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.

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.

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.

Metastatic Pleomorphic Lobular Carcinoma of the Breast to the Hypothalamus Presenting as a Primary Pituitary Lesion Presenting 17 Years Later-Report of a Case and Review of the Literature.

Carcinomas metastatic to the brain are common, however, metastatic disease to the hypothalamic- pituitary region is uncommon and account for less than 3.6% of all resected malignant pituitary tumors. Most metastatic disease in that region derives from a lung or breast primary, with both ductal and lobular carcinoma reported. We report what we believe is the first case of pleomorphic lobular carcinoma metastatic to the hypothalamus. This case is also reaffirms that late metastasis from breast cancer should be considered in the differential diagnosis. It is important for the clinician to consider the clinical history of breast cancer, even when remote, in the differential diagnosis.

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.

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).

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.

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.

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.

Apoplectic leiomyomas: does ethnicity make a difference? a clinicopathologic study.

Apoplectic leiomyomas-benign uterine leiomyomas with morphologic changes including hemorrhage, hypercellularity, mitotic activity, nuclear atypia, and even necrosis-can be difficult to distinguish from uterine leiomyosarcomas. Apoplectic leiomyomas have been associated with hormonal therapy; however, the relationship between apoplectic leiomyomas, hormones, and ethnicity has not received much attention in the literature. We evaluated the relationship of hormonal therapy and ethnicity in 869 women with uterine leiomyomas, 136 of which qualified as apoplectic leiomyomas.Apoplectic leiomyomas were observed in 23.3% (49/210) of women exposed to hormonal therapy compared to 13.2% (87/659) of women not exposed to hormonal therapy (p < 0.0001). Women taking ethinyl estradiol/norethindrone (Lo-Estrin), leuprolide, and medroxyprogesterone were significantly more likely to have apoplectic leiomyomas compared to women taking other hormonal therapies. Apoplectic leiomyomas were observed in 28.9% (44/152) of African-American women compared to 12.4% (79/639) of Caucasian women (p < 0.0001), and this difference remained statistically significant regardless of hormone use. Apoplectic leiomyomas were observed in 22.1% (77/349) of women ≤ 45 years of age compared to 11.3% (59/520) of women > 45 years of age (p < 0.0001), and this difference remained statistically significant regardless of hormone use.This is the largest study to date examining apoplectic leiomyomas in women on known hormonal therapy compared to women with uterine leiomyomas, but not on hormonal therapy. Information about hormonal therapy, ethnicity, and age can be helpful in the diagnostic interpretation of apoplectic leiomyoma.

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.

Pitfalls in Pathology-Nodular Hyperplasia of Bartholin's Gland.

Nodular hyperplasia of the Bartholin's gland is an underreported and extremely rare entity that presents as a solid lesion potentially raising concern for malignancy clinically, most solid lesions at this location are carcinomas. They may also be mistaken for a Bartholin cyst clinically. Nodular hyperplasia is rarer than carcinoma of the Bartholin gland, and hence pathologists may not be familiar with this entity, making it a pitfall in pathologic as well as a clinical diagnosis. Here we report a case originally considered a Bartholin cyst, but raising intraoperative concern due to solid elements. Histological examination of the lesion revealed nodular hyperplasia of Bartholin's gland. Recognition of this entity is important, as it is something that may be encountered by the pathologist.

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.

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.

"Do-not-resuscitate (DNR)" status determines mortality in patients with COVID-19.

We investigatd the influence of do-not-resuscitate (DNR) status on mortality of hospital inpatients who died of COVID-19. This is a retrospective, observational cohort study of all patients admitted to two New Jersey hospitals between March 15 and May 15, 2020, who had, or developed, COVID-19 (1270 patients). Of these, 640 patients died (570 [89.1%] with and 70 [10.9%] without a DNR order at the time of admission) and 630 survived (180 [28.6%] with and 450 [71.4%] without a DNR order when admitted). Among the 120 patients without COVID-19 who died during this interval, 110 (91.7%) had a DNR order when admitted. Deceased positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) patients were significantly more likely to have a DNR order on admission compared with recovered positive SARS-CoV-2 patients (P < 0.05), similar to those who tested negative for SARS-CoV-2. COVID-19 DNR patients had a higher mortality compared with COVID-19 non-DNR patients (log rank P < 0.001). DNR patients had a significantly increased hazard ratio of dying (HR 2.2 [1.5-3.2], P < 0.001) compared with non-DNR patients, a finding that remained significant in the multivariate model. The risk of death from COVID-19 was significantly influenced by the patients' DNR status.

Pitfalls in Frozen Section: A Case of Incidental Papillary Mesothelioma.

Well-differentiated papillary mesothelioma is an uncommon benign, although potentially recurrent mesothelial lesion that occurs in the peritoneum of women over a wide age range. We recently encountered an incidental case sent for frozen section at the time of hysterectomy for endometrial carcinoma. Familiarity with this lesion will help prevent overinterpretation as a serous carcinoma.

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.