Clinical Clinical correlates of histopathological entities of the placenta Admire Matsika PLACENTAL EXAMINATION has a critical research on the understanding of the role in understanding adverse fetal clinical implications of placental lesions in and maternal outcomes in pregnancy. obstetric and neonatal care. Background General and allied health practitioners However, progress in correlating placental This review provides medical caring for pregnant women and neonates pathology with clinical phenotypes has practitioners with an update on new often encounter placental histopathological been hampered by methodological issues terminology and status quo of research on reports with esoteric diagnostic entities of in many studies published.1 Additionally, placental entities of clinical significance contentious clinical significance such as there appears to be a knowledge disparity that may recur in subsequent pregnancy chronic villitis, massive perivillous fibrin between perinatal pathologists reporting and for which alteration of obstetric care deposition, chronic histiocytic intervillositis, microscopic changes seen in the organ and may improve outcomes. With the advent materno-fetal vascular malperfusion and delayed villous maturation. These lesions understanding of the clinical significance of the electronic My Health Record may recur in subsequent pregnancies. of placental histopathological diagnoses by system implemented Australia-wide, obstetric care providers.2 When reported patients will have direct access to their Objective and interpreted correctly, the placenta histopathological reports online. As a The aim of this article is to review the provides useful information that may result, it is likely that general practitioners status quo of placental pathology and research with an emphasis on clinical explain adverse pregnancy outcomes as will find themselves explaining the management implications for some of well as guide further management of the clinical significance of placental pathology these most often reported but less mother, newborn or future pregnancy.3 reports to their patients more frequently understood recurrent clinicopathological Table 1 lists the most important and than before. entities of the placenta. An update on the recurrent histopathological diagnoses This article focuses on the clinical current nomenclature and classification of the placenta with some of the clinical significance of recurrent placental of placental conditions is also provided. steps that may be taken, based on expert entities diagnosable on microscopic Discussion opinion as well as anecdotal and limited examination. Readers are referred to the When reported adequately and interpreted scientific evidence available to date.4 aforementioned Amsterdam Workshop correctly, placental histopathology Other hurdles to a full understanding Group article5 for definitions and provides useful information that may of the clinical significance of placental histological descriptions of these lesions. explain adverse pregnancy outcomes and guides further management of the mother, pathology in obstetric care include the lack Neoplasms of the placenta are extremely newborn or future pregnancy. Empirical of standardisation in nomenclature and rare, often sporadic and non-recurrent and treatments for immune-mediated diagnostic criteria as well as interobserver are not discussed in this article. placental conditions with prednisolone, variability among pathologists.1 To address aspirin, heparin and intravenous these issues, a panel of international immunoglobulins have been reported. expert placental pathologists formulated Ascending intrauterine infection However, evidence-based guidelines for the 2014 Amsterdam classification, Ascending intrauterine infection or management of these conditions are lacking, and more research, including terminology and definitions of placental amniotic fluid infection (AFI) sequence 5 clinical trials, is in order. lesions. Table 2 is a comprehensive list of complicates up to 50% of preterm placental pathology entities incorporating deliveries and is seen in 5–10% of term the new Amsterdam Placental Workshop placentas. Acute chorioamnionitis or Group terminology. This consensus acute subchorionitis imply a maternal nosology is expected to accelerate inflammatory response to ascending 62 Reprinted from AJGP Vol. 50, No. 1–2, Jan–Feb 2021 © The Royal Australian College of General Practitioners 2021 Clinical correlates of histopathological entities of the placenta Clinical infection in the genital tract that has grade loosely correlates with clinical to identify for the specific organism reached the amniotic sac (Figure 1A). severity. Grade 1 AFI is often subclinical, involved. For example, Listeria spp. Conversely, acute funisitis, chorionic while grade 2 lesions are more likely to infection often causes acute villitis vasculitis and umbilical vasculitis be clinically apparent, with higher risk of (Figure 1B) in addition to high-grade implies a fetal response to ascending perinatal morbidity and mortality.6 Stages acute chorioamnionitis, while acute intrauterine infection. The recommended 2 and 3 AFI with fetal inflammatory funisitis due to Candida spp. is typically histopathological grading of AFI is binary response significantly correlate with focal, necrotising and peripherally (grade 1 = mild, and grade 2 = severe), perinatal morbidity and are associated located. Candidal hyphae can be and the staging is three-tiered: stage 1 with increased likelihood of various highlighted with fungal stains by the (early), 2 (intermediate) and 3 (advanced) neonatal conditions including culture- histopathologist; this is considered a for both maternal and fetal inflammatory positive sepsis, respiratory distress and critical result to be conveyed urgently responses.6 neurological impairment.7 to the treating team so that antifungal Studies show some correlation between Some bacteria and fungi elicit therapy may be prescribed in lieu of histopathological stage and duration characteristic patterns of inflammatory the empirical standard triple-antibiotic of clinical AFI, while histopathological response that may direct the pathologist therapy.8 Table 1. Clinical significance of placental histopathological diagnoses Placental diagnosis Suggested clinical action postpartum and in future pregnancy Ascending intrauterine infection (acute subchorionitis, • Correlate with microbiology, culture and sensitivity studies acute chorioamnionitis, acute fetal vasculitis, acute funisitis) • Consider or review antimicrobial treatment for mother and baby • Cervical cerclage in future pregnancy if complicated by recurrent preterm labour Chronic inflammatory condition (chronic villitis, chronic • Screen for viral, treponemal and protozoal (syphilis, toxoplasmosis, deciduitis, chronic chorioamnionitis, chronic histiocytic rubella, cytomegalovirus, herpes simplex [‘STORCH’]) infection intervillositis, eosinophilic T-cell vasculitis • Malarial screen if chronic histiocytic intervillositis predominant High-grade villitis of unknown aetiology (VUE) • Maternal autoimmunity screen • Consider low-dose aspirin, prednisolone, intravenous immunoglobulin in future pregnancy • Specialist obstetric care for possible fetal growth restriction with early delivery in future pregnancy if indicated Idiopathic chronic histiocytic intervillositis • As for VUE • Also consider low molecular weight heparins, hydroxychloroquine in future pregnancy Massive perivillous fibrin deposition and maternal • Consider pravastatin, low-dose aspirin, low molecular weight heparins, floor infarction immunoglobulin Fetal vascular malperfusion • Maternal diabetes screen • Neurological assessment and thrombophilia screen of the neonate • Treat underlying cause where possible Maternal vascular malperfusion • Maternal blood pressure, weight, glucose, liver and renal function assessments • Consider aspirin, specialist obstetric care, early delivery • Long-term maternal cardiovascular disease risk assessment • Specialist obstetric care with early delivery in future pregnancy if indicated Delayed villous maturation • Maternal diabetes screen and review of previous tests • Advice to avoid excessive weight gain in future pregnancy • Fetal movements monitoring in third trimester • Specialist obstetric care with early delivery in future pregnancy if indicated © The Royal Australian College of General Practitioners 2021 Reprinted from AJGP Vol. 50, No. 1–2, Jan–Feb 2021 63 Clinical Clinical correlates of histopathological entities of the placenta Chronic inflammatory to exclude viral and protozoal (eg are due to infections in the developed conditions of the placenta cytomegalovirus, rubella, toxoplasmosis) world.9 In the majority of cases, no A histopathological diagnosis of chronic infections in both mother and fetus. infection is found; this inflammation villitis (Figure 1C) requires the clinician Fewer than 5% of cases of chronic villitis is termed villitis of unknown aetiology (VUE). A binary grading system for chronic villitis and deciduitis is also in use.5 Low-grade chronic villitis, after Table 2. Classification of placental clinicopathological disorders incorporating exclusion of infections, does not have a 2014 Amsterdam Working Group nosology known clinical significance. Conversely, Disease category Placental entity high-grade VUE shows consistent association with adverse pregnancy Infectious conditions • Acute: outcomes including fetal growth of placenta – Maternal inflammatory response: (sub)chorionitis,