DOI:10.2214/AJR.05.2141
AJR 2007; 188:S18-S20
© American Roentgen Ray Society
AJR Teaching File: Diffuse Osteosclerosis with Hepatosplenomegaly
Francis Cloran1 and
Kevin P. Banks2
1 Department of Radiology, Wilford Hall Medical Center, Lackland Air Force Base,
Lackland, TX.
2 Department of Radiology, Brooke Army Medical Center, MCHE-DR, 3851 Roger
Brooke Dr., Fort Sam Houston, TX 78234.
Received December 21, 2005;
accepted after revision May 8, 2006.
The opinions and assertions contained herein are the private views of the
authors and are not to be construed as official or as reflecting the views of
the Department of the Army, the Department of the Air Force, or the Department
of Defense.
Address correspondence to K. P. Banks
(kevin.banks{at}amedd.army.mil).
Keywords: bone • diffuse sclerosis • musculoskeletal system • myelofibrosis
Case History
A 59-year-old man presents with left flank pain.
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Fig. 1B —59-year-old man with left flank pain. Subsequent contrast-enhanced
CT scan of abdomen verifies presence of increased bone density secondary to
organized trabecular thickening and deposition along endosteal cortex.
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Radiologic Description
Frontal radiography of the abdomen (Fig.
1A) shows diffuse osteosclerosis and concurrent severe
splenomegaly and hepatomegaly. Subsequent contrast-enhanced CT of the abdomen
(Fig. 1B) verifies the presence
of increased bone density secondary to organized trabecular thickening and
deposition along the endosteal cortex. The patient went on to MRI, and an
axial T1-weighted MR image (Fig.
1C) through the abdomen shows decreased signal intensity of the
normally bright fatty bone marrow. A coronal T2-weighted MR image
(Fig. 1D) through the spine
reveals homogeneously decreased signal intensity of the marrow.
Differential Diagnosis
The differential diagnosis for increased bone density is metabolic
disorders (such as hyperthyroidism, hypoparathyroidism, renal osteodystrophy),
fluorosis, myelofibrosis, mastocytosis, lymphoma, osteopetrosis, osteoblastic
metastases, Paget's disease, and sickle cell anemia.
The differential diagnosis for low marrow signal intensity on MRI is
fluorosis, myelofibrosis, mastocytosis, lymphoma, osteopetrosis, osteoblastic
metastasis, and Paget's disease.
Diagnosis
The diagnosis is myelofibrosis.
Commentary
Myelofibrosis is considered one of the chronic myeloproliferative disorders
(CMPDs), which is a group of diseases in which too many of certain types of
cells are made in the bone marrow. Other entities in this class of diseases
include essential thrombocytopenia and polycythemia vera; and chronic
neutrophilic, eosinophilic, and myeloid leukemia. These entities are similar
in that all CMPDs display a hyperplastic bone marrow, hematopoiesis
independent of physiologic stimuli, a phase of increased circulating blood
cell concentrations, a tendency to develop marrow fibrosis, and a tendency to
terminate in acute leukemia
[1]. Whereas polycythemia vera
is due to an idiopathic excess of RBCs and essential thrombocytopenia is due
to overproduction of platelets by an unknown cause, myelofibrosis is
characterized by the abnormal maturation of RBCs and granulocytes (a type of
WBC).
Myelofibrosis affects approximately one in 100,000 people; the median age
at diagnosis is 60 years [2].
The biology of myelofibrosis is incompletely understood, and the transforming
event is yet to be identified. The granulocytes, platelets, and RBCs are
monoclonally derived, whereas the fibroblasts are polyclonally derived. There
are no strong candidates for tumor suppressor genes or protooncogenes
responsible for the development of this hemopathy
[3]. Clinical presentations are
heterogeneous; the disease may be asymptomatic in 25% of patients on
presentation. Common initial signs and symptoms include fatigue, weight loss,
easy bruising and bleeding, fever, night sweats, and splenomegaly. Gout and
renal colic due to hyperuricemia from high cell turnover may also be
observed.
Laboratory findings in myelofibrosis include anemia and variable changes in
the neutrophil and platelet counts. The peripheral blood smear classically
reveals nucleated blood cells, reticulocytes, and teardrop-shaped RBCs.
Abnormally large platelets may also be observed. Bone marrow biopsy frequently
reveals fibrosis with variable degrees of marrow hyperplasia
[4].
The radiographic hallmark of myelofibrosis is osteosclerosis (increased
bone density), most commonly found in the axial skeleton and the proximal
aspects of the long bones (humerus and femur)
[4]. Osteosclerosis involves
the replacement of the normal marrow cavity with fibrous tissue with no
trabecular or cortical disorganization. This process is in contrast to
myelosclerosis, in which small spicules of bone obliterate the marrow space.
The differential diagnosis of osteosclerosis is diverse and includes
hematologic disorders (i.e., myelofibrosis, sickle cell anemia, polycythemia,
multiple myeloma, leukemia, mastocytosis), osteoblastic metastases (prostate
carcinoma, breast carcinoma, gastrointestinal adenocarcinoma, carcinoid
tumors, transitional cell carcinoma of the bladder), and metabolic disorders
(renal osteodystrophy, primary hyperparathyroidism, familial hypophosphatemic
osteomalacia, hypervitaminosis D, fluorosis, hypoparathyroidism,
pseudohypoparathyroidism).
The lack of architectural distortion seen with the osteosclerosis of
myelofibrosis—particularly the osteoblastic metastatic processes and
multiple myeloma that predominantly present with irregular foci of abnormal
bone density in the axial skeleton and proximal long bones—is one of the
essential imaging features aiding in the differentiation of this disease from
many of the other disorders in the differential diagnosis. Similarly, the
increased bone density seen in sickle cell disease is due to bone infarcts,
which have an irregular appearance, as do the bone changes of osteopetrosis
and Paget's disease, which are in contrast to the changes characterizing
myelofibrosis.
Although the metabolic disorders can show diffuse osteosclerosis on
radiographic examination as well, they do not result in decreased marrow
signal intensity on MRI. This is because of the marrow or cancellous bone
compartment alterations found in hemopathies such as myelofibrosis, in which
loss of high T1 fatty marrow signal and decreased T2 signal are associated
with the marrow's abnormal hypercellularity. In contrast, metabolic bone
disorders affect only the cortical and trabecular bone, leaving marrow
elements unchanged and therefore having a normal MR appearance. Laboratory
findings (abnormalities in serum parathyroid hormone and calcium and phosphate
levels) will also aid in the diagnosis of this disorder more than
roentgenographic findings will
[5].
The consequences of extramedullary hematopoiesis commonly include
splenomegaly and hepatomegaly and, less commonly, lymphadenopathy. The
severity of these findings can be readily assessed on CT, which can also
provide an assessment of osteosclerosis. The presence of splenomegaly or
hepatomegaly greatly reduces the differential diagnosis because it argues
against metabolic disorders with calcium disturbances and sickle cell anemia
(autoinfarction of spleen), and such a finding is generally not seen in the
neoplastic disorders that can lead to osteosclerosis. Mastocytosis may mimic
myelofibrosis radiographically, but typically skeletal surveys will reveal
osteopenia, and the peripheral blood smear will show eosinophilia
[6].
Treatment options are limited in myelofibrosis. It may be cured by
allogenic bone marrow transplantation
[7]. Other forms of therapy are
palliative and are used primarily to improve anemia (androgens with or without
steroids, thalidomide, splenectomy, splenic radiation), to reduce symptoms
related to organomegaly and hypermetabolism (chemotherapy), or to treat
complications (allopurinol for treatment of hyperuricemia).
Causes of death are variable in myelofibrosis and include leukemic
conversion in 5-20% and overwhelming infection, hemorrhage, cardiovascular
events, thrombosis, renal failure, and hepatic failure.
Objective
The educational objective of this teaching article is to review the
analytic approach to individuals presenting with diffusely increased bones on
radiography or low T1 signal intensity of bone marrow on MRI.
Conclusion
Through careful examination for concurrent imaging findings and the use of
the clinical history, a tailored differential diagnosis can be provided to
maximize the diagnostic yield.
References
- Dameshak W. Some speculations on the myeloproliferative syndromes.
(editorial) Blood 1951;6
: 372-375[Medline]
- Dupriez B, Morel P, Demory JL, et al. Prognostic factors in
agnogenic myeloid metaplasia: a report on 195 cases with a new scoring system.
Blood 1996; 88:1013
-1018[Abstract/Free Full Text]
- Clark DA, Williams WL. Myelofibrosis. In: Lee GR, Foerster J,
Lukens J, et al., eds. Wintrobe's clinical hematology,
10th ed. Philadelphia, PA: Williams & Wilkins, 1999:2390
-2399
- Campbell SE, Bui-Mansfield LT, Fillman ER. Myelofibrosis.
Mil Med 2005; 170:xv
-xix[Medline]
- Vogler JB, Kim JH. Metabolic and endocrine diseases of the
skeleton. In: Grainger RG, Allison D, Adam A, Dixon AK, eds.
Diagnostic radiology: a textbook of medical imaging,
4th ed. London, England: Churchill Livingstone, 2001:1960
-1961
- Parker RI, Metcalf DD. Basophils, mast cells and systemic
mastocytosis. In: Hoffman R, Benz EJ, Shattil SJ, et al., eds.
Hematology: basic principles and practice, 4th ed. New
York, NY: Elsevier, 2005:913
-923
- Smith BD, Moliterno AR. Biology and management of idiopathic
myelofibrosis. Curr Opin Oncol 2001;13
: 91-94[CrossRef][Medline]
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Case History
Radiologic Description
