Cervical Biopsy Specimens Research Articles

Quantification of HPV16 E7 Oncoproteins in Urine Specimens from Women with Cervical Intraepithelial Neoplasia.

We present the validity of using an ultrasensitive enzyme-linked immunosorbent assay (ELISA) for quantifying high-risk human papillomavirus (HPV) 16 E7 oncoproteins in urine specimens as a noninvasive method of analyzing the oncogenic activity of HPV. Some reports claim that the oncogenic activity of HPV is a more relevant clinical indicator than the presence of HPV DNA for estimating malignant potential. In the present study, urine containing HPV16 and related types were selected by uniplex E6/E7 polymerase chain reaction and classified according to the pathologic diagnosis of cervical intraepithelial neoplasia (CIN) in cervical biopsy specimens. Our ultrasensitive ELISA was able to detect attomole levels of HPV16 E7 oncoproteins, and it detected HPV16-positive SiHa cells at >500 cells/mL without detecting HPV18-positive cells. Our ELISA results showed E7 oncoproteins in 80% (4/5) of urine specimens from women with HPV16-positive CIN1, 71% (5/7) of urine specimens from CIN2 patients, and 38% (3/8) of urine specimens from CIN3 patients. Some urine specimens with undetectable E7 oncoproteins were thought to be negative for live HPV 16-positive cells or in an inactivated state of infection. These results provide the basis for assessing oncogenic activity by quantifying E7 oncoproteins in patient urine.

Interobserver reproducibility of cervical histology interpretation with and without p16 immunohistochemistry.

Histopathological diagnosis of colposcopically identified cervical lesions is a critical step for the recognition of cervical cancer precursors requiring treatment. Although there have been efforts to standardize the histologic diagnosis of cervical biopsy specimens, in terms of terminology and use of biomarkers, there is no uniform approach in the pathology community. Adjunctive p16 immunohistochemistry (IHC) can highlight precancer diagnoses, with use recommendations outlined by the Lower Anogenital Squamous Terminology project. We assessed the diagnostic reproducibility of cervical histopathological biopsy specimens with and without p16 staining among 2 expert pathologists. Interpretation of p16 IHC as positive vs negative was highly reproducible (92.5% agreement, κ = 0.85); greater variation was seen in the choice of which biopsy specimens required adjunctive p16 staining (78.0% agreement, κ = 0.43). Adjunctive p16 IHC did not significantly increase diagnostic agreement under multitiered grading systems (benign vs cervical intraepithelial neoplasia [CIN] 1/low-grade squamous intraepithelial lesion vs atypical squamous metaplasia vs CIN2/high-grade squamous intraepithelial lesion [HSIL] vs CIN3/HSIL-CIN3 vs cancer) (65.5% agreement, κ = 0.56 without p16; 70.0% agreement, κ = 0.58 with p16). However, when dichotomizing diagnoses based on clinical management (less than HSIL vs HSIL+), diagnostic agreement increased with p16 IHC (90.5% agreement, κ = 0.79 without p16; 92.0% agreement, κ = 0.84 with p16). For biopsy specimens taken from women positive for human papillomavirus (HPV) type 16, agreement was similar with or without adjunctive p16 (κ = 0.80 without p16; κ = 0.78-0.80 with p16). In contrast, p16 IHC substantially improved diagnostic agreement for cervical biopsy specimens taken from women positive for other high-risk HPV strains, producing improvements in κ from 0.03 to 0.24. Adjunctive p16 immunostaining provides useful information in the evaluation of cervical biopsies for precancer. In our study, we have demonstrated that it is highly reproducible between 2 pathologists, although the decision of which biopsies warrant its use is less so. Furthermore, although p16 IHC showed a limited increase in diagnostic reproducibility for all biopsies included in our study, it did demonstrate a more sizable gain in biopsies negative for HPV 16 but positive for other high-risk genotypes. Further studies are needed to clarify the role of p16 IHC and how it can be optimized for the detection of cervical precancer, particularly in HPV-vaccinated populations where types other than HPV 16 are relatively more important.

Assessing a relation between composition of luminal and tissue microbiota and cervical intraepithelial changes

The incidence of cervical cancer (CC) in Russia remains at a high level and ranks fourth among all cancers. CC is preceded by mild, moderate, and severe cervical intraepithelial neoplasia. Human papillomavirus (HPV) is known to be the main cause for its development being responsible for 99% cancer cases. Despite HPV infection, the oncological process occurs only under certain conditions. There are risk factors that indirectly affect the course and emergence of cervical dysplasia. In recent years, the role of cervico-vaginal microbiome for onset and progression of this pathology has been actively discussed. Many studies evidence that dysbiosis along with cervical intraepithelial dysplasia is associated with increased HPV viral load, additionally allowing to clarify a role of specific microorganisms. Despite the knowledge rapidly accumulating about the nature of vaginal microbiome in cervical precancerous processes, the level of its impact on disease course has not been fully investigated and is of great interest. Identification of microorganisms that affect emergence and progression of this pathology will allow to prevent and apply select approach to treatment of dysbiosis. The aim of our study was to identify a relation between cervical tissue and luminal culturome and severe cervical intraepithelial neoplasia. The study evaluated the microbiota of cervical and cervical canal mucosa biopsy in patients with cervical intraepithelial changes. According to the study results, the Streptococcus genus representatives were significantly more frequent in cervical biopsy specimens in severe dysplasia vs. no cervical intraepithelial changes, whereas cervical canal cultures provided comparable data. Bacteria from the Corynebacterium genus were found in cervical biopsy specimens 3 times more often than in smear from the cervical canal mucous membrane. The microbiota from cervical and cervical canal biopsy specimens differ qualitatively and quantitatively particularly regarding prevalence of Streptococcus spp. representatives being more common in patients with cervical dysplasia. Corynebacterium spp. were detected more often in cervical biopsy specimens than in cervical canal smears. Thus, the method of collecting biological material has a great influence on final results.

P16 expression and recurrent cervical intraepithelial neoplasia after cryotherapy among women living with HIV.

The expression of p16 protein, a surrogate marker for high-risk human papillomavirus (hrHPV), is associated with cervical dysplasia. We evaluated correlates of p16 expression at treatment for high-grade cervical lesions and its utility in predicting the recurrence of cervical intraepithelial lesions grade 2 or higher (CIN2+) following cryotherapy among women with HIV. This is a subgroup analysis of women with HIV in Kenya with baseline cervical biopsy-confirmed CIN2+ who were randomized to receive cryotherapy and followed every six-months for two-years for biopsy-confirmed recurrence of CIN2+. P16 immunohistochemistry was performed on the baseline cervical biopsy with a positive result defined as strong abnormal nuclear expression in a continuous block segment of cells (at least 10-20 cells). Among the 200 women with CIN2+ randomized to cryotherapy, 160 (80%) had a baseline cervical biopsy specimen available, of whom 94 (59%) were p16-positive. p16 expression at baseline was associated with presence of any one of 14 hrHPV genotypes [Odds Ratio (OR) = 3.2; 95% Confidence Interval (CI), 1.03-9.78], multiple lifetime sexual partners (OR = 1.6; 95% CI, 1.03-2.54) and detectable plasma HIV viral load (>1,000 copies/mL; OR = 1.43; 95% CI, 1.01-2.03). Longer antiretroviral therapy duration (≥2 years) at baseline had lower odds of p16 expression (OR = 0.46; 95% CI, 0.24-0.87) than <2 years of antiretroviral therapy. Fifty-one women had CIN2+ recurrence over 2-years, of whom 33 (65%) were p16-positive at baseline. p16 was not associated with CIN2+ recurrence (Hazard Ratio = 1.35; 95% CI, 0.76-2.40). In this population of women with HIV and CIN2+, 41% of lesions were p16 negative and baseline p16 expression did not predict recurrence of cervical neoplasia during two-year follow up.

Predicting Lymph Node Metastasis From Primary Cervical Squamous Cell Carcinoma Based on Deep Learning in Histopathologic Images

We developed a deep learning framework to accurately predict the lymph node status of patients with cervical cancer based on hematoxylin and eosin–stained pathological sections of the primary tumor. In total, 1524 hematoxylin and eosin–stained whole slide images (WSIs) of primary cervical tumors from 564 patients were used in this retrospective, proof-of-concept study. Primary tumor sections (1161 WSIs) were obtained from 405 patients who underwent radical cervical cancer surgery at the Fudan University Shanghai Cancer Center (FUSCC) between 2008 and 2014; 165 and 240 patients were negative and positive for lymph node metastasis, respectively (including 166 with positive pelvic lymph nodes alone and 74 with positive pelvic and para-aortic lymph nodes). We constructed and trained a multi-instance deep convolutional neural network based on a multiscale attention mechanism, in which an internal independent test set (100 patients, 228 WSIs) from the FUSCC cohort and an external independent test set (159 patients, 363 WSIs) from the Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma cohort of the Cancer Genome Atlas program database were used to evaluate the predictive performance of the network. In predicting the occurrence of lymph node metastasis, our network achieved areas under the receiver operating characteristic curve of 0.87 in the cross-validation set, 0.84 in the internal independent test set of the FUSCC cohort, and 0.75 in the external test set of the Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma cohort of the Cancer Genome Atlas program. For patients with positive pelvic lymph node metastases, we retrained the network to predict whether they also had para-aortic lymph node metastases. Our network achieved areas under the receiver operating characteristic curve of 0.91 in the cross-validation set and 0.88 in the test set of the FUSCC cohort. Deep learning analysis based on pathological images of primary foci is very likely to provide new ideas for preoperatively assessing cervical cancer lymph node status; its true value must be validated with cervical biopsy specimens and large multicenter datasets.

Histopathological characteristics and HPV status in cervical biopsy specimens diagnosed as flat condyloma.

HPV infections cause a wide spectrum of pathological changes in lower anogenital epithelium. The aim of this study was to investigate the HPV DNA status and histological findings in cervical biopsy specimens diagnosed as flat condyloma. This study included 20 cervical biopsy specimens diagnosed as flat condyloma. The histopathological criteria and presence of HPV DNA were evaluated. HPV genotyping was determined in HPV-positive specimens using BioEdit software and the results were analyzed in SPSS software. HPV DNA was not found in 30% of specimens and relative frequency of HPV genotypes was: 15% HPV6, 15% HPV11, 5% HPV16, 5% HPV18, 5% HPV53, 5% HPV68, 5% HPV84, 10% HPV45. Relative frequency of histopathological criteria was as below: 100% of specimens had koilocytosis, 100% acanthosis, 15% nuclear immaturity, 100% atypia, 15% mitotic activity, 50% dyskeratosis, 35% parakeratosis and 10% hyperkeratosis. There were significant differences between HPV positivity and two pathologic criteria; multinucleation and hyperkeratosis (P Value: 0.02). Nuclear immaturity was significantly more prevalent in high risk HPV-positive specimens (P Value: 0.03).

Prediction of carcinogenic human papillomavirus types in cervical cancer from multiparametric magnetic resonance images with machine learning-based radiomics models.

This study aimed to evaluate the potential of machine learning-based models for predicting carcinogenic human papillomavirus (HPV) oncogene types using radiomics features from magnetic resonance imaging (MRI). Pre-treatment MRI images of patients with cervical cancer were collected retrospectively. An HPV DNA oncogene analysis was performed based on cervical biopsy specimens. Radiomics features were extracted from contrast-enhanced T1-weighted images (CE-T1) and T2-weighted images (T2WI). A third feature subset was created as a combined group by concatenating the CE-T1 and T2WI subsets. Feature selection was performed using Pearson's correlation coefficient and wrapper- based sequential-feature selection. Two models were built with each feature subset, using support vector machine (SVM) and logistic regression (LR) classifiers. The models were validated using a five-fold cross-validation technique and compared using Wilcoxon's signed rank and Friedman's tests. Forty-one patients were enrolled in the study (26 were positive for carcinogenic HPV oncogenes, and 15 were negative). A total of 851 features were extracted from each imaging sequence. After feature selection, 5, 17, and 20 features remained in the CE-T1, T2WI, and combined groups, respectively. The SVM models showed 83%, 95%, and 95% accuracy scores, and the LR models revealed 83%, 81%, and 92.5% accuracy scores in the CE-T1, T2WI, and combined groups, respectively. The SVM algorithm performed better than the LR algorithm in the T2WI feature subset (P = 0.005), and the feature sets in the T2WI and the combined group performed better than CE-T1 in the SVM model (P = 0.033 and 0.006, respectively). The combined group feature subset performed better than T2WI in the LR model (P = 0.023). Machine learning-based radiomics models based on pre-treatment MRI can detect carcinogenic HPV status with discriminative accuracy.

CD5- and CD10-positive MYC and BCL2 double-expressor diffuse large B-cell lymphoma with MYD88L265P mutation: a case report and literature review

A 75-year-old man who had lymphadenopathy was admitted to our hospital. Histopathological examination of cervical lymph node biopsy specimens showed diffuse proliferation of lymphoma cells with large nuclei. In immunohistochemistry, the lymphoma cells were positive for CD5, CD10, CD20, BCL2, BCL6, and MYC. The patient was diagnosed with CD5- and CD10-positive diffuse large B-cell lymphoma (DLBCL). MYD88L265P mutations have been detected in DLBCL. Partial response was achieved after six courses of R-THP-COP therapy. However, the patient died because of disease progression 18 months after the diagnosis. On autopsy, lymphoma cells were found in the lymph nodes throughout the body, central nervous system, adrenals, and skin. CD5- and CD10-positive DLBCL account for 0.5-1% of DLBCL cases and have a very poor disease prognosis. This is a rare case of CD5- and CD10-positive DLBCL with MYC and BCL2 expressions harboring MYD88L265P mutation.

ASSESSMENT OF UTERINE CERVICAL BIOPSY PATTERN IN FEMALES AT RIMS, RANCHI, JHARKHAND

Aims &amp; objectives - Materials &amp;Assessment of uterine cervical biopsy pattern in females at RIMS, Ranchi, Jharkhand. Methods – Our study is composed of assessment of cervical biopsy specimen received from February 2021 to January 2022. A total of 176 cases of cervical biopsy specimen were examined. Out of 176 cases, the most common diagnosis was MalignantResults – Lesion of the cervix found in 82% cases. Tissue biopsy is a valuable diagnostic procedure. Aim of the study was to know theConclusion – spectrum of disease and their frequency.

The effectiveness of the application of modern diagnostic criteria of cervical pathology

BACKGROUND: Cervical cancer is one of the four most common cancers today and is the second most common cancer among women in developing countries. According to World Health Organization estimates, in 2018, the number of new cases in these countries was 570,000 (84% of all new cases globally). About 311,000 women died of cervical cancer in 2018, with more than 85% of these deaths occurring in low- and middle-income countries. The detection of the disease in its later stages has not significantly reduced since 2018 (32.6% of all cases).&#x0D; AIM: The aim of this study was to compare the information contents of conventional and liquid cytology methods in women with verified human papillomavirus of high oncogenic risk.&#x0D; MATERIALS AND METHODS: We retrospectively analyzed 50 outpatient records of women aged 23 to 65 years who underwent colposcopy (cervical biopsy) based on the results of cervical screening. To establish the diagnosis, all patients underwent examination of smears from the cervix and cervical canal using conventional (n = 25) and liquid (n = 25) cytology methods. A molecular genetic study was carried out to detect high-oncogenic human papillomavirus types (16, 18, 31, 33, 35, 45, 51, 56, 58) in scraping of the cervix by real-time polymerase chain reaction. Women in the both study groups also underwent colposcopy with histological examination of the cervical biopsy specimen. The analysis of the obtained data was carried out using methods of parametric and nonparametric statistics. Inclusion criteria included cytological examination, verified human papillomavirus of high oncogenic risk, and colposcopy. Exclusion criteria included pregnancy and acute infectious diseases.&#x0D; RESULTS: According to the results of histological examination, the percentage of coincidence of cytological and histological diagnosis in the group of women who underwent conventional cytological examination was 48%. The total number of discrepancies in this group was 13 (52.0 9.99%). The number of women infected with human papillomavirus in the both study groups was almost the same (18 in the conventional cytology group and 19 in the liquid cytology group). The most common types of human papillomavirus among the examined patients were the 16th type (9 women) and the 18th type (6 women).&#x0D; CONCLUSIONS: To date, cytological research methods have not lost their relevance, the liquid cytology method being a reliable screening test with high specificity, which reduces the number of unsatisfactory preparations for analysis and false negative results. The most informative for women with type 2 or type 3 of transformation zone is the use of the liquid cytology method.

Correlation between physical characteristics of biopsy specimen and disease of cervical lymph node after contrast-enhanced ultrasound

BackgroundTo investigate the correlation between physical characteristics and disease of cervical lymph node biopsy specimens after contrast-enhanced ultrasound.MethodsAll patients were biopsied after CEUS, 235 patients were divided into three groups A, B and C according to the physical characteristics of specimens: 92 patients in group A were complete tissue specimens; 113 patients in group B were discontinuous tissue specimens. There were 30 patients in group C, including a small number of tissue and floc, purulent and bloody specimens. Pathological examination, pathogen culture examination and Gene X-Pert MIB examination were completed for all patients in the three groups, and statistical analysis was conducted on the integrity and traits of the specimens.ResultsGroup A included 92 intact tissue specimens, 21 with reactive hyperplasia, 17 with lymphoma, 12 with metastatic carcinoma, 13 with lymphadenopathy, 15 with necrotizing lymphadenitis, and rare lymphadenopathy. In group B, 113 patients were treated with intermittent tissue specimens, including infected lymph nodes, lymphoma in 1 case, metastatic carcinoma in 3 cases and sarcoidosis in 1 case. There were 30 patients in group C, including a small amount of tissue and floc, purulent and bloody specimens, all of which were infected lymph nodes. The χ2 value of malignant and benign lymph nodes was 42.401, p = 0.000.ConclusionThe physical characteristics of cervical lymph node biopsy specimens after CEUS are correlated with the disease, which has guiding significance for postoperative specimen selection.

The value of Ki67 for the diagnosis of LSIL and the problems of p16 in the diagnosis of HSIL

p16 and Ki67 are immunohistochemical markers related to cervical squamous intraepithelial lesions. p16 has been widely used to assist in the diagnosis of high-grade squamous intraepithelial lesions. However, a conclusion about the role of Ki67 in the diagnosis of squamous intraepithelial lesions has not been established. The aim of this study was to analyze the role of p16 and Ki67 immunohistochemical staining in assisting cervical squamous intraepithelial lesions. This study performed immunohistochemical staining for p16 and Ki67 on 1024 cervical biopsy specimens at our hospital to compare the differences between p16 and Ki67 in different cervical lesions using the chi-squared test and Fisher’s exact test. This study also evaluated the value of Ki67 for the diagnosis of low-grade squamous intraepithelial lesions (LSILs) using the receiver operating characteristic curve. The results indicated that Ki67 had high specificity and sensitivity in distinguishing LSIL from normal cervix. p16 was diffusely and strongly positive in some LSILs, and some problems were encountered in the interpretation of p16 staining. Therefore, we believe that Ki67 can be used as an immunohistochemical marker to help in the diagnosis of LSIL, to distinguish lesions that are difficult to morphologically determine and to avoid misdiagnosis. The practical application of p16 staining is still problematic. It may be necessary to find other auxiliary means to distinguish this small proportion of cervical lesions.

Histopathological profile of cervical biopsies in northern Malawi: a retrospective cross-sectional study

ObjectivesAccording to the WHO (2014), cervical cancer is the second most common cancer in women globally. More than 85% of the global cervical cancer morbidity and mortality occur in low-income...

Tumoral Morphologic Features From Cervical Biopsies That Are Predictive of a Negligible Risk for Nodal Metastasis and Tumor Recurrence in Usual-type Cervical Adenocarcinomas: A Multi-institutional Study.

The metastatic or recurrent potential of localized human papillomavirus-associated endocervical adenocarcinoma (HPVA EAC) is difficult to predict, especially based upon biopsy alone. Recent analyses of small cohorts indicate that high tumor nuclear grade (TNG) and the presence of necrotic tumor debris (NTD) from HPVA EACs in cervical biopsy specimens are highly predictive of nodal metastasis (NM). In the present study, we aimed to investigate how reliably tumoral morphologic features from cervical biopsy specimens predict NM or tumor recurrence (TR) and patient outcomes in a large cohort of endocervical adenocarcinoma patients. A cohort comprised of 397 patients with HPVA EAC treated at 18 institutions was identified, and cervical biopsies were paired with their associated complete tumor resections for a total of 794 specimens. A variety of tumoral histologic features were examined for each paired specimen, including TNG (assessed on a 3-tiered scale of increasing abnormalities-TNG1, TNG2, TNG3) and NTD (defined by the presence of necrotic and apoptotic tumor cells within tumor glandular lumens admixed with granular and eosinophilic amorphous material and inflammatory cells), which were correlated with outcomes. The distribution of TNG in biopsies was as follows: 86 (21.7%) TNG1, 223 (56.2%) TNG2, and 88 (22.2%) TNG3. NTD was identified in 176 (44%) of the biopsy specimens. The sensitivity, specificity, positive predictive value, and negative predictive value of a TNG1 assignment in the biopsy being predictive of the same assignment in the full resection were 0.82 (95% confidence interval [CI]: 0.7-0.9), 0.895 (0.86-0.93), 0.593 (0.48-0.696), and 0.96 (0.94-0.98), respectively. Respective values for an NTD-negative status were 0.89 (95% CI: 0.83-0.92), 0.715 (0.64-0.77), 0.72 (0.65-0.77), and 0.89 (0.83-0.93), respectively. Compared with the other cases in each category, both TNG1 and an NTD-negative status were each significantly associated with lower rates of NM (odds ratio for TNG1=0.245, 95% CI: 0.070-0.857, P=0.0277; for NTD=0.199, 95% CI: 0.094-0.421, P<0.0001) and TR (odds ratio for TNG1=0.225, 95% CI: 0.051-0.987, P=0.0479; for NTD=0.367, 95% CI: 0.171-0.786, P=0.0099) independent of depth of stromal invasion, lymphovascular invasion, tumor size, FIGO stage, and Silva pattern. Overall, 73/379 (19%) cases were both TNG1 and NTD-negative on the biopsy, and none of these 73 cases showed NM (0%), but a single case (1.4%) showed TR. In contrast, among the 324 biopsies with TNG2/3 and/or presence of NTD, 62 (19.1%) had NM, and 41 (12.9%) had TR. In summary, 2 variables in combination (ie, TNG1 and NTD-negative) identified a subset of HPVA EAC patients-∼19%-with a 0% frequency of nodal metastases and only 1.4% frequency of recurrence. Biopsies highly but imperfectly predicted these features. Nonetheless, these findings may potentially be of clinical utility in the risk stratification of patients with HPVA EACs. This may allow some patients with a minimal risk of nodal metastases and TR to be identified at the biopsy phase, thereby facilitating more personalized, possibly less aggressive treatment.

Prognostic impact of human papillomavirus infection on cervical dysplasia, cancer, and patient survival in Saudi Arabia: A 10-year retrospective analysis.

BACKGROUND: Data on human papillomavirus (HPV) prevalence and survival rates among HPV-infected women are scarce in Saudi Arabia.OBJECTIVE: Assess the prevalence of HPV genotypes in cervical biopsy specimens and its effect on survival over a 10-year timeframe.DESIGN: Retrospective, cross-sectional.SETTINGS: Saudi referral hospital.PATIENTS AND METHODS: Cervical biopsy specimens were collected from women aged 23-95 years old who underwent HPV detection, HPV genotyping, p16INK4a expression measurement using immunohistochemistry. Kaplan-Meier plots were constructed to analyze overall survival rates.MAIN OUTCOME MEASURES: Survival rate of HPV-positive cervical cancer patients.SAMPLE SIZE: 315 cervical biopsy specimens.RESULTS: HPV was detected in 96 patients (30.4%): 37.3% had cervical cancer; 14.2% cervical intraepithelial neoplasia (CIN) III, 4.1% CIN II, and 17.0% CIN I. A significant association was found between HPV presence and cervical cancer (χ2=56.78; P<.001). The expression of p16INK4a was a significant predictor of survival: women who had p16INK4a overexpression had poorer survival rates (multivariate Cox regression, hazard ratio, 3.2; 95% CI, 1.1–8.8). In addition, multivariate models with HPV status and cervical cancer diagnosis showed that HPV status was a significant predictor of survival: HPV-positive women had better survival rates than HPV-negative women.CONCLUSION: These findings suggest that implementing cervical and HPV screening programs may decrease cervical cancer rates and improve survival rates of women in Saudi Arabia.LIMITATION: Single center and small sample size.CONFLICT OF INTEREST: None.

Tumor-to-tumor metastasis of diffuse large B cell lymphoma to gastric adenocarcinoma via CXCL12 (SDF-1)/CXCR4 axis: a case report

BackgroundTumor-to-tumor metastasis is the rare phenomenon in which one tumor exhibits metastatic deposits from another. To the best of our knowledge, there has been no prior reported case of tumor-to-tumor metastasis of a diffuse large B cell lymphoma (DLBCL) to a primary gastric adenocarcinoma.Case presentationA 70-year-old man presented with chest discomfort. An echocardiogram showed the presence of a right ventricular tumor. A positron emission tomogram showed multiple foci of abnormal activity in right cervical lymph nodes, cardiac wall, and stomach. A right cervical lymph node biopsy specimen revealed histological features of DLBCL. An esophagogastroduodenoscopy showed a large circumferential ulceration on the gastric body. Subsequent biopsy revealed adenocarcinoma cells surrounded by infiltrating lymphoma cells. On immunohistochemical staining, lymphoma cells were positive for CXCR4 and adenocarcinoma cells were positive for CXCL12/SDF-1. The patient was treated with six cycles of R-CHOP chemotherapy regimen, resulting in a complete remission.ConclusionsThis patient’s case implies that the interaction between a chemokine and its receptor may be the underlying mechanism for the observed tumor-to-tumor metastasis. Specifically, our case would suggest an involvement of the CXCL12 (SDF-1)/CXCR4 axis in the observed metastasis of DLBCL to primary gastric adenocarcinoma.

Low Nuclear Grade and Absence of Necrotic Tumor Debris from Cervical Biopsy Predict a Negligible Risk for Nodal Metastasis and Tumor Recurrence in Usual Type Cervical Adenocarcinomas: A Multi-Institutional Study

Background: The metastatic or recurrent potential of clinically localized HPV-associated endocervical adenocarcinoma (HPVA EAC) is difficult to predict. There is a need to develop a practical method that can accurately distinguish apparently localized tumors with a high probability of nodal metastasis (NM) or tumor recurrence (TR) at the initial biopsy phase, where findings can be incorporated into management decisions. Methods: This retrospective study included 794 specimens from 397 patients with primary HPVA EAC treated at 19 institutions. For each patient, data from a paired cervical biopsy (prior to surgery, n=397) and resection specimen, including lymphadenectomy (n=397) were reviewed. A variety of tumoral pathologic/histologic features were examined in each paired-specimen, including tumor nuclear grade (TNG) and necrotic tumor debris (NTD). TNG was assigned on a three-tiered scale of increasing abnormalities (TNG1, TNG2, and TNG3). Any relationships with standard clinicopathologic variables and patient outcomes including NM and TR were evaluated. Findings: Biopsy tumors with low-risk histologic features (TNG1 and NTD-negative) showed markedly better outcomes, with a 0% rate of lymph node metastases or lymphovascular invasion (LVI) and a 1.4% (a single case) rate of tumor recurrence. In contrast, biopsies with TNG 2/3 and/or NTD-positive, showed significantly worse outcomes, with a rate of 19.1% NM, a rate of 12.9% TR, and a rate of 9.6% LVI. The findings remained statistically significant on multivariate analyses. Interpretation: The findings may be of potential clinical utility in the risk stratification of patients with HPVA EACs, and may allow patients with a minimal risk of nodal metastases and tumor recurrence to be identified at the biopsy phase, thereby facilitating more personalized, possibly fertility sparing management options. Funding: Mark and Jane Gibson Endowment fund and department start-up fund, UTSW Medical Center; Natural Science Grant of China and Cervical Cancer Research Award, Zhengzhou, China. Declaration of Interest: None to declare. Ethical Approval: The institutional review board at every participating institution approved this study.

P16INK4a Expression of Uterine Cervical Biopsy Specimen in SBMCH

Introduction: The cervix is the lower portion of the uterus which connects this organ to the vagina through the endocervical canal. It is divided into the vagina (portiovaginalis) and one that lies above the vaginal vault (supravaginal portion). The outer surface of the portiovaginalis is known as the ectocervix or exocervix and the portion related to the endocervical canal corresponds to the endocervix. Carcinoma cervix accounts for the most common form of cancer by 13% of all the women affected cancers. The P16INK 4a is a tumour suppressor protein which is a CDKN2A gene product, an inhibitor of cyclin dependent kinase (CDK) 4 and 6 which is encoded by tumour suppressor gene INK 4a.&#x0D; Objective: The present study is to evaluate the P16INK 4a expression in cervical biopsy specimens and to correlate it with the histopatholgical findings.&#x0D; Materials and Methods: Cervical biopsy specimens were processed using rotary microtome and tissue blocks cut in sections of 3-5 μm was taken.&#x0D; Results: P16INK4a expression on cervical biopsy specimen showed that those with inflammatory cervical histology, benign lesions of the cervix along with premalignant lesions of cervix are negative for P 16INK4a and all malignant lesions are P 16INK4a positive.&#x0D; Conclusion: Hence P16INK4a immunoreactivity may be used for the diagnosis of neoplastic lesions of the cervix. But in our study, only a small size sample was positive. So, P16INK4a is used as one of the valuable markers for diagnosing neoplastic lesions of the cervix.

Mesonephric Adenocarcinoma of Uterine Cervix; A Case Report and Review of the Literature

Mesonephric adenocarcinoma of the uterine cervix is an extremely rare tumor of the female genital tract which derives from the remnants of embryonic mesonephric ducts and its prognosis, diagnosis and treatment is rather challenging. We report a case of a 46-year-old woman with history of abnormal uterine bleeding and an enlarged uterine cervix on physical examination without obvious mass lesion. She was clinically underdiagnosed with cervical myoma and mesonephric hyperplasia. After simple hysterectomy, stage IB2 mesonephric adenocarcinoma was diagnosed. Despite adjuvant chemoradiation, she presented with peritoneal and locoregional recurrence in less than a year. So, in the presence of abnormal bleeding and cervical mass, mesonephric hyperplasia in cervical biopsy specimen should be suspected for adenocarcinoma. Radical hysterectomy and complete staging with or without salpingo-oophorectomy is the mainstay of treatment. Despite all ambiguities, due to the small number of reported cases, the overall prognosis seems to be less favorable than conventional cervical adenocarcinoma.

HISTOPATHOLOGICAL STUDY OF COLPOSCOPIC BIOPSY OF CERVICES IN A TERTIARY CARE HOSPITAL (RAJSHAHI MEDICAL COLLEGE) IN BANGLADESH

Introduction: Colposcopy is done to detect cervical cancer and changes that may lead to cervical cancer. We aimed our study to observe the incidence of different pathologies of the cervix in Colposcopic specimens in Rajshahi Medical College of Bangladesh. Materials and Methods: Retrospective data were collected from the routine histopathological laboratory in the department of pathology Rajshahi Medical College and were recorded during a study period of 1 year (July 2019 to June 2020). Observations: Colposcopic biopsy is one of the commonest diagnostic procedures for assessing cervical Pathosis. Out of 641 specimens more than half, 365 specimens (56.50%) were Chronic Cervicitis. In present study, Chronic Cervicitis with squamous metaplasia and Invasive squamous cell carcinoma became the 2nd, 16.39% (105 specimens), and 3rd, 13.42% (86 specimens) most pathology involving the cervix. Cervical polyp, Endocervical and Leiomyomatous constitute 6.39% and 1.57% of the specimens respectively. 4.36% (28 specimens) of the study sample were the Intraepithelial neoplasia (CIN I, CIN II, CIN III). Adenocarcinoma and Clear cell carcinoma constitute 0.79% and 0.16% of the study specimens. 50 % of the cervical squamous cell carcinoma was moderately differentiated and well-differentiated and poorly differentiated squamous cell carcinoma constitutes 30.23% and 19.77% respectively. Conclusions: Colposcopic examination of cervical biopsy specimens helps to detect the exact causes and underlined pathology