Myelolipoma among patients with thalassemia major and rare anemia with iron loading: A not so rare entity
Authors: Paolo Ricchi, Silvia Costantini, Anna Spasiano, Tiziana Di Matola, Patrizia Cinque, Aldo Filosa
Journal: American Journal of Hematology (2016)

We read with particular interest the educational article by Motta et al, describing a case of myelolipoma affecting a patient with Thalassemia Major (TM).1 Overall, they diagnosed four cases of myelolipoma, three originating from the adrenal glands and one from the pelvic region in a population of 190 TM patients (prevalence of 2.1%). The authors confirmed that this benign tumor was composed of variable amounts of mature adipose tissue and islands of hemopoietic elements. In recent times, a case of myelolipoma of posterior mediastinum was also described in a multitransfused, severely iron overloaded patient with congenital dyserithropoietic anemia (CDA).2 Since 2014, following the merging of paediatric and adult thalassemic units, we have been managing ∼190 TM, ∼100 nontransfusion-dependent thalasssemic (NTDT) and ∼60 patients with other rare congenital anemias and hemoglobinopathies. Therefore, we retrospectively evaluated our series to identify cases of myelolipoma. Overall, we collected five cases of myelolipoma, four among TM patients and one among a patient with CDA out the two we are following since last year; no cases were recorded among NTDT patients and no specific clinical symptom were noted in those affected. All tumours were discovered incidentally during ultrasonography (US) and further confirmed by Magnetic Resonance scan. Table 1 describes main characteristics of the patients and of the tumors. Masses were always right-sided, but in two cases were located at renal level and were bilateral, respectively. In the patient with renal bilateral tumor (n.2), four nodules were found. Patient n.1 had also a nodule with diameter =15 mm in the left adrenal gland. Two patients (n.1 and n.4), because of adrenal tumor > 40 mm in diameter ad/or progressive growth, were treated with surgical excision. Two patients had also extramedullary hematopoiesis. All thalassemic patients were under chelation therapy and had normal cardiac T2* value (>20 ms) but wide range of liver iron overload. The patient with CDA, despite never transfused, was severely liver overloaded at the time of diagnosis. All patients had a variety of endocrinological complications consisting of hypogonadism, hypothyroidism, reduced bone density and diabetes mellitus (60%). Patient n. 4 had also some typical radiological and dermal abnormalities of Pseudoxanthoma elasticum-like syndrome (data not shown). Our data on adrenal function, despite limited to current or presurgical ACTH and cortisol level, highlight an increased levels of ACTH in some patients particularly in that with greatest mass and a heterogeneous, in some cases stressful, pituitary-adrenal axis status. Overall, our data confirm that TM and CDA, but not NTDT patients, are at high risk of developing myelolipoma providing the same prevalence estimates as Motta et al in TM population (2,1%). In our TM series, several characteristics of myelolipoma such as early age of cancer onset, bilateral mass in paired organs or multifocal disease, suggest the features of early and chronic exposure to a promoting agent and/or of a hereditary cancer. The pathogenesis of myelolipoma is unclear and probably multifactorial. Motta et al suggested that its growth could be under the control of hematopoietic stimuli. The same authors also correctly underlined both that several cases of myelolipoma were associated with chronic hemolytic anemias or ineffective erythropoiesis and that in a few cases the diagnosis of myelolipoma allowed the retrospective diagnosis of the underlying congenital anemia.1 But, myelolipomas have been also described in the setting of chronic nonerythropoietic stressful conditions such as diabetes mellitus, hypertension, obesity and adrenocorticotropic hormone (ACTH) surplus and/or hypersecretion, such as classical congenital adrenal hyperplasia (CAH).3 Interestingly, it has already been showed that TM patients display high ACTH levels and impaired adrenal response to stimulation tests as a result of adrenal hypofunction and primary adrenal failure, likely induced by iron overload.4 Thus, the increase in ACTH levels may represent a common pathogenetic event between all congenital iron loading anemias, CAH, chronic stressful conditions contributing to raise the risk of developing myelolipoma in these diseases. Further prospective studies are needed to accurately evaluate such a potential relationship in patients with thalassemia. Obviously, the well-recognized relationship between transfusional iron overload and the occurrence of endocrinopathies may justify the particularly increased prevalence of myelolipoma observed in TM patients opposed to NTDT ones. However, further studies are also needed to fully evaluate adrenal steroid secretion and hypothalamic-pituitary-adrenal (HPA) axis function in TM patients and to clarify if iron per se could also play a role in myelolipoma formation.5 In conclusion, myelolipoma appears to be an emerging entity among TM patients and particularly among those with endocrinopathies. These data could suggest that in TM patients a careful US examination of the renal and adrenal district, in order to early detect not only urinary stones disease6 but also pathological masses, is advisable. All authors have no conflict of interest to declare.