Question: A 22-year-old man with sickle cell disease was admitted to our hospital because of abdominal pain. At physical examination, the patient was anemic (2+/4+) and jaundiced (1+/4+), with severe pain at the right hypochondrium. Blood tests showed low hemoglobin (6.1 g/dL), low hematocrit (17%), elevated leukocytes (16,200/mm3), elevated total bilirubin (2.5 mg/dL), elevated indirect bilirubin (2.1 mg/dL), and elevated lactate dehydrogenase (1,198 μ/L). At the time of this hospitalization, he had a malleolar ulcer on his left leg, with no signs of infection. This patient had multiple hospitalizations, mostly for pain crisis due to vaso-occlusive disorders or triggered by infections, mainly acute chest syndrome. He also had a history of malleolar ulcers and was treated for osteomyelitis in the distal third of the tibia. During these hospitalizations, he was treated with intravenous hydration, analgesics, oxygen therapy, blood transfusions, and antibiotics, as needed. As an outpatient, he did not adhere to treatment which included hydroxyurea, folic acid, and painkillers, including opioids. Psychiatry follow-up was required owing to opioid dependence. Unenhanced abdominal computed tomography (CT) was performed and showed a 13 cm mass (arrow) with a hypodense central scar (arrowhead) on the right liver lobe (Figure A), and cholelithiasis with no signs of cholecystitis. Magnetic resonance imaging (MRI) was performed for further characterization and showed that the lesion was mildly hyperintense on T2-WI (Figure B), isointense on T1-WI, and hypovascular (Figure C), with a central scar. The lesion had moderate restricted diffusion (Figures D and E) and no intralesional fat (Figure F). Liver hemosiderosis due to the multiple blood transfusions was characterized by low signal at T2-WI (Figure B) and signal loss at in-phase compared with out-of-phase imaging (∗) (Figure G). What is the most likely diagnosis? See the Gastroenterology website (www.gastrojournal.org) for more information on submitting to Gastro Curbside Consult. The differential diagnosis of a patient with sickle cell anemia and right abdominal pain includes vascular crisis, cholecystitis, appendicitis, pyelonephritis, pancreatitis, and other infections. Vaso-occlusive crisis is a common complication of sickle cell anemia in teenagers and young adults. The diagnosis of vaso-occlusive crisis is made in the context of severe pain and no objective clinical, laboratory, and imaging findings of other infections. This patient did not have any other cause for the abdominal pain according to clinical and laboratory parameters and imaging. He had been hospitalized many times before owing to vascular crisis. The diagnosis of vaso-occlusive crisis was made, and he was treated with analgesics, venous hydration, and oxygen therapy. During abdominal pain assessment, a massive intrahepatic lesion was incidentally found. The differential diagnoses of this finding included mainly hemangioma, focal nodular hyperplasia, adenoma, hepatocellular carcinoma, fibrolamellar hepatocellular carcinoma, abscess, metastasis, and intrahepatic extramedullary hematopoiesis. Hemangioma is the most common benign liver lesion. However, imaging characteristics on CT scan and MRI are different from those seen in this patient. Hemangiomas have marked high signal on T2-WI and nodular peripheral enhancement on arterial phase with centripetal filling in portal and equilibrium phases.3Federle M. Borhani A. Jeffrey R. Woodward P. Diagnostic Imaging: Abdomen.2nd ed. Amirsys, Salt City, Utah2010Google Scholar Focal nodular hyperplasia (FNH) is the second most common benign liver lesion. It occurs more frequently in women and is characterized by mild hyperintense signal on T2-WI and marked hypervascular enhancement on arterial phase that fades to isointensity on portal and equilibrium phases. Large FNHs have a central scar that typically has marked high signal on T2-WI and late enhancement on equilibrium phase. Our patient’s lesion had a bright central scar on T2-WI but it was not hypervascular.3Federle M. Borhani A. Jeffrey R. Woodward P. Diagnostic Imaging: Abdomen.2nd ed. Amirsys, Salt City, Utah2010Google Scholar Adenomas are mostly seen in women. The most common are the steatotic subtype, a hypervascular lesion that contains fat in a nonsteatotic liver, and inflammatory subtype, that occurs in the context of metabolic syndrome as a hypervascular lesion with no fat content in a fatty liver. Our patient was male, and the lesion was not hypervascular.3Federle M. Borhani A. Jeffrey R. Woodward P. Diagnostic Imaging: Abdomen.2nd ed. Amirsys, Salt City, Utah2010Google Scholar Hepatocellular carcinoma (HCC) is found mainly in cirrhotic patients as a focal hypervascular liver lesion with washout on equilibrium phase. More rarely, it can appear as a hypovascular lesion, but in those cases liver biopsy is necessary. Fibrolamellar hepatocellular carcinoma (HCC) is a variant of HCC that occurs in young adults with no gender predominance and may resemble FNH. It usually appears as a large single liver mass with a central scar. It is typically hypervascular with washout or isointense on equilibrium phase. However, the central scar of fibrolamellar HCC is typically hypointense on T2-WI.3Federle M. Borhani A. Jeffrey R. Woodward P. Diagnostic Imaging: Abdomen.2nd ed. Amirsys, Salt City, Utah2010Google Scholar Liver infections may lead to the formation of an abscess, which can present itself as a single lesion or as multiple coalescent lesions. Typically, it has high signal on T2-WI and peripheral enhancement. Surrounding perfusional abnormalities can be seen.3Federle M. Borhani A. Jeffrey R. Woodward P. Diagnostic Imaging: Abdomen.2nd ed. Amirsys, Salt City, Utah2010Google Scholar Single liver metastasis can be hypervascular or hypovascular and usually follows the pattern of the primary tumor. This patient did not have any known primary tumor.3Federle M. Borhani A. Jeffrey R. Woodward P. Diagnostic Imaging: Abdomen.2nd ed. Amirsys, Salt City, Utah2010Google Scholar The main diagnosis for this young patient with sickle cell anemia was extramedullary hematopoiesis (EMH). EMH is a response mechanism that occurs when there is either poor quality of the red blood cells, or insufficient production of these blood elements. Sickle cell disease is characterized by hemolysis that leads to chronic anemia. To maintain the body‘s demand, besides reconversion of yellow to red bone marrow, extramedullary production of erythrocytes can be stimulated. The liver and spleen are the most common sites of EMH, which typically manifests as homogeneous hepatosplenomegaly. It can uncommonly present itself as multiple nodules, and even more rarely as a single nodular lesion. These locations of EMH can be explained by the sites of hematopoiesis in fetal and early stages of life. Common sites of hematopoiesis are the yolk sac, liver, spleen, and bone marrow in the fetus. In early life, hematopoiesis is restricted to the bone marrow. Therefore, EMH must always be considered in the differential diagnoses of masses, nodules, and hepatosplenomegaly in patients with sickle cell anemia. Most patients are asymptomatic or have nonspecific symptoms, such as fatigue.1Roberts A.S. Shetty A.S. Mellnick V.M. Pickhardt P.J. Bhalla S. Menias C.O. Extramedullary haematopoiesis: radiological imaging features.Clin Radiol. 2016; 71: 807-814Abstract Full Text Full Text PDF PubMed Scopus (59) Google Scholar The appearance of EMH on CT and MRI is usually a heterogeneous, hypovascular, soft tissue mass. The signal intensity of EMH varies depending on the degree of iron deposition on the liver, which may be secondary to recurrent blood transfusions. It is usually mildly hypointense on T1-WI and mildly hyperintense on T2-WI. The presence of intralesional fat is typical.1Roberts A.S. Shetty A.S. Mellnick V.M. Pickhardt P.J. Bhalla S. Menias C.O. Extramedullary haematopoiesis: radiological imaging features.Clin Radiol. 2016; 71: 807-814Abstract Full Text Full Text PDF PubMed Scopus (59) Google Scholar Therefore, although EMH was the main hypothesis, a CT-guided biopsy was performed with the use of a 16-gauge Menghini biopsy needle. The histologic analysis showed sickle cells in the sinusoids and extramedullary hematopoiesis: erythroid cells represented by normoblasts (∗) in addition to megakaryocytes (arrows) (Figure H), which confirmed the diagnosis of EMH. Blood transfusion was performed before liver biopsy owing to the high risk of hemorrhage.1Roberts A.S. Shetty A.S. Mellnick V.M. Pickhardt P.J. Bhalla S. Menias C.O. Extramedullary haematopoiesis: radiological imaging features.Clin Radiol. 2016; 71: 807-814Abstract Full Text Full Text PDF PubMed Scopus (59) Google Scholar This patient was followed for 6 years, and the liver lesion remained similar, as shown in contrast-enhanced CT (Figure I). Other findings of our patient include H-shaped vertebrae, a predominance of hematopoietic bone marrow, and multiple areas of bone infarction. During these years he had more than 30 hospitalizations, most due to pain crises, and required recurrent transfusions and continuous analgesia. He had many complications, such as sacroiliac osteomyelitis, episodes of acute chest syndrome, and cholecystitis. He developed sickle cell nephropathy, heart failure with reduced ejection fraction, and mild pulmonary hypertension. The last hospitalization was due to acute chest syndrome, when he developed hemodynamic instability and massive cerebral hemorrhage, leading to brain death. Patients with sickle cell disease should be closely monitored by a multidisciplinary team. Vaccination against encapsulated organisms such as Streptococcus pneumoniae, Haemophilus influenzae type b, and Neisseria meningitidis is important due to autosplenectomy. Psychologic and psychiatric follow-up cannot be forgotten, because these patients suffer from intense pain and frequent hospitalizations and are at risk of developing opioid dependence.2Hoppe C. Neumayr L. Sickle cell disease: monitoring, current treatment, and therapeutics under development.Hematol Oncol Clin North Am. 2019; 33: 355-371.2Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar Many patients with EHM do not require a specific treatment. For symptomatic patients, frequent blood transfusions and radiotherapy can be used to reduce the hematopoietic stimulus. The attending physician should assess the risk-benefit relation and decide on the best treatment.1Roberts A.S. Shetty A.S. Mellnick V.M. Pickhardt P.J. Bhalla S. Menias C.O. Extramedullary haematopoiesis: radiological imaging features.Clin Radiol. 2016; 71: 807-814Abstract Full Text Full Text PDF PubMed Scopus (59) Google Scholar