AJR 2002; 179:1239-1243
© American Roentgen Ray Society
Typical and Atypical Presentations of Extramedullary Hemopoiesis
Christos S. Georgiades1,
Edward G. Neyman1,
Isaac R. Francis2,
Michael B. Sneider2 and
Elliot K. Fishman1
1 Russell H. Morgan Department of Radiology and Radiological Sciences, Johns
Hopkins University School of Medicine and Johns Hopkins Hospital, 601 N.
Caroline St., Baltimore, MD, 21287.
2 Department of Radiology, University of Michigan Medical School, 1301 Catherine
Rd., Ann Arbor, MI 48109.
Received February 11, 2002;
accepted after revision April 5, 2002.
Address correspondence to E. K. Fishman.
Introduction
Hemopoiesis is the formation and maturation of blood elements. Hemopoiesis
normally occurs in the marrow of long bones, the ribs, and the vertebrae of
the adult, in contradistinction to the fetus, in which the principal sites of
hemopoiesis are the yolk sac, spleen, and liver
[1,
2] (Fig.
1A,1B).
When the primary sites of hemopoiesis in the adult fail, as in myelofibrosis
(of many causes) and in hemoglobinopathies (especially thalassemia and sickle
cell disease), various extramedullary sites take on the role of blood
formation. Extramedullary hemopoiesis favors certain sites such as the liver,
the spleen, and the paraspinal regions of the thorax. However, in addition to
these common sites of extramedullary hemopoiesis, the process can involve
virtually any organ or tissue and can often manifest as a mass mimicking a
neoplasm. Symptoms are usually caused by the mass effect. Recognizing the
imaging findings that may be compatible with extramedullary hemopoiesis is
important, because biopsy will exclude a neoplasm and alter management and
prognosis. Equally important is knowledge of the patient's clinical history.
In this article, we present patients with a variety of imaging manifestations
of biopsy-proven extramedullary hemopoiesis.
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Fig. 1A. —Graphs show sites of normal hemopoiesis. In embryo and fetus,
hemopoiesis is initially localized in yolk sac. Within 1-2 months, liver and
spleen begin physiologic extramedullary hemopoiesis, followed by bone marrow.
By birth all extramedullary hemopoiesis ceases.
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Fig. 1B. —Graphs show sites of normal hemopoiesis. After birth, all
normal hemopoiesis occurs in bone marrow of proximal long bones, ribs,
sternum, and vertebrae [1],
which fail over time in that same order.
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Imaging Findings
Thorax
In the thorax, the most common imaging manifestations are paraspinal masses
and rib expansion [3,
4], and these findings are more
frequent in ß-thalassemia than in other causes of extramedullary
hemopoiesis. The paraspinal active hemopoietic masses are well marginated and
show mild homogeneous enhancement on contrast-enhanced CT, whereas old,
burnt-out lesions may show iron deposition or fatty degeneration
[4]. Active hemopoietic masses
are serendipitously found overlying the sympathetic chain (Fig.
2A,2B,2C),
a location that is also favored by paraspinal neurogenic tumors seen in
neurofibromatosis type I; however, neurofibromatosis type I can be easily
excluded on the basis of clinical history. Rib or diploic space expansion is
not uncommon, especially in thalassemia, and results from the contiguous
expansion of the intramedullary marrow (Fig.
3A,3B).
Rarely, hemopoietic elements can involve the precardiac and pleural spaces,
but patients are usually asymptomatic. Cases of extramedullary hemopoiesis
involving the pulmonary interstitium and mimicking an inflammatory or
neoplastic diffuse interstitial process have been reported and have
occasionally resulted in cardiopulmonary insufficiency
[5]. Indirect findings of
failing bone marrow or an increased demand for blood elements include
cardiomegaly and eventual high-output cardiac failure, a not rare complication
in patients with thalassemia. Paraspinal hemopoietic tissues can extend into
the central canal, especially in the thorax, and cause neurologic symptoms
because of spinal cord compression. MR imaging findings, although nonspecific,
can suggest the diagnosis. Suggesting this diagnosis is important because
treatment with steroids and external beam radiation is effective and usually
long-lasting [6].
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Fig. 2A. —23-year-old woman with history of thalassemia and known
extramedullary hemopoiesis. Axial contrast-enhanced CT scan through chest
shows uniformly enhancing paraspinal hemopoietic masses with no bony
erosion.
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Fig. 2B. —23-year-old woman with history of thalassemia and known
extramedullary hemopoiesis. Posteroanterior chest radiograph shows
well-marginated bilateral, paraspinal masses compatible with extramedullary
hemopoietic tissue.
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Fig. 3A. —25-year-old man with ß-thalassemia. Posteroanterior
chest radiograph shows diffuse expansion of ribs and right upper paraspinal
thoracic mass (arrow) compatible with extramedullary hemopoiesis.
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Abdomen and Pelvis
Abdominal involvement usually recapitulates fetal development, with the
most commonly involved organs being the liver and spleen. The classic imaging
finding is that of hepatosplenomegaly
[1] (Figs.
4A,4B
and 5). Involvement of these
organs is usually diffuse, but, as illustrated in Figures
6A,6B
and
7A,7B,
masslike foci of hemopoiesis can be seen
[7,
8] that may be confused with a
neoplastic process. Despite the sometimes massive enlargement of these organs,
their function is rarely affected. Patients usually present with findings of
organomegaly or with vague abdominal symptoms on physical examination.
Patients who require multiple transfusions (i.e., those with thalassemia) can
develop hemosiderosis or hemochromatosis. As a result, on CT the parenchymal
density of the liver (Fig. 6B)
and spleen is increased, whereas on both T1- and T2-weighted MR images signal
is lost because of the deposition of iron. Extramedullary hemopoiesis can
also, rarely, involve the kidneys. Parapelvic hemopoietic masses can be seen
because this location is active during in utero hemopoiesis. However,
occasionally extramedullary hemopoiesis manifests as uniform, enhancing
perinephric masses that appear to engulf the kidneys without however
distorting their shape (Fig.
8A,8B).
This appearance may be confused with bilateral renal lymphoma, and biopsy is
necessary to establish the diagnosis. Masses of hemopoietic elements can
involve the mesentery (Fig.
9A,9B),
presenting as nonspecific lesions that can be mistaken for lymphadenopathy or
metastatic disease. Pelvic hemopoietic masses with predilection for the
presacral region are rare but, in the proper context, should be included in
the differential diagnosis along with other presacral lesions
(Fig. 10), including
chordoma.
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Fig. 4A. —54-year-old woman with long-standing history of myelofibrosis
who presented with abdominal discomfort and gradual onset of shortness of
breath. Posterior (A) and anterior (B) views from
99mTc methylene diphosphonate wholebody bone scans show diffusely
increased activity in massively enlarged liver that compromises lung
volume.
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Fig. 4B. —54-year-old woman with long-standing history of myelofibrosis
who presented with abdominal discomfort and gradual onset of shortness of
breath. Posterior (A) and anterior (B) views from
99mTc methylene diphosphonate wholebody bone scans show diffusely
increased activity in massively enlarged liver that compromises lung
volume.
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Fig. 5. —51-year-old woman with myelofibrosis. Abdominal discomfort
prompted clinic visit during which physical examination revealed large spleen.
Coronal T1-weighted MR image shows massively enlarged spleen. Patient's
symptoms worsened over time, and splenic biopsy was followed by splenectomy.
Pathologic examination revealed diffuse infiltration with immature and mature
heme elements, which is compatible with extramedullary hemopoiesis.
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Fig. 6A. —40-year-old man with sickle cell disease and frequently
recurring painful crises who presented with abdominal pain. Axial unenhanced
CT scan at thoracoabdominal level reveals two uniformly low-attenuation
(compared with liver parenchyma), well-marginated lesions (arrows).
Percutaneous biopsy was diagnostic for foci of extramedullary hemopoiesis.
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Fig. 6B. —40-year-old man with sickle cell disease and frequently
recurring painful crises who presented with abdominal pain. Axial unenhanced
CT scan more caudal than A shows diffusely increased density of liver
parenchyma. Differential diagnosis included primary or secondary
hemochromatosis or hemosiderosis, treatment with amiodarone, and Wilson's
disease.
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Fig. 7B. —53-year-old man with weight loss and abdominal pain. Axial
T2-weighted MR image at same level as A shows mass to be slightly
hyperintense to liver parenchyma. Percutaneous biopsy showed extramedullary
hemopoiesis. Patient was subsequently diagnosed with myelofibrosis.
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Fig. 8B. —56-year-old man with myelofibrosis who presented with flank
and abdominal pain. Axial contrast-enhanced CT scan through kidneys from
current admission reveals bilaterally symmetric enhancing perinephric masses.
Biopsy showed extramedullary hemopoiesis.
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Fig. 9A. —33-year-old man with unspecified myeloproliferative disorder
who presented with abdominal pain. Patient has history of splenectomy for
severe splenomegaly and cavernous transformation of portal vein. Axial
contrast-enhanced CT scan through upper abdomen shows ill-defined mass
(arrow) in porta hepatis infiltrating mesentery along gastrohepatic
ligament.
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Fig. 9B. —33-year-old man with unspecified myeloproliferative disorder
who presented with abdominal pain. Patient has history of splenectomy for
severe splenomegaly and cavernous transformation of portal vein. Axial
gadolinium-enhanced T1-weighted fat-suppressed MR image at same level as
A shows same findings without adding specificity. Percutaneous biopsy
revealed immature hemopoietic elements compatible with extramedullary
hemopoiesis.
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Fig. 10. —48-year-old man with history of hemolytic anemia and
myelofibrosis. Axial unenhanced CT scan through pelvis shows well-marginated
presacral soft-tissue mass (arrow) with no bony erosion. Biopsy was
diagnostic of extramedullary hemopoiesis.
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Discussion
Extramedullary hemopoiesis is a reactive process that results from either
marrow failure (myelofibrosis or infiltrative disease) or ineffective
circulating mature blood elements. The paraspinal thoracic regions, the liver,
and the spleen are the most common sites of involvement by this process, and
familiarity with its cross-sectional appearance and knowledge of the patient's
clinical history are essential to avoid misdiagnosis. Rare manifestations,
some of which we have discussed, include renal and mesenteric pseudotumors and
may need biopsy for definitive diagnosis. Secondary signs of chronic anemia
(i.e., expanded diploic space, signs of hemochromatosis) serve as supportive
evidence of extramedullary hemopoiesis. However, tumorlike lesions still need
definitive diagnosis.
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Introduction
Imaging Findings
