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Surgical resection for hepatocellular carcinoma (HCC) is burdened with a high recurrence rate and a lack of reliable prognostic factors. The aim of this study was to integrate the HCC pathological features with gene mutations to improve the prognostic role of pathological analysis. This is a monocentric prospective study, including 67 patients resected for HCC. All clinical data and histological features were collected, including tumor grade, architecture, margins, microvascular invasion, and microscopic portal vascular invasion (MPVI). Next-generation sequencing (NGS) was performed using a laboratory-developed multi-gene panel, allowing to amplify 330 amplicons (21.77 kb), covering the relevant targets for solid tumor analysis. The most represented mutations were TERT promoter (n = 41, 61.2%), TP53 (n = 18, 26.9%) and CTNNB1 (n = 17, 25.4%). At follow-up, 13 (19.4%) patients experienced HCC recurrence: at multivariate analysis, tumor dimensions (p = 0.040), MPVI (p = 0.010), and TERT mutation (p = 0.034) correlated with recurrence. Dimensions ≥ 4.5 cm (very close to AJCC stage pT3; 9 recurrences, p = 0.041, odd-ratio = 3.7), MPVI (9 recurrences, p = 0.062, OR = 3.3), and TERT (11 recurrences, p = 0.049, OR = 4.4) correlated with disease-free survival also at univariate analysis. The concomitant occurrence of these three variables was present in 7 cases, among which 5 recurred (p = 0.002, OR = 15.94). In conclusion, NGS analysis in resected HCC could not only be used for future therapies but should be integrated with histopathology to predict the risk of tumor recurrence after surgical resection: TERT mutation is among the strongest predictors of tumor recurrence, together with tumor stage (dimensions) and the occurrence of MPVI, which should always be reported separately from the classic MVI., (© 2024. The Author(s).)

One of the goals of pathology is to standardize laboratory practices to increase the precision and effectiveness of diagnostic testing, which will ultimately enhance patient care and results. Standardization is crucial in the domains of tissue processing, analysis, and reporting. To enhance diagnostic testing, innovative technologies are also being created and put into use. Furthermore, although problems like algorithm training and data privacy issues still need to be resolved, digital pathology and artificial intelligence are emerging in a structured manner. Overall, for the field of pathology to advance and for patient care to be improved, standard laboratory practices and innovative technologies must be adopted. In this paper, we describe the state-of-the-art of automation in pathology laboratories in order to lead technological progress and evolution. By anticipating laboratory needs and demands, the aim is to inspire innovation tools and processes as positively transformative support for operators, organizations, and patients., (© 2023. The Author(s).)

Liver biopsy is crucial for the diagnosis of autoimmune hepatitis (AIH), and new reproducible histological criteria would be highly desirable, especially in acute-on-chronic cases. The aims of the present study were (i) to evaluate the AIH histopathological criteria as a function of the time and modality of AIH onset, and (ii) to validate the count of apoptotic bodies in the portal tracts as a histopathological criterion for AIH diagnosis. Sixty-five patients were retrospectively enrolled: 20 underwent biopsy for the first diagnosis and 45 had a previous histological AIH diagnosis. Biopsies were revised, and all histological variables were collected, including the lymphocytic apoptotic bodies in the portal tracts. Clinical and serological data were revised as well. First-diagnosis patients showed a higher grade of inflammation (p = 0.001), but also worse portal fibrosis (p = 0.001). The apoptotic body count was higher in first-diagnosis patients than in follow-up patients (p = 0.002), and it was strongly correlated to inflammation. Using the apoptotic body count among the simplified AIH score variables, the first-biopsy patients in the "definite" category rose from 42 to 68%. Our results confirm the histopathological criteria proposed by the literature and introduce the count of portal apoptotic bodies for the diagnosis of active AIH, especially in first biopsies without other classic features, as well as in AIH diagnostic score, albeit future studies are required to find a definite cutoff., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Arterial calcification is an actively regulated process, with different morphological manifestations. Micro-RNAs emerged as potential regulators of vascular calcification; they may become novel diagnostic tools and be used for a finest staging of the carotid plaque progression. The present study aimed at characterizing the different miRNA-mRNA axes in carotid plaques according to their histological patterns of calcification. Histopathological analysis was performed on 124 retrospective carotid plaques, with clinical data and preoperatory angio-CT. miRNA analysis was carried out with microfluidic cards. Real-time PCR was performed for selected miRNAs validation and for RUNX-2 and SOX-9 mRNA levels. CD31, CD68, SMA, and SOX-9 were analyzed by immunohistochemistry. miRNA levels on HUVEC cells were analyzed for confirming results under in vitro osteogenic conditions. Histopathological analysis revealed two main calcification subtypes of plaques: calcific cores (CC) and protruding nodules (PN). miRNA array and PCR validation of miR-1275, miR-30a-5p, and miR-30d indicated a significant upregulation of miR-30a-5p and miR-30d in the PN plaques. Likewise, the miRNA targets RUNX-2 and SOX-9 resulted poorly expressed in PN plaques. The inverse correlation between miRNA and RUNX-2 levels was confirmed on osteogenic-differentiated HUVEC. miR-30a-5p and miR-30d directly correlated with calcification extension and thickness at angio-CT imaging. Our study demonstrated the presence of two distinct morphological subtypes of calcification in carotid atheromatous plaques, supported by different miRNA signatures, and by different angio-CT features. These results shed the light on the use of miRNA as novel diagnostic markers, suggestive of plaque evolution.

Epidemiological and biological evidence indicates a causal relationship between the presence of proliferative atrophic lesions and the development of prostatic intraepithelial neoplasia (PIN) and prostate cancer. The presence of inflammatory and atrophic lesions of the prostate is widely underestimated and they are not generally mentioned in pathology reports. We performed a histopathological concordance study among eight genitourinary specialists and seven generalist pathologists, using 116 histological slides of prostate lesions, including proliferative atrophic lesions, PIN, and cancer. The overall agreement between all possible pairs of reviewers was 80% for prostate cancer, 67% for PIN, and 49% for proliferative atrophic lesions. When using as gold standard the assessment of a single genitourinary pathologist, the mean agreement percentage increased to 97% for prostate cancer, 92% for PIN, and 72% for proliferative atrophic lesions.

The organic anion transporter peptides (OATP) 1B1 and 1B3 are hepatocytic-specific transporters determinant for the uptake of the contrast media Gd-EOB-DTPA during magnetic resonance, but variably lost in hepatocellular carcinoma (HCC). Here, we studied a series of HCCs from livers that underwent liver transplantation (OLT) and correlated the expression of OATP 1B1/1B3 with HCC morphological features and the expression of the biliary-type keratins K7 and K19, the latter previously correlated with a worse prognosis after OLT. Seventy-five HCCs from 69 OLT patients were evaluated by histology and immunohistochemistry with monoclonal antibodies against OATP 1B1/1B3, K7, and K19. Histopathological and immunohistochemical features were therefore compared to recipient follow-up data. Thirty-four (45%) HCCs were completely OATP-, and 18 (24%) showed positivity for K7 and/or K19. We observed a significant inverse correlation between OATP and K7/19 expression (P < 0.001): all OATP+ cases were K7/19-, while all K7+ and/or K19+ cases were OATP-. Sixteen cases were negative for all antibodies. No correlation was found between histopathological features and immunohistochemistry. Twenty-five recipients experienced HCC recurrence, and ten died from neoplastic recurrence. Neither OATP nor keratin expressions were correlated with HCC recurrence, while OATP negativity significantly correlated with HCC-related death after recurrence (P = 0.036). In conclusion, HCCs show a progressive loss in OATP immunoreactivity that correlates with the gain of a biliary phenotype. Although further studies are required to define these findings better, our results support the idea that OATP could be used together with K7/19 to identify a phenotypical "spectrum" in HCC progression.

Merkel cell carcinoma (MCC) of the skin is a neuroendocrine tumor with characteristic histological and immunohistochemical features. Among various cytogenetic changes, trisomy of chromosome 6 has been reported in 47% of cases using in situ hybridization. Primary tumors, morphologically and immunohistochemically identical to MCCs of the skin, have been described in other organs, including lymph nodes. Here, a cytogenetic study of four cases of MCC of lymph nodes is presented. Four cases of primary MCCs of lymph nodes and ten cases of cutaneous MCCs were studied for chromosome 6 using fluorescent in situ hybridization (FISH). All cases showed typical features of MCC both at hematoxylin and eosin (H&E) and immunohistochemistry. FISH showed trisomy 6 in two out of the four cases ofMCCs of lymph node as well as in 6 out 10 cases of MCCs of skin. Lymph nodal and cutaneous MCCs share same histological and immunohistochemical features, as well as same cytogenetic alteration for chromosome 6. It seems that there are more similarities than differences between cutaneous and lymph nodal MCCs. Whether lymph nodal MCCs are primary tumors or metastases from regressed skin lesions is still questionable, although several findings indicate a primary origin.