49 research outputs found
MULTIPLE RENAL ONCOCYTIC TUMORS: HISTOLOGICAL, IMMUNOHISTOCHEMICAL AND CYTO-GENETICAL COMPARATIVE ANALYSIS
No full textOvarian Clear Cell Carcinoma: From Morphology to Molecular Biology
No full textOvarian clear cell carcinoma (oCCC) is a distinctive subtype of ovarian carcinoma, with peculiar genetic and environmental risk factors, precursor lesions, molecular events during oncogenesis, patterns of spread, and response to treatment. Because of low response to chemotherapy and poor prognosis in advanced stages, there is growing interest in investigating the molecular pathways involved in oCCC development, in order to individualize novel/molecular targeted therapies. Until now, the main molecular genetic changes associated with oCCC remain to be identified, and, although several molecular changes have been reported in clear cell tumors, most studies have analyzed a limited number of cases; therefore, the true prevalence of those changes is not known. The present review will present the clinicopathologic features of oCCC, from morphology to molecular biology, discussing the diagnostic and treatment challenges of this intriguing ovarian carcinoma
Validation of full-remote reporting for cervicovaginal cytology: the Caltagirone-Acireale distributed lab
No full textIntroduction: Cervical cancer is the fourth most common cancer in women, and its prevention is based on vaccination and screening. Screening consists of molecular human papillomavirus (HPV) testing and cytologic analysis of cervical smears, which require expensive equipment and the interaction of numerous professionals such as biologists, cytologists, laboratory technicians, and pathologists. Materials and methods: We centralize the cervical samples from more than 51 clinics in 1 main laboratory, where automated HPV testing is performed. HPV-positive cases are collected and used to prepare a liquid-based cytology slide, which is stained and immediately scanned. The resulting whole-slide images (WSIs) are immediately available in a remote laboratory where they are examined by experienced cytologists using virtual microscopy. This setup was validated by making each of the 3 readers independently diagnose 506 specimens in random order, using both conventional light microscopy (CLM) and WSIs, with a minimum wash-out period of 3 weeks and with a final discussion for all cases. Results: Intraobserver agreement among CLM and WSI ranged from 0.71 to 0.79, and interobserver agreement for the 3 readers compared with the consensus diagnosis was similar for the 2 modes of assessment. Readers subjectively felt confident in their WSI diagnosis for inadequate and negative cases, but less so in other cases. The perceived difficulty was slightly higher in WSI readings. Conclusions: Interobserver agreement in cervicovaginal cytology is moderate and does not vary if the slides are examined conventionally or digitally. Despite higher reported subjective difficulty and lower confidence in the WSI diagnosis, we did not observe a deterioration in diagnostic performance using WSI compared with CLM
Renal oncocytosis: a clinicopathological and cytogenetic study of 42 tumours occurring in 11 patients
No full textRenal oncocytosis is a rare pathological condition characterised by the presence of multiple oncocytic tumours with a spectrum of histological features ranging from renal oncocytoma, hybrid oncocytic tumour and rarely chromophobe renal cell carcinoma, sometimes overlapping. Here we retrospectively analysed histological, immunohistochemical (IHC), and cytogenetic features of 42 lesions in 11 patients with renal oncocytosis, not associated with Birt-Hogg-Dubé syndrome. The histology of all the lesions was blindly reviewed by three dedicated genitourinary pathologists. IHC for cytokeratin 7 (CK7) and fluorescence in situ hybridisation (FISH) for copy number variation of chromosomes 1, 6, 7 and 17 were performed in all 42 nodules. Among the 42 lesions 36 (85.7%) were histologically renal oncocytomas, two (4.76%) 'hybrid oncocytic tumours' (HOT), one (2.4%) clear cell renal cell carcinoma (ccRCC), one (2.4%) papillary renal cell carcinoma (pRCC), one typical angiomyolipoma (2.4%), and one mixed epithelial/stromal tumour of the kidney (2.4%). FISH analysis confirmed the histological diagnosis of all the lesions. We show that most patients with renal oncocytosis harbour benign or low malignant potential tumours that can be treated conservatively
Cerebellar Metastasis From Ovarian Carcinoma Harboring PIK3CA-Activating Mutation: A “Clear” Explanation for Unexpected “Vertigo”
No full textBrain metastasis is a rare and generally late manifestation of an advanced-stage, high-grade serous ovarian carcinoma. Nowadays, the improved control of intra-abdominal disease by surgery and platinum-based chemotherapy results in a longer survival, allowing distant metastasis to implant and grow in the brain parenchyma. Herein, we describe a unique case of a cerebellar metastasis from clear cell ovarian carcinoma that initially presented as a FIGO Stage IC cancer. Surprisingly, 6 mo after surgery, the patient was in good condition with complete disappearance of symptoms and no evidence of recurrence. This relatively good biologic behavior may be explained by the presence of a PIK3CA-activating mutation in exon 9 which as previously reported in the literature, may be associated with better prognosis. To the best of our knowledge, this is the first reported case of cerebellar metastasis from ovarian clear cell carcinoma. In the presence of neurological symptoms, both clinicians and pathologists must be aware of this rare possibility, to assure correct patient management and effective therapeutic options. Generally, the prognosis of epithelial ovarian cancer patients with brain metastases is poor. PIK3CA mutations could be a good prognostic indicator in clear cell carcinomas
Spatial resolution of renal amyloid deposits through MALDI-MSI: a combined digital and molecular approach to monoclonal gammopathies
No full textAims: Identification and characterisation of monoclonal gammopathies of renal significance (MGRS) is critical for therapeutic purposes. Amyloidosis represents one of the most common forms of MGRS, and renal biopsy remains the gold standard for their classification, although mass spectrometry has shown greater sensitivity in this area. Methods: In the present study, a new in situ proteomic technique, matrix-assisted laser desorption/ionisation mass spectrometry imaging (MALDI-MSI), is investigated as an alternative to conventional laser capture microdissection MS for the characterisation of amyloids. MALDI-MSI was performed on 16 cases (3 lambda light chain amyloidosis (AL), 3 AL kappa, 3 serum amyloid A amyloidosis (SAA), 2 lambda light chain deposition disease (LCDD), 2 challenging amyloid cases and 3 controls). Analysis began with regions of interest labelled by the pathologist, and then automatic segmentation was performed. Results: MALDI-MSI correctly identified and typed cases with known amyloid type (AL kappa, AL lambda and SAA). A 'restricted fingerprint' for amyloid detection composed of apolipoprotein E, serum amyloid protein and apolipoprotein A1 showed the best automatic segmentation performance (area under the curve >0.7). Conclusions: MALDI-MSI correctly assigned minimal/challenging cases of amyloidosis to the correct type (AL lambda) and identified lambda light chains in LCDD cases, highlighting the promising role of MALDI-MSI for amyloid typing
EGFR mutant allelic-specific imbalance assessment in routine samples of non-small cell lung cancer
No full textIn non-small cell lung cancer (NSCLC), the epidermal growth factor receptor (EGFR) gene may undergo both mutations and copy number gains. EGFR mutant allele-specific imbalance (MASI) occurs when the ratio of mutant-to-wild-type alleles increases significantly. In this study, by using a previously validated microfluidic-chip-based technology, EGFR-MASI occurred in 25/67 mutant cases (37%), being more frequently associated with EGFR exon 19 deletions (p=0.033). In a subset of 49 treated patients, we assessed whether MASI is a modifier of anti-EGFR treatment benefit. The difference in progression-free survival and overall survival between EGFR-MASI-positive and EGFR-MASI-negative groups of patients did not show a statistical significance. In conclusion, EGFR-MASI is a significant event in NSCLC, specifically associated with EGFR exon 19 deletions. However, EGFR-MASI does not seem to play a role in predicting the response to first-generation EGFR small molecules inhibitors
Androgen deprivation modulates gene expression profile along prostate cancer progression
No full textAndrogen deprivation therapy (ADT) is the standard of care for metastatic prostate cancer and initially induces tumor regression, but invariably results in castration-resistant prostate cancer through various mechanisms, incompletely discovered. Our aim was to analyze the dynamic modulation, determined by ADT, of the expression of selected genes involved in the pathogenesis and progression of prostate cancer (TMPRSS2:ERG, WNT11, SPINK1, CHGA, AR, and SPDEF) using real-time polymerase chain reaction in a series of 59 surgical samples of prostate carcinomas, including 37 cases preoperatively treated with ADT and 22 untreated cases, and in 43 corresponding biopsies. The same genes were analyzed in androgen-deprived and control LNCaP cells. Three genes were significantly up-modulated (WNT11 and AR) or down-modulated (SPDEF) in patients treated with ADT versus untreated cases, as well as in androgen-deprived LNCaP cells. The effect of ADT on CHGA gene up-modulation was almost exclusively detected in cases positive for the TMPRSS2:ERG fusion. The correlation between biopsy and surgical samples was poor for most of the tested genes. Gene expression analysis of separate tumor areas from the same patient showed an extremely heterogeneous profile in the 6 tested cases (all untreated). In conclusion, our results strengthened the implication of ADT in promoting a prostate cancer aggressive phenotype and identified potential biomarkers, with special reference to the TMPRSS2:ERG fusion, which might favor the development of neuroendocrine differentiation in hormone-treated patients. However, intratumoral heterogeneity limits the use of gene expression analysis as a potential prognostic or predictive biomarker in patients treated with ADT
High miR-100 expression is associated with aggressive features and modulates TORC1 complex activation in lung carcinoids
No full textMammalian target of rapamycin (mTOR) is a promising therapeutic target in advanced lung carcinoid patients. However, the mechanisms of mTOR modulation and of responsiveness to mTOR inhibitors are largely unclear. Our aim was to analyze the expression and functional role of specific miRNAs in lung carcinoids as an alternative mechanism targeting mTOR pathway
Multimodal representations of biomedical knowledge from limited training whole slide images and reports using deep learning
No full textThe increasing availability of biomedical data creates valuable resources for developing new deep learning algorithms to support experts, especially in domains where collecting large volumes of annotated data is not trivial. Biomedical data include several modalities containing complementary information, such as medical images and reports: images are often large and encode low-level information, while reports include a summarized high-level description of the findings identified within data and often only concerning a small part of the image. However, only a few methods allow to effectively link the visual content of images with the textual content of reports, preventing medical specialists from properly benefitting from the recent opportunities offered by deep learning models. This paper introduces a multimodal architecture creating a robust biomedical data representation encoding fine-grained text representations within image embeddings. The architecture aims to tackle data scarcity (combining supervised and self-supervised learning) and to create multimodal biomedical ontologies. The architecture is trained on over 6,000 colon whole slide Images (WSI), paired with the corresponding report, collected from two digital pathology workflows. The evaluation of the multimodal architecture involves three tasks: WSI classification (on data from pathology workflow and from public repositories), multimodal data retrieval, and linking between textual and visual concepts. Noticeably, the latter two tasks are available by architectural design without further training, showing that the multimodal architecture that can be adopted as a backbone to solve peculiar tasks. The multimodal data representation outperforms the unimodal one on the classification of colon WSIs and allows to halve the data needed to reach accurate performance, reducing the computational power required and thus the carbon footprint. The combination of images and reports exploiting self-supervised algorithms allows to mine databases without needing new annotations provided by experts, extracting new information. In particular, the multimodal visual ontology, linking semantic concepts to images, may pave the way to advancements in medicine and biomedical analysis domains, not limited to histopathology
