INTRODUCTION:Extra-gastrointestinal stromal tumors (EGISTs) are non-gastrointestinal sarcomas originating from Cajal-like cells. Recent studies show the tumor microenvironment is crucial and highlight the importance of intra-tumoral leukocyte populations in malignancies, which are greatly impacting treatment strategies in EGISTs. AIM AND OBJECTIVES:This study aims to characterize intra-tumoral leukocyte populations in EGISTs, correlating proliferative index (ki67) with leukocyte density and examining age-related effects on proliferative activity and immune response. METHODS:We conducted a retrospective analysis on 25 patients with EGIST who came at "Victor Babes" National Institute of Pathology and Bucharest University Emergency Hospital between January 2007 and June 2020. After excluding five patients, a total of 19 subjects were included in the present study. Immunohistochemistry utilizing CD5, CD20, CD45 and ki67 antibodies identified and assessed intratumoral lymphocytes, analyzed via QuPath software. Statistical analyses included Pearson correlation, Kruskal-Wallis tests and Bonferroni corrections. RESULTS:The mean age of patients diagnosed with EGIST was 51 years; ki67 expression varied among morphological types. Immunohistochemistry revealed distinct tumor-infiltrating lymphocytes (TIL) densities with significant associations between ki67 and TIL-CD05/CD20 positive cells. Age-related correlations were noted, which highlighted complexities within the tumor microenvironment. CONCLUSION:Our findings emphasize the role of the immune microenvironment in EGISTs, showing significant correlations between ki67 expression and TIL densities as well as age-related associations. This study enhances our understanding of EGIST pathophysiology, urging further exploration for improved therapeutic approaches and comprehensive insights into immune responses in EGISTs.

Mediastinal tumors are exceedingly rare during fetal development, presenting significant diagnostic challenges and potentially leading to severe outcomes such as stillbirth or metastatic disease if not promptly identified and managed. Pleuropulmonary blastomas are primitive mesenchymal tumors often linked to mutations in the DICER1 gene, indicating a hereditary pattern associated with other common adult neoplasms with dominant inheritance. This report describes a case involving a 20-year-old Caucasian woman whose pregnancy was complicated by a stillbirth in the second trimester. Initial suspicions of a mediastinal tumor arose from blood tests and ultrasound examinations during pregnancy surveillance. However, the definitive diagnosis of a type II pleuropulmonary blastoma was established through a pathological examination at autopsy. This case underscores the complexities of diagnosing fetal mediastinal tumors and contributes to the sparse literature on neonatal pleuropulmonary blastomas. Our comprehensive review of the differential diagnoses and literature emphasizes the unique characteristics of pleuropulmonary blastoma and its similarities to other soft tissue sarcomas, enhancing understanding of their clinical and genetic profiles.

Ulcerative colitis (UC) is a chronic immune-mediated inflammatory disorder affecting the colon, which displays an increasing incidence worldwide and is characterized by symptoms of rectal inflammation such as rectal bleeding, tenesmus and multiple stools daily. The diagnosis of UC is not easy to establish, therefor an overall interpretation of the clinical manifestations together with the results of the laboratory tests, lower gastrointestinal endoscopic examination (colonoscopy) and histopathology examination findings are advisable. The choice of therapy for ulcerative colitis is based on activity, severity and extension of lesions and may include oral, systemic and topic therapy, as well as surgery. Patients with ulcerative colitis are generally immunocompromised predisposed to opportunistic infections. We present the case of a male aged 70 years diagnosed with ulcerative colitis with insidious evolution under systemic treatment, complicated with Fournier’s gangrene which is a very rare complication of ulcerative colitis that should be kept in mind. A multidisciplinary approach including urologists and colorectal surgeons is the key to define best individualized management.

Anorectal melanoma (ARM) is an extremely rare and aggressive malignancy. There is no standard therapeutic management, mainly due to scarcity of data and randomized control trials regarding the optimal surgical strategy. We present the case of a male patient aged 65 years in our hospital, presenting perineal pain and rectal bleeding. Patient’s performance status (PS) was good. Hematological analysis revealed normocytic normochromic anemia. In the rectoscopy, an anal canal tumor formation was identified. The diagnosis of ulcerated melanoma was confirmed at the histopathological examination. The pelvic MRI detected a circumferential parietal thickening, posteriorly accentuated at the level of the anal canal, about 4.4 cm long, situated 2 cm from the external anal orifice, causing a subtotal lumen stenosis. The patient underwent abdominoperineal resection (APR). Postoperative course was favorable and the patient was discharged on the 13th postoperative day, with no complications. A multidisciplinary cancer care team will prove to be of substantial value, because it may develop a personalized treatment plan for this unusual tumor. Although the therapeutic approach is still controversial, surgery is considered the mainstay therapy.

Chromophobe renal cell carcinoma (CHRCC) is known for morphologic variability. Besides classic morphology, several other patterns like pigmented adenomatoid, multicystic, even papillary were documented. 10 cases of CHRCC composed of small cell population in various percentages that were analysed using morphologic parameters, immunohistochemistry and next generation sequencing. Patients were 5 males and 5 females with 40-78 age range. Size of tumors ranged from 2.2 cm to 11 cm (mean 5.17 cm). Small cell component comprised 10-80% of total tumor volume, the rest was formed by cells with classic morphology. Immunohistochemical profile followed typical CHRCC immunophenotype with positivity for CD117, CK7 among others. Neuroendocrine markers were negative. Mutations of 13 genes were found: DCIER1, FGFR3, JAK3, SUFO, FAM46C, FANCG, MET, PLCG2, APC, POLE, EPICAM, MUTYH, AR. However, only mutation of PLCG2 is listed as pathogenic. Recognition of small cell variant of CHRCC is not problematic in tumors, where “classic” CHRCC component is present. In limited material, like core biopsy, recognising this pattern could be troublesome. Very problematic might be in limited material like core biopsy. From our limited data it seems, that small cell morphology has no influence on prognosis.

Clear cell renal cell carcinoma (CCRCC) is well known for intratumor heterogeneity. An accurate mapping of the tumor is crucial for assessing prognosis, and perhaps this can be linked to potential success/failure of targeted therapies. We assembled a cohort of 7 CCRCCs with prominent vasculature and microvascular hyperplasia (ccRCCPV), resembling those seen in high grade gliomas. A control group of classic CCRCC with no variant morphologies was also included. Both groups were analyzed for clinicopathologic, morphologic, immunohistochemical, and molecular genetic features. No statistically significant differences in mRNA expression of studied genes between the two groups were found. Using NGS panel Trusight Oncology 500 (TSO500), only one clinically significant gene mutation, VHL c.263G > A, p. (Trp88Ter), was found. TMB (Tumor Mutation Burden) and MSI (MicroSatellite Instability) were low, and no copy number variations (CNVs) were detected in the study cohort. Prominent microvascular hyperplasia in CCRCC is a rare phenomenon. From molecular genetic point of view, these tumors do not appear to be different from classic CCRCC. Prognostically, they also demonstrated similar clinical behaviors.

Introduction. Neoplastic microenvironment represents a frequently studied subject in numerous studies. Angiogenesis, as a part of it, is a prognostic factor and a therapeutic target in several neoplastic diseases. Cases presentation. We describe the angiogenetic process in a small series of extra gastrointestinal stromal tumours (EGISTs) and corelate it with the proliferation index. We retrospectively searched our institutions databases for EGIST cases. The resulting data were reviewed by two pathologists. Immu nohistochemistry (IHC) was performed to CASE SERIES

“Some are born great, some achieve greatness, and others have greatness thrust upon them.” ― William Shakespeare, Twelfth Night. Dr. Ondrej Hes clearly belongs to the first category (“born great”), described by William Shakespeare centuries ago. This tribute has been prepared by a group of close friends of Dr. Hes, who had the honor and privilege to know him both personally and professionally over years. On July 2, 2022, Ondrej passed away, a few days after collapsing while running from home to work (his usual routine exercise) outside the hospital in Pilsen (Plzeň) and in the nature that he loved the most. Ondrej was born in Pilsen in former Czechoslovakia on July 21, 1968, to an academic and an artistic family. He received his medical degree in 1993 at the Faculty of Medicine in Pilsen, Charles University. He subsequently completed his postgraduate training in Anatomic Pathology (1996) and went on to obtain his PhD in 2001. In a short period of time, he was promoted to Professor of Pathology at Charles University in 2009. Dr. Hes was a giant in surgical pathology, particularly genitourinary pathology, and especially so in tumors of the kidney. As a world-renowned kidney tumor pathology expert, it is hard to imagine another pathologist who has reviewed as many as renal tumors as Ondrej Hes, through his possibly largest kidney tumor registry in the world and collaborations with pathologists in all five continents. To date, he has published more than 450 peer-reviewed articles, some of which significantly impacted the practice of urologic surgical pathology in the world. His extensive work has been cited over 5300 times, with a remarkable h-index of 47, testament to his significant contribution to our profession and beyond. His curious mind along with extremely friendly and warm personality provided numerous opportunities for him to visit many pathology departments across the globe in search of “orphan renal tumors” (the term he often used for neoplasms that did not currently fit existing classification schemes). Some of the recently described eosinophilic renal tumors, such as eosinophilic solid and cystic renal cell carcinoma (ESC-RCC), low-grade oncocytic tumor (LOT), and eosinophilic vacuolated tumor (EVT) will always remain linked to Ondrej's name, by his instrumental contributions to their first recognition. This is simply a testament to his incredible interest and true passion for patient care. Being an honorable global citizen, Ondrej made numerous and long-lasting real friendships across the world with many pathologists, residents, and fellows. One of his amazing innovative and brilliant ideas was to merge science and friendship, which led him to establish the famous “Kidney Tumor Friends (KTF)” also known as the Pilsen Urogenital Pathology Conference 15 years ago. This is a highly unique academic forum in our field, with focus on exchanging scientific ideas in genitourinary surgical pathology in an environment of rich friendship and recreation. He sometimes joked that eventually the meeting would “have more speakers than audience members,” reflecting the large group of colleagues and collaborators that was generously hosted in the Czech Republic every few years. Ondrej's two main guiding principles in this endeavor were excelling in science while maintaining friendship, which have held true to-date. Ondrej's philosophy in establishing an academic meeting in a non-competitive and relaxed environment has always been appealing to colleagues participating and friends contributing to KTF from around the world. Each KTF meeting led to many scientific collaborations and subsequent publications, including original research and review articles. Ondrej's list of professional achievements and contributions are exemplary with his articles describing new tumor pathology entities, variants/subtypes, diagnostic challenges, and more. He also served numerous international societies, organizations, committees, and working groups, such as the European Society of Pathology (ESP), International Society of Urological Pathology (ISUP), Genitourinary Pathology Society (GUPS), Arkadi M. Rywlin (AMR) International Pathology Slide Seminar Club, and WHO blue books. He was an invited speaker to numerous meetings in the four corners of the globe and had widely lectured around the world on important and challenging genitourinary pathology topics. Ondrej was always a strong believer in education and mentorship. He devoted a major part of his time to teaching medical students, residents, fellows, and junior faculty members. Every year, many pathologists (mostly junior) from all over the world came to Pilsen to train with him and to improve their diagnostic skills in the world of kidney tumors. They also often had the opportunity to collaborate with Ondrej on research projects, some of which led to individuals obtaining their PhDs. Ondrej was a multifaceted individual and a man of wide interests, including sports (he was an avid runner—national championship in the men's 800 m run), photography (some of his professional works were exhibited in Czech museums), art, music, history, politics, and most importantly, ecology. Since his youth, he was interested in nature, especially herpetofauna and entomofauna. In fact, he has authored a number of articles and five books on reptiles and amphibians (his major work and contributions to Pilsen's Zoo is well known). For more than a decade, he was actively involved in the protection and creation of wetlands in the Czech Republic. He founded Eden, an NGO (Non-governmental organization) supporting biodiversity. As he simply stated it “Each of us, even the greatest ecologist, will destroy part of nature in our lifetimes. Come with us to try and repair some of the damage. Let us together protect and recreate nature for future generation” (https://fondeden.cz/). Dr. Ondrej Hes was an incredible scientist and educator, a giant in surgical pathology, a tireless environmentalist, a passionate activist in protecting wildlife and nature, a competitive and friendly athlete, a dedicated husband and a loving father, and an amazing friend. Above all, he was an exceptional human being and an honorable global citizen, whose kindness was readily contagious. His sense of humor was enlightening and inviting; his constant smile, the most heartwarming and genuine. He was always present and ready to help anyone in need. And this reminds us of the 17th century English poet John Bunyan's famous poem: “You have not lived today until you have done something for someone who can never repay you.” And by this virtue, Ondrej Hes certainly lived many lives, and his memory and legacy will remain in our hearts and for generations to come.

Background: Papillary lesions of the breast are a heterogeneous group, encompassing a wide range of lesions. The histologic distinction between papillary breast lesions remains challenging, especially on core biopsy specimens. Aim: This study aimed to determine the rate of upgrade to atypia or malignancy of biopsy-proven papillary lesions on surgical follow-up and to assess for factors associated with an upgrade in Greater Vancouver, BC, Canada. Materials and Methods: This is a retrospective population-based study of all breast papillary lesions diagnosed on core biopsy between 2017 and 2019 in the Fraser Health Authority in Greater Vancouver, Canada. Patients were retrieved from the laboratory information system. Patient demographics, histopathologic, and radiologic findings were analyzed. Results: A total of 269 specimens from 269 patients (mean 61.1 years), including 265 female and 4 male patients, were included in the study. Of the 269 specimens, 129 (48%) were intraductal papillomas and 140 (52%) were atypical papillary lesions. The overall upgrade rate among papillomas was 11.6% (15 of 129) on final excision. The mean age of patients diagnosed with papilloma on core biopsy was significantly younger than those with atypical papillary lesions (55.6 vs 66.1 years, P < .0001). Lesion size in patients with papillomas on core biopsy was significantly smaller than those with atypical papillary lesions (11.1 vs 15.1 mm, P = .001). The upgrade rates in patients <55 and ≥55 years were 4.9% and 13.2%. Size ( P = .004) and atypia on core biopsy ( P = .009) were significantly associated with upgrade. Older age (>55 years) (OR = 5.3, 95% CI: 1.04-27.08) was an independent predictor of upgrade among papillomas. Size, location, and Breast Imaging-Reporting and Data System (BI-RADS) radiologic categories in our study were not associated with predicting the upgrade of papillomas. Conclusion: Our data suggest that the risk of upgrade to atypia or malignancy is sufficient to warrant the excision of benign papillomas of any size in patients aged ≥55 years. In patients younger than 55 years, observation with close clinical and radiological follow-up without surgery may be sufficient. Our findings also support surgical excision of papillomas diagnosed on core biopsy when associated with atypia.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the digestive tract, originating from structures differentiating towards Cajal cells. Due to their morphology and localization, the extragastrointestinal stromal tumors (EGISTs) can be a diagnostic challenge. We investigated a series of 51 EGISTs diagnosed in our institutions, aiming to explore the immunophenotypes and to analyze the process and the utility of the antibodies required for a positive diagnosis. I mmunohistochemical examinations were done for pan-cytokeratin (pan-CK), Ki67, discovered on GIST1 (DOG1) protein and platelet-derived growth factor receptor alpha (PDGFRA), as necessary. The main tumor site was abdominal wall in 43 (84%) cases, most of the tumors showed spindle cell cellularity, followed by mixed and epithelioid type. Twenty-six cases revealed a full conventional immunohistochemical profile with DOG1 positivity. In 10 cases, c-KIT expression was absent but with the preservation of cluster of differentiation (CD)34 positivity, and eight cases were positive for PDGFRA. In our study, we found a subgroup of eight cases presenting in extra-abdominal settings (including one in lung and two in the head-and-neck area). We concluded EGISTs represent a histopathological and immunohistochemically challenging subgroup testing more often negative for c-KIT mutations and positive for PDGFRA compared to GIST. DOG1 remains the marker of choice regardless of tumor site, while CD34 and CD117 should be considered as adjuvants.

été enregistrée entre les groupes en termes de valeurs de Breslow (p = 0,98, test de Kruskal-Wallis). Conclusions. Les trois taches ont des performances similaires dans l’évaluation de la profondeur d’invasion, quelle que soit la méthode utilisée pour la quan-tifier. Le pathologiste devrait envisager d’utiliser une méthode exacte et précise comme une technique de mesurage numérique pour les rapports quotidiens. analyse d’image, indice de Breslow, immunohistochimie. Results. No significantly statistic differences were recorded between groups in terms of Breslow values (p=0.98, Kruskal-Wallis test). Conclusions. All three stains perform similar in eval-uating depth of invasion regardless of the method used to quantify it. The pathologist should consider using an accurate and precise method like a digital measurement technique for daily reports.

Introduction. The identification of the type and site of origin in undifferentiated tumours of unknown primary site using immunohistochemistry is a frequent requirement in pathology practice. There are many histologic lesions that display similar morphologic aspects, with misdiagnosis potentially resulting in over- or undertreatment. This makes the diagnostic accuracy extremely important in the era of targeted therapies. The objective of the study was to evaluate the process of diagnosis in 50 melanoma cases presenting as poorly differentiated or undifferentiated tumours with unknown primary origin, with emphasis on the immunohistochemical algorithm. Methods. 50 cases were selected to analyse the utility of IHC testing in diagnosing poorly differentiated malignancies. The immunohistochemical evaluation was based on the staining percentage of cells: focal positive <50%, diffuse positive >50%, negative (-) 0%. Results. After applying the Fan Lin algorithm, for most of the cases (45), the cytokeratin and CD45 proved negative, while S100 and vimentin were positive in diffuse or zonal patterns. For the 3 cases analysed by applying the Turin algorithm, the first antibody panel consisted in testing CK7/CK20, that showed no expression for all 3 cases. Conclusions. In this study, we demonstrated that the immunohistochemical examination of poorly differentiated malignant tumours is a reliable and valuable test and is recommended as a standard method in diagnosis along with the correlations with clinical and histological data.

Podocytopathies represent a well-studied subgroup of glomerulopathies, being characterized by proteinuria due to damage or dysfunction of podocytes. Glomerular size in podocytopathies has been studied in different population, but only a few studies take in consideration the pediatric population. There are different methods to assess the glomerular size, but most of the studies report the maximal profile area as being the most accurate one. The aim of this study is to determine the range values of glomeruli in pediatric population with glomerulopathies and to establish a correlation between the measured size and several laboratory features. The patients that undergo renal biopsy in the Department of Nephrology, "Maria Skłodowska Curie" Clinical Emergency Hospital for Children, Bucharest, Romania, were divided into two groups: control vs. affected∕patient group. The control group included children that require renal biopsy for renal impairments other than high-range proteinuria (most of them recurrent microscopic asymptomatic hematuria), while the affected group had nephrotic-range proteinuria. Thirty patients were selected to be part of the control group and 30 patients in the affected group. In control group, the mean value diameter was 166.23±13.04 μm, and the area of the glomerulus had a mean value of 19 126.86±3070.83 μm². In the affected group, we obtained the following results: the mean value diameter was 192.42±28.15 μm, while the glomerular cross-sectional area had a mean value of 23 535.55±6456.57 μm². Using the linear regression, we concluded that all the cases with increased-size glomeruli had more urinary protein loss compared with the ones that had small-size glomeruli and low-range proteinuria.

Objectives. Bone tumors are heterogeneous neoplasms, comprising a large spectrum of entities, both benign and malignant. One of the greatest challenges regarding bone and soft tissue pathology is highlighting osteoblastic differentiation in malignant lesions. From the numerous osteoblast-specific markers previously described in the literature, only osteocalcin, osteonectin and RANK have been used in histology studies. More recent proposed markers for osteoblastic differentiation are CD56 and special AT-rich sequence binding protein 2 (SATB2). Giant cell tumour of the bone is a special entity, in the category of intermediate tumors, locally aggressive and rarely metastasising. It is also known to become malignant. Specific markers for giant tumor of the bone are p63 and RANK, the latter being an osteoblastic marker. We investigated the expression of the quoted recent emerged markers, p63, CD56 and SATB2, in 23 bone and soft tissue primary and secondary neoplasms by constructing a tissue microarray paraffin block, and we analysed the impact of using them as a diagnostic marker in current practice.