The challenging boundaries between neoplastic and reactive lymphoproliferations were discussed during the 2024 European Association for Haematopathology/Society for Hematopathology workshop in Dubrovnik, Croatia. Session 3 focussed on the atypical lymphoid proliferations associated with therapeutic interventions. Forty-four cases were submitted representing a broad spectrum of lymphoproliferative disorders (LPDs) encountered in the settings of immunosuppressive and immunomodulatory therapies, various interventions for solid tumor treatment, drug reaction with eosinophilia and systemic symptoms (DRESS), CAR T-cell therapy for B-cell lymphomas, Bruton tyrosine kinase inhibitors (BTKI) for SLL/CLL treatment, ABL-kinase inhibitor dasatinib, and COVID-19 vaccination. The cases of this session highlighted the importance of having sufficient clinical information including drug history and distribution of disease in order to achieve reliable diagnosis. Among LPDs associated with immunosuppressive and immunomodulatory therapies, the most challenging were T- and NK-derived infiltrates as they ranged from non-clonal to clonal. DRESS-associated lymphadenopathy exhibited variable histologic patterns with the most difficult differential diagnosis being with a T-cell lymphoma. LPDs observed after CAR T-cell therapy for B-cell neoplasms exhibited unexpected phenotypes resulting either from lineage switching/transdifferentiation, or from harvested T-cells already harbouring cancer-associated variants. Temporary interruption of BTKI treatment for CLL/SLL due to surgical procedures led to a “Pseudo-Richter transformation” that disappeared after reintroduction of therapy. Dasatinib led to a lymphadenopathy with a peculiar florid follicular hyperplasia that regressed after discontinuation of therapy. The findings of the few thoroughly studied COVID-19 vaccination associated lymphadenopathy cases reflected a disordered immune response. This report describes the most important features for diagnosis of these challenging cases.

Introduction. A single pass albumin dialysis (SPAD) is a form of extracorporeal liver support system for removing albumin-bound toxins and water-soluble substances that accumulate in liver failure (LF). Case report. We presented three patients hospitalized for LF and treated using the SPAD at the University Clinical Center of Vojvodina, Serbia, from 2018 to 2019. Two of the patients presented with acute LF and one with acute-on-chronic LF. A total of 6 SPAD sessions were performed on each patient, resulting in decreased serum bilirubin and bile acid levels and hepatic encephalopathy grade. On discharge from the hospital, the liver function was improved in all the patients. Conclusion. SPAD removes the hepatotoxic substances without improvement of synthetic liver function. It represents a supportive treatment for LF patients who do not respond to the standard of care, offering a longer time for bridging to organ transplantation or spontaneous recovery of the liver function.

Introduction. ?Grey zone Lymphoma?? is associated with various entities. The last published classification of lymphoproliferative neoplasms includes mediastinal grey zone lymphoma. Precise diagnostic criteria are insufficient and establishing a diagnosis is as complex as deciding on treatment options. In this article pathologist and hematologist discuss issues on this topic through case presentation and literature review. Clinical characteristics. It presents in the younger population usually with a mediastinal mass, sometimes large, with compressive symptoms. Pathologic characteristics. Some cases can?t be classified neither as Hodgkin nor Primary mediastinal B-cell lymphoma. Morphology resembles Hodgkin, but with a positive immunophenotype for primary mediastinal or diffuse large B-cell lymphoma, and vice versa. Case report. We presented a case of a 33-year-old male with cervical lymphadenomegaly, B symptoms and clinical deterioration during the diagnostic period. After the first biopsy, differential diagnosis was Epstein-Barr virus-associated lymphoproliferative disorder or classical Hodgkin lymphoma. The second biopsy confirms Epstein-Barr virus-positive diffuse large B-cell lymphoma. The World Health Organization Classification of lymphoproliferative neoplasms - clinical perspective. The term ?grey zone lymphoma? is associated with overlapping diagnosis or uncertainty in diagnosis in more clinical settings than the ones provided in the 5th World Health Organization Classification. Discussion. For now, chemotherapeutic regimen (rituximab-cyclophos phamide, doxorubicin, vincristine, prednisone) stays the standard first line therapy for diffuse large B-cell lymphoma regardless of the Epstein- Barr virus status. Mediastinal grey zone lymphoma treatment varies: chemotherapeutic regimen (rituximab-cyclophos phamide, doxorubicin, vincristine, prednisone) was linked with better outcomes than chemotherapeutic regimen (adriablastin, bleomycin, vinblastine, dacarbazine) +/-R, but for some patients chemotherapeutic regimen (dose adjusted-etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin) might be beneficial. Conclusion. Grey zone lymphoma is a rare hematologic malignancy that needs extensive sampling for correct diagnosis and is still subject to inter-observer variability.

Introduction. Hemophagocytic syndrome (HS) after Bacillus Calmette-Guerin (BCG) immunotherapy is extremely rare in everyday practice. Only three times HS have been reported on in the world until now. BCG is used for preventing the recurrence of superficial tumors of the urinary bladder. The first extensive research was conducted by Morales, since when his treatment protocol has been in use. Severe complications are rarely seen. Case report. A 55 year-old patient in bad condition was transferred to Clinic for urology after second round of BCG immunotherapy (Morales protocol) after transurethral electroresection of bladder tumor (TURBT). Computed tomography (CT) of the abdomen and lesser pelvis was performed, which didn’t indicate any clear signs of organ failure or disease. Hemophagocytic syndrome (HS) after BCG immunotherapy was suspected. During further hospitalization, the patien’s already severe condition further deteorited and became more complicated, in the form of the multiorgan disfunction syndrome (MODS). Death occurred on the sixth day of hospitalization. Conclusion. Secondary HS after BCG immunotherapy is an extremely rare disease that is accompanied by a severe general condition of the patient, with many life-threatening complications that can lead to death. We have presented a case of severe HS after BCG immunotherapy that caused death of the patient. This case was unique because, for the first time, the possible causative agent was isolated-Mycobacteria.

In this paper, pathohistological images of extramedullary hematopoiesis (EMH) in stomach mucosa in a 68-year-old female patient with treated osteomyelofibrosis are presented. The digestive system is a potential but uncommon site of EMH, with the gastric mucosa being particularly rare. According to the available literature, only 12 cases have been described.

Introduction/Objective. There are no reliable tumor markers for non-invasive detection of bladder cancer and monitoring patients after treatment. The role of mast cells in oncogenesis is still unknown. Methods. Our study is an open, longitudinal, prospective follow-up study conducted over six months after surgical treatment of bladder cancer, with preoperative sampling of the first morning urine sample to determine the histamine concentration level. The research included 60 patients of both sexes, aged ? 18 years, with the first presentation of a non-muscle invasive bladder cancer. Patients in the study underwent follow-up control urethrocystoscopy postoperatively. The concentration of mast cells in tumor tissue was specified. Results. The study included 35 (58.3%) men and 25 (41.7%) women with an average age of 70.15 ? 9.38 years. The mean urinary histamine levels before surgery in patients with non-muscle-invasive bladder cancer were 11.06 ? 5.79 ng/mL. The mean urinary histamine levels before surgery (t = 2.46; p = 0.02) and six months after surgery (t = 2.34; p = 0.02) in patients with T1 stage were statistically significantly higher than the urinary histamine levels in patients with Ta stage of urothelial bladder cancer. Patients with higher histamine concentration in urine before surgery had a higher number of mast cells. Conclusion. The mean urinary histamine value before surgery, three, and six months after surgery is statistically significantly lower than the reference urinary histamine values. The urinary histamine values in patients with T1 stage are higher than in patients with Ta stage. Statistically significant correlation between mast cell concentration and histamine was determined before surgery.