A comparison of endoscopy versus pathology sizing of colorectal adenomas and potential implications for surveillance colonoscopy.

BACKGROUND AND AIMS: The aim of this study was to compare endoscopy and pathology sizing in a large population-based series of colorectal adenomas and to evaluate the implications for patient stratification into surveillance colonoscopy. METHODS: Endoscopy and pathology sizes available from intact adenomas removed at colonoscopies performed as part of the Northern Ireland Bowel Cancer Screening Programme, from 2010 to 2015, were included in this study. Chi-squared tests were applied to compare size categories in relation to clinicopathologic parameters and colonoscopy surveillance strata according to current American Gastroenterology Association and British Society of Gastroenterology guidelines. RESULTS: A total of 2521 adenomas from 1467 individuals were included. There was a trend toward larger endoscopy than pathology sizing in 4 of the 5 study centers, but overall sizing concordance was good. Significantly greater clustering with sizing to the nearest 5 mm was evident in endoscopy versus pathology sizing (30% vs 19%, P < .001), which may result in lower accuracy. Applying a 10-mm cut-off relevant to guidelines on risk stratification, 7.3% of all adenomas and 28.3% of those 8 to 12 mm in size had discordant endoscopy and pathology size categorization. Depending on which guidelines are applied, 4.8% to 9.1% of individuals had differing risk stratification for surveillance recommendations, with the use of pathology sizing resulting in marginally fewer recommended surveillance colonoscopies. CONCLUSIONS: Choice of pathology or endoscopy approaches to determine adenoma size will potentially influence surveillance colonoscopy follow-up in 4.8% to 9.1% of individuals. Pathology sizing appears more accurate than endoscopy sizing, and preferential use of pathology size would result in a small, but clinically important, decreased burden on surveillance colonoscopy demand. Careful endoscopy sizing is required for adenomas removed piecemeal.

Postcesarean delivery uterine diffuse intermediate trophoblastic lesion resembling placental site plaque.

We describe a highly unusual lesion characterized grossly by the formation of a cavity within the lower uterine segment and upper endocervix that communicated with bilateral fistulae to both parametria. Histologically, the cavity and fistulous tracts were entirely coated by fibrinous material with underlying intermediate trophoblastic cells with atypical degenerate nuclei, absent mitotic activity, and a low MIB1 proliferation index. The overall cellular morphology of the lesion was similar to that of the well-circumscribed placental site nodule or plaque. Apart from the lining of the fistulae, there was no invasion of the myometrium by the trophoblastic cells. The patient had undergone previous cesarean deliveries; the lesion was related to the surgical site and was probably secondary to the previous surgery. In a review of the literature, we identified only a single previous report of a somewhat similar case. We propose the term uterine diffuse intermediate trophoblastic lesion resembling placental site plaque for this rare condition.

The uptake of cervical cancer screening by renal transplant recipients.

BACKGROUND: Renal transplant recipients are at an increased risk of developing cervical cancer compared to women in the general population. At least annual cervical smear screening is currently recommended, but little information is available regarding the actual uptake of such screening. METHODS: All female renal transplant recipients in one United Kingdom region who were alive with a functioning graft were identified. The uptake and results of cervical smear testing over a 10-year period in this cohort were determined. RESULTS: Of the 173 women eligible for cervical cancer screening, 18 (10%) undertook the recommended number of screening procedures; 56 (32%) had never had a cervical smear performed. The year of transplantation, age at engraftment and the social deprivation status did not significantly influence the uptake of screening (P > 0.05). In those women who were screened, the incidence of smear test abnormalities was 20% in renal transplant recipients compared with 7% in the general population. The cytological findings in the positive smear tests ranged from borderline changes to grade III cervical intraepithelial neoplasia. CONCLUSIONS: The renal transplant population is at higher risk of abnormal cervical cytology, but the uptake of cervical cancer screening is low. The reasons for this low screening rate are unclear, and changes in practice are necessary to improve the uptake of cervical smear testing in women with renal transplants.

Uterine gestational choriocarcinoma developing after a long latent period in a postmenopausal woman: the value of DNA polymorphism studies.

This article reports a uterine gestational choriocarcinoma arising in a 57-year-old woman with a long latent period of 22 years from the last known pregnancy. Diagnosis was made on an endometrial biopsy specimen, and given the age of the patient, the long latent period, and the limited sample, trophoblastic differentiation within an endometrial carcinoma was considered. The results of DNA polymorphism studies illustrated both paternal and maternal alleles within the tumor in equal amounts, confirming the neoplasm to be gestational in origin and to have originated from a nonmolar gestation. The report discusses the value of DNA polymorphism studies in distinguishing gestational from nongestational choriocarcinoma and from trophoblastic differentiation within a carcinoma.

p16 expression in the female genital tract and its value in diagnosis.

p16 is a cyclin-dependent kinase-4 inhibitor that is expressed in a limited range of normal tissues and tumors. In recent years, immunohistochemistry with p16 antibodies has been used as a diagnostic aid in various scenarios in gynecologic pathology. Diffuse (as opposed to focal) positivity with p16 in the cervix can be regarded as a surrogate marker of the presence of high-risk human papillomavirus (HPV). In cervical squamous lesions, p16 is positive in most high-grade cervical intraepithelial neoplasia (CIN) and in some cases of low-grade CIN, usually those associated with high-risk HPV. p16 may be useful to identify small focal high-grade CIN lesions, to distinguish some cases of CIN involving immature metaplastic squamous epithelium from immature metaplastic squamous epithelium not involved by CIN and to distinguish high-grade CIN from benign mimics. Most cervical carcinomas of squamous, glandular, and small cell type are p16-positive. In cervical glandular lesions, p16 is useful, as part of a panel, in the distinction between adenocarcinoma in situ (diffusely positive) and benign mimics, including tuboendometrial metaplasia and endometriosis, which are usually p16-negative or focally positive. p16 may be used, in combination with other markers, to distinguish between a cervical adenocarcinoma (diffuse positivity) and an endometrioid-type endometrial adenocarcinoma (negative or focally positive). Some uterine serous carcinomas are diffusely positive. In the vulva, p16 is positive in HPV-associated vulval intraepithelial neoplasia (VIN) but negative in VIN not associated with HPV. Similarly, HPV-associated invasive squamous carcinomas are p16-positive, whereas the more common non-HPV-associated neoplasms are largely negative or focally positive. In the uterus, p16 positivity is more common and widespread in leiomyosarcomas than leiomyomas, and this may be a useful aid to diagnosis, although problematic uterine smooth muscle neoplasms have not been extensively studied. Metastatic cervical adenocarcinomas in the ovary are usually diffusely p16-positive, and because these may closely mimic a primary ovarian endometrioid or mucinous adenocarcinoma, this may be a valuable diagnostic aid, although p16 expression in primary ovarian adenocarcinomas of these morphologic subtypes has not been widely investigated. Some ovarian serous carcinomas, similar to their uterine counterparts, are p16-positive.

An immunohistochemical comparison between low-grade and high-grade ovarian serous carcinomas: significantly higher expression of p53, MIB1, BCL2, HER-2/neu, and C-KIT in high-grade neoplasms.

Ovarian serous carcinoma (OSC) is the most common ovarian epithelial malignancy. Recently, a dualistic pathway of ovarian serous carcinogenesis has been proposed based on morphologic observations and molecular genetic analysis. In this scheme, low-grade OSC arises in a stepwise fashion from a benign serous cystadenoma through a usual serous borderline tumor through a micropapillary variant of serous borderline tumor. In contrast, the more common high-grade OSC arises de novo from the ovarian surface epithelium or the epithelium of cortical inclusion cysts with an as yet unrecognized precursor lesion. Although the division of OSC into low- and high-grade variants is gaining greater acceptance, and although there is accumulating molecular genetic evidence for this, there is little published information regarding a comparison of protein expression between these two types of OSC. In this study, we have investigated the immunohistochemical expression of a wide range of proteins in cases of low-grade (n = 22) and high-grade (n = 47) OSC. Antibodies used were p53, MIB1, BCL2, WT1, HER-2/neu, C-KIT, osteopontin, and survivin. For all antibodies, except MIB1, cases were scored as 0 (negative or occasional positive cells), 1+ (<10% cells positive), 2+ (10%-25% cells positive), 3+ (26%-50% cells positive), 4+ (51%-75% cells positive) or 5+ (>75% cells positive). For MIB1, the percentage of positive nuclei was calculated. There was a statistically significant higher expression of p53, MIB1, BCL2, HER-2/neu, and C-KIT in high-grade compared with low-grade OSC (P < 0.05). Thirty of 47 (64%) cases of high-grade OSC exhibited 5+ staining with p53 compared with 4 of 22 (18%) low-grade neoplasms. Twelve of 47 (26%) high-grade OSCs exhibited 5+ staining with BCL2 compared with 1 of 22 (5%) low-grade OSCs. The mean MIB1 proliferative index in high-grade OSCs was 55.4% compared with 23.0% in low-grade OSCs. Virtually all cases of both low-grade and high-grade OSCs exhibited diffuse nuclear positivity with WT1 and diffuse cytoplasmic positivity with survivin. Osteopontin expression was variable with no significant difference in expression between low-grade and high-grade OSC. Although expression of both HER-2/neu and C-KIT was significantly higher in high-grade compared with low-grade OSC, only rare cases exhibited strong positivity with these antibodies, which could be of therapeutic value in individual cases, although this would require additional molecular investigations. The significant differences in protein expression between low-grade and high-grade OSC provides further support for a different underlying pathogenesis. In particular, the differences in p53 immunoreactivity are in keeping with the observation that p53 gene mutation is more common in high-grade than low-grade OSC.