Angiogenesis in cervical intraepithelial neoplasia and early-staged uterine cervical squamous cell carcinoma: clinical significance.

The objective of this study is to evaluate angiogenesis in cervical intraepithelial neoplasia (CIN), microinvasive squamous cell carcinoma (MIC), and early-staged squamous cell carcinoma (SCC), stage IB-IIA of the cervix. Microvessel density (MVD) was evaluated and correlated with other pathologic prognostic factors and disease outcomes. Four hundred seventy-four cervical specimens were studied. Among these, 100 were designated normal cervix, 30 CIN1, 32 CIN2, 178 CIN3, 74 MIC, and 60 early-staged SCC. MVD per high-power field (x400) of early-staged SCC, MIC, and CIN3 were significantly higher in comparison to CIN2, CIN1, and control subjects (P<0.05). There was no statistically significant difference in MVD between control group, CIN1, and CIN2. In early-staged SCC, no correlation between MVD and pelvic lymph node status, parametrial involvement, depth of stromal invasion, and lymphovascular space invasion was found. Patients with bad outcomes (recurrence or death) showed no statistically different MVD from the ones who had unremarkable clinical courses.

Role of human papillomavirus DNA testing in management of women with atypical squamous cells of undetermined significance.

To find the sensitivity, specificity, and positive and negative predictive values of the high-risk group human papillomavirus (HPV) DNA testing as a triage tool to detect high-grade squamous intraepithelial lesions (HSILs, ie, cervical intraepithelial neoplasia [CIN] 2 or worse) in women with a cytologic smear showing atypical squamous cells of undetermined significance (ASC-US). All new cases with cytologic smears showing ASC-US that presented in King Chulalongkorn Memorial Hospital from January 2003 to November 2003, excluding known cases of HSILs and pregnancies, were enrolled. Cervical cell samplings were done by cervical cytobrush technique and tested for high-risk group HPV with the Hybrid Capture 2 (HC2) test. All participants were examined under a colposcope. Then cervicographs were taken before colposcopic-directed cervical biopsies were done. Of the 90 ASC-US cases enrolled, the pathologic results were normal in 30.0%, squamous metaplasia in 16.7%, CIN 1 in 37.8%, CIN 2 in 1.1%, CIN 3 in 11.1%, and microinvasive cervical carcinoma in 3.3%. The prevalence of HSILs and the prevalence of high-risk HPV detection were 15.6% and 38.9%, respectively. Using pathologic results from cervical biopsy as the gold standard, the HC2 has the sensitivity, specificity, and positive and negative predictive values of 85.7%, 69.7%, 34.3%, and 96.4%, respectively, to detect HSILs. High-risk group HPV detection can be used as an additional triage test to detect HSILs in women having ASC-US with high sensitivity and negative predictive value.

Coexistence of low and high grade squamous intraepithelial lesions of the cervix: morphologic progression or multiple papillomaviruses?

BACKGROUND: The diagnosis of both low (LSIL) and high (HSIL) grade squamous intraepithelial lesions in the same cervical specimen may reflect classification variation, morphologic progression in situ, and, conceivably, different HPV infections. We addressed these possibilities in cervical specimens previously diagnosed as containing both LSIL (condyloma/CIN1) and HSIL (CIN2/3). METHODS: All cases with a histologic diagnosis of LSIL and HSIL from 1994-1996 were reviewed. On review, lesions were scored as (1) no significant variation in lesion grade (classification discrepancies) and showing a (2) one (CIN1-2) or (3) two (CIN1-3) grade shift in the same case. In cases in which a one or two grade shift was confirmed, low (CIN1) and high (CIN2-3) grade foci were microdissected and extracted DNA analyzed for HPV by PCR and RFLP analysis. RESULTS: Of 98 cases available for review, 58 (59%) did not exhibit significant variation in grade (classification discrepancy), and 40 (41%) showed a one (25) or two (15) grade shift. Of the latter group both LSIL and HSIL foci were HPV(+) in 26 (65. 0%). The same HPV was present in both LSIL and HSIL foci in 15/15 lesions with a one grade shift (CIN1-2). In contrast, a significantly higher proportion of lesions with a two grade shift (CIN1-3) contained two different HPV types (4/11 vs 0/15; P = 0.01). Combinations of HPVs in the low/high grade foci, respectively, included HPV 11/16 (1), 11/16 + 18 (1), and HPV39/16 (2). CONCLUSIONS: Lesions containing LSIL and HSIL which span two grades (CIN1 and CIN2) most likely represent morphologic progression in a single infection. Lesions containing CIN1 and CIN 3 may be attributed to both lesion progression and two coincident infections; the latter sometimes present in the same histologic section. The latter phenomenon has implications for both the diagnosis of CIN and interpretation of "morphologic progression" from very low to high grade in the same case.

The use of two estrogen preparations (a combined contraceptive pill versus conjugated estrogen cream) intravaginally to treat urogenital symptoms in postmenopausal Thai women: a comparative study.

OBJECTIVE: To determine whether the combined contraceptive pill used intravaginally was as effective as the standard conjugated estrogen cream for the treatment of urogenital symptoms in postmenopausal Thai women. SUBJECTS AND METHODS: In a randomized clinical trial, 40 postmenopausal women with urogenital symptoms were randomly allocated to two treatment groups for 8 weeks. The first group (n = 20) received a combined contraceptive pill by the vaginal route, one tablet per week at bedtime for 8 weeks. Each tablet contained 250 microg levonorgestrel plus 30 microg ethinyl estradiol. The second group (n = 20) was given 1 gm of an intravaginal conjugated estrogen cream at bedtime, three times in the first week, twice in the second week, and then once a week for the next 6 weeks (1 gram of conjugated estrogen cream contained 0.625 mg conjugated equine estrogens). Subjects were questioned about their urogenital symptoms, and vaginal cytologic smears, vaginal bacterial cultures, and urine cultures were performed before treatment and after 2, 4, and 8 weeks of therapy. RESULTS: The vaginal pH and the proportion of the fecal type bacteria decreased in both groups, with no statistically significant difference between the groups. The karyopyknotic index and the maturation index were improved during treatment in both groups. An increase in the proportion of lactobacilli were recorded in both groups after therapy, with no significant difference between the two groups. No significant changes were observed in urinary bacteria. The therapy (combined contraceptive pill and estrogen cream) had a marked effect on urogenital symptoms (vaginal dryness, dyspareunia, urinary frequency, and urinary urgency), with impressive improvement comparably in both groups. CONCLUSIONS: A combined contraceptive tablet administered vaginally once a week can alleviate urogenital symptoms in Thai postmenopausal women as effectively as the vaginal estrogen cream. However, the pills are much less expensive and are easily obtained in developing countries.

PIP: A randomized clinical trial conducted in Bangkok, Thailand, investigated whether intravaginal use of a combined oral contraceptive (OC) is as effective for the treatment of urogenital symptoms in postmenopausal women as the standard regimen of conjugated estrogen cream. 40 postmenopausal women (mean age, 54 years) with urogenital symptoms related to estrogen deficiency were allocated to one of two treatment groups for 8 weeks. The first 20 women received one OC (250 mcg of levonorgestrel and 30 mcg of ethinyl estradiol) per week; the remaining 20 women were given estrogen cream (0.625 mg conjugated equine estrogens) at bedtime 3 times in the 1st week, twice in the 2nd week, and weekly for the last 6 weeks. Vaginal pH and the proportion of fecal-type bacteria decreased, the karyopyknotic and maturation indices improved, and the proportion of vaginal colonization with lactobacilli increased in both groups, with no significant differences between treatments. Also recorded in both groups were impressive improvements in vaginal dryness, dyspareunia, urinary frequency, and urinary urgency. No significant changes were observed in urinary bacteria. Combined OCs are less expensive than vaginal estrogen cream and more readily available in developing countries. Since they are as effective as the cream at alleviating urogenital symptoms in postmenopausal women, their use for this purpose merits consideration.

Papillary immature metaplasia (immature condyloma) of the cervix: a clinicopathologic analysis and comparison with papillary squamous carcinoma.

Papillary immature metaplasia (PIM) is a variant of human papillomavirus (HPV) 6 or 11 infection. PIM resembles an immature metaplasia but has filiform papillae, variable cytological atypia, and, frequently, extension into the endocervical canal. Because the unusual morphology and presentation of PIM may cause confusion between this and other benign and malignant papillary neoplasms, we conducted a clinicopathologic analysis of PIM and compared expression of Ki-67 between PIM, condyloma, and papillary carcinoma. Data on patient age, duration of the lesions, and procedures, including cone biopsy, were obtained. The distribution and intensity of staining for Ki-67 in the epithelium was recorded and compared with both condyloma and papillary carcinoma. HPV typing was performed by polymerase chain reaction (PCR) and restriction fragment length pleomorphism analysis (RFLP). Ten of 13 PIMs were HPV 6/11 positive. Three cases contained areas closely resembling condyloma. Eleven cone biopsies were performed on nine cases. Three were found to have a coexisting high-grade squamous intraepithelial lesion that was either HPV 6/11 negative or contained another HPV type. All PIMs displayed variable staining for Ki-67 with a low index of staining in the mid and upper epithelial layers. In contrast, areas of condyloma had significantly stronger staining in areas with viral cytopathic effect (koilocytosis). Six papillary carcinomas were analyzed and displayed moderate to diffuse staining, including staining of the superficial cell nuclei. PIM is a distinct pathological subset of cervical condyloma that frequently is managed by cone biopsy and may persist. The marked reduction in Ki-67 staining in superficial cell layers distinguishes PIM from some condylomata and most HSILs and papillary carcinomas. Immunostaining thus may be helpful in distinguishing PIM from papillary carcinoma, although the differentiation of the two is best made on morphological grounds.

Cytologic correlates of papillary immature metaplasia (immature condyloma) of the cervix.

Papillary immature metaplasia (PIM) of the cervix (immature condyloma) is a variant of low-grade squamous intraepithelial lesions (LSIL). It is frequently associated with human papillomavirus (HPV) types 6 and 11. The purpose of this study was to characterize the cytologic changes associated with this lesion. We analyzed 10 cases of PIM from our files and reviewed the Papanicolaou smears taken proximate to the time of the biopsy. Four cases had either reactive epithelial changes (2 cases) or cytologic findings typical of low-grade SIL, with koilocytosis (2 cases). Six cases displayed a spectrum of metaplastic cells with varying maturation that ranged from atypical reactive cells to atypical immature metaplastic cells. Binucleation was common. Some cells exhibited features characteristic of SIL, although the degree of nuclear atypia generally was less than that associated with high-grade SIL. Papanicolaou smears from all cases were interpreted as atypical (ASCUS) metaplasia or low-grade SIL. Follow-up biopsy in one case revealed a PIM in association with a high-grade SIL, the latter undiagnosed by smear alone. PIM is a distinct histologic entity that can present with a spectrum of cytologic findings. Its recognition histologically can resolve some cytologic/histologic discrepancies. Confusion with an immature HSIL or atypical immature metaplasia can occur in some instances and the diagnosis of PIM by cytology alone is not recommended, unless the diagnosis is qualified.

Intrathoracic lymphangiohemangioma associated with hemothorax: a cause of intrauterine fetal death.

A case is presented of a large intrathoracic lymphangiohemangioma in association with spontaneous hemothorax. The lesion was found in a macerated stillborn infant. The precise nature of the tumor was documented histologically.