Glandular Intraepithelial Neoplasia Research Articles

Morphological Characteristics of Colon Tumors in Mice with Different Tolerance to Hypoxia.

In adult male C57BL/6 mice with high (HR) and low (LR) resistance to hypoxia, morphological features of colon tumors and blood parameters were evaluated 70 days after intraperitoneal injection of azoxymethane and subsequent consumption of 3 cycles of dextran sulfate sodium. On macroscopic analysis, tumors were found in the distal colon in 35% (7 of 20 animals) of HR and 31% (4 of 13 animals) of LR animals. Microscopic analysis of the distal colon revealed tumors in 75% (15 of 20 animals) of HR and 69% (9 of 13 animals) of LR mice. The tumors were presented by areas of glandular intraepithelial neoplasia and adenocarcinomas; the incidence and the area of the tumors did not differ in groups of HR and LR mice. The number of neuroendocrine and goblet cells in the distal colon mucosa in the areas of tumors was similar in the compared groups. However, in both HR and LR mice of the experimental groups, the content of goblet cells in tumors was lower and the content of endocrine cells was higher than in the corresponding control groups. In the peripheral blood, the erythrocyte count and hemoglobin content decreased in HR and LR mice of the experimental groups; the relative number of monocytes increased only in HR mice and the absolute number of lymphocytes and monocytes decreased in LR mice. Thus, 70 days after azoxymethane administration and dextran sulfate sodium consumption, the tumors in mice were presented by glandular intraepithelial neoplasia and adenocarcinomas, and their incidence and area did not differ between animals with different tolerance to hypoxia.

Comparative effectiveness and risk of preterm birth of local treatments for cervical intraepithelial neoplasia and stage IA1 cervical cancer: a systematic review and network meta-analysis.

The trade-off between comparative effectiveness and reproductive morbidity of different treatment methods for cervical intraepithelial neoplasia (CIN) remains unclear. We aimed to determine the risks of treatment failure and preterm birth associated with various treatment techniques. In this systematic review and network meta-analysis, we searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials database for randomised and non-randomised studies reporting on oncological or reproductive outcomes after CIN treatments from database inception until March 9, 2022, without language restrictions. We included studies of women with CIN, glandular intraepithelial neoplasia, or stage IA1 cervical cancer treated with excision (cold knife conisation [CKC], laser conisation, and large loop excision of the transformation zone [LLETZ]) or ablation (radical diathermy, laser ablation, cold coagulation, and cryotherapy). We excluded women treated with hysterectomy. The primary outcomes were any treatment failure (defined as any abnormal histology or cytology) and preterm birth (<37 weeks of gestation). The network for preterm birth also included women with untreated CIN (untreated colposcopy group). The main reference group was LLETZ for treatment failure and the untreated colposcopy group for preterm birth. For randomised controlled trials, we extracted group-level summary data, and for observational studies, we extracted relative treatment effect estimates adjusted for potential confounders, when available, and we did random-effects network meta-analyses to obtain odds ratios (ORs) with 95% CIs. We assessed within-study and across-study risk of bias using Cochrane tools. This systematic review is registered with PROSPERO, CRD42018115495 and CRD42018115508. 7880 potential citations were identified for the outcome of treatment failure and 4107 for the outcome of preterm birth. After screening and removal of duplicates, the network for treatment failure included 19 240 participants across 71 studies (25 randomised) and the network for preterm birth included 68 817 participants across 29 studies (two randomised). Compared with LLETZ, risk of treatment failure was reduced for other excisional methods (laser conisation: OR 0·59 [95% CI 0·44-0·79] and CKC: 0·63 [0·50-0·81]) and increased for laser ablation (1·69 [1·27-2·24]) and cryotherapy (1·84 [1·33-2·56]). No differences were found for the comparison of cold coagulation versus LLETZ (1·09 [0·68-1·74]) but direct data were based on two small studies only. Compared with the untreated colposcopy group, risk of preterm birth was increased for all excisional techniques (CKC: 2·27 [1·70-3·02]; laser conisation: 1·77 [1·29-2·43]; and LLETZ: 1·37 [1·16-1·62]), whereas no differences were found for ablative methods (laser ablation: 1·05 [0·78-1·41]; cryotherapy: 1·01 [0·35-2·92]; and cold coagulation: 0·67 [0·02-29·15]). The evidence was based mostly on observational studies with their inherent risks of bias, and the credibility of many comparisons was low. More radical excisional techniques reduce the risk of treatment failure but increase the risk of subsequent preterm birth. Although there is uncertainty, ablative treatments probably do not increase risk of preterm birth, but are associated with higher failure rates than excisional techniques. Although we found LLETZ to have balanced effectiveness and reproductive morbidity, treatment choice should rely on a woman's age, size and location of lesion, and future family planning. National Institute for Health and Care Research: Research for Patient Benefit.

Follow–up of females with atypical glandular cells on Pap smears

Purpose: Atypical glandular cells (AGC) are often associated with clinically significant lesions, but the interpretation of AGC and the associated lesions on Pap smears remains challenging, even for experienced cytopathologists. The frequency and histologic follow–up of AGC regardless of gland cell type were investigated.&#x0D; Methods: A retrospective review was conducted involving 199,265 cervicovaginal smears which were examined in the Department of Pathology and Cytology of Celje General Hospital between 1 January 2003 and 31 December 2008. We investigated the frequency of AGC on conventional Pap smears and evaluated the follow–up and correlation between cytology results and subsequent biopsy diagnoses over a 6–year period. The data were processed using the statistics program, SPSS. Statistical significance was set at a p&lt;0.05.&#x0D; Results: Between 1 January 2003 and 31 December 2008, a total of 745 women had AGC, representing 0.4% of all Pap smear results. One hundred seventy–two women (23.1%) with an average age of 41 years (range, 17–65 years) had a subsequent histologic examination. There were 79 patients (45.9%) with a clinically significant diagnosis, including 63 patients with high– grade cervical intraepithelial neoplasia, 4 patients with adenocarcinoma in situ, and 12 patients with invasive carcinoma (5 endometrial adenocarcinomas, 5 cervical squamous carcinomas, and 2 other types). Normal histologic findings were present in 65 patients (37.8%), 26 patients had low–grade cervical intraepithelial neoplasia, and 2 patients had low–grade glandular intraepithelial neoplasia.&#x0D; Conclusion: In subsequent biopsy specimens, cytologically AGC are not always glandular or even abnormal. The underlying abnormalities are often so serious that AGC findings require careful clinical and histologic follow–up.

Are we managing our patients correctly following treatment for cervical glandular intraepithelial neoplasia? A review of practice at the Jessop Wing Colposcopy Unit.

Women diagnosed with cervical glandular intraepithelial neoplasia (CGIN) remain at risk of further pre-malignant and malignant disease and require rigorous post-treatment follow-up. We assess the effectiveness and safety of community cervical sampling follow-up in women treated for CGIN. A retrospective study was conducted of women diagnosed with CGIN between April 1, 2013, and March 31, 2019, at Jessop Wing Colposcopy Unit, Sheffield, UK. Of 140 women diagnosed with CGIN, 76had co-existing cervical intraepithelial neoplasia (CIN). Cytologists were significantly more likely to report glandular neoplasia in the absence of co-existing CIN, and high-grade dyskaryosis in its presence (Ps<0.0001). Co-existing CIN was significantly more likely to be present with high or low-grade compared to normal colposcopy findings (P<0.0001). The 6-month test of cure (TOC) was attended by 67% of women (84% within 12months), and the 18-month post-treatment sampling by 52.5% of women (70% within 24months). Colposcopy recalled 96% of women correctly for the 18-month sampling, but 20% of women undertaking primary care samples were incorrectly recalled at 3years instead. When CGIN is diagnosed, two dates for recall should be provided at 6 and 18months post-treatment to the Cervical Screening Administration Service and the centralised screening laboratory ensuring the 18-month post-treatment sample is correctly appointed, preventing women with HPV-negative TOC samples being returned to 3-year recall. Follow-up of CGIN should be closely audited by the centralised laboratories ensuring women with CGIN are not put at additional risk.

Cervical glandular neoplasia referrals and the diagnosis of adenocarcinoma in situ: Correlating cytology, colposcopy findings, and clinical outcomes.

To determine the clinical outcomes of women with possible glandular neoplasia of endocervical type on cervical cytology, and review all diagnoses of cervical adenocarcinoma in situ (AIS) over a 5year period at our institution. A retrospective case-note review was conducted of all women referred to colposcopy with possible glandular neoplasia of endocervical type on cervical cytology or diagnosed with cervical AIS after biopsy or excision, from January 2014 until December 2018 in a London district hospital. Of 55 women referred with possible glandular neoplasia of endocervical type, 47 (85.4%) had a significant pathology on histopathological analysis: AIS (n=22); invasive cancer (n=7); high-grade cervical intraepithelial neoplasia (n=18). Women with a history of borderline abnormality on cervical cytology within the last 5years were significantly more likely to be diagnosed with AIS or invasive cancer (P<.05). For the same period 49 women had histologically proven AIS. Among these 22 (44.8%) were referred as possible cervical glandular intraepithelial neoplasia. Other reasons for referral were the following indications: borderline dyskaryosis (n=13); high-grade dyskaryosis (n=8); low-grade dyskaryosis (n=4); postcoital bleeding (n=2). Due to the raised risk of significant gynaecological pathology in women with possible glandular neoplasia of endocervical type on cervical cytology, excisional biopsy is essential. Colposcopic impression varies significantly and complete excision of the abnormal lesions should be achieved. AIS is a histological diagnosis and should always be considered during colposcopical and cytopathological assessment.

A new one in the classification of benign colon epithelial tumors (WHO, 2019, 5th edition)

The 2019 WHO Classification of Benign Colon Epithelial Neoplasms includes serrated dysplasia, adenomatous polyps, and glandular intraepithelial neoplasia. Serrated dysplasia (ICD-O 8213/0 and 8213/2) is former serrated masses. There is an expected change in its terminology: it is proposed to use the term 'sessile serrated lesion' (SSL) instead of that 'sessile serrated polyp/adenoma' that causes a lot of discussion. The 2019 WHO Classification versus the 2010 WHO classification more clearly defines the TSA criteria: slit-like serration and high elongated cells with pronounced eosinophilic cytoplasm and an elongated pencillate nucleus. The traditional adenomas are renamed in the classification; the term 'adenomatous polyps' that still includes tubular, tubulovillous, and villous adenomas is adopted instead of the term 'adenomas'. The criteria for adenomas remain the same (by the area occupied by villous structures). The 5th edition introduces a separate large section devoted to inflammatory bowel disease-associated dysplasia that is defined as obvious epithelial neoplastic changes that are limited to the basement membrane. The diagnosis can only be used for specific lesions, such as Crohn's colitis and ulcerative colitis.

The Prevalence of High Grade Cervical Intraepithelial Neoplasia (CIN) in a Primary Human Papillomavirus (HPV) Cervical Screening Programme Population with HPV Positive and Cytology Negative Smear Results

High-risk HPV is found in 99.7% of cervical cancers. The causative role of HPV in cervical cancer has led to the inclusion of HPV testing as part of cervical screening. A pilot of HPV testing as primary screening was commenced in 2013 at six pilot sites in England. North Cumbria Integrated Care (NCIC) NHS Foundation Trust took part in the pilot, in which women with an HPV-positive/cytology-negative result were recalled at 12 months. Women with HPV type 16/18 found at initial screening and persisting at 12 months in spite of negative cytology were referred to Colposcopy services at 12 months. Women with smear positive for hrHPV other than 16/18 types were recalled twice at 12 and 24 months before referral to colposcopy. Persistent hrHPV positive/cytology negative smear at 12 and 24 months initiated a colposcopy referral. Objective: To assess the prevalence of high grade CIN and invasive cancer in patients referred to colposcopy services at NCIC NHS Foundation Trust with hrHPV positive/cytology negative smears. Method: The study was conducted at NCIC NHS Foundation Trust between January 2015 and December 2017. Data was collected retrospectively from the colposcopy data base (INFOFLEX). All patients with HPV positive/cytology negative smears seen in colposcopy clinic during the study period were included. Patients with high grade CIN, cervical glandular intraepithelial neoplasia (CGIN) or invasive cancer were recorded. Results: 763 women were included in the study. A total of 50 (6.6%) women had high grade CIN, CGIN or invasive cancer. 40 of these 50 women (80%) were treated by large loop excision of the transformation zone (LLETZ). Conclusion: HPV primary screening is more effective than cytology-based screening. A high grade HPV positive result with negative cytology, persisting for one year in type 16/18 and for two years in other high-risk HPV types, warrants referral for colposcopy, as 6.6% of women in this study had high grade or invasive pathology.

Деструктивно-хірургічні методи лікування патології шийки матки – плюси та мінуси

The prolonged existence of the pathological process in the cervix channel requires not only the medical correction of inflammatory, dyshormonal, immunosuppressive, dysmetabolic changes in the organism that contribute to their occurrence, but also the use of destructive treatments. Unfortunately, this treatment leads to destructive-pathological changes in the cervical epithelium of the cervix and, as a consequence, to the reproductive function of the woman. The objective: to evaluate the regenerative capacity of the cervical epithelium after the application of destructive surgical methods for treating its pathology in women of reproductive age. Materials and methods. On the basis of the Kiev city center of reproductive and perinatal medicine 370 non-pregnant patients with cervical glandular intraepithelial neoplasia were examined and treated. The age of the treated women was 18-45 years. All women were examined cytologically, bacterioscopically, bacteriologically, for the presence of sexually transmitted infections, a diagnosis was made for the human papillomavirus by polymerase chain reaction, histological examination of the biopsy material. In case of detection of a violation of the vaginal biocenosis, etiopathogenetic treatment was carried out taking into account the detected infectious agents and their sensitivity to antibiotics. The treatment regimens were selected individually and differentially. 130 (35.14%) patients underwent cryodestruction of the cervix by the proposed method, 150 (40.54%) patients underwent excision of the cervix with Heims-Rogovenko knives and 90 (24.32%) patients had conical diathermoelectroexcession of the cervix. Results. All patients were treated in accordance with the severity of the process. 138 treated women showed cicatricial deformity of the cervix, in 86 - stenosis of the cervical canal was diagnosed, and in 52 - cervical canal atresia. Conclusion. The use of destructive surgical methods for treating cervical pathology makes it possible to achieve elimination of dysplastic processes. But the frequency of the occurrence of destructive and pathological changes on the surface of the cervix causes a promising search for new methods of influencing the course of the wound process after destructive and surgical treatment to ensure epithelization and preserve the anatomical and functional capacity of the cervical structures. Key words: cervical pathology, reproductive age, destructive, abnormal cervical degenerative surgical treatment.

Detection of occult endocervical glandular dysplasia in cervical conization specimens for squamous lesions

The aim of this work was to evaluate the incidence of occult cervical glandular intraepithelial neoplasia (CGIN) and adenocarcinoma of the cervix (AC) in women treated with CO2-laser conization for cervical intraepithelial neoplasia (CIN) or squamocellular cervical cancer (SCC).The medical records of all women with a histological diagnosis of squamous lesions of the uterine cervix (persistent CIN1, CIN2, CIN3 and SCC) who were subsequently treated with CO2-laser conization at our institution, during the period from January 1991 to December 2014, were analyzed in a retrospective case series.Among the 1004 women fulfilling the study inclusion/exclusion criteria, 77 cases (7.7%) of occult glandular lesions (CGIN and AC) were detected on the final cone specimen (48 cases of occult low-grade cervical glandular intraepithelial neoplasia (LCGIN), 25 cases of occult high-grade cervical glandular intraepithelial neoplasia (HCGIN), and four cases of occult “usual-type” AC). No difference in the mean age between women diagnosed with occult glandular lesions and women without occult glandular lesions on the final specimen emerged (39.1±9.3 vs 38.4±9.4, p=0.5).In women with occult LCGIN on cone specimen, mean follow-up of 48 months was reported (range 7–206 months) and no cases of progression to HCGIN or AC were observed.In conclusion, a relatively high rate of occult glandular lesions was found in women treated for squamous lesions. The natural history of CGIN is still uncertain and, in particular, there are some controversies as to whether LCGIN is a precursor lesion of HCGIN or AC. In this context the role of pathologists become very important since the appropriate diagnosis of these lesions could have potential implications in the clinical management of these patients.

High-risk HPV genotyping PCR testing as a means of cervical cancer and precancerous lesions early screening

To explored high-risk HPV genotyping PCR testing whether as a feasible means for the early screening of cervical cancer and precancerous lesions. From January 2013 to June 2014, 15,192 outpatients in China-Japan Friendship Hospital voluntary were tested by high-risk type HPV genotyping PCR. The average age of them were (33±8) years old. High-risk HPV types genotyping PCR tested by fluorescence PCR technology, in which 13 kinds of high-risk HPV subtypes were detected, including HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and 68. A total of 4,315 cases of them were tested by the liquid-based cytology (LCT), among them with positive of high-risk HPV genotyping tested by PCR (n=2,366) were biopsy under colposcope (648 cases) in those LCT results were positive or LCT negative but HPV16 positive or LCT negative but had the clear clinical symptoms or and non-HPV16 positive but with clear clinical symptoms. (1) Analysis high-risk HPV infection status of 15 192 women. (2) As the pathological diagnosis was the gold standard in the diagnosis of cervical lesions, analysis of the relationship among high-risk HPV infection, virus loads and cervical lesions. (3) To evaluated the value of high-risk HPV genotyping PCR tested method in screening of cervical cancer and precancerous lesions. ⑴ Of 15,192 cases tested by high-risk HPV genotyping PCR, 2,366 cases were HPV positive (HPV infection), the overall infection rate was 15.57% (2,366/15,192), in which a single subtype of HPV infection in 1,767 cases, infection rate was 11.63% (1,767/15,192), and multiple subtypes of HPV infection (two and more subtypes HPV infection) in 599 cases, infection rate was 3.94% (599/15,192). The HPV16, 52 and 58 infections were the most common HPV subtypes in 13 subtypes, the infection rate was 3.95% (600/15,192), 2.86% (435/15,192) and 2.67% (406/15,192), respectively. (2) The most relevant subtypes with cervical intraepithelial neoplasia (CIN) II and even higher lesion were HPV16, 52 and 58, accounted for 57.7% (154/267) of all above CIN II lesions. The most relevant subtype with the cervical glandular intraepithelial neoplasia (CGIN) II or above lesions was HPV18, 3 cases with CGIN II or above lesions were all single HPV18 infection. The pathologic examination positive percentage of patients which HPV virus loads≤10(3) copys/10(4) cells was 18.2% (25/137), while the pathologic examination positive proportion was 33.3% (247/742) which HPV virus loads≥10(4) copys/10(4) cells, there was statistically significant difference between them (χ2=27.06, P=0.000). (3) Sensitivity, specificity, positive predictive value and negative predictive value for detection of CIN II or above using HPV genotyping PCR were 96.11%, 85.76%, 30.94% and 99.70%, respectively. There were a guiding significance for high-risk HPV genotyping PCR tested in screening of cervical cancer and precancerous lesion. HPV16, 52 and 58 were related to the severe cervical squamous epithelial lesions, while HPV18 was related to cervical severe glandular cell pathological changes. HPV genotyping is feasible and economical as the first choice of opportunistic screening in tertiary hospitals.

Stratified mucin-producing intraepithelial lesion (SMILE): report of a case series with associated pathological findings.

Stratified mucin-producing intraepithelial lesion (SMILE) is an uncommon premalignant cervical lesion showing morphological overlap with cervical intraepithelial neoplasia (CIN) and adenocarcinoma insitu (AIS)/cervical glandular intraepithelial neoplasia. Given the limited literature on SMILE, we aimed to document its frequency and assess the associated pathology in a large series of cases. Over a 6-year period, we documented all cases of SMILE and the associated findings. SMILE was diagnosed in 69 specimens from 60 patients (50 loop excisions and 19 punch biopsy specimens), constituting 0.6% of cervical specimens. Overall, SMILE coexisted with high-grade CIN in 93% of cases, AIS in 42%, and a carcinoma in 10%. When SMILE was diagnosed on a cervical punch biopsy, there was high-grade CIN in the follow-up loop in most cases. SMILE was consistently diffusely p16-positive and IMP3-negative. Given the morphological overlap and significant association with high-grade CIN and AIS, we believe that SMILE is best regarded as a form of high-grade reserve cell dysplasia, probably arising from reserve or stem cells with the capacity for multidirectional differentiation. We recommend that management of SMILE should be as for AIS.

High expression of ezrin predicts poor prognosis in uterine cervical cancer

BackgroundEzrin, a member of the ezrin/radixin/moesin (ERM) protein family, plays a pivotal role in tumor invasion and metastasis. This study is aimed to investigate the clinicopathological significance of upregulated ezrin protein expression in uterine cervical cancers.MethodsImmunohistochemical staining of ezrin protein was performed on uterine cervical cancer specimens from 235 patients. For comparison, 239 cases of cervical intraepithelial neoplasia (CIN), 17 cases of cervical glandular intraepithelial neoplasia (CGIN) and 52 normal cervix samples were also included. qRT-PCR was performed on fresh tissues to detect ezrin mRNA expression levels. HPV infection statuses were genotyped by oligonucleotide microarray, and 10-year survival rates were calculated using the Kaplan-Meier method for 109 cervical cancer patients.ResultsApical membranous distribution of ezrin protein was only observed in normal cervical glands, while perinuclear staining was only observed in cervical cancers. Strong cytoplasmic and diffuse localization of ezrin were frequently seen in the cervical cancers compared with the normal counterparts. Furthermore, this strongly positive ezrin expression was significantly higher in cervical cancers than in CIN, CGIN, and normal cervical epithelia. Ezrin overexpression was closely related with poor differentiation, late stage, and lymph node metastasis. Additionally, ezrin overexpression was associated with lower 10-year survival rate for patients with early stage cervical cancer, but not for patients with advanced stage.ConclusionsAberrant localization and overexpression of ezrin might be an independent effective biomarker for prognostic evaluation of cervical cancers.

HISTOPATHOLOGICAL ECTOCERVIX EPITHELIUM CHANGES IN PATIENTS WITH HPV-INFECTION

Aim. To study the histopathological changes in ectocervix epithelium among patients with HPV-infection. Materials and methods. The object of the study – 105 women aged 25 to 39 with PCR-diagnosed HPV-infection. Patients underwent standard gynecological investigation and widened colposcopy with a target (colposcopically oriented) uterine cervix biopsy. Biopsy material was subjected to histological investigation using the generally accepted histological methods. Statistical analysis was performed with the program package Biostat. For the purpose of assessing significance of differences between distribution of qualitative signs in the studied samples, χ 2 criterion and Z criterion were used. Results. Patients with HPV-infection had some morphological variants of changes in uterine cervix mucosa that depends on presence and degree of multilayer pavement epithelium dysplasia. It was established that while CIN is progressing, expression of such HPV-infection signs as manifestation of koilocytosis and hyper-and parakeratosis is reduced. Besides, there is a tendency to chronization of inflammatory changes in uterine cervix lamina as CIN degree is growing. As CIN degree is growing, there is increase in cervical glandular intraepithelial neoplasia degree (CGIN). Conclusion. As a result of histological investigation of biopsy material taken from HPV-infected patients with uterine cervix pathology, regularities of changes in the character of reactive ectocervix processes connected with CIN progressing were established.

Screening for Cervical Cancer and Its Association with Human Papilloma Virus (HPV) among Sudanese Women

This study investigates the presence of human papilloma virus (HPV) on cervical smear among women in Khartoum State. Four hundred specimens were taken from patients who attended different hospitals in Khartoum State during a period from July 2008 to July 2009. The specimens were processed and screened using cytological technique (Papanicolaou stain) and PCR for HPV detection. The pre-cancer cells were detected in 30/400 (7.5%) specimens among which cervical glandular intraepithelial neoplasia (CGIN) was found in one cases 1/30 (0.3%), the details were as follows: mild dyskaryosis was present in 18/30 (4.5%), moderate dyskaryosis in 5/30 (1.3%), and severe dyskaryosis 6/30 (1.5%). On the other hand, screening for HPV among the enrolled subjects revealed high ratio (36.0%). HPV was detected in all cases that had cytological changes except one (29 out of 30 cases (96.7%)). Infections other than HPV were observed during cytological assessment which include T. vaginalis 8 (2.0%), Candida spp. 11(2.8%), and Actinomyces spp. 5 (1.3%). The study concluded that the prevalence of HPV infection is high in Sudanese women (36%) who were revealed as 96.6% in pre-cancer cases and 83.3% in cervical cancer patients.

Cervical glandular intraepithelial neoplasia: a clinicopathologic and immunohistochemical analysis of 80 cases

To assess the clinicopathologic characteristics of cervical glandular intraepithelial neoplasia (CGIN) and to evaluate the usefulness of EnVision immunohistochemistry of various markers in identifying early invasive cervical adenocarcinoma (ICA) and its precursor lesions. Clinical and pathological characteristics of 80 cases of high grade CGIN (HCGIN), 20 ICA, and 20 cervicitis were reviewed along with immunohistochemical studies of p16, Ki-67, CEA, CA125 and bcl-2. The clinical features of HCGIN were similar to those of high grade cervical intraepithelial neoplasia (CIN). Fourty four cases (55.0%) accompanied with CIN and 9 cases (11.3%) accompanied with early cervical squamous cell carcinoma (SCC). The positive rates of p16, CEA and Ki-67 in 80 cases of HCGIN were 100.0%, 63.8% and 73.8%, respectively. The positive rates of p16, CEA and Ki-67 in 20 ICA were 18/20, 16/20 and 20/20, respectively. The positive rates of p16, CEA and Ki-67 in 20 cervicitis were 1/20, 1/20 and 3/20, respectively. There was a significantly increased expression of p16, CEA and Ki-67 in ICA and HCGIN compared with cervicitis (P < 0.01). Ki-67 expression increased in ICA compared to HCGIN (P < 0.05). There was no statistical difference in CEA expression between ICA and HCGIN (P > 0.05). CA125 showed strong but nonspecific expression. Bcl-2 was negative or occasionally positive in each groups. HCGIN is frequently accompanied with CIN and SCC. The combined staining of p16, CEA and Ki-67 provides additional aid in the diagnosis of early stage cervical adenocarcinoma and its precursor lesions. The sensitivity of p16 and Ki-67 markers for HCGIN is higher than that of CEA. CA125 and bcl-2 immunostains offer no helpful in identifying HCGIN.

New developments in endocervical glandular lesions

McCluggage W G (2012) Histopathology New developments in endocervical glandular lesions There is evidence that the prevalence of premalignant and malignant endocervical glandular lesions is increasing in real as well as in apparent terms. In this review, new developments and selected controversial aspects of endocervical glandular lesions are covered, concentrating mainly on premalignant and malignant lesions. The terminology of premalignant endocervical glandular lesions is discussed with a comparison of the World Health Organization classification and the cervical glandular intraepithelial neoplasia (CGIN) system, which is in widespread use in the United Kingdom. Primary cervical adenocarcinomas comprise a heterogeneous group of different morphological types, and while it is known that the majority of these are associated with high-risk human papillomavirus (HPV), it has become clear in recent years that most of the more uncommon morphological types are unassociated with HPV, although they may sometimes be p16-positive. A spectrum of benign, premalignant and malignant cervical glandular lesions exhibiting gastric differentiation is now recognized; these include type A tunnel clusters, typical and atypical lobular endocervical glandular hyperplasia, adenoma malignum and gastric-type adenocarcinoma. The latter is a recently described variant of primary cervical adenocarcinoma which has a different morphological appearance to the usual endocervical type and which is probably associated with different patterns of spread and a worse prognosis. There is accumulating evidence that 'early invasive' cervical adenocarcinomas have an excellent prognosis and are suitable for conservative management. Immunohistochemical markers of value in the distinction between a primary cervical and endometrial adenocarcinoma are discussed. While it is well known that a panel of markers comprising oestrogen receptor (ER), vimentin, p16 and monoclonal carcinoembryonic antigen (CEA) is useful, several major pitfalls are pointed out and this panel of markers is predominantly of value in 'low-grade' adenocarcinomas. A related group of lesions, including cervical ectopic prostatic tissue and vaginal tubulosquamous polyp, are probably derived from para-urethral Skene's glands and may be positive with prostatic markers. Recent developments in cervical neuroendocrine neoplasms are discussed, as these are associated not uncommonly with a premalignant or malignant endocervical glandular lesion.

Review of cytology and histopathology as part of the NHS Cervical Screening Programme audit of invasive cervical cancers

To audit pathology slide reporting in the Cervical Screening Programme in England by reviewing cytology and histology slides from women subsequently diagnosed with invasive cervical cancer. Between April 2007 and March 2010, 6113 women diagnosed with cervical cancer were identified. Cervical cytology and histology slides taken within 10 years of diagnosis were identified and where possible reviewed after a nationally agreed protocol. Reviewers were not blinded to the original reading of each sample. Most cytology samples before 2005 were conventional, most after 2007 liquid based. Of 13,745 cytology results from women developing cervical cancer, 55% were reviewed. The review result was identical for 55% of slides. Of 3759 originally normal slides, only 45% were normal on review: 11% were inadequate, 21% low grade (borderline or mild dyskaryosis) and 23% high grade (moderate dyskaryosis or worse). Of tests originally normal taken over 5.5 years before diagnosis, 14% were upgraded to high grade compared with 37% within 3.5 years of diagnosis. Of 5159 histology specimens recorded within 10 years of diagnosis of a cancer, 3895 were reviewed. Overall, 94% of samples reviewed retained the original diagnosis. One per cent (33/3012) of cancers were downgraded and 5% (6/112) of negative samples were upgraded to cancer upon review (four of which were taken within 2 months of diagnosis). In comparison, 15% (14/91) of cervical glandular intraepithelial neoplasia (CGIN) and 12% (38/314) of cervical intraepithelial neoplasia grade 3 (CIN3) were upgraded to cancer. In spite of the excellent quality of cytology in England, a high proportion of negative cytology taken up to three and a half years before diagnosis were considered to contain abnormal cells by reviewers informed of the subsequent cancer. Continuing these reviews, with a strong focus on education, will ensure a clear understanding of these slides and further reduce the risk of developing cervical cancer.

Risk of significant gynaecological pathology in women with ?glandular neoplasia on cervical cytology

To review the risk of pre-invasive and invasive gynaecological pathology in women referred with cervical cytology reporting ?glandular neoplasia. Review of the case notes of all women referred with cervical cytology reported as ?glandular neoplasia between January 1999 and December 2008 at two UK hospitals: Portsmouth Hospitals NHS Trust and Queen Mary's Hospital Sidcup. The category of 'borderline nuclear change in endocervical cells', result code 8 according to the national health service cancer screening programme (NHSCSP), was excluded from the study. A total of 200 women were identified using the hospitals' pathology computer systems. Invasive carcinoma was found in 48 women (24%): 28 endocervical adenocarcinomas, eight squamous cell carcinomas (SCC), ten endometrial and two ovarian adenocarcinomas. Pre-invasive neoplasia was found in 115 (57.5%), including 14 cervical glandular intraepithelial neoplasia (CGIN), 31 cervical intraepithelial neoplasia (CIN) grade 2/3 and 70 concomitant CGIN and CIN2/3. CIN1/HPV was found in 25, simple endometrial hyperplasia in three and no histological abnormality in three. Thirty-four (70.8%) of 48 invasive carcinomas (of which 23 were endocervical adenocarcinomas) were in asymptomatic women investigated for abnormal cytology. Fourteen of 34 (41.4%) of those with ?glandular neoplasia thought to be endometrial were CGIN or CIN2/3. Colposcopic appearances were normal in 47.6% of women with pure cervical glandular neoplasia (adenocarcinoma or CGIN) compared with 12.8% with squamous cell lesions (CIN2/3 or SCC): P = 0.0001. Thus, colposcopy was more sensitive for detecting squamous cell abnormalities than their glandular counterparts. Although cervical adenocarcinomas are less amenable to prevention by screening than cervical SCC, in our study cervical cytology predominantly detected these abnormalities at their early asymptomatic stages. At least CIN2 was found in 81.5% in women referred with cervical cytology reporting ?glandular neoplasia. A thorough evaluation of the whole genital tract is needed if colposcopy is negative.

MYBL2 (B-MYB) in Cervical Cancer: Putative Biomarker

Cervical cancer is the second most common cancer affecting women worldwide. It is characterized by chromosomal aberrations and alteration in the expression levels of many cell cycle regulatory proteins. MYBL2 is a member of the MYB proto-oncogene family that encodes DNA binding proteins. These proteins are involved in cell proliferation and control of cellular differentiation. Four established cervical cancer cell lines were examined and compared with normal cervix using gene expression profiling and comparative genomic hybridization, and results were correlated to identify potential novel cervical cancer biomarkers. Results were validated using TaqMan polymerase chain reaction, and the potential role of MYBL2 as a clinical biomarker was then evaluated by immunohistochemistry on 30 tissue samples. MYBL2 was found to be overexpressed in the cervical cancer cell lines by gene expression profiling, and this result was confirmed using TaqMan polymerase chain reaction. Analysis of comparative genomic hybridization data indicated that chromosome 20q13.1, which encodes the MYBL2 gene, was amplified in the human papillomavirus (HPV) type 16-positive CaSki and SiHa cell lines but not in the HPV-18-positive HeLa or HPV-negative C33A cell lines. Although MYBL2 staining was predominantly absent in normal cervical epithelium, strong staining (score of 2 or 3) was identified in all cases of cervical intraepithelial neoplasia, cervical glandular intraepithelial neoplasia, and invasive cancer on immunohistochemistry. In addition, strong staining of a population of diffusely scattered single cells is identified. We postulate that these may represent so-called cancer stem-like cells.

The management of cervical glandular intraepithelial neoplasia during pregnancy

"The management of cervical glandular intraepithelial neoplasia during pregnancy." Journal of Obstetrics and Gynaecology, 30(6), pp. 640–641