To collect information on current practices of European pathologists for the handling and reporting of nephrectomy specimens with renal tumours.
A questionnaire was circulated to the members of the European Network of Uropathology, which consists of 343 pathologists in 15 European countries. Replies were received from 48% of members. These replies indicated that nephrectomy specimens are most often received in formalin. Lymph nodes are found in less than 5% of nephrectomy specimens. All respondents give an objective measure of tumour size, most commonly in three diameters. The most common method to search for capsule penetration is to slice tissue outside the tumour perpendicularly into the tumour. The most common sampling algorithm from tumours greater than 2 cm is one section for every centimetre of maximum tumour diameter. Most respondents use the 2004 WHO renal tumour classification although only slightly over half consider small papillary tumours malignant if the diameter is greater than 5 mm. The Fuhrman grading system is widely used. Almost all use immunohistochemistry for histological typing in some cases, while only 7% always use it. The most utilised special stains are CK7 (95%), CD10 (93%), vimentin (86%), HMB45 (68%), c-kit (61%) and Hale's colloidal iron (52%). Only 18% use other ancillary techniques for diagnosis in difficult cases.
While most pathologists appear to follow published guidelines for reporting renal carcinoma, there is still a need for the development of consensus and further standardisation of practice for contentious areas of specimen handling and reporting.
To quantify the benefit of processing each lymph node in its entirety in colorectal cancer specimens.
391 consecutive cases were examined retrospectively to assess how often cases were upstaged to node positive disease by examining each node in its entirety.
7 out of 391 patients were upstaged by this method. However, of those patients, approximately three could have been detected by chance. Therefore, approximately 1% of cases were correctly upstaged. However, six of these seven patients also had at least one additional adverse prognostic factor, and would otherwise have been considered high risk Dukes' B cases.
Processing all slices of each lymph node significantly increases laboratory workload and is of minimal clinical benefit.
The p16INK4A protein (p16) is a cyclin-dependent kinase inhibitor that arrests the cell cycle in the G1 phase.
To explore the potential of p16 as a predictive marker for lymph node (LN) metastasis and prognosis in cervical carcinomas.
145 patients diagnosed with FIGO stage I to IV cervical carcinoma were studied; 95 underwent LN dissection. The expression of p16 protein was studied by immunohistochemistry using tissue microarrays.
Overexpression of p16 was seen in 108 of 145 (74.5%) invasive carcinomas. There was a significant correlation between p16 expression and LN metastasis (p=0.007). Patients with p16 overexpression had poorer survival than patients with p16 underexpression (59.3% vs 83.8% 5-year survival rate, log-rank p=0.015). In univariate analysis, p16 expression was a significant predictor of survival (RR 2.76, p=0.02).
Results suggest that p16 expression is an important predictive factor of LN metastasis in cervical cancer patients. Moreover, p16 overexpression is associated with a poor prognosis. Therefore, immunohistochemical evaluation of p16 expression is of potential value for treatment planning in cervical carcinomas.
Endometrial cancer is one of the most common cancers in women worldwide, but there is a lack of diagnostic markers for early detection of these tumours. The raf kinase inhibitory protein (RKIP) negatively regulates the Raf/MEK/ERK pathway, and the downregulation of RKIP is associated with tumour progression and metastasis in several human neoplasms. The aim of this study was to assess the expression levels of RKIP in endometrial cancer and determine whether this expression correlates with clinical outcome in these patients.
Tissue microarrays constructed using tissue samples from 209 endometrial adenocarcinomas, 49 endometrial polyps and 48 endometrial hyperplasias were analysed for RKIP expression by immunohistochemistry.
The authors found that RKIP expression decreases significantly during malignant progression of endometrial cancer; it is highly expressed in non-neoplastic tissues (polyps 79.6%; hyperplasias 87.5%) and expressed at very low levels in endometrioid adenocarcinomas (29.7%). No correlations were observed between RKIP expression, clinicopathological data and survival.
This study demonstrated for the first time that RKIP expression is lost during the carcinogenic evolution of endometrial tumours and that the loss of RKIP expression is associated with a malignant phenotype. Functional studies are needed to address the biological role of RKIP downregulation in endometrial cancer.
To assess how frequently smoking is cited as a cause of death (COD) on death certificates.
A retrospective study of 2128 death certificates and 236 postmortem reports issued at a large teaching hospital between 2003 and 2009.
Smoking was identified as the underlying COD on only 2 (0.1%) death certificates and included in part II of the death certificate on 10 (0.5%). The two death certificates citing smoking as the underlying COD were in cases of lung cancer and chronic obstructive pulmonary disease. The study included 279 deaths in which these diagnoses were cited on the death certificate and in the majority of these cases the deceased was a smoker or ex-smoker. A review of postmortem reports from the same period failed to identify a single case in which the pathologist cited smoking as causing or contributing to death. In marked contrast to smoking, 57.4% (vs 0.5%) of death certificates, which included diagnoses linked to alcohol use, cited alcohol in part I of the death certificate.
This study demonstrates that smoking is rarely cited on death certificates, even in cases where the causal link with smoking is very strong. There are many reasons why smoking is not cited on death certificates. One frequently cited reason is the reluctance of doctors to stigmatise the deceased. Interestingly, such reluctance did not extend to citing alcohol as a COD. By not recording smoking on death certificates doctors are failing to gather important epidemiological and pathological data.
Carcinomas of the Vaterian system are rare and presumably arise from pre-existing adenomas. According to the cancer stem cell (CSC) hypothesis, only a small subset of tumor cells has the ability to initiate and develop tumor growth. In colorectal cancer, CD44, CD133, CD166 and EpCAM have been proposed to represent CSC marker proteins and their expression has been shown to correlate with patient survival.
To evaluate a potential role of these CSC proteins in tumors of the ampulla of Vater, we investigated their expression in 175 carcinoma, 111 adenoma and 152 normal mucosa specimens arranged in a Tissue Microarray format.
Membranous immunoreactivity for each protein marker was scored semi-quantitatively by evaluating the number of positive tumor cells over the total number of tumor cells. Median protein expression levels were used as cut-off scores to define protein marker positivity. Clinical data including survival time were obtained by retrospective analysis of medical records, tumor registries or direct contact.
The expression of all evaluated marker proteins differed significantly between normal mucosa, adenoma and carcinoma samples. In all markers, we found a tendency towards more constant expression from normal to neoplastic tissue. EpCAM expression was significantly correlated with better patient survival. The increased expression of CD44s, CD166 and CD133 from normal mucosa samples to adenoma and carcinoma was linked to tumor progression. However, there was no statistically significant correlation with survival.
Our findings indicate, that in ampullary carcinomas, loss of expression of EpCAM may be linked to a more aggressive tumor phenotype.
Interleukin-17 (IL-17) has been cast as a major player in angiopoiesis of carcinoma, but its role in hepatic haemangioma is not entirely clear.
The aim of this study is to address the expression levels and the molecular mechanism underlying the role of IL-17 on hepatic haemangioma progression.
20 hepatic haemangioma patients and 15 healthy subjects were included in this study. IL-17 mRNA levels were examined by PCR-based methods and protein levels by western blot. We observed a significant increase in tissue IL-17 mRNA and protein levels in hepatic haemangioma compared to normal liver tissue. Matrix metalloproteinase protein levels were slightly elevated in haemangiomas compared to normal, and IL-6 and phospho-stat3 levels were markedly elevated. However, no differences in mRNA levels of angiogenesis-associated cytokines such as vascular endothelial growth factor were seen in hepatic haemangiomas compared to normal cases taken from donor livers at the time of organ harvest. IL-17 was localised to CD4-positive cells by flow cytometry and to stromal cells and endothelial cells by immunohistochemistry. Owing to the absence of an animal model of haemangioma, we examined the effects of IL-17 on angiogenesis-related functions of vascular endothelial cells in vitro. Notably, IL-17, when added to cell cultures of human umbilical cord-derived endothelial cells, had an effect on the secretion of IL-6 and p-stat3.
Based on these findings, we propose that IL-17 may mediate the angiogenesis in a IL-6-Stat3-dependent manner and play an important role in the pathophysiology of hepatic haemangioma.
During the last decade, whole slide images (WSI) have been used in many areas of pathology such as teaching, research, digital archiving, teleconsultation and quality assurance testing. However, WSI have not regularly been used for routine diagnosis, because of the lack of validation studies.
To test the validity of using WSI for primary diagnosis of skin diseases.
100 skin biopsies and resections which had been diagnosed light microscopically one year previously were scanned at 20x magnification, and rediagnosed by six pathologists (every pathologist assessed his own cases), having the original clinical information available, but blinded to the original diagnoses. The WSI diagnoses were compared to the initial light microscopy diagnosis and classified as concordant, slightly discordant (without clinical consequences) or discordant.
The light microscopy and the WSI based diagnosis were concordant in 94% of the cases. The light microscopy and WSI diagnosis were slightly discordant in 6% of the cases. For one of the slightly discrepant cases the WSI diagnosis was considered better, while the original diagnosis was preferred for the other five cases. There were no discordant cases with clinical or prognostic implications.
Primary histopathological diagnosis of skin biopsies and resections can be done digitally using WSI.
Macrophages constitute a major component of the leucocytic infiltrate of tumours. Human studies show an association between tumour-associated macrophages and tumours with poor prognostic features. In breast cancer, the presence of macrophages has been correlated with increased angiogenesis and poor prognosis but little information is available about the independent prognostic role of macrophages infiltrating breast carcinomas.
This study used immunohistochemistry and tissue microarrays to assess the density and localisation of CD68 macrophages infiltrating 1322 breast tumours and to identify any relationship with clinicopathological factors and patient outcome.
Tumour-infiltrating macrophages were present in the majority of tumours with a predominantly diffuse pattern. The density of distant stromal macrophages (infiltrating stroma away from the carcinoma, median count 14 cells) was higher than intratumoural (median zero cells) and adjacent stromal macrophages (median three cells). Higher total macrophage number was associated with higher tumour grade (rs=0.39, p<0.001), ER and PgR negativity, HER-2 positivity and basal phenotype (p<0.001). In univariate survival analysis, higher numbers of CD68 macrophages were significantly associated with worse breast cancer-specific survival (p<0.001) and shorter disease-free interval (p=0.004). However in multivariate model analysis, the CD68 macrophage count was not an independent prognostic marker.
Macrophages are heterogeneous with different subsets having different functions. The present study suggests that overall macrophage numbers are not related to prognosis in breast cancer. However, further studies are needed to investigate the potential role of different subsets of macrophages.
The HPV-16 virus is well described as a causative agent in cervical cancer.
To individually analyse the transcription profile of the HPV-16 viral genes in patient biopsies of varying grades of cervical dysplasia by a chromogenic in situ hybridisation technique.
19 formalin fixed, paraffin embedded (FFPE) biopsies of cervical dysplasia were analysed by a chromogenic in situ hybridisation protocol using novel long single stranded digoxigenin labelled DNA probes targeted to the individual HPV-16 gene RNAs.
A transcription pattern for all the HPV-16 genes that is always conserved to the upper intermediate and superficial layers of the cervical epithelium and is independent of the level of dysplasia is described. E1 and E6 transcripts were found to express with a uniquely nuclear localisation; all other transcripts had both nuclear and cytoplasmic localisation. E5 oncogene transcripts were abundant in all cases, being equal to or greater than E7. Deep investigation of the E2 RNA transcript showed a potential alternative transcript with a possible novel start codon.
This data represents new information on HPV-16 viral transcription events that bring into question some of the current beliefs on the mechanism of HPV-16 infection in the progression to cervical cancer. Results support high expression of the E5 and E7 oncogenes in cervical dysplasias infected by HPV-16 in contrast to the low levels identified for the E6 oncogene and a possible alternative transcript for the E2 gene. The diagnostic utility of the detection of HPV-16 RNA transcripts is becoming more apparent and a renewed look at their in situ localisation in cervical biopsies could be beneficial.
In order for Chlamydia pneumoniae to play a causative role in chronic human disease, it would need to persist within infected tissue for extended periods of time. Current theory suggests that C pneumoniae may persist at the site of infection via an alternative replicative form, known as an aberrant body.
A panel of C pneumoniae-specific antibodies upregulated by the aberrant body was used to probe tissue specimens from the coronary atheroma from 13 explanted hearts to identify patterns of reactivity in these tissues, as well as to determine the presence and prevalence of C pneumoniae aberrant bodies.
Six of 13 patients had an ischaemic cardiomyopathy secondary to coronary atherosclerosis, while another six patients had an idiopathic, dilated cardiomyopathy. One additional patient, a young (24 years) woman with cardiomyopathy, had no history of atherosclerotic disease. Eleven patients were positive by immunohistochemistry with at least one antibody. Coronary arteries of the two other patients were negative by immunohistochemistry with all antibodies. One of these patients was the 24-year-old woman with grade I disease and no risk factors for coronary artery disease.
The protein antigens of persistent C pneumoniae infection found in the atheromatous lesions from patients in this study could potentially be used as markers to detect such infections and some may be virulence factors or immunogens specific to C pneumoniae, thus serving as target molecules for diagnostic use or therapeutic intervention.
Meticillin-resistant Staphylococcus aureus (MRSA) strains isolated in Tawam Hospital, a tertiary care hospital in the United Arab Emirates, were examined in order to understand the reasons for a doubling of its incidence between 2003 and 2008 while maintaining the same infection control measures.
All consecutive non-duplicate clinically relevant MRSA isolates recovered between January and December 2003 and between May and October 2008 were studied. The antibiotic susceptibility, pulsed field gel electrophoresis, toxin gene, staphylococcal cassette chromosome mec (SCCmec), spa, agr and multilocus sequence types of the strains were tested.
In 2003, typical healthcare-associated (HA-MRSA) genotypes (ST239-MRSA-III, ST22-MRSA-IV and ST5-MRSA-II) represented the majority (61.5%) of the isolates. By 2008 this pattern had changed and clonal types considered as community-associated (CA) MRSA comprised 73.1% of the strains with ST80-MRSA-IV, ST5-MRSA-IV and ST1-MRSA with non-typable SCCmec types being the most frequent. However, further epidemiological investigations showed that only one-third of the CA-MRSA infections were actually acquired in the community, indicating that CA-MRSA clones have entered and spread within the hospital.
The emergence of CA-MRSA clones with subsequent entry to and spread within the hospital has contributed to the increasing incidence of MRSA observed in Tawam Hospital and probably also in other hospitals in the UAE.
In the list of drugs, both licit and illicit, which may cause sudden cardiac death is marijuana. The sentinel paper on cannabis as a trigger for sudden cardiac death is a case crossover study from Mittleman et al, which reported that the elevated risk of triggering myocardial infarction is limited to about the first 2 h after smoking cannabis.
A 49-year-old Caucasian woman underwent a wide local excision for grade 2 lobular carcinoma of the breast with sentinel lymph node biopsy, which revealed no evidence of metastatic disease. Two years later, she underwent a therapeutic bilateral oophorectomy.
The right ovary was entirely normal histologically but in the peripheral cortex of the left ovary, adjacent to an ovarian follicle, there were clusters of fairly uniform small round cells with variable nuclear chromasia, stippled nuclear chromatin and scanty eosinophilic cytoplasm, raising the possibility of metastatic lobular carcinoma (
We present a case of PEL confirmed by pathology without effusion in a 38-year-old man at initial HIV diagnosis.
A 38-year-old man presented with a right axillary swelling, restricted arm movement and chest pain for 3 weeks. He reported weight loss of 4 kg and night sweat without fever and/or chills. On physical examination, we found enlarged neck and axillary lymph nodes with a diameter of 3 cm, movable and hard presentation without tenderness. Elevation of the right shoulder was restricted to 20° with intact circulation and sensitivity.
Lab reports showed a haemoglobin value of 7.8 g/dl, albumin 3.4 g/dl, lactate dehydrogenase 255 U/l and creatinine 1.6 mg/dl. Total serum protein was elevated to...]]>
Gross examination revealed partially oedematous liquefaction of ~4 cm. It showed a papillary structure containing a solid proliferating...]]>