Institute Of Pathology Research Articles

Německý univerzitní patolog v přemetech mimořádné doby. K biografii Franze X. Lucksche (1872–1952)

The pathologist Franz Xaver Lucksch (1872–1952) seems to have been in many ways a rather distinctive personality within the academic landscape of German medicine and medical research in Bohemia. As a member of the generation that grew up during the belle époque, he witnessed all the dramatic turnovers of Central Europe in the twentieth century. A man of considerable scientific ambitions, he became assistant professor (1904) and extraordinary professor (1914) at the Institute of Pathology (Institut für Pathologie) of the German Medical Faculty in Prague under Professor Hans Chiari (1851–1916). Having researched pellagra endemics in Romania in 1910, he returned there in the late 1930s thanks to the support of the Rockefeller Foundation. To the best of our knowledge, he published 48 academic contributions in his lifetime, infectious diseases (including tuberculosis) being the most frequent subject. Lucksch fought in the First World War, ending his military service as a lieutenant colonel of the Austro-Hungarian imperial army. Although he at first considered a professional military career in Austria even after 1918, he eventually returned from Vienna to Prague in 1919. There, he continued his medical work and research as a first assistant, which was the position he held for many years. In public life, he was active in spreading awareness of public health issues – probably in reaction to the autopsies he was carrying out. He emphasised the importance of nutrition and prevention of tuberculosis, a disease highly prevalent in Czechoslovakia at the time. But above all, he focused on physical training (Leibesübungen). In 1929–36, he headed the University Physical Training Centre (Hochschulzentrale für Leibesübungen) at the German University in Prague and the German Educational Course for Physical Training of Teachers. Aside from that, he was also a member of the German Association of Gymnasts. This is how Lucksch became acquainted and rather unfortunately politically involved with Konrad Henlein (1898–1945) and his Nazi movement among the Sudeten Germans of Czechoslovakia. At first, he was an active member but shortly after the German occupation of Bohemia and Moravia in March 1939, he found himself in a rather awkward position when the political movement he had previously endorsed started making problems for his Jewish wife and two children. His son, Franz Lucksch Jr. (1916–1966), became also a physician and made a notable scientific career after 1945. In 1936, Lucksch was appointed interim director of the Institute of Pathology. In the spring of 1939, he retired. As an emeritus, he had two part-time jobs: aside from publishing, he still did some teaching and research at the Institute during the academic year, and, in the remaining period, he worked as a pathologist at the Provincial Institute for the Mentally Ill (Landesanstalt für Geisteskranke) in Kosmonosy (Kosmanos), 65km from Prague. At this institution he performed autopsies of patients who died mainly due to extremely bad conditions. After the war, Lucksch was allowed to stay in Prague, but under rather difficult conditions, including financial issues. In connection with the prosecution of Nazi ‘euthanasia’ crimes in the 1960s, a suspicion emerged that he may have conduced tuberculosis experiments on psychiatric patients. Given the particular circumstances, however, this was highly improbable, neither has anything of that kind been proved in connection with Lucksch.

Significance of Serological Markers in Diagnosis of Acute Dengue Infection: 2021 Outbreak

Objective: To highlight the significance of Dengue anti-IgM and Dengue NS1 antigen in diagnosing Acute Dengue infection. Study Design: Cross-sectional study. Place and Duration of Study: Virology Department, Armed Forces Institute of Pathology, Rawalpindi Pakistan, from Sep to Nov 2021. Methodology: One hundred and fifty Dengue NS1-positive patients of either gender with age≥5 years were included. ELISA tested patients for detection of Dengue anti-IgM antibody. A questionnaire was used to collect demographic and personal data of each patient. Results: Out of 150 dengue NS1 positive samples, 26(17%) were positive for dengue anti-IgM. In collected samples, Dengue serological markers (NS1 and anti-IgM) positivity was observed based on ‘the day of onset of symptoms. On days 1 and 2, 54 and 44 NS1 positive samples were collected, respectively, but no one was found positive for anti-IgM. Anti-IgM was detected on day-3 and onwards. 27% Dengue anti-IgM positivity was found on day-3, which increased gradually as the time of infection increased. On day four, it was 53%; on day 5, it was 55%; on day-6, it was 60%; on day 7, it was 75%; and on day 8, it was 100%. Conclusions: The findings of present study suggested that anti-Dengue IgM antibodies are less significant than the Dengue NS1 antigen in diagnosing acute dengue infection.

ANALYSIS OF THE RESULTS OF PERCUTANEOUS VERTEBROPLASTY OF COMPRESSION FRACTURES OF BODIES OF CHEST AND LUMBAR VERTEBRAE ON THE BACKGROUND OF OSTEOPOROSIS

It is well known that the most frequent complication of osteoporosis is compression fractures of vertebral bodies. In addition to brittleness of the bones and mechanical stress, more and more evidence approving that compression fractures of vertebral bodies are related to many risk factors, such as aging, sex, concomitant morbidities of cardiovascular and cerebrovascular diseases and lifestyle (chronic smoking and alcohol consumption) are collected. Objective. Analyzing the condition of spines of the patients suffering from compression fractures of vertebral bodies on the background of osteoporosis after the performed Percutaneous vertebroplasty (PV). Methods. 553 patients who underwent hospital treatment at the spine pathology clinic of the Sytenko Institute of Spine and Joint Pathology (2005–2022) and underwent PV were examined. Results. The patients were divided into three groups depending on the number of damaged vertebrae. The 1st group included the patients with compression fractures of one vertebra (185 — 33.4 %); the 2nd group included the patients having 2 or 3 deformed vertebrae (216 — 39 %); and the 3rd group included the patients with 4–5 damaged vertebrae (152 — 27.4 %). Stages of compression of vertebral bodies during the X-ray morphometry was as follows before the surgery: I — 349 (24 %) vertebrae; II — 494 (34 %); III — 552 (38 %); and IV — 58 (4 %). We achieved the reduction of the level of compression of vertebral bodies as a result of PV in 20 % of cases (patients who noticed the manifestation of the pain syndrome within 2 weeks mostly suffered from these deformations). Conclusions. The results of analysis of PV of 553 patients with composite material and bone cement in the near and far future provide us an opportunity to state that this surgical treatment is an efficient and safe treatment method (despite the materials used). 40 (24 %) patients out of 165 patients of the group I, 52 (33 %) patients out of 157 patients of the group II and 54 (44 %) patients our of 133 patients of the group III were diagnosed with repeated compression fractures. Summarizing all the above, we should note that the more compression fractures the patient has, the higher the risk of further augmentation of other deformations of vertebral bodies is.

Infiltration of Round Blue Cell Tumors in Bone Marrow

Objective: To identify different types of round blue cell tumors on bone marrow biopsy and their pattern of marrow infiltration. Methodology: This cross-sectional descriptive study was conducted at the Department of Hematology, Armed Forces Institute of Pathology (AFIP), Rawalpindi, from July 2021 to December 2021. A total of 60 diagnosed cases of round blue cell tumors were included. Patients with acute lymphoblastic leukemia (ALL) and those receiving treatment for round blue cell tumors were excluded. Bone marrow aspiration and biopsy were performed. Peripheral film results, clinical observations, and patterns of marrow infiltration of round blue cell malignancies were analyzed using Statistical Package for the Social Sciences (SPSS) version 23. Results: The study revealed a male to female ratio of 2:1, with 40 (66.6%) males and 20 (33.3%) females. The overall average age was 5.69 ± 5.0 years. Ewing sarcoma and rhabdomyosarcoma patients did not exhibit infiltration, while three instances of retinoblastoma (9.37%) and two cases of neuroblastoma (10.52%) did. Immunohistochemistry (IHC) results for synaptophysin and chromogranin were positive for retinoblastoma and neuroblastoma, while S100 results were positive for neuroblastoma infiltration and negative for retinoblastoma. Both retinoblastoma and neuroblastoma showed diffuse, focal, and interstitial patterns of infiltration on trephine biopsy. Conclusion: Small round blue cell tumors were noted in bone marrow infiltration in 5 (8.33%) cases. Early detection of malignant cancers necessitates appropriate medical care, and in more severe cases, the need for neoadjuvant chemotherapy.

Clinical Relevance of Pathological Diagnosis of Hirschsprung's Disease with Acetylcholine-Esterase Histochemistry or Calretinin Immunohistochemistry.

Hirschsprung disease (HD) manifests as a developmental anomaly affecting the enteric nervous system, where there is an absence of ganglion cells in the lower part of the intestine. This deficiency leads to functional blockages within the intestines. HD is usually confirmed or ruled out through rectal biopsy. The identification of any ganglion cells through hematoxylin and eosin (H&E) staining rules out HD. If ganglion cells are absent, further staining with acetylcholine-esterase (AChE) histochemistry or calretinin immunohistochemistry (IHC) forms part of the standard procedure for determining a diagnosis of HD. In 2017, our Institute of Pathology at University Hospital of Heidelberg changed our HD diagnostic procedure from AChE histochemistry to calretinin IHC. In this paper, we report the impact of the diagnostic procedure change on surgical HD therapy procedures and on the clinical outcome of HD patients. We conducted a retrospective review of the diagnostic procedures, clinical data, and postoperative progress of 29 patients who underwent surgical treatment for HD in the Department of Pediatric Surgery, University of Heidelberg, between 2012 and 2021. The patient sample was divided into two groups, each covering a treatment period of 5 years. In 2012-2016, HD diagnosis was performed exclusively using AChE histochemistry (AChE group, n = 17). In 2017-2021, HD diagnosis was performed exclusively using calretinin IHC (CR group, n = 12). There were no significant differences between the groups in sex distribution, weeks of gestation, birth weight, length of the aganglionic segment, or associated congenital anomalies. Almost half of the children in the AChE group, twice as many as in the CR group, required an enterostomy before transanal endorectal pull-through procedure (TERPT). In the AChE group, 4 patients (23.5%) required repeat bowel sampling to confirm the diagnosis. Compared to the AChE group, more children in the CR group suffered from constipation post TERPT. Elevated AChE expression is linked to hypertrophied extrinsic cholinergic nerve fibers in the aganglionic segment in the majority of patients with HD. The manifestation of increased AChE expression develops over time. Therefore, in neonatal patients with HD, especially those in the first 3 weeks of life, an increase in AChE reaction is not detected. Calretinin IHC reliably identifies the presence or absence of ganglion cells and offers multiple benefits over AChE histochemistry. These include the ability to perform the test on paraffin-embedded tissue sections, a straightforward staining pattern, a clear binary interpretation (negative or positive), cost-effectiveness, and utility regardless of patient age. The ability of calretinin IHC to diagnose HD early and time-independently prevented repeated intestinal biopsies in our patient population and allowed us to perform a one-stage TERPT in the first months of life, reducing the number of enterostomies and restoring colonic continuity early. Patients undergoing transanal pull-through under the age of 3 months require a close follow-up to detect cases with bowel movement problems.

Morphological Evaluation and Immunohistochemical Analysis of the Reparative Potential of the Buccal Fat Pad.

Background and Objectives: There are many surgical techniques for oroantral communication treatment, one of which is the buccal fat pad. Of particular interest is the high reparative potential of the buccal fat pad, which may be contributed to by the presence of mesenchymal stem cells. The purpose of this work is to evaluate the reparative potential of BFP cells using morphological and immunohistochemical examination. Materials and Methods: 30 BFP samples were provided by the Clinic of Maxillofacial and Plastic Surgery of the Russian University of Medicine (Moscow, Russia) from 28 patients. Morphological examination of 30 BFP samples was performed at the Institute of Clinical Morphology and Digital Pathology of Sechenov University. Hematoxylin-eosin, Masson trichrome staining and immunohistochemical examination were performed to detect MSCs using primary antibodies CD133, CD44 and CD10. Results: During staining with hematoxylin-eosin and Masson's trichrome, we detected adipocytes of white adipose tissue united into lobules separated by connective tissue layers, a large number of vessels of different calibers, as well as the general capsule of BFP. The thin connective tissue layers contained neurovascular bundles. Statistical processing of the results of the IHC examination of the samples using the Mann-Whitney criterion revealed that the total number of samples in which the expression of CD44, CD10 and CD133 antigens was confirmed was statistically significantly higher than the number of samples where the expression was not detected (p < 0.05). Conclusions: During the morphological study of the BFP samples, we revealed statistically significant signs of MSCs presence (p < 0.05), including in the brown fat tissue, which proves the high reparative potential of this type of tissue and can make the BFP a choice option among other autogenous donor materials when eliminating OAC and other surgical interventions in the maxillofacial region.

[Introduction to renal pathology].

In recent decades, nephropathology has developed worldwide as asubspeciality of pathology, which requires special methodological and technical equipment to process the material and specific clinical and pathological expertise to interpret the findings. These special requirements mean that nephropathology is not available at all pathology institutes, but is carried out on alarge scale in afew highly specialised centres. The history of nephropathology, or in anarrower sense the specialised histopathological examination of kidney biopsies, began in 1958 with the first use or performance of akidney biopsy [1]. It thus replaced the practice of urinalysis, which had been common since the Middle Ages, as adiagnostic tool for kidney diseases. Specialised techniques such as immunofluorescence or immunohistology but also electron microscopy are required to assess specific renal changes, for which the examination of renal biopsies is one of the few remaining routine applications today. In Germany and German-speaking countries, the discipline developed thanks to the work of outstanding people in the field of pathology who were primarily involved in this discipline and had the necessary technical and human resources in their laboratories to ensure that these biopsies could be analysed.

BIOCHEMICAL PARAMETERS OF BLOOD OF LABORATORY ANIMALS IN CASE OF PROLONGED CONTACT WITH THE RESEARCH MATERIAL

The purpose of this study was to determine the biochemical parameters of blood of laboratory animals in prolonged contact with the experimental material&#x0D; Materials and methods. An experimental study was conducted in the laboratories and vivarium of the State Institution "Institute of Spine and Joint Pathology named after Prof. M.I. Sitenko" on 28 white laboratory rats aged 6 months with a body weight of 200 to 250 grams. The animals were randomly divided into two groups: a control group (14 rats) and an experimental group (14 rats), which were exposed to dental glass ionomer cement at a dose of 1.0 mg/kg. Toxic effects were evaluated for 1 month. The blood sampling procedure included tail vein dilation, disinfection, tail fixation, and blood collection. The study was conducted in special conditions with full feeding.&#x0D; Results. The study found no significant negative effects of prolonged use of dental glass ionomer cement (GIC) on kidney function. Analysis of diuresis, urea and creatinine levels in urine and blood serum showed no statistically significant differences between males and females. No sugar, ketones, or protein were detected in the animals' urine. Serum creatinine levels were (65.47±4.6) μmol/l in males and (63.38±7.1) μmol/l in females, while serum urea levels were (4.84±0.47) μmol/l in males and (4.67±0.42) μmol/l in females. Urinary urea levels were (374.35±20.7) mmol/l in males and (371.15±22.3) mmol/l in females.&#x0D; Conclusions. The obtained results of the study indicate statistically significant deviations in the studied indicators of the functional state of the kidneys both in males and females after prolonged use of dental glass-inomer cement based on polyacrylate carboxylate. The presence of sugar, ketones and protein was not detected in the urine of the animals. The analysis of serum creatinine levels showed no statistically significant differences between the conditions, and serum urea levels did not differ between them either. Thus, it can be concluded that the use of glass-inomer cement has no negative effect on the functional state of the kidneys in the studied animals.

A clinicopathological study about the epidemiology of granulosa cell tumors in Lebanon

BackgroundGranulosa Cell Tumors (GCT) are considered the most frequent type of sex-cord stromal tumors. These tumors constitute 3-6% of neoplasms of the ovaries. GCTs are divided into 2 types: Juvenile GCT (JGCT) and Adult GCT (AGCT). Most patients are diagnosed early in the course of the disease and tend to have a favorable prognosis. In the surgical treatment of GCT, two main factors play role in the determination of feasibility of the surgery: age and tumor stage.MethodsA retrospective study was conducted on 65 consecutive female patients diagnosed with ovarian GCT at different hospitals across Lebanon who were referred to the National Institute of Pathology, Beirut-Lebanon, between January 2000 and January 2020. Then, they were divided according to types: adult versus juvenile type. Statistical analysis was carried out using Stata, version 16.ResultsThe incidence of GCT in a Lebanese population was 16.2 per million per year. The mean age of the studied population was 55.6 years. AGCT was the most common with a prevalence of 91% versus 19% for JGCT. Also, inhibine (the most important immunomarker) was found in 77.2% of adult cases. High mitotic index and high tumor size which are predictors for poor prognosis were respectively 20% and 36.9%. Concerning the histopathological features, Grooved nuclei and Exner bodies were less frequently observed in juvenile type (16.7% for both) compared to adult type (36.9%). Most patients with GCT were diagnosed in the early course of disease mainly due to the manifestation of the symptoms as abdominal pain, postmenopausal bleeding or intermenstrual bleeding, and the good diagnosis and screening practices in Lebanon. Regarding the recurrent cases, a significant correlation with high mitotic index (76.9%), high tumor size (92.3%) and advanced stage (46% for stage 3 and 46% for stage 4) was found with a p < 0.05.ConclusionsThe incidence of GCT in the Lebanese population is 16.2 per million per year. The majority of patients with GCT in Lebanon are of Adult type representing around 90% of cases. Older age, high mitotic index and big tumor size are predictors for poor outcomes.

Clinico-Hematological Patterns of Patients Presenting With Erythrocytosis

Objective: To assess the frequency of erythrocytosis and compare the clinical features and haematological parameters in patients presenting with primary and secondary erythrocytosis in the Pakistani population. Study Design: Cross-sectional study. Place and Duration of Study: Armed Forces Institute of Pathology, Rawalpindi Pakistan, from May 2020 to May 2021. Methodology: Eighty-three subjects presenting with marked erythrocytosis (Hb-17 g/dl or more, HCT – 50% or more) were included in the study, while those admitted with conditions leading to spurious polycythaemia or patients on diuretics were excluded. Polycythaemia vera was diagnosed as per revised WHO criteria 2016. Results: Only 23 subjects (27.71%) fulfilled the diagnostic criteria for Polycythaemia vera, while 60 subjects (72.29%) had secondary erythrocytosis. Significant differences were observed in haematological patterns between Polycythaemia vera and Secondary erythrocytosis patients. Of the 23 Polycythaemia vera subjects, 20(86.9%) were males and only 3(13.1%) were females, whereas 35(58.3%) out of 60 subjects with secondary erythrocytosis were males and 25(41.6%) were females (p=0.01). Males showed a higher frequency of Polycythaemia vera and, hence, of Janus Kinase2 positivity than females (Odds ratio=0.23, p=0.02). Conclusion: Polycythemia vera is less common than secondary erythrocytosis in the local population. Males showed a higher frequency of Polycythemia vera and, hence, of Janus Kinase2 positivity than females.

Chronic Granulomatous Disease; Experience of a Rare Primary Immunodeficiency from a Tertiary Care Center in Pakistan

Objective: To determine the clinical parameters, consanguinity of parents, previous family history of primary immunodeficiency (PID) and Neutrophil oxidative index (NOI) of Dihydrorhodamine (DHR) assay in chronic granulomatous disease (CGD). Study Design: Cross-sectional study. Place and Duration of Study: Immunology Department, Armed Forces Institute of Pathology, Rawalpindi, Pakistan, from Jan 2015 to Dec 2020. Methodology: A total of 18 patients with chronic granulomatous disease were diagnosed over six years by Dihydrorhodamine assay on flow cytometry, in our institute. Results: The mean age of patients at the time of symptoms was 4.0±3.01 months, while diagnosis was made at the mean age of 42.02±46.00 months. In 6 years, 13(72%) males and 5(28%) females were diagnosed with chronic granulomatous disease by DHR assay on flow cytometry. Parents of fifteen patients (83%) had consanguineous marriages, and 8(44%) patients had positive family history of PIDs. DHR assay showed two mothers had carrier states. The commonest clinical presentation noted was recurrent respiratory tract infections in 16 (89%) patients, repeated abscesses were seen in 13 (72%) and 5(28%) patients had a history of tuberculosis. Conclusion: Chronic granulomatous disease should be suspected in patients with repeated chest infections (especially with catalase-positive organisms), abscesses, diarrhoea and death of siblings at an early age with undiagnosed PID.

[Histomolecular classification of urothelial carcinoma of the urinary bladder : From histological phenotype to genotype and back].

Of all urothelial carcinomas (UCs), 25% are muscle invasive and associated with a5-year overall survival rate of 50%. Findings regarding the molecular classification of muscle-invasive urothelial carcinomas (MIUCs) have not yet found their way into clinical practice. Prediction of molecular consensus subtypes in MIUCs with artificial intelligence (AI) based on histologic hematoxylin-eosin (HE) sections. Pathologic review and annotation of The Cancer Genome Atlas (TCGA) Bladder Cancer (BLCA) Cohort (N = 412) and the Dr. Senckenberg Institute of Pathology (SIP) BLCA Cohort (N = 181). An AI model for the prediction of molecular subtypes based on annotated histomorphology was trained. For afive-fold cross-validation with TCGA cases (N = 274), an internal TCGA test set (N = 18) and an external SIP test set (N = 27), we reached mean area under the receiver operating characteristic curve (AUROC) scores of 0.73, 0.8 and 0.75 for the classification of the used molecular subtypes "luminal", "basal/squamous" and "stroma-rich". By training on correlations to individual molecular subtypes, rather than training on one subtype assignment per case, the AI prediction of subtypes could be significantly improved. Follow-up studies with RNA extraction from various areas of AI-predicted molecular heterogeneity may improve molecular classifications and thereby AI algorithms trained on these classifications.

Expression of JAK2 V617F Mutation in BCR - ABL Negative Myeloproliferative Neoplasms

OBJECTIVE: To detect the presence of JAK2V617F mutation in BCR - ABL negative myeloproliferative neoplasms and to stratify high risk patients for targeted therapy.PLACE AND DURATION OF STUDY: Department of Haematology, Armed forces institute of Pathology (AFIP), Rawalpindi, from Dec 2023 to Oct 2023.STUDY DESIGN: Descriptive cross sectional studyMETHODOLOGY: A total of 40 consecutive patients of BCR - ABL 1 negative myeloproliferative disorders were included in the study after being diagnosed according to WHO defined haematological criteria for each disorder and performing bone marrow examination under aseptic measures. Informed consent and ethical approval were obtained from each individual. All patients had their blood samples examined for the G-T point mutation (V617F) in the JAK2 gene located on chromosome 9, utilizing allele-specific real-time qualitative polymerase chain reaction (RT-qPCR). Results were analyzed by using SPSS version 22.RESULTS: Out of total 40 patients included in our study 21(52.5%) had Polycythemia Vera (PV), 15 (37.5%) had Primary myelofibrosis (PMF) and 4 (10%) had Essential thrombocythemia (ET). JAK2 mutation was found in 20 (95.2%) patients of PV, 9 (60%) patients of PMF and 2 (50%) patients of ET with a significant p-value of ˂ 0.001.CONCLUSIONS: JAK2 V617F is a useful clinical marker for establishing diagnosis and separating high risk patients for specific targeted therapy.

Uloga ekspresije humanog epididimisnog proteina 4 u odnosu na kliničko-patološke karakteristike tumora bubrega

Introduction: Widespread routine ultrasound diagnostics enables early detection of kidney tumors. However, due to nonspecific symptomatology and signs that usually appear as the disease progresses, there are still patients whose diagnosis is made only in advanced stages of the disease. Aim: Our aim was to investigate the correlation of human epididymis protein 4 (HE4) expression, including the intensity and localization of HE4 positivity, with the clinical and pathohistological characteristics of kidney tumors. Material and Methods: The study included 96 kidney tumors diagnosed between 2010 and 2013 at the Institute of Pathology in Belgrade. Anti-HE4 antibodies were used for immunohistochemical analysis. Demographic, clinical, and pathohistological characteristics were examined in relation to HE4 expression. Results: No correlation was observed between HE4 expression in kidney tumors and patients' gender and the nuclear grade of tumors. However, HE4 expression was significantly more frequent in larger tumors, specifically in T3 and T4 tumors, compared to T1 and T2 tumors (p=0.009; p=0.006, respectively). No correlation was observed between HE4 expression and the pathohistological type of kidney tumors, but it is important to emphasize that membrane expression of HE4, unlike most renal cell carcinomas, was not observed in oncocytomas. Conclusion: It's possible that HE4 plays a role in progression of kidney tumor growth. Membrane expression of HE4 could be used as a new parameter in differentiating renal cell carcinomas from oncocytomas.

Extrapulmonary tuberculosis - A cross-sectional study comparing the utility of Ziehl-Neelsen stain and immunohistochemistry

Background: Tuberculosis (TB) continues to be a significant global health issue despite known causes and effective treatments. Factors such as virulent strains, drug resistance, and the human immunodeficiency virus pandemic, especially in India, contribute to its prevalence. Mycobacterium tuberculosis, the TB agent, can evade immune responses, persisting within host cells. A distinct feature of TB, granuloma formation, can also appear in diseases such as leprosy, histoplasmosis, and non-infectious conditions like Crohn’s disease. Proper diagnosis is vital, as in resource-limited countries, TB treatment often relies on presumptive diagnoses based on imaging and symptoms, leading to high false positive rates. Aims and Objectives: This study aims to compare the utility of Ziehl-Neelsen (ZN) staining and immunohistochemistry (IHC) staining in suspected extrapulmonary TB lesions. Materials and Methods: This is a retrospective cross-sectional study conducted at the Institute of Pathology, Rajiv Gandhi Government General Hospital, Chennai, over a 2-year period from August 2015 to July 2017. Fifty cases out of the 198 suspected extrapulmonary TB lesions were selected for the study. Results: About 12% of cases were positive for acid-fast bacilli by ZN staining, whereas 82% of cases were positive for acid-fast bacilli by IHC staining. P value was found to be &lt;0.001 by McNemar test which was statistically significant. Conclusion: Diagnosing extrapulmonary TB can be challenging because the disease presents with various clinical manifestations and the bacterial load may be low. Immunohistochemistry is superior to ZN staining for localization of the tubercle bacilli and thus can serve as an effective ancillary technique in diagnoses of extrapulmonary TB in formalin-fixed paraffin embedded tissue sections.

Expression of ZAP 70 in Chronic Lymphocytic Leukemia (CLL) and its Correlation with Clinical Stages

Objective: To ascertain the levels of ZAP-70 expression within the context of Chronic Lymphocytic Leukemia (CLL) patients and to subsequently analyze the potential correlations between ZAP-70 expression and the clinical staging of the disease. Study Design &amp; Setting: Cross-sectional, descriptive study. Department of Hematology, Armed Forces Institute of Pathology (AFIP), Rawalpindi from July 2021 to December 2021. Methodology: We included 73 CLL patients of various ages and both genders. and patients having lymphoproliferative disorders other than CLL were excluded. Sysmex XN-3000 was used to do complete blood counts. Diagnosis of CLL was confirmed immunophenotypically by flow cytometry. Samples were processed by standard methods for ZAP70 analysis. Descriptive statistics were expressed in terms of mean ± standard deviation (SD). A Chi-square test was conducted, with a significance level of p-value =0.05 being considered significant. Results: Among 73 patients, 24 were females (32.9%) and 49 were males (67.1%). Females had a mean age of 69.00±9.47 years, whereas males had a mean age of 65.73±11.12 years. ZAP-70 expression was positive in 8 (11%) and negative in 65 (89.0%) cases. The expression of ZAP-70 in CLL and its correlation with Binet Stages was significant (p=0.002). ZAP- 70 expression in males and females showed no significant difference (p 0.059). ZAP-70 analysis showed no significant difference in patients with age more than 60 years from = 60 years of age (p= 0.275) Conclusion: ZAP-70 gene expression should be used in routine laboratory settings and can be correlated with the clinical stages of CLL

Immunohistochemical FAP Expression Reflects 68Ga-FAPI PET Imaging Properties of Low- and High-Grade Intraductal Papillary Mucinous Neoplasms and Pancreatic Ductal Adenocarcinoma.

Pancreatic intraductal papillary mucinous neoplasms (IPMNs) are grossly visible (typically > 5 mm) intraductal epithelial neoplasms of mucin-producing cells, arising in the main pancreatic duct or its branches. According to the current 2-tiered grading scheme, these lesions are categorized as having either low-grade (LG) dysplasia, which has a benign prognosis, or high-grade (HG) dysplasia, which formally represents a carcinoma in situ and thus can transform to pancreatic ductal adenocarcinoma (PDAC). Because both entities require different treatments according to their risk of becoming malignant, a precise pretherapeutic diagnostic differentiation is inevitable for adequate patient management. Recently, our group has demonstrated that 68Ga-fibroblast activation protein (FAP) inhibitor (FAPI) PET/CT shows great potential for the differentiation of LG IPMNs, HG IPMNs, and PDAC according to marked differences in signal intensity and tracer dynamics. The purpose of this study was to biologically validate FAP as a target for PET imaging by analyzing immunohistochemical FAP expression in LG IPMNs, HG IPMNs, and PDAC and comparing with SUV and time to peak (TTP) measured in our prior study. Methods: To evaluate the correlation of the expression level of FAP and α-smooth muscle actin (αSMA) in neoplasm-associated stroma depending on the degree of dysplasia in IPMNs, 98 patients with a diagnosis of LG IPMN, HG IPMN, PDAC with associated HG IPMN, or PDAC who underwent pancreatic surgery at the University Hospital Heidelberg between 2017 and 2023 were identified using the database of the Institute of Pathology, University Hospital Heidelberg. In a reevaluation of hematoxylin- and eosin-stained tissue sections of formalin-fixed and paraffin-embedded resection material from the archive, which was originally generated for histopathologic routine diagnostics, a regrading of IPMNs was performed by a pathologist according to the current 2-tiered grading scheme, consequently eliminating the former diagnosis of "IPMN with intermediate-grade dysplasia." For each case, semithin tissue sections of 3 paraffin blocks containing neoplasm were immunohistologically stained with antibodies directed against FAP and αSMA. In a masked approach, a semiquantitative analysis of the immunohistochemically stained slides was finally performed by a pathologist by adapting the immunoreactive score (IRS) and human epidermal growth factor receptor 2 (Her2)/neu score to determine the intensity and percentage of FAP- and αSMA-positive cells. Afterward, the IRS of 14 patients who underwent 68Ga-FAPI-74 PET/CT in our previous study was compared with their SUVmax, SUVmean, and TTP for result validation. Results: From 98 patients, 294 specimens (3 replicates per patient) were immunohistochemically stained for FAP and αSMA. Twenty-three patients had LG IPMNs, 11 had HG IPMNs, 10 had HG IPMNs plus PDAC, and 54 had PDAC. The tumor stroma was in all cases variably positive for FAP. The staining intensity, percentage of FAP-positive stroma, IRS, and Her2/neu score increased with higher malignancy. αSMA expression could be shown in normal pancreatic stroma as well as within peri- and intraneoplastic desmoplastic reaction. No homogeneous increase in intensity, percentage, IRS, and Her2/neu score with higher malignancy was observed for αSMA. The comparison of the mean IRS of FAP with the mean SUVmax, SUVmean, and TTP of 68Ga-GAPI-74 PET/CT showed a matching value increasing with higher malignancy in 68Ga-FAPI-74 PET imaging and immunohistochemical FAP expression. Conclusion: The immunohistochemical staining of IPMNs and PDAC validates FAP as a biology-based stromal target for invivo imaging. Increasing expression of FAP in lesions with a higher degree of malignancy matches the expectation of a stronger FAP expression in PDAC and HG IPMNs than in LG IPMNs and corroborates our previous findings of higher SUVs and a longer TTP in PDAC and HG IPMNs than in LG IPMNs.

[Artificial intelligence in pathological anatomy].

The review presents key concepts and global developments in the field of artificial intelligence used in pathological anatomy. The work examines two types of artificial intelligence (AI): weak and strong ones. A review of experimental algorithms using both deep machine learning and computer vision technologies to work with WSI images of preparations, diagnose and make a prognosis for various malignant neoplasms is carried out. It has been established that weak artificial intelligence at this stage of development of computer (digital) pathological anatomy shows significantly better results in speeding up and refining diagnostic procedures than strong artificial intelligence having signs of general intelligence. The article also discusses three options for the further development of AI assistants for pathologists based on the technologies of large language models (strong AI) ChatGPT (PathAsst), Flan-PaLM2 and LIMA. As a result of the analysis of the literature, key problems in the field were identified: the equipment of pathology institutions, the lack of experts in training neural networks, the lack of strict criteria for the clinical viability of AI diagnostic technologies.

Myoglobin Cast Nephropathy, A Series of Five Cases

Acute kidney injury is a potential complication of severe rhabdomyolysis, which occur mostly due to excessive release of myoglobin from necrosed muscle cells. The major causes of rhabdomyolysis in Indian subcontinent include wasp sting, snake envenomation, strenuous exercise and seizures, etc. The main pathophysiology of AKI due to tubular obstruction, renal vasoconstriction and tubular damage due to myoglobin casts in the tubular lumen. With raised serum creatinine level these patients also show remarkably high serum creatine phosphokinase (CPK). On light microscopy myoglobin casts present as granular eosinophilic pigment casts, sometimes may mimic haemoglobin casts or bile casts. To differentiate the myoglobin casts from other, immunohistochemistry for myoglobin is used in most of the centers worldwide now days. A good number of patients need haemodialysis and most of them recover well, however early diagnosis and timely intervention is warranted. Here we report five cases of myoglobin cast nephropathy in a year at department of histopathology, Armed Forces Institute of Pathology (AFIP), Dhaka, following different non traumatic causes, diagnosed by immunohistochemistry for myoglobin.

In Ukrainian

The purpose of the review is to find, generalize and analyze scientific data related to the specifics of the interaction of chemotherapeutic official drugs and nanocomposites based on them with malignant cells and tumors, primarily characterized by the emergence of drug resistance, the determination of promising directions and ways to overcome it, and the creation of new effective nanocomposite remedies for use in antitumor chemotherapy. The given data indicate the relevance of the topic. Targeted studies of the resistance of malignant cells and neoplasms to chemotherapeutic drugs have been carried out since the 1990s. The majority of works were performed according to the methodology, that involves the traditional use of chemotherapeutic drugs. In these works, the principle of the multifactorial nature of resistance was determined, the processes and mechanisms of its implementation were studied, related to the reduction of the accumulation of the chemotherapeutic drug in cells, the increase in the activity of detoxification systems, the strengthening of DNA repair processes, the reduction of apoptosis, and autophagy. A number of promising substances and influencing factors contributing to overcoming of resistance have been identified. However, the discovered ways to overcome the resistance of malignant cells and neoplasms to the corresponding drugs are at the stages of laboratory, preclinical, or, in the best case, clinical research. At the same time, it is not excluded that the use of the latest highly effective chemotherapeutic drugs will lead to the emergence of new mechanisms of resistance. Thus, at this time the results of research on the traditional use of chemotherapeutic drugs constitute a significant fundamental and practically important development regarding the determination of mechanisms of drug resistance, however, the problem of its medicinal overcoming remains far from being solved, and the used approaches give the impression of dead ends. With the development of nanotechnology, new scientific directions have been initiated and a significant amount of researches has been carried out, devoted to the creation and search for promising applications in oncology of nanocomposites based on bioinert, biocompatible and bioactive nanoparticle materials and modern chemotherapeutic drugs. It should be emphasized that all these works contain data indicating the advantages of introducing nanocomposite drugs into clinical practice, compared to the use of chemotherapeutic drugs in traditional forms. Against this background, purposeful researches are distinguished carried out by scientists of O.O. Chuiko Institute of Surface Chemistry of National Academy of Sciences of Ukraine and R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology of National Academy of Sciences of Ukraine in the field of creation of modern polyfunctional nanocomposite chemotherapeutic agents for use in antitumor therapy, capable of overcoming drug resistance of malignant cells and neoplasms. So, at O.O. Chuiko Institute of Surface Chemistry of National Academy of Sciences of Ukraine for the first time magnetic fluids were synthesized containing antitumor drugs cisplatin, doxorubicin, gemcitabine, corresponding antibodies, their physicochemical properties were studied, and parameters for standardization were determined. At R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology of National Academy of Sciences of Ukraine the antitumor properties of magnetic fluids were studied. On the basis of magnetic fluid with cisplatin, the first native magnetosensitive oncological drug "Feroplat" has been proposed, which has no analogues in the world. Feroplat is a standardized tool for increasing the effectiveness of chemotherapy and overcoming drug resistance of malignant neoplasms, intended for the delivery of cytostatics directly to the tumor tissue. This ensures its maximum entry into the cells and helps to increase the therapeutic effect. In order to introduce "Feroplat" into production and clinical practice, its preclinical tests were successfully performed. The analysis of the given data indicates the priority of works in the field of creation of new nanocomposite chemotherapeutic drugs for use in antitumor therapy, capable of overcoming drug resistance of malignant cells and neoplasms. The facts of overcoming the drug resistance of malignant neoplasms to cisplatin with the new native oncological drug "Feroplat", as well as high indicators of cytotoxic / cytostatic activity of nanobiocomposites based on saline solution, magnetite and cisplatin, doxorubicin, gemcitabine, etc., may indicate the fundamental need to change approaches to the use of modern antitumor chemotherapeutic agents – by replacing their traditional molecular forms with appropriate nanocomposite forms.