Cervical Biopsy Specimens Research Articles

Histopathological Spectrum of Non-Neoplastic Uterine Cervical Lesions in a Tertiary Care Centre

Background: Uterine cervix in our routine hysterectomies and biopsies from gynecological specimens constitutes major portal for nonneoplastic lesions. Routine histopathological study of suspicious cases enhances early detection of these uterine cervical lesions. Methods: 250 cases of uterine cervical non-neoplastic lesions were evaluated either from hysterectomy or cervical biopsy specimens. The purpose of this study is to analyze and determine the frequency and histomorphological patterns of non-neoplastic cervical lesions at the tertiary care center and to study various metaplasias of the endocervical epithelium. The cervical lesions were subjected to detailed gross and microscopic examination and further classified into various non-neoplastic lesions Result: Our study showed that 48 % of cases featured chronic nonspecific cervicitis. The commonest encountered endocervical epithelial lesions were chronic polypoidal endocervicitis (20%) and squamous metaplasia (36%) and the uncommon lesions included micro glandular adenosis (3.2%), endocervical glandular hyperplasia (4%), diffuse laminar endocervical glandular hyperplasia(0.8%) tunnel clusters (0.4%) and mesonephric rests (0.4%). A majority of the ectocervical lesions includes Koilocytic changes, exocytosis, Suprabasal bulla and prolapse changes like hyperkeratosis and parakeratosis. Conclusion: In the present study we emphasized mainly about nonneoplastic uterine cervical lesions among which Chronic non-specific cervicitis is the most confronted lesion in histopathological specimens. However, there are many lesions that appear to be exuberant and can be misdiagnosed to be malignant. On the basis of this, a detailed histomorphological study of the nonneoplastic lesions of the cervix was taken up and further categorized into various lesions which can cause serious morbidities and detailed histopathological study is considered as the gold standard. DOI: 10.21276/APALM.1405

Immuno-related polymorphisms and cervical cancer risk: The IARC multicentric case-control study.

A small proportion of women who are exposed to infection with human-papillomavirus (HPV) develop cervical cancer (CC). Genetic factors may affect the risk of progression from HPV infection to cervical precancer and cancer. We used samples from the International Agency for Research on Cancer (IARC) multicentric case-control study to evaluate the association of selected genetic variants with CC. Overall, 790 CC cases and 717 controls from Algeria, Morocco, India and Thailand were included. Cervical exfoliated cells were obtained from control women and cervical exfoliated cells or biopsy specimens from cases. HPV-positivity was determined using a general primer GP5+/6+ mediated PCR. Unconditional logistic regression was used to estimate odds ratios (OR) and corresponding 95% confidence intervals (CI) of host genotypes with CC risk, using the homozygous wild type genotype as the referent category and adjusting by age and study centre. The association of polymorphisms with the risk of high-risk HPV-positivity among controls was also evaluated. A statistically significant association was observed between single nucleotide polymorphism (SNP) CHR6 rs2844511 and CC risk: the OR for carriers of the GA or GG genotypes was 0.70 (95% CI: 0.43–1.14) and 0.61 (95% CI: 0.38–0.98), respectively, relative to carriers of AA genotype (p-value for trend 0.03). We also observed associations of borderline significance with the TIPARP rs2665390 polymorphism, which was previously found to be associated with ovarian and breast cancer, and with the EXOC1 rs13117307 polymorphism, which has been linked to cervical cancer in a large study in a Chinese population. We confirmed the association between CC and the rs2844511 polymorphism previously identified in a GWAS study in a Swedish population. The major histocompatibility region of chromosome 6, or perhaps other SNPs in linkage disequilibrium, may be involved in CC onset.

Impact of Consensus Conference Review on Diagnostic Disagreements in the Evaluation of Cervical Biopsy Specimens.

To determine the impact of consensus conferences on the frequency of discrepant cases in a surgical pathology practice. The percentage of discrepancies in cases reviewed at a weekly consensus conference was calculated for the first and last months of a 13-month period. Both interrater agreement and agreement with the consensus diagnoses were assessed. A total of 309 diagnoses were performed for the first month and 518 for the last month. Both absolute and chance-corrected agreement were calculated for each period. Absolute agreement rate increased from 91.2% in the first month to 98.2% in the final month. Chance-corrected agreement increased from 0.80 in the first month to 0.97 in the final month. The consensus conference technique appears to be a useful method to reduce intradepartmental diagnostic discrepancies. Both absolute and chance-corrected agreement are improved by using consensus conferences.

Role of p16/INK4a and Ki-67 as specific biomarkers for cervical intraepithelial neoplasia: An institutional study.

BACKGROUND:P16/INK4a and Ki-67 have emerged as important biomarkers for the detection of high-risk human papilloma virus (HR-HPV) associated dysplastic changes in the cervical biopsy samples. The increasing inter- and intra-observer variability in the diagnosis of dysplastic lesions and immature squamous metaplasia on histopathology has led to the advent of these biomarkers. This study was taken up with an aim to study their role in increasing the diagnostic accuracy in equivocal cases on histopathology.MATERIALS AND METHODS:Fifty cervical biopsy specimens were stained with p16/INK4a and Ki-67 consisting of 10 cases each of cervical intraepithelial neoplasia (CIN I/II/III) along with five cases of squamous metaplasia. Histopathological diagnosis was considered as the gold standard. Statistical analysis was done by kappa statistics, and P value was calculated.RESULTS:The sensitivity and specificity of p16/INK4a and Ki-67 were 76.2%, 87.5%, 90.5%, and 87.5%, respectively. The overall agreement of both the immunostains with histopathological diagnosis was statistically significant (P < 0.05) and the diagnostic accuracy improved when both the stains were used in conjunction.CONCLUSION:Ki-67 and p16/INK4a can be used as complimentary tests in differentiating dysplastic and nondysplastic lesions and help in confirming the histopathological diagnosis. They aid in recognition of dysplasias caused by HR-HPV, which have higher tendency to progress to neoplasia. However, further research is advocated before the widespread use of these markers for screening of dysplasias.

Role of p16, Ki67 and CK17 in differentiating benign lesions, cervical intraepithelial neoplasia(CIN) and atypical immature squamous metaplasia(AIM) of uterine cervix

Cervical intraepithelial neoplasia (CIN) is a premalignant lesion capable of progressing to cervical cancer. Despite the existing well-defined criteria, the histopathological diagnosis is subject to high rates of discordance among pathologists. Aim: To study the role of p16, Ki67 and CK17 in differentiating benign lesions, cervical intraepithelial lesions(CIN) and atypical immature squamous metaplasia (AIM)and to improve intra and interobserver reproducibility of diagnosis of cervical neoplasia. Material and Methods: In a cross sectional study, a total of 75 cervical biopsies including benign lesions (n=24), AIM (n=28), CIN (n=23) were studied and analyzed immunohistochemically using p16, Ki67 and CK17 immunomarkers. Data was evaluated using chi-square test. Results: p16 and Ki 67positivity were observed in 91.3% and 78.26% of CIN and 28.57% of AIM respectively. None of the benign lesions expressed p16 and Ki67while CK17 positivity was observed in 46.42% of CIN and 100% of AIM with 12.5% of benign lesions. Conclusion: The three biomarkers (p16, CK17 and Ki67) had a high degree of sensitivity and specificity and appear to be a useful and reliable diagnostic adjunct to improve the routine diagnosis and reduce interobserver variability in cervical biopsy specimens. Immunohistochemical markers such as p16 alone or with Ki67 represents important tool for the pathologists in distinguishing high grade cervical dysplasia from its benign mimics such as AIM and reactive inflammatory lesion thus avoiding overtreatment. Cervical intraepithelial neoplasia (CIN) is a premalignant lesion capable of progressing to cervical cancer. Despite the existing well-defined criteria, the histopathological diagnosis is subject to high rates of discordance among pathologists. Aim: To study the role of p16, Ki67 and CK17 in differentiating benign lesions, cervical intraepithelial lesions(CIN) and atypical immature squamous metaplasia (AIM)and to improve intra and interobserver reproducibility of diagnosis of cervical neoplasia. Material and Methods: In a cross sectional study, a total of 75 cervical biopsies including benign lesions (n=24), AIM (n=28), CIN (n=23) were studied and analyzed immunohistochemically using p16, Ki67 and CK17 immunomarkers. Data was evaluated using chi-square test. Results: p16 and Ki 67positivity were observed in 91.3% and 78.26% of CIN and 28.57% of AIM respectively. None of the benign lesions expressed p16 and Ki67while CK17 positivity was observed in 46.42% of CIN and 100% of AIM with 12.5% of benign lesions. Conclusion: The three biomarkers (p16, CK17 and Ki67) had a high degree of sensitivity and specificity and appear to be a useful and reliable diagnostic adjunct to improve the routine diagnosis and reduce interobserver variability in cervical biopsy specimens. Immunohistochemical markers such as p16 alone or with Ki67 represents important tool for the pathologists in distinguishing high grade cervical dysplasia from its benign mimics such as AIM and reactive inflammatory lesion thus avoiding overtreatment. Normal 0 false false false EN-IN X-NONE X-NONE /* Style Definitions */ table.MsoNormalTable {mso-style-name:Table Normal; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin-top:0cm; mso-para-margin-right:0cm; mso-para-margin-bottom:10.0pt; mso-para-margin-left:0cm; line-height:115%; mso-pagination:widow-orphan; font-size:11.0pt; font-family:Calibri,sans-serif; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:Times New Roman; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin;}

Intestinal metaplasia in the cervical small biopsy specimen: do we pursue it?

Intestinal metaplasia in the cervical small biopsy specimen: do we pursue it?

Review of Cervical Carcinoma Screening Program in Tamil Nadu – Current Trend and Recommendations from a Histopathologist’s Viewpoint

ABSTRACT Objectives Cervical carcinoma, the commonest carcinoma affecting Indian females, is caused by human papilloma virus (HPV) infection. Primordial prevention and primary prevention with HPV vaccine and cancer screening respectively, can go a long way in preventing this carcinoma. The health system project in Tamil Nadu has done a commendable job in reducing the disease burden by introducing screening programs for cervical carcinoma at the grassroots level, way back in 2005. This study was done to evaluate the cervical biopsy specimens received as a part of this program to compute its incidence, compare the incidence among various districts, and suggest future directions based on our observations. Materials and methods From visual inspection with acetic acid/visual inspection with Lugol’s iodine positive cervical biopsy specimens, 506 were chosen randomly from various districts. Based on histopathological examination, incidence of individual lesions and district-wise incidence were calculated. Predictive factors that determine the progression of these lesions were analyzed based on the literature. Results Out of the 506 cervical biopsy specimens, 34 were unsatisfactory. The incidence of high-grade dysplasia peaked around 31 to 40 years, and squamous cell carcinoma peaked among 51 to 60 years. Madurai ranked high in the incidence of both high-grade dysplasia and carcinoma. Conclusion Incidence of dysplasia and carcinoma in our study was comparable to those seen in the literature. Integration of HPV deoxyribonucleic acid studies into the program can increase the detection rate, detect the progressors, help to identify the HPV species prevalent in an area, and aid in formulating cost-effective HPV vaccine cocktail. How to cite this article Ibrahim SS, Kesavaraj K, Arun M, Ameen SAM, Sankar R. Review of Cervical Carcinoma Screening Program in Tamil Nadu – Current Trend and Recommendations from a Histopathologist’s Viewpoint. J South Asian Feder Menopause Soc 2017;5(1):1-7.

A cross-sectional study of p53 expression in patients with squamous cell carcinoma cervix: A hospital-based study

Context: Cervical cancer is the second most common cancer in women in India and the fourth most common cancer in women worldwide. The p53 is a tumor suppressor gene. Overexpression of p53 is detected by immunohistochemistry (IHC) and it indicates a worsened prognosis in some malignancies. Aims: The present study was undertaken to assess the expression of p53 by IHC in normal cervical epithelium and squamous cell carcinoma (SCC) cervix. The role of p53 as a potential biomarker by correlating p53 expression with clinico-pathological parameters was also studied. Settings and Design: Cross-sectional study. Subjects and Methods: A total of 50 cases of cervical biopsy or hysterectomy specimens of SCC cervix and fifty cases of hysterectomy specimens for other gynecologic causes were included in the study. IHC was used to study the p53 expression in normal and neoplastic cervical epithelium. The p53 positivity was assessed by using a semi quantitative method in SCC cervix. The p53 expression was correlated with various clinico-pathological parameters. Statistical Analysis Used: Data collected was analyzed using appropriate statistical test. Results: All the fifty cases (100%) of SCC cervix showed positive p53 expression. The normal cervical epithelium in 90% cases was p53 negative and 10% showed basal layer positivity. A statistically significant correlation was seen between p53 score and menopausal status ( P = 0.010). Conclusions: Overexpression of p53 is suggestive of high grade of tumor.

Presence of histopathological premalignant lesions and infection caused by high-risk genotypes of human papillomavirus in patients with suspicious cytological and colposcopy results: A prospective study.

In patients with premalignant cervical lesions, human papillomavirus (HPV) infection, at any moment, may be spontaneously eliminated, or may persist or transform cervical epithelium from a lower to a higher degree. Due to that, it is necessary to wisely select the patients who are at high risk of cancer development. The aim of the study was to establish the interdependence between a suspicious Papanicolaou (Pap) test and colposcopy with the infection caused by high-risk genotypes of human papillomavirus and the presence of premalignant cervical lesions. This prospective study used cytological, colposcopy, real-time polymerase chain reaction (PCR) of high-risk genotypes of human papillomavirus and histopathological analysis of cervical biopsy specimen. Out of 2,578 female patients sent to cytological analyses in Clinical Center of Montenegro, during 2012, 2013 and 2014, the study included 80 women who had to submit their biopsy specimens due to a suspicious Pap test and atypical colposcopy results. In the group of 80 (3.1%; n = 80/2,578) of the selected female patients with suspicious Pap test and colposcopy, 2/3 or 56 (70%) of them had cervicitis, and 1/3 or 24 (30%) had cervical intraepithelial neoplasia. The most common type in cervical intraepithelial neoplasia was HPV16 in 8 female patients, ie 61.53% out of the number of infected, or 33.33% out of the total number of premalignant lesions Patients with suspicious Papanicolaou test, colposcopy results and infection which is caused by high-risk HPV infection (HPV 16 in particular) often have premalignant cervical lesions. In these cases, histopathological confirmation of lesions is mandatory, since it serves as a definitive diagnostic procedure.

Multiplex Polymerase Chain Reaction for the Detection of High-risk-Human Papillomavirus Types in Formalin-fixed Paraffin-embedded Cervical Tissues

Detecting high-risk-human papillomavirus (HPV) types has become an integral part of the cervical cancer screening programmes. This study aimed to develop a multiplex polymerase chain reaction (PCR) for identification of HPV types 16 and 18 along with the beta globin gene in formalin-fixed and paraffin-embedded cervical biopsy specimens. A total of 59 samples from patients with cervical abnormalities were tested. HPV 16 positivity was 50% in cervical cancers and 52.9% in cervical intraepithelial neoplasia. Our multiplex PCR protocol can be used as a simple and cost-effective tool for high-risk-HPV detection in cervical cancer screening programmes.

P16INK4a Expression in Cervical Lesions Correlates with Histologic Grading - a Tertiary Level Medical Facility Based Retrospective Study

p16INK4a is a tumor-suppressor protein and cyclin-dependent kinase (cdk) inhibitor that blocks cdk4- and cdk6-mediated pRb phosphorylation to inhibit E2F-dependent transcription and cell-cycle progression. Because the E7 protein of high-risk HPVs inactivates pRB, the resulting overexpression of p16INK4a may be a good marker for infection with high risk HPV types. Immunostaining of p16INK4a allows precise identification of even small CIN or cervical cancer lesions in biopsy sections and can help reduce inter-observer variation in the histopathological interpretation of cervical biopsy specimens. The aims of the present study were to evaluate the expression of p16 INK4a in cervical biopsies and to compare the grade of cervical neoplasia with intensity of staining. The study covered 110 cervical biopsy tissue blocks over a period of 2 years, (85 cases of CIN of varying grade and invasive cervical cancers and 25 of non-neoplastic lesions). Immunostaining with p16INK4a antibodies followed standard operating procedures. The results showed an increasing trend for p16INK4a immunoreactivity from benign to higher grade lesions. Out of 25 cases of non dysplasia (15 cervicitis &10 immature squamous metaplasia), 8%(2/25) showed P16INK4a expression (grade 1). Among low grade lesions like CIN1, 32% (8/25) cases demonstrated P16INK4a expression (grade 1). Some 52.3% (11/21) of CIN2 cases proved positive. The intensity of p16INK4a expression in CIN 2 was grade 1 in 33%, grade 2 in 14% and grade 3 in 4.7% of cases. All the CIN3 lesions and cervical squamous cell carcinomas exhibited grade 3 anti p16INK4a antibody staining. The association of p16INK4a expression with histologic grade of cervical pathology was highly significant (χ2-value:51.81, p<0.0001). The staining intensity increase with higher grade disease was also statistically significant (χ2-value :133.95, p<0.0001).

Hubungan Ekspresi NFκB dengan Respons Radiasi Kanker Serviks Stadium Lokal Lanjut

One of the expected elimination pathways of cancer cells in the process of radiation is apoptosis. Nuclear factor kappa-B (NFkB) is a transcription factor related to the mechanism of apoptosis resistance of a cell, which can affect the post-radiation response. The aim of this study is to assess the relative expression of NFkB in locally advanced cervical cancer and its relation to radiotherapy response. The study was conducted with observational cohort design on January-October 2015. Pre-radiotherapy cervical biopsy specimen was collected from 17 subjects, while only 10 subjects were willing to be taken mid-radiotherapy cervical biopsy specimen. We extracted and analyzed mRNA of NFkB by using qRT-PCR. NFkB relative expression was tested to its correlation with radiotherapy response. This study demonstrated that median of pra-radiotherapy relative expression on subjects with negative response (0.667; SD 0.413) was higher than positive response (0.315; SD 160.298), but not statistically significant (p=0.578). Alteration of mid-radiotherapy NFkB relative expression compared to pra-radiotherapy showed correlation to radiotherapy response. It is concluded that reduced expression of mid-radiotherapy NFkB relative expression plays a role in increasing radiotherapy response. Normal 0 false false false IN X-NONE X-NONE

Effect of Lower Anogenital Squamous Terminology Recommendations on the Use of p16 Immunohistochemistry and the Proportion of High-Grade Diagnoses in Cervical Biopsy Specimens.

The Lower Anogenital Squamous Terminology (LAST) group has recommended that cervical intraepithelial neoplasia (CIN) terminology be replaced by squamous intraepithelial lesion (SIL) terminology, with p16 immunohistochemistry used to separate lesions formerly diagnosed as CIN grade 2 into high-grade SILs (HSILs) and low-grade SILs. This study investigated the impact of these changes on the frequency of p16 testing and the diagnosis of high-grade lesions. Pathology reports for all cervical biopsy specimens in the 1 year before and after the introduction of LAST recommendations (July 2011 to June 2013) were examined. Before and after the implementation of LAST, 365 (15.4%) of 2,376 cases were diagnosed as high grade (CIN 2/3) vs 486 (17.6%) of 2,761 cases diagnosed as HSILs (P = .0343), and p16 was performed 79 (3.3%) times vs 383 (13.9%) times (P < .0001). Immunohistochemistry for p16 increased dramatically as a result of LAST recommendations, and high-grade diagnoses increased.

Study of cervical cytology and its correlation with clinical and histopathological findings

Background: Cancer of the cervix is the second most common cancer among women in the world. It accounts for 12% of all cancers in females. This study aims to evaluate the pattern of cervical cytology and its correlation with clinical and histopathological findings. Materials and Methods: This is 10 years retrospective and prospective study, in which all the Papanicolaou (Pap) smears were reported as per the 2001 Bethesda system. Clinical and histopathological correlation was done in cases where cervical biopsy or total hysterectomy specimens were available. Results: A total of 3791 Pap smears were studied with respect to age group, clinical signs and symptoms, and cytology findings. Cervical biopsy correlation was done in 200 cases. Most of the patients were in age group of 31–40 (35.61%) years. The Pap smear findings revealed 88.02% as negative for intraepithelial lesion or malignancy (NILM), 5.99% epithelial cell abnormality (ECA), and 5.99% were unsatisfactory. ECA comprised atypical squamous cells of undetermined significance (ASCUS) with 2.98%, low-grade squamous intraepithelial lesion with 1.19%, and high-grade squamous intraepithelial lesion with 0.66%. There were 36 cases (0.95%) of malignancy. Sensitivity, specificity, and positive predictive value of Pap smear in diagnosing ECA and malignancy were 89.47%, 88.70%, and 82.92%, respectively. Conclusion: Pap smear test is ideal screening method for cervical carcinoma. Nonspecific inflammation and ASCUS were most common finding among NILM and ECA group, respectively. Biopsy is considered to be the gold standard for carcinoma cervix provided that it is taken from representative areas.

The LAST guidelines in clinical practice: implementing recommendations for p16 use.

To determine the impact of implementing p16 Lower Anogenital Squamous Terminology Standardization Project for HPV-Associated Lesions (LAST) guidelines, we compared p16 use and follow-up data before and after implementation of the guidelines. We reviewed all cervical biopsy specimens diagnosed by two pathologists before and after implementation of the LAST guidelines and calculated the rate of and reason for p16 use across all biopsy specimens, high-grade squamous intraepithelial lesion (HSIL) detection, and follow-up. In total, 1,829 and 1,623 cervical biopsy specimens were reviewed in periods A and B, respectively. Overall p16 use increased from 2.8% to 6.2% (P < .001). Recommendations 2 and 4 increased from 0.16% and 0% of all cervical biopsy specimens in period A to 1.4% and 1.9% in period B, respectively (P < .0001). p16+ HSIL increased from 1.4% to 2.3% (P < .05). The positive predictive value of p16+ HSIL increased from 48% to 76% (P < .05). Implementation of the p16 LAST guidelines resulted in a significant increase in p16 use and a significant increase in the positive predictive value of p16+ HSIL.

The original SPF10 LiPA25 algorithm is more sensitive and suitable for epidemiologic HPV research than the SPF10 INNO-LiPA Extra

Two commercial HPV tests target the same 65bp fragment of the human papillomavirus genome (designated SPF10): the original HPV SPF10 PCR-DEIA-LiPA25 system, version 1, (LiPA25) and the INNO-LiPA HPV Genotyping Extra (INNO-LiPA). The original SPF10 LiPA25 system was designed to have high analytical sensitivity and applied in HPV vaccine and epidemiology studies worldwide. But due to apparent similarities, this test can be easily confused with INNO-LiPA, a more recent assay of which the intended use, i.e., epidemiological or clinical, is currently unclear. The aim was to compare the analytical sensitivity of SPF10 LiPA25 to that of INNO-LiPA on the level of general HPV detection and genotyping. HPV testing by both assays was performed on the same DNA isolated from cervical swab (n=365) and biopsy (n=42) specimens. In cervical swabs, SPF10 LiPA25 and INNO-LiPA identified 35.3% and 29.3% multiple infections, 52.6% and 51.5% single infections, and no HPV type in 12.1% and 19.2%, respectively. Genotyping results were 64.7% identical, 26.0% compatible and 9.3% discordant between both methods. SPF10 LiPA25 detected significantly more genotypes (p<0.001). The higher analytical sensitivity of SPF10 LiPA25 was confirmed by the MPTS123 genotyping assay. HPV positivity by the general probes in SPF10 DEIA was significantly higher (87.9%) than by those on INNO-LiPA (77.0%) (kappa=0.592, p<0.001). In cervical biopsies, SPF10 LiPA25 and INNO-LiPA identified 21.4% and 9.5% multiple types, 76.2% and 81.0% single types, and no type in 2.4% and 9.5%, respectively. Between both tests, the identification of genotypes was 76.3% identical, 14.3% compatible and 9.5% discordant. Overall, significantly more genotypes were detected by SPF10 LiPA25 (kappa=0.853, p=0.022). HPV positivity was higher by the SPF10 DEIA (97.6%) than by the INNO-LiPA strip (92.9%). These results demonstrate that SPF10 LiPA25 is more suitable for HPV genotyping in epidemiologic and vaccine-related studies, due to its higher analytical sensitivity.

HPV testing results and histologic follow-up in women with ASC-H cytology in different age groups

Assessment on human papillomavirus (HPV) testing and disease outcome of atypical squamous cell, cannot exclude high grade squamous intraepithelial lesion (ASC-H) in different age groups is limited in published reports. We reviewed our experience over a 5-year period on ASC-H cytology and correlated age distribution with high-risk HPV (HR-HPV) status and histological follow-up in a large cohort study. Women with ASC-H cytology were retrieved from the hospital database. HR-HPV status and histological diagnoses on cervical biopsy or loop electrosurgical excisional procedure specimens were reviewed and correlated to 5 age groups. Ages of women with ASC-H ranged from 16 to 88 years, with 42% women <30 years and 58% women >30 years. Among 647 cases diagnosed as ASC-H, 96% (618) had HR-HPV testing results, including 68.2% HR-HPV positive and 31.8% HR-HPV negative. HR-HPV positivity of ASC-H gradually decreased from 95.2% in women <20 years to 40.6% in the age group >51 years. Histologic follow-ups were available for review in 80% (517) of the cases. Cervical intraepithelial neoplasia, grade 2 or higher (CIN2+) lesions were found in 40.3% (208) cases, including 92.9% women with HR-HPV-positive/ASC-H and 7.1% of women with HR-HPV-negative/ASC-H. The detection rate of CIN2+ by ASC-H gradually decreased from 51.2% in women <20 years to 18.2% in women >51 years. The majority of postmenopausal women with HR-HPV-negative/ASC-H had atrophy-related change. The specificity of ASC-H cytology in detection of cervical CIN2+ lesions is age-dependent: higher in younger women <30 years, but gradually decreased in women >30 years. The vast majority (93%) of CIN2+ lesions were seen women with HR-HPV-positive/ASC-H. HR-HPV testing improves the accuracy and specificity in women with ASC-H in almost all age groups, especially in age groups older than 40 years.

P16INK4a immunohistochemistry in cervical biopsy specimens: A systematic review and meta-analysis of the interobserver agreement.

The interpretation of cervical biopsy specimens guides management of women with suspected cervical cancer precursors. However, morphologic evaluation is subjective and has low interobserver agreement. Addition of p16(INK4a) immunohistochemistry may improve interpretation. We performed a systematic review and meta-analysis of published data on interobserver agreement of p16(INK4a) positivity using p16(INK4a) immunohistochemistry and of cervical intraepithelial neoplasia grade 2 (CIN2+) and CIN grade 3 (CIN3+) classification using H&E morphology in conjunction with p16(INK4a) in comparison with H&E morphology alone. The literature search revealed five eligible articles. The results show strong agreement of pathologists' interpretation of cervical biopsy specimens as p16(INK4a) positive or negative (pooled κ = 0.90; 95% confidence interval [CI], 0.88-0.92) and significantly higher agreement for a CIN2+ diagnosis with H&E morphology in conjunction with p16(INK4a) (κ = 0.73; 95% CI, 0.67-0.79) compared with H&E morphology alone (κ = 0.41; 95% CI, 0.17-0.65). Also, a slightly higher agreement for CIN3+ can be observed (κ = 0.66; 95% CI, 0.39-0.94 for H&E morphology in conjunction with p16(INK4a) and κ = 0.61; 95% CI, 0.44-0.78 for H&E morphology alone), but this difference was not statistically significant. The published literature indicates improved interobserver agreement of the diagnosis of CIN2+ with the conjunctive use of H&E morphology with p16(INK4a) immunohistochemistry compared with H&E morphology alone.

Skin involvement in diffuse large B‐cell lymphoma detected using positron emission tomography

A 76-year-old Japanese woman presented with lymphadenopathy of the right neck and precordial erythematous thickening of the skin (Fig 1). She had undergone a left mastectomy for early-stage breast cancer 20 years before. She did not receive chemotherapy or radiotherapy at that time and no recurrence had occurred to date. An operative scar was detected on her right chest wall, but she had never experienced lymphedema after the mastectomy. Three months before her referral, she had noticed a pea sized lymph node on her right neck. Because of the enlargement of systemic lymph nodes followed by the development of a precordial skin lesion, she visited the hospital. The cervical lymph node biopsy specimen revealed diffuse proliferation of large abnormal lymphocytes with frequent mitotic figures. The following immunostaining pattern was observed: CD3, negative; CD20, positive; CD79a, positive; and Ki-67, positive (about 70–80% of tumor cells). Accordingly, she was diagnosed with diffuse large B-cell lymphoma (DLBCL). Fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) indicated a high FDG uptake in the skin lesion, as well as in the cervical lymph nodes (Fig 2). (a) Enlarged right cervical and supraclavicular lymph nodes. (b) Precordial erythematous thickening of the skin. (a) Fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) revealed skin involvement (white arrowhead) and mediastinal lymph node swelling as indicated by a high FDG uptake. (b) The high FDG uptake on PET (red arrowhead) appeared to correspond well with the skin lesions in Figure 1b. Several reports have described variability in FDG avidities of histologic lymphoma subtypes.1, 2 To accurately delineate the extent of the disease, FDG-PET is now routinely recommended for the staging of patients with FDG-avid lymphomas, such as DLBCL and Hodgkin's disease.3 Although the relationship between skin involvement in DLBCL and findings from FDG-PET has rarely been reported,2 we speculate that a high FDG uptake on PET corresponds with the skin involvement in DLBCL, as well as in the case of primary cutaneous DLBCL. A skin lesion might be related to a history of breast cancer; however, the patient had never experienced lymphedema after the mastectomy and the precordial lesion developed after systemic lymph node swelling. Thus, skin involvement of DLBCL had no relationship with the previous treatment for breast cancer. We thank Dr Yasumasa Monobe, Department of Pathology, Kawasaki Medical School Kawasaki Hospital, for helpful comments and discussion during drafting of this report. The authors also would like to thank Enago (http://www.enago.jp; Mumbai, India) for the English language review. No authors report any conflict of interest.

Immunological study of cervical biopsy specimen for human papiloma virus

Background: Cervical cancer is one of the most common cancers among women worldwide and its rates are higher in low and middle income countries. India is one not exemplified from the developing countries. Aims: The main aim of the present work is a preliminary prospective screening study to observe the incidence of human papilloma virus (HPV) virus in the specimens of cervical biopsy taken from the patients of gynecology department of Visakha Steel General Hospital, RINL, Visakhapatnam district. Screening procedures like Pap smear, Colposcopy Immunohistochemistry (IHC) were done to identify the prevalence of HPV. It is an effort to assess and also improving the quality of cervical cancer prevention and treatment services in Visakhapatnam district of North coastal Andhra Pradesh. Settings and design: This prospective study was conducted at the department of obstetrics and gynaecology, Visakha Steel General Hospital, RINL, Visakhapatnam district from January 2010 to December 2010. Materials and methods: The Pap test and colposcopic examination were conducted on 161 patients and IHC was done on 24 cervical biopsy patients. Results: The 87.58% of women was observed with abnormal Pap smear among that the severe dysplasia is around 10%. The abnormal cervix was seen by colposcopy is 89.44%. The 24 squamous metaplasia cases were subjected to IHC and 8 cases were found to be positive. Conclusion: Pap smear, colposcopy along with cervical biopsy for HPV can provide enough information for an accurate diagnosis of cervical cancer and also from the future course of action for the treatment of the patients. Keywords: cervical cancer; HPV; Pap smear; colposcope; IHC; screening