AJR 2002; 178:319-325
© American Roentgen Ray Society
Granulocytic Sarcoma (Chloroma)
Imaging Findings in Adults and Children
A. Guermazi1,2,
C. Feger1,
P. Rousselot3,
M. Merad4,
N. Benchaib1,
P. Bourrier1,
X. Mariette4,
J. Frija1 and
E. de Kerviler1
1
Department of Radiology, Saint-Louis Hospital, AP-HP, 1 ave Claude Vellefaux,
75010 Paris, France.
2
Present address: Department of Radiology, University of California at San
Francisco, 350 Parnassus Ave., Ste. 150, San Francisco, CA 94117.
3
Department of Hematology, Saint-Louis Hospital, AP-HP, 75010 Paris,
France.
4
Department of Immuno-Hematology, Saint-Louis Hospital, AP-HP, 75010 Paris,
France.
Received March 15, 2001;
accepted after revision August 14, 2001.
Address correspondence to A. Guermazi.
Introduction
Granulocytic sarcoma, also known as chloroma or extramedullary
myeloblastoma, is a rare solid tumor composed of primitive precursors of the
granulocytic series of WBC that include myeloblasts, promyelocytes, and
myelocytes [1]. This tumor was
first described by Burns in 1811. In 1853, King initially called it chloroma,
because typical forms have a green color caused by high levels of
myeloperoxidase in these immature cells. Rappaport renamed it granulocytic
sarcoma in 1966, because not all of the cells are green; 30% are white, gray,
or brown, depending on the state of oxidation of the pigmented enzyme or the
different cellular enzyme concentrations
[1,
2]. Radiologic descriptions of
granulocytic sarcomas are rare in the literature and consist mainly of case
reports. The aim of this article is to present an overview of the most common
imaging findings of granulocytic sarcoma.
Clinical Records
Granulocytic sarcomas have been observed in patients with acute myelogenous
leukemia, chronic myelogenous leukemia, and other myeloproliferative disorders
such as myelofibrosis with myeloid metaplasia, hypereosinophilic syndrome, or
polycythemia vera [1]. They
occur in 2.5-9.1% of patients with acute myelogenous leukemia and five times
less frequently in patients with chronic myelogenous leukemia. Granulocytic
sarcomas have approximately the same rate of occurrence in both sexes.
Children are more often affected than adults: 60% of patients are younger than
15 years old.
Granulocytic sarcomas may develop during the course of, or as a presenting
sign of, myelogenous leukemia. Less frequently (in up to 35% of patients),
granulocytic sarcomas may precede the hematologic leukemia by months or years
and can, therefore, be difficult to differentiate from lymphoma by clinical,
radiologic, and even anatomopathologic methods. Special staining and
histochemistry studies are required for accurate diagnosis. No prognostic
significance exists between acute leukemic patients with granulocytic sarcomas
and those without. However, patients with granulocytic sarcomas who have
chronic leukemia or myeloproliferative disorders have a negative prognosis,
because these tumors often occur during acute transformation. These sarcomas
are very sensitive to focal irradiation or chemotherapy; they generally
resolve completely in less than 3 months, although they recur in approximately
23% of patients [1].
Patients with granulocytic sarcomas are frequently asymptomatic: 50% of
cases are diagnosed only at autopsy. These tumors can involve any part of the
body, either concurrently or sequentially. They often occur in multiples and
preferentially involve orbits and subcutaneous tissue, but they may also occur
in paranasal sinuses, lymph nodes, bone, the spine, the brain, pleural and
peritoneal cavities, the breasts, the thyroid, salivary glands, the small
bowel, the lungs, or various pelvic organs
[1,
3].
Radiologic Features
Focal soft-tissue masses developing in the course of myelogenous leukemia
may consist of infection, hemorrhage, secondary neoplasms, or granulocytic
sarcoma. Early diagnosis is crucial, because each complication requires
specific therapy [1]. Many of
these lesions can be differentiated on the basis of anamnesis or on the
results of imaging findings.
Central Nervous System
Cerebral granulocytic sarcomas often appear as extraaxial masses. They are
contiguous to meninges or ependyma
[2] and thought to arise from
dural and subarachnoid veins and surrounding adventitia
[3]. Intracranial parenchymal
masses, however, rarely have been reported. Multiplicity of intracranial
lesions has been reported, as well as intraspinal and paraspinal involvement
[2]. Granulocytic sarcomas are
isodense or hyperdense to brain or muscle on unenhanced CT, hypointense or
isointense on T1-weighted MR images, heterogeneously isointense or
hyperintense on T2-weighted MR images, and they typically enhance
homogeneously after injection of contrast medium (Figs.
1A,1B
and
2A,2B,2C,2D).
They may be associated with edema and mass effect. In the setting of myeloid
leukemia, these imaging features suggest granulocytic sarcoma, and, therefore,
biopsy may be avoided [1].
Indeed, the signal intensity and homogeneous contrast enhancement help in the
differentiation of granulocytic sarcoma from hematoma and abscess.
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Fig. 1A. —28-year-old woman with acute myeloblastic leukemia,
readmitted to our hospital 8 months after first remission with 1-week history
of headache, vomiting, and dysphasia. Unenhanced CT scan of brain shows
irregular hyperdense mass with hypodense peritumoral edema in left parietal
lobe.
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Fig. 1B. —28-year-old woman with acute myeloblastic leukemia,
readmitted to our hospital 8 months after first remission with 1-week history
of headache, vomiting, and dysphasia. Unenhanced CT scan shows hyperdense mass
seen in A enhances homogeneously after contrast administration. Biopsy
subsequently revealed brain granulocytic sarcoma.
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Fig. 2B. —58-year-old woman with 2-month history of headache.
Unenhanced T1-weighted MR image in axial plane shows poorly defined right
periventricular lesion that is isointense with gray matter, with
periventricular mass effect.
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Fig. 2C. —58-year-old woman with 2-month history of headache.
T2-weighted MR image in axial plane shows surrounding edema much better than
B and shows relatively hypointense rim of lesion
(arrowheads).
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Fig. 2D. —58-year-old woman with 2-month history of headache.
Contrast-enhanced T1-weighted MR image in axial plane reveals marked
homogeneous enhancement of lesion. Examination of cerebrospinal fluid revealed
blasts, and histologic examination revealed brain granulocytic sarcoma. No
evidence of medullary or systemic disease was found. Seven months later,
patient was diagnosed with systemic acute myeloblastic leukemia with
eosinophils.
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When cranial granulocytic sarcomas are dural-based, they may have imaging
features similar to those of meningioma, although meningiomas usually have
calcifications and hyperostosis rather than bony destruction
[1]. Paraspinal and intraspinal
lesions are also thought to arise from perivenous arachnoid spread of leukemic
cells. Uncommonly, spinal involvement by granulocytic sarcoma may cause
compression of the spinal cord, cauda equina, or nerve roots. Extraosseous
extension of granulocytic sarcoma may occur without obvious bone destruction
(Fig. 3). Spinal granulocytic
sarcoma can be seen as an isodense extradural or intradural mass on CT images.
It has an intermediate signal on T1- and T2-weighted MR images and enhances
homogeneously after contrast medium administration. Differential diagnoses
include paraspinal or intraspinal abscess, hematoma, metastatic lesion, or
primary tumor such neurofibroma and schwannoma. Spinal intramedullary
granulocytic sarcomas, although rare, have also been described.
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Fig. 3. —44-year-old woman with history of acute myeloblastic leukemia
who had medullary and systemic relapse 6 months after autologous bone marrow
transplantation. Contrast-enhanced CT scan of chest shows left paraventebral
soft-tissue mass without bone destruction or epidural extension, which
corresponded to granulocytic sarcoma at biopsy. Complete resolution was
obtained in next 2 months after chemotherapy.
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Head and Neck
Orbital involvement is common in granulocytic sarcoma. It often precedes
the blast phase of systemic disease and may have various forms. Focal masses,
which may arise intraconally or extraconally, are often bilateral,
homogeneous, and well-defined, and they mold to the bone and contiguous
structures, including the sclera and the orbital bones. Only the medial
orbital wall is likely to show dissolution with sinus involvement (Fig.
4A,4B).
The lesions may arise primarily within the orbit, or they may extend into the
orbit from neighboring structures. The primary differential diagnoses of a
retrobulbar orbital mass in a child include rhabdomyosarcoma, metastatic
neuroblastoma, African Burkitt's lymphoma, and idiopathic inflammatory
pseudotumor.
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Fig. 4A. —65-year-old woman with acute myeloblastic transformation of
1-year history of aplastic anemia who presented with ptosis of right eye of
2-week duration. Contrast-enhanced CT scan in coronal plane through mid orbit
reveals soft-tissue mass involving right medial rectus muscle and right
maxillary sinus. Ethmoid mass with bony destruction of left ethmoid cells also
can be seen.
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Fig. 4B. —65-year-old woman with acute myeloblastic transformation of
1-year history of aplastic anemia who presented with ptosis of right eye of
2-week duration. Contrast-enhanced T1-weighted MR image in coronal plane shows
dense and heterogeneous enhancement of lesions. Biopsy subsequently showed
right orbital and paranasal sinus granulocytic sarcoma. Despite therapy,
patient died 6 months later.
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MR imaging findings before surgery are useful because the signal intensity
of lesion tissue is different from that of the contiguous heavily collagenized
sclera. Granulocytic sarcomas usually contain a noteworthy fibrous stroma with
a higher signal than that of the periorbita and sclera. Other ophthalmic
manifestations of granulocytic sarcomas include extraocular muscle or optic
nerve infiltration and intraocular (uveal tract, retina) or ocular adnexal
involvement. Paranasal sinuses and nasopharynx may be involved
[2] and show the same signal
patterns as seen with intracranial granulocytic sarcoma
[3].
Bone and Soft-Tissue Masses
Granulocytic sarcomas of the bone commonly involve vertebral bodies, the
sternum, orbits, cranium, sacrum, and ribs
[4]
(Fig. 5). Granulocytic sarcoma
arises in bone marrow and traverses the haversian canals to reach the
periosteum, resulting in bone lysis and sometimes adjacent soft-tissue masses
and periostitis. The radiographic differential diagnoses are metastatic
neuroblastoma, Ewing's sarcoma, eosinophilic granuloma, and primitive
neuroectodermal tumor in children, and metastasis, plasmocytoma, malignant
fibrous histiocytoma, lymphoma, and osteomyelitis in adults
[1]. Soft-tissue masses may
involve muscles [4], but a
parameningeal location appears to be a preferred site for these masses
[2]. Lesions are slightly
hypodense to muscle at CT and isointense to bone marrow on both T1- and T2-
weighted MR images; they enhance homogeneously after injection of contrast
medium. These imaging patterns are very helpful in differentiating
granulocytic sarcoma from synovitis, arthritis, tumor, hematoma, or abscess
[4].
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Fig. 5. —40-year-old woman with relapse of acute myeloblastic leukemia
who presented with left thoracic pain. Contrast-enhanced CT scan of chest in
axial plane shows soft-tissue mass of chest wall with rib lysis
(arrowheads), which corresponded to granulocytic sarcoma at biopsy.
Complete remission was obtained after chemotherapy and radiation therapy.
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Chest
Intrathoracic granulocytic sarcomas are rare. The mediastinum is the most
common site of involvement. Less commonly affected are the lungs, pleura,
pericardium, and hila. Radiologically, mediastinal granulocytic sarcomas are
often misdiagnosed, especially in patients without leukemia, because thymus or
mediastinal lymph nodes are more suggestive of malignant lymphoma. Lung
manifestations of granulocytic sarcoma consist of alveolar opacities (Fig.
6A,6B),
nodules, or interstitial septal lines (Fig.
7A,7B).
Pleural effusions can be associated with homogeneous and well-circumscribed
pleural masses or nodules. Enlargement due to cardiac tumor or pericardial
effusion has also been described
[5].
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Fig. 6A. —24-year-old man with acute myeloblastic leukemia who
presented with thoracic pain and hemoptysis. Posteroanterior radiography of
chest shows left hilar lymph node enlargement (arrowheads) associated
with left upper air-space consolidation.
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Fig. 6B. —24-year-old man with acute myeloblastic leukemia who
presented with thoracic pain and hemoptysis. Unenhanced CT scan of chest
reveals large irregular nodular opacities. Subsequent biopsy showed
granulocytic sarcoma infiltrating hilar lymph nodes and involving lung
parenchyma. Complete resolution was obtained after chemotherapy and radiation
therapy.
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Fig. 7A. —36-year-old woman with acute myeloblastic leukemia associated
with myelofibrosis who presented with dyspnea. Unenhanced CT of chest shows
large right hilar mass associated with small pleural effusion
(arrowheads).
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Fig. 7B. —36-year-old woman with acute myeloblastic leukemia associated
with myelofibrosis who presented with dyspnea. CT slice 20-mm caudate to
A shows right nodular peribronchial consolidations and some
interstitial septal lines. Biopsy subsequently showed granulocytic sarcoma
involving peribronchial spaces. Patient died 8 days later.
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Abdomen
Hepatic granulocytic sarcomas appear as multiple well-defined solid masses
and are indistinguishable from multiple hepatic metastases or abscesses. One
patient with peribiliary chloroma showed marked intrahepatic biliary
dilatation associated with a heterogeneous hypodense mass anterior to the
bifurcation of the portal vein
[6]. The few digestive
granulocytic sarcomas described in the literature involved the stomach,
jejunum, and colon. Barium examinations and CT show plaquelike wall thickening
and nodular, polypoid, and ulcerated lesions (Fig.
8A,8B,8C).
Centered bowel stricture may also be visible. Granulocytic sarcomas also may
present as an ascitic fluid and may involve the head of pancreas
(Fig. 9) without obstruction
of the main pancreatic duct
[7].
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Fig. 8C. —40-year-old man with unremarkable medical history, admitted
for small-bowel obstruction. Enhanced CT scan of abdomen shows intestinal
involvement with stenosis and parietal thickening associated with ascites and
peritoneal carcinosis. Diagnosis at biopsy was granulocytic sarcoma of small
intestine without evidence of blood or bone marrow involvement. Twenty-one
months later, patient was diagnosed with acute myeloblastic leukemia with
central nervous system and bone marrow involvement.
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Fig. 9. —53-year-old man with acute myeloblastic leukemia who
presented with acute abdominal pain. Enhanced CT scan of abdomen obtained
concurrently with diagnosis shows hypodense mass of head of pancreas
(arrowheads). Biopsy subsequently confirmed diagnosis of pancreatic
granulocytic sarcoma. Six weeks later, after chemotherapy and radiation
therapy, repeated CT showed resolution of pancreatic mass.
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Genitourinary System
Each organ of the genitourinary tract or the retroperitoneum may be
involved: kidneys, ureters, lymph nodes
(Fig. 10), bladder, testicles
(Fig.
11A,11B),
prostate, ovaries, and uterus. In such cases, no one feature is specific for
granulocytic sarcoma, and lesions are frequently misdiagnosed initially as
primary malignancies or lymphomas
[7]. Granulocytic sarcoma of
the ovary usually presents as asymptomatic unilateral or bilateral solid
masses with possible cystic degeneration, hemorrhage, and necrosis.
Granulocytic sarcoma of the uterus more frequently involves the cervix than
the corpus. Either primary or secondary involvement of the vagina or vulva is
rare [8]. Breast granulocytic
sarcoma is uncommon and may be misdiagnosed, mainly as a carcinoma or
lymphoma. It usually affects adults, but one case was reported in an
adolescent patient [9].
Mammography shows a unique or multiple irregular, noncalcified mass with
poorly defined margins. Sonography shows nonhomogeneous masses with
characteristic malignant features, including spiculation, angular margin, and
some acoustic shadowing. At MR imaging, a granulocytic sarcoma is
inhomogeneous on all sequences, hyperintense on T2-weighted images,
hypointense on T1-weighted images; it enhances strongly after administration
of contrast medium [10] (Fig.
12A,12B,12C,12D,12E,12F,12G).
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Fig. 10. —16-year-old boy with relapse of acute myeloblastic leukemia
admitted for intermittent left flank pain. Enhanced CT scan of abdomen shows
left retroperitoneal mass invading psoas and kidney hilum associated with
pyelocaliectasis. Subsequent biopsy confirmed retroperitoneal granulocytic
sarcoma. Remission was obtained after chemotherapy.
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Fig. 11A. —58-year-old man with unremarkable medical history who
presented with swelling of left testicle. Sonogram shows heterogeneous mass of
testis and epididymis. Orchiectomy specimens revealed granulocytic sarcoma,
without blood or bone marrow involvement.
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Fig. 11B. —58-year-old man with unremarkable medical history who
presented with swelling of left testicle. At 3 months, CT scan revealed
abdominal relapse with large partially necrotic lateroaortic mass. At same
time, acute myeloblastic leukemia was diagnosed. CT-guided biopsy (not shown)
revealed retroperitoneal granulocytic sarcoma. Patient died 1 month later of
liver failure resulting from chemotherapy.
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Fig. 12A. —41-year-old woman with history of acute myeloblastic leukemia
associated with abnormal eosinophils who presented with palpable mass in left
breast. (Reprinted with permission from
[10]) Left lateral mammogram
discloses dense, rounded, and spiculated mass of 3-cm diameter with irregular
margins and skin retraction.
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Fig. 12B. —41-year-old woman with history of acute myeloblastic leukemia
associated with abnormal eosinophils who presented with palpable mass in left
breast. (Reprinted with permission from
[10]) Sonogram shows
irregularly shaped nonhomogeneous hypoechoic mass with ill-defined margins and
posterior acoustic shadow.
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Fig. 12C. —41-year-old woman with history of acute myeloblastic leukemia
associated with abnormal eosinophils who presented with palpable mass in left
breast. (Reprinted with permission from
[10]) CT scan of thorax
obtained 3 days after B shows spiculated mass that contains small foci
of necrosis. Skin wall is thickened (arrowhead).
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Fig. 12D. —41-year-old woman with history of acute myeloblastic leukemia
associated with abnormal eosinophils who presented with palpable mass in left
breast. (Reprinted with permission from
[10]) On sagittal MR imaging,
mass is inhomogeneous and hyperintense on STIR image (D), hypointense
on T1-weighted image (E). Mass enhances markedly but inhomogeneously
after gadolinium administration and fat saturation (F). Mass
spiculations and skin thickening also can be seen. Fine-needle breast biopsy
revealed granulocytic sarcoma. Patient received two courses of chemotherapy.
Five weeks later, mass was no longer palpable.
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Fig. 12E. —41-year-old woman with history of acute myeloblastic leukemia
associated with abnormal eosinophils who presented with palpable mass in left
breast. (Reprinted with permission from
[10]) On sagittal MR imaging,
mass is inhomogeneous and hyperintense on STIR image (D), hypointense
on T1-weighted image (E). Mass enhances markedly but inhomogeneously
after gadolinium administration and fat saturation (F). Mass
spiculations and skin thickening also can be seen. Fine-needle breast biopsy
revealed granulocytic sarcoma. Patient received two courses of chemotherapy.
Five weeks later, mass was no longer palpable.
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Fig. 12F. —41-year-old woman with history of acute myeloblastic leukemia
associated with abnormal eosinophils who presented with palpable mass in left
breast. (Reprinted with permission from
[10]) On sagittal MR imaging,
mass is inhomogeneous and hyperintense on STIR image (D), hypointense
on T1-weighted image (E). Mass enhances markedly but inhomogeneously
after gadolinium administration and fat saturation (F). Mass
spiculations and skin thickening also can be seen. Fine-needle breast biopsy
revealed granulocytic sarcoma. Patient received two courses of chemotherapy.
Five weeks later, mass was no longer palpable.
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Fig. 12G. —41-year-old woman with history of acute myeloblastic leukemia
associated with abnormal eosinophils who presented with palpable mass in left
breast. (Reprinted with permission from
[10]) Unenhanced T1-weighted
MR image in sagittal plane shows marked reduction of tumor size.
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Conclusion
Soft-tissue masses arising in patients with myelogenous leukemia may have
several possible causes, including abscess or hematoma. Granulocytic sarcomas
are not common, but they are important to recognize, because they respond more
favorably to focal irradiation than to systemic chemotherapy. CT and MR
imaging are useful in revealing granulocytic sarcomas, delineating their
extent for radiation therapy, planning needle biopsy, and evaluating
therapeutic response. Although their imaging appearance is not specific,
granulocytic sarcomas should be strongly considered whenever a mass is
discovered in a patient with myelogenous leukemia. As a presenting sign of
leukemia, the granulocytic sarcoma may be misdiagnosed as numerous malignant
processes.
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