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      Morphological and immunophenotypical analysis of the spindle cell component in adenomyomatous hyperplasia of the gallbladder

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          Summary

          Background

          Adenomyomatous hyperplasia (AMH) of the gallbladder, reported in 1-8.7% of cholecystectomies, consists of cystically dilated sinuses/glands with a surrounding spindle cell proliferation which is thought to be composed of smooth muscle cells. Myofibroblasts are contractile cells that secrete a variety of biochemical modulators causing a “field-effect”. Myofibroblasts can be immunohistochemically distinguished from smooth muscle cells by their desmin negativity.

          Methods

          Eighteen cases of AMH and five cases each of chronic follicular cholecystitis, chronic cholecystitis, gallbladder carcinoma and 10 colonic diverticular disease were stained with actin and desmin. The percentage of myofibroblasts was estimated by the difference between actin and desmin staining in the same field. Statistical anlysis was performed using SPSS 22.0.

          Results

          The percentage of actin staining was significantly higher in AMH and gallbladder carcinoma compared to chronic follicular and chronic cholecystitis (p = 0.04). The percentage of desmin staining did not show any significant difference between the four groups. The estimated myofibroblastic population was significantly higher in AMH when compared to chronic follicular and chronic cholecystitis (p = 0.005).

          Conclusion

          The spindle cell proliferation around cystically dilated glands in AMH is composed predominantly of myofibroblasts and of smooth muscle cells as previously described. This finding suggest a derangement in epithelial-stromal interactions as the underlying pathophysiology in AMH.

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          Most cited references28

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          The stroma reaction myofibroblast: a key player in the control of tumor cell behavior.

          The cooperation between epithelial and mesenchymal cells is essential for embryonic development and probably plays an important role in pathological phenomena such as wound healing and tumor progression. It is well known that many epithelial tumors are characterized by the local accumulation of connective tissue cells and extracellular material; this phenomenon has been called the stroma reaction. One of the cellular components of the stroma reaction is the myofibroblast, a modulated fibroblast which has acquired the capacity to neoexpress alpha-smooth muscle actin, the actin isoform typical of vascular smooth muscle cells, and to synthesize important amounts of collagen and other extracellular matrix components. It is now well accepted that the myofibroblast is a key cell for the connective tissue remodeling which takes place during wound healing and fibrosis development. Myofibroblasts are capable of remodeling connective tissue but also interact with epithelial cells and other connective tissue cells and may thus control such phenomena as tumor invasion and angiogenesis. In this review we discuss the mechanisms of myofibroblast evolution during fibrotic and malignant conditions and the interaction of myofibroblasts with other cells in order to control tumor progression. On this basis we suggest that the myofibroblast may represent a new important target of antitumor therapy.
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            The myofibroblast: phenotypic characterization as a prerequisite to understanding its functions in translational medicine

            B Eyden (2007)
            Abstract The phrase ‘translational research’conveys the idea of the pursuit of applications for the treatment of human disease.The myofibroblast, long known for having a role in wound-healing, and for its presence in fibrotic conditions and tumour stroma, is becoming a focus for translational research, not least through its increasingly documented role as a tumour-promoting cell.In fibroproliferative conditions, cancer and tissue engineering, the myofibroblast, derived partly and possibly from circulating bone-marrow-derived cells and epithelial-to-mesenchymal transformation, is attracting great attention.In cancer, this cell was initially regarded as a barrier to tumour dissemination, but there is now a growing body of evidence to indicate that it is an active participant in tumour progression.While the involvement of the myofibroblast in these pathological processes is pushing the myofibroblast into the limelight of translational medicine as a target for potential anti-fibrotic and anti-cancer therapy, there are still numerous indications from the literature that the myofibroblast is a poorly understood cell in terms of its differentiation.Partly, this is due to a failure to appreciate the contribution of electron microscopy to understanding the nature of this cell.This paper, therefore, is devoted to detailing the principal phenotypic characteristics of the myofibroblast and promotes the argument that understanding how the myofibroblast carries out its roles in normal biological and in pathological processes will be enhanced by a sound understanding of its cellular differentiation, which in turn arguably demands a significant ultrastructural input.
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              Relationship between gallbladder carcinoma and the segmental type of adenomyomatosis of the gallbladder.

              Specimens from 3197 consecutive and unselected cholecystectomies performed during a 6-year period were studied. Adenomyomatosis of the gallbladder was defined as a lesion characterized by a thickened wall that consisted of Rokitansky-Aschoff sinuses surrounded by proliferated fibromuscular tissue. Adenomyomatosis was found in 279 specimens and classified as one of three types: segmental, fundal, or diffuse. Segmental adenomyomatosis was found in 188 specimens; gallbladder cancer (GBC) developed in 12 (6.4%) of the patients with segmental type adenomyomatosis. GBC developed in the mucosa of the fundal compartment distal to the annular stricture of the segmental type adenomyomatosis in all 12 of these patients. Conversely, GBC developed in 93 (3.1%) of the other 3009 patients (those with fundal alone, diffuse, or no adenomyomatosis). The prevalence of GBC in patients with segmental adenomyomatosis was significantly (P less than 0.025) higher than that of patients without segmental adenomyomatosis. Clinicians should be aware that segmental adenomyomatosis often coexists with GBC.
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                Author and article information

                Journal
                Pathologica
                Pathologica
                PATHOL
                Pathologica
                Pacini Editore srl
                0031-2983
                1591-951X
                01 September 2021
                August 2021
                : 113
                : 4
                : 272-279
                Affiliations
                [1 ] A.M. Rywlin, Department of Pathology, Mount Sinai Medical Center, Miami Beach , FL, USA
                [2 ] Department of Pathology and Clinical Laboratories, Nicklaus Children’s Hospital , Miami, FL, USA
                [3 ]Florida International University, Herbert Wertheim College of Medicine , Miami, FL, USA
                Author notes
                Correspondence Kritika Krishnamurthy Mount Sinai Medical Center, 4300, Alton road, Suite 2400, Miami Beach, Florida 33140 Tel.: 305 674 2277 Fax: 305 674 2999 E-mail: kritikakrishnamurthy@ 123456yahoo.com

                Conflict of interest

                The Authors declare no conflict of interest.

                Article
                10.32074/1591-951X-155
                8488983
                34542543
                b67a1987-cb26-446d-9e9c-9199a1cbf165
                © 2021 Copyright by Società Italiana di Anatomia Patologica e Citopatologia Diagnostica, Divisione Italiana della International Academy of Pathology

                This is an open access journal distributed in accordance with the CC-BY-NC-ND (Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International) license: the work can be used by mentioning the author and the license, but only for non-commercial purposes and only in the original version. For further information: https://creativecommons.org/licenses/by-nc-nd/4.0/deed.en

                History
                : 21 June 2020
                : 24 September 2020
                Page count
                Figures: 3, Tables: 1, Equations: 0, References: 28, Pages: 8
                Categories
                Original Article

                adenomyomatous hyperplasia,myofibroblast,gallbladder,adenomyoma,digital pathology

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