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

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

Impact of a silver layer on the membrane of tap water filters on the microbiological quality of filtered water

<p>Abstract</p> <p>Background</p> <p>Bacteria in the hospital's drinking water system represent a risk for the acquisition of a nosocomial infection in the severely immunocompromised host. Terminal tap water filters may be used to prevent nosocomial Legionnaires' disease. We present data from water samples using an improved kind of tap water filters.</p> <p>Methods</p> <p>In a blinded study on an intermediate care unit of the thoracic surgery department, a modified type of the Germlyser water filter (Aqua-Free Membrane Technology) with a newly-introduced silver layer on the filtration membrane was compared to its preceding type without such a layer on 15 water outlets. We determined growth of <it>Legionella</it>, other pathogenic bacteria, and the total heterotrophic plate count in unfiltered water and filtered water samples after filter usage intervals of 1 through 4 weeks.</p> <p>Results</p> <p>A total of 299 water samples were tested. Twenty-nine of the 60 unfiltered water samples contained <it>Legionella </it>of various serogroups (baseline value). In contrast, all samples filtered by the original water filter and all but one of the water samples filtered by the modified filter type remained <it>Legionella</it>-free. No other pathogenic bacteria were detected in any filtered sample. The total plate count in water samples increased during use of both kinds of filters over time. However, for the first 7 days of use, there were significantly fewer water samples containing >100 CFU per mL when using the new filter device compared with the older filters or taps with no filter. No advantage was seen thereafter.</p> <p>Conclusion</p> <p>The use of this type of terminal water filter is an appropriate method to protect immunocompromised patients from water-borne pathogens such as <it>Legionella</it>.</p