RESUMO
The spleen is among the most common extranodal sites for Hodgkin and non-Hodgkin lymphomas (NHLs); however, among lymphomas arising from the spleen, primary splenic lymphomas (PSLs) are rare. The group of PSLs includes primary splenic diffuse large B-cell lymphoma (PS-DLBCL), splenic red pulp small B-cell lymphoma, splenic marginal zone lymphoma (SMZL), and a splenic hairy cell leukemia variant. Delineating between the PSL variants can be challenging, especially as fine-needle aspirate and core needle biopsy of the spleen are not routinely offered at most medical centers. Herein, we describe the clinical course of 2 representative patients who presented with non-specific gastrointestinal symptoms, the first who was diagnosed with PS-DLBCL and the second who was diagnosed with SMZL. We review and contrast the clinical presentations, imaging techniques, and laboratory findings of these discrete lymphoma variants and offer strategies on how to delineate between these varied splenic processes. We also examine the use of splenectomy and splenic needle biopsy as diagnostics and, in the case of splenectomy, a therapeutic tool. Finally, we also briefly review treatment options for these varied lymphoma sub-types while acknowledging that randomized trials to guide best practices for PSLs are lacking.
RESUMO
BACKGROUND AND AIMS: Melanoma incidence has increased worldwide with a concurrent rise in both primary and metastatic melanomas of the gastrointestinal tract. MATERIALS AND METHODS: This retrospective single-center case series includes patients with histopathology-confirmed primary or metastatic melanoma of the GI tract between 1998 and 2018. RESULTS: Thirty-four patients were identified for inclusion, of whom 7 were primary and 27 were metastatic cases of gastrointestinal melanoma. For both primary and metastatic cases, the majority of patients presented with frank or occult GI bleeding (57.1% and 70.4%). Primary and metastatic lesions were predominantly diagnosed endoscopically (100% and 63.0%), with 71.4% of primary lesions found at the anorectal junction and 51.9% of metastatic lesions in the small bowel. Endoscopically diagnosed lesions were either polypoid (50%) or a luminal mass (37.5%) in the majority of cases. Common features included: amelanotic (83%), ulcerated (50%), and friable (33.3%). All primary patients were treated with surgical excision or resection. Of the metastatic patients, 56% were resected. The median interval between initial primary and gastrointestinal metastases was 65 months (ranging from 1 month to 24 years). At the time of data analysis, 85.7% of primary and 29.6% of metastatic patients remained alive. CONCLUSIONS: The majority of patients in this series were diagnosed endoscopically while investigating a source of gastrointestinal blood loss. Heightened clinical suspicion and recognition of the endoscopic features of gastrointestinal melanoma during evaluation of GI symptoms in a patient with a personal history of primary melanoma are advised.
Assuntos
Endoscopia , Neoplasias Gastrointestinais/patologia , Melanoma/secundário , Neoplasias Cutâneas/secundário , Idoso , Feminino , Hemorragia Gastrointestinal , Humanos , Masculino , Estudos Retrospectivos , Resultado do Tratamento , Melanoma Maligno CutâneoAssuntos
Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/patologia , Doxorrubicina/análogos & derivados , Infecções por Vírus Epstein-Barr/tratamento farmacológico , Doenças Retais/tratamento farmacológico , Rituximab/uso terapêutico , Úlcera/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/imunologia , Antibióticos Antineoplásicos/uso terapêutico , Doxorrubicina/uso terapêutico , Infecções por Vírus Epstein-Barr/imunologia , Infecções por Vírus Epstein-Barr/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Polietilenoglicóis/uso terapêutico , Doenças Retais/patologia , Doenças Retais/virologia , Resultado do Tratamento , Úlcera/patologia , Úlcera/virologiaAssuntos
Alérgenos/efeitos adversos , Arachis/efeitos adversos , Transtornos de Deglutição/induzido quimicamente , Dessensibilização Imunológica/efeitos adversos , Esofagite Eosinofílica/induzido quimicamente , Hipersensibilidade a Amendoim/terapia , Proteínas de Plantas/efeitos adversos , Administração Oral , Adulto , Alérgenos/administração & dosagem , Alérgenos/imunologia , Arachis/imunologia , Biópsia , Budesonida/administração & dosagem , Deglutição , Transtornos de Deglutição/diagnóstico , Transtornos de Deglutição/tratamento farmacológico , Transtornos de Deglutição/fisiopatologia , Dessensibilização Imunológica/métodos , Endoscopia do Sistema Digestório , Esofagite Eosinofílica/diagnóstico , Esofagite Eosinofílica/tratamento farmacológico , Esofagite Eosinofílica/fisiopatologia , Feminino , Glucocorticoides/administração & dosagem , Humanos , Hipersensibilidade a Amendoim/diagnóstico , Hipersensibilidade a Amendoim/imunologia , Proteínas de Plantas/administração & dosagem , Proteínas de Plantas/imunologia , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
We describe the cautionary case of a patient with advanced-stage large B-cell lymphoma (DLBCL). After combination chemotherapy, CT-PET revealed a persistent focus of likely DLBCL for which he received radiotherapy. Follow-up CT-PET showed diffuse hypermetabolic adenopathy and recurrent DLBCL was presumed. As part of clinical trial assessment, multiple biopsies showed non-caseating lymphadenitis consistent with sarcoidosis. No treatment for asymptomatic sarcoidosis was required and 18 months later he remains cancer-free. The presentation of sarcoidosis masquerading as recurrent DLBCL highlights the importance of tissue sampling prior to engaging in toxic and potentially life-threatening chemotherapy and the interesting link between DLBCL and sarcoidosis.
RESUMO
All-trans retinoic acid (ATRA), a derivative of vitamin A, is an essential component in the treatment of acute promyelocytic leukemia (APL). Though considered to be a relatively safe drug, use of ATRA can lead to several side effects such as retinoic acid syndrome and pseudotumor cerebri (PC). PC is a rare disorder characterized by neurologic and ocular signs and symptoms of increased intracranial pressure, but with normal cerebrospinal fluid composition and normal brain imaging. Most of the previous studies suggest that PC, as a complication of ATRA therapy, occurs predominantly in the pediatric age group. Herein, we report a rare case of ATRA-induced PC in a 38-year-old woman undergoing induction treatment for APL. Symptoms improved with discontinuation of ATRA and treatment with acetazolamide. Concomitant administration of medications such as triazole antifungals which influence the cytochrome P-450 system can exacerbate this potential complication of ATRA. In this paper, we also review the current literature, provide a descriptive analysis of clinical features, and discuss the principles of management of ATRA-induced PC.
RESUMO
Chromosome segregation depends on the spindle checkpoint, which delays anaphase until all chromosomes have bound microtubules and have been placed under tension. The Mad1-Mad2 complex is an essential component of the checkpoint. We studied the consequences of removing one copy of MAD2 in diploid cells of the budding yeast, Saccharomyces cerevisiae. Compared to MAD2/MAD2 cells, MAD2/mad2Δ heterozygotes show increased chromosome loss and have different responses to two insults that activate the spindle checkpoint: MAD2/mad2Δ cells respond normally to antimicrotubule drugs but cannot respond to chromosomes that lack tension between sister chromatids. In MAD2/mad2Δ cells with normal sister chromatid cohesion, removing one copy of MAD1 restores the checkpoint and returns chromosome loss to wild-type levels. We conclude that cells need the normal Mad2:Mad1 ratio to respond to chromosomes that are not under tension.
Assuntos
Proteínas de Ciclo Celular/genética , Genes cdc/fisiologia , Cinetocoros/fisiologia , Mitose , Proteínas Nucleares/genética , Proteínas de Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/genética , Segregação de Cromossomos/genética , Diploide , Heterozigoto , Proteínas Mad2 , Saccharomyces cerevisiae/fisiologia , Troca de Cromátide Irmã/genética , Fuso Acromático/genéticaRESUMO
In the highly active antiretroviral therapy era, an increasingly large number of HIV-infected patients are developing non- AIDS-defining cancers (NADCs). As patients survive longer, long-term therapy-related complications take on greater importance. Herein, we describe a patient with AIDS who presented to medical attention with pancytopenia 48 months postchemotherapy with etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (R-EPOCH) for diffuse large B-cell lymphoma. Bone marrow biopsy showed a moderately hypocellular marrow; 51% of the nucleated cells were blasts with myelomonocytic differentiation. Cytogenetic studies revealed an abnormal karyotype with deletion of the long arm of chromosome 11 (11q21) and 2 additional copies of the MLL gene attached to the short arms of chromosome 10 in 80% of the metaphase cells examined. With the diagnosis of therapy-related acute myeloid leukemia (AML) secured, he began induction chemotherapy with idarubicin and cytarabine. Two weeks later, he died of fungal septicemia and multiorgan failure. Through a literature search, we were able to identify 4 additional cases of therapy-related AML in AIDS patients following chemotherapy for lymphomas. The median age of these patients at the time of AML diagnosis was 39 years (range, 33-59 years), the median time from the treatment of lymphoma to AML was 18 months (range, 11-48 months), and the median survival following induction chemotherapy was 4 weeks (range, 2-16 weeks). With many HIV-infected patients surviving alkylator and topoisomerase inhibitor-based treatment and radiation therapy for AIDS-defining cancers and NADCs, long-term follow-up for therapy-related complications assumes greater importance.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia Mieloide Aguda/induzido quimicamente , Linfoma Relacionado a AIDS/tratamento farmacológico , Adulto , Aberrações Cromossômicas , Cromossomos Humanos Par 10/genética , Cromossomos Humanos Par 11/genética , Análise Citogenética , Evolução Fatal , Seguimentos , Histona-Lisina N-Metiltransferase , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Linfoma Relacionado a AIDS/diagnóstico , Linfoma Relacionado a AIDS/genética , Masculino , Proteína de Leucina Linfoide-Mieloide/genéticaRESUMO
The spindle checkpoint prevents chromosome loss by preventing chromosome segregation in cells with improperly attached chromosomes [1, 2 and 3]. The checkpoint senses defects in the attachment of chromosomes to the mitotic spindle [4] and the tension exerted on chromosomes by spindle forces in mitosis [5, 6 and 7]. Because many cancers have defects in chromosome segregation, this checkpoint may be required for survival of tumor cells and may be a target for chemotherapy. We performed a phenotype-based chemical-genetic screen in budding yeast and identified an inhibitor of the spindle checkpoint, called cincreasin. We used a genome-wide collection of yeast gene-deletion strains and traditional genetic and biochemical analysis to show that the target of cincreasin is Mps1, a protein kinase required for checkpoint function [8]. Despite the requirement for Mps1 for sensing both the lack of microtubule attachment and tension at kinetochores, we find concentrations of cincreasin that selectively inhibit the tension-sensitive branch of the spindle checkpoint. At these concentrations, cincreasin causes lethal chromosome missegregation in mutants that display chromosomal instability. Our results demonstrate that Mps1 can be exploited as a target and that inhibiting the tension-sensitive branch of the spindle checkpoint may be a way of selectively killing cancer cells that display chromosomal instability.