Primary adrenal diffuse large B cell lymphoma arising within an adrenal myelolipoma: A case report and review of the literature.

Adrenal myelolipoma (AML) is a benign tumor that consists of mature adipose tissue and bone marrow elements. We report a case of a 57-year-old woman who presented with complaint of lower abdominal discomfort. Computed tomography scan of abdomen and pelvis revealed a mass in the left adrenal measuring 2.0 cm which was radiologically considered to be AML. Pathological evaluation of the lesion showed foci of lymphoid aggregate in a background of AML that were confirmed to be diffuse large B cell lymphoma by immunohistochemistry and gene rearrangement. To our knowledge, this collision tumor has not been reported previously. The clinical, radiological, pathological features, and treatment are discussed.

Small molecule MIRA-1 induces in vitro and in vivo anti-myeloma activity and synergizes with current anti-myeloma agents.

BACKGROUND: Small molecule MIRA-1 induced mutant p53-dependent apoptosis in several types of solid tumours. However, anti-tumour activity of MIRA-1 in haematological malignancies including multiple myeloma (MM) is unknown. In this study, we evaluated the effect of MIRA-1 in MM. METHODS: We examined the anti-tumour activity of MIRA-1 alone or in combination with current anti-myeloma agents in a panel of MM cell lines, primary MM samples, and in a mouse xenograft model of MM. RESULTS: MIRA-1 treatment resulted in the inhibition of viability, colony formation, and migration and increase in apoptosis of MM cells irrespective of p53 status accompanied by upregulation of Puma and Bax and downregulation of Mcl-1 and c-Myc. Genetic knockdown of p53 did not abrogate apoptotic response of MIRA-1. MIRA-1 triggered activation of PERK and IRE-α leading to splicing of XBP1 indicating an association of endoplasmic reticulum stress response. Furthermore, combined treatment of MIRA-1 with dexamethasone, doxorubicin or velcade displayed synergistic response in MM cells. Importantly, MIRA-1 alone or in combination with dexamethasone retarded tumour growth and prolonged survival without showing any untoward toxicity in the mice bearing MM tumour. CONCLUSIONS: Our data provide the preclinical framework for clinical evaluation of MIRA-1 as a novel therapeutic agent to improve patient outcome in MM.

Thalidomide in total therapy 2 overcomes inferior prognosis of myeloma with low expression of the glucocorticoid receptor gene NR3C1.

PURPOSE: Because dexamethasone remains a key component of myeloma therapy, we wished to examine the impact of baseline and relapse expression levels of the glucocorticoid receptor gene NR3C1 on survival outcomes in the context of treatment with or without thalidomide. EXPERIMENTAL DESIGN: We investigated the clinical impact of gene expression profiling (GEP)-derived expression levels of NR3C1 in 351 patients with GEP data available at baseline and in 130 with data available at relapse, among 668 subjects accrued to total therapy 2 (TT2). RESULTS: Low NR3C1 expression levels had a negative impact on progression-free survival (PFS; HR, 1.47; P = 0.030) and overall survival (OS; HR, 1.90; P = 0.002) in the no-thalidomide arm. Conversely, there was a significant clinical benefit of thalidomide for patients with low receptor levels (OS: HR, 0.54; P = 0.015; PFS: HR, 0.54; P = 0.004), mediated most likely by thalidomide's upregulation of NR3C1. In the context of both baseline and relapse parameters, post-relapse survival (PRS) was adversely affected by low NR3C1 levels at relapse in a multivariate analysis (HR, 2.61; P = 0.012). CONCLUSION: These findings justify the inclusion of NR3C1 expression data in the work-up of patients with myeloma as it can significantly influence the choice of therapy and, ultimately, OS. The identification of an interaction term between thalidomide and NR3C1 underscores the importance of pharmacogenomic studies in the systematic study of new drugs.

Mielolipomas adrenales bilaterales como hallazgo incidental / Bilateral adrenal myelolipomas as an incidental finding

Los mielolipomas son tumores benignos raros, no funcionantes, compuestos por tejido adiposo maduro y precursores hematopoyéticos que involucran principalmente a las glándulas adrenales aunque pueden presentarse en localizaciones extraadrenales. Las características clínicas son muy variables, con descripciones de mielolipomas gigantes, bilaterales, asociados a síndromes de hipersecreción hormonal o a sangrado retroperitoneal. Con el incremento de la utilización de técnicas de imagen abdominales en la práctica clínica habitual, se ha observado un aumento de detección de incidentalomas adrenales, entre los cuales pueden encontrarse en raras ocasiones mielolipomas. Se describe el caso de una presentación inusual de mielolipomas adrenales bilaterales asintomáticos como hallazgo incidental en radiografías convencionales de abdomen, junto con un revisión de la literatura referida a estos tumores.

Myelolipomas are rare, non-functioning, benign tumors composed of mature fat tissue and myeloid hematopoietic precursors that involve mainly the adrenal glands and rarely other extra-adrenal tissues. The clinical features are heterogeneous and there are reports of giant and bilateral myelolipomas. Few tumors have been associated with endocrine dysfunction or retroperitoneal bleeding. With the development and wide-spread use of modern imaging techniques, this adrenal entity is sometimes found incidentally during radiology procedures for other reasons. We describe an unusual clinical presentation of asymptomatic bilateral myelolipomas incidentally discovered in abdominal X-Rays.