Margherita Migone De Amicis

A giant adrenal myelolipoma in a beta-thalassemia major patient: Does ineffective erythropoiesis play a role?

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, 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.

Correction to: Prognostic influence of prior chronic obstructive pulmonary disease in patients admitted for their first episode of acute heart failure

In the original publication, the given name and family name of the fifth author Dr Margherita Migone De Amicis were incorrectly published. The correct given name and family name should read as ‘Margherita’ and ‘Migone De Amicis’, respectively

Anemia and splenomegaly: what lies behind?

Dr Migone De Amicis and Dr FattizzoWe report the case of a 32-year-old man admitted to ourInternal Medicine Department for severe anemia andsplenomegaly. Four months before hospital admission, thepatient was admitted to the Emergency Department (ED) ofthe city where he lived, for a flu-like syndrome charac-terized by fever, diarrhea, profuse sweating and severebone pain in his ankles, knees and lumbosacral region. Thelaboratory tests excluded an infectious disease, but showeda severe unexplained microcytic anemia (Hb 5.2 g/dL,MCV 59 fL). The patient was known as beta-thalassemiacarrier, he denied health problems nor blood transfusion inthe past. He was discharged with diagnosis of ‘‘unex-plained anemia in beta thalassemia carrier,’’ and referred tothe Thalassemia Center of his city. The hematologicalwork-up was negative, and he was put on a regularhematological follow-up and a weekly blood transfusionregimen. In the next 3 months, he progressively developedsplenomegaly and motor ability impairment. Physical ex-amination revealed only diffuse cutaneous pallor and amild splenomegaly, confirmed at the abdomen US (spleenbipolar diameter 145 mm). Blood tests, although posttransfusion, documented persistent moderate microcyticanemia (Hb 8.7 g/dL, MCV 69 fL), undetectable hap-toglobin, increased serum ferritin (722 ng/mL) and ery-thropoietin value (414 U/L, n.v. 3.7–31.5). Betathalassemia trait was confirmed by increased HbA2 level(3.3 %) and normal fetal hemoglobin (0.9 %) at the he-moglobin HPLC test. Infections were excluded by commonserologic tests. A whole-body CT scan confirmed thesplenomegaly, and revealed a systemic lymphadenopathy(maximum diameter 25 mm in the neck, abdomen andinguinal regions) and widespread lytic bone lesions(homerus, femur, iliac wings, costal and sacral region, andall the dorsal vertebra), also confirmed by the scintigraphystudy. In the hypothesis of primary bone marrow (BM)disease, a marrow examination was performed. The aspi-rate demonstrated only a trilinear hypoplasia, while the BMhistology revealed the presence of numerous histiocyticlike aggregates. Erdheim–Chester disease was first hy-pothesized, but it was excluded since BRAF gene analysisdid not reveal any mutations [1, 2]. Thereafter, the patientwas discharged as affected by an ‘‘autoimmune diseasewith bone involvement,’’ and he continued to be regularlytransfused. The patient’s general condition progressivelyworsened, and he was therefore referred to our hospital.At admission, the patient complained of a draggingsensation in the abdomen, as a consequence of a massivesplenomegaly. On general physical examination, there wasmarked pallor and bilateral cervical lymphadenopathy(maximum diameter 20 mm). The heart and the lungs were

Prolonged PT and aPTT in a patient with severe proteinuria

Dr. Motta and Dr. Migone: A 70-year-old woman was admitted to our medical unit because of severe leg and pedal edema and peripheral paresthesias gradually developed during the prior 3 months; she was suffering from cramps during the previous week. The patient had a history of hypertension and type 2 diabetes (glycated hemoglobin 6.4 %) well-controlled by oral hypoglycemic drugs for the last 6 years. Ten months prior to admission, blood and urinalysis were normal, ophthalmologic examination and US Doppler of legs arteries did not show pathological signs. Six months before admission, the patient underwent surgery for a carpal tunnel syndrome. She also underwent hysterectomy 20 years prior and cholecystectomy 40 years prior; both surgeries were uncomplicated. The home treatment during the prior 3 months was candesartan/hydrochlorothiazide, allopurinol, nebivolol, amlodipine, gliclazide, cardioaspirin. At admission, the patient was alert and cooperative. Blood pressure was 130/70 mmHg, pulse 98 beats/min and saturation was 96 % on room air. BMI was 34. On examination, she was pale and had severe bilateral legs edema from the knees. Peripheral pulses were good distally. The chest was clear and a 2/6 systolic murmur was heard. The abdomen was obese, soft, non tender, non distended, no hepatosplenomegaly was appreciated; bowel sounds were active. On neurologic examination she complained paresthesias of the extremities, no focal deficits were present. Blood tests revealed a mild renal insufficiency (serum creatinine 1.38 mg/dl, MDRD GFR 40 ml/min/1.73 mq, BUN 91 mg/dl) that rapidly worsened, with severe hyperkalemia and hypoalbuminemia. A nephrotic proteinuria associated with a mild microscopic hematuria was detected (Table 1).