Pegylated interferon-α2a in cutaneous T-cell lymphoma - a multicenter retrospective data analysis with 70 patients.

BACKGROUND: Interferon-alpha is an important therapeutic option for the treatment of the cutaneous T-cell lymphomas (CTCL). Since the approved recombinant interferon-α-2a (IFN-α2a) has no longer been produced since January 2020, pegylated interferon-α2a (pegIFN-α2a) can be used as an alternative treatment, even though it is not approved for the treatment of CTCL. The aim of this multicentre study was to generate comprehensive data on the efficacy and tolerability of pegIFN-α2a in the treatment of CTCL. PATIENTS AND METHODS: A multicenter retrospective study was conducted with 70 patients with CTCL from twelve German skin centers. RESULTS: In total, 70 patients were included in the study, with 57.2% male and a mean age of 58.8 ± 14.9 years. Mycosis fungoides was present in 71.4% of cases and Sézary Syndrome in 28.6%. An overall response rate of 55.2% was observed with pegIFNα-2a therapy. In 50% of cases, therapy was discontinued after 63.6 ± 33.5 weeks. The most common reason for discontinuation was adverse events, which occurred in 68.6% of cases and which were classified as severe in 29.2%. Blood count changes, fatigue and liver toxicity occurred most frequently. CONCLUSIONS: Our analysis provides comprehensive data on the efficacy and tolerability of pegIFNα-2a therapy in patients with CTCL. In terms of response rates and side effect profile, pegIFNα-2a appears to be comparable to IFN-α2a therapy.

Immunoglobulin G4 in primary Sjögren's syndrome and IgG4-related disease - connections and dissimilarities.

Primary Sjögren's syndrome (pSS) is an autoimmune disease, with B cell hyperactivation and autoantibody production as its immunological hallmarks. Although the distinction between immunoglobulin G4-related disease (IgG4-RD) and pSS, based on the presence or absence of certain autoantibodies, seems easy to make, possibility of elevated serum IgG4 concentration and often similar organ involvement may lead to a misdiagnosis. The increased serum concentration of IgG4 in IgG4-RD is not clearly linked to the pathogenesis of IgG-RD and it has been suggested that it may constitute just an epiphenomenon. The aim of this article is to discuss the presence of IgG4 in pSS and IgG4-RD and its potential significance for these two diseases.

Comprehensive analysis of constitutional mismatch repair deficiency-associated non-Hodgkin lymphomas in a global cohort.

BACKGROUND: Constitutional mismatch repair deficiency syndrome (CMMRD) is a rare childhood cancer predisposition syndrome associated with a broad spectrum of malignancies, including non-Hodgkin lymphomas (NHL). Most patients die due to cancer before the age of 20 years. Limited data exist on CMMRD-associated lymphomas and their outcome. METHODS: We conducted a retrospective study including all CMMRD-associated NHL patients registered before 2020 in the European and North American databases or reported by members of the European Intergroup for Childhood Non-Hodgkin Lymphoma (EICNHL). Events considered to define event-free survival included relapse/progression, second malignancy (SML), or death, whichever occurred first. FINDINGS: The analysis included 74 patients, with 20 having multiple metachronous NHL. The median age at diagnosis was 9.4 years. Previous malignancies were reported in 36% of the patients, café au lait spots in 96%, and consanguinity in 54%. The initial lymphoma subtypes were 53 T-cell lymphoblastic lymphomas (T-LBL), four B-lymphoblastic lymphomas, and 17 mature B-cell non-Hodgkin lymphoma (B-NHL). All patients were treated with curative intent, with current chemotherapy regimens adapted to their subtype. The median follow-up was 8.7 years. After the first lymphoma, the 5-year event-free and overall survival rates were, respectively, 23.5% [95% confidence interval (CI): 14.9-35.1] and 61.5% [95% CI: 49.6-72.1]. The 5-year cumulative risk of progression/relapse, SML or death as a first event was 20.8%, 52.9%, and 2.7%. INTERPRETATION: Standard treatments for sporadic NHL are effective in most CMMRD-associated NHL cases, but multiple malignancies, including lymphomas, impair prognosis. Future strategies should evaluate the potential of less genotoxic therapies, including immunotherapy, in preventing SMLs while maintaining effective control of NHL.

CD38, CD39, and BCL2 differentiate disseminated forms of high-grade B-cell lymphomas in biological fluids from Burkitt lymphoma and diffuse large B-cell lymphoma.

High-grade B-cell lymphomas (HGBCL) represent a heterogeneous group of very rare mature B-cell lymphomas. The 4th revised edition of the WHO Classification of Tumors of Hematopoietic and Lymphoid Tissues (WHO-HAEM) previously defined two categories of HGBCL: the so-called double-hit (DHL) and triple-hit (THL) lymphomas, which were related to forms harboring MYC and BCL2 and/or BCL6 rearrangements, and HGBCL, NOS (not otherwise specified), corresponding to entities with intermediate characteristics between diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma (BL), without rearrangement of the MYC and BCL2, and/or BCL6 genes. In the 5th edition of the WHO-HAEM, DHL with MYC and BCL2 rearrangements or THL were reassigned as DLBCL/HGBCL with MYC and BCL2 rearrangements (DLBCL/HGBL-MYC/BCL2), whereas the category HGBCL, NOS remains unchanged. Characterized by an aggressive clinical presentation and a poor prognosis, HGBCL is often diagnosed at an advanced, widespread stage, leading to potential disseminated forms with a leukemic presentation, or spreading to the bone marrow (BM) or other biological fluids. Flow cytometric immunophenotypic study of these disseminated cells can provide a rapid method to identify HGBCL. However, due to the scarcity of cases, only limited data about the immunophenotypic features of HGBCL by multiparametric flow cytometry are available. In addition, identification of HGBCL cells by this technique may be challenging due to clinical, pathological, and biological features that can overlap with other distinct lymphoid malignancies, including Burkitt lymphoma (BL), diffuse large B-cell lymphoma (DLBCL), and even B acute lymphoblastic leukemia (B-ALL). In this study, we aimed to characterize the detailed immunophenotypic portrait of HGBCL, evaluating by multiparametric flow cytometry (MFC) the expression of 26 markers on biological samples obtained from a cohort of 10 newly-diagnosed cases and comparing their level of expression with normal peripheral blood (PB) B lymphocytes (n = 10 samples), tumoral cells from patients diagnosed with B-ALL (n = 30), BL (n = 13), or DLBCL (n = 22). We then proposed a new and simple approach to rapidly distinguish disseminated forms of HGBCL, BL, and DLBCL, using the combination of MFC data for CD38, BCL2, and CD39, the three most discriminative markers explored in this study. We finally confirmed the utility of the scoring system previously proposed by Khanlari to distinguish HGBCL cells from B lymphoblasts of B-ALL. In conclusion, we described a distinct immunophenotypic portrait of HGBCL cells and proposed a strategy to differentiate these cells from other aggressive B lymphoma entities in biological samples.

Splenic cyst deroofing complicated with B lymphoma.

BACKGROUND: Splenic cysts are uncommon and very rarely malignant therefore their treatment isn't standardized. In case of symptomatic cysts different surgical approaches have been suggested. Primary malignant lymphoma of the spleen comprises less than 1% of non-Hodgkin's lymphomas. To our knowledge, only 203 cases of splenic large B-cell lymphoma (LBCL) have been reported to date and only 2 of them were fibrin-associated splenic cysts. CASE PRESENTATION: 27-year-old model with a 19 × 13 cm splenic cyst without data of malignancy in the preliminary study and therefore treated with laparoscopic deroofing. After histological diagnosis of LBCL with a fibrin/EBV-associated splenic pseudocyst, the patient received 4 cycles of Rituximab and a laparoscopic splenectomy was performed due to resurgence of the pseudocyst. No evidence of malignancy has been found during follow up (EBV viral load every 3 months during the first year, PET-CT every 6 months during the first year and annual afterwards) performed after the splenectomy. DISCUSSION AND CONCLUSIONS: The value of tumor markers and radiology for diagnosis of splenic cysts is put into question. Only 60 cases of Fibrin-associated LBCL (FA-LBCL) have been described in the literature therefore there are no treatment guidelines for them even though surgery together with systemic treatment has been the prevalent route with good results in most cases.

Leukemia in pregnancy: Diagnosis and therapeutic approach (Review).

The present study aimed to evaluate the epidemiological, diagnostic and therapeutic data of hematological malignancies in pregnancy. Leukemia in pregnancy is rare, and literature data are not extensive. Risk factors, epidemiology and pathogenesis of these diseases are not fully developed. Furthermore, there is a detailed report on the complications in pregnancy and the overall (per trimester) management of these diseases, specifically their treatment strategy. The possibility of achieving a future pregnancy in women with leukemia is described in the present study. The limited clinical research data currently available is mainly due to the inability to conduct randomized clinical trials for ethical reasons. Further research is needed, firstly due to the importance of these diseases for the pregnant woman and the fetus, and secondly, due to the continuous development of novel anticancer drugs that aim to improve the prognosis of these diseases.

Klinefelter syndrome and cutaneous localization of diffuse large B cell lymphoma: a real connection or a casual association?

Diffuse large B cell lymphoma (DLBCL) is a common aggressive subtype of non-Hodgkin lymphoma, accounting for nearly 30-40% of all cases. This condition can affect the skin both primarily and secondarily. Herein we report a clinical and dermoscopic case of skin metastasis of DLBCL in a patient with Klinefelter Syndrome.

Non-invasive techniques in the clinical diagnosis of cutaneous lymphomas.

In clinical practice, cutaneous lymphomas can be challenging to diagnose or even suspect because they mimic a variety of other inflammatory and neoplastic dermatological conditions. Support for non-invasive skin analysis methods like reflectance confocal microscopy and dermoscopy is still anecdotic. Practically speaking, a deeper and more comprehensive study with a larger number of cases focusing on the effective usefulness of non-invasive techniques should be taken into consideration because they have demonstrated the ability to identify macro and micro features supporting the clinical suspicion of lymphomas, as well as being useful for differential diagnosis and supporting the selection of the biopsy site. The author provides a brief and narrative synopsis of the reflectance confocal microscopy and dermoscopy characteristics of cutaneous lymphomas in this manuscript.

The Current Landscape of Secondary Malignancies after CAR T-Cell Therapies: How Could Malignancies Be Prevented?

Chimeric antigen receptor (CAR) T-cell therapies have revolutionised the field of haematological malignancies by achieving impressive remission rates in patients with highly refractory haematological malignancies, improving overall survival. To date, six commercial anti-CD19 and anti-BCMA CAR T-cell products have been approved by the Food and Drug Administration (FDA) for the treatment of relapsed/refractory B-cell haematological malignancies and multiple myeloma. The indications for CAR T-cell therapies are gradually expanding, with these therapies being investigated in a variety of diseases, including non-malignant ones. Despite the great success, there are several challenges surrounding CAR T-cell therapies, such as non-durable responses and high-grade toxicities. In addition, a new safety concern was added by the FDA on 28 November 2023 following reports of T-cell malignancies in patients previously treated with either anti-CD19 or anti-BCMA autologous CAR T-cell therapies both in clinical trials and in the real-world setting. Since then, several reports have been published presenting the incidence and analysing the risks of other secondary malignancies after CAR T-cell therapies. In this opinion article, the current landscape of secondary malignancies after CAR T-cell therapies is presented, along with a proposed strategy for future research aiming at potentially diminishing or abrogating the risk of developing secondary malignancies after CAR T-cell therapies.

In silico study of some plant compounds as potential anticancer agents targeting MALT1 allosteric domain.

Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) is the only human paracaspase, that serves as an adaptor protein and controls substantial genes expressed in the activation, proliferation of lymphocyte, and immune reactions by triggering the IKK/NF-kB signaling pathway. However, unusual MALT1-mediated NF-kB signaling pathway has been identified in multiple diseases like cancer, therefore making MALT1 a promising therapeutic target. There are scanty numbers of MALT1 inhibitors, thus the need to discover more compounds with less or no toxicity issue, that are cheap and pharmacologically efficient is of pertinence. Hence, our present study was to identify phyto-small molecules that could bind the allosteric interface of MALT1 using in silico methods. Total of 34 plant molecules were selected and screened for druglikeness, after which they were docked via Maestro 11.1 against the allosteric site of MALT1. The molecule with a binding score (kcal/mol) better than the control drug was subjected to molecular dynamics (MD) simulations of 100 ns via Desmond, free energy perturbations, principal component and Pearson correlation analyses. Our findings from this computational study presents cyanidin (-8.822 kcal/mol) as better binder to the allosteric site of MALT1 based on the molecular docking and pharmacokinetic profiling than thioridazine. Similarly, cyanidin-MALT1 complex showed significant stability and exhibiting contacts with critical amino acid residues in the site of interest than thioridazine-MALT1 complex. Hence, cyanidin is a potential allosteric inhibitor of MALT1. However, an urgent need for in vitro and in vivo validations is required to ascertain the efficacy of cyanidin in the fight against cancer and other MALT1-related diseases.

Evaluation of infectious morbidity due to BTK inhibitors in indolent B-cell lymphomas: latest research findings and systematic analysis.

INTRODUCTION: Randomized clinical trials (RCTs) have suggested that BTK inhibitors (BTKis) might increase infectious disease (ID) risk. Systematic analysis of this topic as derived from RCTs and clinical practice is needed. AREAS COVERED: An extensive Medline, Embase, and Cochrane search of peer-reviewed sources reporting on ID morbidity in patients on BTKis was performed (1 January 2014 - 31 December 2013). Contribution of intrinsic immune defects in indolent B-cell lymphomas to this morbidity was carefully considered. EXPERT OPINION: Patients with indolent B-cell lymphomas display a wide range of innate and adaptive immune defects. In addition, BTKi use is linked with an increased signal of upper respiratory tract infections (URTIs) and pneumonias, mainly grade 1-2. These agents also increase the risk of rare invasive fungal infections (IFIs), mainly due to Cryptococcus and Aspergillus spp. with a peak within several months after the start of therapy. More than half of these IFIs are fatal. Research suggests a similar ID risk across 1st, 2nd and 3rd generations of BTKis, all causing B-cell dysfunction due to BTK inhibition, along with off-target functional neutrophil/macrophage alterations. Expanding the knowledge base on ID morbidity in patients on BTKis would facilitate timely diagnosis and treatment, and improve clinical outcomes.

Association of both BCL2 positive and negative follicular lymphoma to clasical Hodgkin lymphoma and/or gray zone lymphoma.

We present a series of 9 follicular lymphomas that progressed/transformed into classical Hodgkin lymphoma (CHL). Three cases of CHL showed a syncytial pattern (SCHL) making the differential diagnosis to Gray zone lymphoma (GZL) challenging. None of these three cases presented in the mediastinum. Based in all molecular data analyzed (BCL2/BCL6 FISH studies, IgH PCR and TNGS with a customized gene panel) we did find clonal relationship between the BCL2-positive FL cases and their CHL components in all cases. The three SCHL/GZL cases showed an activated phenotype according to Hans algorithm, presented the t(14; 18)(q32; q21), two out of three showed B cell markers and all expressed CD30 and p53. Interestingly, we identified three BCL2-negative FL cases with a further diagnosis of CHL expanding the spectrum of these association. In one of these three cases a different mutational profile was found in both the FL and the CHL components. All this data together suggests that CHL associated to BCL2-positive FL could be originated in a common progenitor cell (CPC) that give rise to both FL and CHL, acquiring this last component further genetic events in a linear fashion. On the other hand, no clonal relationship between CHL and BCL2-negative FL could be found, suggesting a fortuity association. Nevertheless, ample series of cases studied with more sensitive techniques are needed to confirm our hypothesis.

Prevalence, clinical features, and survival outcome trends of 627 patients with primary cutaneous lymphoma over 29 years: a retrospective review from single tertiary center in Korea.

The relative frequency of primary cutaneous lymphoma (PCL) subtypes shows wide variation across different geographical regions. This retrospective study was conducted in a tertiary referral center located in Korea to describe the relative frequency, demographics, survival outcomes, and temporal trend in PCL. A total of 627 PCL cases diagnosed between January 1994 and December 2022 were included. The majority of PCL cases (87.2%) were of T-/NK-cell lineage (CTCL), while the remaining cases (12.8%) were B-cell lineage lymphomas (CBCL). The prevalence of mycosis fungoides (MF) in CTCL increased significantly over time, while other CTCL subtypes, including primary cutaneous extranodal NK/T-cell lymphoma and subcutaneous panniculitis-like T-cell lymphoma (SPTCL), decreased in frequency. Notably, the prevalence of CD4-positive small/medium T-cell lymphoproliferative disorder showed a substantial increase over time. Primary cutaneous marginal zone lymphoma was consistently the commonest CBCL subtype. Survival analysis demonstrated that CTCL had a more favorable 5-year overall survival (OS) than CBCL. OS rate of MF, SPTCL, and primary cutaneous peripheral T-cell lymphoma, NOS improved significantly over time. This study provides comprehensive insights into the dynamic change in the relative frequency and overall survival of PCL subtypes over time.

Pyoderma Gangrenosum in a 75-Year-Old Male With Follicular Diffuse Large B-cell Lymphoma.

Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis that characteristically presents with progressive ulcerative lesions. The association of PG with hematological malignancies remains unclear due to its varied clinical presentation. Herein, we report the unusual case of PG in a 75-year-old male with stage III follicular diffuse large B-cell lymphoma. Seven days subsequent to his first dose of rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone (R-CHOP) therapy, he presented to the emergency department with generalized malaise, bilateral lower extremity edema, and ecchymoses with ulcerative wounds on the dorsal of his feet. Due to the rapid progression of the patient's dermatological manifestations and declining clinical status, he required serial surgical wound debridement and a biopsy, which revealed an occlusive vasculopathy with dermal and epidermal necrosis. These pathological findings, along with the patient's clinical presentation, led to the diagnosis of PG. The patient was treated with negative pressure wound therapy, steroids, and tacrolimus ointment, which led to a marked improvement in the appearance of the patient's dermatological features and clinical status.

Cross-talk between immune cells and tumor cells in non-Hodgkin lymphomas arising in common variable immunodeficiency.

INTRODUCTION: CVID is the commonest and most symptomatic primary immune deficiency of adulthood. NHLs are the most prevalent malignancies in CVID. The cross-talk between tumor cells and immune cells may be an important risk factor in lymphomagenesis. AREAS COVERED: The present review highlights immune cell, genetic and histopathological alterations in the CVID-associated NHLs. EXPERT OPINION: CVID patients exhibit some notable immune defects that may predispose to lymphomas. T/NK cell defects including reduced T cells, naïve CD4+T cells, T regs, and Th17 cells, increased CD8+T cells with reduced T cell proliferative and cytokine responses and reduced iNKT and NK cell count and cytotoxicity. B cell defects include increased transitional and CD21low B cells, clonal IgH gene rearrangements, and increased BCMA levels. Increase in IL-9, sCD30 levels, and upregulation of BAFF-BAFFR signaling are associated with lymphomas in CVID. Increased expression of PFTK1, duplication of ORC4L, germline defects in TACI, NFKB1, and PIK3CD, and somatic mutations in NOTCH2 and MYD88 are reported in CVID-associated lymphomas. Upregulation of PD-L1-PD-1 pathway may also promote lymphomagenesis in CVID. These abnormalities need to be explored as prognostic or predictive markers of CVID-associated NHLs by large multicentric studies.

Primary intestinal T-cell and natural killer-cell lymphomas: Clinicopathologic and prognostic features of 79 cases in South China.

OBJECTIVES: Primary intestinal T-cell and natural killer-cell lymphomas (PITNKLs) are aggressive and make pathologic diagnoses in biopsy specimens challenging. We analyzed different subtypes' clinicopathologic features and treatment outcomes. METHODS: Seventy-nine PITNKL cases were characterized by clinical, morphologic, and immunohistochemical features. RESULTS: Among 79 cases of PITNKLs from 2008 to 2017 in our institution, 40 (50.63%) were extranodal NK/T-cell lymphoma, nasal type (ENKTL); 32 (40.51%) monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL); 6 (7.59%) intestinal T-cell lymphoma, not otherwise specified; and 1 (1.27%) indolent T-cell lymphoma of the gastrointestinal tract. Small intestine (n = 47) was the most common site. Monomorphic epitheliotropic intestinal T-cell lymphoma showed distinctive clinicopathologic features from other subtypes with high expression (96.88%) of spleen tyrosine kinase (SYK) and PD-L1 (87.5%) and the poorest prognosis (P < .001). CD30 was highly expressed in ENKTL (9/17, 57.94%) and irrelevant to prognosis (P > .05). CONCLUSIONS: Cases of PITNKL are biologically heterogeneous; most have a dismal prognosis. SYK and PD-L1 expression might be a significant marker for MEITL and helps differential diagnosis.

Assessment of Ki-67 Proliferative Index in Cytological Samples of Nodal B-Cell Lymphomas.

BACKGROUND: The Ki-67 proliferative index (PI) is part of the diagnosis of nodal B-cell lymphoma (nBCL), but its determination in cytological samples is not standardized. We aimed to establish an approach for the accurate determination of the Ki-67 PI in cytological slides to differentiate between indolent and aggressive nBCLs. METHODS: Patients diagnosed with nBCL by fine-needle aspiration biopsy and subsequent excision biopsy were included. Cell suspensions were prepared from biopsy samples for CD3/Ki-67 double immunocytochemical staining and flow-cytometric verification of lymphoma B-cell counts. The Ki-67 PI was assessed by manual counting and eyeballing in cytology and eyeballing in histology. The cut-off values for the differentiation between aggressive and indolent lymphomas were determined for each method. RESULTS: A strong correlation between manual and flow-cytometric counting of lymphoma B cells was confirmed (interclass correlation coefficient (IC coef.) = 0.78). The correlation of the Ki-67 PI determined in cytological and histological slides was also strong (IC coef. > 0.80). Histologically, 55 cases were classified as indolent and 31 as aggressive nBCLs. KI-67 PI cut-off values of 28.5%, 27.5%, and 35.5% were established for manual counting and eyeballing in cytology and eyeballing in histology, respectively, with high sensitivity and specificity. CONCLUSIONS: The Ki-67 PI, assessed by manual counting and eyeballing in cytological samples, accurately differentiates between indolent and aggressive nBCLs.

Prospects for liquid biopsy approaches in lymphomas.

Analytes within liquid biopsies have emerged as promising alternatives to traditional tissue biopsies for various malignancies, including lymphomas. This review explores the clinical applications of one such liquid biopsy analyte, circulating tumor DNA (ctDNA) in different types of lymphoma, focusing on its role in diagnosis, disease monitoring, and relapse detection. Advancements in next-generation sequencing (NGS) and machine learning have enhanced ctDNA analysis, offering a multi-omic approach to understanding tumor genetics. In lymphoma, ctDNA provides insights into tumor heterogeneity, aids in genetic profiling, and predicts treatment response. Recent studies demonstrate the prognostic value of ctDNA and its potential to improve patient outcomes by facilitating early disease detection and personalized treatment strategies Despite these advancements, challenges remain in optimizing sample collection, processing, assay sensitivity, and overall consensus workflows in order to facilitate integration into routine clinical practice.

Prevalence of malignant neoplasms in celiac disease patients - a nationwide United States population-based study.

BACKGROUND: Celiac disease (CeD) is an autoimmune disorder triggered by the immune response to gluten in genetically predisposed individuals. Recent research has unveiled a heightened risk of developing specific malignant neoplasms (MN) and various malignancies, including gastrointestinal, lymphomas, skin, and others, in individuals with CeD. AIM: To investigate the prevalence of MN in hospitalized CeD patients in the United States. METHODS: Using data from the National Inpatient Sample spanning two decades, from January 2000 to December 2019, we identified 529842 CeD patients, of which 78128 (14.75%) had MN. Propensity score matching, based on age, sex, race, and calendar year, was employed to compare CeD patients with the general non-CeD population at a 1:1 ratio. RESULTS: Positive associations were observed for several malignancies, including small intestine, lymphoma, nonmelanoma skin, liver, melanoma skin, pancreas myelodysplastic syndrome, biliary, stomach, and other neuroendocrine tumors (excluding small and large intestine malignant carcinoid), leukemia, uterus, and testis. Conversely, CeD patients exhibited a reduced risk of respiratory and secondary malignancies. Moreover, certain malignancies showed null associations with CeD, including head and neck, nervous system, esophagus, colorectal, anus, breast, malignant carcinoids, bone and connective tissues, myeloma, cervix, and ovary cancers. CONCLUSION: Our study is unique in highlighting the detailed results of positive, negative, or null associations between different hematologic and solid malignancies and CeD. Furthermore, it offers insights into evolving trends in CeD hospital outcomes, shedding light on advancements in its management over the past two decades. These findings contribute valuable information to the understanding of CeD's impact on health and healthcare utilization.