PD-L1 and PD-L2 Mutations in Pediatric Hodgkin Lymphoma: Do They Have Any Prognostic Significance?

Background: Reed-Sternberg cells can escape from the immune system by enhancement of the expression of PD-L1 and PD-L2. Objectives: The aim of the present study was to investigate the significance PD-L1 and PD-L2 gene mutations in childhood Hodgkin Lymphoma's (HL). Methods: The study included 39 pediatric classical HL cases. PD-L1 and PD-L2 mutations were determined by Sanger sequencing. Clinicopathological parameters were obtained from patients' records. Results: Eight cases (20.5%) showed p.R260C mutations, and three (7.7%) p.R234L in the exome 5 of PD-L1 gene. None of the cases had PD-L2 mutations. p.R260C mutation exhibited a significant relationship with older age and nodular sclerosing (NS) histology and was associated with longer event free survival. Conclusions: Although PD-L1 mutational status did not show statistically significance with well-established prognostic factors, our preliminary data indicate that p.R260C mutation of PD-L1 gene may be associated with longer event free survival in older patients and NS histology in pediatric HL.

The 1000 Mitoses Project: A Consensus-Based International Collaborative Study on Mitotic Figures Classification.

Introduction. The identification of mitotic figures is essential for the diagnosis, grading, and classification of various different tumors. Despite its importance, there is a paucity of literature reporting the consistency in interpreting mitotic figures among pathologists. This study leverages publicly accessible datasets and social media to recruit an international group of pathologists to score an image database of more than 1000 mitotic figures collectively. Materials and Methods. Pathologists were instructed to randomly select a digital slide from The Cancer Genome Atlas (TCGA) datasets and annotate 10-20 mitotic figures within a 2 mm2 area. The first 1010 submitted mitotic figures were used to create an image dataset, with each figure transformed into an individual tile at 40x magnification. The dataset was redistributed to all pathologists to review and determine whether each tile constituted a mitotic figure. Results. Overall pathologists had a median agreement rate of 80.2% (range 42.0%-95.7%). Individual mitotic figure tiles had a median agreement rate of 87.1% and a fair inter-rater agreement across all tiles (kappa = 0.284). Mitotic figures in prometaphase had lower percentage agreement rates compared to other phases of mitosis. Conclusion. This dataset stands as the largest international consensus study for mitotic figures to date and can be utilized as a training set for future studies. The agreement range reflects a spectrum of criteria that pathologists use to decide what constitutes a mitotic figure, which may have potential implications in tumor diagnostics and clinical management.

HHV-8 and EBV Positive Lymphoproliferative Disease: A Challenging Case.

Human herpes virus-8 (HHV-8) is linked to four lymphoproliferative diseases: primary effusion lymphoma, HHV-8 positive multicentric Castleman disease (MCD), HHV-8 positive diffuse large B cell lymphoma and HHV-8 positive germinotropic lymphoproliferative disorder (GLPD). The diagnosis of HHV-8 associated lymphoproliferative diseases is quite challenging because each entity is rare and has a wide morphological spectrum. Our aim is to emphasize the overlapping histopathological features of MCD and GLPD as well as to underline the importance of clinicopathological correlation in case these two entities cannot be distinguished by pathological examination. We present here a case of an 82-year-old male patient who was examined for weight loss and multiple lymphadenopathy. Histopathological examination of the axillary lymph node revealed lymphoid follicle structures of varying shapes and sizes, including some atrophic germinal centers. Plasmablast-like cells were notable in some of these areas. HHV-8 and Epstein Barr Virus (EBV) positivity were noted in some of these cells and in a small number of cells in the mantle zone. Based on these findings; a diagnosis of "HHV-8 and EBV positive lymphoproliferative disease" was established. Since HHV-8 positive MCD and GLPD have similar histopathological features, it may not be possible to distinguish these two entities by histopathological examination only. At this point, the importance of clinicopathological correlation becomes more evident, especially in the determination of the treatment protocol to be applied to the patient.

Expression Profile of Selected Antitumor Immune Response Genes in Pediatric Classic Hodgkin Lymphoma.

Classic Hodgkin lymphoma (cHL) is one of the most common pediatric solid tumors and is responsible for cancer-related deaths in children. Therefore, to modulate the active antitumor T-cell immune response in cHL can be a treatment strategy. In the present study, we aimed to investigate the expression profiles of selected antitumor immune response genes in pediatric cHL and their relationships with clinical and prognostic parameters to determine their significance in precision medicine. Thirty-nine pediatric nodal cHL patients were enrolled in the study. We analyzed mRNA expression of selected immune response regulatory genes such as PD-L1, CSF2, CTLA4, CXCL5, IDO1, CXCL8, MIF, NOS2, PDCD1, PTGS2, and TGFß1 using real-time quantitative polymerase chain reaction. Only PD-L1 overexpression was statistically related to bulky disease, advanced tumor stage, and high-risk disease category and seen significantly in Epstein-Barr virus-negative pediatric cHL. No expression profiles were correlated with relapse or survival. We conclude that PD-L1 overexpression in pediatric cHL cases is a strong predictor of high-risk categorization. In addition to being a prognostic biomarker, PD-L1 blockade is also a druggable marker for the targeted therapy in Epstein-Barr virus-negative pediatric Hodgkin lymphoma.

How Does It Feel to Be a Pathologist in Turkey? Results of a Survey on Job Satisfaction and Perception of Pathology.

OBJECTIVE: Job satisfaction affects productivity and professional performance in many aspects; however, there is limited data regarding pathologists' job satisfaction. Hence, in this study, we aimed to evaluate surgical pathologists' job satisfaction in Turkey. MATERIALS AND METHODS: We conducted a 59-item web-based survey questioning respondents' institutional background, history of training, continuing education status/research activities, physical conditions, professional well-being, and job satisfaction level. Likert-type and open/ close ended questions were asked and scored. The participants were also asked to complete the Minnesota Satisfaction Questionnaire-Short Form. RESULTS: Of the 321 respondents, 75% were female, the median age was 41 years (range 28-71 years), experience as a pathologist ranged between 0.12 and 44 years (mean 11.4±9.16 years). Academic pathologists, senior pathologists with ≥20 years of experience, and pathologists working at large institutions and living in developed cities expressed better physical conditions, higher satisfaction with working conditions and, therefore, higher overall job satisfaction (p < 0.05). 98% agreed that pathologists have a critical impact on patient management; however, the majority ( > 80%) thought that patients barely know what pathologists do and other physicians rarely understand the difficulty and limitations in pathology practice. 82% were happy to have chosen pathology but 45% reported to experience the feeling of being "burnt out". CONCLUSIONS: Our findings suggest that younger pathologists are less satisfied with their jobs and a surgical pathologist's job satisfaction increases with the physical and technical quality of the pathology laboratory/institution, and years of experience. Pathologists seem to be aware of their important role in patient management although they think that pathology remains "invisible" to many physicians and patients.

Intussusception Can Be the First Sign of Post-transplant Lymphoproliferative Disease.

Intussusception is usually seen in the pediatric age group and rarely seen in adults. It results in the progression of the proximal segment of the intestine into the distal intestine. A 50-year-old immunosuppressive male patient presented with the complaints of abdominal pain, nausea, vomiting, and no gas or stool discharge for 2 days. He was hospitalized with the presumptive diagnosis of acute abdomen. He has a history of renal transplantation due to chronic renal insufficiency. An explorative laparotomy was performed. The operative findings were compatible with jejunojejunal intussusception, and a segmental small bowel resection and end-to-end anastomosis were performed. The patient was uncomplicated postoperatively and discharged on the fifth postoperative day. The pathology was reported as Epstein-Barr virus negative with diffuse large-cell B lymphoma. In this case report, we aim to report on a jejunojejunal intussusception that was presented as the first sign of post-transplant lymphoproliferative disease.

How does it feel to be a pathology resident? Results of a survey on experiences and job satisfaction during pathology residency.

Residents' career choices and professional motivation can be affected from perception of their role and recognition within a medical team as well as their educational and workplace experiences. To evaluate pathology trainees' perceptions of their pathology residency, we conducted a 42-item survey via a web-based link questioning respondents' personal and institutional background, workplace, training conditions, and job satisfaction level. For the 208 residents from different European countries who responded, personal expectations in terms of quality of life (53%) and scientific excitement (52%) were the most common reasons why they chose and enjoy pathology. Sixty-six percent were satisfied about their relationship with other people working in their department, although excessive time spent on gross examination appeared less satisfactory. A set residency training program (core curriculum), a set annual scientific curriculum, and a residency program director existed in the program of 58, 60, and 69% respondents, respectively. Most respondents (76%) considered that pathologists have a direct and high impact on patient management, but only 32% agreed that pathologists cooperate with clinicians/surgeons adequately. Most (95%) found that patients barely know what pathologists do. Only 22% considered pathology and pathologists to be adequately positioned in their country's health care system. Almost 84% were happy to have chosen pathology, describing it as "puzzle solving," "a different fascinating world," and "challenging while being crucial for patient management." More than two thirds (72%) considered pathology and pathologists to face a bright future. However, a noticeable number of respondents commented on the need for better physical working conditions, a better organized training program, more interaction with experienced pathologists, and deeper knowledge on molecular pathology.