The Missing Link in the Diagnostic Pathway of Prostate Cancer.

Prostate cancer is one of the most common cancers in the Western world. It is among the leading causes of cancer related death. While its incidence and survival increased significantly during the last few decades in Denmark, the mortality rate did not change for patients younger than 80 year old. Development of new techniques, such as multiparametric MRI, helps to increase the accuracy of diagnosis. However, a missing link in the diagnostic pathway may result in mistreatment if an acinar adenocarcinoma of prostate is transformed into a neuroendocrine phenotype such as small cell carcinoma.

Primary cardiac sarcomas may develop from resident or bone marrow-derived mesenchymal stem cells: use of immunohistochemistry including CD44 and octamer binding protein 3/4.

AIMS: To provide evidence that cardiac sarcomas 'not otherwise specified' express markers that might indicate their cellular origin or identify any lines of differentiation. METHODS AND RESULTS: We reviewed all 11 cases of primary undifferentiated cardiac sarcomas found in the archives of the Royal Marsden and Royal Brompton Hospitals, London, UK during the period 2000-2009. Five cases with appropriate consent and archived material were investigated using immunohistochemistry. We found that the spindle, pleomorphic or occasionally epithelioid cell sarcomas showed no lineage-specific differentiation other than partial myofibroblastic or 'myoid' differentiation (all cases). All tumours showed some degree of cytoplasmic positivity for the mesenchymal stem cell marker CD44. In contrast, no nuclear octamer binding protein 3/4 (Oct3/4) expression was seen in any of the tumours, although very patchy cytoplasmic positivity was seen in some tumours. CONCLUSIONS: The cytoplasmic positivity for CD44 and the absence of nuclear Oct3/4 suggest that the cells of these sarcomas may represent 'daughter' stem cells that no longer have the capacity for tumour initiation, but have subsequently developed new lines of partial differentiation. Primary cardiac sarcomas may arise from mesenchymal stem cells with the ability to generate tumours with multilineage differentiation.

Primary glial tumor of the retina with features of myxopapillary ependymoma.

We report a primary retinal tumor with features of myxopapillary ependymoma. The lesion occurred in a 33-year-old man with a long history of phthisis bulbi and a more recent history of pain to the right eye. Enucleated ocular globe revealed a lesion occupying most of the retinal surface. Histologically, the retina was replaced by a tumor composed of spindle cells with fibrillary cytoplasm and round to ovoid nuclei forming fascicles, perivascular pseudorosettes, microcysts, and deposition of extracellular mucins. Calcifications, metaplastic bone, and lymphoplasmacytic inflammatory infiltrate were also seen. Tumor cells expressed GFAP and S-100 and to lesser extent carbonic anhydrase II. The immunoreaction for EMA showed diffuse granular positivity, decorated a few extracellular lumina, and highlighted intracytoplasmic lumina in a few cells. Ultrastructurally, there was accumulation of extracellular material between cells and around capillaries, long interdigitating cytoplasmic processes, extracellular lumina packed with microvilli, a few junctions evident around lumina, and some ciliary basal bodies and ciliary basal rootlets. As control cases, we also investigated expression of EMA and carbonic anhydrase II in an ocular globe with retinal gliosis and three cases of myxopapillary ependymoma of the cauda equina. The lesion described here represents the first example of retinal tumor with features of myxopapillary ependymoma. Pathologic features and particularly expression of carbonic anhydrase II suggest a derivation from intrinsic glial cells of retina otherwise known as Muller cells.

Short term arterial remodelling in the aortae of cholesterol fed New Zealand white rabbits shown in vivo by high-resolution magnetic resonance imaging - implications for human pathology.

High-resolution, non-invasive imaging methods are required to monitor progression and regression of atherosclerotic plaques. We investigated the use of MRI to measure changes in plaque volume and vessel remodelling during progression and regression of atherosclerosis in New Zealand White rabbits. Atherosclerotic lesions were induced in the abdominal aorta by balloon injury and cholesterol feeding. MR images (2D) of the abdominal aorta were acquired with cardiac and respiratory gating using a fast spin echo sequence with and without fat-suppression. In an initial study on rabbits treated for 30 weeks we imaged the aortae with a spatial resolution of 250x250 micrometers with a slice thickness of 2 mm and achieved a close correlation between MRI-derived measurements and those made on perfusion pressure-fixed histological sections (r(1) = 0.83, slope p(1) < 0.01). We subsequently imaged 18 rabbits before and periodically during 12 weeks of cholesterol feeding (progression) followed by 12 weeks on normal diet (regression). Aortic wall (atherosclerotic lesion) volume increased significantly during progression and decreased during regression. In contrast, lumen volume increased during progression and did not change during regression. In conclusion, this study confirms that non-invasive, high-resolution MRI can be used to monitor progression and regression of atherosclerosis, each within 3 months and shows, for the first time in a short-term model, that positive remodelling occurs early during progression and persists through regression of atherosclerotic lesions.

[Past, present and future of digital pathology]. / A digitális patológia múltja, jelene és jövóje.

The four main aspects of applied medical information technology, which change the traditional systems of the entire health service are signal and data processing, digital modelling and interface optimisation. The information technology serving individual clinical specialties including clinical histopathology is changing at each of the four levels resulting in transformation of the communication paradigms. The object of investigation in histopathology is the digital slide, which is accessible throughout the world with no time or geographical limits. It permits the digital modelling of routine histological and/or cytological slide and it also allows measurements by using image analysis or stereology software packages. The electronic slide can be viewed, examined and diagnosed on a computer connected to a microscope, a new interface in diagnostic histopathology. This study describes the main theoretical and practical aspects, including challenges, of digital pathology and it also discusses the conditions required for successful information management. It reviews the experiences of the last one and half decades gained in the field of pathological information technology in Hungary including its main episodes and milestones of development. Introducing its present state, this paper describes the concept and the mode of investigation of the digital slide. It shows the development and use of a virtual microscope in Hungary. Based on know-how including the British experience this review describes the possible uses of digital slides, which by improving communication could have a positive effect on the entire health care system. It summarises the possible and necessary components of a digital pathology laboratory, which may include the new Slide Archive and Communication System (SACS). Using experimental data it mentions the possibility of generating primary digital pathological sample and producing the so called optical biopsy with no need for removing tissue from the patient.

Stromal cells of fibrodysplasia ossificans progressiva lesions express smooth muscle lineage markers and the osteogenic transcription factor Runx2/Cbfa-1: clues to a vascular origin of heterotopic ossification?

Fibrodysplasia ossificans progressiva (FOP) is a rare heritable genetic disorder, which is characterized pathologically by sporadic episodes of explosive growth of mesenchymal cells in skeletal muscle followed by cellular differentiation to heterotopic bone through an endochondral process. This study examined the histological origin and differentiation state of stromal cells in early FOP lesions and investigated the association between the phenotype of these FOP cells and bone formation. Interestingly, FOP lesional stromal cells were found to display characteristics of the smooth muscle (SM) cell lineage and are therefore potentially of vascular origin. These cells co-express multiple SM lineage markers along with multiple proteins associated with bone formation including the obligate osteogenic transcription factor Runx2/Cbfa-1. It is hypothesized that the stromal cells of early FOP lesions may be locally recruited vascular cells or cells of the bone marrow stroma and that these cells maintain the potential (given the correct environmental stimuli) to differentiate along an endochondral ossification pathway.

The image pyramid system--an unbiased, inexpensive and broadly accessible method of telepathology.

Although computerised information technology, including the Internet is broadly used and globally accessible it is still not a significant form of professional communications in diagnostic histopathology. The high cost of interactive dynamic telepathology systems makes their use limited outside the richest economies. In contrast static telepathology systems are relatively cheap but in practice their information content can be heavily biased by the choice of images sent by the consulting pathologist. The degree of this bias may be regarded simply as the amount of information transferred to a remote location expressed as a percentage of the total information present in the histological sample. We refer to this as the percentage of explicit versus implicit information. Another major source of bias may be found in the information transmitted in written or verbal discussion with a remote consultant. We have developed a system of static telepathology, the image pyramid, which attempts to minimise bias by transferring all of the information in a section to the consultant. It is inexpensive and should prove to be widely accessible.