Criteria for placental examination for obstetrical and neonatal providers.

Pathologic examination of the placenta can provide insight into likely (and unlikely) causes of antepartum and intrapartum events, diagnoses with urgent clinical relevance, prognostic information for mother and infant, support for practice evaluation and improvement, and insight into advancing the sciences of obstetrics and neonatology. Although it is true that not all placentas require pathologic examination (although alternative opinions have been expressed), prioritization of placentas for pathologic examination should be based on vetted indications such as maternal comorbidities or pregnancy complications in which placental pathology is thought to be useful for maternal or infant care, understanding pathophysiology, or practice modifications. Herein we provide placental triage criteria for the obstetrical and neonatal provider based on publications and expert opinion of 16 placental pathologists and a pathologists' assistant, formulated using a modified Delphi approach. These criteria include indications in which placental pathology has clinical relevance, such as pregnancy loss, maternal infection, suspected abruption, fetal growth restriction, preterm birth, nonreassuring fetal heart testing requiring urgent delivery, preeclampsia with severe features, or neonates with early evidence of multiorgan system failure including neurologic compromise. We encourage a focused gross examination by the provider or an attendant at delivery for all placentas and provide guidance for this examination. We recommend that any placenta that is abnormal on gross examination undergo a complete pathology examination. In addition, we suggest practice criteria for placental pathology services, including a list of critical values to be used by the relevant provider. We hope that these sets of triage indications, criteria, and practice suggestions will facilitate appropriate submission of placentas for pathologic examination and improve its relevance to clinical care.

Abnormal Uterine Involution May Lead to Atony and Postpartum Hemorrhage: A Hypothesis, With Review of the Evidence.

Uterine involution has 2 major components-(1) involution of vessels; and (2) involution of myometrium. Involution of vessels was addressed by Rutherford and Hertig in 1945; however, involution of myometrium has received little attention in the modern literature. We suggest that the pathophysiology of myometrial involution may lead to uterine atony and postpartum hemorrhage. The myometrium dramatically enlarges due to gestational hyperplasia and hypertrophy of myocytes, caused by hormonal influences of the fetal adrenal cortex and the placenta. After delivery, uterine weight drops rapidly, with physiologic involution of myometrium associated with massive destruction of myometrial tissue. The resulting histopathology, supported by scientific evidence, may be termed "postpartum metropathy," and may explain the delay of postpartum menstrual periods until the completion of involution. When uterine atony causes uncontrolled hemorrhage, postpartum hysterectomy examination may be the responsibility of the perinatal pathologist.Postpartum metropathy may be initiated when delivery of the baby terminates exposure to the hormonal influence of the fetal adrenal cortex, and may be accelerated when placental delivery terminates exposure to human chorionic gonadotrophin (HCG). This hypothesis may explain why a prolonged third stage of labor, and delays in management, are risk factors for severe hemorrhage due to uterine atony.

Molecular Features of Preinvasive and Invasive Vulvar Neoplasms.

OBJECTIVES: Neoplasms arising from the vulva are uncommon and comprise various subtypes. Given the recent advancements in the molecular aspects of oncologic pathology and how they have impacted cancer treatment, an understanding of recent innovations in the molecular features of vulvar lesions is important. MATERIALS AND METHODS: Systematic literature search was performed on PubMed, Google Scholar, and Scopus databases for molecular and genetic characteristics of vulvar neoplasms. Peer-reviewed literature published in English is included. RESULTS: Squamous cell carcinoma (SCC) and its precursors are the predominant neoplasm at this site. Human papillomavirus (HPV) plays a crucial role in the pathogenesis of some of these lesions. Human papillomavirus-associated SCC follows the carcinogenic pathway driven by viral proteins E6 and E7 while HPV-independent SCC shows a high incidence of mutation of TP53 and CDKN2A genes. Mutations in the genes involving the PI3K-Akt pathway play an important role in the pathogenesis of both types of SCC. Among other vulvar malignancies, melanoma, and vulvar Paget disease (VPD) pose a significant clinical challenge and have unique molecular characteristics. Compared with dermal cutaneous melanoma, vulvar melanoma shows a higher rate of mutation of cKIT and NRAS genes and a lower rate of mutations in BRAF . Less than 20% of VPD shows amplification of ERBB2 and seldom shows mutation in genes involving the PI3K-Akt pathway. CONCLUSIONS: Several potentially targetable molecular pathways have emerged as they have been shown to be involved in the tumorigenesis of SCC, melanoma, and VPD.

Angiosarcoma of the Uterus: A Systematic Review.

Primary uterine angiosarcoma is an extremely rare neoplasm. Due to its rarity, knowledge regarding this malignancy is limited to a few scattered case reports. To better understand the prognostic factors and optimal management of these neoplasms, we have performed a systematic analysis of the disease. A systematic literature search of this entity yielded 25 reported cases of this entity. In addition, we searched the National Cancer Institute Surveillance, Epidemiology, and End Results database to find 4 additional cases and added a case diagnosed in our institution. We analyzed the patients' demographic characteristics and the different treatment protocols utilized to treat this malignancy. Patients were primarily treated by surgery with or without adjuvant chemotherapy and radiotherapy. Survival analysis was performed to examine the role of various factors in the outcome for the patients. There was no correlation with age of diagnosis, or treatment modality used, however, better outcomes were seen in patients presenting with smaller sized tumors. Our study is the first attempt to systematically study this rare malignancy in hopes of leading to a more standardized, evidence-based, and improved treatment protocol.

Mixed chorangioma and leiomyoma of the placenta, with a brief review of nontrophoblastic placental lesions.

Chorangioma is the most common type of primary non-trophoblastic tumor of the placenta, usually identified incidentally on ultrasound or at delivery. Leiomyomas within the placenta have been described, though they are rare and usually of maternal origin. We present an unusual case of a placental tumor with combined histopathologic and immunohistochemical features of both chorangioma and leiomyoma. A 39-year-old woman was found to have an echogenic placental mass at 33 weeks of gestation on ultrasound, that was thought to be a chorangioma. They followed up weekly, and performed a cesarean section at 39 weeks, due to concern for intrauterine growth restriction. No fetal or maternal complications occurred. Grossly, a 9-cm, red-brown mass with a broad-based stalk was identified on the fetal surface of the placenta near the periphery. Microscopically, the lesion was found to display characteristic features of chorangioma, with vascular proliferation, which stained positive for CD34 and CD31. SMA and caldesmon immunohistochemical staining was also positive, highlighting the proliferation of smooth muscle throughout the neoplasm. Literature review revealed a single additional case with similar characteristics.

A comprehensive review of paratubal lesions.

Paratubal lesions comprise a large number of entities. Preoperative diagnosis is often limited to mass and location, with histology required to establish a more definitive diagnosis. The purpose of this review is to review the literature and summarize benign and malignant paratubal lesions to better understand what can arise in this area.

Extrauterine endometrial stromal sarcoma: A systematic review and outcome analysis.

Endometrial stromal sarcoma (ESS) is the second most common uterine mesenchymal neoplasm. ESS can arise from extrauterine locations without any uterine involvement and is called extrauterine ESS (EESS). The epidemiological features of EESS are not well-known. Moreover, the factors affecting its outcome have not been systemically studied. The treatment of EESS closely follows that of uterine ESS, comprised of different combinations of surgical management, hormone therapy, chemotherapy, and radiation therapy. However, the effectiveness of different treatment protocols for EESS has not been studied. Here, we have performed a systematic review of all reported cases of EESS in the English literature. We further performed a meta-analysis of the outcome data and investigated how the patients' age, tumor site, tumor size, and management affect the overall and progression-free survival of the patients. We found that tumor site and mode of treatment significantly affected the overall survival and progression-free survival of the patients. Tumor size significantly affected overall survival but not progression-free survival, while the age at diagnosis did not affect patient outcome. As far as we know, ours is the first systematic study of this rare malignancy with an emphasis on outcome analysis.

The relationship of myometrial histopathology (metropathy) to myometrial dysfunction and clinical manifestations.

Myometrial morphology and myometrial physiology have been considered to be separate entities; however, observations of myometrial morphology and associated dysfunctions suggest a relationship between myometrial morphology and myometrial physiology that deserves further exploration. Although myometrial electrical activity can be monitored by electrohysterogram, the association of increased myometrial contractions with an increase in electrical activity (due to an increase in gap junctions) is typically not evaluated. Although the association of increased myometrial contractions with increase in pain can be monitored by tocometry and intrauterine pressure catheters, respectively, this is generally not done in the non-pregnant uteri. Although standard morphologic evaluations routinely include evaluation with special stains and immunohistochemistry in other organ systems, such as skeletal and cardiac muscle, these evaluations are not standard or routine for myometrium in hysterectomies. The purpose of this review is to discuss non-neoplastic myometrial histology, with consideration of the potential value of using tools to measure variations in myometrial physiology, in order to reliably correlate myometrial histology with myometrial function (and dysfunction).

Nonsquamous Lesions of the Vulvar Skin and Subcutaneous Tissue: A Review (Part 2).

OBJECTIVE: The aim of this second article was to complete part 1 review of nonsquamous lesions of the vulvar skin and subcutaneous tissue (Journal of Lower Genital Tract Disease, 2021), clinically and pathologically, based on the fifth edition of the World Health Organization tumor classification. MATERIALS AND METHODS: A database search of PubMed and Google Scholar was performed between 1970 and 2021, using the search terms "vulva," "lower genital tract," and "non-squamous lesions." The search was limited to "human gynecological pathology." Full article texts were reviewed, and reference lists were screened for additional articles. We excluded abstracts and articles written in the non-English language. RESULTS: An initial list of 400 articles was identified. Thirty-seven articles discussed clinicopathological features of nonsquamous lesions of the vulvar skin and subcutaneous tissue. CONCLUSIONS: Clinicopathological features of nonsquamous lesions of the vulvar skin and subcutaneous tissue as categorized by the updated World Health Organization classification are presented.

Metastatic Neoplasms to the Vulva-A Review.

INTRODUCTION: Metastatic neoplasms to the vulva are rare and can pose a diagnostic dilemma. As identification of the primary site can influence patient treatment and prognosis, correct diagnosis is important. METHODS: PubMed was searched for applicable publications using the terms vulva, vulvar neoplasms, metastasis, and vulvar metastasis. RESULTS: Most neoplasms metastatic to the vulva originate from other genital sources; however, extragenital primary neoplasms can also metastasize to the vulva. Vulvar metastases often occur in the setting of widespread disease. CONCLUSIONS: It is important to consider biopsy for appropriate histologic and immunohistochemical studies, as well as consider patient history to establish the primary site of metastatic lesions to the vulva, allowing optimal therapy.

Annular Indentation of the Ventricles in a Stillborn: A Case Report and Literature Review.

BackgroundIdiopathic indentation of the cardiac ventricles in a fetus has not been previously reported. Reported cases of congenital ventricle indentation are either caused by pericardial abnormalities or myocardial defects. Case report: We describe an incidental finding of annular indentation of the lower part of both ventricles in a stillborn male. The fetus was well-developed and the cause of stillborn was pronounced cord entanglement twice around the neck. Conclusion: Circumferential indentation of ventricles is distinguished from constrictive pericarditis and other myocardial defects as histologically the three layers of endocardium, myocardium, and pericardium are intact.

The pathogenesis of abnormal uterine bleeding in myopathic uteri.

It has been suggested that impaired venous drainage and endometrial vascular ectasia (EMVE), secondary to increased intramural pressure, explains abnormal bleeding in fibroid uteri. Striking EMVE with extravasated red blood cells (ecchymosis) has also been seen in uteri with grossly obvious myometrial hyperplasia (MMH), suggesting that increased intramural pressure can cause EMVE in the absence of fibroids. EMVE with MMH may explain the century old association of clinically enlarged uteri with abnormal bleeding, and this same mechanism may be operative in myopathic uteri with grossly obvious adenomyosis. EMVE with associated thrombosis, ecchymosis, and/or stromal breakdown is commonly seen in random sections of hysterectomies for bleeding. EMVE may also be associated with endothelial hyperplasia, consistent with a reaction to endothelial injury due to impaired venous drainage. This further supports the theory that EMVE bleeds when thrombosis occurs, due to Virchow's Triad (stasis, endothelial injury, and hypercoagulability). EMVE may be "the lesion for which surgery was performed" in hysterectomies with otherwise unexplained bleeding.

Nonsquamous Lesions of the Vulvar Skin and Subcutaneous Tissue: A Review (Part 1).

OBJECTIVES: This article aimed to review "nonsquamous lesions of the vulvar skin and subcutaneous tissue" clinically and pathologically, based on the fifth edition of the World Health Organization tumor classification. MATERIALS AND METHODS: A database search of PubMed and Google Scholar was performed between 1970 and 2021, using the search terms "vulva," "lower genital tract," and "nonsquamous lesions." The search was limited to "humans," "gynecopathology," and "dermatopathology." Full article texts were reviewed. Reference lists were screened for additional articles. We excluded articles written in the non-English language and abstracts. RESULTS: A list of 600 articles was identified. Another screening identified 68 articles for clinicopathological features of nonsquamous lesions of the vulvar skin and subcutaneous tissue. In the first part of this review, we cover 5 major groups of nonsquamous lesions of the vulvar skin and subcutaneous tissue including (1) glandular tumors and cysts, (2) adenocarcinomas of other types, (3) germ cell tumors of the vulva, (4) neuroendocrine neoplasia, and (5) hematolymphoid hyperplasia and neoplasia. The rest of the major topics including mesenchymal tumors of the lower genital tract, melanocytic lesions, and metastasis will be discussed in the second part of this review. CONCLUSIONS: Clinicopathological features of nonsquamous lesions of the vulvar skin and subcutaneous tissue as categorized by the updated World Health Organization classification are presented.

Diagnostic Criteria for Differentiated Vulvar Intraepithelial Neoplasia and Vulvar Aberrant Maturation.

OBJECTIVE: The aim of the study was to describe the features required for diagnosis of differentiated vulvar intraepithelial neoplasia (dVIN) and vulvar aberrant maturation (VAM). MATERIALS AND METHODS: The International Society of the Study of Vulvovaginal Diseases tasked the difficult pathologic diagnoses committee to develop consensus recommendations for clinicopathologic diagnosis of vulvar lichen planus, lichen sclerosus, and dVIN. The dVIN subgroup reviewed the literature and formulated diagnostic criteria that were reviewed by the committee and then approved by the International Society of the Study of Vulvovaginal Diseases membership. RESULTS: Differentiated vulvar intraepithelial neoplasia is the immediate precursor of human papillomavirus (HPV)-independent vulvar squamous cell carcinoma and shows a spectrum of clinical and microscopic appearances, some overlapping with HPV-related neoplasia. The histopathologic definition of dVIN is basal atypia combined with negative or nonblock-positive p16 and basal overexpressed, aberrant negative, or wild-type p53. The most common pattern of dVIN is keratinizing with acanthosis, aberrant rete ridge pattern, and premature maturation. The morphologic spectrum of keratinizing dVIN includes hypertrophic, atrophic, acantholytic, and subtle forms. A few dVIN cases are nonkeratinizing, with basaloid cells replacing more than 60% of epithelium. Vulvar aberrant maturation is an umbrella term for lesions with aberrant maturation that arise out of lichenoid dermatitis and lack the basal atypia required for dVIN. CONCLUSIONS: Evaluation of women at risk for dVIN and VAM requires a collaborative approach by clinicians and pathologists experienced in vulvar disorders. Close surveillance of women with lichen sclerosus and use of these recommendations may assist in prevention of HPV-independent squamous cell carcinoma through detection and treatment of dVIN and VAM.

Craniorachischisis with Exencephaly.

BACKGROUND: Neural tube defects can be as mild as spina bifida, to as severe as anencephaly, with only a fraction of these cases presenting as both craniorachischisis and exencephaly. Case report: The G3, P1011 mother was 25-years old, who at an estimated fetal gestational age of 17 weeks had a fetal diagnosis of anencephaly based on a sonogram, resulting in elective pregnancy termination. The female fetus had an open neural tube defect, consisting of craniorachischisis and exencephaly. No abnormalities were noted in any other organs. Conclusion: Although mostly associated with anencephaly, craniorachischisis can also be associated with exencephaly in early pregnancy.

Percutaneous Route of Life: Chylothorax or Total Parenteral Nutrition-Related Bilateral Pleural Effusion in a Neonate?

OBJECTIVE: Peripherally Inserted Central Catheter (PICC) lines are an essential tool in the management of premature neonates. Pleural effusion (PLE) secondary to the leakage of alimentation into the pleural cavity is an encountered complication of central-line total parenteral nutrition (TPN) administration. Methods: We review a case of a premature neonate who suffered large, bilateral PLE after insertion of an upper extremity PICC line for TPN. Results: Pleural fluid biochemical analysis confirmed PICC line infiltration, predominantly with monocytes, low protein, high triglycerides and high glucose. These results favored TPN leakage over chylothorax. Conclusions: To our knowledge, this is the first case of bilateral PLE due to PICC complication in a neonate, which highlights the importance of chylothorax differential diagnosis, the role of autopsy, and the need for clinical precautions when providing premature neonates with high osmolarity TPN.

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.

Placental Pathology in Covid-19 Positive Mothers: Preliminary Findings.

This study describes the pathology and clinical information on 20 placentas whose mother tested positive for the novel Coronovirus (2019-nCoV) cases. Ten of the 20 cases showed some evidence of fetal vascular malperfusion or fetal vascular thrombosis. The significance of these findings is unclear and needs further study.

High-Risk Human Papillomavirus Identification in Precancerous Cervical Intraepithelial Lesions.

OBJECTIVE: This review aims to summarize the currently available human papillomavirus (HPV) testing methods for precancerous cervical intraepithelial lesions. MATERIALS AND METHODS: A literature search of PubMed using key words "high-risk HPV, precancerous cervical intraepithelial lesions, FDA-approved HPV tests, p16 IHC, Ki 67 IHC, fluorescent in situ hybridization for HPV, Pap smear, HPV vaccines, HPV tests using self-collected samples, and next-generation sequencing" was performed between January 1 and June 14, 2019. The package inserts of the Food and Drug Administration-approved HPV tests were obtained from the companies' Web sites. RESULTS: Multiple morphology-based, immunohistochemical staining and nucleic acid HPV tests were reviewed, including the material required, methodologies, result interpretations, as well as their advantages, limitations, and futures. The structure of HPV and its natural history of infection and transmission were touched on as well for a better understanding of these testing methods. CONCLUSIONS: Human papillomavirus tests are a critical component for cervical cancer screening, and understanding of these tests helps test results interpretation and patients' triage.

Reproductive outcomes following a ruptured ectopic pregnancy.

Purpose: To determine the effect of ruptured ectopic pregnancies on the rate of future intrauterine pregnancies.Materials and Methods: This was a retrospective study of patients at a University-affiliated hospital with a history of an ectopic pregnancy between January 1991 to December 2016. All patients that underwent a salpingectomy for a tubal ectopic pregnancy were considered for this study. Intrauterine pregnancy rates for patients with a history of a ruptured ectopic pregnancy were compared to those with non-ruptured ectopic pregnancies. Fisher's exact test was used for analysis.Results: During the study period, 77 patients met the inclusion criteria. In this cohort, 14 patients with a history of a tubal ruptured ectopic pregnancy had achieved pregnancy within 12 months, compared to 24 patients in the non-ruptured group (52% vs 48%, p = 0.81). The rate of intrauterine pregnancies, compared to repeat ectopic pregnancy, in both the ruptured and non-ruptured group, was 71% (p > 0.99).Conclusion(s): Ruptured ectopic pregnancies did not adversely affect the rate of intrauterine pregnancy within 12 months of rupture when compared to non-ruptured ectopic pregnancies.