Case of the S e a s o n

By Alka Kumar, Shashi Aggarwal, and kyne Noel de Tilly

A 35-YEAR-OLD MAN presented to the hospital with right upper quadrant pain.

He had long-standing history of failure to thrive. A computed tomography (CT) scan and mag- netic resonance (MR) scan were obtained (Figs 1 and 2).

Fig 1. A noncontrast enhanced CT scan at the level of the lower chest.

Fig 3. A TI weighted (A) and a T 2 weighted (B) axial MR images of the upper abdomen.

ABBREVIATIONS

CT, computed tomography; MR, magnetic reso- nance; EMH, extramedullary hematopoiesis.

Fig 2. A non-contrast-enhanced CT scan of the upper abdomen.

From the Department of Diagnostic Imaging, St. Michael's Hospital, Toronto, Ontario, Canada, and the Department of Radiology, Boston University Medical Center, Boston, MA.

Address reprint requests to Alka Kumar, MD, Dept of Radiology, Boston University Medical Center, 88 E Newton St, Boston, MA 02118.

Copyright © 1995 by W.B. Saunders Company 0037-198X/95/3002-000155. 00/0

Sem/nars/n Roentgeno/ogy, Vol XXX, No 2 (April), 1995: pp 99-101 99

100 KUMAR, AGGARWAL, AND DE TILLY

DIAGNOSIS

Thalassemia Major with ExtramedulIary Hematopoiesis in the Liver

In Figure 1, a non-contrast-enhanced CT scan at the level of lower thorax shows cardio- megaly and bilateral paraspinal masses. All the visualized bones show diffuse expansion with thinning of trabeculae typical of erythropoietic marrow hyperplasia. Figure 2 is a non-contrast- enhanced CT scan of the upper abdomen show- ing a large, well-defined, slightly hyperdense-to- isodense mass in the left lobe of liver with central areas of low attenuation consistent with necrosis. The liver also shows overall increased density. Note surgical clips in the gallbladder fossa from previous cholecystectomy. The pa- tient has also had splenectomy. A Tl-weighted axial MR image (TR/TE/NEX, 500/20/4) at the same level (Fig 3) shows the liver mass to be of low signal intensity similar to that of the liver. Proton density and T2-weighted images at the same level also showed signal intensity of the hepatic mass to be the same as that of the surrounding liver (Fig 3B). Central areas of high signal intensity correspond to necrotic areas seen on the CT scan. Isointensity of the mass to the liver on all pulse sequences confirms the diagnosis of extramedullary hematopoiesis (EMH).

Thalassemias are a heterogeneous group of congenital anemias in which there is a defect in synthesis of one or more subunits of hemoglo- bin. Among these, thalassemia major, or Cooley's anemia, is the most severe form of congenital anemia, and is characterized by marked relative excess of a-chain production. These patients manifest features of both ineffec- tive erythropoiesis and peripheral hemolysis, resulting in marked stimulus for compensatory changes of red cell production such as marrow expansion and extramedullary erythropoiesis.

Clinical manifestations appear in the first few months of life and consist of manifestations of severe anemia that needs to be treated by transfusions. Other clinical features include wasting, malnourishment, slow rate of growth with delay in secondary sex characters, and bony deformities caused by marrow expansion. Also seen are features related to iron overload caused

by repeat transfusions. Cardiomegaly, hepato- megaly, and splenomegaly are invariably pre- sent. Pigmented gallstones are common be- cause of increased bilirubin from peripheral hemolysis. These patients also have a peculiar skin color because of a combination of pallor, icterus, and increased melanin deposition. 1 The life span is shortened, and most of the patients with severe anemia manifest signs of significant hemosiderosis caused by repeat transfusions. As a result, abnormalities of endocrine, cardiac, and hepatic function are common. Death is caused by myocardial siderosis leading to arryth- mias and/or congestive failure. Treatment con- sists of supportive therapy in the form of trans- fusion and splenectomy to help increase life span of red cells. Iron chelation therapy is also used to mobilize extra iron.

Diagnosis of thalassemia should be consid- ered for any patient with severe hemolytic anemia of microcytic hypochromic type. Periph- eral smear shows abnormal size and shape of red blood cells with target and tear drop cells. Hemoglobin electrophoresis shows increased amount of hemoglobin F.

Radiologically, there is a diverse array of findings that can be seen as a result of marrow expansion, EMH, peripheral hemolysis, and changes of iron overload. Skeletal changes are typical, with almost all the bones showing mar- row expansion and cortical thinning with coarse trabeculae caused by hypertrophy of erythropoi- etic marrow. Nutrient foramina are prominent especially in hands because of increased vascu- lar supply to the marrow. Skull bones show typical 'hair-on-end' appearance because of increased marrow in the diploic spaces along with proliferation of erythropoietic marrow along the periosteum. The femora show Eden- meyer flask deformity. Other skeletal deformi- ties with delayed skeletal maturation are com- mon. Pathological fractures may be seen. It is not uncommon to see changes of EMH through- out the body in severe cases. The most common location is paraspinal, where the typical appear- ance is that of bilateral paraspinal masses. These areas are actually contiguous with bony marrow and contained by periostcum. Other common sites are spleen and lymph nodes. Some uncommon sites of EMH include spinal

CASE OF THE SEASON 101

cord (where it can give rise to cord compres- sion), liver, and perirenal areas where EMH masses may cause obstructive uropathy. Diffuse involvement of liver is more common than focal masses particularly in disease entities that oblit- erate normal marrow space. A periportal form of EMH seen as hypodense areas around the portal tracts has also been reported. 2 Dewar et aP described a case of a large, solitary intrahe- patic EMH tumor in a patient with thalassemia. Typically on ultrasonography these focal masses of EMH in the liver appear hypoechoic relative to the liver. Reported CT findings are those of a well-defined, hypodense, heterogeneous mass. These lesions may show heterogeneous contrast enhancement on CT and MR. 3 Most lesions would show signal intensity similar or slightly hyperintense to liver on T2-weighted images because hepatic lesions are infiltrative in nature with hematopoietic cells interspersed with nor- mal liver sinusoids. 4 The EMH mass in the liver needs to be distinguished from hepatoceUular carcinoma because there is increased incidence of the latter in hemochromatosis. Typically, neoplasms including hepatocellular carcinoma show much higher signal intensity on T2- weighted images than is seen with EMH. Changes related to hemosiderosis include in- creased density of liver and spleen (if splenec- tomy has not been performed), heart, and pancreas because of iron deposition. On MR, all these organs with increased iron deposition show abnormally low signal on T1- and T2- weighted images because of paramagnetic effect of iron. Magnetic resonance also has been used to quantitate liver iron with variable success.

Cardiomegaly usually is caused by a combina- tion of severe anemia and hemosiderosis. Most of these patients would have evidence of prior cholecystectomy and splenectomy.

If the conglomeration of findings such as are seen in this case is encountered, the diagnosis is certain. In other hemolytic anemias such as sickle cell disease, the changes are not this severe, extramedullary hematopoiesis is not a common feature, and clinical history as well as infarcts in various organs are common because of repeated sickle cell crisis. In congenital hemolytic anemias, typically EMH is seen in the vicinity of hematopoietically active bones. Further, EMH may sometimes be seen with acquired disorders that cause marrow oblitera- tion. In this setting, EMH is generally wide- spread with frequent involvement of the liver and abdominal lymph nodes. However, involve- ment of the liver is typically diffuse, and focal lesions are uncommon. If only liver changes are considered, ie, hepatomegaly, increased den- sity, and focal masses, glycogen storage disease type 1 (VonGierke's) enters the differential diagnosis. However, usually the liver density in such cases is mixed because of a combination of high-density glycogen and low-density fat. There is an increased incidence of hepatic adenomas and hepatocellular carcinomas in glycogen stor- age disease type 1. Gaucher's disease, another lysosomal storage disease, usually has a differ- ent clinical manifestation. Although there is hepatosplenomegaly, changes of iron overload, peripheral hemolysis, and EMH are not seen in Gaucher's disease.

REFERENCES

1. Cooper RA, Bunn HF: Hemolytic anemias, in Braun- wald E, Isselbacher KJ, Petersdorf RG, et al (eds): Harri- son's Principles of Internal Medicine (ed 11). New York, NY, McGraw Hill, 1987

2. Kobayashi A, Sugihara M, Kurosaki M, et al: CT characteristics of intrahepatic, periportal, extramedullary hematopoiesis. J Comput Assist Tomogr 13:354-356, 1989

3. Dewar G, Leung NW, Ng HK, et al: Massive, solitary, intrahepatic, extramedullary hematopoiesis tumor in thalas- semia. Surgery 107:704-707, 1990

4. W~trshauer DM, Schieble r ML: Intrahepatic extramed- ullary hematopoiesis: MR, CT, and sonographic appear- ance. J Comput Assist Tomogr 15:683-685, 1991