80 research outputs found
Practical Approach to the Diagnosis of the Vulvo-Vaginal Stromal Tumors: An Overview
Background: The category of the "stromal tumors of the lower female genital tract" encompasses a wide spectrum of lesions with variable heterogeneity, which can be nosologically classified on the basis of their morphologic and immunohistochemical profiles as deep (aggressive) angiomyxoma (DAM), cellular angiofibroma (CAF), angiomyofibroblastoma (AMFB) or myofibroblastoma (MFB). Despite the differential diagnosis between these entities being usually straightforward, their increasingly recognized unusual morphological variants, along with the overlapping morphological and immunohistochemical features among these tumours, may raise serious differential diagnostic problems. Methods and Results: The data presented in the present paper have been retrieved from the entire published literature on the PubMed website about DAM, CAF, AFMB and MFB from 1984 to 2021. The selected articles are mainly represented by small-series, and, more rarely, single-case reports with unusual clinicopathologic features. The present review focuses on the diagnostic clues of the stromal tumours of the lower female genital tract to achieve a correct classification. The main clinicopathologic features of each single entity, emphasizing their differential diagnostic clues, are discussed and summarized in tables. Representative illustrations, including the unusual morphological variants, of each single tumour are also provided. Conclusion: Awareness by pathologists of the wide morphological and immunohistochemical spectrum exhibited by these tumours is crucial to achieve correct diagnoses and to avoid confusion with reactive conditions or other benign or malignant entities
Solitary fibrous tumor of the orbital region: report of a case with emphasis on the diagnostic utility of STAT-6
The wide morphological spectrum of deep (Aggressive) angiomyxoma of the vulvo-vaginal region: A clinicopathologic study of 36 cases, including recurrent tumors
Background: Deep angiomyxoma (DAM) is currently included in the category of "specific stromal tumors of the lower female genital tract", along with angiomyofibroblastoma, cellular angiofibroma and myofibroblastoma. Given the high rate of local recurrences, it is crucial to recognize DAM from other tumors that possess indolent behaviour. In the present paper, we analyzed the morphological and immunohistochemical features of 42 surgically-resected vulvo-vaginal DAMs (36 primary and 6 recurrent lesions) in order to widen the morphological spectrum of this uncommon tumor. Methods: A series of 36 cases of surgically-resected primary vulvo-vaginal DAMs were retrospectively collected. Locally recurrent tumors were also available for six of these cases. Results: Out of the primary tumors, 25 out of 36 exhibited the classic-type morphology of DAM. In the remaining cases (11/36 cases), the following uncommon features, which sometimes coexist with one another, were observed: (i) alternating myxoid and collagenized/fibrous areas; (ii) hypercellular areas; (iii) neurofibroma-like appearance; (iv) perivascular hyalinization; (v) microcystic/reticular stromal changes; (vi) "microvascular growth pattern"; (vii) perivascular cuffing; (viii) nodular leiomyomatous differentiation; (ix) hypocellular and fibro-sclerotic stroma. Among the six locally recurrent tumors the following features were observed: (i) classic-type morphology; (ii) hypocellular fibro-sclerotic stroma; (iii) extensive perivascular hyalinization, lumen obliteration and formation of confluent nodular sclerotic masses; (iv) hypercellularity. Immunohistochemically, the neoplastic cells of classic-type DAM in both primary and recurrent tumors were diffusely stained with desmin, suggesting a myofibroblastic nature; in contrast, the neoplastic cells showing elongated fibroblastic-like morphology and set in collagenized/fibrosclerotic stroma in both primary and recurrent tumors were negative or only focally stained with desmin, which is consistent with a fibroblastic profile. Conclusion: Although diagnosis of DAM is usually straightforward if typical morphology is encountered, diagnostic problems may arise when a pathologist is dealing with unusual morphological features, especially hypercellularity, extensive collagenous/fibrosclerotic stroma or neurofibroma-like appearance
Parkin isoforms expression in lung adenocarcinoma
PARK2, also known as parkin, is a gene mutated in autosomal recessive juvenile parkinsonism and it has been shown to exhibit E3 ubiquitin ligase activity. However it seems to fulfill also a wide spectrum of protective functions. Recent studies have demonstrated that parkin is an important regulator of process that maintain mitochondrial quality and it is also implicated in proteasomal degradation of toxic substrates. This gene has been also shown to be genetically altered and/or aberrantly expressed in a wide variety of human cancers including lung cancer (Cesari et al., 2003; Veeriah S. et al., 2010). Although many alternatively spliced isoforms have been identified, until now studies have been focused on the full-length isoform (D’Agata and Cavallaro, 2004). To characterize the role of parkin isoforms in lung tumorigenesis we analyzed their expression pattern in human lung adenocarcinomas. These data were correlated to their expression pattern either in human lung epithelial carcinoma (A549) or in human normal bronchial epithelial (BEAS-2B) cell lines. Western blot and immunofluorescence analyses were performed by using two antibodies recognizing different domains of the full length protein. Immunoblots showed that lung adenocarcinomas express parkin isoforms of 50, 37 and 20 kDa. Their expressions were significantly increased in A549 as compared to BEAS-2B, suggesting that parkin isoforms might be involved in cancer progression. In order to characterize some functions of these isoforms, both cell lines were cultured in complete medium or serum starved medium and treated with the proteasome inhibitor MG132 or with carbonyl cyanide 3- clorophenylhydrazone (CCCP), a uncoupling agent that dissipates the mitochondrial membrane. Data obtained revealed that each treatment affects pattern expression of parkin isoforms. These results suggest that some parkin isoforms might be molecular markers of lung adenocarcinoma
Parkin isoforms expression in gliomas
Parkin (PARK2) is one of the largest genes in the human genome encoding for an E3 ubiquitin ligase. Its mutation is the cause of early-onset Parkinson’s disease, but recently it is linked to other pathologies including cancer. Parkin acts as a tumor suppressor. It displays a wide neuroprotective activity by promoting the removal of damaged mitochondria via mitophagy and increasing proteasomal degradation of toxic substrates. PARK2 primary transcript undergoes to an extensive alternative splicing, which enhances transcriptomic diversification and protein diversity in tissues and cells. To date, GenBank lists 26 human PARK2 transcripts corresponding to 21 different alternative splice variants. These transcripts show different expression patterns and encode for proteins with different functions, molecular weight and isoelectric point. Previous studies identified inactivating somatic mutations and frequent intragenic deletions of PARK2 in human cancers including gliomas (Veeriah et al., 2010). Recently, it has been demonstrated that Parkin pathway activation is predictive for the survival outcome of patients with glioma (Yeo et al., 2012). However, these papers focused on the expression of full length Parkin. In the present work we analyzed the expression pattern of Parkin isoforms in astrocytomas of different grade and we investigated their functions in a human glioblastoma multiforme cell line. Immunoblotting analysis by using two specific antibodies revealed that Parkin expression is generally higher in malignant glioblastoma than in less invasive astrocytomas, indicating a correlation between expression pattern of Parkin isoforms and tumor malignancy. Serum deprivation or treatment with a proteosome inhibitor MG132 or with carbonyl cyanide 3-chlorophenylhydrazone (CCCP), an uncoupling agent that dissipates the cells mitochondrial membrane potential, increased expression of 100-55-50 kDa parkin isoforms in glioma cells as compared to controls. These results, consistent with other studies, demonstrated a functional connection between Parkin expression, mitochondrial integrity and endoplasmic reticulum stress (Bouman et al., 2011). Parkin isoforms expression was also confirmed by confocal microscopy analysis. These results suggest that the characterization of some PARK2 isoforms may be usefull clinically to develop a prognostic tool in patients with brain tumor
The cancer patient and cardiology
Advances in cancer treatments have improved clinical outcomes, leading to an increasing population of cancer survivors. However, this success is associated with high rates of short- and long-term cardiovascular (CV) toxicities. The number and variety of cancer drugs and CV toxicity types make long-term care a complex undertaking. This requires a multidisciplinary approach that includes expertise in oncology, cardiology and other related specialties, and has led to the development of the cardio-oncology subspecialty. This paper aims to provide an overview of the main adverse events, risk assessment and risk mitigation strategies, early diagnosis, medical and complementary strategies for prevention and management, and long-term follow-up strategies for patients at risk of cancer therapy-related cardiotoxicities. Research to better define strategies for early identification, follow-up and management is highly necessary. Although the academic cardio-oncology community may be the best vehicle to foster awareness and research in this field, additional stakeholders (industry, government agencies and patient organizations) must be involved to facilitate cross-discipline interactions and help in the design and funding of cardio-oncology trials. The overarching goals of cardio-oncology are to assist clinicians in providing optimal care for patients with cancer and cancer survivors, to provide insight into future areas of research and to search for collaborations with industry, funding bodies and patient advocates. However, many unmet needs remain. This document is the product of brainstorming presentations and active discussions held at the Cardiovascular Round Table workshop organized in January 2020 by the European Society of Cardiology.</p
Evaluation and management of chemotherapy-induced cardiotoxicity in breast cancer: a Delphi study
Metabolic carbonyl reduction of anthracyclines — role in cardiotoxicity and cancer resistance. Reducing enzymes as putative targets for novel cardioprotective and chemosensitizing agents
- …