The HPV-DNA Test in Pregnancy: A Review of the Literature.

Human papillomavirus (HPV) is a virtually necessary cause of cervical cancer, and HPV genotypes are categorized either as high-risk or low-risk based on their potential to cause malignancy of the cervix. HPV-DNA detection is used widely for screening women at risk. However, its clinical significance is not proven sufficiently in pregnancy. The aim of this review was to summarize published data referring to the integration of the HPV-DNA test in cervical cancer screening during pregnancy. PubMed and Scopus were searched for articles investigating the HPV-DNA test during pregnancy as a primary association; greater interest was placed on studies published after 2000. Retrieved articles reported similarities or discrepancies in the HPV-DNA test in pregnant women compared to those who are not pregnant, its accuracy, and its integration in cervical cancer screening. The HPV-DNA test may constitute a helpful tool utilized for monitoring, risk stratification, and triage of cases that require colposcopy. If combined with the HPV-mRNA test, this might improve its specificity. However, when compared to HPV-DNA detection rates in non-pregnant women, the results were ambiguous, without giving the opportunity to draw safe conclusions. Both those findings and the high cost hold it back from wide use. Hence, the Papanicolaou smear (Pap smear) is still the first-line diagnostic tool and colposcopy-guided cervical biopsy is the "gold standard" method for the management of cervical intraepithelial neoplasia (CIN) treatment during pregnancy.

A Large Exophytic Tumor of the Cervix Causing Vaginal Bleeding in Pregnancy: A Case Report.

Vaginal bleeding in the second and third trimesters of pregnancy is usually due to placental causes, namely placental abruption and placenta previa. Other causes include uterine rupture, vasa previa, and hematologic disorders. However, benign or malignant lesions of the vagina and the cervix may also cause vaginal bleeding or spotting. Although cervical cancer in pregnancy is rare, about 8% of pregnant women have an abnormal Pap smear and 3% of the total cervical cancers are diagnosed during pregnancy. We report a case of a 20-week pregnant woman who presented with vaginal bleeding; a visual inspection revealed a large exophytic lesion of the cervix. The Pap smear demonstrated a low-grade squamous intraepithelial lesion (LSIL) related to human papillomavirus (HPV) infection. The differential diagnosis based on the findings of the colposcopy included invasive cervical carcinoma, warty lesions, and perishable lesion. A cesarean section and the removal of the cervical tumor were scheduled and carried out as planned at 37 weeks of gestation. The histologic examination showed extensive lesions of low-grade squamous intraepithelial cervical neoplasia (LSIL/CIN1). Despite the fact that exophytic tumors of the cervix are extremely rare, in women presenting with vaginal bleeding or spotting during the second or third trimester of pregnancy, the ultrasound scan must be followed by a visual inspection of the vagina and the cervix.

Presence of HPV 16 and HPV 18 in Spermatozoa and Embryos of Mice.

BACKGROUND/AIM: Sperm cells are competent to integrate exogenous DNA into their genome. We sought to clarify Human Pappiloma Virus (HPV) internalization in spermatozoa and early preimplantation embryos. MATERIALS AND METHODS: Sperm was incubated with plasmid vectors containing the complete genome of human HPV 16 and HPV 18 tagged with the green fluorescent protein (GFP) gene, to investigate HPV 16 and HPV 18 integration in mouse spermatozoa. Oocytes were in vitro fertilized with preincubated spermatozoa to investigate HPV 16 and HPV 18 potential transfer to mouse embryos. RESULTS: Spermatozoa were able to internalize constructs of cloned high-risk HPV either as integrated or as episomal DNA. Constructs of cloned HPV can also be transferred to mouse embryos, through in vitro fertilization of the oocytes by mouse spermatozoa. CONCLUSION: Viral DNA transmission to the early mouse embryo via sperm, highlights the effect of HPV in reproductive cells and preimplantation development.

Extramedullary Leukemia, Presenting at the Cervix of the Uterus.

Extramedullary relapse of leukemia is encountered more often than in the past. The reason is that leukemia survival rates increase with improved treatment schemes. We present a rare case of involvement of the cervix of the uterus in an adult B Acute Lymphocytic Leukemia (B-ALL) survivor. Relapses affect various organs but rarely the female genital tract. Nevertheless, in this case, a woman with a history of induced amenorrhea due to treatment for leukemia presented to the gynecologist because of vaginal spotting. Colposcopy evaluation of the vagina/cervix, sonography and cytological and histological sampling established the diagnosis of leukemia relapse in the cervix of the uterus. Under these circumstances, our study highlights the rare extramedullary presentation of leukemia in the cervix of the uterus of a young lady considered to be disease-free and listed for bone marrow transplantation. In this rare case of relapse in the cervix of the uterus, Pap smears alarmed physicians, and radiology examinations assisted the diagnostic workup. Still, only biopsy, microscopic evaluation, and immunohistochemistry studies established the exact diagnosis. Prognosis in the situation of extramedullary disease relapse in the female genital tract was poor, but gynecologists' high suspicion led to a prompt diagnosis. Survival is in general limited, but together with high suspicion, multidisciplinary team involvement is imperative to improve the reduced chances of survival.

Breast metastasis from uterine leiomyosarcoma diagnosed by fine needle aspiration: a case report.

BACKGROUND: Leiomyosarcomas of the breast are a rare subgroup of primary breast sarcomas. Even more rare is breast metastasis of an extramammary leiomyosarcoma. To date, only 4 cases have been reported in the literature. CASE: We report a case of breast metastatic leiomyosarcoma in a 58-year-old woman with a prior history of uterine leiomyosarcoma, resected 18 months earlier. The breast mass was palpable and a fine needle aspiration (FNA) was performed. The microscopic examination showed cellular smears composed of loosely structured clusters and tissue fragments of spindle-shaped and polygonal or rounded malignant cells in disorderly arrangement. The tumor cells were medium- or large-sized, with basophilic cytoplasm and enlarged, irregular, hyperchromatic nuclei with nucleoli. Tumor giant cells and multinucleation were also present. The morphologic features along with immunocytochemical positivity for desmin, muscle-specific actin and vimentin indicated the diagnosis of a metastatic leiomyosarcoma. CONCLUSION: FNA cytology can be a reliable method for the diagnosis of leiomyosarcoma. The morphologic criteria in combination Swith the clinical history and the immunocytochemical findings can indicate a definitive diagnosis and avoid additional painful and time-consuming diagnostic procedures for the appropriate patient's further clinical management.

Serum levels, and bone marrow immunohistochemical expression of, vascular endothelial growth factor in patients with chronic myeloproliferative diseases.

Current data suggest that angiogenesis plays a significant role in the pathogenesis and progression of chronic myeloproliferative diseases (cMPDs). In the present study, we evaluated serum levels of vascular endothelial growth factor (VEGF) in 83 patients with cMPDs [myelofibrosis with myeloid metaplasia (MMM, n = 25), essential thrombocythaemia (ET, n = 40), polycythaemia vera (PV, n = 8) and chronic myeloid leukemia (CML, n = 10)] and in 27 healthy individuals. Serum VEGF levels were significantly increased in patients with cMPDs compared to healthy individuals (all p values were < or = 0.05) and were significantly correlated with bone marrow microvessel density (MVD) (p = 0.0013). In addition, the immunohistochemical expression of VEGF protein in bone marrow biopsy specimens were analyzed in 61 patients with cMPDs, (ET, n = 36 and MMM, n = 25) and in 27 healthy individuals. The cellular distribution of VEGF expression was similar in bone marrow specimens of patients and healthy individuals. VEGF protein was detected mainly in erythroid cells, whereas myeloid cells and megakaryocytes exhibited a variable expression of the protein. The percentage of bone marrow VEGF positive cells was positively correlated with serum levels of VEGF (p = 0.001). The results of the present study suggest that, VEGF is a major angiogenetic factor in patients with cMPDs and contributes to the pathogenesis of these diseases.

Immunohistochemical study of apoptosis-related Bcl-2 protein and its correlation with proliferation indices (Ki67, PCNA), tumor suppressor genes (p53, pRb), the oncogene c-erbB-2, sex steroid hormone receptors and other clinicopathological features, in normal, hyperplastic and neoplastic endometrium.

The bcl-2 gene codes for a protein which functions to inhibit apoptotic cell death, that involves an intrinsic normal cell death program. Bcl-2 overexpression was originally described in a follicular lymphoma, but more recently bcl-2 expression has been observed in a variety of other human neoplasms. Variation in the frequency of apoptosis in hormone-sensitive tissues, such as the endometrium, is known to occur as a result of hormonal changes in both physiological and pathological circumstances. In this study we examined bcl-2 protein expression in a total of 170 samples of endometrial tissues (18 proliferative endometrium, 14 secretory endometrium, 35 adenomatous hyperplasia and 103 carcinomas). The results were compared with p53, pRb and c-erbB-2 proteins expression, estrogen and progesterone receptors status, with the proliferative activity and with clinicopathological features. The expression of bcl-2 protein was lower in the group of carcinomas, when compared with the cases of adenomatous hyperplasia (p < 0.0001), normal proliferative (p < 0.0001) and secretory endometrium (p = 0.07). In normal proliferative endometrium bcl-2 expression was correlated with PCNA (p = 0.026) and in secretory endometrium it was correlated with ER status (p = 0.042). In hyperplasias, bcl-2 was correlated with PCNA (p = 0.019) and the PR (p = 0.007) expression. In carcinomas, decreased bcl-2 expression was associated with increased tumor grade (p = 0.04). A positive relationship between bcl-2 expression and pRb, as well as PCNA score (p = 0.014 and p = 0.001, respectively), was also found. These results indicate that bcl-2 expression may play a role in the inhibition of apoptosis in endometrial carcinoma and its expression seems to be associated with tumor differentiation and cell proliferation.