AJR 2003; 180:109-113
© American Roentgen Ray Society
Mineralization in Musculoskeletal Leiomyosarcoma: Radiologic—Pathologic Correlation
Charles H. Bush1,
John D. Reith2 and
Suzanne S. Spanier2
1 Department of Radiology, University of Florida College of Medicine, P. O. Box
100374, Gainesville, FL 32610-0374.
2 Department of Pathology, University of Florida College of Medicine, P. O. Box
100275, Gainesville, FL 32610-0275.
Received June 15, 2001;
accepted after revision July 2, 2002.
Address correspondence to C. H. Bush.
Abstract
OBJECTIVE. Mineralization in leiomyosarcoma, a malignant tumor of
smooth muscle, has not been widely recognized. In this article, we report our
experience with four cases of primary leiomyosarcoma of soft tissue or bone in
which mineralization was visible on either radiography or CT. In none of the
cases was the diagnosis of leiomyosarcoma considered before biopsy. In one
case of a soft-tissue leiomyosarcoma, the presence of mineralization was a
factor that led to the misinterpretation of the needle biopsy specimen as
soft-tissue osteosarcoma.
CONCLUSION. Histologically, mineralization in leiomyosarcoma appears
to be caused by either nonneoplastic ossification or dystrophic mineralization
in the tumor. This feature can cause leiomyosarcomas to be confused with other
neoplasms.
Introduction
Leiomyosarcoma is a malignant mesodermal neoplasm associated with smooth
muscle differentiation, accounting for 5-10% of soft-tissue sarcomas. Although
leiomyosarcoma most commonly arises in the abdominal cavity, retroperitoneum,
skin, and subcutaneous tissues
[1,
2], this tumor can also occur
in the deep soft tissues of the musculoskeletal system, often from a large- or
medium-sized vein. Vascular smooth muscle cells may also be the source of the
occasional primary leiomyosarcoma arising in bone, which since the advent of
immunoperoxidase techniques has been the subject of multiple reports
[3,4,5,6,7,8].
Reports about the imaging features of primary leiomyosarcoma of bone
describe a typical lesion as having an aggressive osteolytic appearance on
radiography accompanied by permeation, endosteal erosion, fine periosteal
reaction; and an occasional pathologic fracture
[5]. Primary leiomyosarcoma of
bone most commonly occurs in the long bones of the lower extremities,
particularly the distal femur
[4,
7]. Only a few studies about
the radiologic features of soft-tissue leiomyosarcoma have been reported. A
large series describing the CT appearance of 118 cases of soft-tissue
leiomyosarcomas located mainly in the abdomen and pelvis described the lesions
as frequently large; often containing areas of low attenuation; and frequently
accompanied by hepatic, pulmonary, mesenteric, and osseous metastases
[9]. This series included 37
extravisceral leiomyosarcomas and mentioned no tumors with mineralization.
Another series of 13 cases of soft-tissue leiomyosarcomas of the extremities
found radiographic evidence of calcifications in only two tumors
[10].
Mineralization in primary leiomyosarcoma of bone has not been reported to
the best of our knowledge. In fact, the total absence of sequestered bone
fragments and intralesional calcification in the tumor was specifically noted
in a recent series of 33 patients with leiomyosarcoma
[4]. It is reasonable to
conclude from all these studies that mineralization in leiomyosarcoma is rare.
The purpose of this report is to identify cases in our files of primary
musculoskeletal leiomyosarcoma having mineralization visible on either
radiography or CT and to correlate the imaging with the pathologic
findings.
Materials and Methods
The database at our institution, a major tertiary referral center for
orthopedic oncology, was searched for all records since 1988 to find cases
with the diagnosis of leiomyosarcoma. All diagnoses were made by light
microscopy with sections stained by H and E, and the diagnoses were confirmed
with immunohistochemical stains for smooth muscle actin and muscle-specific
actin (HHF-35). The patients without preoperative radiography or CT, those who
had a prior primary leiomyosarcoma in other organ systems, those referred for
reexcision of the tumor bed, and those with a final diagnosis that was in
doubt were excluded.
For all the patients, radiographs of the tumors had been obtained at our
institution; however, because this study is retrospective, many of the
patients had only cross-sectional images obtained at outside institutions, and
many of the imaging studies differed in terms of the type of scanner, the
technique used, and the quality of the images. All CT examinations at our
institution were performed on a helical scanner (CT 9800 Quick or HiSpeed
Advantage; General Electric Medical Systems, Milwaukee, WI) at 140 kVp with a
3- to 5-mm section thickness. All MR imaging at our institution was performed
using either a 1.5-T system (Signa; General Electric Medical Systems) or a
1.0-T system (Magnetom; Siemens Medical Systems, Iselin, NJ); the MR imaging
studies always included T1- and T2-weighted sequences.
A total of 24 patients with primary leiomyosarcoma were identified, and
their imaging studies were reviewed by a board-certified fellowship-trained
musculoskeletal radiologist with extensive clinical experience. Eight patients
with primary leiomyosarcoma of bone and 16 patients with leiomyosarcoma of
soft tissue were identified. Five of the patients with bone lesions were women
and three were men; the subjects ranged in age from 29 to 61 years. Of the
patients with soft-tissue tumors, 11 were women, five were men, and they
ranged in age from 23 to 71 years.
Four patients (17%) with radiologic evidence of mineralization in their
tumors were identified. Because the pattern of mineralization in tumors can
give important clues to the diagnosis, mineralization in the leiomyosarcomas
in this series was further described as ossification (by the presence of
clear-cut outer cortex formation, trabeculation, or lamellated bone on
radiography or CT) or amorphous. These four patients, two of whom had a tumor
that arose in soft tissue and two of whom had a tumor that arose in bone, form
the basis for this report. Other imaging features of the tumors, such as tumor
dimensions, contrast enhancement, and location of mineralization were also
noted. All diagnoses were reviewed and confirmed by one of two experienced
musculoskeletal pathologists using both conventional histologic sections and
immunohistochemical stains. Mineralization in the tumors was characterized as
ossification only when foci of woven bone containing osteocytes and rimmed by
cells that were unquestionably osteoblasts were identified in the tumors.
Dystrophic calcification was characterized by amorphous, acellular basophilic
material deposited in the tumor.
Results
The clinical data are summarized in
Table 1. Radiographs from
initial presentation were available for all patients. Three of the four
lesions contained mineralization that was easily seen on radiography. The
mineralization in the right tibial lesion had a dense amorphous appearance
(Fig. 1A). In the patient with
the right third rib lesion, the mineralization in the tumor was visualized
only on CT (Fig. 2A), and the
density of the mineralization was seen to increase between serial CT
examinations after the tumor was irradiated. In the left triceps lesion, the
tumor contained a small region of amorphous dense mineralization
(Fig. 3A) that was seen on CT
to be confined to the center of the tumor
(Fig. 3D). Comparison of
unenhanced and contrast-enhanced axial sections through this tumor showed its
soft-tissue-attenuation periphery prominently enhanced after the IV
administration of iodinated contrast material. The right elbow lesion
contained a curvilinear region of ossification
(Fig. 4A).
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Fig. 1A. —52-year-old woman with primary leiomyosarcoma of right
proximal tibia. Anteroposterior radiograph shows mildly expansile, reasonably
well-defined lesion that contains sizable component of dense mineralization
(arrows).
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Fig. 2A. —28-year-old man with primary leiomyosarcoma of right third
rib. Posteroanterior radiograph obtained at presentation (not shown) showed
subtle lytic lesion of right third rib. Axial unenhanced CT scan reveals faint
mineralization (arrowheads) within tumor.
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Fig. 3D. —42-year-old man presented with left elbow leiomyosarcoma.
Axial CT scan obtained 9 months after B and C with IV contrast
material shows enhancing soft-tissue mass (arrow) with peripheral
enhancement and central mineralization (arrowhead).
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In the three lesions that underwent MR imaging, the actual regions of
mineralization were of low signal intensity on both T1- and T2-weighted images
(Figs. 3B,
3C, and
4B). The nonmineralized
regions of the tumors were isointense relative to muscle on T1-weighted images
and variably hyperintense relative to muscle on T2-weighted images. Comparison
of signal intensities between unenhanced and contrast-enhanced T1-weighted
sequences showed all three of these tumors prominently enhanced after the IV
administration of gadolinium-based paramagnetic contrast material. In the
right elbow lesion, MR imaging showed that its curvilinear region of
ossification contained tissue in its center that was isointense relative to
fat on all sequences (Fig.
4B), unlike the signal intensity exhibited by the rest of the
tumor.
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Fig. 3B. —42-year-old man presented with left elbow leiomyosarcoma.
Axial T1-weighted (B) and T2-weighted (C) MR images obtained 6
weeks after A show mass to be of mostly low signal intensity
(arrow). Patient was lost to follow-up for 9 months, when CT and MR
imaging were performed again.
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Fig. 3C. —42-year-old man presented with left elbow leiomyosarcoma.
Axial T1-weighted (B) and T2-weighted (C) MR images obtained 6
weeks after A show mass to be of mostly low signal intensity
(arrow). Patient was lost to follow-up for 9 months, when CT and MR
imaging were performed again.
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Fig. 4B. —54-year-old woman who presented with soft-tissue
leiomyosarcoma of right elbow. T2-weighted MR image shows low-signal-intensity
region of ossification inside larger soft-tissue mass (arrowheads).
Center of this ossific region contained tissue (arrow) that was
isointense to fat on all sequences. Tumor was irradiated before resection.
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The leiomyosarcomas arising in soft tissue had similar gross pathologic
findings. Each tumor was well demarcated from the adjacent tissues and had a
firm, tan—white cut surface. When we cut each tumor, we felt a gristly
sensation, which was caused by the mineralization. The two tumors originating
in bone were similar to those arising in soft tissue. Each tumor had a
somewhat nodular, firm, tan—white appearance. Areas of mineralization
were evident on the cut surface as yellowish gritty areas.
The histopathologic findings of all cases were similar. Each tumor was
composed of brightly eosinophilic spindle cells with moderate cytologic
atypia. Mitoses ranged from one of 10 to 10 of 10 high-power fields. The left
tibial tumor had a small component of focal coagulative necrosis, with the
mineralization in this lesion consisting of a combination of dystrophic
calcification and reactive bone formation (Figs.
1B and
1C). The area of necrosis in
this tumor did not contain any mineralization. Reactive bone formation was
seen scattered throughout the right rib tumor
(Fig. 2B). In the left triceps
tumor, the mineralization primarily resulted from dystrophic calcification
between tumor cells occurring at the center of the lesion, with that tumor
having an extensive component of necrosis that was not mineralized. Bone
formation in the right elbow tumor was sufficiently mature to contain central
adipose tissue and scattered marrow elements
(Fig. 4C).
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Fig. 1B. —52-year-old woman with primary leiomyosarcoma of right
proximal tibia. Photomicrograph of histologic section from leiomyosarcoma
shows that dense, cortical-type bone (arrows) is centrally located in
tumor. (H and E, x200)
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Fig. 1C. —52-year-old woman with primary leiomyosarcoma of right
proximal tibia. Photomicrograph of histologic section from tumor shows dense,
dystrophic mineralization (arrows) in different part of tumor. (H and
E, x400)
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Fig. 2B. —28-year-old man with primary leiomyosarcoma of right third
rib. Posteroanterior radiograph obtained at presentation (not shown) showed
subtle lytic lesion of right third lib. Photomicrograph of histologic section
from tumor shows reactive bone (arrows) throughout tumor. (H and E,
x200)
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Fig. 4C. —54-year-old woman who presented with soft-tissue
leiomyosarcoma of right elbow. Photomicrograph of histologic section from
excised tumor shows leiomyosarcoma of soft tissue with area of ossification
(arrows) seen on radiograph (A) and MR image (B)
containing fatty marrow (F). T = tumor. (H and E, x100)
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Discussion
Mineralization in tumors may be caused by ossification, calcification, or a
combination of both. Ossification may be produced by the neoplasm, as is seen
in osteosarcoma, or may arise from peripheral or trapped nonneoplastic
fibroblastic mesenchyme stimulated to produce reactive or metaplastic bone
[11], as is occasionally seen
in synovial sarcoma [12].
Calcification is usually associated with the deposition of insoluble calcium
salts, often in necrotic tissues, of variable chemical composition. Sometimes
the pattern and density of the mineralization are radiographically distinctive
enough to suggest the diagnosis. The peripheral ossification of myositis
ossificans, the "rings and arcs" of chondrosarcoma and
enchondroma, and the phleboliths of a hemangioma are all examples. However,
mineralization can also appear nonspecific on radiography.
In this small series, the mineralization shown on imaging was caused by
both reactive bone formation in the tumors and dystrophic calcification with
deposition of insoluble calcium phosphate salts. The presence of
mineralization in the tumors caused some diagnostic difficulty with two of the
four patients in our series. In the left triceps leiomyosarcoma, the
mineralization in the tumor was at the center of the lesion. This feature,
combined with central low signal intensity in the lesion on both T1- and
T2-weighted MR images suggested the diagnosis of a soft-tissue osteosarcoma,
with reversal of the zonation phenomenon seen in myositis ossificans
[11]. Furthermore, the
strongly positive alkaline phosphatase reactivity of the biopsy sample of the
tumor also at first supported a diagnosis of soft-tissue osteosarcoma.
Milchgrub et al. [12]
reported that a similar initial conclusion from an incisional biopsy occurred
in their series. In one of four patients with a calcifying synovial sarcoma,
the tumor was thought to be a parosteal osteosarcoma. In our study group, the
tibial lesion was also thought to be an intramedullary osteosarcoma on the
basis of preoperative imaging, and the diagnosis of leiomyosarcoma was never
considered until the tumor was biopsied.
The fact that four cases of mineralization in primary leiomyosarcomas of
bone and soft tissue in this report were identified on radiography or CT in a
small series of 24 patients suggests than mineralization in this tumor may not
be as infrequent as previously thought. Possibly, the dystrophic nature of the
mineralization observed in two of our four cases of leiomyosarcoma is akin to
the previously reported dystrophic mineralization seen in some soft-tissue
leiomyomas [13]. We speculate
that the paucity of prior reports of mineralization in leiomyosarcoma in the
literature reflects the increased sophistication in the tools of both
pathologists and radiologists in diagnosing and staging this tumor. The recent
widespread availability of immunohistochemical reagents, such as those for
smooth muscle actin, desmin, and muscle-specific actin, has caused many tumors
that would have formerly been called high-grade spindle-cell sarcoma to be
classified as leiomyosarcoma. Furthermore, the increased use of CT in the
evaluation of bone and soft-tissue masses, particularly in the chest wall,
retroperitoneum, and gluteal regions, may allow increased detection of
radiographically occult mineralization in tumors. Mineralization in one of our
four cases, the right third rib lesion, was not visible on chest radiography;
this lesion was shown only on CT.
The major drawbacks of our retrospective study are the skewed nature of our
database and the variable use and quality of the available cross-sectional
imaging of the subjects. Our center is a tertiary referral center for
orthopedic oncology; thus, our patient population differs from the patient
population examined on CT by McLeod et al.
[9]. Many of our patients
presented to our institution with CT scans that had been obtained at an
outside institution; despite the often poor quality of these examinations, CT
was often not repeated.
In summary, mineralization in leiomyosarcoma may be more common than has
been previously recognized and may occur as either reactive nonneoplastic
ossification or as dystrophic calcification. Recognition that occasional
mineralization occurs in leiomyosarcomas is important because this feature may
lead to both radiologic and pathologic confusion with other sarcomas.
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Abstract
Introduction
