RESUMO
There is a known association of primary nonseminomatous mediastinal germ cell tumors (NSMGCT) and hematologic malignancy in younger males not linked to treatment. When combined these two rare entities convey a very poor prognosis. Here we report a 16-year-old male with an anterior mediastinal mass diagnosed as a malignant germ cell tumor based on elevation of serologic markers. He was found to have acute leukemia with megakaryocytic differentiation several days later. We focus our report on the pathologic findings, including a review of the literature, and a novel molecular analysis of the germ cell tumor.
Assuntos
Leucemia/patologia , Neoplasias do Mediastino/patologia , Neoplasias Embrionárias de Células Germinativas/patologia , Neoplasias Testiculares/patologia , Doença Aguda , Adolescente , Diagnóstico Diferencial , Humanos , Leucemia/diagnóstico , Masculino , Neoplasias do Mediastino/diagnóstico , Neoplasias Embrionárias de Células Germinativas/diagnóstico , Neoplasias Testiculares/diagnósticoRESUMO
Brentuximab vedotin (BV) and nivolumab are increasingly utilized as a novel regimen in patients with relapsed/refractory classical Hodgkin lymphoma (cHL). A 26-year-old male presented to the hospital with refractory diabetic ketoacidosis and multiple electrolyte abnormalities, 9 days after the first dose of brentuximab vedotin and nivolumab for recurrent classical Hodgkin lymphoma. During his hospitalization, he developed multi-organ failure. His workup showed elevated cytokine levels concerning severe cytokine release syndrome (CRS) and hemophagocytic lymphohistiocytosis (HLH)-like syndrome. Despite treatment with CRS- and HLH-directed therapies, his clinical status deteriorated due to ongoing multifactorial shock and worsening multi-organ dysfunction, and comfort care measures were eventually pursued. To our knowledge, there have been no other cases reported of HLH-like syndrome after the combination of BV and nivolumab in patients with cHL. This case of a fatal adverse event following one dose of BV and nivolumab underscores the vital need for close monitoring of patients receiving this treatment regimen.
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Cerebral glucose hypometabolism (CGHM) is characterized by diffuse or focal reduction in uptake of glucose by the brain as determined on a FDG PET-CT. We report a case of lymphoma-associated cerebral glucose hypometabolism (LA-CGHM) in a patient with hepatosplenic T-cell lymphoma (HSTCL) whose neuropsychiatric symptoms were resolved with glucose supplementation. PET-CT scan showed diffuse cerebral hypometabolism in addition to focal hypermetabolism in the liver related to lymphomatous involvement. He responded rapidly to infusion of 10% dextrose with complete resolution of neurological symptoms on two separate occasions and was later maintained on oral glucose without relapse. While his neuropsychiatric symptoms improved, his aggressive lymphoma and chemo-refractory disease ultimately led to his demise. We suggest that LA-CGHM can cause neuropsychiatric manifestations which can be reversed by intensive glucose supplementation.
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Multiple myeloma (MM) is a plasma cell malignancy and most patients eventually succumb to the disease. Chimeric antigen receptor (CAR) T cells targeting B-Cell Maturation Antigen (BCMA) on MM cells have shown high-response rates, but limited durability. CD229/LY9 is a cell surface receptor present on B and T lymphocytes that is universally and strongly expressed on MM plasma cells. Here, we develop CD229 CAR T cells that are highly active in vitro and in vivo against MM plasma cells, memory B cells, and MM-propagating cells. We do not observe fratricide during CD229 CAR T cell production, as CD229 is downregulated in T cells during activation. In addition, while CD229 CAR T cells target normal CD229high T cells, they spare functional CD229neg/low T cells. These findings indicate that CD229 CAR T cells may be an effective treatment for patients with MM.
Assuntos
Imunoterapia Adotiva/métodos , Mieloma Múltiplo/terapia , Receptores de Antígenos de Linfócitos T/imunologia , Família de Moléculas de Sinalização da Ativação Linfocitária/metabolismo , Animais , Anticorpos/imunologia , Linfócitos B/metabolismo , Humanos , Células K562/imunologia , Masculino , Camundongos Endogâmicos NOD , Mieloma Múltiplo/patologia , Receptores de Antígenos de Linfócitos T/metabolismo , Família de Moléculas de Sinalização da Ativação Linfocitária/genética , Família de Moléculas de Sinalização da Ativação Linfocitária/imunologia , Linfócitos T/imunologia , Linfócitos T/transplante , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
INTRODUCTION: We describe peripheral blood smear, bone marrow morphology, histopathology, immunohistochemistry, including BRAF V600E, and molecular testing results of patients with metastatic melanoma to the bone marrow. METHODS: We performed a retrospective review for patients with metastatic melanoma to the bone marrow at our institution. Bone marrow morphology, histology, immunophenotyping, and cytogenetic/molecular genetic testing were reviewed, and BRAF V600E immunohistochemistry was performed. Results were compared to the literature. RESULTS: We identified four patients with metastatic melanoma to the bone marrow presenting with at least one cytopenia. Two of the four patients had leukoerythroblastosis, with three patients having atypical cells on bone marrow aspirate/touch preparation, and all patients had aggregates of atypical cells on biopsy. Immunohistochemistry for S100, Melan A, and HMB45 confirmed the diagnosis in all patients, and BRAF V600E immunohistochemistry was detected in two of four patients, which correlated with molecular testing findings. Review of the literature found 27 total patients, with normocytic anemia and leukoerythroblastosis as common peripheral blood smear findings. CONCLUSIONS: Features including cytopenias (typically anemia), leukoerythroblastosis, and morphology of cohesive, large atypical cells in aspirate and biopsy, and immunohistochemical expression for S100, Melan A, and HMB45 were present in patients with metastatic melanoma. BRAF V600E immunohistochemistry is useful as a surrogate marker of molecular results. Regardless of clinical history, at the time of the bone marrow biopsies, hematologic malignancies are in the main differential diagnosis and very rarely included metastatic melanoma, likely due to the under-recognized metastatic potential of melanoma to the bone marrow.
Assuntos
Células da Medula Óssea , Neoplasias da Medula Óssea , Melanoma , Mutação de Sentido Incorreto , Proteínas Proto-Oncogênicas B-raf , Células da Medula Óssea/metabolismo , Células da Medula Óssea/patologia , Neoplasias da Medula Óssea/diagnóstico , Neoplasias da Medula Óssea/genética , Neoplasias da Medula Óssea/metabolismo , Neoplasias da Medula Óssea/patologia , Feminino , Humanos , Imuno-Histoquímica , Masculino , Melanoma/diagnóstico , Melanoma/genética , Melanoma/metabolismo , Melanoma/patologia , Pessoa de Meia-Idade , Metástase Neoplásica , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas B-raf/metabolismoRESUMO
CONTEXT.: B-cell lymphomas exhibit balanced translocations that involve immunoglobulin loci and result from aberrant V(D)J recombination, class switch recombination, or somatic hypermutation. Although most of the breakpoints in the immunoglobulin loci occur in defined regions, those in the partner genes vary; therefore, it is unlikely that 2 independent clones would share identical breakpoints in both partners. Establishing whether a new lesion in a patient with history of lymphoma represents recurrence or a new process can be relevant. Polymerase chain reaction (PCR)-based clonality assays used in this setting rely only on evaluating the length of a given rearrangement. In contrast, next-generation sequencing (NGS) provides the exact translocation breakpoint at single-base resolution. OBJECTIVE.: To determine if translocation breakpoint coordinates can serve as a molecular fingerprint unique to a distinct clonal population. DESIGN.: Thirty-eight follicular lymphoma/diffuse large B-cell lymphoma samples collected from different anatomic sites and/or at different time points from 18 patients were analyzed by NGS. For comparison, PCR-based B-cell clonality and fluorescence in situ hybridization studies were performed on a subset of cases. RESULTS.: IGH-BCL2 rearrangements were detected in all samples. The breakpoint coordinates on derivative chromosome(s) were identical in all samples from a given patient, but distinct between samples derived from different patients. Additionally, 5 patients carried a second rearrangement also with conserved breakpoint coordinates in the follow-up sample(s). CONCLUSIONS.: Breakpoint coordinates in the immunoglobulin and partner genes can be used to establish clonal relatedness of anatomically/temporally distinct lesions. Additionally, an NGS-based approach has the potential to detect secondary translocations that may have prognostic and therapeutic significance.
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Impressões Digitais de DNA , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Linfoma Folicular/genética , Linfoma Difuso de Grandes Células B/genética , Rearranjo Gênico , Humanos , Cadeias Pesadas de Imunoglobulinas/genética , Hibridização in Situ Fluorescente , Proteínas Proto-Oncogênicas c-bcl-2/genética , Translocação GenéticaRESUMO
Anaplastic lymphoma kinase-positive large B-cell lymphoma (ALK+ LBCL) is a very rare and aggressive subtype of diffuse large B-cell lymphoma characterized by ALK rearrangement. Immunophenotypically, the tumor cells are typically negative for common B-cell markers, T-cell markers, and CD30; however, they express markers of terminally differentiated B cells/plasma cells such as CD38, CD138, and MUM-1/IRF4. The diagnosis of ALK+ LBCL can be challenging, and often a large panel of immunostains is required to exclude other hematopoietic and nonhematopoietic neoplasms. To date, approximately 130-140 cases have been reported, but here we report the first known case of ALK+ LBCL with unusual CD33 expression.
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This article highlights the most common morphologic features identified in the bone marrow after chemotherapy for hematologic malignancies, growth-stimulating agents, and specific targeted therapies. The key is to be aware of these changes while reviewing post-therapeutic bone marrow biopsies and to not mistake reactive patterns for neoplastic processes. In addition, given the development and prevalent use of targeted therapy, such as tyrosine kinase inhibitors and immune modulators, knowledge of drug-specific morphologic changes is required for proper bone marrow interpretation and diagnosis.
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Antineoplásicos/farmacologia , Medula Óssea/efeitos dos fármacos , Medula Óssea/patologia , Neoplasias Hematológicas/tratamento farmacológico , Atrofia/induzido quimicamente , Citocinas/farmacologia , Neoplasias Hematológicas/patologia , Humanos , Mesilato de Imatinib/farmacologia , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Lenalidomida , Agonistas Mieloablativos/farmacologia , Necrose , Rituximab/farmacologia , Talidomida/análogos & derivados , Talidomida/farmacologiaRESUMO
OBJECTIVES: Based on previous molecular studies, a small fraction of primary mediastinal (thymic) large B-cell lymphoma (PMBL) demonstrates MYC alterations. However, no studies have evaluated MYC protein expression by immunohistochemistry (IHC) with follow-up fluorescence in situ hybridization (FISH) analysis. We aim to evaluate the clinicopathologic importance of MYC IHC expression in PMBL. METHODS: Three pathologists independently evaluated MYC IHC expression in 32 cases of PMBL for percent tumor positivity and nuclear intensity. FISH analysis for MYC rearrangement was performed on cases with high MYC IHC expression. Clinical data including treatment, follow-up, and outcome were also reviewed in a subset of cases. RESULTS: Variable MYC protein expression by IHC was detected in 30 (94%) of 32 cases of PMBL. One-third of the positive cases (10/30) showed high MYC IHC expression of at least 30% nuclear positivity. FISH analyses for MYC rearrangement on these 10 cases were negative. Review of clinical data on a subset of cases with high and low MYC IHC expression showed no differences in clinical outcome. CONCLUSIONS: MYC protein expression by IHC is present in most PMBLs. Increased MYC protein expression can be seen in one-third of the cases; however, it does not correlate with genetic abnormalities by FISH. There is also no significant impact of MYC protein expression on clinical outcomes.