Benign osseous metaplasia of the breast infiltrated by invasive pleomorphic lobular carcinoma: A case report.

INTRODUCTION AND IMPORTANCE: Benign osseous metaplasia (BOM) is a rare entity, with only few cases reported in the breast. Here we present an unusual case of pleomorphic lobular carcinoma of the breast infiltrating BOM, discuss potential mimics and review the literature. CASE PRESENTATION: An 86 year-old female presented with right breast lump for two weeks. Clinical examination revealed a palpable mass, associated with skin tethering and nipple inversion. Mammography and ultrasound showed a densely calcified lesion associated with parenchymal distortion. Core biopsy confirmed malignancy and the patient underwent mastectomy and sentinel lymph node biopsy. Histological assessment showed a 45 mm mass of benign bone trabecula infiltrated by invasive grade 2 lobular carcinoma of classic and pleomorphic types with nodal positivity (2/2). The patient received adjuvant radiotherapy to chest wall and axilla for 3 months. She remains well on aromatase inhibitors after 9 months of follow up. CLINICAL DISCUSSION: Few cases of breast BOM have been reported in the literature commonly in association with benign lesions such as fibroadenomas. So far, only two cases associated with invasive classic lobular carcinoma have been reported in the literature. The main differential is metaplastic (mesenchymal/ matrix producing) carcinoma, in which the osseous component is malignant and the cancer if often of a high grade, basal phenotype. CONCLUSION: We present the first case of BOM of the breast associated with invasive pleomorphic lobular carcinoma. Awareness of the entity and distinction from metaplastic carcinoma and malignant phyllodes with heterologous element are important to ensure appropriate patient management.

Association of estrogen, progesterone and follicle stimulating hormone receptor polymorphisms with in vitro fertilization outcomes.

Despite the advances in in vitro fertilization (IVF), the implantation success rate for infertile women remains approximately only 15%. In this study, we sought to determine whether implantation failure after repeated IVF treatments is influenced by the presence of common variants in estrogen α, progesterone and follicle stimulating hormone receptor genes. The study population included three groups of women: group 1 were 50 women who had the transfer of ≥3 high-quality embryos during the IVF procedure without ever having had a clinical pregnancy; group 2 were 50 women who achieved a clinical pregnancy after ≤3 high-quality embryos transfers and group 3 were 50 control subjects who achieved a clinical pregnancy without any fertility therapy that resulted in a one live-born infant. Genotype analysis was performed using polymerase chain reaction and Sanger sequencing for rs6165, rs6166, rs2234693, rs9340799. While progesterone receptor single nucleotide polymorphism (SNP)  was genotyped based on the amplicon size, the repeats for the ESR1 TA-repeat polymorphism were calculated based on the fragment length. A higher frequency of the heterozygote AG genotype was observed in the infertile groups when compared to controls. Significantly, an allele combination of T of rs2234693, A of rs9340799; S of ESR1 (TA), A of rs6166, G of rs6165 and del of PROGINS had a higher frequency in women who had a successful IVF outcome compared to women who had an unsuccessful IVF outcome, indicating a possible protective combined genotype that could reduce a negative outcome during IVF. This study has demonstrated that combining several candidate genes is needed to assess which may play a role in fertility. ABBREVIATIONS: CI: confidence interval; COH: controlled ovarian hyperstimulation; DNA: deoxyribonucleic acid; ESR: estrogen receptors; FSH: follicle stimulating hormones; FSHR: FSH receptor; IVF: in vitro fertilization; PGR: progesterone receptors; SNP: single nucleotide polymorphism.

A Study on the Role of Estrogen Receptor Gene Polymorphisms in Female Infertility.

BACKGROUND: Female infertility is often of unknown etiology and is a significant medical problem. It occurs when implantation does not occur; a fertilized embryo fails to survive after implantation; or when the egg cannot move from the ovary to the uterus. The aim of this study was to analyze the role of estrogen receptor 1 (ESR1) genotypes in female infertility. METHODS: Blood samples were collected from 114 women with infertility undergoing infertility treatment. Samples were also collected from 115 age-matched control women with at least one live child and with no history of infertility or abortions. Genomic DNA was isolated from the blood samples, and genotyping of the ESR1 gene was performed using polymerase chain reaction-restriction fragment length polymorphism. RESULTS: The study revealed the presence of two single nucleotide polymorphisms (SNPs) in the ESR1 gene, PvuII and XbaI. Individual analyses of these two polymorphisms showed that the XbaI heterozygote was significantly increased in controls compared to cases (odds ratio-0.39, confidence interval-0.21 to 0.74, p-0.005). The combined analysis of the PvuII and XbaI genotypes showed no significant difference between the case and control samples. CONCLUSION: Analysis of the Pvull and Xba1 polymorphisms of the ESR1 gene, demonstrated that the XbaI heterozygote was significantly increased in controls indicating a protective effect.

Asymptomatic bacteriuria in pregestational diabetic pregnancies and the role of group B streptococcus.

We sought to determine if gravidas with pregestational diabetes mellitus (DM) are at increased risk for asymptomatic bacteriuria (ASB) compared with nondiabetic gravidas. This is a retrospective case-control study of 150 pregnant patients with pregestational DM and 294 nondiabetic controls. Rates of ASB and any colony count of group B streptococcus (GBS) bacteriuria were reviewed. The incidence of ASB among pregestational diabetics was higher compared with nondiabetic gravidas (18% versus 8.2%, odds ratio [OR] 2.47, 95% confidence interval [CI] 1.37 to 4.45). GBS was the most common organism in diabetic gravidas (26%). There was no difference in incidence of ASB recurrence (OR 1.26, 95% CI 0.37 to 4.36), but antibiotic resistance was higher in the control group (OR 0.28, 95% CI 0.09 to 0.91). Diabetic gravidas with ASB or any level of GBS bacteriuria had higher hemoglobin A (1c) values compared with diabetics without ASB (8.31 +/- 1.89 versus 7.31 +/- 1.84, P = 0.0035). Our results demonstrate that gravidas with DM are at increased risk of ASB including GBS bacteriuria compared with non-diabetic gravidas.

Duration of antimicrobial prophylaxis for group B streptococcus in patients with preterm premature rupture of membranes who are not in labor.

OBJECTIVE: The purpose of this study was to determine the duration of the time that is needed to eradicate group B Streptococcus (GBS) in pregnant women with preterm premature rupture of membranes (PPROM). STUDY DESIGN: A retrospective cohort study was performed of pregnant women with PPROM from January 1, 2000, through December 31, 2005. Vaginal/rectal cultures were performed on admission and repeated daily. Patients received antibiotics until cultures were negative for 3 consecutive days. RESULTS: Two hundred fourteen women were identified with PPROM; 169 of the women met the inclusion criteria. Thirty-three patients were GBS positive on admission and had negative cultures by day 3. Neonatal sepsis occurred in 19 neonates (11.2%); 3 neonates (16%) were from mothers who tested positive for GBS on admission, and 16 neonates (84%) were from mothers who tested negative on admission. There were no cases of neonatal sepsis because of GBS. CONCLUSION: A 3-day regimen of antibiotic prophylaxis appears to be adequate to eradicate GBS from the genital tract of patients with PPROM.

Is testing for cytomegalovirus and cystic fibrosis indicated in members of a nonwhite pregnant population in whom the fetus has an echogenic bowel?

The purpose of this study was to determine whether testing for cystic fibrosis (CF) and cytomegalovirus (CMV) infection is necessary in African-American and Hispanic gravidas in whom the fetus had an echogenic bowel. This retrospective study consisted of only African American and Hispanic patients in whom the fetus had an echogenic bowel, referred to the Maternal and Fetal Medicine unit at New Jersey Medical School for a specialized ultrasound, between June 30, 2004, and March 31, 2005. Sixty-five patients met the inclusion criteria for our study. Maternal serum testing for CF was done in 32 patients and all newborns were screened for the disease. There were no positive results for CF. CMV serology was tested in 38 patients and there were no cases of acute congenital CMV infection. In our population of 65 patients, there was one intrauterine growth restricted (IUGR) fetus and five intrauterine fetal demise (IUFD). Although all patients who were tested for CMV infection tested negative, the true incidence in our selected population may be underestimated because some of our patients were not tested. There were no cases of congenital CMV infection and all newborn screening tests for CF were negative. Prenatal diagnosis of fetal echogenic bowel was associated with a 7.6% incidence of IUFD and 1.6% incidence of IUGR.

From oogonia to mature oocytes: inactivation of the maternal centrosome in humans.

The fine structure of human oogonia and growing oocytes has been reviewed in fetal and adult ovaries. Preovulatory maturation and the ultrastructure of stimulated oocytes from the germinal vesicle (GV) stage to metaphase II (MII) stage are also documented. Oogonia have large nuclei, scanty cytoplasm with complex mitochondria. During folliculogenesis, follicle cell processes establish desmosomes and deep gap junctions at the surface of growing oocytes, which are retracted during the final stages of maturation. The zona pellucida is secreted in secondary follicles. Growing oocytes have mitochondria, Golgi, rough endoplasmic reticulum (RER), ribosomes, lysosomes, and lipofuscin bodies, often associated with Balbiani bodies and have nuclei with reticulated nucleoli. Oocytes from antral follicles show numerous surface microvilli and cortical granules (CGs) separated from the oolemma by a band of microfilaments. The CGs are evidently secreted by Golgi membranes. The GV oocytes have peripheral Golgi complexes associated with a single layer of CGs close to the oolemma. They have many lysosomes, and nuclei with dense compact nucleoli. GV breakdown occurs by disorganization of the nuclear envelope and the oocyte enters a transient metaphase I followed by MII, when it is arrested and ovulated. Maturation of oocytes in vitro follows the same pattern of meiosis seen in preovulatory oocytes. The general organization of the human oocyte conforms to that of most other mammals but has some unique features. The MII oocyte has the basic cellular organelles such as mitochondria, smooth endoplasmic reticulum, microfilaments, and microtubules, while Golgi, RER, lysosomes, multivesicular, residual and lipofuscin bodies are very rare. It neither has yolk nor lipid inclusions. Its surface has few microvilli, and 1-3 layers of CGs, aligned beneath the oolemma. Special reference has been made to the reduction and inactivation of the maternal centrosome during oogenesis. The MII spindle, often oriented perpendicular to the oocyte surface, is barrel-shaped, anastral and lacks centrioles. Osmiophilic centrosomes are not demonstrable in human eggs, since the maternal centrosome is nonfunctional. However, oogonia and growing oocytes have typical centrioles, similar to those of somatic cells. The sperm centrosome activates the egg and organizes the sperm aster and mitotic spindles of the embryo, after fertilization.

Telomere length in the newborn.

Telomere length is similar in different organs of the human fetus but variable among fetuses. During extrauterine life telomere length is highly variable among individuals and longer in women than men. In the present work we addressed the following questions: 1) Are there sex-related differences in telomere length at birth? 2) Is there synchrony (i.e. correlation in length) of telomeres in tissues within the newborn? 3) Is the variability in telomere length among newborns as large as that in adults? We studied normal male and female newborns who donated DNA samples from three sources: white blood cells, umbilical artery, and foreskin. Telomere length was measured by the mean length of the terminal restriction fragments (TRF). TRF length was not different between male and female newborns. It was highly synchronized among the DNA samples from white blood cells, umbilical artery and skin within individual donors but exhibited a high variability among donors. We conclude that there is no evidence for the effect of sex on telomere length at birth, suggesting that longer telomeres in women than men arise from a slower rate of telomeric attrition in women. The variability in telomere length among newborns and synchrony in telomere length within organs of the newborn are consistent with the concept that variations in telomere length among adults are in large part attributed to determinants (genetic and environmental) that start exerting their effect in utero.

Successful pregnancy in a patient with a 46,XY karyotype.

OBJECTIVE: To report a case of successful pregnancy in a patient with 46,XY karyotype with primary ovarian failure. DESIGN: Case report. SETTING: Fertility Research Center, G.G. Hospital, Chennai, Tamil Nadu, India. PATIENT(S): A 27-year-old woman with hypoplastic uterus, normal fallopian tubes on both sides, and gonadal dysgenesis. INTERVENTION(S): Chromosomal analysis, diagnostic laparoscopy, donor oocyte program, gamete intrafallopian transfer, and gonadectomy. MAIN OUTCOME MEASURE(S): Response to hormone replacement therapy and the probability of achieving a pregnancy by a tubal procedure. RESULT(S): Treatment was successful, and the patient delivered a live baby. CONCLUSION(S): A hypoplastic uterus of patients with the 46,XY karyotype can be stimulated by the use of cyclical steroid therapy to accommodate pregnancy and facilitate tubal procedures in patients with normal fallopian tubes.

Varicella vaccination during early pregnancy: a cause of in utero miliary fetal tissue calcifications and hydrops?

BACKGROUND: It is the purpose of this article to describe a suspected association of inadvertent vaccination with varicella vaccine during early pregnancy with the subsequent development of in utero miliary fetal tissue calcifications and fetal hydrops detected by sonogram at 15 weeks of gestation. CASE: This is a case presentation of a pregnant patient who received varicella vaccination during the same menstrual cycle that she became pregnant, and is supplemented by a literary review. The fetus developed miliary fetal tissue calcifications and fetal hydrops detected by a targeted sonogram at 15 weeks gestation. CONCLUSION: Varicella vaccination during early pregnancy may be a cause of miliary fetal tissue calcifications and fetal hydrops.