Specimens Of Uterine Cervix Research Articles

Polarimetric imaging for cervical pre-cancer screening aided by machine learning: ex vivo studies.

Wide-field imaging Mueller polarimetry is an optical imaging technique that has great potential to become a reliable, fast, non-contact in vivo imaging modality for the early detection of, e.g., deceases and tissue structural malformations, such as cervical intraepithelial neoplasia, in both clinical and low-resource settings. On the other hand, machine learning methods have established themselves as a superior solution in image classification and regression tasks. We combine Mueller polarimetry and machine learning, critically assess the data/classification pipeline, investigate the bias arising from training strategies, and demonstrate how higher levels of detection accuracy can be achieved. We aim to automate/assist with diagnostic segmentation of polarimetric images of uterine cervix specimens. A comprehensive capture-to-classification pipeline is developed in house. Specimens are acquired and measured with imaging Mueller polarimeter and undergo histopathological classification. Subsequently, a labeled dataset is created within tagged regions of either healthy or neoplastic cervical tissues. Several machine learning methods are trained utilizing different training-test-set-split strategies, and their corresponding accuracies are compared. Our results include robust measurements of model performance with two approaches: a 90:10 training-test-set-split and leave-one-out cross-validation. By comparing the classifier's accuracy directly with the ground truth obtained during histology analysis, we demonstrate how conventionally used shuffled split leads to an over-estimate of true classifier performance . The leave-one-out cross-validation, however, leads to more accurate performance with respect to newly obtained samples that were not used to train the models. Combination of Mueller polarimetry and machine learning is a powerful tool for the task of screening for pre-cancerous conditions in cervical tissue sections. Nevertheless, there is a inherent bias with conventional processes that can be addressed using more conservative classifier training approaches. This results in overall improvements of the sensitivity and specificity of the developed techniques for "unseen" images.

Crosscut and Covey-Tunnel Clusters-Uterine Cervix

Tunnel clusters of uterine cervix articulate as a subtype of nabothian cyst delineating spherical aggregates of twenty to fifty intensely adherent tubules. Characteristically, lesion demonstrates a complex configuration of endocervical glands with multicystic dilatation. Subcategorized as type A and type B variants, type A tunnel clusters are constituted of miniature, non cystic endocervical glands whereas type B tunnel clusters exemplify cystic dilatation of endocervical glands. Of obscure aetiology, tunnel clusters are posited to represent a sub-involution within foci of endocervical glandular hyperplasia. Tunnel clusters are asymptomatic or may be associated with mucoid vaginal discharge. Type A tunnel clusters are composed of miniature, elongated, non-cystic endocervical glands layered with columnar to low cuboidal epithelium with mucinous cytoplasm, apical vacuoles and basal nuclei. Type B tunnel clusters are comprised of cystically dilated endocervical glands layered with bland, cuboidal or flattened epithelium and permeated with inspissated mucin. Tunnel clusters appear immune reactive to PAX2 wherein type A tunnel clusters with gastric metaplasia appear immune reactive to HIK1083. Tunnel clusters of uterine cervix require segregation from neoplasms such as minimal deviation adenocarcinoma or adenoma malignum, conventional endocervical adenocarcinoma, adenocarcinoma in situ, nabothian cysts and mesonephric remnants or mesonephric hyperplasia of uterine cervix. Tunnel clusters may be appropriately discerned with cogent histological examination of surgical tissue specimens of uterine cervix, appear devoid of precise, applicable therapeutic strategies and do not necessitate alleviation.

Immunohistochemical expression of P16 and Ki-67 in uterine cervical neoplasms

To study the expression of Ki-67 and p16 in neoplastic lesions of uterine cervix and to evaluate the prognostic significance of tumour differentiation, histological type, stage and grade, depth of tumour invasion and lymphovascular invasion in women with neoplasia of uterine cervix. This study was performed on 50 biopsies and surgically resected specimens of uterine cervix, which were fixed in 10% formalin, processed, paraffin embedded and cut into 3-5 microns thickness, stained with hematoxylin and eosin stains and immunohistochemical staining by p16 and Ki-67 antibodies was performed and studied. Majority of cases of invasive carcinoma cervix were large cell non-keratinizing squamous cell carcinoma, 58 cases (48.2%). Majority of cases of invasive carcinoma cervix were seen in stage 2B, 40 (40.8%) cases followed by stage 3B, 24 (24.4%) cases. Out of 18 cases of large cell non-keratinizing squamous cell carcinoma, 12 (66.7%) showed 3+ positivity for Ki-67. 7 (53.8%) cases of stage 2A showed 3+ positivity, 3 (23.1%) cases each showed 2+ positivity for p16. 7 (36.8%) cases of moderately differentiated SCC showed 3+ positivity, 4 (21.1%) showed 2+ positivity and 5 (26.3%) showed 1+ positivity of Ki-67. Out of 10 stable patients, 4 (40.0%) showed negative p16 immunoexpression and all the 3 cases (100%) with recurrence showed 2+ positivity and 2 (100%) patients with metastasis showed 3+ positivity. Out of 10 stable patients, 6 (60%) showed negative Ki-67 immunoexpression and all the 3 (100%) cases with recurrence showed 3+ positivity and one each (50.0%) patient with metastasis showed 2+ positivity and 3+ positivity. p16 and Ki-67 immunomarkers are useful as a diagnostic and prognostic tool in cases with recurrence and metastasis, helping in early detection of disease progression.

Clinico-Histomorphological Spectrum of Non-Neoplastic Lesions of the Uterine Cervix at a Tertiary Care Center of a Remote Indian Island

The uterine cervix is liable to suffer from several neo¬plastic and non-neoplastic gynaecologic lesions commonly seen in sexually active women. It is important to categorize and recognize the histomorphological features of cervical non-neoplastic lesions for better management of the patient. The present study was undertaken to study the microscopic features of the uterine cervix in non-neoplastic lesions. It was a retrospective cross-sectional study conducted over a period of two years in Department of Pathology. The study included 282 specimens of uterine cervix received at histopathology section. Detailed clinical details including age, parity, clinical findings and provisional diagnosis were noted. Out of these 282 specimens, 27.3% (77/282) were from cervical biopsy either endocervical curettage or punch biopsy, and 72.7% (205/282) were hysterectomy specimen. Most common clinical symptoms was irregular/excessive menses (44.68%, 126/282) followed by white discharge per vaginum (34.4%, 97/282). Out of 282 of the cases, 80.5% (227/282) showed chronic non-specific cervicitis (CNSC) followed by endocervical polyp (33/282, 11.7%) followed by squamous metaplasia (21/282, 7.4%). Koilocytic change was seen in 3.2% of cases (9/282). One case each for granulomatous cervicitis, microglandular hyperplasia, tunnel cluster, and condyloma acuminata was also noted. CNSC is the most common inflammatory lesion followed by endocervical polyp and squamous metaplasia. Prevalence of HPV related koilocytosis and condylomata acuminata is low in the study area as compared to other parts of India.

Polarimetric measurement utility for pre-cancer detection from uterine cervix specimens.

Prior work demonstrated significant contrast in visible wavelength Mueller matrix images for healthy and pre-cancerous regions of excised cervical tissue. This work demonstrates post-processing compressions of the full Mueller matrix that preserve detection performance. The purpose of this post-processing is to understand polarimetric measurement utility for computing mathematical observers and designing future imaging protocols. The detection performance of the full Mueller matrix, and both linear and non-linear parameters of the Mueller matrix will be compared. The area under the receiver operating characteristic (ROC) curve, otherwise known as the AUC, is the gold standard metric to quantify detection performance in medical applications. An AUC = 1 is perfect detection and AUC = 0.5 is the performance of guessing. Either the scalar retardance or the 3 smallest eigenvalues of the coherency matrix yield an average AUC of 0.94 or 0.93, respectively. When these four non-linear parameters are used simultaneously the average AUC is 0.95. The J-optimal Channelized Quadratic Observer (J-CQO) method for optimizing polarimetric measurements demonstrates equivalent AUC values for the full Muller matrix and 6 J-CQO optimized measurements. The advantage of this optimization is that only 6 measurements, instead of 16 for the full Mueller matrix, are required to achieve this AUC.

Cervicitis: How Often Is It Non-specific!

Uterine cervix is most often reported as 'non specific cervicitis'. It is an effort to encourage specific reporting and thereby avoiding the term 'non specific' to a possible extent. The study is carried out on 613 specimens of uterine cervix received at Department of Pathology, Aarupadai Veedu Medical College, Pondicherry, between 1(st) January 2010 to 31(st) December 2012. Histopathology slides of all the cases were studied for the presence of specific features of various inflammatory lesions. RESULTS are expressed in percentage. Chronic nonspecific cervicitis was the commonest inflammatory lesion constituting 89.23% of the cases. Other inflammatory lesions were follicular cervicitis in 6.85%, chronic cervicitis with koilocytosis in 3.75% and only one case (0.16%) of tuberculosis was observed. Importance of these benign lesions of the uterine cervix lies in the fact that some of them like Chlamydia, Papilloma infection have specific treatment and some of them form differential diagnosis for malignant lesions and some progress to malignancy.

Promoter hypermethylation of CDH13, DAPK1 and TWIST1 genes in precancerous and cancerous lesions of the uterine cervix

Aberrant DNA methylation is an early event in carcinogenesis and could serve as an additional molecular marker for the early diagnosis. The study was performed to investigate the promoter methylation of DAPK1, CDH13, and TWIST1 genes in uterine cervix lesions in an effort to examine whether this epigenetic event is involved in the process of cervical carcinogenesis, and whether it might be used as a molecular marker of cervical lesions. We conducted a retrospective study of 60 uterine cervix specimens, including 8 normal tissue samples, 10 benign lesions, 28 precancerous lesions (CIN1–3), and 14 squamous cell carcinomas (SCC). DNA hypermethylation was investigated using methylation-specific PCR. Immunohistochemistry was used to find p16 INK4A overexpression. No hypermethylated promoters were detected in normal tissues and benign lesions. However, promoter hypermethylation of CDH13, TWIST1, and DAPK1 increased progressively from CIN1 to cancer, reaching values higher than 50% for cancer. DAPK1 and CDH13 displayed a significantly increased frequency of promoter methylation with progressively more severe cervical neoplasia ( p < 0.05). A statistically significant association was observed between p16 INK4A expression and hypermethylation of DAPK1, TWIST1, and CDH13 ( p < 0.0001). Hypermethylation of CDH13, DAPK1, and TWIST1 promoters is an early event in the initiation and progression of cervix neoplasia. CDH13, DAPK1, and TWIST1 genes are potential biomarkers of cervical cancer risk.

P16 INK4A overexpression in precancerous and cancerous lesions of the uterine cervix in Tunisian women

Uterine cervix cancer is an important public health problem in developing countries. However, there is a substantial lack of inter-observer diagnostic reproducibility for its precursor lesions (CIN1). The study was performed to evaluate the usefulness of p16 INK4A overexpression as a surrogate marker for uterine cervix precancerous lesions and high-risk human papillomavirus (HPV) infection. We conducted a retrospective study of 87 uterine cervix specimens, including 7 normal tissue samples, 17 benign lesions, 34 precancerous lesions, 22 invasive squamous cell carcinomas (SCC), and 7 adenocarcinomas. Immunohistochemistry was used to find p16 INK4A overexpression. HPV infection was detected by PCR. No immunoreactivity for p16 INK4A was detected in normal tissue or benign lesions. p16 INK4A immunoreactivity was focal in CIN1, whereas strong and diffuse immunoreactivity for p16 INK4A was uniformly observed in both the nucleus and the cytoplasm of all CIN2 and 3, as well as in those of invasive SCC and adenocarcinomas. A statistically significant association was observed between p16 INK4A overexpression, lesion grade, and high-risk HPV infection ( p < 0.0001). p16 INK4A overexpression is a useful additional marker for the interpretation of problematic uterine cervical lesions and can help to reduce the variability during evaluation of suspicious biopsies of the uterine cervix.

Adipose Tissue: A Normal Constituent of the Uterine Cervical Stroma

Mature adipose tissue present in the uterine cervix is not well documented, and believed to represent heterotopic tissue. The purpose of this study was to determine the frequency and histogenesis of adipose tissue in a series of uterine cervix specimens. A total of 100 consecutive cervical loop electrosurgical excision procedure (LEEP) and cone biopsies from patients of mean age 28 years (range: 15 to 57 yr) were examined. The cervix in 30 hysterectomy specimens was also examined. The presence of cervical stromal and parametrial fat, pathologic diagnosis, number of prior cervical biopsies, and prior pregnancies were documented. In a subset, immunohistochemical stains were performed using S-100, and also CD31, CD34, and D2-40 to exclude dilated lymphatics. Mature fat was identified in 17/100 cone/LEEP cases and 2/30 hysterectomy specimens. Fat was located in deep cervical stroma among large vessels in 15/19 (79%) of these cases, and superficially beneath the mucosa admixed with endocervical glands in 4/19 (21%) cases. Patients with cervical fat in cone/LEEP specimens were of mean age 36 years (range: 21 to 57 yr), of which 65% had a squamous intraepithelial lesion and 35% reactive cervicitis. Those with cervical fat in cone/LEEP tissue had on average 2 prior cervical biopsies/case (range: 0 to 5), compared with 1.7 biopsies/case (range: 0 to 10) in those without identifiable fat. These patients with cervical fat had 1 pregnancy/case, whereas those without had 1.7 pregnancies/case. Mature adipose tissue is a normal stromal constituent of the uterine cervix, which may be identified in up to 15% of excision specimens. The presence of cervical fat seems to be unrelated to patient age, parity, parametrial adipose tissue, inflammation, or prior trauma.

Effect of using templates on the information included in histopathology reports on specimens of uterine cervix taken by loop excision of the transformation zone.

AIM: To determine the change in information relayed from histopathologists to clinicians by using templates for reporting specimens of uterine cervix sampled by loop excision of the transformation zone (LETZ)....

Deregulation of the G1/S phase transition in cancer and squamous intraepithelial lesions of the uterine cervix: A case control study

High-risk types of HPV express the oncoproteins, E6 and E7, that can inactivate TP53 and RB1, respectively, and thus take control of both cell cycle and apoptosis. Herein, the mRNA expression profiles of 24 G1/S checkpoint genes were analysed in cancer and squamous intraepithelial lesions (SIL) of the uterine cervix. In total 35 squamous cervical carcinomas, 26 high-grade SIL (HSIL), 33 low-grade SIL (LSIL) tissues, and 28 normal uterine cervix specimens as controls were assessed by RT-PCR. Five genes were found to be upregulated only in tumours, RBL2, E2F2, CDK6, CCNE1 and MYC; eight in tumours and HSILs, E2F1, E2F3, E2F5, CCND1, CDK2, CDKN1B, PCNA and POLA, and five in tumours, HSILs and LSILs, TP53, E2F4, CDKN1A, CDKN2A and DHFR. MDM2 was found to be upregulated in SIL, while RBL1 was found to be downregulated in all three groups of cases. TP73 exhibited lower levels in carcinomas; however, its exon 13-containing isoforms were increased and exon 2-containing isoforms were reduced in both cancer and HSIL. Three genes, RB1, CDK4 and CDKN2D, did not exhibit any significant alteration in gene expression. Hierarchical clustering revealed that this set of G1/S checkpoint genes was able to discriminate the total 122 samples into groups of disease and non-disease with only 8 exceptions (6.6%). Our data suggest that deregulation of G1/S phase transition in cervical carcinogenesis is a progressive process. Certain clusters of genes are activated very early in pre-cancerous SILs while others are activated later, during malignant transformation. The ability of this array of markers to identify disease status suggests that it could be used for diagnostic purposes.

The demonstration of papilloma virus in cervical dysplasia and/or neoplasia.

Thirty-three random biopsy specimens of uterine cervix were studied by immunoperoxidase technique to evaluate the presence of HPV antigen in dysplastic and neoplastic cells. Four cases of mild dysplasia, nine cases of moderate to severe dysplasia, two cases of carcinoma in situ and one case of invasive carcinoma were associated with condylomatous lesions. Intranuclear dark-brown precipitates were observed in superficial and intermediate zones of the dysplastic epithelium. Positive reaction was seen in condylomatous epithelium associated with neoplasia. No nuclear precipitates were observed in carcinoma cells, but one noncondylomatous lesion with moderate dysplasia showed positive intranuclear staining. These preliminary findings suggest that papilloma viruses may play a role in the development of human cervical neoplasias.