Effect of diabetes on endometrial cancer recurrence and survival

ObjectiveThe purpose of this study was to investigate the influence of diabetes mellitus (DM) on cancer stage at diagnosis, cancer recurrence, and survival of endometrial cancer (EC) patients and the influence of the treatment of EC on glycaemic control, treatment, and complications of DM.MethodsIn this retrospective cohort study all 1644 patients with EC newly diagnosed in 2000–2008 and recorded in the population-based Eindhoven Cancer Registry (ECR) were included. In addition, from this total cohort a subcohort was selected for additional data collection and analyses, including 193 EC patients with DM and an age-matched sample of 195 EC patients without DM. Patients with FIGO stage IV as well as non-endometrioid histology were excluded.ResultsIn the total cohort EC patients with DM had a significantly higher age (69 years vs. 64 years), higher FIGO stages and more additional comorbidities compared to EC patients without DM. The 5-year overall survival rate for EC patients with DM was significantly lower than for EC patients without DM (68% vs. 84%). After adjusting for age, stage, period of diagnosis, cardiovascular disease, and treatment, this significant effect of DM on overall mortality persisted (HR 1.4, 95% CI: 1.0–1.8). Subcohort analyses showed that EC patients with DM were diagnosed more often with a higher body mass index (BMI) (34 kg/m² vs. 30 kg/m²) and EC was not significantly associated with changes in DM characteristics over time. Although the 5-year overall survival rate for EC patients with DM was significantly lower in the subcohort, for EC-specific mortality (n = 388) no statistically significant effect of DM was observed after adjustment for FIGO stage (HR = 1.7, 95% CI: 0.7–3.9).ConclusionsEC patients with DM compared to those without had worse patient characteristics, a higher FIGO stage, similar recurrence rates and worse overall survival.     

A nomogram for predicting lymph node metastasis in superficial esophageal squamous cell carcinoma

Superficial esophageal squamous cell carcinoma (SESCC) is defined as carcinoma with mucosal or submucosal invasion, regardless of regional lymph node metastasis (LNM). The lymph node status is not only a key factor to determine the training strategy, but also the most important prognostic factor in esophageal cancer. In this study, we establish a clinical nomogram for predicting LNM in patients with SESCC. A predictive model was established based on the training cohort composed of 711 patients who underwent esophagectomy for SESCC from December 2009 to June 2018. A prospective cohort of 203 patients from June 2018 to January 2019 was used for validation. Favorable calibration and well-fitted decision curve analysis were conducted and good discrimination was observed (concordance index [C-index], 0.860; 95% confidence interval [CI], 0.825–0.894) through internal validation. The external validation cohort presented good discrimination (C-index, 0.916; 95% CI, 0.860–0.971). This model may facilitate the prediction of LNM in patients with SESCCs.     

Prognostic impact of histological grade and vascular invasion compared with tumour cell proliferation in endometrial carcinoma of endometrioid type

AIMS: The relative impact of different prognostic factors is important for endometrial carcinoma patients. The aim of our study was to examine the combined value of histological grade [International Federation of Gynaecology and Obstetrics (FIGO)] and vascular invasion in comparison with tumour cell proliferation assessed by mitotic count and Ki67. The recently proposed binary architectural grade was also evaluated, in addition to age, depth of myometrial infiltration and FIGO stage in our population-based series of 237 endometrioid carcinomas. METHODS AND RESULTS: The tumours were studied for several histological features, including FIGO grade, binary grade, vascular invasion, mitotic count, myometrial invasion and expression of Ki67. FIGO grade was significantly associated with all investigated histological features, including Ki67 expression. Vascular invasion was significantly more frequent in FIGO grade 3 tumours, and was associated with a diffusely infiltrative growth pattern, solid growth, necrosis and deep myometrial invasion. All variables showed a highly significant relationship with patient survival in univariate analysis. In multivariate models, FIGO grade, vascular invasion, and proliferation assessed by Ki67 expression all had independent prognostic influence in this population-based study. Comparing tumour cell proliferation (Ki67) with vascular invasion as a marker of metastatic spread, the latter had a stronger survival impact. CONCLUSIONS: Vascular invasion and tumour cell proliferation measured by Ki67 both had independent prognostic influence, and should be considered to identify aggressive tumours of the endometrioid subtype.     

CD105- and CD31-assessed microvessel density in laryngeal carcinoma biopsies as a predictor of recurrence after exclusive primary surgery

PurposeSurgery is currently indicated as a unimodal therapeutic approach with curative intent in selected laryngeal squamous cell carcinomas (LSCCs) ranging from stage I to III. The main aim of this study was to evaluate the prognostic role of CD105- and CD31-assessed microvessel density (MVD) in biopsy and in surgical specimens from a cohort of consecutive stage I-III LSCCs who had undergone exclusive primary surgery, according to current guidelines.Materials and methodsCD105- and CD31-assessed MVD were analyzed in paired biopsies and surgical specimens of 24 consecutive cases of LSCC who underwent exclusive surgery.ResultsOn biopsy specimens, CD105- and CD31-assessed MVD were positively associated with recurrence risk (hazard ratio [HR] 1.266, p = 0.0034 and HR 1.265, p = 0.0081, respectively). In surgical specimens, CD105- and CD31-assessed MVD were significantly associated with disease-free survival (DFS) (HR 1.213, p = 0.0016 and HR 1.237, p = 0.0023 respectively). Considering a stratification based on median value, recurrence risk was higher in patients with a CD105-assessed MVD>0 in both biopsies and surgical specimens (HR 11.005, p = 0.0326 and HR 34.483, p = 0.0311). No significant differences in terms of recurrence risk were found for CD31-assessed on biopsies or on surgical specimens.ConclusionsThis study supports the role of biopsy CD105-MVD as a predictor of recurrence after exclusive surgery for LSCCs. Further prospective studies are mandatory to better characterize the prognostic role of CD105-MVD evaluated on biopsies to develop novel criteria to identify patients at higher risk of recurrence for more aggressive approaches or adjuvant treatment.     

Surgical treatment of endometrial cancer in developing countries: reasons to consider systematic two-step surgical treatment

OBJECTIVE:The aim of this study was to determine the lymph node status in a large cohort of women with endometrial cancer from the public health system who were referred to an oncology reference center in Brazil to identify candidates for the omission of lymphadenectomy based on clinicopathological parameters.METHODS:We retrospectively analyzed a cohort of 310 women with endometrial cancer (255 endometrioid, 40 serous, and 15 clear cell tumors) treated between 2009 and 2014. We evaluated the histological type, grade (low vs. high), tumor size (cm), depth of myometrial invasion (≤50%, >50%) and lymphovascular space invasion to determine which factors were correlated with the presence of lymph node metastasis.RESULTS:The factors related to lymph node involvement were tumor size (p=0.03), myometrial invasion (p<0.01), tumor grade (p<0.01), and lymphovascular space invasion (p<0.01). The histological type was not associated with the nodal status (p=0.52). Only twelve of 176 patients (6.8%) had low-grade endometrioid carcinoma, tumor size ≤2 cm and <50% myometrial infiltration.CONCLUSIONS:The omission of lymphadenectomy based on the histological type, grade, tumor size and depth of myometrial invasion is not likely to have a large impact on the surgical treatment of endometrial cancer in our population because most patients present with large and advanced tumors. New strategies are proposed that prioritize hysterectomy performed in a general hospital as soon as possible after diagnosis, followed by an evaluation of the need for lymph node dissection at a reference center.     

S100P as a marker for poor survival and advanced stage in gallbladder carcinoma

AimsGallbladder carcinomas usually present in advanced stages and has a dismal prognosis despite modern imaging techniques and aggressive surgical intervention. Identification of biologic markers for early diagnosis and improved therapeutic strategies is thus of paramount importance. S100P has been identified in a variety of malignant neoplasms of the gastrointestinal and pancreaticobiliary systems, but it is not yet known if S100P expression is associated with clinically-relevant characteristics of gall bladder carcinoma. The aims of the present study were: 1) to investigate the relationship between S100P expression and histological type, grade, tumor-node-metastasis stage, presence of vascular invasion, perineural invasion and necrosis; and 2) to evaluate for any S100P-defined difference in the risk for tumor recurrence or death.MethodImmunostains for S100P were performed on 4 tissue microarray blocks containing 91 cases of gall bladder carcinoma.ResultThe intensity of S100P staining was significantly associated with pathological T stage 4 (p = 0. 0238). Staining intensity ≥3 in ≥25% tumor cells was associated with pathological T stage 4 (p = 0.0005). A higher S100P immunoreactivity score (IRS) was significantly associated with higher TNM stage (p = 0.0341). Age (p = 0.0485), presence of vascular invasion (p = 0.0359), pathological T stage (p = 0.0291) and TNM stage (p = 0.0153) were significantly associated with tumor recurrence. Intense S100P reactivity was associated with decreased overall survival [hazard ratio = 9.614; 95% confidence interval (CI), 1.873–49.338; p = 0.0067].ConclusionOur findings indicate that S100P over-expression is a potential prognostic marker for gall bladder carcinoma and is significantly associated with advanced tumor stage and poorer survival.     

Early identification of high-risk patients with recurrent acute pancreatitis progression to chronic pancreatitis

IntroductionThe aim of the study was to develop a simple tool for early identification of high-risk patients with recurrent acute pancreatitis (RAP) progression to chronic pancreatitis (CP) in primary hospitals or outpatient clinics.MethodsThis retrospective cohort study included 265 patients with RAP.ResultsA nomogram for RAP progression to CP was developed and the C-index of the model was 0.817 (95% CI: 0.72–0.91). Patients were divided into two risk groups according to the nomogram prediction scores and a higher proportion of patients in the high-risk group progressed to CP.ConclusionsThe nomogram provided a means of predicting which patients were at high risk of progression to CP.     

Node negative colorectal cancer patients: assesment of high-risk features on recurrence

BackgroundThe introduction of population-based screening programs for colorectal cancer (CRC) results in less patients with advanced disease. There is an increase in the amount of node negative CRC, which makes adequate risk stratification for this particular group of patients necessary. The addition of more risk factors to the conventional histological high-risk factors is investigated in this retrospective study.Patients and MethodsA cohort of 227 node negative (stage I and II) CRC patients who were not treated with adjuvant chemotherapy were selected from two previously conducted cohort studies. Detailed histopathological examination was performed by two independent observers and molecular background (BRAF/RAS mutations, microsatellite status (MSI)) was studied. Univariate analyses were used to analyse differences in histological and mutational characteristics between patients with and without recurrence. P-values below 0.05 were considered statistically significant.ResultsPoorly differentiated histology (p:0.002), BRAF mutation (p:0.002) and MSI status (p:0.006) were found significant relevant risk factors that were related to recurrent disease. Poorly differentiated histology was associated with intermediate/high tumor budding (TB) (p:0.001), a BRAF mutation (p:0.001) and MSI status (p:0.001). A combination of all three features (poorly differentiated histology, BRAF and MSI) was more often present in the recurrence group.ConclusionsRecurrence in node negative CRC patients could be better predicted when molecular features such as, BRAF mutation and MSI status are incorporated into a model with poorly differentiated CRC. Therefore, these features might help in the selection of patients who possibly will benefit from adjuvant treatment.     

Development and validation of a comprehensive radiomics nomogram for prognostic prediction of primary hepatic sarcomatoid carcinoma after surgical resection

Objective: This study aimed to establish and validate a radiomics nomogram comprised of clinical factors and radiomics signatures to predict prognosis of primary hepatic sarcomatoid carcinoma (PHSC) patients after surgical resection.Methods: In this retrospective study, 79 patients with pathological confirmation of PHSC and underwent surgical resection were recruited. A radiomics nomogram was developed by radiomics signatures and independent clinical risk factors selecting from multivariate Cox regression. All patients were stratified as high risk and low risk by nomogram. Model performance and clinical usefulness were assessed by C-index, calibration curve, decision curve analysis (DCA) and survival curve.Results: A total of 79 PHSC were included with 1-year and 3-year overall survival rates of 63.3% and 35.4%, respectively. The least absolute shrinkage and selection operator (LASSO) method selected 3 features. Multivariate Cox analysis found six independent prognostic factors. The radiomics nomogram showed a significant prediction value with overall survival (HR: 7.111, 95%CI: 3.933-12.858, P<0.001). C-index of nomogram was 0.855 and 0.829 in training and validation set, respectively. Decision curve analysis validated the clinical utility of this nomogram. There was a significant difference in the 1-year and 3-year survival rates of stratified high-risk and low-risk patients in the whole cohort (30.6% vs. 90.1% and 5.6% vs. 62.4%, respectively, P < 0.001).Conclusion: This radiomics nomogram serve as a potential tool for predicting prognosis of PHSC after surgical resection, and help to identify high risk patients who may obtain feeble survival benefit from surgical resection.     

Prognostic significance of intrahepatic lymphatic invasion in colorectal liver metastases

BackgroundIntrahepatic lymphatic invasion is an adverse prognostic factor after hepatectomy for colorectal liver metastases (CLMs). However, most patients in previous reports had liver resection before the era of FOLFOX/FIRI-based chemotherapy.MethodsForty-six patients who underwent hepatectomy for CLMs from 2004 to 2020 were evaluated. We histologically evaluated portal invasion, intrahepatic lymphatic invasion, and biliary invasion on hematoxylin-eosin slides. We also collected the following clinicopathologic factors: gender, age, timing, the number and maximum size of CLMs, preoperative tumor markers, neutrophil/lymphocyte ratio, location, and lymph node metastases of primary cancer, and chemotherapy after hepatectomy. A multivariate Cox proportional hazard model was used to define the relationship between overall (OS) or disease-free survival (DFS) and clinicopathologic factors.ResultsHistological invasions were portal invasion in 8 (17.4 %), intrahepatic lymphatic invasion in 6 (13.0 %), and biliary invasion in 5 (10.9 %). Chemotherapy for recurrence after hepatectomy (n = 29) was performed in 22 and 14 of those who received FOLFOX/FIRI-based chemotherapy. By multivariate analysis, the number of CLMs (p < 0. 01) and presence of intrahepatic lymphatic invasion (p = 0.02) were independent predictors of recurrence. The number of CLMs (p = 0.02) and prehepatectomy carcinoembryonic antigen level (p = 0.02), but not intrahepatic lymphatic invasion (p = 0.18), were independent predictors of survival using multivariate analysis.ConclusionsThe presence of intrahepatic lymphatic invasion adversely affected patient's DFS, but not OS in patients with CLMs in the era of FOLFOX/FIRI chemotherapy. FOLFOX/FIRI-based chemotherapy might improve OS, even in patients with positive intrahepatic lymphatic invasion.     

Histological subtypes in triple negative breast cancer are associated with specific information on survival

Much research has focused on finding novel prognostic biomarkers for triple negative breast cancer (TNBC), whereas only scattered information about the relation between histopathological features and survival in TNBC is available. This study aims to explore the prognostic value of histological subtypes in TNBC.A multicenter retrospective TNBC cohort was established from five Dutch hospitals. All non-neoadjuvantly treated, stage I-III patients with estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 negative breast cancer diagnosed between 2006 and 2014 were included. Clinical and follow-up data (overall survival; OS, relapse free survival; RFS) were retrieved and a central histopathological review was performed.Of 597 patients included (median follow up 62.8 months, median age at diagnosis 56.0 years), 19.4% developed a recurrence. The most prevalent histological subtypes were carcinoma of no special type (NST) (88.4%), metaplastic carcinoma (4.4%) and lobular carcinoma (3.4%). Collectively, tumors of special type were associated with a worse RFS and OS compared to carcinoma NST (RFS HR 1.89; 95% CI 1.18–3.03; p = 0.008; OS HR 1.94; 95% CI 1.28–2.92; p = 0.002). Substantial differences in survival, however, were present between the different histological subtypes.In the presented TNBC cohort, special histological subtype was in general associated with less favorable survival. However, within the group of tumors of special type there were differences in survival between the different subtypes. Accurate histological examination can provide specific prognostic information that may potentially enable more personalized treatment and surveillance regimes for TNBC patients.     

Clinicopathological analysis of recurrence and progression of low-grade papillary urothelial carcinoma of the urinary bladder: Predicting the outcome

BackgroundUrothelial carcinoma of the urinary bladder is the most common malignancy of the urinary system. Patients with low grade papillary urothelial carcinoma (LGPUC) usually have a low risk for tumor recurrence and progression; yet a subset of patients develop recurrence or grade/stage progression to high-grade papillary urothelial carcinoma (HGPUC). The clinicopathological and molecular factors that contribute to this progression are yet to be determined.ObjectivesIn our study, we aimed to assess the incidence and clinicopathological factors associated with tumor recurrence/progression of LGPUC.MethodsUsing a pathological database of surgical specimens from patients who underwent bladder biopsies and/or transurethral resection of bladder tumors (TURBTs) between August 01, 2011, and July 31, 2021, at a large academic medical center, a single-center retrospective cohort analysis was performed, and medical charts of patients were reviewed.ResultsOf the total 258 patients included, 157 (60.9 %) had “no recurrence”, 85 (32.9 %) had ≥1 “recurrence of LGPUC”, and 16 (6.2 %) had “grade progression to HGPUC”. The mean follow-up time was 31.5 ± 32 months. Patients with “grade progression” and “recurrence of LGPUC” had larger mean tumor size on initial biopsy and multiple lesions on initial cystoscopy compared to those with “no recurrence.” Interestingly, former smokers had 2.5- and 8.5-times higher risk of recurrence of LGPUC and grade progression, respectively.ConclusionSince the majority of our patients did not develop recurrence, we question whether there is tendency to overclassify the papillomas as LGPUC based on the 2004 WHO/ISUP consensus grading classification.     

A simple nomogram for predicting early complications in patients after primary knee arthroplasty

BackgroundThis study sought to construct a nomogram for patients based on preoperative and intraoperative variables to individually predict the likelihood of complications within 30 days after primary knee arthroplasty.MethodsData were obtained from the medical record of patients who underwent primary knee arthroplasty at our institution from 2015 to 2018. Preoperative and intraoperative factors were collected critically. Predictor variables include 15 common complications occurring within 30 days. The predictive model was developed using multivariable logistic regression and least absolute shrinkage and selection operator regression. Clinical usefulness and calibration of the predicting model were assessed using C-index, calibration plot, receiver operating curve, and decision curve analysis. Internal validation was assessed using the bootstrapping validation.ResultsThe prediction nomogram identified six variables associated with complications, including hemoglobin, tourniquet time, operative time, estimated intraoperative blood loss, American Society of Anesthesiologists Classification (ASA class) and type of anesthesia. The model displayed good discrimination with a C-index of 0.822 (95% confidence interval: 0.760–0.884), an area under the curve of 0.822 and good calibration. High C-index value of 0.810 could still be reached in the interval validation. Decision curve analysis showed that the nomogram was clinically useful when intervention was decided at the complications possibility threshold in the three percent to 100% range.ConclusionWe constructed and validated a nomogram for predicting the probability of postoperative complications within 30 days after primary knee arthroplasty. Our nomogram may prove to be a useful tool for guiding physicians in terms of their decisions.     

Composite enteric-type adenocarcinoma-carcinoid of the nasal mucosa

The authors describe a patient whose nasal neoplasm demonstrated histological characteristics of both a moderately differentiated intestinal-type adenocarcinoma and an atypical carcinoid (well-differentiated neuroendocrine carcinoma). The adenocarcinoma displayed a predominantly papillary architecture, immunohistochemically positive staining for intestinal markers, and ultrastructural features (microvilli with long roots) characteristic of intestinal differentiation. The carcinoid component was argyrophilic, was immunoreactive with chromogranin, gastrin, and serotonin, and displayed ultrastructurally characteristic G and EC cells. The neoplasm recurred twice, and the tumor tissue from the second recurrence was composed only of neuroendocrine cells, indicating that this component was more resistant to the therapy (surgery and radiotherapy) employed. The patient died from an intracranial recurrence 5 months after the last combined surgical and radiotherapic treatment. Because of its unfavorable prognosis, a neuroendocrine-exocrine tumor should not be grouped with typical carcinoids or with well-differentiated papillary sinonasal adenocarcinomas, which seem to be less aggressive.     

Phyllodes tumor of the breast clinical experience and outcomes: A retrospective cohort tertiary hospital experience

BackgroundPhyllodes tumor (PT) accounts for <1% of all breast tumors worldwide. Based on their microscopic features, these tumors are classified into benign, borderline, and malignant. This study aimed at evaluating the clinical experience and the clinicopathologic features of PT.MethodsA retrospective cohort study of 46 female patients with histologically diagnosed PT. Data collection and evaluation was done on patient demographics, preoperative radiological assessment and pathology, surgical procedure, post-surgery pathological evaluation, radiation therapy (RT), and follow-up.ResultsThe median age at diagnosis was 42 years and young premenopausal patients (median age 35 years) had malignant PT. Forty-five patients underwent core needle biopsy (CNB) with high sensitivity and the positive predictive value (82.2% and 97.4% respectively). Thirty-nine patients (86.7%) underwent conservative surgery and 6 (13.3%) had a mastectomy. Twenty-seven (58.6%) were classified as benign, 11 (23.9%) as borderline and only 8 (17.4%) as malignant PT. Malignant PT had the greatest median tumor size (13 cm). Mortality and recurrence rates were 4.3% and 2.2% respectively. RT was administered in 6 patients (13.0%), 5 having malignant and 1 borderline PT. The metastatic rate was found to be 6.5%.ConclusionPT are rare breast tumors with variable biologic behavior and heterogenous clinicopathological findings. Young, premenopausal women with large tumors may have malignant PT with a risk of recurrence and metastasis. Core needle biopsy is a reliable tool for diagnosis of PT with strict follow-up recommended for large tumors diagnosed as fibroadenoma on CNB. Surgical management must ensure a tumor-free margin on excision to reduce recurrence.     

Relationship of Oncotype Dx score with tumor grade,size, nodal status,proliferative marker Ki67 and Nottingham Prognostic Index in early breast cancer tumors in Saudi Population

BackgroundOncotype Dx is a 21-gene recurrence score, which is used as a diagnostic tool for the recurrence of breast cancer. It is also used to determine the benefit of chemotherapy for breast cancer in early stages. This study investigates the relationship of Oncotype Dx with pathological prognostic markers of protein Ki 67, Nottingham Prognostic Index (NPI) and tumor grade.MethodsData for early breast cancer patients treated at our tertiary care center was collected for statistical analysis. Data for patients from 2014 to 2018 was recorded for patient's age, ER/PR status, Ki 67, nodal status, tumor grade, NPI along with Oncotype Dx score. Metric measurements were described as mean ± SD and the non-metric data was represented by frequency (%). Chi-square or Fisher's exact tests as well as logistic regression was applied to assess the associations at 95% CI.ResultsAmong 156 breast cancer patients, the mean age was 55.7 ± 9.4 years. The tumors were classified into Grade-I (12.8%), Grade-II (67.3%) and Grade-III (19.9%). Ki67 score was 12.8 ± 12.0 and NPI score was 3.7 ± 0.8. The mean Oncotype Dx score was 17.0 ± 9.1; it was 14.1 ± 6.8 for Grade-I tumors; 15.7 ± 7.5 for grade -II tumors; and 23.2 ± 12.3 for grade-III tumors [Mean Oncotype Dx score across Tumor grades was compared by ANOVA (η = 0.121), p < 0.001]. While logistic regression analyses for the dichotomized Oncotype Dx higher score (≥25) was significantly associated with grade-III tumors odds ratio (OR) = 13.72 (95% CI: 1.62–115.89), higher Ki67 (>20) OR = 14.40, (95% CI: 1.44–143.71), average NPI score (2.41–3.40), OR = 13.60, (95% CI: 1.57–117.94) to poor NPI (>5.4). The association of Oncotype Dx with age, tumor size and nodal status was statistically not significant.ConclusionsThis study revealed that age, Ki67, tumor size and nodal status did not have a statistically significant impact on Oncotypye Dx recurrence score in the targeted patient population. There was a significant correlation of low grade node negative patients with Oncotype Dx while high grade node negative patients had poor correlations with Oncotype Dx. The use of Oncotype Dx has shown to be less cost-effective and has no noticeable association with improved life expectancy in the targeted patient population (i.e., hormone positive, node negative cases) in comparison with current clinical practices in Saudi Arabia and it is less likely to be cost-effective in this group of patients.     

Protein expression status in mucosal and submucosal portions of early gastric cancers and their predictive value for lymph node metastasis

We aimed to find out predictive markers for lymph node (LN) metastasis of early gastric carcinoma (EGC) by separating evaluation of protein expression in mucosa and submucosa considering tumor heterogeneity. We selected 37 pN1–3 EGCs and depth‐ and size‐matched 31 pN0 EGCs as training set and 72 EGCs including 14 pN1–3 EGCs as test set. Protein expression for β‐catenin, E‐cadherin, N‐cadherin, galectin‐3, c‐MET, TrkB, and Ki‐67 was assessed by immunohistochemistry in mucosal (‐m) and submucosal (‐sm) portions of tumor. In the training set, Ki67‐m was higher than in Ki67‐sm (mean ± SD: 82.67 ± 11.99% vs 61.79 ± 22.53%, p < 0.001). Altered E‐cadherin‐sm, high Ki67‐m, and high Ki67‐sm were correlated with LN metastasis (p < 0.05) and Ki67‐sm was independent with lymphatic invasion and desmoplasia (p = 0.015 by multivariate logistic analysis). The test set confirmed Ki67‐sm and E‐cadherin‐sm as predictors of LN metastasis (p < 0.05). Submucosal EGCs with ≥2 predictive factors out of high Ki67‐sm, altered E‐cadherin‐sm, large tumor size (≥3 cm), diffuse type histology, and present lymphatic invasion yielded 100% sensitivity and 90.9% specificity for prediction of LN metastasis in 21 submucosal EGCs of test set. The proliferative activity of tumor in submucosa is suggested to be an independent predictor for LN metastasis in EGC.     

Postmenopausal status, hypertension and obesity as risk factors for malignant transformation in endometrial polyps

OBJECTIVES: We analyzed clinical data and pathological features of six cases of malignant endometrial polyps, to compare these with other examples reported in literature and to define the features of endometrial cancer arising in polyps. Moreover, to clarify the mechanisms of carcinogenesis in malignant endometrial polyps we examined the expression of cyclooxygenase-2 (COX-2), P53 and Ki 67 and their relationships with clinicopathologic characteristics. METHODS: The surgical pathology files of the Pathology Department of Parma University were searched for cases of endometrial polyps with nests of endometrial carcinomas, from the years 2002-2005. Clinical records, histological slides of endometrial curetting, hysterectomy with salpingo-oophorectomy specimens and pelvic lymph nodes were reviewed in each case. The main pathological features analyzed were histological types of endometrial cancer and the stage of development of neoplasm. The presence of other malignancies in the genital tract were also considered. Immunohistochemical staining was done using antibodies COX-2, p53 and Ki 67. RESULTS: In our study, all malignant endometrial polyps had been detected in postmenopausal women. The majority of our patients with malignant endometrial polyps had risk factors for the development of endometrial carcinoma such as hypertension, obesity and unopposed estrogen therapy. Unlike other studies, no patients had a history of previous breast carcinoma and Tamoxifen treatment. The most common subtypes of endometrial carcinoma in malignant polyps are endometrioid carcinoma and serous papillary carcinoma. Endometrial carcinoma arising in endometrial polyps is an early endometrial carcinoma with good prognosis, except for papillary serous carcinoma, which can be associated with multiple omental involvement, despite low stage of development in the uterus. Immunohistochemical study showed that COX-2 expression was found in cytoplasm of tumor cells and this was elevated in all cases, independently of the grade and the stage of development of the malignancy, histological subtype and deep invasion of myometrium. P53 and Ki 67 expression, detected in the nuclei of neoplastic cells, was not correlated with COX-2 immunoreactivity, but these markers were associated with more advanced stage, grading, and histologic subtypes of tumor. CONCLUSIONS: Postmenopausal status, hypertension, obesity could all be considered as risk factors for carcinomatous transformation within endometrial polyps in women without a history of breast carcinoma and Tamoxifen treatment. However, our series is small (only six cases considered) and further studies are necessary to confirm this hypothesis. In the current study, immunohistochemical data reveal that COX-2 expression may be associated with the carcinogenesis in endometrial carcinomas arising in endometrial polyps, but this antibody is not correlated with tumor aggressiveness, P53 and Ki 67 expression. P53 and Ki 67 overexpression, instead, are associated with advanced stage, histologic subtype and deep myometrial invasion of neoplasm.     

An unusual cribriform variant of salivary basal cell tumours: a clinicopathological study of 22 cases

Tian Z, Hu Y, Wang L, Li L, Zhang C & Li J
(2012) Histopathology  61, 921–929 An unusual cribriform variant of salivary basal cell tumours: a clinicopathological study of 22 cases Aims: To clarify the clinicopathological characteristics of salivary basal cell tumours exhibiting cribriform architecture, and to discuss the differential diagnosis of these tumours with regard to adenoid cystic carcinoma (AdCC). Methods and results: Eighteen basal cell adenomas (BCAs) and four basal cell adenocarcinomas (BcACs) with at least a 10% area of cribriform morphology were collected, and the histological and immunohistochemical features were evaluated. The majority of tumours showed the typical histological patterns of basal cell tumours, in addition to cribriform architecture. In some areas, the periphery of cribriform nests had a palisade arrangement. Focal capsular infiltration, but not invasion of surrounding normal tissue, was detected in 14 of 18 BCAs. The capsules were absent or incomplete and mainly accompanied by focal invasion in BcACs. Cystic degeneration was observed in 12 of 22 tumours. The Ki67 labelling index of basal cell tumours was significantly lower than that of cribriform AdCCs (P = 0.001). All patients had a good outcome after a follow‐up of 15–96 months. Conclusions: The cribriform variant shares most of the clinicopathological features of conventional basal cell tumours. Admixtures of cribriform and trabecular or tubulo‐trabecular subtypes, peripheral palisading, cystic changes, non‐invasive or low‐grade invasive growth patterns and a low Ki67 labelling index may be useful for distinguishing basal cell tumours with a cribriform architecture from AdCCs.     

Challenges in pathological assessment of endoscopic resections

Endoscopic resections (ERs) are performed for early (T1) cancers mostly of the esophagus, stomach and colorectum, offering a minimally invasive and tissue-preserving alternative to traditional surgical resection. Proper preparation and handling of these specimens is key to allow accurate histological assessment of parameters which will dictate the curative, or non-curative, nature of the procedure. Many histological features have been identified which correlate with risk of recurrence and/or nodal metastases, thereby dictating the need for further management. These include histological subtype of the lesion, grade, depth of invasion, margin status, tumor size, lymphovascular invasion and tumor budding [at least in the colon]. This review article will discuss the ideal specimen preparation and discuss each of these histological parameters in turn, as they pertain to the esophagus, stomach and colorectum, highlighting potential caveats and pitfalls to be aware of when reporting these specimens.