DOI:10.2214/AJR.06.1500
AJR 2007; 189:209-218
© American Roentgen Ray Society
Radiologic Spectrum of Extramedullary Relapse of Myelogenous Leukemia in Adults
Jan Fritz1,2,
Wichard Vogel3,
Roland Bares4 and
Marius Horger1
1 Department of Diagnostic Radiology, Eberhard-Karls-University Tübingen,
Hoppe-Seyler-Strasse 3, 72076 Tübingen, Germany.
2 Russell H. Morgan Department of Radiology and Radiological Science, Johns
Hopkins University School of Medicine, Baltimore, MD 21287.
3 Division of Oncology, Department of Internal Medicine,
Eberhard-Karls-University Tübingen, Tübingen, Germany.
4 Division of Nuclear Medicine, Department of Diagnostic Radiology,
Eberhard-Karls-University Tübingen, Tübingen, Germany.
Received November 22, 2006;
accepted after revision February 5, 2007.
Address correspondence to J. Fritz
(jan.fritz{at}gmx.net).
Abstract
OBJECTIVE. Chloroma, also know as granulocytic sarcoma, is a
localized extramedullary tumor composed of malignant cells of the myeloid cell
line. It occurs most frequently secondary to a history of myelogenous leukemia
as extramedullary relapse. New treatment regimens, including allogeneic stem
cell transplantation, extensive use of donor lymphocyte infusion, and second
transplantation, are associated with increased rates of chloroma of up to 21%.
The purpose of this article is to highlight the sites of involvement as well
as the morphologic and imaging features of chloroma in patients with
myelogenous leukemia.
CONCLUSION. Allogeneic stem cell transplantation now represents the
treatment of choice for leukemia and for patients with leukemia relapse.
Therefore, the rate of chloroma is likely to increase. Because clinical and
laboratory data are frequently not indicative, radiologic diagnosis of
chloroma will become more important.
Keywords: leukemia • oncologic imaging • oncology
Introduction
Chloroma, also known as granulocytic sarcoma, is a localized extramedullary
tumor composed of malignant cells of the myeloid cell line, most frequently
occurring in myelogenous leukemia. Markedly elevated rates of up to 21% have
been reported after allogeneic bone marrow transplantation
[1]. One hypothesized mechanism
for this increased incidence is the inability of antileukemic effector cells
to function at natural barriers or in the presence of microenvironmental
conditions [2].
Chloroma requires early diagnosis because a focal relapse could eventually
be cured by local therapy (e.g., radiation)
[3]. Diagnosis, however, proves
to be challenging because clinical and laboratory data are frequently not
indicative. Radiologic findings are nonspecific, and because of the great
variety of structures involved, there is considerable risk for misdiagnosis
and delay in therapy. An awareness of potential sites of involvement and
morphologic and imaging features should aid radiologists in consideration of
granulocytic sarcoma in the differential diagnosis.
Imaging Characteristics
Chloroma may occur at any part of the body, but the most common sites of
occurrence are breast, subcutaneous tissues, and bone
[4–7].
Lesions generally present as a soft-tissue nodule or mass or as a diffuse
infiltrative process. Imaging features of CT, MRI, and sonography are
frequently similar to those of lymphoma
[6–8].
Whole-body 18F-FDG PET is useful in staging patients suspected of
having extramedullary relapse of myelogenous leukemia because lesions may show
increased glycolytic activity. Combined PET/CT may increase specificity and
aid in guiding the biopsy.
CNS
Chloroma may directly affect the CNS in various ways
[9]. Intraaxial chloroma can
involve the cerebrum, cerebellum, or cranial nerves
(Fig. 1). Edema, hemorrhage, or
mass effect may be present. Extraaxial masses show continuous growth with the
meninges (Fig. 2) or ependyma
and are thought to arise from dural and subarachnoid veins. Leptomeningeal or
subarachnoidal disease is also known as leukemic meningitis. Spinal chloroma
is rarely encountered.
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Fig. 1 —21-year-old man with chloroma of mandibular branch (V3) of
trigeminal nerve. Coronal contrast-enhanced T1-weighted MR image shows altered
signal intensity of Meckel's cave (arrow) and right mandibular nerve
in continuation throughout foramen ovale caused by chloroma. Trigeminal nerve
was only site of involvement in this patient who complained of neuralgia.
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Fig. 2 —37-year-old man with pachymeningeal chloroma. T2-weighted
coronal MR image shows small left parasagittal meningeal mass near superior
sagittal venous sinus (white arrow) showing T2 hyperintensity. In
addition, there is right hemispheric glioma (black arrows) with large
perifocal edema and compression of right lateral ventricle.
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Head and Neck
Involvement of the lips, gingiva, nose, and facial skin is common
[4,
5]. Although such involvement
is generally detected early, deep infiltration may sometimes lead to bone
destruction (Figs. 3A and
3B) and expansion into the
paranasal sinus. Differentiation from carcinoma or lymphoma requires biopsy.
Orbital and paranasal chloroma may mimic carcinoma.
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Fig. 3A —22-year-old man with chloroma of upper lip and vestibular
mucosa. Axial contrast-enhanced CT scans at level of maxilla show infiltration
of upper vestibular mucosa with involvement of upper lip and its frenulum.
These images also show almost symmetric growth of tumor (arrows),
which has already destroyed maxilla (region 12–13), invading hard
palate.
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Fig. 3B —22-year-old man with chloroma of upper lip and vestibular
mucosa. Axial contrast-enhanced CT scans at level of maxilla show infiltration
of upper vestibular mucosa with involvement of upper lip and its frenulum.
These images also show almost symmetric growth of tumor (arrows),
which has already destroyed maxilla (region 12–13), invading hard
palate.
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Breast
Chloroma of the breast (Figs.
4A and
4B) may manifest as single or
multiple masses [6]. Margins
are generally ill defined and spicular or may be rounded, mimicking other
tumors of the breast. On mammogramphy images, lesions are typically irregular
and hyperdense. Thus, dense breast parenchyma may mask these tumors. On
sonography, an irregularly shaped heterogeneous hypoechoic mass with
ill-defined margins and possible posterior acoustic shadow is found. Doppler
sonography images usually show hypervascularized masses
(Fig. 4B). Contrast-enhanced MR
images may show washout, making differentiation from other breast masses
difficult.
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Fig. 4A —32-year-old woman with chloroma of breast. Axial unenhanced
CT scan of chest shows dense, ovoid 3-cm mass (arrows) embedded in
left breast parenchyma, which is isodense to surrounding parenchyma and
musculature. Asymmetry between breasts led to detection of this chloroma. Note
also solitary pulmonary nodule with cavitation in left lung caused by septic
embolism.
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Fig. 4B —32-year-old woman with chloroma of breast. B-mode sonogram
shows heterogeneous slightly hypoechoic mass with ill-defined margins, whereas
color Doppler signal indicates multiple strong caliber arterial feeder vessels
and draining veins.
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Heart
Chloroma involving the heart (Figs.
5A and
5B) has been described
sporadically [10]. All layers,
chambers, and valves of the heart may be involved. Echocardiography may show
an intracavitary, intramural, intrapericardial, or paracardial mass, but there
are no specific features allowing differentiation from other cardiac tumors or
even thrombus. CT and especially MRI are capable of visualization of the
entire cardiac involvement.
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Fig. 5A —40-year-old man with chloroma of heart. Axial
contrast-enhanced cardiac CT scan shows circular involvement of right heart
along tricuspid valve with intramural growth and secondary infiltration of
pericardium (arrows). There is also segmental thickening of
interatrial and interventricular septum. Consecutive large pericardial
effusions were drained.
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Fig. 5B —40-year-old man with chloroma of heart. Multiplanar
reconstruction contrast-enhanced cardiac CT shows relative hypodensity of mass
due to high vascular density of normal myocardium (white arrow).
Echocardiography (not shown) disclosed tricuspid valve insufficiency. Note
also right ventricular electrode of bipolar pacemaker (black arrows)
and pericardial drain (asterisk).
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Lung and Mediastinum
Pulmonary chloroma is rare
[4]. It may manifest as large
alveolar opacities (Fig. 6A),
interstitial septal thickening, or multiple parenchymal nodularities
[6,
7]
(Fig. 6B). Concomitant pleural
and mediastinal involvement is common. A positive air bronchogram can be
present in early stages. In later stages, however, large masses typically
compress adjacent lung parenchyma. In the nodular form, cavitation may occur,
making differentiation from lung abscesses or fungal infection impossible.
Mediastinal chloroma is mostly indicated by enlarged lymph nodes.
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Fig. 6A —Chloroma of lung. Axial CT scan of chest in 43-year-old man
shows infiltrative growth patterns. Partial upper lobe atelectasis is caused
by central bronchus stenosis (not shown) due to proximal peribronchial
chloroma. Most of mass seen in right upper lobe represents chloroma, leading
to enlargement of the involved pulmonary lobe.
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Pleura
Chloroma of the pleura often presents as nodular or plaquelike lesions
(Figs. 7A,
7B, and
7C) usually accompanied by
pleural effusion.
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Fig. 7A —Pleural chloroma. Axial contrast-enhanced CT scan at level of
cardiac ventricles in 60-year-old man with pleural chloroma shows plaquelike
granulocytic sarcoma (arrow) along right parietal costal pleural
lining.
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Fig. 7B —Pleural chloroma. Axial contrast-enhanced CT scan at level of
left atrium in same patient reveals pulmonary involvement (arrow) of
collapsed right lower lung lobe accompanied by pleural infiltration.
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Fig. 7C —Pleural chloroma. Axial contrast-enhanced CT scan in
28-year-old woman at level of aortic arch shows epipleural chloroma (white
arrow) in paravertebral location extending to ipsilateral neuroforamen
(black arrow).
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Liver
Chloroma of the liver (Fig.
8) usually presents as solitary or multiple well-defined masses
that can reach several centimeters in diameter
[6]. It cannot be
differentiated from other hepatic tumors; however, it shares some of the
imaging characteristics of lymphoma. A rare form of chloroma spreads along the
peribiliary space (Fig. 9) and
can be accompanied by biliary obstruction
[11]. Similar findings have
been described in lymphoma, sarcoidosis, breast carcinoma, and others.
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Fig. 8 —47-year-old man with chloroma of liver. Coronal
contrast-enhanced CT scan of liver shows multifocal granulocytic sarcoma as
homogeneously hypodense hepatic masses (arrows). On sonograms,
hepatic chloromas presented as homogeneously hypoechoic masses (not
shown).
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Fig. 9 —39-year-old man with chloroma of liver. Coronal
contrast-enhanced CT scan of liver shows peribiliary granulocytic sarcoma
(arrows) in patient presenting with mild jaundice several months
after allogeneic hematopoietic cell transplantation, consistent with
extramedullary relapse of myelogenous leukemia.
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Bowel, Peritoneum, Omentum
In barium studies, CT, MRI, or colonography, lesions may be nodular,
polypoid, or ulcerated or may appear as solitary or multiple plaquelike wall
thickening [12]. Segmental
bowel wall thickening (Fig.
10A) usually presents without stenosis and shows similarity to
infectious, benign, or malignant bowel diseases. Differentiation from
non-Hodgkin's lymphoma or adenocarcinoma is not possible. Chloroma of the
appendix can mimic acute inflammation
[13]. Gastrointestinal
chloroma is often accompanied by plaquelike or nodular masses
(Fig. 10B) along the
peritoneum forming a typical interface sign
[6]. These masses are
nonspecific, mimicking peritoneal seeding associated with other
malignancies.
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Fig. 10A —33-year-old woman with chloroma of bowel, peritoneum, and
omentum. Axial (A) and coronal (B) contrast-enhanced CT scans of
abdomen reveal intestinal chloroma presenting as segmental wall thickening of
colon (white arrow, A). Note also ill-defined bowel margins
and increased, diffuse wall enhancement (black arrow, A). Note
reticular and small nodular thickening of peritoneum and greater omentum
(arrows, B) representing chloroma.
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Fig. 10B —33-year-old woman with chloroma of bowel, peritoneum, and
omentum. Axial (A) and coronal (B) contrast-enhanced CT scans of
abdomen reveal intestinal chloroma presenting as segmental wall thickening of
colon (white arrow, A). Note also ill-defined bowel margins
and increased, diffuse wall enhancement (black arrow, A). Note
reticular and small nodular thickening of peritoneum and greater omentum
(arrows, B) representing chloroma.
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Testis and Adnexa
Testicular chloroma (Fig.
11) is more common than adnexal chloroma
[14,
15]
(Fig. 12). Sonography helps in
determining tumor extent and guiding biopsy. Echogenicity is generally
homogeneous in smaller tumors. Doppler sonography typically shows
hypervascular lesions. On CT or MRI, testicular and adnexal tumors show
homogeneous density and signal intensity with strong contrast enhancement.
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Fig. 12 —33-year-old woman with chloroma of adnexa. Axial
contrast-enhanced CT scan of pelvis shows enlargement of left adnexa
representing chloroma seeding (arrow) in patient also presenting with
bowel-wall infiltration.
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Muscle
Muscular chloroma is usually isodense compared with surrounding muscles on
unenhanced CT images. Both T1- and T2-weighted MR images show isointense and
mildly hyperintense tumors relative to uninvolved muscle
[16]. Homogeneous enhancement
of variable intensity may be seen after IV contrast administration on both CT
and MRI (Figs. 13A,
13B, and
13C). MRI characteristics are
nonspecific. Important differential diagnoses are lymphoma and myositis
related to graft-versus-host disease, infection (pyomyositis), eosinophilia,
and focal nodular myositis.
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Fig. 13A —Chloroma of skeletal muscle. Two coronal contrast-enhanced CT
scans of pelvis in 49-year-old man show different forms of muscular
infiltration (arrows) causing swelling of muscle belly with increased
peripheral enhancement and partial central hypodensity.
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Fig. 13B —Chloroma of skeletal muscle. Two coronal contrast-enhanced CT
scans of pelvis in 49-year-old man show different forms of muscular
infiltration (arrows) causing swelling of muscle belly with increased
peripheral enhancement and partial central hypodensity.
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Fig. 13C —Chloroma of skeletal muscle. Coronal T2-weighted MR image
with fat saturation in 55-year-old woman shows increased signal intensity
(arrow). There was increased contrast enhancement on T1-weighted MR
sequences (not shown).
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Bone
In symptomatic chloroma, skeletal involvement is usually present. Commonly
involved sites include the orbits, sacrum, sinuses, spine, sternum, and ribs
[6,
7]. The tumor is thought to
begin in the bone marrow (Figs.
14 and
15) and has a propensity for
ligamentous and periosteal involvement (Figs.
16A and
16B), which most likely occurs
by migration through haversian canals
[8]. In later stages, osseous
infiltration presents mainly as a focal radiolucent zone or sclerosis
(Fig. 17). Untreated chloroma
of the bone leads to severe osseous destruction and pathologic fracture.
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Fig. 14 —66-year-old man with intramedullary chloroma. Sagittal
multiplanar reconstruction image of unenhanced CT of left femur shows multiple
intramedullary nodules (arrows) of different density. There is no
involvement of cortical bone or surrounding soft tissue.
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Fig. 15 —25-year-old woman with chloroma of bone. Sagittal T2-weighted
fat-saturated MR image shows granulocytic sarcoma with homogeneous signal
hyperintensity in tibial head (arrows), strongly enhancing after IV
gadopentetate dimeglumine (not shown).
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Fig. 16A —40-year-old man with chloroma of bone. Axial T1-weighted
gadolinium-enhanced MR image shows large, homogeneously enhancing granulocytic
sarcoma of left fibular head (black arrows). Expansive growth of this
tumor compresses surrounding muscles. Circular growth around fibular bone
suggests medullary origin. Note also mild enhancement of medullary space
(white arrow).
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Fig. 16B —40-year-old man with chloroma of bone. Whole-body
18F-FDG PET image (left figure part) shows increased focal
FDG uptake (standardized uptake value average, 5.6) (black arrow).
Fused coronal PET/CT image (right figure part) shows extraosseous
extension (white arrow). No additional foci were found.
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Fig. 17 —44-year-old woman with chloroma of bone. Axial CT scan at
level of femoral condyles (bone window setting) shows subtle sclerosis
(arrows) in right lateral femoral condylus caused by granulocytic
sarcoma.
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Skin
Chloroma of the skin may present as ill-defined nodules (Figs.
18A and
18B) or may be infiltrative
(Fig. 19). Isolated
subcutaneous lesions may resemble fatty necrosis or abscess.
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Fig. 18A —Chloroma of skin. Two axial contrast-enhanced CT scans show
subcutaneous granulocytic sarcoma presenting as ill-defined nodule
(arrow, A) or diffuse infiltration of subcutaneous tissue
(arrows, B). Patient in A is 51-year-old man; patient
in B is 47-year-old man.
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Fig. 18B —Chloroma of skin. Two axial contrast-enhanced CT scans show
subcutaneous granulocytic sarcoma presenting as ill-defined nodule
(arrow, A) or diffuse infiltration of subcutaneous tissue
(arrows, B). Patient in A is 51-year-old man; patient
in B is 47-year-old man.
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Fig. 19 —19-year-old man with subcutaneous granulocytic sarcoma of
skin. B-mode sonogram shows heterogeneous, centrally hypoechoic mass
(asterisk) with dorsal acoustic enhancement. Power Doppler signal
indicates increased surrounding vascularity.
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Conclusion
Radiologic diagnosis of chloroma will become increasingly important in the
future because new therapy strategies (repeated donor lymphocyte infusion,
second transplantation, and intensive pretreatment) will change the frequency
and known clinical appearance of myeloid leukemia
[2]. Knowledge of the potential
sites of relapse and their imaging features will aid in accurate diagnosis and
treatment.
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Abstract
Introduction
