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An Important Pattern of Placental Injury

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An Important Pattern of Placental Injury Placental Chorangiosis: An Important Pattern of Placental Injury Banu DOĞAN GÜN1, Figen BARUT1, H. Alper TANRIVERDİ2, Sükrü Oğuz ÖZDAMAR3, Aykut BARUT1 Zonguldak-Turkey OBJECTIVE: Chorangiosis is an infrequently diagnosed placental lesion characterized by placental capillary proliferation. In this study we present 10 cases of chorangiosis with histological and immunhis- tochemical features and described the clinical effects on fetal outcome. STUDY DESIGN: Ten cases of chorangiosis (7%) diagnosed in 150 placentas examined at our institution between 2002 and 2004 were evaluated. Chorangiosis was defined as the presence of a minimum of 10 villi, each with 10 or more vascular channels, in 10 or more areas of three or more random areas when using an x10 objective. Beside histopathological criteria, histochemical and immunohistochemical staining was also applied. RESULTS: Chorangiosis was most commonly associated with cesarean section (60%), preterm birth and neonatal intensive care (40%), Apgar scores of 5 minute or less (30%), maternal disease and drug ingestion (30%). Also intervillous hemorrhage (80%), placental calcification (60%), placentomegaly (40%), umbilical cord knots (40%), chorioamnionitis (40%), perivillous fibrin (40%) and umbilical vein dilatation (40%) were commonly observed placental findings in chorangiosis cases. CONCLUSION: Chorangiosis should be considered as an important sign of placental injury associated with hy poxia in utero. Histopathological recognition of these lesions might help to determine the underly ing and proximate causes of fetal injury. (Gynecol Obstet Reprod Med 2006; 12:176-179) Key Words: Chorangiosis, Chorangiomatosis, Chorangioma, Villous capillary, Angiogenesis Villous capillary lesions of the placenta are a heterogene- for each case which was diagnosed as chorangiosis. ous group of possibly interrelated lesions. Among these, T he placentas were weigh ed aft er removal o f the cord s chorangiosis is defined as an alteration of the terminal villo- and membranes. Multiple sections from each placenta, inclu- us characterized by an abnormal growth of fibrous and vas- ding one from the cord and one from the membrane roll, we- cular tissues with an increased number of capillaries in pla- re examined microscopically. The tissue was fixed in 10% 1 cen tal areas. Chorangiosis has not been studied extensively; buffered formalin, embedded in paraffin, and stained with its etiology is unknown, but believed to be related to chronic hematoxylin-eosin. hypoperfusion and hypoxia.1,2 Chorangiosis was diagnosed as the presence of a mini- In this study, we evaluated 10 cases of chorangiosis and mum of 10 villi, each with 10 or more vas cular chann els, in determined the clinical, placental and histopathologic featu- 10 or more areas of three or more random, noninfarcted pla- res, and emphasized the importance of recognizing these le- cental areas when using a x10 objective acco rding to the cri- sions. teria established by Altshuler.1 Material and Methods Subsequently, for each cas e one repres entative placent al sections was evaluated by histochemical stains for reticulin From January 2002 to December 2004, 150 placentas re- (Gomori’s reticulin stain) and by immunohistochemical stu- ceived in the Zonguldak Karaelmas University Hospital Pat- dies by using streptavidin biotin peroxidase method and anti- hology Department were examined. Clinical features, pla- bodies specific for CD31 (monoclonal, mouse, clone: cental histopathological and gross findings were reviewed JC/70A, NeoMarkers, CA, USA) and PD-ECGF (monoclo- nal, mouse, clone: P-GF.44C, NeoMarkers, CA, USA). 1Zonguldak Karaelmas University, Faculty of Medicine, Department of Pathology, Zonguldak, Turkey. 2Bursa Acıbadem Hospital, Department Results of Obstetrics and Gynecology, Bursa, Turkey. 3Zonguldak Karaelmas University, Faculty of Medicine, Department of Obstetrics and Of the 150 placentas examined 10 (7%) had cho ran gio- Gynecology, Zonguldak, Turkey sis. None of the case had multiple gestations. The gestational Address of Correspondence Banu Doğan Gün ages of the associated newborns ranged from 28 to 40 we- eks; one case (10%) in 20 to 32 weeks, 5 (50%) in 33 to 37 Zonguldak Karaelmas weeks and 4 (40%) in 38 to 40 weeks. Universitesi Tip Fakultesi Patoloji Anabilim Dalı T he evaluated clinical and placental d ata o f mothers an d fetuses whose placentas were diagnosed as having chorangi- Kozlu, Zonguldak, Turkey osis was listed in Table 1. Submitted for Publication: 10.06.2006 T he incidences o f clinical conditions most commonly as- Accepted for Publication: 21.09.2006 sociated with chorangiosis were; cesarean section, 6 (60%); 176 Gynecology Obstetric & Reproductive Medicine 2006; 12:176-179 177 Table 1. The evaluated clinical and placental data Clinical data Placental data Gestational age Gross Placental weight Poor obstetric history Placental shape and color Diabetes mellitus Infarction Eclampsia/preeclampsia Umbilical cord abnormalities Maternal infection Meconium staining Maternal drug ingestion Amnion nodosum Other maternal disease Cyst and tumors Cesarean section Histopathologic Chorioamnionitis Oligohy droamnios Villitis Multiple birth Calcification Birth weight Chorangiosis Prematurity/postmaturity Fetal nucleated erythrocytes Neonatal intensive care Periv illous fibrin Neonatal/perinatal death Dysmaturity Premature rupture of membranes Umbilical vasculopathy preterm birth and neonatal intensive care, 4 (40%); Apgar Histochemical stain for reticulin revealed a thin, well-defi- scores of 5 minute or less, 3 (30%); maternal disease and ned basement membrane that surrounds capillaries (Figure 2). drug ingestion, 3 (30%); premature rupture of the membra- nes, 2 (20%); toxemia or maternal hypertension, 2 (20%); neonatal death, 1 (10%); congenital anomaly, 1 (10%); dia- betes mellitus, 1 (10%). Of the 10 placentas with chorangiosis, the incidence o f each o f the following items were; intervillous hemorrhage 8 (80%), placent al calci fication 6 (60%), placentomeg aly, 4 (40%), umblical cord knots 4 (40%), chorioamnionitis 4 (40%), perivillous fibrin 4 (40%), umblical vein dilatation 4 (40%), pl acent al in farction 2 (20%), meconium staining o f membranes 2 (20%), placent al cyst 1(10 %); umbilical vein thrombosis 1 (10%). Chorangiosis was defined in terms of the number of the capillary vascular loops in the terminal villi. Histopathologi- Figure 2. Capillaries in chorangiosis are surrounded by a thin cally we diagnosed chorangiosis (Figure 1a-b) by applying basement membrane (Reticulin, x100). 1 the critera of Altshuler described above. Figure 1. Hypercapillarized terminal villi, each having 10 or more Figure 3. Immunostaining with CD 31 demonstrates more capillary (a) H&E, x100, (b) H&E, x200. capillaries (Biotin streptavidin peroxidase, DAB, x400). 178 Gün et al. Immunohistochemically capillary endothelial cells sho- capillary proliferation and cytotrophoblast and can result in wed uniform positivity with CD31; demonstrating more ca- elevated maternal serum hCG levels.3 pillaries than were easily discernible by hematoxylin-eosin Chorangiosis is predominantly a lesion of terminal villi. stain (Figure 3). The expression of PD-ECGF in the endo- A number of angiogenic factors, vascular growth factors are thelial cells was present in five of our cases (Figure 4). thought to have a part in terminal villogenesis. Capillary and stromal overgro wth is charact eristic o f pl acent as in diabet es mellitus and Beckwith-Wiedemann syndrome, which can show mesenchymal dysplasia and villous capillary lesions.8,9 Although we found high frequency of placentomegaly (60%) among placentas with chorangiosis, just one of our cases had diabetes mellitus. Chronic hypoperfusion or tissue hypoxemia is the well- known stimulus that cause growth factors such as VEGF, PDGF and TGF-β, produced by mesenchymal and trophob- lastic cells. Initiation of angiogenesis depends on VEGF, while continued capillary growth and development depend on PDGF dependent differentiation of pericytes, which pro- duces angiopoetins that control remodeling of the primary Figure 4. PD-ECF positivity of capillary endothelia (Biotin vascular plexus into a mature capillary bed. Finally endothe- streptavidin peroxidase, DAB, x200). lial cells and pericytes lead to the activation of TGF-β, which inhibits further growth and promotes terminal diffe- Discussion rentiation of the mature capillary.10,11 We demonstrated PD- In this study, we determined chorangiosis in approxima- ECGF reactivity in 5 of 10 cases. In negative cases, we tely 7% of examined placentas, comparable to other reported might hypothesize that angiogenesis has become stable or series.1,2 Most placentas with chorangiosis were delivered perhaps is presently going on. ≤37 weeks’ gestation and it was not seen at less than 28 Another alternative proposal for the pathogenesis is that, weeks. It may probably take time to develop chorangiosis, the increase in the macrophage-derived growth factors, such so this hypothesis would explain why we had seen chorangi- as tumor necrosis factor-α may play a role in chorangiosis.2 osis in the advanced weeks. In some series, villitis was demonstrated in chorangiosis ca- ses.1,2 We noted an increas e o f the p ercentage o f cho rioam- Chorangiosis has been correlated with increas ed neonat al nionitis (40%) in our series; however villitis or necrotizing death, major congenital malformations, preterm delivery and funisitis were not accompanied. placental ab ruption. 1,3,4 It is frequently
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