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Intraductal carcinoma of the prostate (IDCp) is a distinct neoplastic entity, and although recognized for some time, it was included for the first time in the histologic classification of prostate cancer in the 2016 publication of World Health Organization. IDCp represents an intraductal or intra-acinar proliferation of malignant cells, with preservation of the basal cell layer. Even though IDCp is usually accompanied by a high-grade invasive component, low-grade invasive carcinoma can rarely be seen adjacent to the lesion. Even rarer is the incidence of isolated IDCp in needle biopsies, while a few such cases have been reported in prostatectomy specimens. We report 2 cases with isolated IDCp without any invasive component. A review of the literature is performed including the diagnostic challenges of IDCp and its morphologic mimics, immunohistochemical markers, molecular aspects, and prognostic implications. Even though it is not yet clear whether IDCp represents an intraductal spread of invasive cancer or a precursor of invasive carcinoma, the existence of isolated IDCp reinforces the idea that, at least in some of the cases, IDCp is a precancerous lesion. Further molecular studies need to be performed in order to clarify its pathogenesis. © The Author(s) 2020.

We report an unusual case of endometrial adenocarcinoma with a malignant giant cell component which is a rare type of poorly differentiated endometrial adenocarcinoma.

DNA methylation is responsible for gene silencing in varioustumour types and is mediated by five DNA methyltransferases(DNMT1, 2, 3a, 3b, 3 L). The purpose of the present study was toexplore the expression of DNMTs in borderline and malignant ovariantumours.

Solitary fibrous tumor (SFT) is a neoplasm typically arising in the pleura. Yet, extrapleural cases have been described and are a common cause of diagnostic pitfalls, especially when met in unusual sites. We report the clinical and pathological features of a case of SFT arising in a rather unusual site, the urinary bladder, the seventh reported to date in the English literature and the first with long term follow-up. Differential diagnosis from other spindle cell neoplasms of the bladder can be problematic. Prognosis of this neoplasm is obscure and long-term follow-up is required for all cases of solitary fibrous tumor. Solitary fibrous tumor is a rare mesenchymal tumor of the urinary bladder, but should always be considered in the differential diagnosis of spindle cell neoplasms encountered in the lower genital tract. Eur Rev Med Pharmacol Sci

Colorectal cancer is associated with deregulation of apoptotic and proliferative processes. The purpose of this study was to investigate the presence of apoptosis and proliferation in colorectal cancer and evaluate their possible correlation with classic prognostic markers and patients' survival. Tumors from 117 patients, followed for 44-142 months, were studied immunohistochemically using the anti-bcl-2 and anti-Ki-67 antibodies. Apoptotic body index (ABI) was assessed by a standard TUNEL method. The bcl-2 protein was detected in 65% of adenocarcinomas with increased expression in low-grade and early-stage tumors. No association was noted between bcl-2 expression and proliferative activity, ABI, or patients' survival. A positive correlation was observed between ABI and proliferation (P < 0.05). Apoptosis was more frequently observed in advanced tumor stage or high-grade neoplasms. Cox analysis revealed that only tumor stage and grade constituted independent prognostic factors. The study suggests that there is a possible deregulation of the mechanisms that control bcl-2 expression in high-grade and advanced-stage colorectal carcinomas. Regulation of apoptosis is a complex phenomenon and other factors, including tumor heterogeneity, may be involved. Dig Dis Sci

CD44 is an adhesion molecule involved in cell-to-cell and cell-to-matrix interactions. Recent evidence indicates a role of CD44 in tumor growth and metastatic potential of tumor cells. Moreover, it is widely known that the p53 tumor suppressor gene controls cell proliferation and loss of its normal function may lead to carcinogenesis. To investigate the role of these biomarkers in renal cancer, we analyzed the immunohistochemical distribution of CD44's expression on formalin fixed paraffin embedded tissue from 67 renal cell carcinomas and correlated with clinicopathologic parameters as well as with p53 suppressor gene expression. The monoclonal antibodies CD44 and p53 were applied to the tissues using the streptavidin biotin peroxidase method after microwave antigen retrieval. For CD44 and p53 more than 10% membranous and 5% nuclear staining, respectively, were estimated as positive. CD44's membranous immunoreactivity was detected in 24/67 tumors (35%) and mostly in carcinomas of clear/granular cell type. Nine tumors expressed nuclear immunoexpression of p53 protein (13.4%). Statistically significant correlation was noted between CD44 expression and nuclear grade (P < 0.001), tumor stage (P < 0.001), vascular invasion (P < 0.05) and p53 expression (P < 0.01). These results suggest that CD44s and p53 are markers of tumor progression in renal cell cancer. Urol Oncol

Dendritic cells (DCs) are antigen-presenting cells and mature from precursor CD34+ stromal cells (dendritic interstitial cells [DICs]) or monocytes. The aim of the present study was to gain insight into the local immune response to various thyroid lesions. We investigated, immunohistochemically, the presence of S-100+ DCs and CD34+ DICs in 13 papillary carcinomas, 10 follicular carcinomas, 7 follicular adenomas, 1 Hurthle cell carcinoma, 1 Hurthle cell adenoma, 2 medullary carcinomas, 6 undifferentiated carcinomas, and 3 nodular goiters. Dense infiltrates of S-100+ DCs were noted in the majority of papillary carcinomas (mean: 66.4), while moderate infiltrates were observed in follicular adenomas (mean: 23.3), follicular carcinomas (mean: 23.5), and undifferentiated carcinomas (mean: 31.6). The remaining lesions showed slight infiltrates of scattered DCs. DICs were noted exclusively in neoplastic lesions, specifically at the periphery and within the tumor capsule. The increased number of DCs in papillary carcinomas is possibly correlated with their good prognosis. The specific distribution of DICs suggests a possible contribution to growth regulation of thyroid neoplasms. Endocr Pathol

BACKGROUND: Transforming growth factors-beta (TGF-betas) are multifunctional polypeptides with crucial role as regulators of cellular growth and differentiation. It has been reported that TGF-beta1 plays a biphasic action on tumorigenesis thus inducing or inhibiting malignant properties of the epithelial cells. METHODS: TGF-beta1 expression was analyzed in 56 patients with gastric carcinoma by immunohistochemical methods and compared with the expression of p21, p53, and Ki67, as well as with angiogenesis. The correlation of these markers with clinicopathological parameters was also evaluated. RESULTS: TGF-beta1 expression was detected in 71% of tumors and was more frequent in adenocarcinomas of the intestinal type (p < 0.001). Positivity of p21WAF1, and p53 was observed in 32% and 51% of the tumors, respectively. A high Ki67 proliferating index was detected in 53.5% of the tumors. TGF-beta1 expression was significantly correlated with p21 expression (p < 0.001) and was inversely correlated with microvessel density. p21 expression was also higher in tumors with low proliferating index (p < 0.01). There was no apparent correlation between the expression of these markers and tumor stage, depth of invasion, or lymphnode metastases. CONCLUSION: The findings show that TGF-beta1 may be involved in the activation of the cdk inhibitor p21WAF1 in gastric adenocarcinomas, suggesting p53-independent induction of p21 in gastric cells. TGF-beta1 does not seem to contribute to the alteration of the angiogenic status of these tumors. Int J Gastrointest Cancer

In the present paper we review the results of our study on the use of monoclonal antibodies Y13,259 to the ras p21 and MYC1 9E10 to the c-myc p62 oncoprotein products in human tumors and tumorlike conditions of the colorectum. A total of 78 tissue sections were analyzed immunohistochemically and revealed the following: 42 adenocarcinomas with 8 normal mucosae adjacent to the tumor, 25 adenomas (with or without dysplasia and with in situ carcinoma) and 3 hyperplastic polyps. Parallel tissue sections were used in order to compare ras and c-myc oncoproteins. Reviewing our results we made the following remarks: 1. All adenocarcinomas but one were expressed with both oncoproteins, most of them being strongly positive. 2. All adenomas were positive for ras p21, and all but two were also positive for c-myc p62. An interesting point is that the degree of staining intensity increased in accordance with the degree of dysplasia and/or in situ carcinoma association. 3. The hyperplastic polyps, as well as all normal mucosae were negative.

Peer reviewed: True, Tumour-infiltrating lymphocytes (TILs) reflect antitumour immunity. Their evaluation of histopathology specimens is influenced by several factors and is subject to issues of reproducibility. ONEST (Observers Needed to Evaluate Subjective Tests) helps in determining the number of observers that would be sufficient for the reliable estimation of inter-observer agreement of TIL categorisation. This has not been explored previously in relation to TILs. ONEST analyses, using an open-source software developed by the first author, were performed on TIL quantification in breast cancers taken from two previous studies. These were one reproducibility study involving 49 breast cancers, 23 in the first circulation and 14 pathologists in the second circulation, and one study involving 100 cases and 9 pathologists. In addition to the estimates of the number of observers required, other factors influencing the results of ONEST were examined. The analyses reveal that between six and nine observers (range 2-11) are most commonly needed to give a robust estimate of reproducibility. In addition, the number and experience of observers, the distribution of values around or away from the extremes, and outliers in the classification also influence the results. Due to the simplicity and the potentially relevant information it may give, we propose ONEST to be a part of new reproducibility analyses.

Stromal tumour infiltrating lymphocytes (sTILs) are a strong prognostic marker in triple negative breast cancer (TNBC). Consistency scoring sTILs is good and was excellent when an internet-based scoring aid developed by the TIL-WG was used to score cases in a reproducibility study. This study aimed to evaluate the reproducibility of sTILs assessment using this scoring aid in cases from routine practice and to explore the potential of the tool to overcome variability in scoring. Twenty-three breast pathologists scored sTILs in digitized slides of 49 TNBC biopsies using the scoring aid. Subsequently, fields of view (FOV) from each case were selected by one pathologist and scored by the group using the tool. Inter-observer agreement was good for absolute sTILs (ICC 0.634, 95% CI 0.539–0.735, p &lt, 0.001) but was poor to fair using binary cutpoints. sTILs heterogeneity was the main contributor to disagreement. When pathologists scored the same FOV from each case, inter-observer agreement was excellent for absolute sTILs (ICC 0.798, 95% CI 0.727–0.864, p &lt, 0.001) and good for the 20% (ICC 0.657, 95% CI 0.561–0.756, p &lt, 0.001) and 40% (ICC 0.644, 95% CI 0.546–0.745, p &lt, 0.001) cutpoints. However, there was a wide range of scores for many cases. Reproducibility scoring sTILs is good when the scoring aid is used. Heterogeneity is the main contributor to variance and will need to be overcome for analytic validity to be achieved.

Microinvasion is the smallest morphologically identifiable stage of invasion. Its presence and distinction from in situ carcinoma may have therapeutic implications, and clinical staging also requires the recognition of this phenomenon. Microinvasion is established on the basis of several morphological criteria, which may be difficult and not perfectly reproducible among pathologists. The aim of this study was to assess the consistency of diagnosing microinvasion in the breast on traditional haematoxylin and eosin (HE) stained slides and to evaluate whether immunohistochemistry (IHC) for myoepithelial markers could improve this. Digital images were generated from representative areas of 50 cases stained with HE and IHC for myoepithelial markers. Cases were specifically selected from the spectrum of in situ to microinvasive cancers. Twenty-eight dedicated breast pathologists assessed these cases at different magnifications through a web-based platform in two rounds: first HE only and after a washout period by both HE and IHC. Consistency in the recognition of microinvasion significantly improved with the use of IHC. Concordance rates increased from 0.85 to 0.96, kappa from 0.5 to 0.85, the number of cases with 100 % agreement rose from 9/50 to 25/50 with IHC and the certainty of diagnosis also increased. The use of IHC markedly improves the consistency of identifying microinvasion. This corroborates previous recommendations to use IHC for myoepithelial markers to clarify cases where uncertainty exists about the presence of microinvasion. Microinvasive carcinoma is a rare entity, and seeking a second opinion may avoid overdiagnosis.

Isolated tumour cells and micrometastases represent two different staging categories and are often dealt with differently when identified in sentinel lymph nodes of breast cancer patients. The reproducibility of these categories was found to be suboptimal in several studies. The new edition of the TNM (Tumour Node Metastasis) is expected to improve the reproducibility of these categories. Fifty cases of possible low-volume nodal involvement were represented by one to four digital images and were analysed by members of the European Working Group for Breast Screening Pathology (EWGBSP). The kappa value for interobserver agreement of the pN (TNM) staging categories and of the isolated tumour cells category were 0.55 and 0.56 reflecting moderate reproducibility, and the kappa of the micrometastatic category (0.62) reflected substantial reproducibility. This is an improvement over the results gained on the basis of the previous edition of the TNM. Maximal adherence to the category definitions supplemented by explanatory texts in the staging manual should result in more homogeneous nodal staging of breast cancer.

The Ki67 labelling index (LI – proportion of staining cells) is widely used to reflect proliferation in breast carcinomas. Several cut-off values have been suggested to distinguish between tumours with low and high proliferative activity. The aim of the current study was to evaluate the distribution of Ki67 LIs in breast carcinomas diagnosed at different institutions by different pathologists using the method reflecting their daily practice. Pathologists using Ki67 were asked to provide data (including the LI, type of the specimen, receptor status, grade) on 100 consecutively stained cases, as well as details of their evaluation. A full dataset of 1709 carcinomas was collected from 19 departments. The median Ki67 LI was 17% for all tumours and 14% for oestrogen receptor-positive and HER2-negative carcinomas. Tumours with higher mitotic counts were associated with higher Ki67 LIs. Ki67 LIs tended to cluster around values ending with 5 or 0 both in cases where the values were obtained by counting the proportion of stained tumour cell nuclei and those where the values were obtained by estimation. On the basis of the distribution pattern described, some currently used Ki67 LI cut off values are not realistic, and it is proposed to select more realistic values ending with 0 or 5. The Ki67 labelling index (LI - proportion of staining cells) is widely used to reflect proliferation in breast carcinomas. Several cut-off values have been suggested to distinguish between tumours with low and high proliferative activity. The aim of the current study was to evaluate the distribution of Ki67 LIs in breast carcinomas diagnosed at different institutions by different pathologists using the method reflecting their daily practice. Pathologists using Ki67 were asked to provide data (including the LI, type of the specimen, receptor status, grade) on 100 consecutively stained cases, as well as details of their evaluation. A full dataset of 1709 carcinomas was collected from 19 departments. The median Ki67 LI was 17% for all tumours and 14% for oestrogen receptor-positive and HER2-negative carcinomas. Tumours with higher mitotic counts were associated with higher Ki67 LIs. Ki67 LIs tended to cluster around values ending with 5 or 0 both in cases where the values were obtained by counting the proportion of stained tumour cell nuclei and those where the values were obtained by estimation. On the basis of the distribution pattern described, some currently used Ki67 LI cut off values are not realistic, and it is proposed to select more realistic values ending with 0 or 5. © 2014 Elsevier Ltd.