Pregnancy and postpartum outcomes in a universally tested population for SARS-CoV-2 in New York City: a prospective cohort study.

OBJECTIVE: To describe differences in outcomes between pregnant women with and without coronavirus dsease 2019 (COVID-19). DESIGN: Prospective cohort study of pregnant women consecutively admitted for delivery, and universally tested via nasopharyngeal (NP) swab for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using reverse transcription-polymerase chain reaction. All infants of mothers with COVID-19 underwent SARS-CoV-2 testing. SETTING: Three New York City hospitals. POPULATION: Pregnant women >20 weeks of gestation admitted for delivery. METHODS: Data were stratified by SARS-CoV-2 result and symptomatic status, and were summarised using parametric and nonparametric tests. MAIN OUTCOME MEASURES: Prevalence and outcomes of maternal COVID-19, obstetric outcomes, neonatal SARS-CoV-2, placental pathology. RESULTS: Of 675 women admitted for delivery, 10.4% were positive for SARS-CoV-2, of whom 78.6% were asymptomatic. We observed differences in sociodemographics and comorbidities among women with symptomatic COVID-10 versus asymptomatic COVID-19 versus no COVID-19. Caesarean delivery rates were 46.7% in symptomatic COVID-19, 45.5% in asymptomatic COVID-19 and 30.9% in women without COVID-19 (P = 0.044). Postpartum complications (fever, hypoxia, readmission) occurred in 12.9% of women with COVID-19 versus 4.5% of women without COVID-19 (P < 0.001). No woman required mechanical ventilation, and no maternal deaths occurred. Among 71 infants tested, none were positive for SARS-CoV-2. Placental pathology demonstrated increased frequency of fetal vascular malperfusion, indicative of thrombi in fetal vessels, in women with COVID-19 versus women without COVID-19 (48.3% versus 11.3%, P < 0.001). CONCLUSION: Among pregnant women with COVID-19 at delivery, we observed increased caesarean delivery rates and increased frequency of maternal complications in the postpartum period. Additionally, intraplacental thrombi may have maternal and fetal implications for COVID-19 remote from delivery. TWEETABLE ABSTRACT: COVID-19 at delivery: more caesarean deliveries, postpartum complications and intraplacental thrombi.

h-Caldesmon, a novel smooth muscle-specific antibody, distinguishes between cellular leiomyoma and endometrial stromal sarcoma.

The difficulty in distinguishing between smooth muscle and endometrial stromal-derived neoplasms of the uterine corpus is a notorious and clinically relevant problem in pathology of the female genital tract. Immunohistochemistry offers some aid in resolving this difficulty, because the expression of smooth muscle markers is reputed to indicate smooth muscle derivation. This expression, however, is not entirely specific, and difficult cases may still present in which immunohistochemistry is of little help. To explore this problem, the authors evaluated the expression of traditional muscle markers and high-molecular-weight caldesmon (h-cal), an actin and tropomyosin binding protein that has recently been described as a useful muscle marker, in uterine leiomyosarcoma (LMS), cellular leiomyomata (CL), and endometrial stromal sarcoma (ESS). Formalin-fixed and paraffin-embedded tissue sections from nine LMSs, 11 CLs, and 12 ESSs were evaluated with commercially available monoclonal antibodies against smooth muscle actin (SMA), desmin, and h-cal. Established morphologic criteria were used to classify the neoplasms. We found that there was, as expected, a significant difference in the expression of traditional smooth muscle markers (SMA and desmin) between tumors derived from smooth muscle and those derived from endometrial stroma (p = 0.005 for LMS and 0.013 for CL). We further found that h-cal was most useful in distinguishing between CL and ESS (p = 0.01). A significant difference between h-cal expression in LMS versus ESS was not found. Of note, one ESS expressed both SMA and desmin but lacked h-cal expression. Our findings confirm the most useful immunohistochemical data to date; smooth muscle neoplasms are generally distinguishable from endometrial stromal tumors by the expression of conventional muscle markers. We also report here that h-cal is useful more specifically in the differentiation of CL from ESS.

Complete hydatidiform mole with a coexistent embryo.

We describe a case of a complete hydatidiform mole with a coexistent embryo. A 19-year-old Hispanic woman presented with an intrauterine pregnancy at 7 weeks gestational age. An ultrasound evaluation at that time showed a gestational sac and fetal heart activity was observed. Four weeks later, subsequent ultrasound study revealed no evidence of an embryo, and a pattern consistent with a hydatidiform mole. Dilation and curettage was subsequently performed that showed a classic hydatidiform mole on histological examination. Chromosome analysis revealed a normal 46,XX karyotype. DNA was extracted from the placental tissue, as well as maternal and paternal blood. Molecular genetic analysis was; performed with four variable number of tandem repeats (VNTR) probes and showed the placental tissue to consist of only paternal DNA with two genomic copies of each allele studied. These findings are consistent with the diagnosis of complete hydatidiform mole and its origin from an empty ovum fertilized by a single sperm. This is the first reported case of a living embryo coexistent with a complete hydatidiform mole documented by genetic analysis.

Placental site trophoblastic tumor: human placental lactogen and pregnancy-associated major basic protein as immunohistologic markers.

Placental site trophoblastic tumor (PSTT) consists of a neoplastic proliferation of intermediate or extravillous trophoblast (also known as X cells). Pregnancy-associated major basic protein (pMBP) is a marker for placental intermediate trophoblast. We compared the distribution of pMBP and human placental lactogen (hPL) in 24 PSTT and 3 exaggerated placental site (EPS) specimens using two distinct immunohistologic methods. Statistical analyses were used to compare staining intensities in metastatic and nonmetastatic lesions. By immunofluorescence, 77% of the PSTT specimens and 100% of the EPS specimens stained with antibodies to pMBP, and the pMBP was localized in intermediate trophoblast and surrounding extracellular areas. By immunohistochemistry, 78% of the PSTT specimens and 100% of the EPS specimens stained for pMBP with a pattern comparable with that of immunofluorescence. Likewise, by immunohistochemistry, hPL stained 96% of the PSTT specimens and 100% of the EPS specimens. Immunohistochemical staining intensities for pMBP and hPL correlated (r2 = +.24; P = .013), but hPL staining was mainly confined to intermediate trophoblast and was more intense. Anti-pMBP tended to stain metastatic PSTT weakly. Thus, pMBP is a useful marker for intermediate trophoblast tumors and could help distinguish these from other forms of trophoblastic disease.

Features of cancer in nonagenarians and centenarians.

OBJECTIVE: To describe the incidence rates and sites of cancer, the causes of death, and gender and ethnic variations in patients with cancer in a population of people 90 years of age and older. DESIGN: Analysis of the 14,088 cases of cancer in this age group, accessioned by the California Cancer Registry from 1988 through 1993, and comparison with those less than age 90. MEASUREMENTS: Incidence rates and numbers and percents of cases with various features (gender, ethnicity, site of tumor, stage, causes of death). RESULTS: The peak age-specific incidence (ASI) of cancer is in the group 80 to 84 years of age. Those 90 to 94 years of age had a higher ASI than any group except those ages 75 to 89. There are ethnic variations in the sites of cancer in people aged 90 or older. Colorectal cancer accounts for more than one-fifth of the new cases of cancer in people 90 or older. In women aged 90 or older, the most common sites of cancers are colorectal, breast, and lymphoma/leukemia. In men of the same age, prostate, colorectal, and lung/bronchus are the most common sites. As age increases, fewer people have their cancers staged, and for lung/bronchus, prostate, and breast, more cancers are first diagnosed in the distant stage in people aged 90 and older. Of the people with cancer who die, the proportion dying of cancer decreases as age increases. CONCLUSION: Cancer is a common disease in nonagenarians and centenarians and will be an increasing healthcare problem. Knowledge of its features is essential to those planning, delivering, and financing health care.

Maternal melanoma metastatic to the placenta: a case report and review of the literature.

Metastases of maternal cancer to the placenta and fetus are rare in cases of maternal primary malignancy. This report describes a case of malignant melanoma metastatic to the placenta, reviews the literature, and discusses the clinical significance. A 33-year-old woman presented at 30 weeks' gestation with multiple metastases from a malignant melanoma diagnosed 4 years previously. Rapid maternal deterioration necessitated premature cesarean delivery, and maternal death occurred 7 days later. The placenta showed multiple metastases of malignant melanoma. The infant, however, is alive and well at 7 months of age. Melanoma in pregnancy rarely results in metastasis to the conceptus, but when it does occur there may be fatal consequences to the fetus. Therefore, the placenta should be thoroughly examined for metastasis, which, if present, should alert the clinician to monitor the infant for development of malignant disease.

Macroscopic examination of the placenta immediately following birth.

Macroscopic examination of the placenta can be performed readily by the healthcare providers present at the time of birth. It can be accomplished with a basic knowledge of placental pathology and a general understanding of the abnormalities and variations that affect the placenta. These observations can easily be entered into the medical record and may often provide information about intrauterine life that will help the future care of both mother and infant.

Gestational choriocarcinoma.

The malignant transformation of trophoblast is interesting to contemplate, as trophoblast normally behaves in a manner that is interpreted as indicative of malignancy. First of all, trophoblasts show "controlled invasion" at the placental site as part of the normal process of implantation. Secondly, it is estimated that 100,000 syncytiotrophoblastic cells are deported to the maternal circulation daily and these are commonly identified in the pulmonary circulation of pregnant women (38). These trophoblastic cells do not ordinarily produce disease and presumably are rejected by the mother, unlike true metastases. When trophoblastic malignancy does develop, however, the trophoblast continues to invade and grow without limit, eventually metastasizing and ultimately leading to death. Choriocarcinoma is, therefore, unique in that it represents a malignant transformation of a tissue that inherently has "invasive" and "metastatic" properties. It is also the only tumor which contains DNA foreign to the host, as it is derived from a conception which contains paternal genetic material. Thus, choriocarcinoma is a complex neoplasm, and to study it, one must study and understand graft rejection, immunologic mechanisms and a multitude of genetic concepts in addition to the mechanisms of invasion and metastasis.

Mucin histochemistry of ovarian borderline tumors of mucinous and mixed-epithelial types.

Mucin histochemistry was studied in 23 intestinal-type mucinous borderline tumors, 21 endocervical-like mucinous borderline tumors, and 24 mixed-epithelial borderline tumors. The latter two tumors, which are of müllerian type, had a mucin composition similar to that of normal endocervix, with abundant neutral and acidic mucins in approximately equal amounts and a slight predominance of sialomucins over sulfomucins. Intestinal-type mucinous borderline tumors showed several patterns that most closely resembled gastric mucosa with varying degrees and types of intestinal metaplasia. In conclusion, mucin histochemistry shows striking differences between these two types of müllerian borderline tumors compared with intestinal-type mucinous borderline tumors and confirm the subclassification of mucinous borderline tumors into intestinal and endocervical types.

Mural nodules in common epithelial tumors of the ovary.

The occurrence of mural nodules in cystic common epithelial tumors of the ovary is well established, but differences in terminology and difficulties in histopathologic interpretation have hampered adequate understanding of their differential diagnoses and prognoses. Using immunohistochemistry and ultrastructural analyses supplementally, we studied two cases, one a serous cystadenocarcinoma with nodules of undifferentiated sarcoma, the other a mucinous cystadenocarcinoma with mural nodules of anaplastic carcinoma. Based on these cases and a review of 48 cases in the literature, we propose a standardized terminology. Mural nodules may be either reactive or neoplastic. Neoplastic mural nodules may be composed of benign elements, carcinoma, carcinoma with reactive elements, sarcoma, or an admixture of carcinoma and sarcoma; the latter category has some similarities to malignant mixed mesodermal tumors. The prognosis of patients with malignant mural nodules is poor, with 50% mortality. Strict morphologic criteria supplemented by immunohistochemistry aids in the sometimes difficult differential diagnosis among these types of mural nodules.

Trophoblastic lesions of the placental site.

The trophoblast of the chorionic villi as well as the hydatidiform mole and choriocarcinoma have been recognized and studied for many years. However, the trophoblast comprising the implantation site, chorionic plate, chorion laeve, cell islands and septa have only in recent years received attention in the literature. These "extravillous" trophoblastic cells were originally referred to as "X" cells due to doubt regarding their derivation from either maternal or fetal tissue (70). Subsequent studies determined that they were trophoblastic in origin (42), but the term X-cell is still in use today by some researchers (30, 4). Due to continued uncertainty regarding their nature and origin, many other terms have been used including syncytial wandering cells (21), placental site trophoblast, placental site giant cells (42), extravillous trophoblast (25), extravillous cytotrophoblast, nonvillous trophoblast, and intermediate trophoblast (49). Light microscopic and immunohistochemical studies have led to elucidation of specific morphologic and biochemical features of the extravillous trophoblast (48-50) which is commonly designated as the "intermediate trophoblast". Lesions of the "intermediate" or extravillous trophoblast of the placental site include the exaggerated placental site, the placental site trophoblast tumor and the recently described placental site nodule. This article will review the clinical and pathologic features of these lesions, their differential diagnosis, treatment, and prognostic factors after discussion of the origin, nature and definition of the "intermediate" trophoblast.

Morbidity, mortality, and placental pathology in excessively long umbilical cords: retrospective study.

The purpose of this study was to compare specific fetal, maternal, and placental factors, including neonatal morbidity and mortality, in infants with umbilical cords (UCs) of normal length to the same factors in infants with excessively long umbilical cords (ELUCs). We performed an 18-year retrospective chart review of the medical records of mothers and infants with ELUCs (926 cases) and normal-length UCs (200 cases) and recorded maternal factors, fetal factors, and neonatal outcomes. Corresponding placental pathologic reports and slides were reviewed. Statistical analysis comparing the two groups included univariate and multivariate analyses. ELUCs were significantly associated with certain maternal factors (systemic diseases, delivery complications, increased maternal age), fetal factors (non-reassuring fetal status, respiratory distress, vertex presentation, cord entanglement, fetal anomalies, male sex, increased birth weight), gross placental features (increased placental weight, right-twisted cords, markedly twisted cords, true knots, congestion), and microscopic placental features (nucleated red blood cells, chorangiosis, vascular thrombi, vascular cushions, meconium, increased syncytial knots, single umbilical artery). Some of these histopathologic features have previously been associated with fetal hypoxia and/or altered blood flow in the placenta. Infants with ELUCs were found to be at a significantly increased risk of brain imaging abnormalities and/or abnormal neurological follow-up. In addition, mothers with a history of an ELUC are at increased risk of a second long cord.

B-lineage lymphoblastic lymphoma is a clinicopathologic entity distinct from other histologically similar aggressive lymphomas with blastic morphology.

BACKGROUND: The authors present clinical, histopathologic, and immunophenotypic data regarding B-lineage lymphoblastic lymphoma (B-LBL), a rare entity that has not been extensively studied. To emphasize some of its unique clinical characteristics, the authors compare B-LBL with a group of histologically similar, very aggressive lymphomas, T-lineage lymphoblastic lymphoma (T-LBL) and the blastoid variant of mantle cell lymphoma (BVMCL); all were evaluated concurrently. METHODS: Clinical data were obtained on 29 patients with very aggressive lymphomas (12 B-LBLs, 10 T-LBLs, and 7 BVMCLs) from whom paraffin-embedded material was available. The diagnoses were confirmed on review of the hematoxylin and eosin-stained slides and the immunophenotype data. RESULTS: The mean age of patients with B-LBL was 39 years. Patients presented with both lymph node and extranodal disease, although involvement of the mediastinum and bone marrow was infrequent. Four were Stage I, 3 were Stage II, 2 were Stage III, and 3 were Stage IV. B-LBL patients were treated primarily with cyclophosphamide, hydroxydaunomycin, vincristine, and prednisone (CHOP), and one patient underwent allogeneic bone marrow transplantation. The mean follow-up time was 30 months. Seven of 11 had no evidence of disease at 48 months, whereas 4 patients were dead of disease at 5.6 months. The overall median survival was 24 months. The clinical characteristics of B-LBL patients differed significantly from those of T-LBL patients; there was more frequent bone marrow and mediastinal involvement in T-LBL cases (P = 0.03 and 0.04, respectively). T-LBL patients were also less likely to achieve a complete remission than B-LBL patients (P = 0.02). The mean age of BVMCL patients significantly exceeded that of B-LBL patients (P = 0.03). CONCLUSIONS: The authors believe that the distinction of B-LBL from its histologic mimics, T-LBL and BVMCL, has important clinical implications. Patients with B-LBL present differently from those with the other very aggressive lymphomas studied, and they achieve complete remissions more often than T-LBL patients.

Tumor suppressor gene, cell surface adhesion molecule, and multidrug resistance in Müllerian serous carcinomas: clinical divergence without immunophenotypic differences.

OBJECTIVES: We hypothesize that differences in the expression of selected tumor suppressor genes, cell surface adhesion molecules, and multidrug resistance glycoproteins could account for some of the reported differences between uterine serous carcinoma (USC) and extrauterine serous carcinomas (ESC), including ovarian and primary peritoneal carcinoma (OSC and PSC, respectively). METHODS: We studied the expression of the following antigens in 20 USCs, 20 OSCs, and 10 PSCs: p53 and mdm-2 (tumor suppressor genes), CD44 and CD44v6 (cell surface adhesion molecules), and the p-glycoprotein (a multidrug resistance protein recognized by two antibodies, C494 and JSB1). We further studied chemotherapeutic drug resistance by examining reports prepared using the Oncotech Extreme Drug Resistance Assay from 24 of the 50 study patients. Clinical data were obtained from medical record review. RESULTS: USC, OSC, and PSC patients were similar with respect to mean age at diagnosis, mean gravidity, mean parity, personal history of breast cancer, percentage treated with chemotherapy, and survival at 3 and 5 years postdiagnosis. Significant clinical differences included a high prevalence of nulliparity in OSC (P = 0.05), a low prevalence of Caucasian race in USC (P = 0.008), a paucity of stage I patients in OSC and PSC (P = 0.03), a high prevalence of familial breast cancer in OSC (P = 0.06), and superior 2-year survival in OSC (P = 0.02). Seventy-five percent of USCs, 52% of OSCs, and 60% of PSCs expressed p53. Five percent of USCs, 19% of OSCs, and 0% of PSCs expressed mdm-2. Forty percent of USCs, 33% of OSCs, and 10% of PSCs expressed CD44. None of the USCs, OSCs, or PSCs expressed CD44v6. Sixty-one percent of USCs and OSCs and 82% of PSCs expressed C494 while 17% of USCs, 19% of OSCs, and 20% of PSCs expressed JSB1. None of these apparent differences was statistically significant. USC, OSC, and PSCs patients did not demonstrate significant differences with respect to extreme drug resistance. However, the following trends were noted (P = 0.06): more prevalent low drug resistance for cyclophosphamide in OSC compared with USC and more prevalent extreme drug resistance for etoposide in OSC compared with USC. CONCLUSIONS: Therefore, despite significant clincial differences, the USCs and ESCs in our series do not differ significantly with respect to the expression of the tumor suppressor genes, cell surface adhesion molecules, and drug resistance proteins studied. It is premature, however, to recommend that USCs and ESCs should be treated identically.

Cyclin D1 expression in high-grade endometrial carcinomas--association with histologic subtype.

Endometrial endometrioid adenocarcinoma (EC) and serous carcinoma (ESC) are associated with different epidemiologic risk factors, precursor lesions, morphology, and survival outcomes. They also possess distinct molecular profiles. We investigated the expression of cyclin D1, a member of the G1 cyclin family that regulates the G1/S transition in the cell cycle, and estrogen and progesterone receptors (ERs and PRs, respectively) in a group of ECs and ESCs matched for histological grade. We also sought to correlate the expression of cyclin D1 with ER and PR because cyclin D1 has been reported to stimulate transcription of ER- and PR-regulated genes (1,2). We hypothesize that cyclin D1 expression covaries with histologic subtype and is related to the expression of ER and PR. Twenty ESCs and 21 ECs were examined histologically and evaluated immunohistochemically for cyclin D1, ER, and PR using commercially available monoclonal antibodies in archival, formalin-fixed, and paraffin-embedded tissue. Three ESCs (15%) and 10 ECs (48%) expressed cyclin D1 (p = 0.02). Twelve ESCs (60%) and 16 ECs (76%) expressed ER, which is not significantly different. ER-positive ECs were significantly more likely to express cyclin D1 compared with ER-positive ESCs (p = 0.03), but a relationship between cyclin D1 and ER expression in EC was not found. We also did not find a significant relationship between cyclin D1 and PR expression. Therefore, cyclin D1 expression in poorly differentiated endometrial carcinomas is associated with endometrioid histology. This is consistent with pathobiologic divergence in poorly differentiated endometrial carcinomas.

Endometrioid ovarian carcinoma in a premenarchal girl: report of a case.

In children and adolescents, ovarian neoplasms are predominantly germ cell and sex cord stromal tumors. Carcinomas are quite rare, and, in particular, endometrioid adenocarcinomas are extremely rare in this age group. We report the case of a 13-year-old girl with FIGO stage I, grade I endometrioid adenocarcinoma of the ovary. To our knowledge this is the first report of an endometrioid carcinoma of the ovary occuring in the premenarchal age group and only the second case reported before age 15. Our patient has been treated by conservative surgery without postoperative chemotherapy. Menarche occured 3 months after surgery. Twelve months after surgery she is free of disease.