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New opportunities and the adoption of digital technologies will transform the way pathology professionals and services work. Many areas of our daily life as well as medical professions have experienced this change already which has resulted in a paradigm shift in many activities. Pathology is an image-based discipline, therefore, arrival of digital imaging into this domain promises major shift in our work and required mentality. Recognizing the physical and digital duality of the pathology workflow, we can prepare for the imminent increase of the digital component, synergize and enjoy its benefits. Development of a new generation of laboratory information systems along with seamless integration of digital imaging, decision-support, and knowledge databases will enable pathologists to work in a distributed environment. The paradigm of 'cloud pathology' is proposed as an ultimate vision of digital pathology workstations plugged into the integrated multidisciplinary patient care systems. [ABSTRACT FROM AUTHOR]

Extremely large medical images, like ones of virtual slide microscopy, are beyond some limitations of the DICOM standard (e.g., a 4 Gbyte barrier, caused by 32-bit architecture). Some solutions and trade-offs have been already proposed and included in the DICOM standard (e.g., usage of JPEG2000 image compression standard, JPEG2000 interactive protocol [JPIP] and division of the images into smaller parts for placing them in the PACS). These new features lead to implementation of alternative interaction solutions simultaneously in the same PACS to serve both images of typical size (e.g., radiological) and large size virtual slide microscopy images. The paper deals with problems of (a) constructing a data and interaction model of images within PACS, (b) searching for criteria to assess image content complexity and to reach an efficient division of virtual slide microscopy images into tiles; (c) providing both the conventional DICOM services and the image interchange using JPIP. [ABSTRACT FROM AUTHOR]

A recurring issue with microstructure studies is specimen lighting. In particular, microscope lighting must be deployed in such a way as to highlight biological elements without enhancing caustic effects and diffraction. We describe here a high frequency technique due to address this lighting issue. First, an extensive study is undertaken concerning asymptotic equations in order to identify the most promising algorithm for 3D microstructure analysis. Ultimately, models based on virtual light rays are discarded in favor of a model that considers the joint computation of phase and irradiance. This paper maintains the essential goal of the study concerning biological microstructures but offers several supplementary notes on computational details which provide perspectives on analyses of the arrangements of numerous objects in biological tissues. [ABSTRACT FROM AUTHOR]

Managing patients with kidney allografts largely depends on biopsy diagnosis which is based on semiquantitative assessments of rejection features and extent of acute and chronic changes within the renal parenchyma. Current methods lack reproducibility while digital image data-driven computational models enable comprehensive and quantitative assays. In this study we aimed to develop a computational method for automated assessment of histopathology transformations within the tubulointerstitial compartment of the renal cortex. Whole slide images of modified Picrosirius red-stained biopsy slides were used for the training (n = 852) and both internal (n = 172) and external (n = 94) tests datasets. The pipeline utilizes deep learning segmentations of renal tubules, interstitium, and peritubular capillaries from which morphometry features were extracted. Seven indicators were selected for exploring the intrinsic spatial interactions within the tubulointerstitial compartment. A principal component analysis revealed two independent factors which can be interpreted as representing chronic and acute tubulointerstitial injury. A K-means clustering classified biopsies according to potential phenotypes of combined acute and chronic transformations of various degrees. We conclude that multivariate analyses of tubulointerstitial morphometry transformations enable extraction of and quantification of acute and chronic components of injury. The method is developed for renal allograft biopsies; however, the principle can be applied more broadly for kidney pathology assessment., (© 2024. The Author(s).)

In breast cancer (BC), pathologists visually score ER, PR, HER2, and Ki67 biomarkers to assess tumor properties and predict patient outcomes. This does not systematically account for intratumoral heterogeneity (ITH) which has been reported to provide prognostic value. This study utilized digital image analysis (DIA) and computational pathology methods to investigate the prognostic value of ITH indicators in ER-positive (ER+) HER2-negative (HER2-) BC patients. Whole slide images (WSIs) of surgically excised specimens stained for ER, PR, Ki67, and HER2 from 254 patients were used. DIA with tumor tissue segmentation and detection of biomarker-positive cells was performed. The DIA-generated data were subsampled by a hexagonal grid to compute Haralick's texture indicators for ER, PR, and Ki67. Cox regression analyses were performed to assess the prognostic significance of the immunohistochemistry (IHC) and ITH indicators in the context of clinicopathologic variables. In multivariable analysis, the ITH of Ki67-positive cells, measured by Haralick's texture entropy, emerged as an independent predictor of worse BC-specific survival (BCSS) (hazard ratio (HR) = 2.64, p-value = 0.0049), along with lymph node involvement (HR = 2.26, p-value = 0.0195). Remarkably, the entropy representing the spatial disarrangement of tumor proliferation outperformed the proliferation rate per se established either by pathology reports or DIA. We conclude that the Ki67 entropy indicator enables a more comprehensive risk assessment with regard to BCSS, especially in cases with borderline Ki67 proliferation rates. The study further demonstrates the benefits of high-capacity DIA-generated data for quantifying the essentially subvisual ITH properties., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Ki67 has potential clinical importance in breast cancer but has yet to see broad acceptance due to inter-laboratory variability. Here we tested an open source and calibrated automated digital image analysis (DIA) platform to: (i) investigate the comparability of Ki67 measurement across corresponding core biopsy and resection specimen cases, and (ii) assess section to section differences in Ki67 scoring. Two sets of 60 previously stained slides containing 30 core-cut biopsy and 30 corresponding resection specimens from 30 estrogen receptor-positive breast cancer patients were sent to 17 participating labs for automated assessment of average Ki67 expression. The blocks were centrally cut and immunohistochemically (IHC) stained for Ki67 (MIB-1 antibody). The QuPath platform was used to evaluate tumoral Ki67 expression. Calibration of the DIA method was performed as in published studies. A guideline for building an automated Ki67 scoring algorithm was sent to participating labs. Very high correlation and no systematic error (p = 0.08) was found between consecutive Ki67 IHC sections. Ki67 scores were higher for core biopsy slides compared to paired whole sections from resections (p ≤ 0.001; median difference: 5.31%). The systematic discrepancy between core biopsy and corresponding whole sections was likely due to pre-analytical factors (tissue handling, fixation). Therefore, Ki67 IHC should be tested on core biopsy samples to best reflect the biological status of the tumor., (© 2022. The Author(s).)

Extremely large medical images, like ones of virtual slide microscopy, are beyond some limitations of the DICOM standard (e.g., a 4 Gbyte barrier, caused by 32-bit architecture). Some solutions and trade-offs have been already proposed and included in the DICOM standard (e.g., usage of JPEG2000 image compression standard, JPEG2000 interactive protocol [JPIP] and division of the images into smaller parts for placing them in the PACS). These new features lead to implementation of alternative interaction solutions simultaneously in the same PACS to serve both images of typical size (e.g., radiological) and large size virtual slide microscopy images. The paper deals with problems of (a) constructing a data and interaction model of images within PACS, (b) searching for criteria to assess image content complexity and to reach an efficient division of virtual slide microscopy images into tiles; (c) providing both the conventional DICOM services and the image interchange using JPIP.

Unlabelled: Fabry's disease is an X-linked inborn error of glycosphingolipid metabolism caused by a deficiency of the lysosomal hydrolase alpha-galactosidase A. Due to deficiency of this enzyme activity, a progressive lysosomal accumulation of glycosphingolipids, in particular globotriaosylceramide, takes place within endothelial cells and cells of the vascular and nervous systems, myocardial cells, endothelial, and mesangial and epithelial cells of the kidney, eventually leading to organ dysfunction. The degree of renal involvement generally correlates with the progression of glycosphingolipid accumulation and may lead to renal insufficiency and failure. Renal dysfunction can progress to end-stage renal failure, which usually occurs in the third to fifth decade of life. The prevalence of this disease among males on chronic hemodialysis is different in various countries. Screening for alpha-galactosidase A deficiency by blood spot tests was performed among 536 male dialysis patients in all 42 hemodialysis centers in Lithuania in the period of April-June, 2005. All tests, showed normal galactosidase A enzymatic activity., Conclusion: No patient with suspicion of Fabry's disease was found by this screening method.

A retrospective study of 1363 native kidney biopsies, performed at Lithuanian nephrology units and investigated at the National Center of Pathology during the period of 2000-2006, was carried out. Inflammatory glomerulopathies constituted 63.6% of all primary glomerulopathies (834 cases); IgA nephropathy was the most frequent disease (35.0%). The incidence of membranoproliferative glomerulonephritis decreased from 22.6% reported in Lithuania previously (1995-1999) to 16.7% in this study; however, it was still higher compared to most European countries. Extracapillary proliferative glomerulonephritis and diffuse endocapillary proliferative glomerulonephritis accounted for 9.1% and 4.4%, respectively. Noninflammatory glomerulopathies were relatively rare: focal and segmental glomerulosclerosis made up 14.8%; minimal change disease, 9.7%; membranous nephropathy, 7.4%. However, their incidence increased compared to the previously reported in 1995-1999 (9.5%, 5.8%, and 4.3%, respectively). It can be concluded that inflammatory glomerulopathies were predominant in Lithuania in 2000-2006; however, these glomerulopathies were less prominent as compared to the previously reported data in 1995-1999.

Objective: To delineate technical aspects of vascular models with intracranial aneurysm in vitro production, suitable for angiographic imaging., Material and Methods: Wax (K2 exact, S-U-CERAMO-CAPS-WAX), Girtl's mass, gelatin, and silicone (Silicone 10015 Den Braven, Elastosil 7683/25, Elite Double 32 Shore-A, Rema-Sil) were used for model production. Construction of models was based on T-shaped plastic tube connections and lost core techniques. Images of rotational angiography, glass tubes with aneurysm, and casts obtained in human specimen were used as samples of cerebral arteries., Results: Technical aspects of vascular models production were delineated in experience of eight silicone models produced. M1 was hand made with basilar tip aneurysm; M2 was obtained according to angiography images with internal carotid artery supraclinoid part bifurcation to anterior and middle cerebral artery aneurysm. BM1 and BM2 casts were made using glass tubes with lateral aneurysm, M3--from T-shaped plastic tubes with lateral aneurysms. M4, M5, and M6 were formed using casts obtained in human specimen with basilar tip aneurysm., Conclusions: Silicone of two components is practical for casts of cerebral arteries in human specimen production. Gelatinous solution 50 degrees C diluted 1:1 with water can be used for copies of arterial casts production. Wax materials are unsuitable for making casts in a human specimen.

Unlabelled: The pathogenesis of an immune complex-mediated membranoproliferative glomerulonephritis (IMPGN) involves persistent deposition of circulating immune complexes in the glomeruli caused by persistent antigenemia. We have previously reported relatively high incidence of IMPGN in Lithuania. The objective of our study was to evaluate potential causes of persistent antigenemia in the patients with IMPGN., Material and Methods: Forty-five patients with IMPGN diagnosed on renal biopsy during 2000-2002 were retrospectively evaluated for the presence of persistent bacterial or viral infections, autoimmune diseases and other associated medical conditions. Patients with established diagnosis of systemic lupus erythematosus (SLE) before the biopsy were not included in the study., Results: A great majority (20; 44%) of the patients were found to have persistent bacterial infections of various localization. Four patients (9%) were infected with hepatitis B virus (HBV). Three (7%) patients were eventually diagnosed with SLE and another 3 (7%) had other associated pathology. In the remaining 15 (33%) patients, IMPGN remained idiopathic. Testing for hepatitis C virus (HCV) antibody was performed in 36 patients (12 of them with idiopathic IMPGN) and was negative in all patients. Testing for HCV RNA was not performed. Patients with bacterial infections were significantly younger compared to the group of idiopathic IMPGN (36.5+/-19.1 and 53.8+/-16.4, respectively, p=0.01). We conclude that persistent bacterial infection was a major potential source of antigenemia in our patients with IMPGN, particularly in the younger patients, while HBV and HCV infection was rarely detected.

Two hundred eighty patients underwent renal biopsy during the period of 1995-1999 in five nephrological centers of Lithuania. All renal biopsies materials were examined in the State Center of Pathology. In 20 patients (7.1%) membranous nephropathy was found. The main clinical presentation at the moment of renal biopsy were nephrotic syndrome (55%) and arterial hypertension (55%). Glomerulosclerosis was found in 30% of patients, interstitial fibrosis--in 40% of patients. The results of analysis showed multiple risk factors for renal failure progression: initial renal failure (p=0.000), systolic and diastolic hypertension (p=0.009 and p=0.009), proteinuria (=1 g/l, =3 g/l) (p=0.026). Membranous nephropathy was found to have a relatively good long-term prognosis - the renal survival rate in 5 years was 84.2%. Kaplan-Meier survival analysis showed that initial renal failure was risk factor (logrank p=0.018, Breslov p=0.032) associated with development of end-stage renal disease in 5 years.

Cyclosporin A (CsA) is an effective immunosuppressive drug for the prophylaxis of rejection after organ transplantation. However, CsA is potentially toxic to various tissues: kidney, liver, pancreas, nervous system, etc. The aim of this study was to ascertain the frequency of CsA nephrotoxicity incidence according to the changes in graft biopsy material and its association with whole blood CsA levels. Data were obtained from 30 recipients after cadaver or living related kidney transplantation. All patients (pts) were divided into two groups: Gr1 included 17 pts with biopsy evidence of CsA damage and Gr2 -13 pts without these changes. The mean age of recipients (38.6+/-11.3 vs 34.6+/-13.3), donor and recipient human leucocyte antigen (HLA) match (2.5/6 vs 2.3/6), cold ischemic time (12.0+/- 9.3 h vs 13.8+/-10.3 h), percentage of kidney from cadaver donors (64.7% vs 69.2%) were similar in both groups. Comparison of CsA blood levels (>200 ng/ml) between Gr1 and Gr2 revealed statistically significant differences (70.6% vs 15.4%, p<0.05), correspondingly. The mean CsA blood level was higher in Gr1 (328.7+/-153.8 ng/ml vs 202.4+/-145.6 ng/ml, p<0.03). Thus, we suggest that CsA nephrotoxicity is associated with elevated CsA levels of more than 200 ng/ml. Biopsy is a very important criteria that helps to distinguish CsA nephrotoxicity and acute rejection.

A retrospective study of 316 patients, who underwent renal biopsy, during the period of 1995-1999 in five nephrological centers of Lithuania. All renal biopsy materials were investigated in the State Center of Pathology. Male:female ratio was 204:112, the mean age 41.4 (SD 16.7) yrs., range 15-80. The main indications for renal biopsy were nephrotic syndrome (29.1%), hematuria and nonnephrotic proteinuria (27.8%). The leading type of kidney damage was primary glomerulonephritis--194 (69.3%), which was 2.4 times more frequent in males than in females. The dominant types of primary glomerulonephritis were IgA nephropathy--30.4%, membranoproliferative glomerulonephritis--26.8%, membranous nephropathy--10.3% and focal segmental glomerulosclerosis--9.8%. Renal amyloidosis was found even in 8.6% of all renal biopsies.

Collapsing glomerulopathy is a pattern of renal injury that has emerged along with the epidemic of HIV infection. The disease process is now increasingly recognized in non-HIV patients. In HIV and non-HIV patients the disease shares many clinical and pathologic features, and, we presume, pathogenetic factors. The disease entity is characterized by very heavy proteinuria frequently combined with rapidly progressive renal failure, poor outcome, glomerular collapse with hyperplasia and other degenerative changes of the visceral epithelial cells, and prominent tubulointerstitial injury with frequent microcystic changes. HIV-associated nephropathy has a higher prevalence in blacks, high frequency of intra-endothelial tubuloreticular inclusions, and prominent microcystic tubular changes. These differences, however, are not sufficient to predict the patient's HIV status from the biopsy findings alone. Collapsing glomerulopathy can also develop in association with lymphoproliferative disorders, systemic lupus erythematosus-like and other autoimmune diseases, other immune deficiency syndromes and viral infections, and in the context of immunosuppressive therapy.