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Genes May 2024Primary cutaneous lymphomas (PCLs) are a heterogeneous group of lymphoproliferative disorders caused by the accumulation of neoplastic T or B lymphocytes in the skin.... (Review)
Review
Primary cutaneous lymphomas (PCLs) are a heterogeneous group of lymphoproliferative disorders caused by the accumulation of neoplastic T or B lymphocytes in the skin. Sézary syndrome (SS) is an aggressive and rare form of cutaneous T cell lymphoma (CTCL) characterized by an erythroderma and the presence of atypical cerebriform T cells named Sézary cells in skin and blood. Most of the available treatments for SS are not curative, which means there is an urgent need for the development of novel efficient therapies. Recently, targeting cancer metabolism has emerged as a promising strategy for cancer therapy. This is due to the accumulating evidence that metabolic reprogramming highly contributes to tumor progression. Genes play a pivotal role in regulating metabolic processes, and alterations in these genes can disrupt the delicate balance of metabolic pathways, potentially contributing to cancer development. In this review, we discuss the importance of targeting energy metabolism in tumors and the currently available data on the metabolism of Sézary cells, paving the way for potential new therapeutic approaches aiming to improve clinical outcomes for patients suffering from SS.
Topics: Humans; Sezary Syndrome; Skin Neoplasms; Energy Metabolism; Animals
PubMed: 38790264
DOI: 10.3390/genes15050635 -
Medical Molecular Morphology May 2024A 67-year-old man underwent renal transplantation in his twenties. He developed refractory pleural effusion, with many large lymphocytes with severe atypia and mitosis...
A 67-year-old man underwent renal transplantation in his twenties. He developed refractory pleural effusion, with many large lymphocytes with severe atypia and mitosis in the effusion, indicating malignant lymphoma. He finally died of respiratory failure. An autopsy revealed atypical lymphocytes positive for CD3, CD4, and CD30 and negative for CD8, CD20, PAX5, human herpesvirus (HHV) 8, and Epstein-Barr virus-encoded small RNAs by immunohistochemistry and in situ hybridization. Atypical lymphocytes also had T-cell receptor gene rearrangements Jβ2, Jγ2, and Jδ1 and chromosomal aberrations der(8)t(1;8)(q21;p21), add(13)(q12), add(14)(q32), and add(16)(q12-13). A few atypical lymphocytes were present at other sites. We finally diagnosed this case as monomorphic T-cell post-transplant lymphoproliferative disorder with features of HHV8-negative primary effusion lymphoma. A literature review only identified six cases (four HHV8-negative, two HHV8-positive) of effusion lymphoma of T-cell type, including the present case. Interestingly, about half of HHV8-negative and HHV8-positive cases had a history of renal transplantation in their twenties. All cases showed tumor CD30 expression, whereas CD4 and CD8 expressions were inconsistent. These findings indicated that this lymphoma may be associated with post-transplant lymphoproliferative disorder by renal transplantation at a young age, although further cases need to be analyzed.
PubMed: 38780761
DOI: 10.1007/s00795-024-00388-x -
Journal of Clinical Immunology May 2024RHOH, an atypical small GTPase predominantly expressed in hematopoietic cells, plays a vital role in immune function. A deficiency in RHOH has been linked to...
RHOH, an atypical small GTPase predominantly expressed in hematopoietic cells, plays a vital role in immune function. A deficiency in RHOH has been linked to epidermodysplasia verruciformis, lung disease, Burkitt lymphoma and T cell defects. Here, we report a novel germline homozygous RHOH c.245G > A (p.Cys82Tyr) variant in a 21-year-old male suffering from recurrent, invasive, opportunistic infections affecting the lungs, eyes, and brain. His sister also succumbed to a lung infection during early adulthood. The patient exhibited a persistent decrease in CD4 T, B, and NK cell counts, and hypoimmunoglobulinemia. The patient's T cell showed impaired activation upon in vitro TCR stimulation. In Jurkat T cells transduced with RHOH, a similar reduction in activation marker CD69 up-regulation was observed. Furthermore, the C82Y variant showed reduced RHOH protein expression and impaired interaction with the TCR signaling molecule ZAP70. Together, these data suggest that the newly identified autosomal-recessive RHOH variant is associated with T cell dysfunction and recurrent opportunistic infections, functioning as a hypomorph by disrupting ZAP70-mediated TCR signaling.
Topics: Humans; Male; Young Adult; Homozygote; Jurkat Cells; Lymphocyte Activation; Opportunistic Infections; Pedigree; Receptors, Antigen, T-Cell; Recurrence; T-Lymphocytes; ZAP-70 Protein-Tyrosine Kinase
PubMed: 38775840
DOI: 10.1007/s10875-024-01735-4 -
RMD Open May 2024Patients with X linked agammaglobulinemia are susceptible to enterovirus (EV) infections. Similarly, severe EV infections have been described in patients with impaired...
OBJECTIVE
Patients with X linked agammaglobulinemia are susceptible to enterovirus (EV) infections. Similarly, severe EV infections have been described in patients with impaired B-cell response following treatment with anti-CD20 monoclonal antibodies (mAbs), mostly in those treated for haematological malignancies. We aimed to describe severe EV infections in patients receiving anti-CD20 mAbs for immune-mediated inflammatory diseases (IMIDs).
METHODS
Patients were included following a screening of data collected through the routine surveillance of EV infections coordinated by the National Reference Center and a review of the literature. Additionally, neutralising antibodies were assessed in a patient with chronic EV-A71 meningoencephalitis.
RESULTS
Nine original and 17 previously published cases were retrieved. Meningoencephalitis (n=21/26, 81%) associated with EV-positive cerebrospinal fluid (n=20/22, 91%) was the most common manifestation. The mortality rate was high (27%). EV was the only causal agents in all reported cases. Patients received multiple anti-CD20 mAbs infusions (median 8 (5-10)), resulting in complete B-cell depletion and moderate hypogammaglobulinemia (median 4.9 g/L (4.3-6.7)), and had limited concomitant immunosuppressive treatments. Finally, in a patient with EV-A71 meningoencephalitis, a lack of B-cell response to EV was shown.
CONCLUSION
EV infection should be evoked in patients with IMIDs presenting with atypical organ involvement, especially meningoencephalitis. Anti-CD20 mAbs may lead to impaired B-cell response against EV, although an underlying primary immunodeficiency should systematically be discussed.
Topics: Humans; Enterovirus Infections; Male; Female; Antibodies, Monoclonal; Antigens, CD20; Middle Aged; Adult; Meningoencephalitis; Aged; Rituximab; B-Lymphocytes; Agammaglobulinemia; Inflammation
PubMed: 38772678
DOI: 10.1136/rmdopen-2023-004036 -
Journal of Cutaneous Pathology May 2024Mycosis fungoides (MF) has been widely reported to mimick a considerable number of different dermatoses, including scarring alopecia, bullous dermatoses or cysts, and...
Mycosis fungoides (MF) has been widely reported to mimick a considerable number of different dermatoses, including scarring alopecia, bullous dermatoses or cysts, and comedones. In atypical presentations, histopathology is essential for the diagnosis. We present two cases of MF with clinical urticarial lesions and a striking blood involvement that responded to mogamulizumab treatment. Histopathologically, both cases had classic MF features and shared a peculiar immunophenotype, with positivity for CD25 and FOXP3. Differential diagnoses included urticarial lymphomatoid drug reactions and other lymphomas, like T-cell prolymphocytic leukemia, atypical Sézary syndrome, or adult T-cell lymphocytic leukemia. A low suspicion threshold is necessary for the diagnosis of atypical presentations of MF.
PubMed: 38769716
DOI: 10.1111/cup.14642 -
Research Square May 2024Ductal carcinoma (DCIS) constitutes an array of morphologically recognized intraductal neoplasms in the mammary ductal tree defined by an increased risk for subsequent...
Ductal carcinoma (DCIS) constitutes an array of morphologically recognized intraductal neoplasms in the mammary ductal tree defined by an increased risk for subsequent invasive carcinomas at or near the site of biopsy detection. However, only 15-45% of untreated DCIS cases progress to invasive cancer, so understanding mechanisms that prevent progression is key to avoid overtreatment and provides a basis for alternative therapies and prevention. This study was designed to characterize the tumor microenvironment and molecular profile of high-risk DCIS that grew to a large size but remained as DCIS. All patients had DCIS lesions >5cm in size with at least one additional high-risk feature: young age (<45 years), high nuclear grade, hormone receptor negativity, HER2 positivity, the presence of comedonecrosis, or a palpable mass. The tumor immune microenvironment was characterized using multiplex immunofluorescence to identify immune cells and their spatial relationships within the ducts and stroma. Gene copy number analysis and whole exome DNA sequencing identified the mutational burden and driver mutations, and quantitative whole-transcriptome/gene expression analyses were performed. There was no association between the percent of the DCIS genome characterized by copy number variants (CNAs) and recurrence events (DCIS or invasive). Mutations, especially missense mutations, in the breast cancer driver genes and were common in this high-risk DCIS cohort (47% of evaluated lesions). Tumor infiltrating lymphocyte (TIL) density was higher in DCIS lesions with TP53 mutations (p=0.0079) compared to wildtype lesions, but not in lesions with mutations (p=0.44). Immune infiltrates were negatively associated with hormone receptor status and positively associated with HER2 expression. High levels of CD3+CD8- T cells were associated with good outcomes with respect to any subsequent recurrence (DCIS or invasive cancer), whereas high levels of CD3+Foxp3+ Treg cells were associated with poor outcomes. Spatial proximity analyses of immune cells and tumor cells demonstrated that close proximity of T cells with tumor cells was associated with good outcomes with respect to any recurrence as well as invasive recurrences. Interestingly, we found that myoepithelial continuity (distance between myoepithelial cells surrounding the involved ducts) was significantly lower in DCIS lesions compared to normal tissue (p=0.0002) or to atypical ductal hyperplasia (p=0.011). Gene set enrichment analysis identified several immune pathways associated with low myoepithelial continuity and a low myoepithelial continuity score was associated with better outcomes, suggesting that gaps in the myoepithelial layer may allow access/interactions between immune infiltrates and tumor cells. Our study demonstrates the immune microenvironment of DCIS, in particular the spatial proximity of tumor cells and T cells, and myoepithelial continuity are important determinants for progression of disease.
PubMed: 38766192
DOI: 10.21203/rs.3.rs-4126092/v1 -
Frontiers in Oncology 2024Richter transformation refers to the progression of an initially slow-growing small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL) into an aggressive...
BACKGROUND
Richter transformation refers to the progression of an initially slow-growing small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL) into an aggressive lymphoma, typically diffuse large B-cell lymphoma (DLBCL) or Hodgkin lymphoma.
CASE PRESENTATION
The patient presented with a rapid onset of localized cervical swelling, accompanied by monoclonal B-cell lymphocytosis displaying a CLL immunophenotype. The histopathological analysis identified a Burkitt lymphoma (BL) located in the submandibular gland and adjacent lymph node. The patient's bone marrow displayed a minor infiltration of monoclonal B-cells with a CLL immunophenotype (< 10%). Molecular analysis demonstrated the presence of the same monoclonal rearrangement in the framework region (FR3 region) of the immunoglobulin heavy chain () locus. High-throughput sequencing of the immunoglobulin heavy and light chains also confirmed the presence of the same rearrangement in SLL/CLL and in the Burkitt lymphoma sample, but also highlighted the presence of a second rearrangement in the Burkitt lymphoma cells, not shared with the SLL/CLL cells in the bone marrow. The patient was treated with DA-EPOCH-R, which lead to a complete metabolic response.
CONCLUSION
This report provides an exceptionally rare description of a CLL-type monoclonal B-cell lymphocytosis transforming into a very aggressive Burkitt lymphoma in a treatment naïve patient.
PubMed: 38764580
DOI: 10.3389/fonc.2024.1296238 -
Communications Biology May 2024B cells are important in tuberculosis (TB) immunity, but their role in the human lung is understudied. Here, we characterize B cells from lung tissue and matched blood...
B cells are important in tuberculosis (TB) immunity, but their role in the human lung is understudied. Here, we characterize B cells from lung tissue and matched blood of patients with TB and found they are decreased in the blood and increased in the lungs, consistent with recruitment to infected tissue, where they are located in granuloma associated lymphoid tissue. Flow cytometry and transcriptomics identify multiple B cell populations in the lung, including those associated with tissue resident memory, germinal centers, antibody secretion, proinflammatory atypical B cells, and regulatory B cells, some of which are expanded in TB disease. Additionally, TB lungs contain high levels of Mtb-reactive antibodies, specifically IgM, which promotes Mtb phagocytosis. Overall, these data reveal the presence of functionally diverse B cell subsets in the lungs of patients with TB and suggest several potential localized roles that may represent a target for interventions to promote immunity or mitigate immunopathology.
Topics: Humans; B-Lymphocytes; Lung; Mycobacterium tuberculosis; Phenotype; Tuberculosis; Tuberculosis, Pulmonary; B-Lymphocyte Subsets; Male; Female; Adult
PubMed: 38755239
DOI: 10.1038/s42003-024-06282-7 -
The Journal of Dermatological Treatment Dec 2024Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma. This study was conducted to evaluate efficacy and safety of interferon (IFN) α-2a...
Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma. This study was conducted to evaluate efficacy and safety of interferon (IFN) α-2a combined with phototherapy for early-stage MF. Thirteen patients with early-stage MF received subcutaneous injections of IFN α-2a at 3 million IU combined with phototherapy three times per week for 6 months. Treatment efficacy was measured by changes in body surface area (BSA) score and modified severity-weighted assessment tool (mSWAT) score at 1, 3, and 6 months after treatment. Histopathologic examinations of skin lesions were performed before and after treatment. After 3 months of treatment, all 13 patients achieved a partial response, and BSA and mSWAT scores were significantly lower than those at baseline ( < 0.001). After 6 months, BSA and mSWAT scores were significantly lower than those at baseline ( < 0.001) and after 3 months ( < 0.05). Eleven patients achieved complete remission and two patients achieved a partial response (overall response rate, 100%). Histopathologic examination showed a significant decrease in the number of atypical lymphocytes in both epidermis and dermis. No severe adverse effects occurred. IFN α-2a in combination with phototherapy may be an effective and safe alternative modality for early-stage MF.
Topics: Humans; Mycosis Fungoides; Male; Middle Aged; Female; Prospective Studies; Skin Neoplasms; Adult; Interferon alpha-2; Treatment Outcome; Aged; Injections, Subcutaneous; Interferon-alpha; Combined Modality Therapy; Phototherapy; Neoplasm Staging; Recombinant Proteins
PubMed: 38754985
DOI: 10.1080/09546634.2024.2350231 -
Clinical Laboratory May 2024The goal was to explore the cognition of diagnosis and treatment level of IgG4-related diseases mainly involving lymph nodes. (Review)
Review
BACKGROUND
The goal was to explore the cognition of diagnosis and treatment level of IgG4-related diseases mainly involving lymph nodes.
METHODS
The clinical manifestations, laboratory indicators, histopathology, and therapeutic effects of a patient with IgG4-RD suspected of lymphoma were analyzed and the relevant literature was reviewed.
RESULTS
Lymph node biopsy showed reactive hyperplasia of lymph node tissue. The liver biochemical indexes were abnormal and the bone marrow smear showed atypical lymphocytes. Lymph node section: IgG4+ cells > 100/HPF (IgG4/IgG > 40%). The serum IgG4 level was 17,200 mg/L, and the diagnosis was IgG4-RD. Oral glucocorticoids took effect after 2 weeks, and no significant enlargement of lymph nodes was observed.
CONCLUSIONS
For the diagnosis of IgG4-RD, at present, histopathology is still the gold standard, but a single result cannot diagnose the disease. Comprehensive judgment should be made by combining clinical symptoms, serum IgG4 level and imaging results to prevent misdiagnosis and missed diagnosis, and to avoid over-diagnosis. Short-term hormonal diagnostic therapy may be used in highly suspected patients who cannot be diagnosed. Once diagnosed, standardized medication, adhere to follow-up, regular review, to prevent recurrence and adverse drug reactions.
Topics: Humans; Immunoglobulin G; Immunoglobulin G4-Related Disease; Liver Diseases; Glucocorticoids; Lymph Nodes; Male; Middle Aged
PubMed: 38747922
DOI: 10.7754/Clin.Lab.2023.231218