areas on camera-captured printed images. In addition, since MCC may be considered as the cutaneous counterpart of digestive neuroendocrine carcinomas (NECs), we decided to stratify MCCs using the available and efficient Ki67 threshold of 55%, which was found prognostic in digestive NECs. This choice was also supported by the Youden index analysis. In addition, we analyzed the prognostic value of other clinico-pathologic parameters using both univariate and multivariate analysis. Ki67 index appeared significantly associated with prognosis at univariate analysis together with stage IV, lack of MCPyV, and p63 expression, but not at the multivariate analysis, where survival resulted independently influenced by p63 expression and tumor stage, only

Risk perception and affective state on work exhaustion in obstetrics during the COVID-19 pandemic

A multicenter cross-sectional survey study involving four Italian University Hospitals was performed to test the hypothesis that negative affect and positive affect (affective dimensions) mediate the association between risk perception (perceived risk of infection and death; cognitive dimensions) and the feeling of work exhaustion (WE) among obstetrics healthcare providers (HCPs) during the Coronavirus Disease 2019 (COVID-19) pandemic. Totally, 570 obstetrics HCPs were invited to complete the 104-item IPSICO survey in May 2020. A theoretical model built on the tested hypothesis was investigated by structural equation modelling. The model explained 32.2% of the WE variance. Only negative affect mediated the association between cognitive dimensions and WE and also the association between WE and psychological well-being before the pandemic, experiences of stressful events, female gender, and dysfunctional coping. Non-mediated associations with WE were observed for work perceived as a duty, experience of stressful events, support received by colleagues, and the shift strategy. Only previous psychological well-being, support by colleagues, and shift strategies were inversely associated with WE. Based on study results, monitoring negative than positive affect appears superior in predicting WE, with practical implications for planning psychological interventions in HCPs at the individual, interpersonal, and organizational levels

Neuroendocrine neoplasms of the breast: diagnostic agreement and impact on outcome

The classification of breast neuroendocrine neoplasms (Br-NENs) was modified many times over the years and is still a matter of discussion. In the present study, we aimed to evaluate the diagnostic reproducibility and impact on patient outcomes of the most recent WHO 2019 edition of breast tumor classification, namely, for neuroendocrine tumors (NETs) and neuroendocrine carcinomas (NECs). This multicentric observational study included 287 breast neoplasms with NE differentiation. The cases were blindly classified by three independent groups of dedicated breast and/or endocrine pathologists following the 2019 guidelines. Diagnostic concordance and clinical impact were assessed. We observed only a moderate overall diagnostic agreement across the three centers (Cohen’s kappa 0.4532) in distinguishing NET from solid papillary carcinomas (SPCs) and no special type carcinomas (NST) with NE differentiation. Br-NENs were diagnosed in 122/287 (42.5%) cases, subclassified as 11 NET G1 (3.8%), 84 NET G2 (29.3%), and 27 NEC (9.4%), the latter group consisting of 26 large-cell and 1 small-cell NECs. The remaining 165/287 (57.5%) cases were labeled as non-NEN, including SPC, mucinous, NST, and mixed NE carcinomas. While NET and non-NEN cases had a comparable outcome, the diagnosis of NECs showed negative impact on disease-free interval compared to NETs and non-NENs (p = 0.0109). In conclusion, the current diagnostic classification of Br-NENs needs further adjustments regarding morphological and immunohistochemical criteria to increase the diagnostic reproducibility among pathologists. Our data suggest that, apart from high-grade small- and large-cell NECs, Br-NENs behave like non-NEN breast carcinomas and should be managed similarly

ACTH-producing tumorlets and carcinoids of the lung: clinico-pathologic study of 63 cases and review of the literature.

Adrenocorticotropic hormone (ACTH)-secreting lung carcinoids represent the principal cause of ectopic Cushing syndrome, but the prevalence of ACTH expression and the association between ACTH production and Cushing syndrome in lung carcinoids have scarcely been investigated. In addition, available information on the prognostic meaning of ACTH production is controversial. The aims of this multicentric retrospective study, also including a review of the literature, were to describe the clinico-pathologic features of ACTH-producing lung carcinoids, to assess recurrence and specific survival rates, and to evaluate potential prognostic factors. To identify ACTH production in 254 unselected and radically resected lung carcinoids, we used a double approach including RT-PCR (mRNA encoding for pro-opiomelanocortin) and immunohistochemistry (antibodies against ACTH and β-endorphin). Sixty-three (24.8%) tumors produced ACTH and 11 of them (17.4%), representing 4.3% of the whole series, were associated with Cushing syndrome. The median follow-up time was 71 months. The 10-year overall and specific survival rates were 88.5% and 98.2%, respectively, with difference neither between functioning and nonfunctioning tumors nor between ACTH-positive and ACTH-negative carcinoids. At univariate analysis, histological type (typical or atypical) and Ki67 index significantly correlated with tumor recurrence. The literature review identified 172 previously reported patients with functioning ACTH-secreting lung carcinoids, and the meta-analysis of survival showed that 92% of them were alive after a mean follow-up time of 50 months. Our results demonstrate that ACTH-producing lung carcinoids are not rare, are not always associated with Cushing syndrome, and do not represent an aggressive variant of lung carcinoid