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Inverted papilloma (IP) of the urinary tract is classified by the World Health Organisation as a non-invasive urothelial tumour with normal to minimal cytological atypia of the neoplastic cells. During the 1980s, it came under suspicion of having a premalignant or malignant potential and of being concurrent with urothelial cell carcinoma (UCC). This quandary has been proven difficult to solve, due to the fact that IP is very rare and literature mostly consists of case reports with varying levels of information, making strong meta-analyses problematic. New immunohistochemical techniques and genetic approaches are more frequently being used in the attempt to achieve better classifications, prognosis and treatment of lesions hereunder IP. This review will, in our awareness, be the first to combine the knowledge from retrospective studies with these new approaches for determining a possible premalignant potential and concurrency with UCC and subsequently outline a recommendation for follow-up.

Liver collagen proportionate area (CPA) assessed by computer-assisted digital image analysis has been proposed as an accurate and objective histological variable for subclassifying cirrhosis. The study aimed to examine the relationship between CPA and relevant clinical parameters in cirrhotic patients and to evaluate the sampling variability for CPA. The study included 48 consecutive liver transplantation patients with established cirrhosis. Hepatic venous pressure gradient (HVPG) and serum markers of liver failure were determined prior to transplantation. CPA was assessed in the explanted livers. In 20 of the livers, CPA was measured in more than one tissue sample. CPA showed significant correlations with HVPG and with various surrogate markers of hepatic dysfunction including albumin, bilirubin, INR, MELD score and Child-Pugh score. CPA reliably discriminated HVPG ≥10 mmHg, termed 'clinically significant portal hypertension' (area under receiver operator curve: 0.923, p0.001; odds ratio: 1.209, p = 0.003). CPA measured on tissue blocks showed no significant sampling variability (p0.5). In conclusion, the study correlated portal hypertension and hepatic dysfunction with the amount of collagen in cirrhotic livers. The findings support the presumption of CPA as a useful histological marker for subclassifying cirrhosis and as a helpful supplement to the qualitative description of hepatic architectural changes in routine pathology.

Whole slide imaging (WSI) has been used in conjunction with virtual microscopy (VM) for training or proficiency testing purposes, multicentre research, remote frozen section diagnosis and to seek specialist second opinion in a number of organ systems. The feasibility of using WSI/VM for routine surgical pathology reporting has also been explored. In this review, we discuss the utility and limitations of WSI/VM technology in the histological assessment of specimens from the prostate. Features of WSI/VM that are particularly well suited to assessment of prostate pathology include the ability to examine images at different magnifications as well as to view histology and immunohistochemistry side-by-side on the screen. Use of WSI/VM would also solve the difficulty in obtaining multiple identical copies of small lesions in prostate biopsies for teaching and proficiency testing. It would also permit annotation of the virtual slides, and has been used in a study of inter-observer variation of Gleason grading to facilitate precise identification of the foci on which grading decisions had been based. However, the large number of sections examined from each set of prostate biopsies would greatly increase time required for scanning as well as the size of the digital file, and would also be an issue if digital archiving of prostate biopsies is contemplated. Z-scanning of glass slides, a process that increases scanning time and file size would be required to permit focusing a virtual slide up and down to assess subtle nuclear features such as nucleolar prominence. The common use of large blocks to process prostatectomy specimens would also be an issue, as few currently available scanners can scan such blocks. A major component of proficiency testing of prostate biopsy assessment involves screening of the cores to detect small atypical foci. However, screening virtual slides of wavy fragmented prostate cores using a computer mouse aided by an overview image is very different from screening glass slides using a microscope stage. Hence, it may be more appropriate in this setting to mark the lesional area and focus only on the interpretation component of competency testing. Other issues limiting the use of digital pathology in prostate pathology include the cost of high quality slide scanners for WSI and high resolution monitors for VM as well as the requirement for fast Internet connection as even a subtle delay in presentation of images on the screen may be very disturbing for a pathologist used to the rapid viewing of glass slides under a microscope. However, these problems are likely to be overcome by technological advances in the future.

Riber-Hansen R, Vainer B, Steiniche T. Digital image analysis: a review of reproducibility, stability and basic requirements for optimal results. APMIS 2012; 120: 276–89. Digital image analysis (DIA) is increasingly implemented in histopathological research to facilitate truly quantitative measurements, decrease inter-observer variation and reduce hands-on time. Originally, efforts were made to enable DIA to reproduce manually obtained results on histological slides optimized for light microscopy and the human eye. With improved technical methods and the acknowledgement that computerized readings are different from analysis by human eye, recognition has been achieved that to really empower DIA, histological slides must be optimized for the digital ‘eye’, with reproducible results correlating with clinical findings. In this review, we focus on the basic expectations and requirements for DIA to gain wider use in histopathological research and diagnostics. With a reference to studies that specifically compare DIA with conventional methods, this review discusses reproducibility, application of stereology-based quantitative measurements, time consumption, optimization of histological slides, regions of interest selection and recent developments in staining and imaging techniques.

Ghrelin is a hormone produced by specialized neuroendocrine cells located in the fetal pancreas. In the adult, ghrelin has multiple effects, but in the fetus the role of ghrelin and the distribution of ghrelin-producing cells is not well documented. The aim of this study was to describe and quantitate the number of ghrelin positive cells in the pancreas during gestation. The material consisted of pancreatic tissue from 19 fetuses at different gestational ages. Immunohistochemical staining was performed, and the expression was quantitated using an automated digital image analysis system. The results showed ghrelin-producing cells as scattered single cells in ductular structures and acini throughout the gestation. From midgestation they were also found in the periphery of the islets as a rim of cells. A tendency towards a high ghrelin expression during early gestation and a stable expression from midgestation to term was observed. In conclusion, the effects of fetal ghrelin are not fully understood, but the varying distribution of ghrelin positive cells indicates different effects of ghrelin during development.

Histopathological grading of prostate cancer (PCa) is associated with significant interobserver variability. This, as well as clinical consequences of histopathological re-evaluation, was investigated. In 350 patients, histopathological re-evaluations of prostate biopsies were compared with primary pathology reports and with histopathology of the radical prostatectomy specimen. The consequences of re-evaluation for clinical workup and treatment of patients according to local algorithms were determined. For Gleason score (GS), complete agreement between primary report and re-evaluation was found in 76.9%. The cancers were assessed with higher GS at re-evaluation in 25.0% of patients in cases with primary GS ≤ 6, while scores were devaluated in 3.0% and 10.3% of the patients with primary GS = 7 and ≥ 8, respectively. Strategies for clinical evaluation and treatment were changed as a result of the biopsy re-evaluations in 19.7% and 13.1% of patients, respectively. Gleason scoring based on the radical prostatectomy specimen was higher than in both primary reports and re-evaluation of biopsies. Although a relatively high degree of concordance was found between biopsy assessments, the significant trend towards higher Gleason scoring at re-evaluation, leading to frequent changes in clinical assessments and surgical strategy, justifies re-evaluation of PCa biopsies in patients with primary GS ≤ 6.

The intensive research of recent years has suggested that the cause of ulcerative colitis (UC) involves a genetic predisposition to an uncontrolled or unbalanced immune response to luminal or epithelial antigens or against other external factors. Intercellular adhesion molecule-1 (ICAM-1) is pivotal for the influx of neutrophil granulocytes into colonic mucosa, and gene analyses have found polymorphisms in the gene encoding ICAM-1, indicating that changes in ICAM-1 function may be involved in the pathogenesis of UC. Clinical trials of the ICAM-1 antisense oligonucleotide Alicaforsen, which inhibits the synthesis of ICAM-1, have shown positive results in the treatment of patients with left-sided (distal) UC. In addition to emphasizing the central role of ICAM-1 in active stages of UC, the results provide hope for the development and introduction of a more specific and efficient treatment for UC than those currently available. This review discusses the results from studies on the expression of ICAM-1 in colonic tissue from patients with UC.

Alpha-methylacyl coenzyme A racemase (AMACR or P504S) is a mitochondrial and peroxisomal protein present in a variety of human cells. Demonstration of increased expression is used diagnostically in prostatic adenocarcinoma. AMACR is also produced by normal hepatocytes and it has been postulated that the demonstration of AMACR expression or its pattern of distribution is useful in the diagnosis of hepatocellular carcinoma (HCC) (Jiang et al., Hum Pathol 2003;34, Guzman et al., Appl Immunohistochem Mol Morphol 2006;14, Li et al., J Exp Clin Cancer Res 2008;27). The aim of the present study was to evaluate whether immunohistochemical staining for AMACR can be used in a routine histopathologic setting. Immunohistochemical staining for AMACR was performed on paraffin-embedded tissue from livers resected for HCC during 1980-2006 at Rigshospitalet, Copenhagen, Denmark (n = 44). Tumor sections as well as surrounding non-neoplastic tissues were studied. In both tumor and non-tumor tissues, intracellular localization and staining pattern were assessed and the staining intensity of AMACR was graded. The fraction of stained tumor cells was not significantly different from that of stained non-tumor cells in the same patients (p = 0.97). A significantly lower staining intensity was observed in clear cell areas (p = 0.005), but the AMACR expression did not correlate with the HCC type and could not distinguish neoplastic from non-neoplastic liver cells. AMACR is not applicable as a tool in the histopathologic diagnosis of HCC.

Long-term inflammation of the colonic mucosa during chronic inflammatory bowel disease with alternating periods of ulceration and healing may lead to the formation of finger-like projections, so-called filiform polyps. In rare cases, several filiform polyps form large tumour masses, termed giant filiform polyposis. We present a case of giant obstructing filiform polyposis in a patient without previous evidence of chronic bowel inflammation. The resected ascending colon from a 37-year-old woman was evaluated macroscopically and microscopically, and the presence of gene polymorphisms was studied by means of multiplex capillary electrophoresis single-strand conformation polymorphism assay, DNA sequencing, TaqMan analysis, and restriction enzyme cleavage. The giant filiform polyposis was restricted to a 15 cm segment of the ascending colon, and the remaining colonic mucosa was entirely without inflammatory changes. During the post-operative follow-up period, the patient developed symptoms and signs of distal bowel inflammation. Gene polymorphism studies were inconclusive as to Crohn's disease. In conclusion, we present an unusual pathological entity of giant filiform polyposis, which developed relatively rapidly in a colon without any history or macroscopic changes suggestive of chronic inflammatory bowel disease. Although the patient subsequently developed symptoms in keeping with Crohn's disease, studies of genetic polymorphism were unable to confirm this notion, and colorectal tissue has not been sampled postoperatively for histological evaluation.