Dina Sameh Soliman

Primary mediastinal large B-cell lymphoma (PMBL) is a subtype of non-Hodgkin B-cell lymphoma that most frequently occurs in young adults and is thought to reflect neoplastic transformation of thymic medullary B-cells. We characterized 59 PMBL cases from the Atlas of Blood Cancer Genomes Project. The cohort was predominantly young (median age 35), female (62%), and included individuals from diverse racial backgrounds. Most individuals presented with low-stage disease, favorable ECOG performance status, and high overall survival rate at last follow-up (89%). Whole transcriptome sequencing of 49 PMBL cases revealed gene expression profiles distinct from diffuse large B-cell lymphoma, not otherwise specified (DLBCL, NOS), both activated B cell-like (ABC) and germinal center B cell-like (GCB) cell-of-origin subtypes. PMBLs showed significantly higher expression of thymic B cell-associated genes (p=0.032), supporting their presumed thymic origin. Whole exome and targeted sequencing confirmed recurrent mutations in JAK/STAT, NF-κB signaling, and DNA damage response pathways, with frequent aberrant somatic hypermutation (aSHM) affecting multiple genes. Recurrent copy number alterations included gains at 9p and 12, and losses at 13q. As in prior studies, CIITA rearrangements with diverse partners were recurrent. Although PMBL generally demonstrates excellent outcomes, aSHM-positive cases exhibited inferior progression-free survival (p=0.031), suggesting aSHM as a potential adverse prognostic marker. Our findings further refine the genomic landscape of PMBL and provide new insights into the biology of this neoplasm, with implications for prognostic stratification.

Background: Philadelphia-negative myeloproliferative neoplasms (MPNs), including essential thrombocythaemia (ET), polycythaemia vera (PV), and myelofibrosis (MF), usually affect older adults, but a subset occurs in adolescents and young adults (AYA). Regional age-stratified data remain limited. Methods: We retrospectively studied Philadelphia-negative MPN patients managed at the National Center for Cancer Care and Research from 2014 to 2024. Patients were classified as AYA (15– 39 years) or older adults (≥ 40 years). Clinical, laboratory, molecular, thrombotic, bleeding, transformation, and survival outcomes were analyzed by subtype. Risk categories followed institutional disease-specific practice; analyses were descriptive and unadjusted. Results: The cohort included 220 patients: 79 ET, 47 MF, and 94 PV; 76 (34.5%) were AYA. Low-risk disease predominated in AYA ET (p< 0.001) and PV (72.4% vs 35.4%; p=0.002), partly reflecting age-based risk definitions. In ET (molecular n=30 vs 49), CALR was 16/30 (53.3%) versus 19/49 (38.8%) and JAK2 was 6/30 (20.0%) versus 21/49 (42.9%); MPL, triple-negative, and unavailable categories were 2, 4, and 2 versus 2, 6, and 1, respectively. In MF (n=11 vs 36), JAK2 was 4 (36.4%) versus 18 (50.0%), CALR 4 (36.4%) versus 10 (27.8%), MPL 0 versus 2 (5.6%), triple-negative 1 (9.1%) versus 3 (8.3%), and unavailable data 2 (18.2%) versus 3 (8.3%). In PV (n=29 vs 65), JAK2 V617F was 28 (96.6%) versus 63 (96.9%) and JAK2 exon 12 was 1 (3.4%) versus 2 (3.1%). Overall survival did not differ by age. Conclusion: AYA patients with Philadelphia-negative MPNs demonstrated age-related differences in risk classification, molecular profile, and thrombotic phenotype, while overall survival was comparable to older adults. Larger prospective multicenter studies are warranted.

Hairy Cell Leukemia (HCL) is a rare, chronic B-cell lymphoproliferative neoplasm characterized by the accumulation of abnormal lymphocytes in the bone marrow and spleen. Although outcomes are generally favorable with current therapies, data from diverse geographic and ethnic populations remain limited. This study highlights the disease clinicopathologic characteristics, treatment, and outcome within one center in the Middle East. A retrospective analysis was conducted on patients diagnosed with HCL at a tertiary care center, meeting the 5th edition WHO and ICC 2022 diagnostic criteria. Clinical, laboratory, and pathological data were extracted from institutional records. Twenty-two patients were identified. The cohort represented diverse nationalities across Asia, Africa, Europe, and North America. Most cases were detected incidentally, while others presented with constitutional symptoms, abdominal pain, or febrile neutropenia. All but one case were classic HCL. Most expressed Pan B-cell markers, though a few showed aberrant loss of CD19, PAX-5, or CD103. The BRAF V600E mutation was detected in 82% of the tested cases. Treatment regimens included Cladribine alone or with Rituximab, yielding high response rates and minimal toxicity. Five-year overall survival was 100%. In this multiethnic Middle Eastern and North African cohort, HCL predominantly affected middle-aged men and was often incidentally detected. Cladribine-based therapy achieved durable remissions with excellent survival, highlighting consistent efficacy across diverse populations.

Introduction: Concurrent chronic myeloid leukemia (CML) and chronic lymphocytic leukemia (CLL) in the same patient are rare and may be overlooked when leukocytosis is attributed to a single hematologic process. We report a case of synchronous CML and CLL identified at initial presentation, highlighting the diagnostic value of integrating morphology, immunophenotyping, cytogenetics, and molecular testing. Case Presentation: A 44-year-old man presented with progressive weight loss and back pain and was found to have leukocytosis with neutrophilia, absolute lymphocytosis, eosinophilia, and basophilia. Peripheral blood smear and flow cytometry supported CLL, whereas reverse-transcription polymerase chain reaction and cytogenetics demonstrated e13a2 BCR::ABL1 and t(9;22)(q34;q11.2), confirming concomitant CML in chronic phase. Bone marrow examination showed hypercellularity with granulocytic hyperplasia and nodular lymphoid infiltrates, and fluorescence in situ hybridization detected 13q14.3 deletion in the lymphoid clone. Imatinib 400 mg daily was initiated but was replaced with dasatinib 100 mg daily because of intolerance. At 14 months of follow-up, the patient remained clinically stable on dasatinib, with early molecular response at 3 months and major molecular response at 12 months, while the CLL remained under observation without indication for CLL-directed therapy. Conclusion: This case highlights the diagnostic complexity of synchronous hematologic malignancies and the importance of comprehensive multimodal evaluation when clinical, morphologic, and laboratory findings are not fully explained by a single diagnosis. Treating the clinically dominant clone while monitoring the second clone may be appropriate when the latter is asymptomatic.

Introduction: Systemic mastocytosis (SM) is a clonal disorder characterized by abnormal accumulation of mast cells in various tissues and is categorized into distinct subtypes per the World Health Organization (WHO) 2022 classification. When SM is associated with another hematologic neoplasm, typically of myeloid lineage, it is classified as systemic mastocytosis with an associated hematologic neoplasm (SM-AHN). Coexistence with plasma cell dyscrasias is rare, with fewer than 15 published cases involving either smoldering multiple myeloma (SMM) or multiple myeloma (MM). ALECT-2 amyloidosis, a non-immunoglobulin-derived amyloid subtype, is typically isolated to the kidneys and has not been previously reported in context of SM-AHN. Case Presentation: We describe the first documented case of concurrent SMM, SM-AHN, and ALECT-2 amyloidosis in a 67-year-old male of Egyptian descent with stage 3B chronic kidney disease and proteinuria. Diagnostic workup revealed lambda-restricted plasma cell infiltration, KIT D816V-positive multifocal mast cell aggregates, and renal-limited ALECT-2 deposits confirmed by mass spectrometry. Serum immunofixation electrophoresis showed a monoclonal lambda free light-chain band without a corresponding intact heavy-chain M-protein, and serum protein electrophoresis showed no M-spike. The patient was managed with active surveillance, and the available records document approximately 24 months of follow-up. Conclusion: This case highlights the diagnostic and clinical implications of overlapping hematologic and renal disorders, underscores the role of proteomic amyloid typing in avoiding misdiagnosis, and explores potential pathogenic interplay between mast cells, plasma cells, and the marrow microenvironment. This case also underscores the importance for clinicians remaining vigilant and considers the possibility of non-AL amyloidosis, even when a plasma cell disorder diagnosis has been documented.

Post cytotoxic myeloid neoplasms signify a heterogenous pool of poorly understood hematologic neoplasms with unfortunate survival and ineffective therapies. There is a lack of consensus on prognostic indicators, primarily due to the heterogenous disease spectrum encompassing different pathological, cytogenomic and original disease variables. This retrospective, single-center study over 10 years duration on MN-pCT cases diagnosed at NCCCR, a member of Hamad Medical Corporation. The study aimed to analyze clinicopathologic and cytogenomic characteristics, identify key prognostic predictors, and assess their impact on mortality through univariate and multivariate analyses. We identified 42 MN-pCT patients, noting a 31.7% prevalence of autoimmune diseases as primary condition, which is higher than previously reported. TP53 was the most frequently mutated gene, found in 28.6% of tested cases. Significant determinants of a shorter latency period included prior exposure to alkylating agents and TP53 positivity (by NGS or IHC) (P < 0.05). Younger patients (≤ 50 years) exhibited longer survival (P = 0.018). Poor prognostic markers included dyserythropoiesis (P = 0.045), MPO downregulation (P = 0.026), mutated TP53 (NGS/IHC) (P = 0.004), and failure to achieve CR (P = 0.002). Multivariate Cox regression identified both a latency period of ≥ 5 years and TP53 positivity (detected by either NGS or IHC) as statistically significant independent factors associated with reduced overall survival (P < 0.05). It is important to highlight that P53 mutation by NGS was a common parameter identified by the multivariate analysis that adversely impacted both MN-Pct survival and OS. This study stands as a significant contribution to our understanding of the clinicopathologic characteristics and prognostic predictors of MN-pCT in MENA region. It also underscores the existence of adverse prognostic factors, extending beyond the genetic influences and emphasizing the necessity of recognizing it as a distinct entity in the future classification systems.

Background: Eptifibatide is a known antiplatelet that is used in patients undergoing percutaneous coronary intervention for ACS, and it is proven to have a positive outcome. Despite thrombocytopenia not being reported in the pivotal trials, the emerging literature associated this link. We aim to further investigate this association and provide real-world data from a single centre. Methods: A retrospective study was conducted in Heart Hospital at Hamad Medical Corporation from 2016 to 2022. All patients admitted with ACS and received Eptifibatide were included in the study. Patients with confirmed secondary causes of thrombocytopenia were excluded. The data is reported in the form of mean, median, standard deviation, interquartile range, and percentage. Results: Twenty-six patients met the inclusion criteria, with an average age of 54 ± 11 years, and all patients were males. The baseline platelets count was 157 ± 80, and haemoglobin was 14 ± 2. Fourteen patients had platelets drop by more than 50% of their baseline. Thrombocytopenia developed after eptifibatide infusion by 36 ± 29. The average haemoglobin post-eptifibatide infusion was 13.5 ± 1.7 g/dL. Three patients required platelet transfusion, 23 patients were managed conservatively, and one patient died. Conclusion: Eptifibatide can cause life-threatening thrombocytopenia, which can be simply reversed by ceasing the infusion. However, platelet transfusion might be necessary in some patients. Neither the mechanism nor the risk factors are clear, and further studies are recommended to understand this association better.

Introduction: Core-binding factor-acute myeloid leukemia (CBF-AML) is characterized by t(8;21) or inv(16)/t(16;16) chromosomal rearrangements. Methods: In this retrospective study of 71 CBF-AML cases from Qatar’s National Center for Cancer Care and Research (2013–2022), we analyzed clinicopathological characteristics and survival outcomes. Results: The cohort was predominantly male (76%) with a median age of 40 years, and 96% were de novo AML. The t(8;21) translocation was more frequent (69%) than inv(16)/t(16;16). Patients under 40 years showed higher white blood cell counts and blast percentages. Standard “3 + 7” induction chemotherapy (used in 69% of cases) achieved remission in 67% of patients. Median overall survival was 81% at 37 months, with median progression-free survival of 34 months. No significant survival differences were observed based on FLT3-ITD status, translocation type, complex karyotype, KIT mutation status, or allogeneic stem cell transplantation (performed in 19% of patients), though patients under 60 years demonstrated better survival outcomes. Conclusions: This study highlights CBF-AML heterogeneity and challenges established prognostic markers, suggesting a need for risk stratification reassessment, treatment strategy optimization, ELN guideline implementation, and continuous molecular monitoring.

Background: Erdheim-Chester disease (ECD) is a recently recognized clonal hematopoietic neoplasm characterized by activating alterations in the MAPK pathway. It involves multi-organ accumulation of abnormal histiocytes, leading to nonspecific clinical manifestations due to inflammation and fibrosis caused by histiocytic infiltration. Case Presentation: We present a 45-year-old male with nonspecific clinical symptoms and progressive skin and abdominal lesions. Multiple tissue biopsies revealed fibrohistiocytic infiltration but provided an inconclusive diagnosis. Imaging studies showed extensive fibrosis in the perinephric regions on CT and sclerotic foci in long and pelvic bones on PET/CT. Bone marrow biopsy revealed abnormal histiocytes with multinucleated giant forms, prominent emperipolesis, active hemophagocytosis, and condensed hemosiderin deposition. Immunohistochemistry showed positive histiocytes for CD68, CD163, and partially for S-100. Molecular analysis confirmed the BRAFV660E mutation, establishing a diagnosis of ECD with atypical histologic features and findings overlapping with Rosai-Dorfman (mixed histiocytosis). The diagnosis was challenging due to extensive fibrosis, the lack of typical histopathologic features of ECD, in addition to concurrent involvement by Rosai-Dorfman cells (mixed histiocytosis), activated macrophages, and dense hemosiderin deposition – a morphologic characteristic not previously described in ECD. Unfortunately, the diagnosis was delayed by 6 years, which tragically led to a fatal outcome. Conclusion: The case highlights the need to recognize that ECD diagnosis requires integrating histopathology with clinical and radiographic findings. It emphasizes the importance of awareness of mixed histiocytosis features and the role of detecting BRAF mutations, even through immunohistochemistry, in suspected histiocytic neoplasms. Extensive bone marrow involvement by ECD is rarely described. To our knowledge, there are no prior reports of bi-phenotypic (concurrent) ECD/RDD mixed histiocytosis affecting the bone marrow.

Background: Plasmacytoma of the skull base is a rare manifestation of plasma cell neoplasm with only a few cases documented in literature involving young adults. Plasmacytoma can be an isolated solitary lesion or a secondary manifestation of multiple myeloma (MM). In this study, we report the clinical and radiological characteristics, management, and outcomes of patients under the age of 40 who presented with skull base plasmacytoma and associated neurological manifestations. Additionally, we share our experience in treating a rare case of skull base plasmacytoma diagnosed during pregnancy, in which the patient exhibited a favorable response to myeloma treatment initiated after delivery.Case Series: Four patients were identified, comprising one pregnant female and three male patients, with a median age of 36 years (range 33–37 years). The main presenting symptoms were headache, dizziness, and cranial nerve palsy. All patients received underwent systemic myeloma therapy and radiotherapy with three patients also underwent autologous stem cell transplantation (ASCT). Notably, all patients achieved complete remission.Conclusion: Skull base plasmacytoma represents a rare manifestation of plasma cell neoplasms, underscoring the importance of considering it in the differential diagnosis of skull base lesions to ensure early intervention and avoid potential serious complications. Throughout our series, the cornerstone of therapy involved radiotherapy, systemic myeloma therapy, and ASCT, all of which elicited a favorable response in every case.