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This paper suggests that normal and morbidly adherent placentation may be viewed best in terms of trophoblastic stem cells and the mutually exclusive branches of the trophoblastic differentiation pathway\u2014villous trophoblast (VT), interstitial and endovascular nonvillous trophoblast (NVT) at the implantation site, and a positional variation in the chorion. Based on cases of hysterectomies for morbid adherence seen over 30 years at a community hospital, analyzed with routine keratin stains, with actin and trichrome stains as indicated, and with attempts at ultrasonography-pathology correlation, we present selected observations. In true accreta, the site of morbid adherence was to dilated basal plate vessels infiltrated by endovascular NVT, with scant interstitial NVT, and normal myometrium. It appeared that excess blood flow into the placenta was due to excessively deep keratin-positive endovascular NVT that spread\u2014independently of interstitial NVT\u2014in an angiocentric fashion in both accreta and increta. Retroplacental abnormalities were due to myometrial destruction by interstitial NVT in increta, sometimes requiring actin stains for detection; and to an admixture of markedly dilated endometrial glands and vessels in true accreta, best appreciated with keratin stains. Variations of depth and extent in increta may be due to variations in myometrial tone, and in the protease-antiprotease balance. Morbidly adherent fetal membranes are described, and the role of caesarean section scars in incretas is addressed.<\/jats:p>","DOI":"10.2350\/15-05-1641-oa.1","type":"journal-article","created":{"date-parts":[[2015,10,22]],"date-time":"2015-10-22T14:48:46Z","timestamp":1445525326000},"page":"320-333","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":33,"title":["Placenta Accreta and Placenta Increta: An Approach to Pathogenesis Based on the Trophoblastic Differentiation Pathway"],"prefix":"10.1177","volume":"19","author":[{"given":"Stewart F.","family":"Cramer","sequence":"first","affiliation":[{"name":"Department of Pathology, Rochester General Hospital, University of Rochester School of Medicine, Rochester, NY 14621, USA; and Department of Pathology, Rutgers New Jersey Medical School, Newark, NJ 07103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debra S.","family":"Heller","sequence":"additional","affiliation":[{"name":"Department of Pathology, Rochester General Hospital, University of Rochester School of Medicine, Rochester, NY 14621, USA; and Department of Pathology, Rutgers New Jersey Medical School, Newark, NJ 07103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2016,7,1]]},"reference":[{"key":"bibr1-15-05-1641-OA.1","volume-title":"Diagnostic Pathology\u2014Placenta","author":"Heerema-McKenney A","year":"2013"},{"key":"bibr2-15-05-1641-OA.1","doi-asserted-by":"publisher","DOI":"10.2350\/06-10-0174.1"},{"key":"bibr3-15-05-1641-OA.1","doi-asserted-by":"crossref","unstructured":"Kraus FT, Redline RW, Gersell DJ, Nelson DM, Dicke JM. 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