Scanning electron microscopy of the human fallopian tube.

Fallopian tubes from women of reproductive and postmenopausal ages were examined by scanning electron microscopy. The surface topography of these Fallopian tubes is described and illustrated.

Statistical model of the natural history of cervical carcinoma. II. Estimates of the transition time from dysplasia to carcinoma in situ.

Estimates are presented of the transition probabilities and transition times from dysplasia to carcinoma in situ of the uterine cervix based on a statistical model of the natural history of this disease. The estimates, obtained from a longitudinal study of 557 women, were contrasted with prevalence rates obtained in a self-selected sample of over 11,000 women from Barbados, West Indies. These two independent sets of estimates, based on two different experimental designs, were shown to be concordant. The formula for the computation of the standard deviation of these estimates was given, together with the results of this computation for the observed sample data. The effects of those covariables that have been associated with the incidence of cervical neoplastic disease on these estimates were examined. The transition times and probabilities were associated with the total number of pregnancies but were not dependent on age at first coitus or age at first pregnancy. The results of this investigation provide an index of the history of cervical neoplastic disease that might be of use in contrasting the experience of different subsets of the population with respect to their transition probabilities and transition times through the several stages of the disease process.

Association between human papillomavirus type and clonal status of cervical squamous intraepithelial lesions.

BACKGROUND: Lesions that are histologically classified as precursors of cervical cancer, which are often referred to as squamous intraepithelial lesions (SILs), represent a heterogeneous clinical entity that can be associated with many different types of human papillomaviruses (HPVs) and have a variable biologic behavior. Approximately one half of low-grade SILs behave as non-neoplastic, productive viral lesions that frequently regress spontaneously, whereas the other half behave as neoplasms and either persist or progress to a histologically higher grade lesion. Identification of biomarkers that reliably differentiate those low-grade SILs with the properties of a non-neoplastic viral infection from those with the properties of neoplasia would provide a more rational basis for decisions about disease management. Since monoclonality is a hallmark of neoplasia irrespective or organ site, clonal status might represent one such biomarker. PURPOSE: To better understand the pathobiology of SILs, we analyzed the clonality of low-grade and high-grade SILs and compared their clonal status with their associated HPV types. METHODS: One hundred forty formalin-fixed, paraffin-embedded cervical biospy and loop electrosurgical specimens, originally diagnosed as SILs, were obtained from the pathology archives of both the Columbia-Presbyterian Medical Center and Kyto Diagnostics in New York. Clonality was determined with the use of a polymerase chain reaction (PCR) based method that detects nonrandom X-chromosome inactivation. This PCR-method amplifies a polymorphic region of the androgen receptor gene that is flanked by several differentially methylated enzyme sites. The same tissue was also analyzed for HPV DNA with the use of PCR and both L1 and E6 "consensus" primers. RESULTS: All 25 evaluable cases of high-grade SILs were determined to be monoclonal. Although 54 (68%) of 79 evaluable low-grade SILs were monoclonal, 25 (32%) of 79 low-grade SILs were polyclonal. A strong association was observed between HPV type and clonal status, with a total of 71 (47 low-grade and 24 high-grade) SILs determined to be monoclonal and containing HPV types 16, 18, 31, 33, 35, 39, 45, 56, 58, or 65. In contrast, 22 (92%) of the 24 low-grade SILs that contained another type of HPV were polyclonal (Fisher's exact test, two-sided, P

Human papillomavirus DNA testing for cervical cancer screening in low-resource settings.

BACKGROUND: In many low-resource settings, there are barriers to cytologic screening for cervical cancer. This study evaluates human papillomavirus (HPV) DNA testing as an alternative screening method. METHODS: Cervical samples from 2944 previously unscreened South African women aged 35-65 years were tested for high-risk types of HPV with the use of the Hybrid Capture I (HCI) assay. Women also had a Pap smear, direct visual inspection of the cervix, and Cervicography(TM). Women positive on any screening test were referred for colposcopy. Samples from women with biopsy-confirmed, low-grade squamous intraepithelial lesions (SILs) (n = 95), high-grade SILs (n = 74), or invasive cervical cancer (n = 12) and a random sample of women with no cervical disease (n = 243) were retested for HPV DNA with the use of the more sensitive Hybrid Capture II (HCII) assay. All P values are two-sided. RESULTS: High-risk HPV DNA was detected in 73.3% and 88.4% of 86 women with high-grade SIL or invasive cancer and in 12.2% of 2680 and 18.1% of 243 women without evidence of cervical disease, with the use of the HCI and HCII assays, respectively. HPV DNA testing with the HCII assay was more sensitive than cytology for detecting high-grade SIL and invasive cancer (McNemar's test, P =.04), and testing with the HCI assay was of equivalent sensitivity (P =.61). Cytology had a statistically significantly better specificity (96.8%) than either the HCI assay (87.8%) or the HCII assay (81.9%) (P<.01). Receiver operating characteristic curves identified test cutoff values that allow HPV DNA testing to identify 57% of women with high-grade SIL or cancer, while classifying less than 5% of women with no cervical disease as HPV DNA positive. CONCLUSIONS: HPV DNA testing has a sensitivity equivalent to, or better than, that of cytology. Since HPV DNA testing programs may be easier to implement than cytologic screening, HPV testing should be considered for primary cervical cancer screening in low-resource settings.

Carcinoembryonic antigen in human ovarian neoplasms.

The presence and location of carcinoembryonic antigen (CEA) was examined in tissue sections of 14 mucinous and 13 serous cystadenomas and cystadenocarcinomas of the ovary. CEA was demonstrated in the mucinous tumors but was not present in the serous tumors. In the mucinous tumors, CEA was located in the glycocalyx and apical portions of the absorptive-type epithelium, with only trace quantities in goblet cells, a pattern identical to that seen in colonic neoplasms. Endocervical-type epithelium in the mucinous tumors contained little or no CEA.

Adenoacanthosis of endometrium: a clinicopathologic study in premenopausal women.

Adenoacanthosis of the endometrium is a disorder characterized by glandular hyperplasia with squamous metaplasia. A clinicopathologic study was done of 10 cases, the majority of which were referred for consultation as atypical hyperplasia of adenoacanthoma. All of the patients were premenopausal and ranged in age from 19 to 45 years: they presented with abnormal bleeding or infertility. In four cases the adjacent endometrium was normal cycling endometrium; two were associated with chronic endometritis, and two were present within endometrial polyps. Three patients responded conservative therapy; in two others, hysterectomy disclosed no residual lesion. Although adenoacanthosis has certain morphologic features mimicking adenoacanthoma, it can be distinguished from this lesion by its growth pattern and cytologic features. Whether adenoacanthosis is a cancer precursor is unknown, but the potential reversibility of the lesion warrants conservative therapy, particularly in women of childbearing age.

Chlamydial endometritis. A histological and immunohistochemical analysis.

A series of 90 endometrial biopsies and curettings originally diagnosed as chronic endometritis were reviewed and histological findings of plasma cells, lymphoid infiltrate, stromal necrosis, acute inflammation, lymphoid follicles, and epithelial atypia were correlated with the demonstration of chlamydial antigens by the immunoperoxidase technique. Chlamydial antigens were localized within endometrial epithelial cells in four cases. Although these four cases represented only 4% of the total number, chlamydial immunoperoxidase positivity was best discriminated by the severity of the inflammation and the presence of an acute inflammatory infiltrate. Among cases of severe endometritis 22% were chlamydia-positive, and in those cases with an associated acute inflammatory infiltrate, 57% were positive. A high index of suspicion of chlamydial infection should exist when severe endometritis is diagnosed in patients with clinical histories of post-abortal state, pelvic inflammatory disease, secondary infertility or menometrorrhagia, and chronic pelvic pain.

Nuclear DNA and histologic studies of genital lesions in diethylstilbestrol-exposed progeny. II. Intraepithelial glandular abnormalities.

This study has analyzed the nuclear DNA content of intraepithelial glandular lesions in diethylstilbestrol (DES)-exposed offspring. The endocervical cells and endometrial-tubal cells present in the vaginal adenosis and pericervical collars had a euploid distribution. However, greater proliferative activity was found among the endometrial-tubal cells. In the cells of vaginal adenosis of a postpartum woman without a confirmed history of maternal exposure to DES, a polyploid pattern was found, indicating that endometrial-tubal cells underwent hyperplastic changes under the influence of hormonal stimulation. In an atypical adenosis derived from endometrial-tubal cells, an aneuploid pattern was found. Based on these findings, it is suggested that endometrial-tubal cells have a greater proliferative potential than endocervical cells.

A modified terminology for cervical intraepithelial neoplasia.

Recent data are consistent with the concept that human papillomavirus (HPV) is etiologically important in the causation of cervical squamous cell cancer. There appear to be certain important events in the process of HPV infection and neoplasia. It is suggested that the terminology of the HPV-related precursor lesions be modified and that two terms, rather than three, would best satisfy the requirements of both science and clinical care. The "early" lesions should be referred to as "low-grade cervical intraepithelial neoplasia (CIN) with HPV-related changes" and the lesions that have the features of cancer precursors as "high-grade CIN."

A comparison of slot blot, southern blot, and in situ hybridization analyses for human papillomavirus DNA in genital tract lesions.

Genital tract lesions were analyzed for human papillomavirus (HPV) DNA by in situ hybridization using probes of HPVs 6/11, 16/18, and 31/33/35. All of the HPVs detected in vulvar and perianal condylomata by in situ hybridization were HPV 6/11-related, whereas the majority of HPVs detected in cervical intraepithelial grade I lesions were types 16/18- and 31/33/35-related. None of the lesions with histologic features equivocal for HPV infection had detectable HPV DNA by in situ hybridization, though some did contain HPV DNA sequences as ascertained by filter hybridization analysis. The sensitivity of in situ hybridization was compared with that of filter hybridization (slot blot and/or Southern blot). The correlation was high (28 of 30) for cases that contained HPVs 6/11 or 16, as deduced by filter hybridization, and was much less (ten of 29) for cases that contained HPVs distinct from types in the filter hybridization probe cocktail (HPVs 6/11, 16, 18, 31, 35 and 51). There was a high concordance between the results of Southern blot hybridization and slot blot hybridization analyses, especially with cases that contained HPVs 6/11 and 16. In situ hybridization, slot blot, and Southern blot hybridization analyses are all very effective in detecting the common HPV types (HPVs 6/11 or 16). In situ hybridization is useful in differentiating cervical lesions that contain HPV 6/11 from those that contain HPV 16 or other types with oncogenic potential. However, filter hybridization is superior to in situ hybridization when analyzing cases with histologic findings equivocal for HPV infection or cases that contain HPV types related to, but distinct from, the types included in the probe.

Cryotherapy and carbon dioxide laser management of cervical intraepithelial neoplasia: a controlled comparison.

Two hundred patients with cervical intraepithelial neoplasia were treated alternately by cryotherapy and carbon dioxide laser therapy on an outpatient basis after appropriate triage with colposcopy, cervical biopsy, and endocervical curettage. Results of treatment were not significantly different from one another, with failure occurring in 7% of patients treated with cryotherapy and 11% of those treated with carbon dioxide laser therapy. The cryotherapeutically treated patients had less pain but more discharge than those treated by the carbon dioxide laser. The laser patients' cervices healed more rapidly than did the cervices treated with cryotherapy. There appears to be no advantage in replacing cryotherapy with carbon dioxide laser therapy.

Collaborative study on hysteroscopic sterilization procedures. Preliminary report.

Preliminary results of a retrospective study of 773 cases of hysteroscopic sterilization are presented. Of the 524 cases tested for tubal patency, 186 (35.5%) were considered failures either because of incomplete blockage of the tubes or pregnancy. Fifty-nine pregnancies (23.7%) were reported in the 249 cases which were not tested for tubal patency. In the total population 25 complications were designated as major, for a major complication rate of 3.2%. These included uterine perforation, bowel damage, peritonitis, ectopic preganncy, and 1 death from bowel perforation with peritonitis. The implications of these excessively high failure and complication rates are discussed, and plans are described for further analysis of the data.

Human papillomavirus DNA in situ hybridization may be used for the quality control of genital tract biopsies.

Biopsies of human papillomavirus (HPV)-related lesions of the lower female genital tract were studied using in situ hybridization for HPV DNA. The probes included HPV types 6, 11, 16, 18, 31, 33, 35, 41, 43, 44, 45, 51, 52, and 56. In cervical intraepithelial neoplasia (CIN) 1 lesions, 64 of 70 (91%) of formalin-fixed tissues were HPV DNA-positive; in vulvar condylomata, 34 of 36 (94%) were positive. Only two of 52 (4%) of the lesions diagnosed as equivocal for CIN 1 or condyloma were positive. Higher-grade CIN and vulvar intraepithelial neoplasia lesions had a lower rate of HPV DNA positivity. It is suggested that in situ hybridization may be used as a quality control procedure for the histologic diagnosis of HPV-related lesions.

Pearly penile papules: absence of human papillomavirus DNA by the polymerase chain reaction.

Pearly penile papules clinically resemble the sexually transmitted papular variant of genital condylomata. Histologically, however, pearly penile papules consist of fibropapillomata that lack the characteristic morphologic features of human papillomavirus (HPV) infection. To study the possible association of HPV infections with pearly penile papules, we examined tissue specimens from 13 men with pearly penile papules with and without associated penile condylomata. Biopsy specimens were tested for the presence of HPV DNA by the polymerase chain reaction. None of the pearly penile papules contained HPV DNA sequences, whereas four of seven cases clinically suspected of being condylomata associated with pearly penile papules contained HPV DNA. These results confirm that pearly penile papule lesions do not contain HPV DNA; therefore, the distinction between pearly penile papules and penile condylomata is clinically significant.

Human papillomavirus DNA in fomites on objects used for the management of patients with genital human papillomavirus infections.

We investigated the possibility that human papillomavirus (HPV) DNA could be present on objects that are used for the management of patients with genital HPV infections. Human papillomavirus DNA was identified by filter hybridization in swabs taken from eight of 16 (50%) of surgical gloves. Similarly, HPV DNA was found in 23 of 62 (37%) and one of 62 (1.6%) of biopsy forceps before and after sterilization in 30% tincture of Savlon for 30 minutes, respectively. Five of 22 (23%) and one of 22 (4.5%) of cryoprobe tips tested positive for HPV DNA before and after cleaning with 90% ethanol solution for 1 minute, respectively. The rate of HPV DNA positivity after sterilization is low. Whether HPV on fomites is infectious was not evaluated in this study. Washing and soaking them in detergents containing 2% glutaraldehyde or heating them to 100C or higher should be adequate. Use of separate gloves for manual examination of the external and internal anogenital tract is advisable.

Human papillomavirus DNA in CO2 laser-generated plume of smoke and its consequences to the surgeon.

Carbon dioxide laser energy is absorbed by intracellular water but not by proteins or nucleic acids. The possibility of dispersing viral DNA during laser therapy of human papillomavirus (HPV)-containing genital infections was explored using a filter hybridization technique. Samples were taken using dacron swabs from 110 patients in nine separate treatment sessions as well as from five pre-filter canisters, four fume vacuum tubes, and from the nasopharynx, eyelids, and ears of the laser surgeon before and after laser surgery. The viral RNA probes were specific for groups of HPV types 6/11, 16/18, and 31/33/35. Human papillomavirus DNA was identified in swabs from 65 of 110 (60%) of histologically unequivocal condylomata and cervical intraepithelial neoplasias. One of the five pre-filter canisters (20%) tested was HPV DNA-positive after laser treatment of 65 patients; it contained HPV DNA type 6. The four fume vacuum tubes tested in the remaining 45 patients were HPV DNA-negative, as were the nasopharynx, eyelids, and ears of the operator. Although HPV DNA may be released during laser vaporization of genital HPV infections, contamination of the operator is unlikely provided appropriate equipment for evacuating HPV DNA-positive smoke is used.

The incidence of asymptomatic uterine anomalies in women undergoing transcervical tubal sterilization.

The incidence of congenital anomalies of the uterus has generally been obtained from studies of women undergoing evaluation for infertility, and has been reported as 1-10%. However, the true incidence of uterine malformations is not known. This study reviews hysterosalpingograms obtained for evaluation of tubal closure after transcervical sterilization in normal multiparous women using methylcyanoacrylate and the FEMCEPT device. Of the 840 hysterosalpingograms studied, 16 congenital uterine anomalies were identified, for an incidence of 1.9%. The presence of anomalies in this population of women may more closely represent the incidence of congenital uterine anomalies in the general population.

Treatment of cervical intraepithelial neoplasia using the loop electrosurgical excision procedure.

In selected patients with cervical intraepithelial neoplasia (CIN), outpatient ablative procedures represent a readily accepted and highly effective treatment modality. The recently introduced loop electrosurgical excision procedure offers a quick and simple alternative to cryotherapy and laser ablation for treating CIN, and has the distinct advantage of allowing both diagnosis and treatment of selected patients at a single visit. This report presents our clinical experience treating 432 patients with CIN using the loop electrosurgical excision procedure on an outpatient basis. Small loop electrodes were used to excise CIN lesions in 275 patients, and large loop electrodes were used in 157. When performed on an outpatient basis under local anesthesia, loop excision was well tolerated by patients with only minimal discomfort. Post-treatment bleeding occurred in less than 2% of the subjects and responded to either recauterization or packing of the cervix. Post-treatment stenosis occurred in less than 1%. The success rate of the loop electrosurgical excision procedure, as defined by absence of cytologic, histologic, or colposcopic lesions 4-48 months after therapy, was 80% for women treated using the small loop electrodes. Ninety percent of all patients treated using the large loop electrodes were free of disease during 6-12 months of follow-up. For women being treated for primary (as opposed to recurrent) disease, the success rate with large loop electrodes was 94%.

Comparison of specimens removed by CO2 laser conization and the loop electrosurgical excision procedure.

A comparison is made of the histologic changes in the cervical epithelium and stroma following CO2 laser conization and office excisional biopsy of cervical tissue using the loop electrosurgical excision procedure. In both types of specimens, two zones of thermal injury were detected. The zone at the margin of resection measured approximately 50 microns in thickness and was characterized by extensive carbonization and charring. The other zone was much more variable in thickness and characterized by tissue coagulation, but lacked charring. No significant difference in the biocharacteristics or extent of thermal damage was detected between the methods. For 11 specimens obtained with the CO2 laser, the coagulated zone ranged from 130-750 microns in greatest thickness; the mean thickness was 411 microns. For 40 specimens obtained using the loop procedure, the range of thickness of the coagulated zone was 150-830 microns, and the mean thickness was 396 microns. The difference in the mean value of thermal injury (measured in microns) between the laser and loop procedures was not significant (Student t test; P = .79). Extensive areas of carbonization and epithelial distortion at the margins of excision were only occasionally present in specimens obtained by the electrosurgical excision procedure but almost invariably present in CO2 laser specimens. However, in all cases it was possible to evaluate the epithelium and the stroma both histologically and cytologically.

Pitfalls in the diagnosis of endometrial neoplasia.

One hundred consecutive cases of hyperplasia of the endometrium were referred to the Sloane Hospital for Women. The referral diagnoses and consultation diagnoses were compared for the purpose of analyzing common diagnostic problems in interpretation of endometrial hyperplasias and the use of diagnostic terminology as it applies to prognosis and therapy. The consultation diagnosis was a down grade of the original diagnosis in 69% of the reviewed cases. The most common endometrial pathology misinterpreted as hyperplasia was endometrial polyps, followed by the endometrial metaplasias, and architectural distortion caused by necrosis and mechanical artifact. In 14% of the referral diagnoses, the use of terminology was vague, with such terms as endometrial, epithelial, or glandular hyperplasia, and did not communicate the prognostic intent of the referring pathologist to the consulting physician. The careful use of endometrial diagnostic terms accompanied by a statement of the system of classification used and its corresponding clinical intent is suggested.