Pathology research international最新文献

Primary eosinophilic gastroenteritis and colitis (EGE) is a rare entity with unspecific clinical and endoscopic findings. Validated histopathologic criteria for confirming the diagnosis are lacking, because numeric values for normal or elevated concentrations of eosinophils in mucosal biopsies are varying between observers. To quantify this interobserver variance, we had the same set of 30 slides of eosinophilic-rich mucosal biopsies from the ileum and colon systematically reviewed by a panel of six independent pathologists, each with more than a ten-year experience in the field. Using a highly standardized biopsy and slide preparation protocol, we ruled out any influence by the preparation, the patient, the endoscopist, the endoscopes and calipers used, the sampling site, the fixation and staining method, and the microscopic field sizes. Still, all numeric results differed between pathologists up to a factor greater than 30. Calculated positive or negative diagnosis of EGE differed up to a factor greater than 8. A theoretical incidence for EGE calculated from these numbers differed by a factor greater than 1500. We conclude that eosinophil counts in mucosal biopsies from the lower gastrointestinal tract are subject to a very high interobserver variance. Until further research provides objective and validated methods for standardization, all epidemiologic numbers derived from histopathologic findings may have to be questioned. When diagnosing individual patients with EGE, overall morphologic picture together with clinical and endoscopic findings is more important than numeric eosinophil count.

Background and objective: Evidence for the roles of matrix metalloproteinases-9 (MMP-9) in the healing process of diabetic foot ulcers has remained unclear. We therefore aimed to demonstrate the relationship of MMP-9 with the wound healing process and determine its potential usefulness in predicting the wound healing outcome.

Methods: Twenty-two patients with diabetic foot ulcer were recruited. The wound size was determined, and the wound fluid was collected for the measurement of MMP-9 levels using an ELISA during the 12-week follow-up period regularly. The patients were categorized as good healers and poor healers when the wound area reduction was ≥ 50% and < 50% at week 4 when compared to the initial wound size at week 0.

Results: Median wound fluid MMP-9 levels in the poor healer group were shown to be significantly higher than those in the good healer group (1.03 pg/µg protein vs. 0.06 pg/µg protein, p = 0.001), and the levels fluctuated throughout the 12-week follow-up period. In contrast to the poor healer group, the MMP-9 levels were demonstrated to be constantly low throughout the follow-up period in the good healer group. ROC analysis showed that the MMP-9 level of 0.38 pg/µg protein was able to predict the wound healing outcome with the sensitivity of 81.8%, the specificity of 64.6%, and the area under the curve of 0.901 (CI 0.78-1.03, p = 0.001).

Conclusion: These findings suggested that determination of wound fluid MMP-9 levels might become a promising biomarker predicting wound healing outcomes and a novel potential therapeutic target for diabetic foot ulcers.

Aim: Antigenic expression in epithelial cells can be heterogeneous which may pose a problem in immunohistochemical (IHC) analysis of tumor markers, in particular, predictive markers like HER2. Studies have shown that epithelial cells have distinct apical and basolateral domains which are separated by tight junctions. The cell membrane in these two domains has a different composition of macromolecules and hence can have variable antigen expression on immunohistochemistry. In our study, we aimed to investigate this phenomenon of basolateral versus circumferential IHC staining of HER2 in gastric/GE adenocarcinoma.

Methods: We selected 45 cases of gastric/GE adenocarcinoma and evaluated equal number of specimens (15 each) showing well-differentiated, moderately differentiated, and poorly differentiated morphology. All cases had 3+ HER2 score as per CAP guidelines. HER2-membrane staining pattern in all specimens was analyzed.

Results: Cases with well-differentiated morphology showed only basolateral or lateral membrane staining in most cases. Poorly differentiated adenocarcinoma samples showed circumferential staining (both basolateral and luminal) in all cases with highly significant p value. Mixed staining pattern was observed in moderately differentiated cases. Diffuse expression of E-cadherin in well-differentiated adenocarcinoma and loss in poorly differentiated tumors were also statistically significant.

Conclusion: These findings suggest that HER2 in gastric epithelium has a polarized distribution which is maintained by the fence function of tight junctions. With progression to high grade cancer, the glandular structural differentiation in gastric mucosa is lost, along with disruption of tight junctions. This leads to loss of cell polarity and migration of antigens across the membrane.

Background: Classification of patients with anti-neutrophil cytoplasmic antibody-associated glomerulonephritis (ANCA-GN) into histological classes is useful for predicting a patient's risk of progression to end-stage renal disease (ESRD). However, even in the worst prognostic group, the 5-year end-stage renal disease-free survival rate is as high as 50%.

Objectives: To investigate those prognostic factors indicative of progression to ESRD in patients with ANCA-GN and sclerosing histology.

Methods: Patients from the Norwegian Kidney Biopsy Registry between 1991 and 2012 who had biopsy verified pauci-immune glomerulonephritis, positive ANCA serology, and sclerosing histology were included. Cases with ESRD during follow-up were identified via linkage with the Norwegian Renal Registry. Potential prognostic factors with relevant cut-offs were compared in patients with and without progression to ESRD during follow-up.

Results: Of 23 included patients, 10 progressed to ESRD. ESRD patients had a lower initial estimated glomerular filtration rate (eGFR; 21 versus 52 ml/min/1.73 m²) and a lower percentage of normal glomeruli (4% versus 15%). Five-year risks of ESRD with eGFR >15 versus ≤15 ml/min/1.73 m² were 77% and 15%, with percentage normal glomeruli >10% versus ≤10%, 83% and 39%.

Conclusions: eGFR and percentage of normal glomeruli are strong risk factors for ESRD in ANCA-GN with sclerosing histology.

Background: The diagnosis of Osteosarcoma (OSA) is not always straightforward. OSA may resemble Other Primary Bone Tumours (OPBT). The diagnosis of osteosarcoma is sometimes difficult especially in a very small specimen. Immunohistochemistry is one of ancillary testing types that can help the diagnosis of many tumours. The aim of this study was to evaluate the validity of Osteocalcin (OCN) and Alkaline Phosphatase (ALP) immunohistochemistry in discriminating OSA from OPBT.

Method: This study included 50 selected human primary bone tumours, 25 cases of OSA and 25 cases of OPBT. Immunohistochemical evaluation of OCN and ALP was done for all cases. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and overall accuracy were calculated.

Result: The mean age of OSA and OPBT patients was 19.6 ± 13.6 and 40.0 ± 16.3 years, respectively. Osteocalcin was positive in 17/25 (68%) cases of OSA and 16/25 (64%) cases of OPBT (p = 0.061). Alkaline Phosphatase was positive in 24/25 (96%) cases of OSA and 5/25 (20%) cases of OPBT (p < 0.001). The sensitivity of OCN in OSA diagnosis was 68%, with specificity, PPV, NPV, and overall accuracy being 36%, 52%, 53%, and 52%, respectively. The sensitivity of ALP in OSA diagnosis was 96%, with specificity, PPV, NPV, and overall accuracy being 80%, 82.7%, 95.2%, and 88%, respectively.

Conclusion: ALP immunohistochemistry is useful in discriminating OSA from OPBT. ALP is superior to OCN in OSA diagnosis. OCN cannot be used to differentiate between OSA and OPBT.

Objective: B lymphocyte infiltration in the tumor microenvironment has been proposed to play pivotal roles in tumor progression. Heat shock protein 70 (HSP70) expressed by tumor cells can induce antitumor immune response. Few studies have examined the clinicopathologic relationship between tumor infiltrating B lymphocyte and HSP70 expression in human cancer. So far, there is no complete knowledge on the relationship in oral squamous cell carcinoma (OSCC). The present study was conducted to evaluate the relationship between tumor infiltrating B lymphocyte and HSP70 expression in OSCC, as well as the clinical outcome.

Materials and methods: In this retrospective study, the immunohistochemical analysis of 50 OSCC specimens was performed using CD20 and HSP70 antibodies. The relationship between markers' expression and clinicopathologic data was evaluated using Mann-Whitney test, Chi-square test, logistic regression model, and Spearman's correlation coefficient.

Results: The data analysis showed significant correlation between peritumoral CD20⁺ B lymphocyte infiltration and lymph node metastasis (P = 0.047). Furthermore, HSP70 expression was significantly correlated with stage (P = 0.003), lymph node metastasis (P < 0.001), and tumor size (P = 0.044). However, no relationship was observed between B lymphocyte infiltration and HSP70 expression.

Conclusion: The results suggest that peritumoral B lymphocyte infiltration and HSP70 expression level have significant association with OSCC and may be considered as prognostic indicators in OSCC. Thus, evaluation of B cells as therapeutic targets in OSCC patients is recommended.

Tartar emetic (TE) was the first drug used to treat leishmaniasis. However, its use was discontinued due to high toxicity. Association of TE with liposomes is a strategy to reduce its side effects. Pegylated liposomes (Lpeg) present lower rates of uptake by macrophages and prolonged circulation compared to their nonpegylated counterparts. However, repeated administration of Lpeg can cause an Accelerated Blood Clearance (ABC) phenomenon, whereby recognition of liposomes by antibodies results in faster phagocytosis. This work evaluated the effect of TE administration on histopathological aspects and the effect of the ABC phenomenon on targeting and toxicity in mice. Our results show that treatment with free or liposomal TE had no effect on the erythrocyte count, on liver and spleen weight, and on hepatic, splenic, and cardiac histology in mice. Severe lesions were observed on the kidneys of animals treated with a single dose of free TE. Treatment with TE in Lpeg after induction of ABC phenomenon caused a significant increase in Sb level in the liver without toxicity. Furthermore, mice treated with TE in liposomes showed normal renal histopathology. These results suggest site-specific targeting of Sb to the liver after induction of ABC phenomenon with no toxicity to other organs.

Objective. Secretory carcinoma is a recently described entity with characteristic immunoprofile and ETV6 (12p13) rearrangement. Before its initial description, it was generally diagnosed as acinic cell carcinoma (ACCi). We evaluated immunoprofile and ETV6 rearrangement in cytological and surgical cases of previously diagnosed ACCi, in an attempt to identify any misclassified SC. Methods. Fifteen cytology and surgical cases of ACCi diagnosed over a 13-year period were retrieved and subjected to immunohistochemistry for S-100, mammaglobin, GATA-3 and DOG-1 as well as FISH for ETV6 (12p13). Results. Of the 8 cytology cases, only 1 was positive for S100, GATA-3, and mammaglobin, and negative for DOG-1. It also demonstrated ETV6 rearrangement and was reclassified as SC. The same immunoprofile was present in 2 of the 13 surgical cases. ETV6 rearrangement characterized by 3' interstitial deletion was detected in one of these cases and was reclassified as SC. Immunohistochemistry and ETV6 rearrangement were useful in identifying 2 (13.3%) cases misclassified as ACCi. Conclusions. Characteristic immunoprofile and ETV6 gene rearrangement may prove useful in identifying cases of SC. The presence of ETV6 3' interstitial deletion in one of our cases suggests that there may be additional ETV6 related genetic alterations contributing to the pathogenesis of SC.

Objective: Anal cytology is being increasingly used as part of anal cancer screening in patients at high risk for anal neoplasia. Most studies in anal cytology have focused on correlating the abnormal anal Pap smear with histopathologic outcomes. The aim of this study was to document histopathologic or repeat anal cytology outcomes in patients with unsatisfactory cytology.

Materials and methods: Unsatisfactory anal Pap tests in high risk male patients were correlated with follow-up histopathologic diagnoses or cytology.

Results: 1205 anal tests were performed during the study period and 214 (17.8%) were unsatisfactory. Adequate follow-up cytology was available in 75 cases and revealed epithelial cell abnormality (ECA) in 40% [30/75] (atypical squamous cells of undetermined significance (ASCUS) [20%] and low-grade squamous intraepithelial lesions (LGSIL) [20%]) and was negative for intraepithelial lesion or malignancy (NILM) in 60% [45/75] of cases. 28.7% of unsatisfactory Pap smears had unsatisfactory repeat cytology. Histopathological follow-up on these unsatisfactory Pap smears revealed anal intraepithelial neoplasia (AIN) 1 and AIN 2/3 or 2/3+ in 39% and 18% of the total number of biopsy cases, respectively.

Conclusions: High risk male patients with unsatisfactory Pap smears are at significant risk of epithelial cell abnormality and histopathologically verifiable anal intraepithelial lesions.