Thin-layer cytology findings of small cell carcinoma of the lower female genital tract. Review of three cases with molecular analysis

OBJECTIVE: To describe the thin-layer cytology findings of small cell carcinoma of the low female genital tract, with histologic correlation and human papillomavirus (HPV) genotyping. STUDY DESIGN: The authors reviewed the clinical findings, thin-layer cytology and histologic features of small cell carcinoma of the lower female genital tract (cervix or vagina) occurring in three postmenopausal Chinese women at Pamela Youde Nethersole Eastern Hospital, Hong Kong, over a four-year period, from January 1998 to December 2001. Molecular techniques for HPV screening and genotyping using the polymerase chain reaction and restriction fragment length polymorphism were employed on the cytologic specimens. RESULTS: The thin-layer preparations were of moderate to high cellularity. There were loose aggregates of or isolated small round cells with a high nuclear/cytoplasmic ratio, thin but irregular nuclear membrane, hyperchromatic nuclei, inconspicuous nucleoli and scanty cytoplasm. Tumor cell cannibalism was commonly found. Small groups of tumor cells with nuclear molding were noted. There was also obvious tumor diathesis in the background. The necrotic debris was admixed with isolated small round cells, apoptotic bodies and nuclear dust. Associated koilocytosis or squamous intraepithelial lesions were not seen. Histologic examination of the tumor biopsies showed classic features of small cell carcinoma associated with squashing artifacts and vascularized stroma. Molecular analysis revealed the presence of HPV DNA (either type 18 or 16) in all the three liquid-based cytology samples. CONCLUSION: While the cytomorphologic features of small cell carcinoma of the cervix or vagina in thin-layer preparations are slightly different from those in conventional smears, due mainly to the absence of smearing effect, recognition of the subtle but characteristic appearance can enhance the accuracy of the cytologic diagnosis. The association between HPV and primary small cell carcinoma of the lower female genital tract was confirmed by this study.     

Cytology of clear cell carcinoma of the female genital tract in fine needle aspirates and ascites

OBJECTIVE: To define the cytomorphologic features of clear cell carcinoma (CCC) of the female genital tract. STUDY DESIGN: The study consisted of four CCCs of the female genital tract in which clinical and histologic confirmation had been done. Cytologic findings were evaluated with May-Grünwald-Giemsa (MGG) stain of three cases of fine needle aspiration (FNA) material and peritoneal fluid cytology. All the FNA materials were obtained from metastatic supraclavicular lymph nodes. RESULTS: We report here the cytomorphologic features of three FNA biopsies and peritoneal fluid cytology from four patients. Primary tumors from patients with aspiration material from supraclavicular lymph nodes were located in the ovary in two patients and vagina in one. The peritoneal fluid cytology was obtained from a patient with uterine cervical tumor. Cytologic findings were similar in all preparations. The cells had abundant, pale, finely vacuolated cytoplasm with indistinct cytoplasmic membranes. The nuclei were round to oval, with fine chromatin. The characteristic feature of CCC of the genital tract was basement membrane-like substance. This hyaline extracellular material stained pinkish to purple-red in MGG preparations and was frequently observed within the cancer cell clusters. In ascitic fluid, psammoma bodies were also observed. CONCLUSION: The cytomorphologic characteristics of CCC of the genital tract are distinctive, and the entity may easily be diagnosed even at metastatic locations.     

Immunological responses to semen in the female genital tract

When spermatozoa, seminal plasma and semen extender reach the uterus and interact with local leukocytes and endometrial cells, several immune mechanisms are initiated which have immediate, mid-term and long-term effects on ovulation, sperm cell selection, fertilization and pregnancy success by assuring the acceptance of fetal tissues. This report gives an overview on relevant key immune mechanisms following roughly the time axis after insemination. Detailed knowledge regarding these mechanisms will aid maximizing reproductive efficiency in livestock production. In the future, the many species involved will require a more comparative approach, since evidence is growing that endometrial physiology and the response to varying amounts and compositions of seminal plasma, various semen extenders, and variable numbers of spermatozoa also provoke different immune responses.     

Non-small cell lung carcinoma cell motility, rac activation and metastatic dissemination are mediated by protein kinase C epsilon

Background

Protein kinase C (PKC) ε, a key signaling transducer implicated in mitogenesis, survival, and cancer progression, is overexpressed in human primary non-small cell lung cancer (NSCLC). The role of PKCε in lung cancer metastasis has not yet been established.

Principal Findings

Here we show that RNAi-mediated knockdown of PKCε in H358, H1299, H322, and A549 NSCLC impairs activation of the small GTPase Rac1 in response to phorbol 12-myristate 13-acetate (PMA), serum, or epidermal growth factor (EGF). PKCε depletion markedly impaired the ability of NSCLC cells to form membrane ruffles and migrate. Similar results were observed by pharmacological inhibition of PKCε with εV1-2, a specific PKCε inhibitor. PKCε was also required for invasiveness of NSCLC cells and modulated the secretion of extracellular matrix proteases and protease inhibitors. Finally, we found that PKCε-depleted NSCLC cells fail to disseminate to lungs in a mouse model of metastasis.

Conclusions

Our results implicate PKCε as a key mediator of Rac signaling and motility of lung cancer cells, highlighting its potential as a therapeutic target.     

女性生殖道微生态屏障

随着感染微生态学的发展,尤其是宿主-微生物相互作用的研究深入,越来越多的研究发现,新的微生态屏障在维持宿主健康方面发挥着重要作用。微生态屏障包括微生物屏障,机械屏障,免疫屏障和化学屏障四个部分。其中机械屏障是微生态屏障的基础,微生物屏障是微生态屏障的关键,免疫屏障是微生态屏障的核心,化学屏障是微生态屏障的有机组成部分。微生态屏障可维持宿主生境的微生态平衡,防止病原微生物的入侵和感染的发生。     

Pathogenicity of Ureaplasma urealyticum and Ureaplasma parvum in the lower genital tract of female BALB/c mice

The aim of this study was to establish a murine model of lower genital tract infection by Ureaplasma urealyticum and Ureaplasma parvum and evaluate differences in pathogenicity of five serotypes. BALB/c female mice were divided into seven groups (five mice in each group), including five groups infected in the lower genital tract after treatment with estradiol with U. urealyticum serotypes 4 and 8 and U. parvum serotypes 1, 3, and 6, respectively, and two control groups of untreated mice and estradiol treated mice. The presence of infection was determined on solid and liquid culture media. Tumor necrosis factor-alpha (TNF-α) expression in lower genital tract secretions was determined by PCR, and morphological and histological changes of the lower genital tract were observed. The genital secretions of all inoculated mice were positive for U. urealyticum and U. parvum on culture in both liquid and solid media. TNF-α expression at 7 and 14 days after infection was markedly increased as compared with that of the controls. Morphological changes of the external genitalia included hair loss and erosions, and histological examination revealed infiltration by inflammatory cells. The five serotypes tested were all found to be pathogenic, and the pathogenicity varied with serotype 4 showing the greatest pathogenicity.     

Nerves immunoreactive to vasoactive intestinal polypeptide in the porcine female genital tract

The immunoreactivity of vasoactive intestinal polypeptide (VIP) was localized at the light-microscopical level in cryostat sections using a peroxidase-antiperoxidase technique or at the electron-microscopical (EM) level in glutaraldehyde-fixed, resin-embedded sections, using an immunogold technique, of tissue samples from the genital tract of cycling pigs. X-ray micro-analysis of glutaraldehyde-dichromate-fixed sections was used to discriminate noradrenaline-containing nerves. VIP immunoreactivity was localized to nerves associated to some degree with epithelial cells, blood vessels and non-vascular smooth muscle. VIP nerves were most concentrated in the cervix and the uterus, localized in the submucosa, the muscle layers and the adventitia. Nerve profiles were also seen accompanying blood vessels in the endometrium, running close to the uterine glands. In the oviduct, VIP nerves had a similar localization though less dense. At the EM level, the immunogold localization confirmed the above-mentioned results, VIP being localized in synaptic vesicles. Nerve terminals without VIP reactivity had an EM appearance of cholinergic nerve terminals or were chrome positive (noradrenaline-containing) at X-ray micro-analysis, thus being adrenergic terminals. It is concluded that the porcine female genital tract is well innervated, along with adrenergic and cholinergic components, by VIP-containing nerves.     

Group B streptococci in the female genital tract.

Vaginal carriage rates of group B streptococci among 250 women attending a clinic for sexually transmitted diseases, 123 attending family planning clinics, and 110 in labour wages were 36.0%, 17-1% and 6.4% respectively. The presence of group B streptococci was not associated with a vaginal discharge or the use of oral contraceptives in the non-pregnant women, or with the isolation of Neisseria gonorrhoeae or Trichomonas vaginalis from the women attending the clinic for sexually transmitted diseases. Serotyping showed a predominance of types II and III in non-pregnant women and an overall incidence of non-typable strains of 14.8%. There was no relationship between serotype and antibacterial susceptibility.     

Vaccines for Chlamydia infections of the female genital tract.

Genital infection with Chlamydia trachomatis is an escalating global public health concern causing considerable morbidity and socioeconomic burden worldwide. Although antibiotics are used to treat symptomatic urogenital infections, chlamydial infection remains asymptomatic in approximately 50% of infected men and 70% of infected women. The major clinical manifestations of genital chlamydial infection in women include mucopurulent cervicitis, endometritis and pelvic inflammatory disease. Genital infection with C. trachomatis markedly enhances the risk for reproductive tract sequelae in women, including tubal factor infertility, chronic pain and ectopic pregnancy. Definitive infection control of chlamydial infections will likely be achievable through a safe and efficacious vaccine. This will require identifying protective chlamydial antigens in animal models as well as identifying effective adjuvants and delivery systems that target subunit vaccines to immune inductive sites or secondary lymphoid tissues, and will be safe for use in humans.     

Ovarian programming of gamete progression and maturation in the female genital tract

Whilst the rate of displacement and migration of sperm cells in the female reproductive tract of rodents, farm animals and humans has attracted attention for at least 50 years, the overriding purpose of sperm transport has not always been kept in focus. This report is concerned with spermatozoa that can penetrate the egg investments and promote formation of a zygote, judgements involving a surgical approach and subsequent phase-contrast microscopy. A minimum period of 6–8 hours was required for such spermatozoa to be established in the oviducts in sheep and cows mated at the onset of oestrus. Sperm were then arrested in the caudal 12 cm of the isthmus for 17–18 hours or more until just before the moment of ovulation, when they were activated and displaced onwards to the site of fertilization at the ampullary-isthmic junction. The time-scale of these events differs in pigs as a result of the intra-uterine site of ejaculation and the 40-hour interval between the onset of oestrus and ovulation, but the pre-ovulatory sequestering of viable spermatozoa in the caudal tip of the oviduct is conspicuous for 36 hours or more. This function of the oviduct appears to be under local control from ovarian follicular hormones and, as judged by sperm motility and membranous changes, so does the process of capacitation. Completion of capacitation is interpreted as a peri-ovulatory event.