A rare case of ovarian hemangioma in a 30-year-old nulligravid woman.

A 30-year-old nulligravid woman with a history of polycystic ovarian syndrome presented for evaluation of left adnexal mass. The patient was referred to the gynecologic oncology clinic after endorsing signs of abdominal pain for a month and the pelvis ultrasound demonstrated hypoechoic solid mass in the left ovary. Magnetic resonance imaging with T1- and T2-weighted images demonstrated progressive centripetal "filling-in" of the mass suggesting a unique variation of malignant ovarian mass, similar to what is seen in hepatic hemangioma. Upon resection of the ovarian mass, pathology reported that the mass was filled with numerous small blood vessels with single later of endothelial cells confirming the diagnosis of ovarian hemangioma, capillary-type-a rare finding.

Diagnosis of Congenital Cytomegalovirus (cCMV) in an Asymptomatic Neonate on Placental Pathology.

Congenital Cytomegalovirus (cCMV) is the most common intrauterine infection, with an incidence of 0.5% to 1.3% in the United States of America (USA). The majority of cCMV infections are asymptomatic at birth. In this case report, we present a full-term neonate who was admitted to the neonatal intensive care unit (NICU) for early onset sepsis and had an incidental finding in the placenta suggestive of Cytomegalovirus infection that was later confirmed on polymerase chain reaction (PCR) test in the blood. The infant was further evaluated for signs of CMV infection: complete blood count (CBC), head ultrasound, audiology, and ophthalmology exams were performed that did not show any abnormality. He was discharged home with audiology, ophthalmology, primary care, and infectious disease specialties follow-up appointments. Our case emphasizes the role of placental examination in looking for evidence of CMV infection so that infants can be diagnosed as well as followed up appropriately and necessary interventions can be provided on time for the best possible outcomes.

Metastatic Phyllodes Tumor in a Patient With Beckwith-Wiedemann Syndrome.

Beckwith-Wiedemann syndrome (BWS) is an epigenetic disorder of imprinting on the chromosome 11p15 region that presents with clinical features, such as macroglossia, abdominal wall defects, neonatal hypoglycemia, hemihypertrophy, and embryonal tumors. Phyllodes tumors (PTs) are rare fibroepithelial tumors that account for 0.3% to 1% of breast tumors and present in women aged 35 to 55 years. Here we describe a rare case of metastatic malignant phyllodes tumor in a 27-year-old woman with BWS and uniparental disomy (UPD) of chromosome 11p15.5. To our knowledge, this is the first case report in literature to describe metastatic malignant phyllodes tumor in a woman with BWS.

Does in utero meconium passage in term stillbirth correlate with autopsy and placental findings of hypoxia or inflammation?

BACKGROUND: The cause of meconium passage in utero is controversial, traditionally being considered evidence of fetal stress and hypoxia, and also associated with intra-amniotic inflammation/infection. It is now recognized to also occur in the absence of fetal stress. Autopsy studies have shown that many term stillborns (SB) have hypoxic/ischemic brain injury and other evidence of stress preceding the time period immediately before demise, including acute thymic involution (ATI); however, these findings, along with placental findings, have not been previously correlated with meconium-stained amniotic fluid (MSAF). METHODS: 35 structurally normal singleton term SB (21 early term, 14 full/late term) with complete autopsies, including brain and placental examination, were identified. MSAF was visually identified at delivery and confirmed on the placental examination. Autopsy evaluation included brain injury and ATI. Placental evaluation included maternal and fetal vascular malperfusion and acute and chronic inflammatory lesions. Demographic and clinical features were compared. RESULTS: 18 (51%) SB had MSAF, and 17 (49%) had clear amniotic fluid (CAF). The was no significant difference in brain injury in the MSAF vs CAF group, including older gray matter injury (karyorrhexis) (67% vs 47%), recent gray matter injury (red neurons, but no karyorrhexis) (28% vs 35%), white matter injury (50% vs 29%), and hemorrhage (22% vs 24%). Severe ATI was more frequent in the MSAF vs CAF group (61% vs 24%, p = .04). There was no significant difference in placental lesions between groups, including acute maternal inflammation (39% vs 18%), acute fetal inflammation (6% vs 6%), fetal vascular malperfusion (11% vs 18%), maternal vascular malperfusion (39% vs 35%), and chronic inflammatory lesions (39% vs 29%). The MSAF group was more likely to be full/late term than early term (72% vs 28%), in contrast to the CAF group (6% vs 94%) (p = .0001). There was no difference in other clinical factors evaluated. CONCLUSIONS: 51% of term SB had MSAF, and, in contrast to the CAF group, these were significantly more likely to be full/late term. Brain injury was frequent in both MSAF and CAF groups, supporting hypoxia as the mechanism of demise in most of these SB. No placental lesions correlated with MSAF, including inflammation. This suggests that hypoxia is the cause of the MSAF in these SB, but that some additional biologic factor present in the full/late term SB, but not present in the early term SB, including possibly gastrointestinal maturation, is necessary for the meconium passage.

A Pregnant Woman With Hemoptysis and Diffuse Pulmonary Nodules.

CASE PRESENTATION: A 22-year-old woman who was 36 weeks pregnant presented with a 4-day history of cough, hemoptysis, and exertional dyspnea. She had no fever, night sweats, or weight loss. The review of system was otherwise negative. Her medical history was notable for a spontaneous first-trimester abortion a year ago. At that time, she had a transvaginal ultrasound scan that showed a gestational sac with no fetal movement. A post-abortion ultrasound scan revealed no residual fetal parts.

Chronic Inflammatory Placental Lesions Correlate With Bronchopulmonary Dysplasia Severity in Extremely Preterm Infants.

OBJECTIVE: Correlation of BPD with placental pathology is important for clarification of the multifactorial pathogenesis of BPD; however, previous reports have yielded varying results. We report placental findings in no/mild BPD compared to moderate/severe BPD, and with and without pulmonary hypertension (PH). METHODS: Eligible infants were 230/7-276/7 weeks gestational age. BPD was defined by the need for oxygen at ≥28 days with severity based on need for respiratory support at ≥36 weeks. Acute and chronic inflammatory placental lesions and lesions of maternal and fetal vascular malperfusion were examined. RESULTS: Of 246 eligible infants, 146 (59%) developed moderate/severe BPD. Thirty-four (23%) infants developed PH, all but 1 being in the moderate/severe BPD group. Chronic deciduitis (32% vs 16%, P = .003), chronic chorioamnionitis (23% vs 12%, P = .014), and ≥ 2 chronic inflammatory lesions (13% vs 3%, P = .007) were more frequent in the moderate/severe BPD group. Development of PH was associated with placental villous lesions of maternal vascular malperfusion (30% vs 15%, P = .047). CONCLUSIONS: The association of chronic inflammatory placental lesions with BPD severity has not been previously reported. This supports the injury responsible for BPD as beginning before birth in some neonates, possibly related to cytokines associated with these chronic inflammatory lesions.

Clinical Characteristics of Mother-Infant Dyad and Placental Pathology in COVID-19 Cases in Predominantly African American Population.

Objective In this currently evolving coronavirus disease 2019 (COVID-19) pandemic, the evidence is scarce about the impact of COVID-19 infection on women in labor and neonates in an inner city African-Americans (AA) population. The objective of this study was to evaluate the clinical outcomes and placental pathology in mother-infant dyads in COVID-19 cases. Study Design Retrospective chart review was conducted on 34 COVID-19 positive mother-infant dyads to study their baseline characteristics and outcomes. Placental pathology was reviewed by two perinatal pathologists. Results COVID-19 was noted in 3% of pregnant women who delivered in our institution. The majority (82%) of them were asymptomatic. Out of the four mothers who were symptomatic, only three (9%) required supplemental oxygen. None of them required invasive ventilation. All the neonates tested negative for COVID-19 at 24 hours of age. There were no gross or microscopic pathological abnormalities detected that could be definitely associated with any COVID-19 related complications during pregnancy in any of the 34 placentas. Conclusion COVID-19 does not appear to increase morbidity and mortality among pregnant women and their neonates in a predominantly AA population. Our study did not find any evidence of vertical transmission of COVID-19 infection nor any specific findings on placental pathology. Key Points Majority of women infected by coronavirus disease 2019 (COVID-19) during labor were asymptomatic.None of the newborns tested positive for COVID-19 at 24 hours of age.Placental pathology findings were nonspecific in COVID-19 mothers.

Disorders of placental villous maturation are present in one-third of cases with spontaneous preterm labor.

OBJECTIVES: Spontaneous preterm labor is an obstetrical syndrome accounting for approximately 65-70% of preterm births, the latter being the most frequent cause of neonatal death and the second most frequent cause of death in children less than five years of age worldwide. The purpose of this study was to determine and compare to uncomplicated pregnancies (1) the frequency of placental disorders of villous maturation in spontaneous preterm labor; (2) the frequency of other placental morphologic characteristics associated with the preterm labor syndrome; and (3) the distribution of these lesions according to gestational age at delivery and their severity. METHODS: A case-control study of singleton pregnant women was conducted that included (1) uncomplicated pregnancies (controls, n=944) and (2) pregnancies with spontaneous preterm labor (cases, n=438). All placentas underwent histopathologic examination. Patients with chronic maternal diseases (e.g., chronic hypertension, diabetes mellitus, renal disease, thyroid disease, asthma, autoimmune disease, and coagulopathies), fetal malformations, chromosomal abnormalities, multifetal gestation, preeclampsia, eclampsia, preterm prelabor rupture of the fetal membranes, gestational hypertension, gestational diabetes mellitus, and HELLP (hemolysis, elevated liver enzymes and low platelet count) syndrome were excluded from the study. RESULTS: Compared to the controls, the most prevalent placental lesions among the cases were the disorders of villous maturation (31.8% [106/333] including delayed villous maturation 18.6% [62/333] vs. 1.4% [6/442], q<0.0001, prevalence ratio 13.7; and accelerated villous maturation 13.2% [44/333] vs. 0% [0/442], q<0.001). Other lesions in decreasing order of prevalence included hypercapillarized villi (15.6% [68/435] vs. 3.5% [33/938], q<0.001, prevalence ratio 4.4); nucleated red blood cells (1.1% [5/437] vs. 0% [0/938], q<0.01); chronic inflammatory lesions (47.9% [210/438] vs. 29.9% [282/944], q<0.0001, prevalence ratio 1.6); fetal inflammatory response (30.1% [132/438] vs. 23.2% [219/944], q<0.05, prevalence ratio 1.3); maternal inflammatory response (45.5% [195/438] vs. 36.1% [341/944], q<0.01, prevalence ratio 1.2); and maternal vascular malperfusion (44.5% [195/438] vs. 35.7% [337/944], q<0.01, prevalence ratio 1.2). Accelerated villous maturation did not show gestational age-dependent association with any other placental lesion while delayed villous maturation showed a gestational age-dependent association with acute placental inflammation (q-value=0.005). CONCLUSIONS: Disorders of villous maturation are present in nearly one-third of the cases of spontaneous preterm labor.

Classification and reporting guidelines for the pathology diagnosis of placenta accreta spectrum (PAS) disorders: recommendations from an expert panel.

The terminology and diagnostic criteria presently used by pathologists to report invasive placentation is inconsistent and does not reflect current knowledge of the pathogenesis of the disease or the needs of the clinical care team. A consensus panel was convened to recommend terminology and reporting elements unified across the spectrum of PAS specimens (i.e., delivered placenta, total or partial hysterectomy with or without extrauterine tissues, curetting for retained products of conception). The proposed nomenclature under the umbrella diagnosis of placenta accreta spectrum (PAS) replaces the traditional categorical terminology (placenta accreta, increta, percreta) with a descriptive grading system that parallels the guidelines endorsed by the International Federation of Gynaecology and Obstetrics (FIGO). In addition, the nomenclature for hysterectomy specimens is separated from that for delivered placentas. The goal for each element in the system of nomenclature was to provide diagnostic criteria and guidelines for expected use in clinical practice.

Disorders of placental villous maturation in fetal death.

Objective The aims of this study were to ascertain the frequency of disorders of villous maturation in fetal death and to also delineate other placental histopathologic lesions in fetal death. Methods This was a retrospective observational cohort study of fetal deaths occurring among women between January 2004 and January 2016 at Hutzel Women's Hospital, Detroit, MI, USA. Cases comprised fetuses with death beyond 20 weeks' gestation. Fetal deaths with congenital anomalies and multiple gestations were excluded. Controls included pregnant women without medical/obstetrical complications and delivered singleton, term (37-42 weeks) neonate with 5-min Apgar score ≥7 and birthweight between the 10th and 90th percentiles. Results Ninety-two percent (132/143) of placentas with fetal death showed placental histologic lesions. Fetal deaths were associated with (1) higher frequency of disorders of villous maturation [44.0% (64/143) vs. 1.0% (4/405), P < 0.0001, prevalence ratio, 44.6; delayed villous maturation, 22% (31/143); accelerated villous maturation, 20% (28/143); and maturation arrest, 4% (5/143)]; (2) higher frequency of maternal vascular malperfusion lesions [75.5% (108/143) vs. 35.7% (337/944), P < 0.0001, prevalence ratio, 2.1] and fetal vascular malperfusion lesions [88.1% (126/143) vs. 19.7% (186/944), P < 0.0001, prevalence ratio, 4.5]; (3) higher frequency of placental histologic patterns suggestive of hypoxia [59.0% (85/143) vs. 9.3% (82/942), P < 0.0001, prevalence ratio, 6.8]; and (4) higher frequency of chronic inflammatory lesions [53.1% (76/143) vs. 29.9% (282/944), P < 0.001, prevalence ratio 1.8]. Conclusion This study demonstrates that placentas of women with fetal death were 44 times more likely to present disorders of villous maturation compared to placentas of those with normal pregnancy. This suggests that the burden of placental disorders of villous maturation lesions is substantial.

Do Increased Intra-alveolar Squamous Cells at Autopsy Correlate With Acute Fetal Asphyxia?

It is a generally held concept that finding increased aspirated amniotic fluid squames at autopsy supports a diagnosis of acute fetal asphyxia, the massive aspiration of squames being an indicator of terminal gasping. To evaluate this concept, we identified autopsies on 15 third-trimester stillborns with clinical acute placental abruption (acute asphyxia); 13 also had thymic petechiae and none had severe acute thymic involution, findings also supporting acute asphyxia. Thirty third-trimester stillborns with findings supporting a subacute or chronic mode of death, including severe thymic involution and absence of thymic petechiae, comprised the comparison group. Intra-alveolar squames were scored as 0, no squames; 1+, scattered squames singly or in small groups; and 2+, squames in many alveoli, at least focally in compacted clusters. In all cases, the squames were patchily distributed, and none received a score of 0. In the abruption group, the intra-alveolar squames were scored as 1+ in 12 (80%) and as 2+ in 3 (20%) cases, while in the comparison group, the squames were scored as 1+ in 20 (67%) and 2+ in 10 (33%) cases (P = NS). There was also no difference in the quantification of intra-alveolar squames in term compared to preterm stillborns. In conclusion, quantification of intra-alveolar squames did not aid in separating an acute mode of death (acute asphyxia) from subacute or chronic modes of death.

Umbilical Artery Thrombosis with Associated Acute and Severe Fetal Growth Restriction and Transient Severe Protein S Deficiency: Report of a Case with Prenatal Ultrasound Diagnosis Allowing for Timely Intervention and Good Outcome.

BACKGROUND: Thrombosis of one of the umbilical arteries can be associated with adverse pregnancy outcomes such as stillbirth and severe intrauterine growth restriction (IUGR). CASE: A 21-year-old gravida 1 patient, with a history of 3-vessel cord at 20 weeks, presented at 29 weeks with a single umbilical artery. The estimated fetal weight measurements at 26 weeks, 29 weeks, and 31 weeks were at the 27th percentile, the 26th percentile, and less than the 5th percentile, respectively. At 33 weeks, amniotic fluid index became abnormal at 2.3 cm and fetal heart tracing revealed spontaneous prolonged decelerations, and a cesarean delivery was performed. Placental pathology showed thrombosis of one of the umbilical arteries. At birth, a transient protein S deficiency was detected (activity 13%) and resolved at two months of age (activity 66%). The baby had an uneventful clinical course since birth. CONCLUSION: The recognition of reduction of umbilical arteries from two to one allowed for timely intervention with good outcome in this case. Thrombosis of umbilical vessels may be associated with a deficiency in coagulation proteins such as protein S.

The frequency and type of placental histologic lesions in term pregnancies with normal outcome.

Objective To determine the frequency and type of histopathologic lesions in placentas delivered by women with a normal pregnancy outcome. Methods This retrospective cohort study included placental samples from 944 women with a singleton gestation who delivered at term without obstetrical complications. Placental lesions were classified into the following four categories as defined by the Society for Pediatric Pathology and by our unit: (1) acute placental inflammation, (2) chronic placental inflammation, (3) maternal vascular malperfusion and (4) fetal vascular malperfusion. Results (1) Seventy-eight percent of the placentas had lesions consistent with inflammatory or vascular lesions; (2) acute inflammatory lesions were the most prevalent, observed in 42.3% of the placentas, but only 1.0% of the lesions were severe; (3) acute inflammatory lesions were more common in the placentas of women with labor than in those without labor; (4) chronic inflammatory lesions of the placenta were present in 29.9%; and (5) maternal and fetal vascular lesions of malperfusion were detected in 35.7% and 19.7%, respectively. Two or more lesions with maternal or fetal vascular features consistent with malperfusion (high-burden lesions) were present in 7.4% and 0.7%, respectively. Conclusion Most placentas had lesions consistent with inflammatory or vascular lesions, but severe and/or high-burden lesions were infrequent. Mild placental lesions may be interpreted either as acute changes associated with parturition or as representative of a subclinical pathological process (intra-amniotic infection or sterile intra-amniotic inflammation) that did not affect the clinical course of pregnancy.

Meconium staining of the amniotic fluid and the presence and severity of acute placental inflammation: a study of term deliveries in a predominantly African-American population.

OBJECTIVE: To determine frequency, stage and grade of placental histologic acute maternal inflammatory response (MIR) and fetal inflammatory response (FIR) in meconium-stained amniotic fluid (MSAF) in our predominantly African-American population. METHODS: Term placentas with MSAF (n = 310) were evaluated for MIR/FIR, including stage/grade, and compared with placentas with clear amniotic fluid (AF) (n = 250). MIR/FIR were also evaluated in thick compared to thin MSAF subgroups. Selected demographic and clinical features were compared. RESULTS: MIR and FIR were present in 57.7 and 40.3% of the MSAF compared to 44.0 and 29.2% of the clear AF group, respectively (p = .001 and .008). MIR with FIR was present in 35.8% of the MSAF compared to 25.2% of the clear AF group (p = .008); however, there was no significant difference in frequency of MIR without FIR between groups. There was no significant difference in frequency of MIR/FIR in thick compared to thin MSAF; however, thick MSAF was associated with higher FIR stage compared to thin MSAF (29.2 versus 5.4%, p = .004). This association was not seen with MIR stage or MIR/FIR grade. CONCLUSIONS: Histologic MIR and FIR are frequent findings in MSAF. Thick MSAF is associated with higher FIR stage when compared to thin MSAF.

Does vitamin D deficiency affect placental inflammation or infections among very low birth weight infants?

OBJECTIVE: Examine the association between placental inflammation and neonatal infections, and 25OH vitamin D (25OH D) levels at birth among very low birth weight infants (VLBWI). STUDY DESIGN: Serum 25OH D levels were measured in 89 VLBWI (≤1250 g) and 47 mothers on day one, and in 78 infants on day 21. Placentas were examined for maternal and fetal inflammation. Infants were divided into deficient (≤10 ng/ml) and adequate (>10 ng/ml) groups based on 25OH D levels on day 1. RESULTS: Mean ± SD maternal levels of 25OH D (21 ± 9 ng/ml) correlated with infants' levels (15 ± 8 ng/ml), (p < .001). 25OH D levels were lower in deficient (32/89) than in adequate group (8 ± 2 versus 20 ± 7 ng/ml, p = .011). Infants' 25OH D levels rose significantly by day 21 (p < .001). Univariate analyses showed no differences between infant groups in maternal or fetal inflammation, or neonatal infections (p > .05). Logistic regression analyses revealed no association between deficient 25OH D levels and the odds of maternal or fetal inflammation or other infections. Levels of 25OH D did not correlate with severity of placental inflammation. CONCLUSIONS: Deficient levels of 25OH D at birth are not associated with the occurrence of placental inflammation or neonatal infections among VLBWI.

Are amniotic fluid neutrophils in women with intraamniotic infection and/or inflammation of fetal or maternal origin?

BACKGROUND: Neutrophils are the most abundant white blood cells found in the amniotic cavity of women with intraamniotic infection and/or inflammation. The current belief is that these neutrophils are of fetal origin. However, abundant neutrophils have been found in the amniotic fluid of women with a severe acute maternal inflammatory response but without a severe fetal inflammatory response in the placenta, suggesting that these innate immune cells can also be of maternal origin or a mixture of both fetal and maternal neutrophils. OBJECTIVE: We sought to investigate the origin of amniotic fluid neutrophils from women with intraamniotic infection and/or inflammation and to correlate these findings with acute histologic maternal and fetal inflammatory responses in the placenta. STUDY DESIGN: Amniotic fluid was collected from 15 women with suspected intraamniotic infection and/or inflammation (positive microbiological cultures and/or interleukin-6 concentrations ≥2.6 ng/mL). Amniotic fluid neutrophils were purified by fluorescence-activated cell sorting, DNA was extracted, and DNA fingerprinting was performed. DNA fingerprinting was also performed in the umbilical cord and maternal blood DNA. Fluorescence in situ hybridization was assayed in women with male neonates. Blinded placental histopathological evaluations were conducted. RESULTS: First, DNA fingerprinting revealed that 43% (6/14) of women who underwent a single amniocentesis had mostly fetal neutrophils in the amniotic fluid. Second, DNA fingerprinting showed that 36% (5/14) of the women who underwent a single amniocentesis had predominantly maternal neutrophils in the amniotic fluid. Third, DNA fingerprinting indicated that 21% (3/14) of the women who underwent a single amniocentesis had an evident mixture of fetal and maternal neutrophils in the amniotic fluid. Fourth, DNA fingerprinting revealed that a woman who underwent 2 amniocenteses (patient 15) had fetal neutrophils first, and as infection progressed, abundant maternal neutrophils invaded the amniotic cavity. Fifth, fluorescence in situ hybridization confirmed DNA fingerprinting results by showing that both fetal and maternal neutrophils were present in the amniotic fluid. Sixth, most of the women who had predominantly amniotic fluid neutrophils of fetal origin at the time of collection delivered extremely preterm neonates (71% [5/7]). Seventh, all of the women who had predominantly amniotic fluid neutrophils of maternal origin at the time of collection delivered term or late preterm neonates (100% [6/6]). Eighth, 2 of the women who had an evident mixture of fetal and maternal neutrophils in the amniotic fluid at the time of collection delivered extremely preterm neonates (67% [2/3]), and the third woman delivered a term neonate (33% [1/3]). Finally, most of the women included in this study presented acute maternal and fetal inflammatory responses in the placenta (87% [13/15]). CONCLUSION: Amniotic fluid neutrophils can be either predominantly of fetal or maternal origin, or a mixture of both fetal and maternal origin, in women with intraamniotic infection and/or inflammation. The findings herein provide evidence that both fetal and maternal neutrophils can invade the amniotic cavity, suggesting that both the fetus and the mother participate in the host defense mechanisms against intraamniotic infection.

CXCL10 and IL-6: Markers of two different forms of intra-amniotic inflammation in preterm labor.

PROBLEM: To determine whether amniotic fluid (AF) CXCL10 concentration is associated with histologic chronic chorioamnionitis in patients with preterm labor (PTL) and preterm prelabor rupture of the membranes (PROM). METHOD OF STUDY: This study included 168 women who had an episode of PTL or preterm PROM. AF interleukin (IL)-6 and CXCL10 concentrations were determined by immunoassay. RESULTS: (i) Increased AF CXCL10 concentration was associated with chronic (OR: 4.8; 95% CI: 1.7-14), but not acute chorioamnionitis; (ii) increased AF IL-6 concentration was associated with acute (OR: 4.2; 95% CI: 1.3-13.7) but not chronic chorioamnionitis; and (iii) an increase in AF CXCL10 concentration was associated with placental lesions consistent with maternal anti-fetal rejection (OR: 3.7; 95% CI: 1.3-10.4). (iv) All patients with elevated AF CXCL10 and IL-6 delivered preterm. CONCLUSION: Increased AF CXCL10 concentration is associated with chronic chorioamnionitis or maternal anti-fetal rejection, whereas increased AF IL-6 concentration is associated with acute histologic chorioamnionitis.

Mutations in IFT-A satellite core component genes IFT43 and IFT121 produce short rib polydactyly syndrome with distinctive campomelia.

BACKGROUND: Skeletal ciliopathies comprise a spectrum of ciliary malfunction disorders that have a profound effect on the skeleton. Most common among these disorders is short rib polydactyly syndrome (SRPS), a recessively inherited perinatal lethal condition characterized by a long narrow chest, markedly shortened long bones, polydactyly and, often, multi-organ system involvement. SRPS shows extensive locus heterogeneity with mutations in genes encoding proteins that participate in cilia formation and/or function. RESULTS: Herein we describe mutations in IFT43, a satellite member of the retrograde IFT-A complex, that produce a form of SRPS with unusual bending of the ribs and appendicular bones. These newly described IFT43 mutations disrupted cilia formation, produced abnormalities in cartilage growth plate architecture thus contributing to altered endochondral ossification. We further show that the IFT43 SRPS phenotype is similar to SRPS resulting from mutations in the gene encoding IFT121 (WDR35), a direct interactor with IFT43. CONCLUSIONS: This study defines a new IFT43-associated phenotype, identifying an additional locus for SRPS. The data demonstrate that IFT43 is essential for ciliogenesis and that the mutations disrupted the orderly proliferation and differentiation of growth plate chondrocytes, resulting in a severe effect on endochondral ossification and mineralization. Phenotypic similarities with SRPS cases resulting from mutations in the gene encoding the IFT43 direct interacting protein IFT121 suggests that similar mechanisms may be disrupted by defects in these two IFT-A satellite interactors.

Adrenal Histologic Stress-related Changes in Third Trimester Stillbirth.

Adrenal histologic changes, including compact cell change (CCC), cystic change (CYC), and adrenal hemorrhage (AH), and their clinical correlations have only infrequently been investigated in stillbirth. We evaluated 75 third trimester singleton stillborns with complete autopsies (30 term and 45 preterm). A total of 58 had unexplained stillbirth and 17 had clinical placental abruption. The mothers were predominantly African-American (89%). CCC and CYC were diagnosed as cytoplasmic eosinophilia and cystic cavities in the definitive cortex, respectively. Adrenal changes were correlated with acute thymic involution (ATI), thymic petechiae, and clinical features, including abruption. CCC, CYC, and AH were present in 58 (77%), 51 (68%), and 15 (20%) of the 75 stillborns, respectively. CCC and CYC were frequently seen together ( P < .001). CCC and CYC were associated with higher ATI grade ( P < .001 and P = .010, respectively). The presence of CCC, but not CYC, was associated with absence of thymic petechiae ( P = .013) and was more frequent with unexplained stillbirth compared to abruption ( P = .017). AH was associated with lower ATI grade ( P = .002), with thymic petechiae ( P < .001), and with abruption ( P = .004). CYC was associated with diabetes ( P = .015). Overall, CCC and CYC were frequent findings and correlated with higher ATI grade, suggesting similar causes and time frames. CCC, but not CYC, correlated with unexplained stillbirth compared to abruption, but its high frequency in both groups limits its usefulness in their separation. AH was more frequent in the abruption group and correlated with lower ATI grade and thymic petechiae, supporting an association with sudden asphyxial death.