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Objective To investigate the clinical features and diagnosis and treatment of RAS-associated autoimmune lymphoproliferative disorder (RALD). Methods We reported the clinical data of a case of RALD diagnosed and treated in our hospital in 2019, and reviewed relevant literature on RAS variation retrieved using the keywords “NRAS”, “KRAS”, and “RALD” through PubMed, CNKI, and Wanfang Data between January 2000 and November 2023. Results The patient was hospitalized due to recurrent fevers for 1.5 months with a 1.5 years history of thrombocytopenia. The physical signs included an appearance of mild anemia, an abdominal bulge, a hard liver palpable up to 5 cm below the costal margin, and the spleen edge up to 3 cm below the costal margin. CD4-CD8- cells accounted for 2.3% of lymphocytes. The degranulation of NK cells decreased. Gene sequencing detected a somatic mutation in exon 2 of the NRAS gene c.38G>A(p.G13D). A total of 32 cases of RALD were retrieved, including 13 cases caused by NRAS somatic mutations and 19 cases caused by KRAS somatic mutations. The main clinical features of the 32 patients included splenomegaly, autoimmune anemia, thrombocytopenia, hypergammaglobulinemia, mononuc-leosis, a normal or slightly elevated proportion of double-negative T cells. Conclusion RALD is characterized by hepatosplenomegaly and autoimmunity, and gene testing is helpful for its diagnosis.

Background: Epstein–Barr virus-positive mucocutaneous ulcer is one of the mature B-cell lymphoproliferative diseases occurring in patients with immune dysfunction including those with immunosuppressive treatment such as methotrexate. Case presentation: A Japanese elderly man in his 80s with rheumatoid arthritis on methotrexate was admitted to our hospital complaining persistent pharyngeal pain. Laboratory tests revealed severe pancytopenia, elevated C-reactive protein, and increased creatinine levels. An otolaryngological examination showed ulceration of the right tonsil, from which diagnostic biopsy was performed. The diagnosis of Epstein–Barr virus-positive mucocutaneous ulcer was made and bone marrow aspiration revealed hypocellularity and megaloblastic changes. Pancytopenia was improved after discontinuing methotrexate, and repeated bone marrow aspiration test revealed recovery of normal cellularity and disappearance of dysplasia, confirming the diagnosis of methotrexate intoxication. Tonsil ulcer was improved only with discontinuation of methotrexate, which strongly supported the diagnosis of EBV-MCU. Conclusion: Our case suggested that even this best prognosis form of lymphoproliferative disease could lead to fatal complications if not appropriately managed. [ABSTRACT FROM AUTHOR]

Post-transplantation primary central nervous system lymphoma (PT-PCNSL) is a rare neoplasm that occurs in immunocompromised patients. It can manifest months or years after transplantation, presenting with various neurological symptoms. A 64-year-old woman, who had received a liver transplant due to autoimmune hepatitis, presented with generalized weakness, headache, and confusion. Further investigation revealed multiple ring-enhancing lesions in the right frontal and temporoparietal regions on brain MRI. A brain biopsy confirmed the diagnosis of PT-PCNSL. This case underscores the importance of considering PT-PCNSL in the differential diagnosis of contrast-enhancing brain lesions in post-transplant patients. Timely recognition of PT-PCNSL is crucial for appropriate management and improved outcomes. To the best of our knowledge, this report describes the first instance of isolated CNS lymphoma in a liver transplant recipient, due to autoimmune hepatitis, successfully brought to complete remission with a rituximab-methotrexate regimen. [ABSTRACT FROM AUTHOR]

In 2022, two updated classification systems for lymphoid neoplasms were published by the World Health Organization (WHO Classification of Haematolymphoid Tumours, 5th edition, referred to hereafter as WHO-HAEM5) and the International Consensus Conference (ICC) (Alaggio et al. in Leukemia 36(7):1720–1748, 2022; Campo et al. in Blood 140(11):1229–1253, 2022). Both classifications were conceived by both pathologists and clinicians with expertise in the field. The reasons for this have been reviewed previously (Arber et al. in Virchows Arch 482(1):1–9, 2023; Cree in Leukemia 36(7):1701–1702, 2022, Leukemia 36(11):2750, 2022). Given that both groups were using data-driven processes and consensus and used the revised 4th edition of the WHO Classification of Haematolymphoid Tumours (WHO-HAEM4R) as a starting point, it is not entirely surprising that the resulting classifications are quite similar. However, they are not identical and reflect preferences or approaches for certain unsettled areas as well as preferred terminology. In this review, we will compare nomenclature of the WHO-HAEM5 and ICC classifications, focusing on lymphoid neoplasms and lymphoproliferative disorders (LPDs). [ABSTRACT FROM AUTHOR]

Macrolide antibiotic azithromycin is widely used in clinical practice to treat respiratory tract infections and inflammatory diseases. However, its mechanism of action is not fully understood. Given the involvement of the CD27 pathway in the pathophysiology of various T-lymphocyte-mediated inflammatory, autoimmune, and lymphoproliferative diseases, we examined the impact of AZM on CD27 regulation and potential consequences on CD4+ and CD8+ T-cell phenotypes. Using cellular immunology approaches on healthy donors' peripheral blood mononuclear cells, we demonstrate AZM-mediated downregulation of surface CD27 expression as well as its extracellular release as soluble CD27. Notably, AZM-exposed CD27high (hi) cells were defective in their ability to expand compared to CD27intermediate (Int) and CD27low (lo) subsets. The defective CD27hi subset expansion was found to be associated with impaired cell proliferation and cell division. At the molecular level, the CD27hi subset exhibited lower mTOR activity than other subsets. Functionally, AZM treatment resulted in marked depletion of helper CD4+ (Th1) and cytotoxic CD8+ T-lymphocyte (Tc1)-associated CXCR3+CD27hi effector cells and inhibition of inflammatory cytokine IFN-g production. These findings provide mechanistic insights on immunomodulatory features of AZM on T-lymphocyte by altering the CD27 pathway. From a clinical perspective, this study also sheds light on potential clinical benefits observed in patients on prophylactic AZM regimens against various respiratory diseases and opens avenues for future adjunct therapy against Th1- and Tc1-dominated inflammatory and autoimmune diseases. [ABSTRACT FROM AUTHOR]

The clinical significance of an abnormal free light chain (FLC) test, performed due to unspecific complains in the absence of a known plasma cell dyscrasia (PCD) or lymphoproliferative disease (LPD), is not fully elucidated. We investigated the importance of an abnormal FLC ratio (FLC-R) in this setting. Patients registered in the Maccabi Healthcare Services database, tested for FLC during 2007–2023 without previously documented PCD/LPD or increased total protein (TP) level, were reviewed. Demographics, co-morbidities, and laboratory tests were recorded. FLC-R was defined as normal (0.26–1.65) or slightly (slAb 0.1–0.26/1.65–4), moderately (mAbn 0.1–0.05/4–8) and significantly abnormal (sigAb- < 0.05 or > 8). Factors associated with PCD/LPD and overall survival were identified. In total, 8,661 patients, 2,215 (25.6%) with abnormal FLC-R [2,090 (24.1%)-slAb, 65 (0.75%)-mAbn and 60 (0.7%)-sigAb], were analyzed. Almost none had anemia nor acute renal failure. 14% had concomitant increased immunoglobulins. Within a median follow-up of 52 months, 943 were diagnosed with PCD (816-MGUS, 127-MM/Amyloidosis/plasmacytoma) and 48 with LPD. Median time to PCD and LPD were 19 and 28 months. Multivariate analysis found slAb (HR = 1.8, CI95%:1.53–2.12, p < 0.001), mAbn (HR = 6.3, CI95%:4.16–9.53, p < 0.001), and sigAb FLC (HR = 10.4, CI95%:7.0–15.35, p < 0.001), to be associated with PCD/LPD diagnosis. Decreased IgG, increased IgA, and concomitant comorbidities predicted PCD, whereas increased IgM predicted LPD. Older age, male gender, anemia, decreased albumin, increased IgG and concomitant comorbidities, predicted shorter survival. Our large study emphasizes the independent clinical significance of abnormal FLC-R as a predictor of PCD/LPD diagnosis even in patients with normal TP level, promoting early detection of PCD/LPD. [ABSTRACT FROM AUTHOR]

The digital revolution in healthcare, amplified by the COVID-19 pandemic and artificial intelligence (AI) advances, has led to a surge in the development of digital technologies. However, integrating digital health solutions, especially AI-based ones, in rare diseases like Waldenström macroglobulinemia (WM) remains challenging due to limited data, among other factors. CURATE.AI, a clinical decision support system, offers an alternative to big data approaches by calibrating individual treatment profiles based on that individual's data alone. We present a case study from the PRECISE CURATE.AI trial with a WM patient, where, over two years, CURATE.AI provided dynamic Ibrutinib dose recommendations to clinicians (users) aimed at achieving optimal IgM levels. An 80-year-old male with newly diagnosed WM requiring treatment due to anemia was recruited to the trial for CURATE.AI-based dosing of the Bruton tyrosine kinase inhibitor Ibrutinib. The primary and secondary outcome measures were focused on scientific and logistical feasibility. Preliminary results underscore the platform's potential in enhancing user and patient engagement, in addition to clinical efficacy. Based on a two-year-long patient enrollment into the CURATE.AI-augmented treatment, this study showcases how AI-enabled tools can support the management of rare diseases, emphasizing the integration of AI to enhance personalized therapy. [ABSTRACT FROM AUTHOR]

Epstein-Barr virus (EBV) related post-transplant lymphoproliferative disorder (EBV-PTLD) is a life-threatening complication after hematopoietic stem cell transplantation (HSCT) or solid organ transplantation (SOT), for which no standard therapeutic means have been developed. Significant increase expression of natural killer group 2 member D ligands (NKG2DLs) was observed on B-lymphoblastoid cells of EBV-PTLD, indicating NKG2DLs as potential therapeutic targets for treatment of EBV-PTLD. In this study, the recombinant constructs of NKG2D CAR and IL-15/IL-15Rα-NKG2D CAR were generated with a retroviral vector and then transduced to human T cells to produce NKG2D CAR-T and IL-15/IL-15Rα-NKG2D CAR-T cells, respectively. B-lymphoblastoid cell lines (B-LCLs) and the xenografted mouse models were established to evaluate the efficacy of these CAR-T cells. IL-15/IL-15Rα-NKG2D CAR-T cells exhibited superior proliferation and antigen-specific cytotoxic effect compared to NKG2D CAR-T, as IL-15/IL-15Rα signaling promoted the expansion of less differentiated central memory T cells (TCM) and increased expression of CD107a and IFN-γ. Moreover, EBV DNA load was dramatically reduced, and 80% B-LCL cells were eliminated by IL-15/IL-15Rα-NKG2D CAR-T cells after co-culturing. In-vivo study confirmed that IL-15/IL-15Rα-NKG2D CAR-T cell therapy significantly enhanced antiviral efficacy in mice, as the serum load of EBV after IL-15/IL-15Rα-NKG2D CAR-T cell infusion was 1500 times lower than the untreated control (P < 0.001). The enhanced efficacy of IL-15/IL-15Rα-NKG2D CAR T cells was probably due to the IL-15/IL-15Rα signaling improved homing and persistence of NKG2D CAR-T cells in vivo, and increased the production of IFN-γ, Perforin, and Granulysin. In conclusion, NKG2D CAR-T cells co-expressing IL-15/IL-15Rα promoted the central memory CAR T cell proliferation and improved the homing and persistence of CAR T cells in vivo, resulting in enhanced anti-tumor and anti-viral effects in treating EBV-PTLD. [ABSTRACT FROM AUTHOR]

Introduction: Agarose gel‐based conventional and real‐time allele‐specific polymerase chain reaction (AS‐PCR) assays are currently used for sensitive detection and quantification of MYD88 L265P mutation. Visual inspection of an agarose gel can often be ambiguous. We propose a new allele‐specific quantification PCR (AS‐qPCR) assay, PlentiPlex™ MYD88 Waldenström lymphoma qPCR assay, that uses Intercalating Nucleic Acid (INA®) technology for increased affinity and specificity. Methods: This study compares PlentiPlex™ MYD88 Waldenström lymphoma qPCR assay with conventional AS‐PCR. We included a total of 102 peripheral and bone marrow blood samples from 94 patients with a lymphoproliferative disorder. Droplet digital PCR (ddPCR) was used as a third method in case of discrepancy. Results: A positive percent agreement of 100% (95% CI 0.92–1.0) and a negative percent agreement of 98% (95% CI 0.90–1.0) were found between the conventional AS‐PCR and the AS‐qPCR methods. Including the ddPCR results to validate the discrepant cases, the sensitivity and specificity of PlentiPlex™ MYD88 Waldenström lymphoma qPCR Assay were 1.0 (95% CI 0.97–1.0) and 1.0 (95% CI 0.96–1.0), respectively. Conclusion: Our data demonstrate that PlentiPlex™ MYD88 Waldenström lymphoma qPCR assay is a fast, highly sensitive, and specific method for the detection of MYD88 L265P compared with conventional AS‐PCR. [ABSTRACT FROM AUTHOR]

Background: Epstein–Barr virus (EBV) is a herpesvirus linked to nine different human tumors and lymphoproliferative disorders. Immunosuppression promotes EBV‐driven malignancies. The most frequent EBV‐induced malignancies are lymphomas and nasopharyngeal carcinoma. By promoting smooth muscle proliferation, EBV can induce EBV‐associated smooth muscle tumors (EBV‐SMT). EBV‐SMT is a rare oncological entity for which no current guideline for diagnosis or management exists. Data on posttransplant EBV‐SMT (PT‐SMT) are scarce in kidney transplant recipients. Methods: We conducted a national multicentric retrospective study and collected cases among transplantation centers in France. Kidney transplant recipients experiencing histologically proven PT‐SMT were included. We collected data on demographic characteristics of patient, history of kidney transplantation, history of PT‐SMT, evolution of graft function, and patient survival. Results: Eight patients were included. The median age at PT‐SMT diagnosis was 31 years (range 6.5–40). PT‐SMT occurred after a median delay of 37.8 months after transplantation (range 6–175). PT‐SMT management consisted in immunosuppressive regimen minimization in all patients. Introduction of mTOR inhibitors was performed in two patients. Four patients (50%) needed chemotherapy. Surgical resection was performed in four patients. At last follow‐up after PT‐SMT diagnosis (median 33 months (range 17–132)), five patients were considered in complete remission, and two patients had died. Two patients experienced graft rejection; two resumed dialysis (25%). All patients with available data presented with impaired graft function at last follow‐up. Conclusion: PT‐SMT is a subacute and progressive disease during kidney transplantation. Even if the risk of developing PT‐SMT is low in kidney transplant recipients (0.07% in our cohort), PT‐SMT is associated with significant graft loss, possibly due to reduced immunosuppression. Developing guidelines could help transplantation teams better manage these patients. [ABSTRACT FROM AUTHOR]

Background: Chronic immunosuppression following pancreas transplantation carries significant risk, including posttransplant lymphoproliferative disease (PTLD). We sought to define the incidence, risk factors, and long‐term outcomes of PTLD following pancreas transplantation at a single center. Methods: All adult pancreas transplants between February 1, 1983 and December 31, 2023 at the University of Minnesota were reviewed, including pancreas transplant alone (PTA), simultaneous pancreas–kidney transplants (SPK), and pancreas after kidney transplants (PAK). Results: Among 2353 transplants, 110 cases of PTLD were identified, with an overall incidence of 4.8%. 17.3% were diagnosed within 1 year of transplant, 32.7% were diagnosed within 5 years, and 74 (67.3%) were diagnosed after 5 years. The overall 30‐year incidence of PTLD did not differ by transplant type—7.4% for PTA, 14.2% for SPK, and 19.4% for PAK (p = 0.3). In multivariable analyses, older age and Epstein‐Barr virus seronegativity were risk factors for PTLD, and PTLD was a risk factor for patient death. PTLD‐specific mortality was 32.7%, although recipients with PTLD had similar median posttransplant survival compared to those without PTLD (14.9 year vs. 15.6 year, p = 0.9). Conclusions: PTLD following pancreas transplantation is associated with significant mortality. Although the incidence of PTLD has decreased over time, a high index of suspicion for PTLD following PTx should remain in EBV‐negative recipients. [ABSTRACT FROM AUTHOR]

The International Pediatric Transplant Association convened an expert consensus conference to assess current evidence and develop recommendations for various aspects of care relating to post‐transplant lymphoproliferative disorders (PTLD) after pediatric solid organ transplantation. This report addresses the outcomes of deliberations by the PTLD Management Working Group. A strong recommendation was made for reduction in immunosuppression as the first step in management. Similarly, strong recommendations were made for the use of the anti‐CD20 monoclonal antibody (rituximab) as was the case for chemotherapy in selected scenarios. In some scenarios, there is uncoupling of the strength of the recommendations from the available evidence in situations where such evidence is lacking but collective clinical experiences drive decision‐making. Of note, there are no large, randomized phase III trials of any treatment for PTLD in the pediatric age group. Current gaps and future research priorities are highlighted. [ABSTRACT FROM AUTHOR]

The classification of primary cutaneous lymphomas and lymphoproliferative disorders (LPD) is continuously evolving by integrating novel clinical, pathological and molecular data. Recently two new classifications for haematological malignancies including entities of cutaneous lymphomas were proposed: the 5th edition of the WHO classification of haematolymphoid tumours and the International Consensus Classification (ICC) of mature lymphoid neoplasms. This article provides an overview of the changes introduced in these two classifications compared to the previous WHO classification. The main changes shared by both classifications include the downgrading of CD8+ acral T‐cell lymphoma to CD8+ acral T‐cell LPD, and the recognition of entities that were previously categorized as provisional and have now been designated as definite types including primary cutaneous small or medium CD4+ T‐cell LPD, primary cutaneous gamma/delta T‐cell lymphoma, primary cutaneous CD8+ aggressive epidermotropic cytotoxic T‐cell lymphoma, Epstein–Barr virus‐positive mucocutaneous ulcer. Both classifications consider primary cutaneous marginal zone B‐cell clonal neoplasm as an indolent disease but use a different terminology: primary cutaneous marginal zone lymphoma (WHO) and primary cutaneous marginal zone LPD (ICC). The 5th WHO classification further introduces and provides essential and desirable diagnostic criteria for each disease type and includes chapters on reactive B‐ or T‐cell rich lymphoid proliferations formerly referred as cutaneous pseudolymphomas, as well as histiocyte and CD8 T‐cell rich LPD in patients with inborn error of immunity. As already emphasized in previous lymphoma classifications, the importance of integrating clinical, histological, phenotypic and molecular features remains the crucial conceptual base for defining cutaneous (and extracutaneous) lymphomas. [ABSTRACT FROM AUTHOR]

Methotrexate (MTX) may induce immunosuppression and facilitate the onset of lymphoproliferative disorders (LPD). Most cases of MTX-LPD occur in patients with rheumatoid arthritis; the incidence is high in Japan. Vitreoretinal lymphoma (VRL) is a rare non-Hodgkin's lymphoma that can masquerade as steroid-resistant chronic uveitis, leading to fatal diagnostic delay. A 68-year-old woman exhibited optic disc swelling and retinal vasculitis causing floaters in the right eye. She was undergoing long-term MTX treatment for rheumatoid arthritis; she previously had been diagnosed with MTX-LPD, which regressed upon discontinuation of MTX. Steroid therapy was ineffective for optic disc swelling and retinal vasculitis; her best-corrected visual acuity decreased to 20/400. Vitreous biopsy revealed VRL, which was successfully treated with high-dose MTX-based systemic chemotherapy and intravitreal injections of MTX. To our knowledge, this is the first case report of VRL in a patient with an autoimmune disease who have a history of MTX-LPD. [ABSTRACT FROM AUTHOR]

Chimeric Antigen Receptor T-cell (CAR-T) therapies are transforming the treatment of B-cell lymphoproliferative disorders and multiple myeloma, yet global access challenges and barriers for their implementation persist. Global access disparities persist, particularly for persons living in low and middle-income countries and for underserved populations in high income countries. In this review we address patient-related factors including age, comorbidities, fitness, race and ethnicity, and geographic location for CAR-T access. Also, we review disease-related and health system barriers like disease biology, potential for short and long-term toxicity, insurance access, referrals, supply and manufacturing, regulation, costs and treatment center capacity. Lastly, alternatives for overcoming these barriers exemplified by research efforts worldwide are discussed, emphasizing the need for a multifaceted approach from all stakeholders to improve global accessibility and ensure equitable access and improved outcomes for patients worldwide. [ABSTRACT FROM AUTHOR]

B-cell prolymphocytic leukemia (B-PLL) was recognized as a distinct entity in the fourth edition of the World Health Organization (WHO) classification for hematolymphoid neoplasms (WHO-HAEM4); however, its de novo presentation has been removed from the upcoming 5th edition classification (WHO-HAEM5). We present a case of a 65-year-old man with leukocytosis, fatigue, and no organomegaly by imaging. Bone marrow examination showed a prolymphocytoid population comprising 78% of the marrow elements. After thorough exclusion of other entities by clinical parameters and ancillary methods, we concluded that this case represents a de novo case of B-PLL. [ABSTRACT FROM AUTHOR]

Simple Summary: We present flow cytometry and clonality evaluation as a reliable and useful method for characterizing feline lymphomas. Neoplastic cell size is a crucial factor for prognosis. We have developed a novel system for cell sizing by flow cytometry that was 82–90% concordant with the gold standard of cytology. Moreover, from our retrospective analysis of survival for small versus large cells, we saw consistency between both methodologies. These results highlight the utility of our approach in providing prognostic insights. Feline lymphoma, a prevalent cancer in cats, exhibits varied prognoses influenced by anatomical site and cellular characteristics. In this study, we investigated the utility of flow cytometry and clonality analysis via PCR for antigen receptor rearrangement (PARR) with respect to characterizing the disease and predicting prognosis. For this purpose, we received fine needle aspirates and/or blood from 438 feline patients, which were subjected to flow cytometry analysis and PARR. We used a subset of the results from patients with confirmed B- or T-cell lymphomas for comparison to cytological or histological evaluation (n = 53). Using them as a training set, we identified the optimal set of flow cytometry parameters, namely forward scatter thresholds, for cell size categorization by correlating with cytology-defined sizes. Concordance with cytological sizing among this training set was 82%. Furthermore, 90% concordance was observed when the proposed cell sizing was tested on an independent test set (n = 24), underscoring the reliability of the proposed approach. Additionally, lymphoma subtypes defined by flow cytometry and PARR demonstrated significant survival differences, validating the prognostic utility of these methods. The proposed methodology achieves high concordance with cytological evaluations and provides an additional tool for the characterization and management of feline lymphoproliferative diseases. [ABSTRACT FROM AUTHOR]

Primary cutaneous T cell lymphomas (CTCL) are a heterogenous group of non-Hodgkin lymphomas derived from skin-homing T cells. These include mycosis fungoides and its leukemic variant Sezary syndrome, as well as the CD30+ lymphoproliferative disorders. In this review, we provide a summary of the current literature on CTCL, with a focus on the immunopathogenesis and treatment of mycosis fungoides and Sezary syndrome. Recent advances in immunology have provided new insights into the biology of malignant T cells. This in turn has led to the development of new therapies that modulate the immune system to facilitate tumor clearance or target specific aspects of tumor biology. [ABSTRACT FROM AUTHOR]

Purpose: Natural killer (NK) cells are traditionally identified by flow cytometry using a combination of markers (CD16/CD56/CD3), because a specific NK-cell marker is still missing. Here we investigated the utility of CD314, CD335 and NKp80, compared to CD16/CD56/CD3, for more robust identification of NK-cells in human blood, for diagnostic purposes. Methods: A total of 156 peripheral blood (PB) samples collected from healthy donors (HD) and patients with diseases frequently associated with loss/ downregulation of classical NK-cell markers were immunophenotyped following EuroFlow protocols, aimed at comparing the staining profile of total blood NK-cells for CD314, CD335 and NKp80, and the performance of distinct marker combinations for their accurate identification. Results: NKp80 showed a superior performance (vs. CD314 and CD335) for the identification of NK-cells in HD blood. Besides, NKp80 improved the conventional CD16/CD56/CD3-based strategy to identify PB NK-cells in HD and reactive processes, particularly when combined with CD16 for further accurate NK-cell-subsetting. Although NKp80+CD16 improved the identification of clonal/tumor NK-cells, particularly among CD56- cases (53%), aberrant downregulation of NKp80 was observed in 25% of patients, in whom CD56 was useful as a complementary NK-cell marker. As NKp80 is also expressed on T-cells, we noted increased numbers of NKp80+ cytotoxic T-cells at the more advanced maturation stages, mostly in adults. Conclusion: Here we propose a new robust approach for the identification of PB NK-cells, based on the combination of NKp80 plus CD16. However, in chronic lymphoproliferative disorders of NK-cells, addition of CD56 is recommended to identify clonal NK-cells, due to their frequent aberrant NKp80- phenotype. [ABSTRACT FROM AUTHOR]

Background: The NFLymSI-18 is a patient-reported outcome measure comprised of the highest priority symptoms, emotional concerns, treatment side effects, and other concerns identified by lymphoma patients and oncologists. This study assessed the content validity of the NFLymSI-18 for patients with indolent B-cell non-Hodgkin's lymphoma (iNHL), with a focus on the Disease-Related Symptoms Physical (DRS-P) subscale. Methods: Patients with a confirmed iNHL diagnosis who had received one or more lines of treatment were recruited during clinic visits. Patients described their symptoms, treatment side effects, and emotional concerns related to iNHL in a semi-structured interview. Qualitative data were analyzed using NVivo10. Results: Data saturation was obtained by the 18th interview. Most participants (67%) had follicular lymphoma. 28% of participants had marginal zone lymphoma, and one participant had lymphoplasmacytoid lymphoma/Waldenström macroglobulinemia. Mean age of the 18 participants was 67 years. 56% of the sample was male. Most participants (67%) had a college or advanced degree. When asked to describe their iNHL symptoms, patients most often discussed swelling (n = 14), fatigue (n = 11), and pain (n = 8). The following symptoms were mentioned by three patients each: anxiety, appetite loss, rash, sleep disruption, trouble breathing, and malaise. Mapping of NFLymSI-18 content to these concerns showed the instrument includes all those most frequently mentioned symptoms. Conclusions: This study supports the content validity of the NFLymSI-18, including its DRS-P Subscale, for patients with iNHL. The instrument shows strong validity for the most referenced symptoms of swelling, fatigue, and pain. The diversity of additional symptoms reported by patients is consistent with the heterogeneous symptomology of iNHL. [ABSTRACT FROM AUTHOR]

Background Objective Methods Results Conclusion Primary cutaneous CD4+ small/medium T‐cell lymphoproliferative disorder (PCSM‐LPD) is an increasingly recognized entity with heterogeneous management strategies that may include radiotherapy.Our aim was to characterize treatment options for PCSM‐LPD, with a focus on the role of radiotherapy.This is a retrospective review of 46 patients seen in the Cutaneous Lymphoma Program at the University of Texas MD Anderson Cancer Center, with a clinicopathologic review consistent with PCSM‐LPD. All patients were biopsied and underwent observation, topical/intralesional steroids, and/or radiotherapy. Patients were confirmed to have residual disease prior to radiotherapy.All patients achieved a complete response (CR). Sixteen patients (35%) received focal radiotherapy, with a CR in 15 (94%). The CR rate following ultra‐low‐dose radiotherapy (4 Gy in 1–2 fractions) was 92%. There was no grade 3 toxicity after radiotherapy. Thirty patients were managed without radiotherapy, with excision and observation or steroids.Primary cutaneous CD4+ small/medium T‐cell lymphoproliferative disorder has excellent outcomes, and management strategies may include observation following biopsy, steroids, or radiation. Ultra‐low‐dose radiotherapy results in excellent outcomes with limited toxicity and is effective for persistent lesions after steroidal therapy. [ABSTRACT FROM AUTHOR]

Background: Epstein-Barr virus-associated lymphoproliferative disorders (EBV-LPDs) are a group of disorders involving lymphoid tissues or lymphocytes. The epidemiology and economic burden of hospitalized children with EBV-LPDs in China have not been well studied. This study aimed to reveal the epidemic characteristics and disease burden of EBV-LPDs among the Chinese hospitalized children, providing strategies for the prevention and management. Methods: This study was based on the FUTang Updating medical REcords (FUTURE) database of China and collected the medical records from 27 tertiary children's hospitals between January 2016 and December 2021 in China, counting five types of EBV-LPDs, namely EBV-positive T-cell lymphoproliferative disease, NK/T cell lymphoma, extranodal NK/T-cell lymphoma (nasal type), systemic EBV-positive T-cell lymphoproliferative disease of childhood and posttransplant lymphoproliferative disorders. We conducted a retrospective syhthesis and analysis of the epidemiological characteristics, expenses, length of stay (LOS), as well as complications among hospitalized children diagnosed with five types of EBV-LPDs and compared parameters using appropriate statistical tests. Results: The study described 153 children aged 0–18 years hospitalized with EBV-LPDs from 2016 to 2021 in the FUTURE database. The male-to-female ratio was 1.10:1, and more than half of the age distribution was in the 6–12 y group. Among EBV-LPDs cases, EBV+ T-LPD accounted for the largest proportion (65.36%). Complications were presented in 93 children with EBV-LPDs, mainly hemophagocytic lymphohistiocytosis (HLH). The median LOS of NKTL was 26.5 days [interquartile range (IQR) = 3–42], which was the longest among EBV-LPDs. The median hospitalization cost of PTLD was 10 785.74 United States dollars (IQR = 7 329.38–16 531.18), which was the heaviest among EBV-LPDs. Conclusions: Compared with the total number of hospitalized children in China during the same period and in the same age group, the proportion of EBV-LPD is very low. EBV-LPD can develop in all age groups, but it is more common in school-age children. Among 5 EBV-LPDs, the disease with the highest proportion is EBV+ T-LPD. The overall disease burden of EBV-LPD was heavy, especially the economic burden. HLH was one of the most common complications, which could directly affect the burden of patients because of prolonged hospitalization. These data are taken from a very large database, illustrating the epidemiological and economic burden of EBV-LPDs hospitalized children in China, which enriched the existing epidemiological and disease burden content of EBV-LPDs. [ABSTRACT FROM AUTHOR]

Budd-Chiari syndrome (BCS) is characterized by hepatic venous outflow tract obstruction and is commonly associated with an underlying hypercoagulable state. Systemic amyloidosis is a disorder characterized by systemic deposition of misfolded proteins leading to end organ damage. Amyloidosis is commonly associated with coagulation abnormalities, mainly leading to increased bleeding diathesis. Here, we report a case of amyloid light chain (AL) amyloidosis presenting as BCS. A 40-year-old man presented with abdominal distension along with anorexia and weight loss. On evaluation, he had severe hypoalbuminemia, raised alkaline phosphatase, and non-visualization of hepatic veins on abdominal imaging. Further evaluation confirmed the diagnosis of AL amyloidosis with renal, cardiac, and hepatic involvement. AL amyloidosis rarely can present with BCS. A high index of suspicion is needed as symptoms can be variable and non-specific. [ABSTRACT FROM AUTHOR]

Background: Hydroa vacciniform is a rare chronic photodermatosis that may be related to Epstein-Barr virus infection. Additionally, it is associated with progressive deformity and the risk of developing cutaneous lymphomas. Methods: This is a descriptive observational study detailing a photodermatosis in a male pediatric patient, who presented with chronic blisters and ulcers in photoexposed areas, along with progressive deformity and a history of exposure to Epstein-Barr virus. Results: Histopathology revealed an angiocentric lymphocytic infiltrate suggestive of hydroa vacciniform and the immunohistochemistry markers for cutaneous lymphoma associated with Epstein-Barr virus were positive. Conclusions: This is a report of a hydroa vacciniform-like lymphoma with previous exposure to Epstein-Barr virus, without systemic involvement. It is characterized by an aggressive histological and immunohistochemical pattern with unknown prognosis. [ABSTRACT FROM AUTHOR]

Background: Recurrence, even after years from the last treatment, characterizes lymphoproliferative disorders. Therefore, patients in complete remission from the disease should be followed up with periodic clinical checks. There is not a consensus on the role of imaging for this aim, because the radiological techniques used at the time of diagnosis expose patients to a risk of ionizing radiation damage. Whole-body magnetic resonance imaging with diffusion-weighted imaging (WB-MRI-DWI) has given similar results to gold standard techniques in detecting lymphoma in the involved sites without ionizing radiation. In this retrospective real-life study, we aimed to assess the accuracy of WB-MRI-DWI during follow-ups of lymphoma patients in terms of sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Methods: Lymphoma patients who were subject to at least one WB-MRI-DWI during follow-up between February 2010 and February 2022 were enrolled. Results: Based on our investigation, the calculated sensitivity of WB-MRI-DWI was 100% (95% CI: 99.4–100.0), the specificity was 98.6% (95% CI: 97.4–99.3), PPV was 79% (95% CI: 75.9–81.9), and NPV was 100% (95% CI: 99.4–100.0). Conclusions: Despite the possibility of poor patient compliance and the identification of false positives, WB-MRI-DWI examination demonstrated an excellent sensitivity in ruling out the disease relapse. [ABSTRACT FROM AUTHOR]

Pediatric solid organ transplant (SOT) recipients face a challenging balance between immunosuppression and graft rejection. While Epstein–Barr Virus (EBV) and cytomegalovirus (HCMV) are known contributors to post-transplant lymphoproliferative disease and graft rejection, respectively, the roles of herpesvirus 6 and 7 (HHV6 and HHV7) and the impact of these herpesviruses on cytokine levels remain unclear, leading to gaps in clinical practice. In this associative study, we measured 17 cytokines using a Bio-Plex assay in a meticulously curated plasma sample pool (N = 158) from pediatric kidney and liver transplant recipients over a one-year follow-up period. The samples included virus-negative and virus-positive cases, either individually or in combination, along with episodes of graft rejection. We observed that the elevation of IL-4, IL-8, and IL-10 correlated with graft rejection. These cytokines were elevated in samples where HCMV or HHV6 were detected alone or where EBV and HHV7 were co-detected. Interestingly, latent EBV, when detected independently, exhibited an immunomodulatory effect by downregulating cytokine levels. However, in co-detection scenarios with β-herpesviruses, EBV transitioned to a lytic state, also associating with heightened cytokinemia and graft rejection. These findings highlight the complex interactions between the immune response and herpesviruses in transplant recipients. The study advocates for enhanced monitoring of not only EBV and HCMV but also HHV6 and HHV7, providing valuable insights for improved risk assessment and targeted interventions in pediatric SOT recipients. [ABSTRACT FROM AUTHOR]

Lymphomas of the eye and ocular adnexa are rare lymphoproliferative diseases of the ocular and ocular adnexal tissue. The incidence of these diseases has been rapidly increasing over the past few decades. The exact pathogenesis remains unknown, but it is postulated to be multifactorial and includes genetic aberrations, epigenetic and environmental factors, infectious agents, and chronic antigenic stimulation. The majority of ocular and ocular adnexal lymphomas are of B-cell origin, except for eyelid lymphomas, which are more often of T-cell type. Lymphoproliferative diseases of ocular and ocular adnexal structures are either primary, when they arise in the eye, orbit, lacrimal gland, eyelid, and/or conjunctiva, or secondary extranodal manifestation of systemic lymphoma. Diagnosis is challenging and requires a multidisciplinary approach involving ophthalmologists, dermatologists, oncologists, and radiation oncologists. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Rituximab‐induced serum sickness (RISS) is a rare complication of Rituximab (RTX) in immunobullous disorders. Clinicians should be aware of the occurrence of serum sickness symptoms during RTX administration, and prompt initiation of corticosteroid therapy is crucial in these patients. Additionally, RISS may occur with subsequent RTX doses and patients should be counseled accordingly. Rituximab (RTX) is a chimeric monoclonal anti‐CD20 antibody which has gained approval for the treatment of various autoimmune and lymphoproliferative disorders. While RTX‐induced minor reactions, including immediate infusion‐related reactions, are common, serum sickness is rare. Limited data exist regarding rituximab‐induced serum sickness (RISS) in pemphigus vulgaris (PV) and mucous membrane pemphigoid (MMP). We report two cases of RISS following RTX administration in PV and MMP patients. Both patients presented with typical symptoms of serum sickness after RTX infusion, necessitating drug cessation and corticosteroid therapy for resolution. RISS represents a rare complication of RTX therapy. Clinicians should maintain awareness of serum sickness presentations during and post‐RTX administration. [ABSTRACT FROM AUTHOR]

Post-transplant lymphoproliferative disorder (PTLD) is a common secondary malignancy after transplantation, which has been recognized as a life-threatening complication. Hodgkin lymphoma (HL)-type PTLD is the rarest of four subtypes of PTLD, which has no treatment guideline due to its rarity. HL-type PTLD includes classical HL-type PTLD (cHL-PTLD) and HL-like PTLD. In our study, we reported the case of successful treatment using brentuximab vedotin (BV) plus sirolimus for a patient with classical HL-type PTLD in detail. Lymph node biopsy showed a picture of classical HL with mixed cellularity subtype, and immunophenotyping suggested CD30 strong positivity. Due to his impaired physical condition, we decided against intensive chemotherapy and started BV treatment with immunosuppressive agents switched to sirolimus. The 66-year-old patient with cHL-PTLD had achieved a durable complete remission for over a 1-year follow-up period. Additionally, we analyzed the clinical profile and outcomes in PTLD patients who used BV monotherapy or combined therapy by literature review. In summary, this case-based review might provide clues that treatment of cHL-PTLD with new modalities such as BV monotherapy or combination therapy, together with improvements in the immunosuppressive regimens like sirolimus, might be a feasible and chemotherapy-free approach, but warrants further evaluation in a larger patient cohort. [ABSTRACT FROM AUTHOR]

Background: De novo malignancies (DNMs) are a major adverse event after solid organ transplantation; however, their characteristics and recent trends after living‐donor liver transplantation (LDLT) remain unclear. Methods: We retrospectively reviewed 1781 primary LDLT recipients (1990–2020) and annually calculated standardized incidence ratios (SIRs) of DNMs compared to the age‐adjusted Japanese general population. Results: After 21 845 person‐years follow‐up, 153 DNM lesions (8.6%) were identified in 131 patients (7.4%). The incidence was 0.007 person‐years. DNMs included 81 post‐transplant lymphoproliferative disorders (PTLDs), 14 colorectal, 12 lung, and 12 gastric cancers, and so on. Comorbid DNMs significantly worsened recipient survival than those without (p <.001). The 5‐ and 10‐year recipient survival after DNM diagnosis were 65% and 58%, respectively. Notably, SIR1993–1995: 8.12 (95% CI: 3.71–15.4, p <.001) and SIR1996–1998: 3.11 (1.34–6.12, p =.01) were significantly high, but had decreased time‐dependently to SIR2005–2007: 1.31 (0.68–2.29, p =.42) and SIR2008–2010: 1.34 (0.75–2.20, p =.33), indicating no longer significant difference in DNMs development. Currently, however, SIR2014–2016: 2.27 (1.54–3.22, p <.001) and SIR2017–2019: 2.07 (1.40–2.96, p <.001) have become significantly higher again, reflecting recent aging of recipients (>50 years) and resultant increases in non‐PTLD DNMs. Furthermore, characteristically in LDLT, the fewer the donor‐recipient HLA‐mismatches, the less the post‐transplant DNMs development. Conclusion: DNM development after LDLT was significantly higher than in the general population due to higher PTLD incidence (1993‐1998), but once became equivalent (2005‐2013), then significantly increased again (2014‐2019) due to recent recipient aging and resultant increase in solid cancers. [ABSTRACT FROM AUTHOR]

Lymphoproliferative disease virus (LPDV) was first documented in wild turkeys in North America in 2009. LPDV infection is often subclinical but can manifest as lymphoid proliferation or round cell neoplasia. Despite high prevalence across many sampled areas corresponding to declining populations of wild turkeys, knowledge regarding LPDV pathogenesis, risk factors for disease development, and associated impacts on population dynamics are unknown. To understand transmission, viral shedding, and tissue tropism, we inoculated 21 domestic turkeys via the oral cavity, crop, nasal cavity, subcutis, or coelomic cavity. For 12 weeks, oropharyngeal swabs, cloacal swabs, and whole blood were collected weekly. At 1 week postinoculation, 3 turkeys (3/21; 14%) had detectable LPDV proviral DNA in blood by polymerase chain reaction, and 10 developed DNAemia (50%; 10/20) by 12 weeks. LPDV proviral DNA was intermittently detected in oropharyngeal and cloacal swabs. Splenomegaly was the most consistent gross finding in DNAemic birds (8/11; 73%). Lymphoid hyperplasia in the spleen was the most significant microscopic finding (9/11; 82%). Three turkeys (3/11; 27%) developed round cell neoplasia characterized by sheets of pleomorphic, round to polygonal cells in the adrenal gland, bone marrow, skin, small intestine, and/or spleen. LPDV was detected in the spleen and bone marrow from all turkeys with DNAemia and all neoplasms. Our study establishes that infection and disease with North American LPDV from wild turkeys can be experimentally reproduced in domestic turkeys, laying the groundwork for future investigations into LPDV pathogenesis, development of diagnostic techniques, and understanding the impacts of LPDV on wild turkey populations. [ABSTRACT FROM AUTHOR]