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Sudden death due to massive hemorrhage after a mini-invasive ambulatory diagnostic procedure is extremely rare. Fine-needle aspiration (FNA) of thyroid nodules is very safe, displaying a low rate of complications, all of which mild and often self-limiting. In few cases do these complications necessitate surgical decompression, and rarely does FNA of a thyroid nodule lead to the death of the patient.We report a case of sudden death caused by respiratory insufficiency after compression of the vascular and nervous structures of the neck and obstruction of the upper airways by hemorrhages dissecting the thyroidal and perithyroidal tissues in a 78-year-old woman. These hemorrhages were the result of vascular lacerations caused during diagnostic FNA of a nodule suspected of malignancy. In such cases, it is important to conduct a complete autopsy and histological analysis to ascertain the origin of massive hemorrhage involving the structures of the neck and to attribute the cause of death to the aforementioned procedure. The forensic pathologist must bear in mind that even extremely small damage, such as that produced by a fine needle, may cause a fatal hemorrhage in subjects with a subverted anatomo-pathological picture (such as, for example, the massive fibrosis of an organ).

Spontaneous preterm birth (PTB) complicates about 12% of pregnancies worldwide, remaining the main cause of neonatal morbidity and mortality. Spontaneous preterm birth PTBs is often caused by microbial-induced preterm labor, mediated by an inflammatory process threatening both maternal and newborn health. In search for novel predictive biomarkers of PTB and preterm prelabor rupture of the membranes (pPROM), and to improve understanding of infection related PTB, we performed an untargeted mass spectrometry discovery study on 51 bioptic mid zone amnion samples from premature babies. A total of 6352 proteins were identified. Bioinformatics analyses revealed a ranked core of 159 proteins maximizing the discrimination between the selected clinical stratification groups allowing to distinguish conditions of absent (FIR 0) from maximal Fetal Inflammatory Response (FIR 3) stratified in function of Maternal Inflammatory Response (MIR) grade. Matrix metallopeptidase-9 (MMP-9) was the top differentially expressed protein. Gene Ontology enrichment analysis of the core proteins showed significant changes in the biological pathways associated to inflammation and regulation of immune and infection response. Data suggest that the conditions determining PTB would be a transversal event, secondary to the maternal inflammatory response causing a breakdown in fetal-maternal tolerance, with fetal inflammation being more severe than maternal one. We also highlight matrix metallopeptidase-9 as a potential predictive biomarker of PTB that can be assayed in the maternal serum, for future investigation.

INTRODUCTION We conducted a retrospective analysis of cases of sudden unexpected infant death (SUID) referred to the SIDS-ALTE Center of the Liguria Region (Italy) from 2010 to 2018. In all cases, the death scene was inspected, and a multidisciplinary post-mortem evaluation was conducted. Our aim was to analyze the epidemiological data and etiological distribution. EVIDENCE ACQUISITION We examined 15 cases initially classified as sudden infant death. EVIDENCE SYNTHESIS In all cases, the death was initially unexplained. Seven cases involved males and eight involved females. Their mean age was 67.47 days; the youngest victim was 2 days old, while the oldest was 8.5 months (253 days). In 7 cases, the post-mortem analysis showed an infection of lung. In 4 cases, the prone position of the infant during sleep was identified as a risk factor. Only in one case the cause of death remains unexplained, and it was classified as sudden infant death syndrome II according to San Diego Classification. CONCLUSIONS In the forensic approach to cases of SUID, it is always important to conduct a thorough multidisciplinary investigation. In order to avoid procedural errors that might compromise the post-mortem investigation, it is necessary to consider the medical and social history of both mother and child, in addition to the circumstances of the death. Moreover, a complete pediatric post-mortem examination and multidisciplinary discussion are required in order to identify potentially important causative or contributory factors.

Objective To assess the differential diagnostic significance of a series of quantitative and qualitative variables of the cerebellar vermis in fetuses with posterior fossa cystic malformation, including Dandy-Walker malformation (DWM), vermian hypoplasia (VH) and Blake's pouch cyst (BPC). Methods This was a retrospective study of confirmed cases of DWM, VH and BPC, diagnosed at the Fetal Medicine and Surgery Unit of the Federico II University between January 2005 and June 2013 or the Fetal Medicine and Surgery Unit of G. Gaslini Hospital between July 2013 and September 2017. All included cases had good-quality three-dimensional (3D) volume datasets of the posterior fossa, acquired by transvaginal ultrasound through the posterior fontanelle. The midsagittal view of the posterior fossa was the reference view for the study. We assessed brainstem-tentorium angle and brainstem-vermis angle (BVA), as well as craniocaudal (CCVD) and anteroposterior (APVD) vermian diameters and vermian area (VA), which were normalized by biparietal diameter (BPD) to take into account gestational age (CCVD/BPD × 100, APVD/BPD × 100 and VA/BPD × 100, respectively). Finally, the position of the fourth ventricular choroid plexus (4VCP) was defined as normal ('up') or abnormal ('down'), relative to the roof/cyst inlet of the fourth ventricle. Results We analyzed 67 fetuses with posterior fossa malformations (24 cases of DWM, 13 of VH and 30 of BPC). The mean gestational age at diagnosis was 23.6 weeks. Regardless of gestational age, the BVA differed significantly between the three groups, and the VA/BPD was able to differentiate between VH and BPC. In differentiating between VH and BPC, the greatest areas under the receiver-operating characteristics curve were those for VA/BPD ratio. The 4VCP position was down in all cases of DWM and VH, while it was up in all cases of BPC. Conclusions Our data support the concept that VA/BPD ratio and 4VCP position may be used to differentiate between DWM, VH and BPC in the fetus. In our series, the position of the 4VCP had the highest accuracy, but a larger number of VH cases should be evaluated to confirm that an up position of the 4VCP indicates BPC while a down position indicates DWM or VH. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

International audience; Group 3 innate lymphoid cells (ILC3) have been detected in both murine and human decidual tissues where they are thought to play a relevant role in the induction and maintenance of pregnancy. However, limited information exists on the molecular mechanisms that regulate these cells, including immune checkpoints. Here, we show that ILC3 express the inhibitory checkpoints programmed cell death (PD-1) and T cell immunoglobulin and mucin domain containing protein 3 (TIM-3) during the first trimester of pregnancy and that these receptors could regulate production of cytokines, including IL-22, IL-8, and TNF-α, induced by IL-23. We also show that the intermediate extravillous trophoblast (iEVT) expresses high levels of the PD-1-ligand PD-L1, suggesting that PD-1/PD-L1 interaction may regulate ILC3 function at the feto-maternal interface. Our present data provide the first evidence that human decidual ILC3 express a functional PD-1. It is possible that an altered expression or function of PD-1 may break the immune-tolerance resulting in pregnancy failure.

Acute bacterial meningitis in infants and newborns represents a medical emergency and a significant cause of mortality and morbidity worldwide. Moraxella catarrhalis has been considered a microorganism with low pathogenic potential, and only in exceptional cases has it been found to cause meningitis in infants and immunocompetent people. We will now document an unusual case of an unexpected and sudden death of a 40-day-old infant due to acute meningitis from M. catarrhalis, apparently asymptomatic and subsequently diagnosed by an autopsy. According to our knowledge this is the first case of unexpected infant death due to undiagnosed M. catarrhalis meningitis.The suggested case, as well as for the rarity of such a fatal event, should be considered a caution to pediatrics and neonatologists for M. catarrhalis can cause paucisymptomatic meningoencephalitis in infants which can be potentially fatal.From a forensic point of view, an autopsy accompanied by a multidisciplinary assessment is always necessary in cases of unexpected infant deaths to identify the causes.

SUMMARY: Fetal vascular malperfusion includes a continuum of placental histologic abnormalities increasingly associated with perinatal brain injury, namely arterial ischemic stroke. Here, we describe the clinical-neuroimaging features of 5 neonates with arterial ischemic stroke and histologically proved fetal vascular malperfusion. All infarcts involved the anterior territories and were multiple in 2 patients. In 2 neonates, there were additional signs of marked dural sinus congestion, thrombosis, or both. A mixed pattern of chronic hypoxic-ischemic encephalopathy and acute infarcts was noted in 1 patient at birth. Systemic cardiac or thrombotic complications were present in 2 patients. These peculiar clinical-radiologic patterns may suggest fetal vascular malperfusion and should raise the suspicion of this rare, underdiagnosed condition carrying important implications in patient management, medicolegal actions, and future pregnancy counseling.

Objective: The objective of the study are to describe (a) the technical aspects and (b) the anatomical boundaries of the fetal third ventricle (3V) on the midsagittal sonographic view and to assess (c) different biometric parameters in normal and abnormal fetuses and (d) and their reproducibility. Methods: This study included 67 normal and 50 CNS anomalies fetuses which include (1) obstructive severe ventriculomegaly (SVM; atrial width ≥ 15 mm), (2) moderate ventriculomegaly (10-14.9 mm), and (3) corpus callosum agenesis (ACC). All underwent transvaginal 3D neurosonography of the midsagittal view of the 3V. The following parameters were measured: area, perimeter, craniocaudal and anteroposterior (AP) diameters, interthalamic adhesion diameter (ITAD), wedge angle, and the ratio between the last 2 variables (ITAD/WA). Repeatability was also assessed. Results: The ITAD and the ITAD/WA are significantly different between normal fetuses and the SVM (P ≤.001). Interthalamic adhesion diameter of ≤7.1 mm is able to identify SVM with 98.6% accuracy (CI: 0.92-0.99). In ACC cases, the AP diameter is significantly shorter than both normal fetuses and ventriculomegaly. Intraobserver/interobserver reliability was good for most variables. Conclusions: Transvaginal neurosonography enables visualization of the normal and abnormal fetal third ventricle. An ITAD

The term “Lotus Birth” identifies the practice of not cutting the umbilical cord and of leaving the placenta attached to the newborn after its expulsion until it detaches spontaneously, which generally occurs 3–10 days after birth. The first reported cases of Lotus Birth date back to 2004 in Australia. Supporters of such a procedure claim that the newborn is better perfused, endowed with a more robust immune system and “less stressed”. However, it should be pointed out that histopathological study of the placenta is increasingly being requested in order to investigate problems of an infective nature or dysmaturity affecting the foetus, and situations of risk affecting the mother. Moreover, from the legal standpoint, there is no uniform position on the question of whether the placenta belongs to the mother or to the newborn. Lastly, a proper conservation of the embryonic adnexa is very difficult and includes problems of a hygiene/health, infectivological and medico-legal nature. The authors analyzed all these aspect in the Italian legislative framework, reaching the conclusion that Lotus Birth is inadvisable from both the scientific and logical/rational points of view.

Biliary atresia (BA) is a fatal condition resulting in the lack of effective biliary drainage leading invariably to liver failure and cirrhosis within a year, and it is often lethal within a few months in the absence of corrective surgery or liver transplantation. In fact, BA is the most common indication for pediatric liver transplantation.Herein, we present a rare case of unexpected infant death due to BA diagnosed only postmortem in a context of child neglect and carelessness on the part of the parents. It emerged from the clinical history that after a few months, the parents no longer took their daughter to any medical checkups despite the indications and express recommendations for follow-up. The autopsy revealed agenesis of the gallbladder with BA and complete disruption of the hepatic architecture and parenchyma from biliary cirrhosis. Histological examinations documented severe biliary cirrhosis from hypoplasia of the biliary ducts.The child neglect in this case proved fatal inasmuch as an early diagnosis by a pediatrician would have likely allowed appropriate surgical treatment, thus avoiding the untimely death of the child. We highlight the importance of educating and informing parents (especially the disadvantaged) in matters of health. At the same time, primary care physicians should closely monitor the conditions and development of infants so as to recognize the early warning signs and symptoms of BA, bearing in mind that a timely diagnosis and proper surgical treatment can save the lives of most of these children.

INTRODUCTION Hepatic hemangiomas (HH) are benign vascular tumors, and when large, may contribute to fetal morbidity/mortality. Chorangiosis is placental villus capillary hypervascularity, probably linked with fetal hypoxia. CASE REPORT We present a macrosomic stillbirth at 39 + 3 weeks of gestation with congestive heart failure (CHF) and myocardial infarction. A giant right hepatic lobe HH was present, along with placental chorangiosis. CONCLUSION A common pathogenetic pathway between congenital HH and placental chorangiosis has not been reported. Our case suggests that the effects of HH and chorangiosis increase the risk of late fetal loss due to the high-output CHF.

Background and aim: The studies of Nobel laureate Robert Geoffrey Edwards led to the first in vitro fertilization and embryo transfer in 1978. Since then, reproductive medicine has made huge advances. Methods available to sterile couples now include: purchasing oocytes and sperm, uterus surrogacy, pre-implantation or pre-natal diagnosis, embryo/fetal selection. Here we highlight the fact that combinations of existing technologies could threaten the non-marketability of human life. Methods: We searched PubMed and websites to find articles regarding assisted reproduction techniques. Results: These methods, taken separately, provide support for natural fertilization, but when used together, they may lead to genuine “baby factories”. In poor countries, such “factories” exist and often act illegally. Conclusions: We highlight the need for deeper bioethical studies and better legislation regarding the combined use of medically-assisted reproductive techniques. (www.actabiomedica.it)

PURPOSE OF INVESTIGATION To propose a multidisciplinary protocol for postmortem disclosure of complex fetal malformations, comparing ultrasound, computed tomography (CT), magnetic resonance imaging (MRI), and autopsy in a case of conjoined ischiopagus twins. MATERIALS AND METHODS A screening second-trimester ultrasound diagnosed ischiopagus twins at 20 gestational weeks in a 31-year-old woman without any previous ultrasound examination. The couple decided for pregnancy termination. The formalin-fixed fetuses underwent full-body CT, MRI, and autopsy. RESULTS ultrasound accurately diagnosed ischiopagus twins. CT was very accurate in the description of bone components. MRI allowed better visualization of the visceral organs than CT. Only autopsy could disclose the aspect of the two gastrointestinal tracts and the external genitalia. CONCLUSIONS Prenatal ultrasound represents the standard diagnostic exam for conjoined twins. CT-MRI virtual autopsy (virtopsy) may be an option if the couple refuses to authorize necropsy or may be useful to plan a minimally invasive autopsy preserving the external phenotype.

PURPOSE OF INVESTIGATION Hydatidiform mole (HM) is an abnormal pregnancy characterized by proliferation of cytotrophoblast and syncytiotrophoblast and vesicular swelling of placental villi. The fetus or embryo can be absent or abnormal. HMs can be complete or partial. CASE REPORT A case of diginyc partial HM at 12 weeks of gestational age was referred to the present center of prenatal diagnosis. The patient showed ovarian hyperstimulation syndrome. At ultrasonography, increased fetal nuchal translucency (NT) with fetal anomaly was evident, without sonographic signs of placental mole. Pregnancy was terminated with legal abortion. RESULTS Partial HM (PHM) was suspected by ultrasonographic fetal markers with ovarian hyperstimulation syndrome, but the diagnosis was performed only with fluorescent in situ hybridization. In particular fetal NT appeared increased also in diginyc mole. CONCLUSION In order to improve the detection rate of PHM, routine histological examinations may be associated to fluorescent in situ hybridization in all cases of fetal anomalies.

The heterozygous PHOX2B gene mutation is related to congenital central hypoventilation syndrome (CCHS). It is characterized by defective autonomous nervous system development leading to inadequate breathing response to hypoxia and hypercapnia, leading to hypoventilation especially during non-REM sleep, but also during waking in the more severe cases. Herein we report a case of sudden death in a 28-day-old child. The mother reported the infant was found lying on her own bed in the prone position. The infant was wearing a romper and lying in her crib without any blanket or other objects. At autopsy no significant pathological findings were detected. Histologically, sparse aspirated milk residues were present in some lung fields. Toxicological and microbiological examinations were within the norm. The initial postmortem investigation ruled out any readily identifiable cause of death. However, genetic analysis revealed a rare heterozygous 21bp in-frame deletion of the polyalanine coding sequences of the PHOX2B gene. In-frame contractions of the poly-Ala tract of the PHOX2B gene have already been reported in patients with symptoms suggestive of sporadic hypoventilation, apparent life-threatening events or neonatal respiratory distress.

ObjectiveThe aim of this study was to investigate the frozen section (FS) accuracy in tailoring the surgical staging of patients affected by endometrial cancer, using 2 different risk classifications.Methods/MaterialsA retrospective analysis of 331 women affected by type I endometrial cancer and submitted to FS assessment at the time of surgery. Pathologic features were examined on the frozen and permanent sections according to both the GOG33 and the Mayo Clinic algorithms. We compared the 2 models through the determination of Landis and Koch kappa statistics, concordance rate, sensitivity, specificity, positive predictive value, and negative predictive value for each risk algorithm, to assess whether there are differences in FS accuracy depending on the model used.ResultsThe observed agreement between the frozen and permanent sections was respectively good (k = 0.790) for the GOG33 and optimal (k = 0.810) for the Mayo classification. Applying the GOG33 algorithm, 20 patients (6.7%) were moved to an upper risk status, and 20 (6.7%) were moved to a lower risk status on the permanent section; the concordance rate was 86.5%. With the Mayo Clinic algorithm, discordant cases between frozen and permanent sections were 19 (7.6%), and the risk of lymphatic spread was underestimated only in 1 case (0.4%); the concordance rate was 92.4%. The sensitivity, specificity, positive predictive value, and negative predictive value for the GOG33 were 92%, 94%, 92%, and 93%, whereas with the Mayo algorithm, these were 98%, 91%, 77%, and 99%, respectively.ConclusionsAccording to higher correlation rate and observed agreement (92.4% vs 86.5% and k = 0.810 vs 0.790, respectively), the Mayo Clinic algorithm minimizes the number of patients undertreated at the time of surgery than the GOG33 classification and can be adopted as an FS algorithm to tailor the surgical treatment of early-stage endometrial cancer even in different centers.

Innate lymphoid cells (ILCs) have a central role in innate defenses against pathogens, lymphoid organogenesis, and tissue remodeling. They have been detected in human decidua, however, their role in this tissue remains unclear. Successful pregnancy requires an early inflammatory phase favoring implantation and tissue remodeling as well as a subsequent regulatory phase to prevent fetal rejection and supporting neoangiogenesis. Here, we show that, during the first trimester of pregnancy, neutrophils infiltrate decidua basalis and are more abundant in normal pregnancy than in spontaneous miscarriages. Decidual neutrophils localize in proximity of NCR+ILC3, which may influence neutrophil migration and survival given their production of CXCL8 and granulocyte macrophage colony-stimulating factor (GM-CSF). Moreover, NCR+ILC3-derived GM-CSF was found to induce the expression of heparin-binding EGF-like growth factor and IL1ra in neutrophils, two proteins/cytokines involved in tissue remodeling and maintenance of pregnancy. Our data suggest that the simultaneous presence of NCR+ILC3 and neutrophils in decidual tissues and their possible cross talk, may have a role in the early phases of pregnancy.

Intra-articular venous malformations (IAVM) of the knee represent a rare group of low-flow vascular malformations, mainly reported in the literature as synovial hemangiomas, usually with an onset in early childhood. The main symptoms and signs are knee pain, swelling, and hemarthrosis. These lesions are slowly progressive and can lead to chronic synovitis and joint damage. Confusing nomenclature and classification of these lesions have often led to misdiagnosis and inappropriate treatment. We report our experience in the treatment of 14 consecutive patients affected by knee IAVM.We carried out a retrospective study based on the review of the medical records and diagnostic imaging of the patients admitted to our department from October 1999 to June 2009, and discharged with the final diagnosis of IAVM of the knee.We observed 14 consecutive patients (8 boys, 6 girls); the median age at symptom onset was 5 years (range, 2.5 to 13 y). Magnetic resonance imaging was diagnostic in all cases. Surgical resection associated with a wide synoviectomy was the therapeutic procedure of choice in all cases. Within 6 months after surgery and physiotherapy, all the patients were symptom free with a full or at least acceptable knee range of motion. CD34 staining carried out in the last 7 cases of our series showed labeling of the endothelium of the thick-walled vessels, whereas the endothelium of the thin-walled vascular spaces was not stained. This finding of unstained vascular spaces suggests that a component of lymphatic vessels mixed with dysplastic blood vessels may be frequently present in these abnormalities.Magnetic resonance imaging plays a pivotal role in identifying the lesion. Surgical excision is always indicated and should be performed as early as possible to avoid lesion progression and to reduce the risk of chondral degeneration. According to the microscopic features of our resected specimens, we suggest that these lesions of the knee should be more properly named as IAVM instead of hemangiomas.Level IV.

Placental Site Trophoblastic Tumor (PSTT) is a rare form of Gestational Trophoblastic Disease (GTD). Approximately 200 cases have been reported in the literature. This disease has unpredictable biological behavior, whereas approximately 10-15% have clinically malignant evolution. We present the case of a 21-year old woman at first pregnancy without known previous abortion at 25 weeks of amenorrhea who was admitted to the hospital for hyperemesis, hepatic problems and important weight loss registered during the last few months. Few days after the admission, the patient suddenly died before the doctors can reach a diagnosis. A forensic investigation for medical malpractice was initiated. Samples collected from uterus at the autopsy revealed large trophoblastic cells with eosinophilic cytoplasm. Deposition of fibrinoid material was noticed between trophoblastic cells. Tumor cells dissected through the myometrium and invaded into the vascular spaces. Specimens of the lungs revealed numerous small neoplastic emboli into the vessels. We show autopsy and histological findings of PSTT in a young woman, which are very rarely described in the literature and we discuss the medico-legal implications related to the great difficulties of the gynecologists who faced this rare condition in term of diagnosis and prediction of biological behavior, outlining effective therapeutic approaches.

Conflicting results have been reported about the clinical value of fluorodeoxyglucose (FDG) imaging in predicting the risk of rupture of abdominal aortic aneurysm (AAA). The present study tests the hypothesis that FDG uptake is low in asymptomatic noninflammatory AAA due to the low cell density in aneurysmal walls.Positron emission tomography (PET)/CT imaging was performed in 12 consecutive candidates for AAA surgical repair and in 12 age- and sex-matched controls. At intervention, aneurysmal walls were cut into three sequential blocks. Block A was frozen to cut three 5-μm slices for incubation with 2-3 MBq of FDG for 5 min. Block C was first incubated with the same tracer solution for the same time and subsequently frozen to cut three 5-μm slices. Autoradiographic images were coregistered with immunohistochemical pictures of cell density, type and DNA synthesis as assessed on block B.No visible uptake in abdominal aorta occurred in any patient or control subject. Immunohistochemistry documented a severe loss of wall structure, with low numbers of cells. Tracer retention directly correlated with overall cell density and with prevalence of cells synthesizing DNA. The metabolic nature of FDG uptake was confirmed by the selective effect of preliminary freezing that decreased tracer content by 90% in regions with high cell density and only by 34% in cold acellular areas.The loss of tissue structure and the marked decrease in cell density account for the low prevalence of positive findings at FDG PET imaging, at least in asymptomatic patients bearing AAAs whose diameter is close to surgical indication.

The objective of our study was to evaluate the usefulness of immunohistochemical (IHC) staining techniques in the etiological diagnosis of non-immune hydrops fetalis (NIHF). The records of all 1,098 autopsies performed between January 1987 and May 2008, by the Division of Fetal Pathology of the University of Genoa, were reviewed and all 79 fetuses diagnosed with NIHF were re-evaluated. Additional IHC staining using antibodies that specifically stain blood and lymph vessels (CD31, CD34, smooth muscle actin antibody, D2-40) were performed. Results were compared to results from the literature. Our results showed that in 67/79 cases, evaluation by standard autopsy protocol led to an etiologic diagnosis. Furthermore, we were able to identify the pathogenetic mechanisms that eventually caused NIHF in 42/79 cases. Adding IHC staining to all evaluations identified the pathogenetic mechanism in a further 17 cases (total 59/79 cases). Lymphatic dysplasia was diagnosed by standard autopsy protocol in 1/79(1.3%), while adding IHC staining resulted in 18/79 (22.8%) cases being diagnosed (P=0.0001). The present rate of 22.8% of lymphatic dysplasia in non-immune hydrops fetalis is significantly higher than reported in the literature (36/818 or 4.4%; P=0.01). In conclusion, specific IHC staining techniques aimed at detecting lymphatic dysplasia are needed and should be mandatory in autopsies of fetuses with non-immune hydrops fetalis. (C) 2010 Wiley-Liss, Inc

Objective:To compare the risk status for lymph nodal metastasis at frozen section in endometrial cancer by applying a model based on tumor grade and myometrial involvement.Study Design:A retrospective analysis was performed on 174 early-stage endometrial cancer patients on whom an intraoperative frozen section was requested. Patients were retrospectively divided into low, intermediate, and high risk for lymph nodal involvement based on tumor grade and myometrial invasion based on Gynecologic Oncology Group 33 data. Concordance of risk status at frozen and permanent sections was performed.Results:Risk status at frozen and permanent sections were highly correlated (P < 0.01). Agreement between frozen and permanent sections was substantial (κ = 0.625). In 16% of the cases, frozen section underestimated the risk when compared with permanent section.Conclusion:Relying on intraoperative frozen section of the uterus to assess risk status for lymph nodal involvement in early-stage endometrial cancer patients leads to suboptimal management in a substantial number of cases.

The Mummies of Saints represent a peculiar category in Italian scene; they are very different for each type of mummification, suffer from numerous environmental interference and rituals,from conservation work or handling repeated over time. An analytical and critical review of all known cases and an inventory is presented. In the present work the topics of canonic recognitions is briefly considered. The study of the bodies of the Saints is characterized by particular techniques and by very close bonds that first puts the conservation of the venerable rest to analytical study of them. However, these investigations are of particular interest not only in the anthropological, paleopathological and biological profile but also from an historical, cultural, religious, literary and artistic point of view.

One of the main problems of microsurgery for lymphedema consists of the discrepancy between the excellent technical possibilities and the subsequently insufficient reduction of the lymphoedematous tissue fibrosis and sclerosis. Appropriate treatment based on pathologic study and surgical outcome have not been adequately documented. Over the past 25 years, more than 1000 patients with peripheral lymphedema have been treated with microsurgical techniques. Derivative lymphatic micro-vascular procedures has today its most exemplary application in multiple lymphatic-venous anastomoses (LVA). For those cases where a venous disease is associated to more or less latent or manifest lymphostatic pathology of such severity to contraindicate a lymphatic-venous shunt, reconstructive lymphatic microsurgery techniques have been developed (autologous venous grafts or lymphatic-venous-Iymphatic-plasty - LVLA). Objective assessment was undertaken by water volumetry and lymphoscintigraphy. Subjective improvement was noted in 87% of patients. Objectively, volume changes showed a significant improvement in 83%, with an average reduction of 67% of the excess volume. Of those patients followed-up, 85% have been able to discontinue the use of conservative measures, with an average follow-up of more than 7 years and average reduction in excess volume of 69%. There was a 87% reduction in the incidence of cellulitis after microsurgery. Microsurgical lymphatic-venous anastomoses have a place in the treatment of peripheral lymphedema and should be the therapy of choice in patients who are not sufficiently responsive to nonsurgical treatment. Improved results can be expected with operations performed earlier at the very first stages of lymphedema. © 2006 Wiley-Liss, Inc. Microsurgery 26: 65–69, 2006.

BACKGROUND: This study aims to evaluate the completeness of full thickness disc resection in the treatment of deep endometriotic bowel lesions. METHODS: This study comprised 16 women with bowel endometriotic lesions requiring segmental resection. For the purpose of the study, before intestinal resection, nodulectomy was performed. The presence of endometriotic infiltration in direct continuity with the removed nodule and the presence of fibrosis in the area surrounding the nodule were histologically evaluated. RESULTS: In seven out of 16 cases (43.8%; 95% CI, 19.8‐70.1), endometriosis was found in the bowel wall adjacent to the site of nodulectomy; the infiltration was visible in the muscular layer in all cases. In cases of incomplete nodulectomy, the muscular layer of the bowel segment surrounding the endometriotic nodule contained limited or no fibrosis. CONCLUSIONS: Full thickness disc resection is not complete in $40% of women with bowel endometriosis. Our finding that fibrosis in the muscular layer, the main landmark during surgical resection, does not always surround bowel endometriotic lesions might explain why incomplete resection may occur.

We assessed the immunohistochemical expression of p53 and c-erbB-2 oncoproteins in 13 ovarian endometrioid adenocarcinomas arising from endometriosis (group 1) and compared the findings with 15 otherwise similar cases without associated endometriosis (group 2). Tumors in group 1 showed a higher expression of both p53 and c-erbB-2 (p = 0.015 and p = 0.048, respectively). The expression of the two proteins was also significantly associated in group 1 (p = 0.013) but not in group 2 (p = 0.63) tumors. The different pattern of expression of p53 and c-erbB-2 in the two groups suggests that different molecular pathways may be involved in their pathogenesis.

Objective This study reviews the surgical pathology reports of post-partum hemorrhages to support clinicians in malpractice litigation and, potentially, to enhance pregnancy-related diagnoses. Study design This work is a retrospective study of surgical pathology reports of term pregnancies between January 2000 and January 2012 selected from the Surgical Pathology database of the I.R.C.C.S Azienda Ospedaliera Universitaria San Martino-IST (Istituto Nazionale per la Ricerca sul Cancro, Genoa). Results Ninety-five revision reports were identified (0.22% “placenta accrete,” 0.46% “non-accreta placental tissue retention,” and 0.31% “no placental fragments retention”). Secondary post-partum hemorrhages occurred in 0.3%, and primary PPH occurred in 0.05%, regardless of the group examined. Both types of PPH were most often associated with vaginal deliveries (58%). The most frequent endometrial finding was post-partum endometritis (43%). The entire placenta was submitted to the pathologist in 22/95 cases (23%). Hypermaturity and/or villous immaturity were the main histological patterns. Conclusions This review supports the hypothesis that the pathological placenta abnormalities observed, rather than underlying myometrium abnormalities, may underlie the contractile failure and the incomplete removal of the placenta. For these reasons, the authors emphasized the importance of investigating the placenta in cases of complicated deliveries not associated with PPH to support clinicians in malpractice claims.

In this article, the authors present a case of intrauterine foetal death (IUFD). The post-mortem histologic examination revealed placental mesenchymal dysplasia (PMD), a rare human placental disorder. Moreover, cases of PMD are often misdiagnosed as partial mole. The mother was a 26-year-old Italian, whose pregnancy, her first, had been uneventful until week 34⁺⁴ of gestation when IUFD suddenly occurred. The 2350 g male foetus showed no external abnormalities and the karyotype was 46, XY. The placenta weighed 450 g, the chorionic disk was round shaped, measuring 19.5-20.5 cm in diameter and had many enlarged villous structures. Histologically, the parenchyma showed abnormally enlarged and focally hydropic stem villi. Many of them were also surrounded by a fibrinoid material. Neither abnormal trophoblastic proliferation nor inclusion was observed in the examined sections. Causes and pathogenesis of PMD are still unclear and it is difficult to make a diagnosis solely on prenatal ultrasound during pregnancy. Generally, the correct diagnosis is reached only after the histological analysis of the placenta. However, obstetricians and gynaecologists should consider PMD also when a normal looking foetus is accompanied by a molar placenta (index factor for placentomegaly). The authors stress the importance of cooperation and information exchange among clinical and forensic pathologists, neonatologists, obstetricians and gynaecologists to avoid medical malpractice court proceedings in cases of IUFD.

Objectives A significant number of women diagnosed with atypical endometrial hyperplasia (AEH) on endometrial biopsy will be diagnosed with endometrial cancer (EC) on the hysterectomy specimen at permanent section. Surgical treatment for AEH and EC differ substantially. We have assessed the concordance in EC between frozen and permanent sections on patients undergoing hysterectomy for AEH. Materials and methods A retrospective review of 66 frozen sections on patients undergoing hysterectomy for AEH was performed. Frozen and permanent section diagnoses were categorized as negative or positive for malignancy. Permanent section carcinomas were classified as low or high risk based on their histopathology, myometrial invasion and differentiation. Correlation between frozen and permanent section and sensitivity, specificity, PPV, NPV and accuracy of frozen section in predicting EC in permanent section were calculated. Likelihood of diagnosing EC on frozen section was compared based on risk stratification at permanent section. Results Frozen and permanent sections revealed malignancy in 43.9% and 56% of the patients respectively. 94.1% of high risk carcinomas were identified as EC at frozen section as compared to 55% of low risk EC. Concordance was good (κ=0.75). Sensitivity, specificity, NPV, PPV and accuracy in predicting EC at frozen section were 73%, 93.1%, 73% and 93.1% respectively. Carcinomas were detected at frozen section significantly more often if they were at high risk. Conclusions The substantial agreement between frozen and permanent sections allows minimizing under- and overtreatment of women undergoing hysterectomy for AEH. High risk EC are efficiently identified in frozen section.

Objective. To evaluate the prevalence of defective placental adhesion (DPA) in voluntary termination of second-trimester pregnancy and the risk of DPA recurrence in subsequent pregnancies. Methods. We retrospectively reviewed the records of all patients who underwent voluntary second-trimester pregnancy termination in the period between January 2000 and December 2009. In all cases, the fetus and the placenta were submitted to pathological examination accordingly to our clinical protocol. Results. Four hundred twenty-seven cases of voluntary termination of second-trimester pregnancy were included in the study. Ten histologically confirmed cases of placenta accreta were observed (2.3%). Two patients with histological diagnosis of placenta accreta were lost at follow-up. Among the eight remaining patients, six had further pregnancies. Overall, nine pregnancies were recorded, and placenta accreta recurred in one patient. Conclusions. This study shows that DPA occurs in 2.3% of second-trimester voluntary termination of pregnancy; these patients should have an accurate ultrasound examination of the placenta in subsequent pregnancies.

Natural killer (NK) cells are the main lymphoid population in the maternal decidua during the first trimester of pregnancy. Decidual NK (dNK) cells display a unique functional profile and play a key role in promoting tissue remodeling, neoangiogenesis, and immune modulation. However, little information exists on their origin and development. Here we discovered CD34 + hematopoietic precursors in human decidua (dCD34 + ). We show that dCD34 + cells differ from cord blood- or peripheral blood-derived CD34 + precursors. The expression of IL-15/IL-2 receptor common β-chain (CD122), IL-7 receptor α-chain (CD127), and mRNA for E4BP4 and ID2 transcription factors suggested that dCD34 + cells are committed to the NK cell lineage. Moreover, they could undergo in vitro differentiation into functional (i.e., IL-8– and IL-22–producing) CD56 bright CD16 − KIR +/− NK cells in the presence of growth factors or even upon coculture with decidual stromal cells. Their NK cell commitment was further supported by the failure to undergo myeloid differentiation in the presence of GM-CSF. Our findings strongly suggest that decidual NK cells may directly derive from CD34 + cell precursors present in the decidua upon specific cellular interactions with components of the decidual microenvironment.

A of a case of cornual pregnancy associated with initial transformation to choriocarcinoma is reported. Appropriate monitoring of HCG titers following conservative management of ectopic pregnancy is important not only to diagnose persistent ectopic gestation, but to avoid missing trophoblastic disease, albeit rarely.

This study analyzed by immunofluorescence staining the sympathetic innervation in the bowel adjacent to the endometriotic lesion and in the healthy tissue at the border of the resected specimen. Sympathetic nerve fibers are significantly reduced in the mucosal and muscular layer near the endometriotic lesions; in contrast, sensory nerve fiber density is not altered in the area near the endometriotic lesions.

Background The 5-HT4 receptor agonist prucalopride enhances large intestinal contractility by facilitating acetylcholine release through activation of 5-HT4 receptors on cholinergic nerves and is effective in patients with constipation. Patients with intestinal endometriosis can present with constipation. We investigated in vitro whether large intestinal endometriotic infiltration influences contractility and facilitation of acetylcholine release by prucalopride. Methods Sigmoid colon or rectum circular muscle strips were obtained at the level of an endometriotic nodule with infiltration of the Auerbach plexus, and at a macroscopically healthy site at least 5 cm cranially from the nodule, in patients undergoing laparoscopic colorectal resection because of symptomatic bowel endometriosis. Responses to muscarinic receptor stimulation and to electrical field stimulation (EFS), and the facilitating effect of prucalopride on acetylcholine release were evaluated. Key results The EC50 and Emax of the contractile responses to the muscarinic receptor agonist carbachol did not differ between healthy and lesioned strips. EFS-induced on-contractions were not different between the healthy and lesioned strips, while the non-nitrergic relaxant responses induced by EFS were decreased in the lesioned strips. The facilitating effect of prucalopride on acetylcholine release in healthy strips was similar to that reported before in macroscopically healthy colon tissue of patients with colon cancer; in lesioned strips, the effect of prucalopride was fully maintained in 6/8 patients and absent in two. Conclusions & inferences Large intestinal endometriosis does not lead to a systematic interference with the cholinergic facilitating effect of prucalopride.

In many cases of early spontaneous abortion (ESA), no reasonable etiology can be documented. However, some of these cases show abnormal decidual vessels that could be overlooked when examined on hematoxylin and eosin (H&E) slides alone. Diagnostic accuracy could be improved by the use of a limited histochemical (HC) and immunohistochemical (IHC) panel. We reviewed 1,095 ESAs, selecting 176 cases with abnormal decidual vessels and subclassifying them into three groups on the basis of decidual vascular pattern. Various HC and IHC stainings were performed in order to assess their use in improving diagnostic sensitivity. Histological findings on H&E were recorded and compared to the results obtained with HC and IHC. A variable role in the improvement of morphologic details was demonstrated for all three tested HC stainings (periodic acid-Schiff, Masson's trichrome, Weigert's stain for fibrin) and for two of the IHC markers (smooth muscle actin, human placental lactogen). In many cases of ESA, only compatibility diagnoses can be formulated. However, using a limited panel of HC and IHC stainings, some significant findings can be more reliably reported, allowing the pathologist to acquire confidence in his routine diagnostic work.

We describe the histological examination of 18 aborted fetuses that had increased nuchal translucency (NT) between 11+0 and 13+6 weeks' gestation. The aim of this study was to assess the corresponding NT anatomic features by immunohistochemical (IHC) investigation. A morphological study was performed using lymphatic and blood endothelial specific markers, as well as smooth muscle actin (SMA). We found that all 18 cases were D2-40 positive, CD31 positive, and CD34 negative, suggesting the presence of nuchal lymph vessel ectasia. We found that 12/18 cases were SMA staining positive and 6/18 cases were SMA negative, suggesting that 6/18 cases had nuchal cystic lymphangiectasia, whereas 12/18 had cystic hygromas. The present data seem to confirm the reasonable hypothesis that lymphangiogenesis plays a relevant role in nuchal edema, increased NT, and that increased NT is the result of a lymphatic malformation or a delayed development of the lymphatic system.

The authors present a case of stillbirth in which histologic examination of the placenta provides the opportunity to make a definitive diagnosis of a death due to fetal thrombotic vasculopathy (FTV). Establishing the etiology in cases of stillbirth may avoid medical malpractice litigation. The better knowledge of the cause of stillbirths also helped obstetricians to recognize factors that could have prejudiced future pregnancies.

Metastatic breast cancer is rare in the female genital tract, and when present it more commonly tends to involve ovary or endometrium; uterine cervix is only occasionally involved. This condition poses differential diagnostic problems in the settings of clinical and pathological investigations.An asymptomatic 78-year-old woman came to our attention in the context of routine gynecological surveillance; clinical examination disclosed enlarged uterine body and cervix. Our patient then underwent computed tomography and magnetic resonance imaging that outlined the possibility of cervical cancer with parametrial involvement. Moreover, a suspect mass was found on the mammogram in the left breast. Breast surgical excision was performed, which revealed invasive breast carcinoma, while synchronous cervical biopsy discovered distant metastasis in the uterine cervix. On histological examination, both lesions showed non-cohesive architectural pattern consistent with lobular morphology; anyway, to rule out primary poorly differentiated cervical cancer, appropriate immunohistochemical panel was performed, which confirmed the mammary derivation of the tumor. Due to disseminate disease, the patient underwent multisystemic medical treatment including radiotherapy, chemotherapy and hormone therapy, and she is still alive at 30-month follow-up.Genital tract metastases in patients with known breast carcinoma can present with abnormal vaginal bleeding, but they often are asymptomatic. Therefore, only strict gynecological surveillance of these patients can permit early detection of these secondary lesions. Aggressive treatment of isolated cervical metastasis should be performed when feasible; otherwise, systemic chemotherapy with taxane could be sufficient in increasing survival. It should be emphasized that, in most cases, only accurate immunohistochemical investigation, particularly if performed on the primary lesion as well, can solve differential diagnostic problems and allow the clinician to establish appropriate treatment.

During the first trimester of pregnancy NK cells represent >50% of the lymphoid cells present in the human decidua where they reside in close contact with trophoblast cells. Because in decidual tissues NK cell activation and function may be induced by this interaction, we analyzed the cellular ligands recognized by activating NK receptors expressed on trophoblast cells. We show that these cells primarily express the NKp44 and DNAM-1 ligands and that interaction between these ligands and their corresponding receptors results in NK cell triggering. While activated peripheral blood NK (pNK) cells lysed the trophoblast cell lines JAR and JEG3, decidual NK (dNK) cells did not. On the other hand, they released VEGF, SDF-1, IP10 and large amounts of IL-8. Interaction with K562 target cells was exploited to induce optimal NK cell triggering, allowing a parallel, quantitative assessment of both cytolytic activity and cytokine production elicited by dNK cells. While dNK cells were unable to kill K562 even at high effector:target (E:T) ratios, they released large amounts of IL-8 also at low E:T ratios, a scenario compatible with dNK trophoblast cells interaction occurring within decidual tissues.

The exhumation of the natural mummies of Beata Margherita di Savoia (1390-1464) and of St. Caterina Fieschi Adorno (1447-1510) has not been followed by autopsy or histological exams. The aim has been to preserve the integrity of the saints' corpses. We have thus proceeded to a confrontation between data gathered from chronicles and hagiographies and radiological exams and macroscopic observations. The article aims at establishing a model for a multidisciplinar approach to paleopathological research, integrating historical research and medical knowledge.

Three cases of a squamous cell carcinoma with a prominent myxoid stroma are reported. One case in a 70-year-old woman had presented as a lump in the breast, the other two presented as polypoid lesions of the larynx and cervix uteri in a 65-year-old man and 61-year-old woman, respectively. The carcinomatous component was immersed in abundant extracellular mucosubstances. In addition to occasional squamous pearls, it displayed immunocytochemical evidence of high-weight keratin present in the neoplastic cells and, in one case, desmosomal attachment under electron microscopy. The extracellular mucosubstances proved to be similar to those seen in connective tissue. The differential diagnosis with histologically similar lesions has been taken into consideration, and it has been suggested that this newly described entity showing abundant myxoid stroma has to be distinguished from numerous benign and malignant myxoid soft tissue tumors.

We report on a patient with a bowel endometriotic nodule that was hypointense on both T1- and T2-weighted magnetic resonance imaging (MRI); histologic examination revealed that the MRI appearance of the nodule was due to the presence of extensive fibrosis. Bowel endometriotic nodules with extensive fibrosis and limited endometrial tissue have a signal intensity similar to that of the muscle on both T1- and T2-weighted images. In these patients, additional techniques such as multislice computed tomography enteroclysis may be used for adequate diagnosis before surgery.

Bowel endometriosis opens a new frontier for the gynecologist, as it forces the understanding of a new anatomy, a new physiology, and a new pathology. Although some women with bowel endometriosis may be asymptomatic, the majority of them develop a variety of gastrointestinal complains. No clear guideline exists for the evaluation of patients with suspected bowel endometriosis. Given the fact that, besides rectal nodules, bowel endometriosis can not be diagnosed by physical examination, imaging techniques should be used. Several techniques have been proposed for the diagnosis of bowel endometriosis including double-contrast barium enema, transvaginal ultrasonography, rectal endoscopic ultrasonography, magnetic resonance imaging, and multislice computed tomography enteroclysis. Medical management of bowel endometriosis is currently speculative; expectant management should be carefully balanced with the severity of symptoms and the feasibility of prolonged follow-up. Several studies demonstrated an improvement in quality of life after extensive surgical excision of the disease. Bowel endometriotic nodules can be removed by various techniques: mucosal skinning, nodulectomy, full thickness disc resection, and segmental resection. Although the indications for colorectal resection are controversial, recent data suggest that aggressive surgery improves symptoms and quality of life.ObstetriciansGynecologists, Family Physicians.After completion of this article, the reader should be able to describe the varied appearance of bowel endometriosis, recall that it is difficult to diagnose preoperatively, and explain that surgical treatment offers the best treatment in symptomatic patients through a variety of surgical techniques which is best accomplished with a team approach.