A giant adrenal myelolipoma in a beta‐thalassemia major patient: Does ineffective erythropoiesis play a role?
Authors: Irene Motta, Leonardo Boiocchi, Paola Delbini, Margherita Migone De Amicis, Elena Cassinerio, Daniele Dondossola, Giorgio Rossi, Maria Domenica Cappellini
Journal: American Journal of Hematology (2016)

A 40-year-old thalassemia major (genotype b0 cod39/b1 IVSI-110) patient, regularly transfused with three units of packed red cells every three weeks with an average pre-transfusion hemoglobin level of 100 g/L, presented in 2002 with a right abdominal mass measuring 7.5 cm of maximum width found incidentally during the annual ultrasound (US) examination of the abdomen.A subsequent MRI showed radiological features suggestive for extramedullary hematopoiesis (EMH) thus the mass was periodically monitored.In 2009, because of the progressive increase in mass volume, hydroxyurea therapy was started at increasing dosage up to 15 mg/kg per day.In 2014 and 2015, a US evaluation showed a rapidly increasing volume of the abdominal mass.A computed tomography (CT) scan of the abdomen and pelvis with intravenous iodine contrast (Image 1) showed a huge well circumscribed retroperitoneal poly-lobed mass in the right abdomen measuring 19 3 15 3 25 cm 3 , originating from the right adrenal gland and displacing the liver medially and the right kidney caudally and anteriorly; moreover, it compressed the inferior vena cava and displaced the mesenteric vessels.The mass was poorly vascularized with low contrast enhancement and marked heterogeneity, primarily due to the presence of fat tissue.At this time the radiological features were more suggestive of either an angiomyolipoma or a myelolipoma rather than EMH.Laparotomy was performed and a 3.5 kg encapsulated tumor (Image 1) attached to the right adrenal gland was removed.Gross examination showed a soft yellow to red cut surface with focal areas of hemorrhage.Extensive sampling was performed given the size of the mass and microscopic examination showed typical features of myelolipomas, with varying proportions of mature adipose tissue admixed with trilineage hematopoiesis (Image 1).A thin rim of residual adrenal tissue was present at the edge of the mass.Myelolipoma is a rare tumor that accounts for approximately the 4% of adrenal tumors.Some cases are associated with chronic hemolytic anemias or ineffective erythropoiesis, including both transfusion dependent and transfusion independent thalassemia [1-4], sickle cell anemia [5,6], and hereditary spherocytosis [7,8].In a few cases the diagnosis of myelolipoma allowed the retrospective diagnosis of the underlying congenital anemia [5,8].These associations suggest that the tumor is under the control of hematopoietic stimuli.It has been demonstrated that the first hematopoietic activity, known as primitive hematopoiesis, appears in the blood islands of the yolk sac.However, the first hematopoietic stem cells (HSC), defined by their capacity for long-term and multi-lineage engraftment in adult recipients, appear in the mammal embryo in the (AGM) region, and then home to the fetal liver [9,10].We demonstrated by flow cytometry that the mass of our patient contained erythroid precursors (Image 1).Hence, residual HSC in organs derived from the AGM region in patients with ineffective erythropoiesis might be the source of the tumor mass.In our cohort of 190 patients affected by transfusion dependent thalassemia, we observed four cases of myelolipoma, three originating from the adrenal glands and one from the pelvic region.Further investigations involving a greater number of patients are needed to establish the prevalence of a tumor that might be underestimated in patients affected by diseases with chronic anemia and ineffective erythropoiesis.