Valeria Ascoli

Purpose Due to overdiagnosis, the incidence of thyroid cancer (TC) has increased in high-income countries, including Italy. Efforts have been made to address this issue since the mid-2010s, but more information is needed about how TC incidence has changed. We aim to examine the trend in TC incidence in the Lazio Region (central Italy) and assess the impact of the 2014 Italian Consensus for the Classification and Reporting of Thyroid Cytology (ICCRTC) to identify potential changes in TC diagnosis. Methods To identify TC cases, we conducted a population-based study (period 2007–2019) using the data from the Lazio Region Cancer Registry (5.8 million residents). We calculated the annual age-standardized incidence rates of TC for both sexes and analyzed the impact of ICCRTC on monthly incidence rates using segmented linear regression applied to interrupted time-series (ITS). Results Throughout the 13 years, there was a significant decline in TC annual incidence rates, more pronounced in females. Our results are consistent with reports from outside Europe (United States and South Korea). Following ICCRTC implementation in 2014, a step-change reduction in both sexes was revealed. Conclusions Our study indicates a significant decrease in the incidence of TC, particularly among females. The ITS analysis highlights the possible role of ICCRTC in reducing overdiagnosis. As the Lazio Region reflects the Italian population in terms of various demographic, health, and lifestyle indicators, our findings can be applicable at the national level.

Metastatic urothelial carcinoma is a rare cause of pleural effusions. We report a case of urothelial carcinoma of the upper urinary tract in an oldest‐old male patient, a smoker, with situs inversus totalis, that presented uniquely with malignant pleural effusion at presentation without evidence of a primary tumor on imaging. Cytological smears of the massive left pleural effusion revealed epithelioid neoplastic cells arranged in short cords, small‐to‐large clusters, and raspberry‐like morules, mimicking mesothelioma; cell block preparations highlighted the presence of tubules and nest‐like structures. The tumor cells showed a high nuclear‐to‐cytoplasmic ratio, nuclear grooves, and mitotic figures. Cytomorphologic features coupled with the immunophenotype of neoplastic cells (p63, GATA3, and uroplakin II positive) allowed the diagnosis of metastatic urothelial carcinoma and a possible nested subtype. These findings were supported by a total body computed tomography (CT) showing no evidence of a mass in the bladder or elsewhere in the urinary tract but a concentric parietal thickening of the proximal left ureter, suggesting malignancy. To our knowledge, a malignant effusion as a primary manifestation of urothelial carcinoma with nest‐like features originating in the upper urinary tract has never been described previously. Our case focuses on the value of cell block in the working‐up of neoplastic effusions by revealing the architectural pattern of an uncommon malignancy and the correlation between cytopathology and imaging gross findings to reach an accurate diagnosis.

Introduction: The asbestos industry began its operations in Colombia in 1942 with the establishment of an asbestos-cement facility in Sibaté, located in the Department of Cundinamarca. Despite extensive asbestos use and production in Colombia, the country lacks a reliable epidemiological surveillance system to monitor the health effects of asbestos exposure. The Colombian health information system, known as SISPRO, did not report mesothelioma cases diagnosed in the municipality, posing a significant challenge in understanding the health impacts of asbestos exposure on the population of Sibaté. Methods: To address this issue, an active surveillance strategy was implemented in Sibaté. This strategy involved conducting door-to-door health and socioeconomic structured interviews to identify Asbestos-Related Diseases (ARDs). Validation strategies included a thorough review of medical records by a panel of physicians, and the findings were communicated to local, regional, and national authorities, as well as the general population. Results: The active surveillance strategy successfully identified a mesothelioma cluster in Sibaté, revealing the inadequacy of the existing health information system in monitoring asbestos-related diseases. The discovery of this cluster underscores the critical importance of implementing active surveillance strategies in Colombia, where governmental institutions and resources are often limited. Conclusion: The findings of this study emphasize the urgent need for Colombia to establish a reliable epidemiological surveillance system for asbestos-related diseases (ARDs). Active surveillance strategies can play a crucial role in identifying mesothelioma clusters and enhancing our understanding of the health effects of asbestos exposure in low- and middle-income countries.

Primary effusion lymphoma (PEL) is a large B-cell lymphoma growing within body-cavities caused by the Kaposi sarcoma-associated herpesvirus (KSHV)/human herpesvirus-8 (KSHV/HHV-8). It is mainly reported in HIV-infected patients. The uncommon occurrence in the elderly supports a form paralleling classic Kaposi sarcoma (KS), i.e. classic PEL, whose characteristics are relatively underexplored. To better understand the diagnostic modalities and clinical-epidemiological features of classic PEL, articles reporting cases of PEL were identified through MEDLINE/EMBASE databases (January 1998-July 2020) and screened according to PRISMA guidelines to extract individual-level data. A comparison was also performed between classic PEL and classic KS to evaluate similarities and differences. We identified 105 subjects (median age 77 years; 86% males), mainly from Mediterranean countries (52%, first Italy) and Eastern Europe (7%). Common comorbidities were heart failure (32%), cirrhosis (16%), and malignancy (20%) including lymphoid neoplasms. Pleural cavity was the commonest site (67%). PEL diagnosis was based on cytomorphology (89%), evidence of KSHV/HHV-8 infection (94%), EBV co-infection (28%) and clonality of IGH (59%), IGK (14%), TRG (9%) alone or in multiple combinations. Compared to KS, age (P<.001), gender-ratio (P=.08) and mortality (P<.001) were significantly higher in PEL, whereas the frequency of PEL as a second primary was similar (P=.44). This is the first systematic review of classic PEL case reports highlighting heterogeneity and lack of a uniform multidisciplinary approach at diagnosis, in the absence of specific guidelines as it happens for rare cancers. It is conceivable that classic PEL is still underdiagnosed in Mediterranean countries wherein KSHV/HHV-8 is endemic.

BACKGROUND: Primary effusion lymphoma (PEL) is a very rare non‐Hodgkin lymphoma caused by human herpesvirus‐8 (HHV8) that grows in liquid phase within body cavities. The diagnosis of PEL is based on cytology but requires confirmatory ancillary tests. PEL occurs mainly in association with HIV infection. This study describes 9 cases of PEL in HIV‐negative patients and compares their characteristics with 10 HIV‐associated cases of PEL diagnosed at a single institution in Italy between 1995 and 2019.METHODS: Clinical records were reviewed for demographic data, comorbidities, laboratory abnormalities, and outcome. PEL samples were evaluated for cytomorphology, immunophenotype, immunoglobulin (IG)/T cell receptor (TR) rearrangements, and HHV8 and Epstein‐Barr virus (EBV) viral loads in effusion supernatants.RESULTS: HIV‐unrelated PEL occurred in 8 elderly patients (7 men, 1 woman) and 1 young adult with primary antibody deficiency. Cytology revealed HHV8‐positive lymphoma cells lacking B/T cell antigens and exhibiting 2 cell patterns (polymorphous or monotonous). IG was clonally rearranged in all cases; aberrant TRG occurred in 2 cases. Effusion supernatants had more than 10⁶ HHV8 DNA copies per mL and variable loads of EBV DNA. Compared with HIV‐associated PEL, the HIV‐negative cohort was characterized by older age, less frequent association with Kaposi sarcoma and/or multicentric Castleman disease, comparable but less abnormal laboratory parameters, and a nonsignificant survival benefit. PEL cases with low apoptosis were associated with better prognosis.CONCLUSION: To the best of our knowledge, our case series of HIV‐unrelated PEL is the largest thus far, expands the spectrum of cytological findings, and supports the need for a multidisciplinary approach in the diagnostic workup.

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a very rare CD30-positive ALK-negative T-cell non-Hodgkin lymphoma included as a provisional entity in the 2017 WHO classification of lymphoid neoplasms. BIA-ALCL arises as proliferating cells over the surface of the implant. It is generally an indolent disease if confined within the fibrous capsule. In contrast, mass and/or infiltration beyond the capsule is much more aggressive. This report describes a case of infiltrative BIA-ALCL with massive pleural effusion containing hallmark BIA-ALCL cells showing the characteristic morphologic appearance of high-grade anaplastic lymphoma, CD30-positive but ALK-negative with variable staining for T-cell antigens. Detailed cytological features of BIA-ALCL in pleural fluid are described along with the results of a literature search performed for BIA-ALCL cases with pleural effusion. This report expands the spectrum of BIA-ALCL pathology to include chest wall involvement and pleural effusion.

Objective: The Italian reporting system for thyroid cytology classifies indeterminate lesions as TIR3A (low risk) or TIR3B (high risk) and is meant to provide practical guidance rather than a detailed consideration of morphological features. We aimed to assess which cytological features have the most diagnostic value and whether they are effective in classifying nodules as either TIR3A or TIR3B and in predicting histological outcomes.Methods: Thyroid fine‐needle aspirates from 111 indeterminate nodules were reviewed blinded to clinical information, TIR3A/TIR3B classification, and histology in order to assess which cytological features (pooled into artefacts, smear background, architectural and nuclear atypia, and oncocytes) differentiate TIR3A from TIR3B, and benign from malignant histological outcomes.Results: Of the cytological features examined, those specific for TIR3B included high cellularity, nuclear atypia, oncocyte predominance and transgressing vessels. Features specific for TIR3A included artefacts, low cellularity and oncocyte sparseness. Other features, such as microfollicules/trabeculae, were non‐specific. Due to the different distributions of these features, three TIR3B subgroups were identifiable: follicular lesions with oncocytic changes, pure follicular lesions, and follicular lesions with nuclear atypia, whereas no subgroups were identifiable in TIR3A. Nuclear atypia was a significant indicator of malignancy, whereas oncocyte predominance was not a reliable predictor of malignancy. High cellularity and microfollicules/trabeculae were not indicative of any histological outcome.Conclusions: The majority of the assessed features were good predictors of histological outcomes. The TIR3A category included undefined nodules due to the absence of characterising features, whereas the TIR3B category included nodules with a greater number of distinguishing features.

Background: The important diagnostic challenge facing the cytopathologist is whether a mesothelial proliferation on effusions represents a malignant mesothelioma (MM) or a benign mesothelial hyperplasia (MH). Here, we evaluated the diagnostic utility of BAP1 immunohistochemistry (IHC) in distinguishing between reactive and neoplastic mesothelial cells.Methods: In pleural and peritoneal effusions from 147 patients with diagnosed MM or with a differential diagnosis of MM and MH, the expression of BAP1 was examined by IHC on paraffin‐embedded cell blocks (n = 121) and biopsies (n = 44). Included were also synchronous and methacronous cytology/biopsy pair samples. BAP1 IHC was evaluated for nuclear staining as positive or negative on target mesothelial cells, with appropriate internal control.Results: In MM cases, loss of BAP1 nuclear staining was observed in 76.5% of the cell blocks and 47.5% of the biopsies. All BAP1‐negative cases with a differential diagnosis of benign and malignant mesothelial proliferations were MM at follow‐up. All MH cases, the 29% of epithelial MM and the 90% of nonepithelial MM, retained BAP1 expression. Synchronous and methacronous biopsy/cytology pairs showed matching BAP1 results.Conclusion: In effusions with mesotheliomatous cells or atypical mesothelial cells of uncertain significance, negative BAP1 IHC strongly supports a diagnosis of MM. With prudence in interpreting immunostaining, BAP1 may be included in IHC panels for MM cytodiagnosis, given its high specificity and sensitivity.