RESUMEN
The use of immunotherapy in transplant recipients is considered a contraindication because of very high risks for graft loss. The graft loss is to be expected because cytotoxic T-lymphocyte-associated protein-4 and programmed death 1 pathways are implicated in graft tolerance. In this case report, we describe a woman with recurrent, disseminated hepatocellular carcinoma who was successfully treated with nivolumab, an immune checkpoint inhibitor.
RESUMEN
Neuroendocrine neoplasms (NENs) represent a diverse group of tumors arising from neuroendocrine cells. Current World Health Organization (WHO) classification is based on tumor differentiation and grade defined by mitotic rate and/or Ki-67 index to determine prognosis and treatment options. However, some NENs do not meet WHO pathology criteria due to morphologic heterogeneity and this leads to management challenges. WHO defines poorly differentiated NENs of the gastrointestinal tract as having morphologically large or small cell features with marked elevation of Ki-67. We present a unique clinical case that does not fit either growth pattern and also has heterogeneity with a well-differentiated component. This case report and literature review highlights the current limitations of the WHO classification of small bowel NENs and the subsequent challenges in management decisions for the patients.
RESUMEN
Primary neuroendocrine carcinoma of the breast (NECB) is a rare malignant tumor with controversial biological behavior and a lack of data guiding treatment decisions due to its scarcity. Cancer gene-expression profiling tests provide a better indication of clinical prognosis and help determine the best clinical management versus the traditional clinical and pathological parameters. This is a report of a NECB with a genetic assay that showed a low-risk tumor despite high-grade and poorly differentiated histopathological features. Patient outcomes correlate with the low risk classification without the need for adjuvant chemotherapy despite the standard clinical-pathologic approach. Analysis of cancer related genes expression and outcomes in historical NECB may elucidate new insight of this rare disease.
Asunto(s)
Neoplasias de la Mama/genética , Recurrencia Local de Neoplasia/genética , ARN Mensajero/análisis , Neoplasias de la Mama/patología , Neoplasias de la Mama/terapia , Femenino , Perfilación de la Expresión Génica , Humanos , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/terapiaRESUMEN
We report a NUMA1-PDGFRB fusion in a myeloproliferative neoplasm with eosinophilia in a 61-year old man, with response to imatinib mesylate therapy. A t(5;11) chromosome translocation involving bands 5q32 and 11q13.4 was identified by metaphase chromosome analysis, and rearrangement of the platelet-derived growth factor receptor beta (PDGFRB) gene on 5q32 was demonstrated by FISH using a PDGFRB break-apart probe set. Bacterial artificial chromosome (BAC) FISH mapping of the PDGFRB fusion partner gene narrowed the breakpoint at 11q13.4 to a 150 kb genomic region containing three genes, including NUMA1. Mate pair sequencing analysis demonstrated NUMA1-PDGFRB fusion. The fusion protein includes coiled-coil domains of nuclear mitotic apparatus protein 1 (NuMA1, involved in protein homodimerization and heteroassociation) and tyrosine kinase domains of PDGFRB. Diverse rearrangements involving the PDGFRB gene have been identified in myeloid and lymphoid neoplasms with eosinophilia, but rearrangement of the nuclear mitotic apparatus protein 1 (NUMA1) gene has previously been reported in a human malignancy in only one instance, a NUMA1-RARA fusion caused by a t(11;17) translocation in a patient with acute promyelocytic leukemia. The NUMA1-PDGFRB fusion is the second instance of rearrangement of NUMA1, encoding an element of the mitotic apparatus, in human cancer.
Asunto(s)
Antígenos Nucleares/genética , Eosinofilia/tratamiento farmacológico , Mesilato de Imatinib/uso terapéutico , Trastornos Mieloproliferativos/tratamiento farmacológico , Proteínas Asociadas a Matriz Nuclear/genética , Receptor beta de Factor de Crecimiento Derivado de Plaquetas/genética , Proteínas de Ciclo Celular , Cromosomas Humanos Par 11/genética , Cromosomas Humanos Par 5/genética , Eosinofilia/genética , Humanos , Masculino , Persona de Mediana Edad , Trastornos Mieloproliferativos/genética , Proteínas de Fusión Oncogénica/genética , Translocación Genética , Resultado del TratamientoRESUMEN
Sickle cell anemia is one of the most common autosomal recessive diseases in the world. Patients with sickle cell anemia have variable penetrance and it is hard to predict the risk and timing of complications. It is characterized by a point mutation in the beta-globin gene (GAG --> GTG) and the production of hemoglobin S. The latter leads to decreased deformability of the red blood cells (RBCs) that adhere to endothelia cells culminating in vascular occlusion and its sequelae of tissue ischemia and organ damage. Moreover, sickled RBCs undergo intravascular hemolysis and accelerated erythropoesis. The hallmarks of this disease are shortened RBC survival and vaso-occlusive crises. For the past ten years, the pathophysiology of this disease has been better elucidated and has led to significant improvements in the standard of care. Vaso-occlusion is now understood to be a complex event that involves abnormal interactions between RBCs, leukocytes, endothelial cells and the coagulation pathways. The field of translational research in sickle cell anemia has expanded greatly and has led to new clinical trials with new therapeutic agents and strategies. In this paper, we review the drugs that are now being investigated in the treatment of sickle cell anemia.