Introduction
 Part 1 - Powerpoint Presentation
Part 2 - Powerpoint Presentation
At some point in their training, pathologists learn that the diagnosis of bone lesions should not be
undertaken without first reviewing their corresponding clinical radiographs. If a pathologist strictly
adheres to this philosophy, the orthopedic surgeon will eventually provide the patient's X-rays (better
to share x-rays than get no diagnosis). When this happens, a pathologist who knows little about x-ray
interpretation may begin to feel like a dog running and barking at passing cars (if the car ever stopped
and the dog jumped inside, what would the dog do with it?). This is because pathologists are seldom
taught in their residencies how radiographic data are actually incorporated into the formulation of
histologic diagnosis.
The purpose of this workshop is to emphasize the reasons why characteristic biological alterations of
bone give rise to reproducible radiographic findings. While a single workshop cannot teach one to be a
radiologist or an orthopedic pathologist, its intent is to make you appreciate some of the logic in
pathoradiologic correlation. More importantly, you will understand the limitations and potential danger
of histodiagnosis of bone lesions without radiographic information.
X-rays are electromagnetic waves of about one Angstrom in length. The degree of their ability to
penetrate matter is related to their energy level and the electron density of the matter being x-rayed;
the energy is absorbed or scattered by electron clouds. Substances of lower electron densities are thus
more easily penetrated. Nuclei can also absorb x-rays, however, the nucleus occupies so little space in
the atom (1/100,000th) that even in atoms with many nuclear particles (lead, osmium etc.) the
nuclei play practically no role in x-ray absorption. The state of matter of the substance also plays a
role in radiodensity. For example, while the atoms of the heavier noble gases (eg. Krypton, Radon) are
capable of electron absorption, their wide spacing in a gas renders them completely radiolucent. X-rays
also have the ability to sensitize a photographic emulsion, but they do so much more slowly than visible
light because the reaction is photochemical and x-rays are in the wrong part of the electromagnetic
spectrum to produce photochemical reactions. In order to accelerate this process, photographic film used
in x-rays is placed in a cassette, which has a fluorescent coating inside. When X-rays strike this
coating, there is secondary emission of light, which strikes the film, making a contact print inside the
light tight cassette. Precipitation of silver in the emulsion takes place as a result of this secondary
photochemical reaction, which results in exposure of the film [14].
A radiographic image results from the absorption, scatter, and transmission of the primary X-ray beam
emitted from the tube as it passes through tissues to strike the fluorescent screen of the cassette and
the secondary exposure of the photographic emulsion. The image generated is essentially a large
photographic negative that results from different degrees of exposure of the photographic emulsion by
X-ray and light photons. Since bone, calcium salts, and heavy metals (being of higher electron
density/atomic number) permit fewer photons to pass through to the film, the areas of the processed film
in the paths of these objects remain clear (or white). Since soft tissues are lower in electron density,
fewer X-ray photons are absorbed. Because of this, the corresponding areas of the radiographs are
proportionately darkened. Soft tissues can further be divided into those of water density (including
cartilage, tendon and ligament, blood, and muscle) and fat. The tissues with water density absorb more
x-ray energy than fat, and this can often be seen when the two are contrasted with one another in soft
tissue x-rays (fat planes are more radiolucent than muscles). Gases absorb even less X-radiation, and
film exposure is even darker under areas with gas or air in the x-ray path. Radiographic examination of
a joint, for example, shows bones as white structures separated by a thin dark space and surrounded by
indistinct zones of grey. While the soft tissues of the joint cannot be distinguished from each other,
changes in the adjacent ossified tissues may be observed and those alterations in the interposed tissues
can be evaluated indirectly. For example, if articular cartilage in a joint is destroyed, there is
usually closer approximation of adjacent bony structures and secondary changes in the articular surfaces
or their margins.
When observing a radiograph, one must remember to think in three dimensions. While a radiographic
image is a two-dimensional representation of anatomy and pathophysiology taking place in three
dimensions, this fact is easily forgotten. For example, an X-ray of a long bone appears to have two
compact outer zones corresponding to the cortex and a lace-like or hazy central portion corresponding to
the medullary cavity. A three-dimensional construct, however, reminds us that the x-ray beam transects
two thicknesses of cortex in the region our mind's eye assumes is medullary. The reason that we perceive
the outer regions as denser is because the x-ray beam path crosses a greater thickness of compact bone in
travelling through this region of the cortex. Most of the radiographic image that we infer as medullary,
therefore, is derived from a stream of photons passing through two cortices. Consequently, a lesion
confined to the medullary cavity that is less radiodense than bone is virtually invisible on a plain
x-ray. In fact, routine radiographic studies are so insensitive that a lesion that is purely destructive
must destroy about 40% of the bone in the beam path in order to be perceived. In other words, almost an
entire cortical thickness must be absent to see a bone destroying lesion. The same 40% loss relationship
holds true for cancellous bone volume in the metaphyseal portions of long bones. Lesions with associated
calcification or production of radiodense bone matrix are additive with bone that is already present and
are more easily visualized on an ordinary x-ray
[1,
15]
.
Other factors also add to confusion in routine radiographs. The radiographic image is due to a
photon beam projected onto a cassette. Even if a patient is in contact with the cassette, the portions
of the patient facing away from the cassette are magnified on the film. In addition, a large proportion
of soft tissue shadows on plain x-rays are produced by Compton scattering,
which resultswhen electrons give off secondary photons at varying angles. These magnification
effects and extra emissions contribute to loss of sharpness, or "image blur" [12].
It is also important to remember that a radiographic image is influenced by conditions that can be
technically controlled. For example, if voltage potential to the cathode ray tube is increased, photons
of higher energy are produced. The resulting radiographs will accentuate the bony structures and
overpenetrate the soft tissues. The same effect may be achieved by increasing the exposure time at a
given voltage, however, this effect is limited by the amount of time a subject can remain motionless
[12,
14]
.
Several general considerations need to be weighed when examining bone radiographs. Since
bone lesions tend to follow reproducible patterns in age, skeletal distribution, and radiographic
appearance, a few questions must be answered when examining x-ray studies [1].
The bone containing the lesion as well as that part of the bone actually involved by the
process should be identified, since specific types of lesions not only predilect certain bones but
certain parts of bones. The patient's age is an important consideration. Primary tumors such as
osteosarcoma and Ewing's sarcoma primarily affect young individuals. Giant cell tumor and chondrosarcoma
predilect the mature skeleton. Metastatic carcinoma seldom occurs prior to the fifth decade. Clinically
uninvolved bones should also be examined, since metabolic diseases, which may mimic tumors, usually
affect the entire skeleton to some extent. Other factors, such as whether a lesion is solitary or
multifocal, involves the joint, or possesses features characteristic for matrix production are also
important considerations.
The radiographic assessment of bone lesions depends upon a consideration of bone structure and the
manner in which osseous tissues respond to the presence of a pathological process. Bone reacts to
structural abnormalities in a similar manner whether the lesion is a space-occupying neoplasm, an
inflammatory disease, or a metabolic process; the variations are those of degree [11]. In general, the
response of osseous tissue to a pathologic process is some combination of bone reabsorption and new bone
formation [8]. The radiographic appearance depends upon the relative dominance of each process in the
bone in addition to any characteristics unique to the lesional tissue itself.
The most important radiographic assessment of the biologic potential of a pathological
process is the definition of its border and that of the surrounding normal bone. The area between the
lesion and where the bone is obviously normal is sometimes referred to as the transition zone [3]. In general, better-demarcated transition zones are indicative
of more benign processes because a slowly progressing process enables the host bone to remodel in
response to the lesion. A process indolent enough to produce a well-demarcated transition zone will not
penetrate the intertrabecular marrow spaces of the cancellous bone adjacent to the advancing edge of the
lesion. In the same way, a benign lesion may push up against the endosteal cortex. Over time, there may
be erosion of the inner cortex due to osteoclast activity, however, benign lesions do not have the
ability to penetrate the cortex nor to extend into its vascular canals.
The radiographic appearance of a lesion is described as geographic
if its transition zone is well- defined [5]. This type of intraosseous extension implies that
osteoclastic reabsorption of bone at the periphery of the lesion destroys bone at about the same rate as
the lesion grows. Since osteoclast activity is a slow phenomenon, this infers that the lesion is slowly
growing and probably benign. Examination of the interface between the tumor and adjacent normal bone
reveals an abrupt transition between lesional tissue and normal bone and marrow. A geographic appearance
is described as marginated if there is, in addition, surrounding bony
sclerosis [6]. Ability of the host bone to produce bony sclerosis at the periphery of a destructive
lesion implies an even more benign behavior. The histological interface between the lesion and adjacent
bone reveals a variable amount of bone between the two. If the lesion is aggressive or a low-grade
malignancy, it grows at a faster rate and has the capacity to penetrate the marrow of the intertrabecular
spaces and the Haversian and Volkmann canals of the cortex. In addition, the bone parts associated with
slower tumor growth respond by osteoclastic activity resulting in irregular areas of radiolucency with
less defined borders. The x-ray appearance of such lesions of intermediate and irregular growth has been
described as moth-eaten [5]. The most highly malignant neoplasms infiltrate
intertrabecular spaces and cortical vascular canals at so rapid a rate that reabsorption of large foci by
osteoclastic activity does not have time to proceed, except near the oldest areas of the lesion.
Radiographs of this type of bone destruction are termed permeative [5]. The
tumor occupies areas in the bone that normally contain structures of the same radiodensity as the tumor
cells, often without a significant degree of osseous reabsorption. Bony abnormalities may be subtle, but
there is usually a large tumor volume present; often it is associated with a large soft tissue mass.
Later in its evolution, there will be diffuse linear or lenticular defects, which coalesce, and the
extensive nature of the process becomes obvious.
The presence and type of periosteal reaction also influence general radiographic assessment of the
biological behavior of bone lesions. The periosteum is loosely connected to the bone during childhood
and adolescence. Its Sharpey fibers shorten and become less lax as the skeleton matures, resulting in
its tighter adherence to the cortex in adulthood. The periosteum consists of an outer, tough fibrous
layer and an inner germinative layer, or cambium
layer. Even though the periosteum is invisible on routine x-rays, any process that causes
the separation of cambium layer from the underlying cortex stimulates osteoblastic activity by the
periosteum. When subperiosteal new bone is formed by these osteoblasts, a radiodense periosteal reaction
begins to appear on routine x-rays. The character of this periosteal reaction depends upon the patient's
age and the nature of the underlying process. In general, more continuous and solid periosteal reactions
indicate more indolent underlying lesions because it takes time to form an organized and continuous
periosteal reaction [3]. If the continuous periosteal reaction is solid, it results in the formation of
a thickened cortex, which may be linear or fusiform depending upon the overall manner of periosteal new
bone formation. In the case of some small benign lesions that cause disproportionate periosteal
irritation such as osteoid osteoma, the periosteal new bone may actually obscure the lesion in the plain
radiographs.
Interrupted periosteal reactions are more often indicative of a malignant process. The most
important of these is the Codman angle, in which the periosteal reaction is single-layered, attached to
the cortical surface at one end, and extends away from the cortex at the other end. This configuration
forms an open radiodense angle without ossification being visible in the plain x-rays at its other end.
While Codman angles may occasionally be indicative of benign lesions, they are often characteristic of
processes having rapid expansion and are usually associated with sarcomas. Multiple layers of continuous
periosteal bone reactions consisting of concentric strata of periosteal new bone often separated by
loose, vascular connective tissue produce a type of reaction, termed "onion-skin" by radiologists [10].
While this type of reaction is associated with benign conditions if the new bone layers are continuous,
it may be associated with malignant tumors such as Ewing's sarcoma if it is discontinuous. Complex
periosteal reactions such as a "hair-on-end" or "sunburst" patterns are also indicative of very rapid
growth if they are interrupted [1], and may consist of a mixed combination of reactive and neoplastic
bone. The same complex periosteal reactions may be indicative of benign processes if they are
continuous. Regardless of its periosteal reaction, any lesion thought to be a bone neoplasm should be
considered malignant if there is a soft tissue mass associated with an intraosseous tumor without visible
physical disruption of the cortex.
Sensitivity of routine x-rays may be increased with the use of conventional (plane) tomography and
with computer assisted tomography (CT scan). In plane tomography, the x-ray source and X-ray films are
moved in opposite directions about a stationary point calculated to fall in the desired plane of a
patient to be studied. Taking successive images and continually moving the pivot point between source
and film results in a series of planes or slices in which objects in a given plane are in focus but in
which structures not in the plane of interest are intentionally blurred. [14] The same effect is
achieved by "panning" in general photography. When objects in a photograph are moving in a linear
direction, a still photograph with the camera on a tripod will result in the moving object appearing
blurred and the background appearing sharply focused. If the camera is "panned," the camera is moved in
the same linear direction as the moving object at approximately the same rate of speed while the shutter
is opened. This results in the object appearing relatively sharp while the background is intentionally
blurred due to camera motion. This technique is very useful in identifying subtle fracture lines,
particularly when exuberant fracture callus associated with undisplaced fractures may masquerade
clinically as osteosarcoma [4]. The use of plane tomography has been limited by the advent of
Computerized Axial Tomography.
In Computerized Axial Tomography, multiple x-ray sources pass through the patient in an
axial direction. Each source of x-rays usually has its own corresponding x-ray detector. A computer
calculates the difference between the energy leaving the source and that reaching the detector and plots
the difference by Fourier transform into a two-dimensional image, which is essentially a map of
radiodensity [13]. A CT scan is essentially what one would get if the body could be frozen solid, sliced
into one centimeter thick slices, and a plain X-rays could then be prepared by placing each slice on a
cassette and making a contact radiograph of each slice [9]. Moreover, the thickness of each slice can be
manipulated to as thin as one millimeter. In addition, the computer can be manipulated to preferentially
examine the soft tissue or bone selectively from the same data obtained in one scan [7]. The density of
any area of a CT study can be measured to the accuracy of 1/10 of the density of a cubic centimeter of
water, or a Hounsfield unit [9]. This means that CT scanning is extremely
sensitive when compared to conventional x-rays. Keep in mind, however, that CT is not specific; i.e., it
does not give a picture of the process as a whole in the same way as a radiograph. The techniques are
complementary and one should not serve as a substitute for the other. This is one reason that scout
x-rays are done prior to the performance of a CT scan. The technique insures that the areas of interest
are included in the areas sliced by the CT scans. In addition, the gantry of earlier CT scanners
essentially limited the planes of body imaging to axial (crosswise). In these machines, in order for a
CT scan to be displayed in any other plane, many axial slices must be reconstructed indirectly by
computer in the desired view subjecting a patient to an increased total radiation dose. In the newer CT
scanners, the sources and detectors can move opposite to one another not only axially, but also
helically, which gives more recent CT scanners a greater capability to produce scans in sagittal,
coronal, or other non-axial views.
Magnetic Resonance Imaging (MRI) is the newest imaging technique to come into use in bone radiology.
Although the images produced resemble CT, there is no ionizing radiation used in the technique, because
the portion of the electromagnetic spectrum used to generate these images is in its radiofrequency
portion. Resonance is a physical phenomenon in which an object absorbs energy from an external energy
source. The energy absorption is most efficient when the frequency of the external energy source matches
the natural frequency of the object absorbing the energy. The object, in turn, gives off this energy at
the same natural frequency. The phenomenon of resonance is easily demonstrated by juxtaposing two tuning
forks with the same natural frequency. When one tuning fork is struck and placed in proximity
to the other tuning fork, the oscillating sound waves of the first tuning fork are absorbed by the
second. In turn, the same note may be heard coming from the second tuning fork. Nuclear magnetic
resonance uses the same principle, however, radio waves rather than sound waves induce the resonance
signal, and the resonance signal itself is derived from the spin of nuclear particles.
While nuclear magnetic resonance can be induced in any substance with an odd number of protons or
neutrons [9], most of the magnetic resonance imaging performed on patients effectively reflects their
tissue content of hydrogen nuclei [7]. If one were to imagine protons as minute spinning tops, the
spinning of each top would create a unique spin axis or dipole moment for each proton. The motion of
this axis is wobbly and referred to as precession [9]. Since the protons spin in more or less random
directions, the net dipole moments in numerous directions normally cancel one another under ordinary
natural conditions. In a magnetic resonance imager, a patient is placed inside a very strong magnetic
field, which causes alignment of the dipole moments along the axis of the magnetic field lines. A pulse
of radiofrequency is then given to the patient at the Larmor frequency [9].
This frequency is that necessary to make protons resonate at any given magnetic field strength, and is
directly proportional to the field strength. In general, this frequency is 42.6 megahertz (million
cycles per second) per one Tesla of field strength. When this frequency is given to the patient in a
magnetic field, the protons acqire this energy and resonate at the same frequency. While they resonate,
the protons give off radio waves at the Larmor frequency, and a radiofrequency detector is able to record
this radio signal. In addition, the extra energy imparted to the protons from the radiofrequency pulse
momentarily deflects their magnetic dipoles out of the plane of the strong magnetic field. The resonance
signal can only come from those atoms having an odd number of protons. This is because nuclei with even
numbers of protons have half their dipole moments pointing in opposite directions. The net effect is
that the net resonance signal of atoms with even numbers of protons and neutrons is exactly cancelled
out. Since the resonance signal from each nucleus is produced by the one extra odd nuclear particle,
hydrogen, with a single proton, is the ideal atom for MRI measurements. When the radiofrequency pulse is
discontinued, resonance diminishes because the proton dipole moments soon return to the prevailing
direction of the magnetic field without an additional burst of energy. The time necessary for the return
of the protons to the direction of the magnetic field is the relaxation time.
The measurement of the intensity of this resonance (signal intensity) with respect to various
relaxation time constants yields certain characteristics, which help to differentiate different kinds of
tissue from each other. The most common of these time constants are known as T1 and
T2. T1 is defined as the time it takes for the loss of 63% of the radiofrequency
signal energy. T2 is defined as the time it takes for 63% of signal loss due to dephasing.
The net resonance signal is derived from a very large number of subatomic particles. At the instant of
radiofrequency pulse, all of these particles are in synchronous in terms of their magnetic dipole
moment. As time progresses, the precessing of the particles becomes assymetric. This results in radio
waves that arrive out of phase at the signal detector. The addition of the peaks and troughs of these
waves tends to dampen the received signal and makes the apparent signal loss greater. As a result,
T2 is almost always shorter than T1. As in CT scanning, the signals from the
tissue are plotted by Fourier transform, but since there are no X-rays, the shades of grey are not
imparted by absorption, scatter, and penetration. Instead, brightness is directly related to the
strength of the detected signal. Because the signal is externally detected instead of absorption of
x-ray energy measured, MRI can image directly in any plane chosen by the operator without having to scan
many sections and indirectly reconstruct them (as in CT Scanning). Interpreting MRI in simple diagnostic
fashion does not require that a physician must understand the physical principles of MRI, just as in
order to drive an automobile one does not have to be an auto mechanic. What is required is a general
knowledge of anatomy combined with an awareness of the typical signals generated by various tissues in
MRI. Adipose tissue, for example, generates a bright signal in T1 weighted images and a
slightly less bright signal in T2 weighted images. Fluid generates a slight signal in T1
weighted images and a bright signal in T2 weighted images. Muscle generates a slight
signal in T1 weighted images and very slightly increased signal in T2 weighted
images. Significantly, since cortical bone does not contain free water, it fails to generate a
significant signal regardless of the sequence of radiofrequency energy measured, so cortical bone always
appears black on MRI studies. On the other hand, since the medullary cavity of the bone contains adipose
tissue and marrow, the signal inside the bone can be very bright, but varies according to the proportion
of adipose tissue relative to hematopoietic marrow. This means that the borders of intramedullary tumors
can often be well demarcated by MRI, but that cortical destruction can not. The spatial resolution is
not as good for MRI as it is in CT scanning, but this is likely to improve as the technology is further
refined [7]. On the other hand, the degree of contrast is much better in MRI than it is in CT [2].
Consequently, MRI is useful for the imaging of soft tissue abnormalities associated with bone lesions as
well as demonstrating their intramedullary extent, but it gives little information about the bone itself.
The ten cases for this short course have not been selected because they are diagnostic
difficulties but because they illustrate certain reproducible points about pathoradiographic correlation
that are useful in diagnosis.
Case 1: Non-ossifying fibroma, proximal tibia (fibrous cortical defect), 16 year-old male.
Powerpoint Presentation
These curettings are from a cortical lesion of the tibia in a 16 year-old male
discovered incidentally in the diagnostic work up of a sports-related injury. The x-rays demonstrate a
fairly large radiolucent defect located in the right medial meta-diaphysis. The lesion is eccentric, and
involves both the cortex and medullary cavity, as demonstrated in the CT scan taken through the lower
level of the lesion. The external border is scalloped and has a sclerotic rim. The presence of the
external sclerotic border is the surest radiographic sign of the benignity of this lesion, and the
combination of above findings is virtually pathognomonic for non-ossifying fibroma. The most common form
of non-ossifying fibroma is termed fibrous cortical defect or metaphyseal fibrous defect, and it
represents the most frequently encountered space-occupying lesion found in bone. It occurs in
approximately one in four growing children [16] and may represent an aberration of intramembranous
ossification (probably of periosteal origin) rather than a true neoplasm. It is usually solitary,
although approximately one in four patients have more than one non-ossifying fibroma. Multiple
non-ossifying fibroma associated with multiple café-au-lait spots has been termed Jaffe-Campanacci
syndrome [18] and more recently, non-ossifying fibromas associated with giant cell reparative granulomas
have been described as a manifestation of ocular-ectodermal syndrome [21].
Radiographically, fibrous cortical defects are typically intracortical, small and
elliptical, radiolucent, eccentric and metaphyseal. They have a scalloped, radiodense border not only
reflecting their benignity but also implying that the surrounding bone has the ability to react to their
presence by directing intracortical forces around them. Their major radiologic differential diagnosis
includes chondromyxoid fibroma and aneurysmal bone cyst, although they do not usually expand the bone.
Despite the self-limiting size of fibrous cortical defects, they are easily seen radiographically because
most of the thickness of a single cortex is replaced by radiolucent fibrohistiocytic tissue and because
the surrounding sclerosis further delineates them from the adjacent cancellous bone. While some authors
refer to them as non-ossifying fibromas only when they enlarge and involve the medullary cavity [20],
both fibrous cortical defects and non-ossifying fibromas have the same histology. The lesion is
moderately cellular and, for the most part, the cells are either spindle-shaped with pointed nuclei or
polyhedral with vesicular nuclei, conforming to what would be identified as a fibrohistiocytic lesion.
The presence of larger polyhedral cells with vesicular nuclei and ill-defined cell borders as well as
occasional and sometimes numerous foamy histiocytes reinforce the idea of a histiocytic content. There
are usually multinucleated, osteoclast-like giant cells; these may be so numerous histologically as to
suggest giant cell tumor. Giant cell tumor is, however, not a very tenable diagnosis in a skeletally
immature individual, especially when the lesion does not extend to an articular surface. In addition,
the cells are arranged in a rather typical storiform pattern. Despite the lack of true nuclear
pleomorphism, mitotic activity is occasionally identified, and it is not unusual in this lesion. There
can be obvious confusion between this lesion and malignant fibrous histiocytoma if the very
characteristic benign radiographic findings are not taken into account and the lesion is particularly
hypercellular. Non-ossifying fibromas are usually curetted if there is an atypically aggressive
radiographic appearance [19] or if an impending pathologic fracture is feared. If there has been an
actual fracture at the site, there may be repair bone incorporated into and about the lesion. Again, it
is very important that early repair reactions associated with non-ossifying fibromas are not mistaken for
osteosarcoma. Pathologic fracture has also been reported with features simulating primary aneurymsmal
bone cyst [17].
Most fibrous cortical defects are recognized for what they are and not usually biopsied.
Their natural course is for spontaneous healing which may be recognized by an eccentric, scalloped
radiodensity prior to its disappearance from the cortex.
Points to Remember:
 | Usually asymptomatic and affects up to one in four individuals |
| Located in the metaphyseal cortex |
| Eccentric, radiolucent, scalloped border with surrounding sclerosis |
| Ordinarily is not biopsied, but may be curetted if fracture is present or impending. |
| If fractured, the presence of callus may be mistaken for bone forming tumors |
|
|
Case 2: Paget's Disease- Mixed and late phase, distal femur of a 63 Year Old Male
Powerpoint Presentation
This 63 year-old man began having pain in the region of his left knee more than a year ago.
The pain was accompanied by local tenderness, swelling, and increased local temperature, and had
progressed to involve at least two thirds of his thigh over the past year. His left knee, although not
acutely tender, was stiff and caused pain upon flexion or extension, and physical examination revealed a
decreased range of motion. The two plain x-rays distributed are derived from the proximal left femur and
the left knee at the time of presentation. Both are virtually diagnostic of Paget's disease, although
that from the knee is more characteristic of late phase disease and that from the proximal femur is more
characteristic of its earlier lytic phase. The radiograph from the proximal femur demonstrates a
radiolucent, destructive process characterized by a loss of cortical demacation and incrased diameter of
the femoral diaphysis. The radiolucent process ends proximally several centimeters distal to the lesser
trochanter with a very sharp, demarcated wedge-shaped transition zone, the tip of the radiolucency
pointing cephalad, and the bone proximal to the lucency being radiographically unremarkable. The bone in
the distal femur shows areas of radiolucency alternating with areas of osteosclerosis. This
osteosclerosis demonstrates visibly coarse trabeculae, some areas showing diffuse coarseness. The
diameter of the distal femur is increased relative to the diameter of the proximal tibia, resulting in
secondary osteoarthritis with narrowing of both medial and lateral compartments of the knee. This is
what accounts for the patient's current knee stiffness. The wedge or flame-shaped radiolucency combined
with the bone remodeling are virtually diagnostic for Paget's disease. The same can be said for the
mixed osteosclerosis and osteolytic lesions of the distal femur.
Paget's disease of bone, otherwise known as "Osteitis Deformans" was first described by Sir
James Paget in 1877 and is often asymptomatic [30]. Usually a localized condition, this disease is due
to abnormal activity of osteoclasts with apparent uncoupling of osteoblast and osteoclast activity. As a
result of this increased progressive and multifocal albeit transient osteoclastic activity, there is bone
reabsorption early in the course of the disease. This is followed by a mixture of bone formation and
bone destruction and eventuates in irregular osteosclerosis. This leads to variable radiographic
appearances depending on the phase of the disease. On one hand there may be striking radiolucency due to
the increased bone reabsorption. On the other hand, the compensatory osteoblastic activity leads to bone
formation and subsequently resulting in coarsely trabeculated sclerosis or increased radiodensity. The
resulting x-ray often has areas of increased density with a cotton wool-like appearance interspersed by
radiolucent areas
[25,
29]
. In long bones the process often starts at one end or both and spread towards
the center. The junction between the normal and diseased bone is demarcated as an advancing wedge of
rarefaction frequently described as "flame-like". As the process advances, there may be cortical
remodeling with actual diametric increase of the bone; Paget's disease is one of the few conditions that
enlarge bone diameter in mature adults. Due to combined thickening of the cancellous bony trabeculae and
cortical reabsorption there is loss of cortico-medullary demarcation. In the skull, the increased
radiolucency sometimes causes well-demarcated circular radiolucent areas that have been described as
"osteoporosis circumscripta." With time, there may be enlargement of the skull, and often there is
blurring of the diploë. In scintigraphic studies, isotope uptake is increased. Virtually any bone can
be involved, however, this disease typically involves the skull, spine, pelvis and femurs of individuals
over the age of 40. Less commonly, the disease is multifocal (polyostotic) or generalized.
Histologically there are three phases to this abnormal bone assembly, sometimes called " matrix
madness." First there is an osteolytic phase characterized by active
osteoclastic reabsorption associated with an extremely vascular fibrous tissue filling the marrow
spaces. This is followed by a mixed osteoclastic-osteoblastic phase in which, in addition to the
exuberant osteoclastic activity leading to bony scalloping and large resorption cavities, there is
appositional new bone formation by prominent osteoblasts. This ends ultimately in a burned out
quiescent osteosclerotic phase with a characteristic "mosaic" pattern formed
as result of abnormal remodeling with increased number of irregularly intersecting reversal type cement
lines [23]. Reversal cement lines are those formed when osteoclastic activity is followed by osteoblast
activity. They are distinguished from arrest type cement lines in that lamellar architecture is
contiuous on both sides of an arrest line whereas it is different on opposite sides of a reversal cement
line. The irregular and random nature of the way the bone is reconstructed in Paget's disease leads to
vulnerability under stress. There may be microfractures leading to bowing deformities, or frank
pathologic fractures as stress irregularly propagates forces through the abnormal bone structure.
Laboratory findings include elevated serum alkaline phosphatase and increased urinary hydroxyproline
although levels of calcium and phosphate tend to be normal unless there is immobility of the affected
bones. The clinical presentation is often with pain secondary to complications such as fractures or
osteorthritis. The latter occurs due to bone enlargement and increased endochondral ossification of the
articular cartilage accelerated by the increased endosteal vascular supply. The increased vascular
supply may also result in secondary high-output cardiac failure in individuals with some degrees of
underlying intrinsic cardiac disease. A rare complication (1-2% of patients with Paget's disease) is the
development of sarcoma [26] presenting clinically as pain and palpable mass. Radiographically, an
osteolytic lesion with cortical breakthrough without periosteal reaction and accompanied by a soft tissue
mass is a sign of malignancy in a pre-existing Paget's bone. Histologically the sarcoma can take any
form including osteosarcoma, malignant fibrous histiocytoma, fibrosarcoma, chondrosarcoma and malignant
giant cell tumor with mixed patterns in some cases. The prognosis is uniformly poor with a 5 year
survival of 8% [25]. The only benign tumor described in association with Paget's disease is a giant-cell
tumor most commonly involving the skull and facial bones, although the relationship of this entity with
giant-cell reparative granuloma has been emphasized [29]. It has been noted that many patients with this
giant cell lesion have ancestry in Avellino, Italy [25].
The cause of Paget's disease is unknown. Previous reports of an infective etiology [31] with
ultrastuctural demonstration of virus particles (Paramyxovirus) have not been reproducible. Studies have
demonstrated measles virus nucleocapsid transcripts in circulating blood cells in patients with Paget's
disease [32] and osteoclasts containing the gene for the measles nucleocapsid have been described as
having a Pagetic phenotype [28]. On the other hand, attempts to find measles and canine distemper virus
RNA in cultured pagetic bone cells and in Pagetic osteoclasts have been fruitless
[22,
27]
. There has
been some evidence for genetic linkage of Paget's disease of bone with up to 40% of patients having
affected first degree relatives [24]. In the absence of malignant transformation or cardiac failure,
Paget's disease is not a life-threatening condition, which is usually discovered incidentally or at
autopsy.
Points to Remember:
| Unique non-metabolic disorder of skeletonusually seen in individuals older than 40 characterized by uncoupling of osteoblastic and osteoclastic activity. |
| Skull, pelvis, spine and femur are commonly affected. |
| Radiological features include early wedge-shaped radiolucencies and later, irregularly radiodense areas resulting in indistinct cortices and coarse trabeculations. |
| Three phases are distinguished microscopically:
a) osteolytic
b) osteolytic-osteoblastic
c) osteosclerotic (burnt-out) resulting in a prominent mosaic pattern characterized by increased and irregular reversal type cement lines . |
| Predisposition to development of fracture, deformity, cardiac failure, sarcoma. |
|
|
Case 3: Osteochondroma - 10 year-old male with a hard mass on his left leg.
Powerpoint Presentation
This growing child had noticed a firm bump, just superolateral to his left knee. The mass was
noticed because it had become tender and it was thought to have recently increased in size. The plain
radiograph is virtually diagnostic for osteochondroma. There is a pedunculated osseous lesion three
centimeters above the lateral femoral condyle. The lesion is internally trabeculated, and its interior
is in continuity with the interior of the femur. At the same time, the femoral cortex is in continuity
with the cortex of the lesion. The outer margin of the lesion is smooth, and there are no significant
calcifications in the soft tissue overlying the lesion. The histology correlates very well with the
radiographic image. The lesion is comprised of a thin hyaline cartilage cap which transforms to bone at
its base by a process that is identical with endochondral ossification. Its hyaline cartilage is
reminiscent of a normal growth plate, and in young individuals is similar to the zones of growth seen in
a typical epiphyseal growth plate. The underlying bone is cancellous and continuous with the medullary
cavity of the host bone, and this is demonstrable because in the sections, one can see that the outside
of the lesion is composed of a thin cortex with an overlying periosteum continuous with the perichondrium
overlying the cartilage cap. The cartilage cap can not be seen on the plain radiograph because cartilage
has the radiodensity of water and is penetrated identically to the surrounding soft tissues.
Although osteochondromas are usually classified as benign tumors, they almost certainly arise as
defects or malformations of the growth plate in the process of endochondral ossification [36]. Growth
plate cartilage experimentally implanted beneath the periosteum of animals has produced lesions
histologically identical to osteochondromas [34]. That the growth plate grows longitudinally and not
axially is probably due to the thin delimiting plate of bone and fibrocartilage that surround its
circumference, the so-called ring of DeLaCroix. Human osteochondromas are thought to arise from defects
in the epiphyseal rings of DeLaCroix that effectively produce the same anatomic relationship as produced
by growth plate transplants in experimental animals. There is then a defect in the cortex filled with
cartilage that proliferates by endochondral ossification and is covered by periosteum. The newly formed
bone added to the surface of the bone on the metaphyseal side of the growth plate may be sessile or
pedunculated. The cancellous bone inside in direct continuity with the medullary cavity of the
underlying bone and the outer forming cortex of the new bone is in continuity with the cortex of the
surrounding normal bone. This can be demonstrated both radiographically and histologically. On the
outer surface of the enlarging bony mass is the cap of cartilage derived from the altered growth plate.
So long as the skeletal growth continues, the bony protruberance expands by endochondral ossification.
The residual cartilage can be demonstrated histologically and it has a thin overlay of vascular
fibroconnective tissue (perichondrium) which is in continuity with the periosteum surrounding the new
bony stalk and the cortex to which it is attached. Radiographically, the cartilage cap and its overlying
perichondrium are virtually invisible because cartilage and fibrous tissue have same radiodensity as the
surrounding soft tissues. The zone of calcification of the cartilage may be seen radiographically
because of its intense concentration of amorphous calcification. The intertrabecular spaces of the
osteochondroma contain fatty or hematopoietic marrow, just as do those in the medullary cavity of a
mature bone. All of the features can be seen in the study sections. A typical osteochondroma thus has
all the features of a maturing bone and is covered by cartilage that not only functions as a growth
plate, but also, in fact, was derived from the growth plate. Although the vast majority of
osteochondromas are solitary, there is an autosomally dominant inherited condition, multiple hereditary
exostoses (multiple hereditary osteochondromas) in which numerous osteochondromas develop in patients
from affected families. This disease, which causes disruption in the anatomical continuity of the
epiphyseal rings of many growth plates usually results in diaphyseal and metaphyseal bone remodeling
abnormalities.
Recently, point mutation analyses have been identified in both the hereditary multiple form of
osteochondroma as well as in solitary osteochondroma
[33,
35,
38]
. While point mutations point toward
evidence that osteochondroma is really a neoplastic transformation, these studies have not examined the
corresponding growth plates in the same patients, nor does this account for the lack of osteochondroma
growth seen after closure of growth plates. Other studies have inferred that the cartilage proliferation
of osteochondroma is actually derived from overlying fibrous tissue and are related to fibroblast growth
factor receptor expression [37]. Note that the cartilage cap of both solitary and multiple
osteochondromas can be a benign precursor of chondrosarcoma although malignant transformation of
osteochondroma is much more common in multiple hereditary exostoses. Since the cartilage cap usually
regresses after the adolescent growth spurt any spontaneous enlargement of a known osteochondroma after
skeletal maturity is clinically ominous sign. While pain related to an osteochondroma may be a sign of
malignancy, it may be simply due to neural encroachment or irritation, fracture of the stalk of an
osteochondroma or development of a soft tissue bursa overlying the cartilage cap ("bursa exostotica")
with secondary inflammation or even with intrabursal hemorrhage. Preoperative evaluation of the
thickness of the cartilaginous cap is perhaps best accomplished with magnetic resonance imaging because
the water content of hyaline cartilage has a hyperintense signal intensity with T2 weighted images. If
the cartilage cap of an osteochondroma measures three or more centimeters in thickness it may be best to
consider the lesion a chondrosarcoma even if the cellularity itself is not ominous.
Points to Remember:
| Developmental defects or malformations of growth plate. |
| Enlarging bony mass at outer surface of cortex which expands during skeletal growth |
| Internal contiguity with the medullary cavity; externally with the cortex. |
| A prominent cartilage cap covered by a thin rim of perichondrium in continuity with the periosteum. |
| Radiographically, the cap and perichondrium are invisible although sometimes the zone of calcification is prominent. MRI T2-weighted images show a hyperintense signal of the hyaline cartilage cap. |
| Cartilage cap thickness does not usually exceed 1-2 cm. A cap thickness of more than 3 cm may be indicative of transformation to chondrosarcoma, however, this should always be confirmed histologically. |
|
|
Case 4: Parosteal Osteosarcoma, distal femur, 30 year-old male
Powerpoint Presentation
This lesion is a variant of osteosarcoma, with a low grade biological potential originating
on the surface of a bone. It usually presents itself clinically as a painless mass growing over a long
time course [7]. Radiographically, the lesion is juxtacortical in location with dense ossification at
the center and less dense ossification at its periphery [7]. Its peak age incidence is in the third and
fourth decades, and 80% of the time it arises on the posterior surface of the distal femur.
Juxtacortical osteosarcoma is sometimes used as a synonym for parosteal osteosarcoma, but "juxtacortical"
is more properly used as a generic term that includes at least three other types of surface osteosarcomas
that have been described in the medical literature. In Dedifferentiated parosteal osteosarcoma [44], a
high-grade osteosarcoma develops within an otherwise typical low-grade parosteal osteosarcoma. It has
been stated that such dedifferentiation may occur in as many as one in five cases of low-grade parosteal
osteosarcoma. High-grade surface osteosarcoma may appear radiographically similar or identical to
parosteal osteosarcoma, but histologically it is entirely a high-grade sarcoma that happens to have
arisen on the surface of a bone [43]. It is, of course, possible that some examples of high-grade
surface osteosarcoma represent dedifferentiated parosteal osteosarcomas in which the high-grade tumoral
component has completely replaced the low grade component. Periosteal osteosarcoma [42] is a type of
surface osteosarcoma that is intermediate in degree of malignancy between the usual parosteal
osteosarcoma (in which surgery alone is almost always curative) and conventional osteosarcoma (which has
a high potential for distant metastases). Unlike the other varieties of surface osteosarcomas, the
extracellular matrix of periosteal osteosarcoma, is primarily composed of cartilage, with osseous
differentiation usually being a minor component. Radiographically, there is another important difference
between periosteal osteosarcoma and the other variants of juxtacortical osteosarcoma. Periosteal
osteosarcoma usually is situated on the surfaceof a bone beneath the
periosteum. When the tumor grows, there is elevation of the cambium layer of the periosteum and usually
a periosteal bony reaction that is visible on radiographs. The remaining types of juxtacortical
osteosarcoma arise on the surface of the bone external to the cambium layer.
When these tumors increase in size, there is no elevation of the cambium layer of periosteum and usually
no periosteal response. This feature is of more than theoretical importance, because if there is
penetration of the tumor through the cortex into the medullary cavity, the presence or absence of a
periosteal reaction may be the key feature that permits its classification into central or surface type.
In the illustrated case, the radiographs reveal a radiodense surface lesion in the classic location
for low-grade parosteal osteosarcoma. The lesion is less radiodense away from the cortex and denser
toward the cortical surface, because the most mature bone matrix is closest to the cortex and the least
mature (and mineralized) matrix is at the outermost and advancing edge. The plain X-ray also shows a
radiolucent line that is present between the neoplasm and the underlying cortex. This corresponds to the
interposed periosteum and is radiolucent because it is soft tissue situated between the calcified cortex
and the tumor matrix (illustrated well by the gross specimen). Note that while the gross specimen
reveals that there is no obvious tumor in the medullary cavity, this information cannot be inferred for
certain with any combination of preoperative plain x-rays alone. In this instance, the value of a CT
scan may be appreciated, for it yields information that makes the conventional radiographs more
meaningful. The preoperative CT scan in this case reveals that the marrow cavity is not involved. In
addition, it shows that the apparent tumor within the bone is due to the extension of the tumor around the cortex. The area in which the tumor is fixed to the cortical surface
and the areas in which the periosteum is interposed between tumor and cortex are delineated with great
clarity.
Histologically, the tumor displays long, somewhat parallel "streamers" [41] of bone which are usually
immature (woven) in collagen orientation. The tumor stroma producing this bone is fibroblastic, and the
nuclei are relatively bland with indistinct nucleoli and fairly scant mitotic activity. Without
radiographic and clinical correlation, it is difficult to believe that this constitutes a malignant
neoplasm with the potential for metastatic behavior.
Because the tumor arises on the bone surface, the most important radiographic differential diagnosis
to exclude is osteochondroma. The lack of continuity with the medullary cavity radiographically and the
presence of intertrabecular fibrous stroma rather than hematopoietic or fatty marrow excludes
osteochondroma from diagnostic consideration. These features are very important to keep in mind since
occasionally parosteal osteosarcoma actually has a cartilaginous cap. In this case, there is a very
significant amount of hyaline cartilage in an overlying cap; in fact almost 40% of this mass is composed
of cartilage. This is demonstrated both by the MRI pictures and the gross and specimen radiographs, but
to all intents and purposes it is invisible in the plain x-rays and CT scans. The sections distributed
were given out not for the demonstration of cartilage, but for the correlation of the radiolucent zone
between the base of the lesion and the femoral cortex. On the section, it is very clear that this
corresponds to the periosteum entrapped between the lesion and the cortex. The next radiographic
differential diagnosis to consider is heterotopic ossification, or so-called myositis ossificans arising in a juxtacortical location. The CT scan eliminates
this possibility for two reasons. First, myositis ossificans almost always has a cleavage plane
completely separating it from the bone regardless of how many CT cuts are examined. Secondly, myositis
ossificans is zoned both radiographically and histologically [40]. The area of greatest maturation is at
the periphery, reflected in increased radiodensity on the outside and radiolucency at the center. This
is the opposite of what is present in the radiographs of case 5. This appearance reflects the
histological findings in myositis ossificans, in which the least mature areas in the center of the lesion
may be cellular and atypical and the most mature areas are at the periphery. If the lesion is detected
early in its evolution, myositis ossificans may thus be mistaken for a sarcoma if the central portion
only is biopsied, particularlyin the absence of a radiograph. In the mature lesion, the external portion
of the lesion may appear corticated on x-ray and may actually be composed of mature compact bone. The
inside of the lesion may be replaced by fatty marrow, so that both radiologically and pathologically
mature myositis ossificans comes to resemble the cross section of a long bone.
Points to Remember:
| A surface lesion arising, in 80% of cases, on the posterior distal femur |
| The lesion is low-grade in about 90% of cases |
| The medullary cavity is usually spared |
| There is cartilage formation in about one-third of cases |
| The lesion is more radiodense closer to the cortex and less radiodense peripherally |
|
|
Case 5: Polyostotic Fibrous Dysplasia, 26 year-old female with Albright-McCune Syndrome.
Powerpoint Presentation
This 26 year-old female has a history of limb length discrepancy and limp going back to her
childhood. Her menarche began at age 9 and she has obvious café-au-lait spots of her trunk with highly
irregular borders. She complained of increasing pain in her left hip, which had become much worse
recently, causing her to seek medical help. When seen by an orthopedic surgeon, she had severe pain and
could bear practically no weight. The radiographs distributed demonstrate a marked varus deformity of
the left femoral neck associated with a non-displaced fracture. It is probably this fracture that
accounts for the patient's recent increase in pain. The quality of the bone is obviously abnormal both
in its shape and in the distribution of its radiodensity. The femur is increased in diameter and shows a
loss of the normally tapered funnel shape of the metadiaphysis. The lateral femoral cortex is thinned
and shows internal scalloping. These changes are characteristic of slow remodeling and are associated
with areas of irregular intraosseous mixed radiolucency and radiodensity. The coarsely enlarged and
deformed femur that results is termed a "shepherd's crook deformity," and this radiographic appearance,
while not pathognomonic, is characteristic of fibrous dysplasia.
The histologic section demonstrates a bone-forming fibrous lesion filling the medullary cavity,
encroaching upon the endosteal femoral cortex, and attenuating its thickness. The collagen of the lesion
is loose textured, vascular, and paucicellular. It contains irregularly intersecting spicules of
cancellous bone disposed in irregular curlicues. Most of the sections also demonstrate the production of
a few nodular foci of hyaline cartilage interspersed amongst the bone spicules. If you looked at the
sections through crossed polarizers, you would have observed that almost all of these bone spicules are
composed of immature or woven bone. Even though the bone contains osteocytes, there is no appositional
osteoblastic activity, and the osteocytes within the spicules do not appear to arise from incorporated
osteoblasts. In short, there is no histological evidence that these spicules are derived from
osteoblastic activity. In polarized light, in fact, the fabric of the woven bone appears to be
continuous with the fabric of the surrounding fibrous tissue. In other words, the histology is
consistent with bone being formed directly within and by the fibrous tissue (so-called "metaplastic"
bone).
The plain x-ray reveals that this is a space-occupying lesion, but the tissue orientation of the
lesion can be inferred from the fact that there is almost no mature lamellar bone with interspersed
fibrous tissue. This means that none of the bone antedates the fibrous lesion but, instead, is produced
by it. The normal contents of the medullary cavity in the femoral neck consist of 25% cancellous bone
and 75% marrow. The normal contents in the metadiaphysis of the femur are almost entirely yellow marrow
in an adult. This means that the radiodensity of the femur in any single plain x-ray view of the
metadiaphysis is derived from attenuation of the x-ray beam by cortex. Since this space-occupying lesion
in the medullary cavity is composed of fibrous tissue and immature bone, it is more radiodense than the
yellow marrow, which normally occupies this space and tends to produce a cloudy appearance on the plain
x-ray. This characteristic appearance is referred to as "ground glass" by the radiologist, because of
its resemblance to smoked or shaved glass. Some areas within this ground glass lesion are more
radiolucent than the normal femur at this site. This phenomenon is presumably due to cortical
attenuation. In summary, even though the substance of the lesion is more radiodense than the normal
marrow at this site, the fact that portions of the cortex are eroded gives the lesion a mixed radiodense
and radiolucent appearance. Although these comments have addressed the lesion in the left proximal
femur, the plain radiograph also demonstrates that there are multiple confluent radiolucent lesions in
the supra-acetabular region of the left innominate bone as well as in the pubis and in the ischium.
The major differential diagnosis of multiple radiolucent lesions includes metastatic carcinoma and a
metabolic bone disease, but this patient has no history of a primary carcinoma and she is quite young.
She has no known metabolic alterations and her right pelvis and femur have bone of normal quality. On
the other hand, she has large, circumscribed radiodense and radiolucent lesions of her left tibia and
fibula. In short, her bone problems are polyostotic and monomelic (affecting one limb bud). The fact
that there are multiple lesions with modeling abnormalities having an indolent radiographic appearance
effectively rules out the diagnosis of low grade central osteosarcoma, which may have a striking
microscopic resemblance to fibrous dysplasia. The only cogent diagnosis left when the radiographic and
histologic features are combined is polyostotic fibrous dysplasia.
Fibrous dysplasia is a space-occupying developmental lesion of bone forming mesenchymal tissue, the
central feature of which is an inability to produce mature bone. Since it is a mesenchymal developmental
lesion, fibrous dysplasia is capable of producing any tissue types that normal bone precursors can
manufacture. Most often, it consists of fibrous tissue producing immature bone, but it may contain
fibrous tissue with very little bone, and it may also produce cartilage. The ability to produce bone,
cartilage, and fibrous tissue is shared by fracture callus and by osteosarcoma, so the histological
characteristics must be very carefully correlated with the radiographic appearance. Occasionally,
fibrous dysplasia may produce cartilage in such exuberant amounts that it has been referred to as
fibrocartilaginous dysplasia and even mistaken for cartilage tumors radiographically. Fibrous dysplasia
usually affects the skeleton in one focus and is then referred to as monostotic fibrous dysplasia, a
variant that often has no symptoms and is often identified incidentally. It is particularly common in
the ribs, where it may not present until the latter decades of life. Solitary fibrous dysplasia is
self-limited, requires no specific treatment, and if completely curetted, the bone often returns to
normal. Polyostotic fibrous dysplasia may affect the bones of one limb bud (monomelic polyostotic
fibrous dysplasia) or affect multiple bones in several limbs (polymelic polyostotic fibrous dysplasia).
The greater the number of skeletal lesions, the greater the chances of growth abnormalities, bone
deformities, and earlier discovery, and patients are managed orthopedically according to symptoms. When
the diagnosis can be made a history and thorough physical examination may reveal other abnormalities.
The association of polyostotic fibrous dysplasia, irregularly bordered truncal café-au-lait spots,
and an endocrinopathy, often precocious puberty, defines Albright-McCune syndrome. Activating mutations
of protein GS have been described not only in patients with Albright-McCune syndrome [48] but in their
fibrous dysplasia tissue [49] leading to supposition regarding possible mechanisms of inheritance.
Increased amounts of c-fos oncogene protein have been described in tissue
derived from fibrous dysplasia [45], and clonal chromosomal abnormalities have also been described [47]
Patients with Albright-McCune syndrome are noted to have an increased incidence of hyaline cartilage in
their fibrous dysplasia. A more recently described association between polyostotic fibrous dysplasia
and soft tissue myxomas has been described and is known as Mazabraud's syndrome [46].
Points to Remember
| A developmental, possibly hamartomatous lesion |
| Affects the medullary cavity but not the cortex |
| Lesions often resemble "ground glass" radiographically |
| Fibrous tissue replaces marrow; immature bone synthesized |
| Lesions may be monostotic or polyostotic |
| Bone may be enlarged |
| Some patients have other associated systemic abnormalities. |
|
|
Case 6: Aneurysmal Bone Cyst, proximal right fibula of a 15 year-old male
Powerpoint Presentation
This teenager had complained of pain and swelling in the lateral part of his lower leg for less than
3 months. Physical examination revealed a tender fullness just below the area of right fibular head.
The plain x-rays reveal a highly expansile, radiolucent lesion of the fibular diaphysis which is slightly
bubbly in appearance. While the lesion is confined to inside the fibula, the residual cortex is
paper-thin. At its inferior border with the cortex, there is a continuous, layered, thickened periosteal
reaction forming a buttress at the base of the lesion. Of great importance radiographically is that the
lesion is considerable wider than the diameter of the proximal fibular growth plate. The MRI studies
demonstrate that the lesion consists of multiple confluent locules. The sagittal views show that the
signal differs from locule to locule. The axial MRI panels demonstrate that the locules contain
fluid-fluid levels, which have been reported to be fairly sensitive and moderately specific for
aneurysmal bone cyst [52]. These imaging studies correlate very well with the corresponding histologic
sections. The tissue consists of alternating solid and cystic areas, the latter of which are filled with
blood. The solid areas are composed of bland spindle cells and polyhedral cells that occasionally show
osteoblastic differentiation and are in some foci, involved in bone production. Interspersed within the
solid tissue are multinucleated, osteoclast-like giant cells, which tend to cluster about extravasated
blood or near areas of hemosiderin. There are many very small capillary-sized blood vessels, and there
is a progression in the caliber of these vessels to a sinusoidal appearance. The large cystic areas are
blood-filled spaces lined by fibrovascular tissue containing multinucleated giant cells, and a few
contain wisps of new bone formation. Although there is a rather flattened lining of the sinusoids, there
is no really distinct endothelial layer as would be found in true vascular sinusoids. Although there is
some mitotic activity, no mitoses are atypical and the cells possess rather bland nuclei. There is no
histological evidence of any other specific type of lesional tissue identified. These features define
aneurysmal bone cyst.
Jaffe and Lichtenstein first defined aneurysmal bone cyst as an expansile lesion of the bone
consisting mainly of a blood-filled cavity [54]. Its name is derived from the fact that it usually
causes dilatation of the bone in much the same way that an aneurysm dilates an artery. The lesion was
also defined as an entity separate from giant cell tumor and other lesions containing giant cells [53].
Aneurysmal bone cysts usually present in individuals who are skeletally immature, in contrast to those
with giant cell tumors. They are multilocular, cystic, and arise both in bone and as a secondary event
in some lesions of soft tissue
[50,
55]
. They may be associated with an injury or alteration in the
vascular supply of the bone, which may eventuate in the destructive and expansile process, related to the
pressure of extravasated blood [53]. While studies of the pressure in the cysts, venograms, and the fact
that there is no clotting in the venules suggest that they are connected actively to the host capillary
network [51],
MRI studies demonstrating fluid-fluid levels indicate that the blood contained in the cysts
is stagnant but not clotted. The fluid levels are derived from sedimentation of the blood cells, which
give a hypointense resonance signal in T2-weighted images, from the plasma, which gives a
hyperintense resonance signal in T2-weighted images. The separation of the fluid levels is
time dependent and is analogous to a sedimentation rate or to the packing of blood cells in a
centrifuge. The phenomenon is also view dependent; while it can be seen in sagittal and especially in
axial views, it is not seen in coronal views (in this orientation, the image is either completely above
the fluid level within the plasma or below the fluid level within the blood cell column). It has been
postulated that intraosseous hemorrhage may provoke an aneurysmal bone cyst or a solid lesion such as
giant-cell reparative granuloma [53].
Aneurysmal bone cysts are sometimes divided into so-called primary and secondary varieties. Although
both varieties are identical histologically, in primary aneurysmal bone cyst there is no underlying
associated bone alteration demonstrable, whereas in secondary aneurysmal bone cyst there the process
develops in association with some other pre-existing condition. Approximately half of aneurysmal bone
cysts are of the secondary variety, and very often the underlying lesion may be identified only
histologically. Although they are indolent lesions, aneurysmal bone cysts may be locally aggressive and
are prone to recurrence. When they occur in closely opposed bones such as the spine, they may even
extend from one bone into another.
The term solid aneurysmal bone cyst [56] has been applied to
some bone lesions containing hemorrhage and features of giant cell reparative granuloma that are expanded
and occur in sites that are usual for aneurysmal bone cyst. While the terms "cyst" and "solid" are
mutually exclusive, recent studies by Oliviera et.al. demonstrated similar additions to oncogene loci
CDH111 and USP6 in a majority of primary aneurismal bone cysts and in most of the so-called solid
aneurysmal bone cysts tested by FISH analysis [54b]. Interestingly, the oncogene abnormality was not
demonstrable in any case of so-called secondary aneurysmal bone cyst, suggesting that while the changes
of secondary ABC may resemble primary ABC, the lesions may in fact have completely diverse etiologies.
Radiographically, aneurysmal bone cysts are radiolucent lesions, which are usually eccentric and
asymmetric. Early in their evolution they may not be expansile, but as they enlarge, they usually appear
blown out. Interestingly, aneurysmal bone cysts are amongst the very few osseous lesions that are
capable of growing to enormous size and destroying considerable amounts of bone in periods measured in
weeks. In a narrow bone such as the fibula, eccentricity and asymmetry rapidly disappear as diagnostic
criteria because the lesion early in the evolution of aneurysmal bone cyst extends across the narrow
diameter of the bone. On the other hand, when these criteria are lost, the destructive lesion is almost
always wider than the epiphyseal growth plate.
The most important differential diagnoses to consider are secondary aneurysmal bone cyst, giant cell
tumor, and telangiectatic osteosarcoma. Being unable to find any other lesion associated with the bone
cyst eliminates secondary aneurysmal bone cyst. Giant cell tumor is eliminated radiographically because
the patient is not skeletally mature and because the metaphyseal lesion does not extend to the articular
surface of the bone. It is eliminated histologically because the mononuclear cell background appears
reactive and because the giant cells are not randomly and evenly distributed. Telangiectatic
osteosarcoma, which is invariably radiolucent and often appears expansile, is perhaps the most important
lesion besides ABC that may display fluid-fluid levels on MRI. Histologically, it usually displays
obvious nuclear pleomorphism and cellular features consistent with a malignant tumor even in the absence
of abundant bone formation.
Points to Remember:
| Lesion of unknown etiology that causes eccentric, asymmetric bone expansion |
| Associated with an underlying lesion in approximately 50% of cases |
| Very unusual after the age of 20 |
| Lesions may be partly solid, but almost always are blood-filled. The fluid-fluid levels seen on MRI are indicative of static blood flow. |
| The histology is not specific and the diagnosis is one of exclusion. |
|
|
Case 7: Giant Cell Tumor, left humeral head in a 45 year-old female.
Powerpoint Presentation
This 45 year-old female who presented with swelling and pain of her left shoulder and pain on
shoulder motion was found to have a decreased range of motion and severe tenderness of the left shoulder
on physical examination. The plain radiograph demonstrates a large, expansile and radiolucent lesion of
her humeral head, and there is a fairly abrupt transition zone between the lesion and normal bone.
Radiographically, giant cell tumors are eccentric, radiolucent lesions that arise in the mature
skeleton. They usually extend from the area of the bone that constituted the metaphysis during skeletal
growth to an articular or apophyseal surface. Because they involve the subarticular bone and cartilage,
the pain associated with giant cell tumors often resembles that of a monoarticular arthritis. Giant cell
tumor frequently destroys much of the cortex, yet periosteal reactions and soft tissue masses in the
absence of pathological fractures are unusual. Despite the degree of local destruction on radiographs,
there is often a fairly circumscribed transition zone with the normal cancellous bone and the marrow,
implying that bone destruction does not necessarily mean aggressive behavior. This feature may be
explained based upon the concept that the multinucleated giant cells in the tumor behave like
osteoclasts, so that the tumor has the capacity to destroy bone at its interface with tumor irrespective
of secondary osteoclast activation. In fact, it has been demonstrated that the mononuclear cells of
giant cell tumor secrete cytokines and differentiation factors, which are both chemotactic for monocytes
and enhance osteoclast differentiation [59]. In addition, at least one study of giant cell tumor in an
in vitro reabsorption model has suggested that the mononuclear stromal cells may reabsorb bone matrix
directly [58].
The CT scan in this case shows that the cortex at the base of the humeral head has internal erosion
and destruction. The MRI study shows a mixed signal intensity, which indicates some heterogeneity in the
lesion. In addition, it demonstrates the eccentricity of the lesion from anterior to posterior as well
as a hypointense signal on T1, T2, and proton density images. In the T1-
weighted image, there is a sharp distinction of the tumor from the marrow adipose tissue,
reinforcing the impression of a sharp transition zone. None of the plain radiographs indicate
calcification or endochondral ossification, and the further lack of hyperintense T2-weighted
images practically eliminates chondrosarcoma as a diagnostic consideration (cartilage gives the same
signal as fluid which is hyperintense on T2). The other major primary bone neoplasms to
consider with this radiographic appearance are fibrosarcoma and malignant fibrous histiocytoma, which are
deceptively circumscribed radiographically and often show no periosteal reaction. Aneurysmal bone cyst
is a minor radiographic consideration because of the expansile nature of this lesion. On the other hand,
not only is this patient probably too old to have aneurysmal bone cyst, the MRI indicates that the amount
of fluid in this lesion is not consistent with aneurysmal bone cyst. Finally, since the patient is over
40 years of age, metastatic carcinoma must also be considered in the radiographic differential diagnosis.
The histology immediately narrows the list of diagnostic possibilities to those lesions containing
large numbers of multinucleated giant cells, for these cells are the most prominent feature of the lesion
at low power. The cellular stroma of this lesion consists of a sea of mononuclear cells, which vary in
shape from polyhedral to spindle-shaped. There is a moderate mitotic rate, and the cell borders are
rather indistinct. The multinucleated giant cells are uniformly and randomly distributed amongst the
mononuclear cells, which lack the pleomorphism and the prominent storiform pattern of malignant fibrous
histiocytoma. At the lower powers, the lesion appears syncytial due to the combination of evenly mixed
mononuclear and multinucleated giant cells with a lack of distinct cell borders. The nuclei of both
types of cells are similar. The mitotic rate, which is brisk in some sections, is confined to the
mononuclear spindle cell component.
While these constellation of findings is characteristic for giant cell tumor, a few cautionary
statements must be made. Occasionally in hyperparathyroid states, a so called "brown tumor" (an aberrant
reparative lesion containing hemosiderin and multinucleated giant cells) may be mistaken for a giant cell
tumor if the background fibroblasts are plump and mitotically active and if the giant cells happen to be
evenly distributed. The value of radiographs in such a case is that since hyperparathyroidism is a
metabolic disease, it is unusual for all other bones, particularly the hands, to have a normal x-ray
appearance. Finally, it is important to know the patient's biochemical status to absolutely rule out
hyperparathyroidism. This should include several baseline determinations of serum calcium, inorganic
phosphate, chloride and BUN/creatinine. Giant cell reparative granuloma, a non-neoplastic lesion often
confused with brown tumor of hyperparathyroidism and giant cell tumor, often resembles giant cell tumor
radiographicallly but usually affects the jaws, hands, and feet [57]. Giant cell tumors may rarely be
multifocal; when they are axial, they may be associated with Paget's disease.
Points to Remember:
| A tumor of skeletally mature individuals. |
| X-ray reveals eccentric, radiolucent lesion located in the metaphysis that extends to an articular surface or an apophysis. |
| Transition zone with surrounding bone is well demarcated. |
| Cortical destruction, typically without any periosteal reaction. |
| Very unusual in a non-sacral flat bone in the absence of Paget's disease. |
| Microscopically, a cellular tumor with evenly distributed giant cells admixed with mononuclear cells nuclear features similar to giant cells. |
| Differential Diagnosis – Brown Tumor of Hyperparathyroidism. |
|
|
Case 8: Osteosarcoma, high grade - 16 year-old male with distal femur mass
Powerpoint Presentation
This highly malignant neoplasm demonstrates most of the classical radiographic features of
malignant bone tumors in general and of osteosarcoma in particular. Osteosarcomas tend to occur in the
metaphyses of growing bones and their site of skeletal predilection is proportional to the rate of
skeletal growth. It is not then surprising that most frequent sites affected are the distal femur and
the proximal tibia, which have the most rapid rates of skeletal growth in the body. It is also true that
osteosarcomas have a higher incidence in tall individuals than in short individuals. In dogs, they are
more common in large breeds than in small breeds. This tumor is distinguished radiographically by
radiodensity, which is a direct consequence of extracellular bone matrix production by the tumor cells.
This radiodensity is rather diffuse and resembles a sheet of raw cotton or cumulus clouds (as described
by Dr. Robert Freiberger, Chairman Emeritus, Department of Radiology, The Hospital for Special Surgery).
The radiograph also shows areas of radiolucency associated with radiodense areas, implying that the
lesion not only produces bone matrix but is also destructive, and has areas within it that do not
ossify. Another sign of malignancy is the absence of a discernible radiological transition zone, that
is, the x-ray does not show a defined exterior border where the tumor stops and where normal bone begins.
Finally, there is a sub-periosteal soft tissue mass which contains indistinct radiodensities composed of
vertically disposed bone spicules somewhat parallel to one another between the cortex and periosteum and
discontinuous in a so-called "sun-burst" reaction. It may be secondary to production of tumor bone
matrix, organizing subperiosteal bone production, or an admixture of both [62]. Because the new
spicules are discontinuous, the periosteal new bone formation is probably happening at a rapid rate; this
is a suspicious sign for an underlying malignancy. In between the sunburst reaction, there are rather
indistinct and confluent clouds of irregular radiodensity; these are characteristic of the irregular
ossification that is typical of osteosarcoma tumor matrix. In the lateral radiograph, there is a
so-called: "Codman's triangle," characterized by interrupted subperiosteal new bone that intersects the
cortex at an acute angle.
Histologically, the stroma of this tumor varies in cellularity, and its cells are sometimes
spindle-shaped, sometimes rather polyhedral, and occasionally resemble osteoblasts. Their nuclei are
most often vesicular with prominent nucleoli; they are also hyperchromatic and somewhat pleomorphic. The
mitotic rate is very high, and atypical mitoses are numerous. The tumor cells infiltrate the
intertrabecular spaces between pre-existent mature bone trabeculae and surround and replace the marrow
adipose tissue. The new bone formation is mainly disposed in microtrabeculae which first appear in wisps
but then become more coarse and widened. These new trabeculae are woven in their collagen fiber
pattern.
While sunburst periosteal reactions and Codman triangles are not in themselves specific for a
malignant tumor, either one is highly suggestive of a malignancy in the presence of an underlying
destructive intraosseous lesion. The Codman's Triangle is due to the confluence of subperiosteal new
bone and the underlying cortex and occurs just underneath the periosteum where it begins to separate from
the cortex. This thin shell of subperiosteal new bone seldom contains any tumor, and is usually far from
the tumor mass itself. On the other hand, the farther the free end of the periosteal new bone of the
Codman's triangle is from its point of cortical attachment, the more likely a subperiosteal biopsy will
be positive for tumor. Radiographic discontinuity of the periosteal reaction is characteristic of
malignant tumors. Both these features are well visualized upon examination of the specimen. The
specimen x-ray is somewhat more helpful in distinguishing true tumor bone formation from that formed by
the periosteum in the sunburst reaction. Here the ossified matrix tends to be irregular, less vertically
striate, and occupies the spaces between the parallel, more regular spicules of bone.
Microscopically, osteosarcoma is a heterogenous neoplasm with varying histological features
in different lesions and different areas of the same tumor. Since this is a matrix producing tumor, the
relationship between the tumor cells and the matrix is very important for the diagnosis. Evidence of
direct osteoid or bone production by sarcomatous tumor cells is essential for definitive diagnosis. The
predominant matrix component can be osteoblastic, chondroblastic, or fibroblastic. The tumor cells,
however, as noted in the sections invariably show areas of pink osteoid, sometimes admixed with other
matrix components. The sarcoma cells often are undifferentiated with pleomorphic spindle or round cells
or may have dense eosinophilic cytoplasm with eccenteric nuclei resembling osteoblasts, which on occasion
take on an epithelioid appearance. Mitotic figures are common including atypical ones. The osteoid
matrix of the tumor in early stages is made up of a dense fibrillary eosinophilic substance, which
separates and enmeshes the tumor cells. This, in turn, leads to a microscopic appearance of a lace-like
pattern well demonstrated in the sections. As ossification increases this unmineralized osteoid
eventually undergoes mineralization producing clearly recognizable trabeculae of woven bone. If a very
large amount of bone matrix is synthesized relative to the number of tumor cells, this matrix may
actually crowd out the obvious malignant cells, a process that Jaffe referred to as "normalization."
The major differential diagnosis is fracture callus, which may also produce bone,
cartilage, and fibrous tissue, thus emphasizing the utmost importance of clinical and radiographic
correlation and being able to discern true cytologic evidence for malignancy. In addition, fibrous
dysplasia may synthesize the same matrix elements and can be mistaken for the low-grade variant of
conventional osteosarcoma. Well-selected biopsy in combination with adequate review of radiographic
findings has facilitated histodiagnosis of osteosarcoma with ever-smaller biopsy techniques [61]. Modern
multi-modality chemotherapy has been successful in improving the prognosis. Tumor response to
chemotherapy as measured histologically is an important prognostic indicator for long term survival,
although more recently it has been suggested that the disease free survival is significantly influenced
by the tumor volume, patient age, and histologic subtype [60].
Points to remember:
| Tumor of fastest growing bones (commonly distal femur and proximal tibia) usually metaphyseal and usually in adolescents. |
| X-ray reveals radiolucent and radiodense areas without a well-defined transition zone. Sub-periosteal soft tissue masses may be evident as a sunburst periosteal reaction or as a Codman's triangle. |
| Microscopically, a bone-forming tumor with heterogenous histology. Identification of bone or osteoid synthesis by tumor cells is a prerequisite for diagnosis. |
| Prognosis is multifactorial, however, oncologists need for pathologists to evaluate the degree of necrosis if there has been neo-adjuvant (pre-operative) chemotherapy. |
|
|
Case 9: Chondrosarcoma - Right proximal femur in a 47 year-old male
Powerpoint Presentation
A 47 year-old male presented with right hip pain, worse at night. Spontaneous pain in any
cartilaginous lesion, while not a specific symptom, is suspicious for a malignant tumor. The
radiographic appearance of this lesion is also strongly suggestive of chondrosarcoma. The lesion is
radiolucent and occupies an ill-defined region below the trochanteric region of the femur, and its
borders are not distinct. Not only has there been focal erosion of the inner cortex, there is also focal
thickening of the cortex. This finding means that there has been both destruction of the cortex and slow
production of additional cortex external to the original cortex due to steady and gradual pressure
transmitted from the tumor to the cambium layer of the periosteum. The radiolucent lesion within the
bone contains a few stippled and ring-like densities characteristic of cartilage matrix. The lesion is
radiolucent because the cartilage has the same radiodensity as water. This history combined with these
radiological findings is virtually diagnostic of chondrosarcoma.
Benign cartilage tumors (enchondromas) are almost always asymptomatic and it is unusual for benign
cartilage tumors to become spontaneously tender unless there has been trauma or some other complication.
They are most common in the short tubular bones of the hands and feet and in the long tubular bones of
the extremities. The majority of benign cartilage tumors of hands, feet and long bones occur on the
metaphyseal side of the epiphyseal plate. They extend from the primary spongiosa all the way to the
center of the diaphyses and are thought to represent residua of non-reabsorbed cartilage derived from the
growth plate or from remnants of cartilage enlagen. Cartilage tumors are
radiolucent, and they calcify only if they become fairly large. There is sometimes encroachment of the
lesion on the inner cortex accompanied by cortical scalloping due to the pressure erosion of the cortex.
It is not unusual for an asymptomatic enchondroma to develop a pathologic fracture, because the hands and
feet are the most traumatized sites in the body. If a fracture has occurred, there may be a rather
cellular repair process with callus admixed with that of the lesion.
It is important to recognize that in the fingers and toes, a high degree of cellularity in a
cartilage lesion does not automatically imply malignancy. A lesion that might histologically represent a
low-grade chondrosarcoma, if it is derived from the pelvis usually means a benign lesion in the digits
[64]. This illustrates the pivotal role of radiographic correlation in the diagnosis of cartilage tumors
of long standing.
Histologically, this tumor is only moderately cellular. The chondrocytes are not so much arranged in
nodular aggregates as they are loosely and randomly, although the cartilage matrix itself is lobular.
The chondrocyte nuclei are enlarged and show both intranuclear detail and nucleoli. Double and multiple
chondrocyte nuclei per lacuna are easily found. There are no giant chondrocytes. There is also
significant necrosis of chondrocytes without accompanying calcification or ossification; this feature
suggests poorly controlled growth in a cartilage tumor and is ominous. On the other hand, mitotic
activity is virtually undetectable. Mitotic activity is uncommon in all but the highest-grade
chondrosarcomas [64] and has been used reproducibly in grading systems [63]. Even more recently,
expression of MIB-1 has shown a significant association with local recurrence and death in chondrosarcoma
[65]. Most importantly, the cartilage matrix of this lesion is present between intertrabecular spaces of
mature viable osseous trabeculae and within Haversian canals of viable cortical bone. This microscopic
evidence of permeation is histologically diagnostic for malignancy, regardless cellularity, nuclear
atypism, or mitotic activity. A benign cartilage tumor has a pushing border that does not infiltrate
intertrabecular spaces and especially Haversian systems of the cortex.
The tumor matrix grows characteristically in lobules of varying size, but these lobules may be
several centimeters in diameter because of the ability of hyaline cartilage to grow without a dedicated
vascular supply. The stippled areas in the x-rays represent irregular aggregates of calcification within
the cartilage. As this calcification progresses, water diffusion is inhibited and the cartilage becomes
more ischemic; it then becomes necrotic. This is followed by the same kind of neovascularization that is
seen on the metaphyseal side of a growth plate, and then by endochondral ossification. If the
endochodral ossification is within the center of the lobule, it comes to resemble popcorn on the plain
x-ray. If the endochondral ossificiation takes place at the periphery of the lobules, the bone is
deposited in incomplete arcs, and if it completely surrounds the cartilage lobules, it resembles rings
[64]. These are all features of a malignant cartilage tumor. In a long bone or a pelvic bone, the
diagnosis of a low-grade chondrosacoma may be made if either the radiograph or the histology demonstrate
features of malignancy. In a hand or foot bone, the diagnosis of malignancy in a cartilage tumor usually
requires the demonstration of malignant features both in the radiographs and in the histology.
Points to Remember:
| Presents with spontaneous pain, which may awaken the patient at night. Usually situated in the proximal long tubular bones or in the flat bones. |
| May present as a painless mass, particularly if arising in an osteochondroma. |
| Radiological appearance of a cartilage lesion (radiolucent with stippled calcifications & ring-like ossifications) with erosion of the inner cortex. The cortex may show irregular thickening. There may be a soft tissue mass. |
| Histologically variably cellular, randomly distributed chondrocytes with enlarged nuclei containing nucleoli and having visible internal detail. |
| Chondrocytes may have multiple nuclei per lacunae and involvement of intertrabecullar spaces of mature cancellous bone and within Haversian canals. Giant chondrocytes may be present. Mitoses point to a higher grade. |
| Cartilage lesions of small bones of hands and feet are almost always benign. |
|
|
Case 10: Metastatic Meningioma, left tenth rib of a 72 year-old man
Powerpoint Presentation
This 72 year-old man who was described by the operating surgeon as "otherwise healthy with no
significant past medical history" came into the emergency room of his local hospital complaining of pain
of acute onset in the lower left side of the thorax. Physical examination revealed a localized area of
tenderness associated with a palpable bump on the lower lateral chest wall. The x-rays demonstrate that
this area corresponded to the lateral portion of the left tenth rib, in which there was a sharply
circumscribed, expansile radiolucency involving the entire thickness of a 3-cm. segment of the rib. A CT
scan performed on the site revealed a sharply circumscribed, expansile radiolucency with thinning of the
cortex that demonstrated foci of complete cortical destruction, so functionally there was a non-displaced
pathologic fracture. No other clinical studies were performed in this patient, and the thoracic surgeon
opted to remove the entire segment of rib including the osseous defect and a segment of normal osseous
margin and surrounding soft tissue.
The approach to differential diagnosis of radiolucent lesions in the elderly is pragmatic. Any
radiolucent lesion presenting as a pathologic fracture in an individual older than 40 years of age should
be considered metastatic carcinoma until proven otherwise. Myeloma and malignant lymphoma are other
possibilities but are statistically less probable. Primary osseous lesions producing small,
circumscribed radiolucencies with fractures presenting in the ribs of elderly patients include fibrous
dysplasia and enchondroma. Soft tissue tumors may affect the ribs, particularly benign nerve sheath
tumors because of the relationship with intercostal nerves. While nerve sheath tumors may erode the
ribs, they are eccentric and not centered in the ribs. This lesion is not a soft tissue tumor
radiologically because it is centered in the bone and causes symmetric, fusiform osseous expansion with
internal cortical thinning.
The clinical choices are to work the patient up before choosing to biopsy the lesion, doing a closed
or open biopsy of the lesion, or excising the lesion. The reasons for making the designated choices
include the overall physical condition of the patient, the affordability of the workup, and the time
element involved. Metastatic carcinoma to bone is derived from primary tumors of the lungs, breast,
kidney, prostate, or thyroid in 80% of cases. Consequently, a pre-biopsy work up should include CT of
the chest/abdomen, sometimes with abdominal ultrasound, a good rectal examination with a PSA level drawn
before digital prostatic manipulation, a thyroid scan after careful neck palpation, and a breast exam
including mammography in females. One might include a bone scan to rule out other osseous lesions and a
skeletal survey if the bone scan is positive (several lesions are much more likely to represent
metastases than primary tumors). Myeloma is usually silent on a bone scan even when visible on the x-ray
provided there is no fracture. A serum protein electrophoresis and urine for Bence-Jones protein is
useful in multiple myeloma but is less fruitful in solitary plasmacytoma. All of this work up, it should
be remembered, takes time and money. It is advantageous because it may do something that the pathologist
can not: actually name the site of the primary tumor. It is disadvantageous because the patient might
find it hard to wait for a diagnostic work up and because the insurance company may not agree to pay for
it.
A needle biopsy or an open biopsy may be fraught with complications. For example, metastatic renal
cell carcinoma may result in barely controllable bleeding even from a skinny needle biopsy tract. In the
event that the defect turns out to be a malignant primary bone tumor, the biopsy tract must be excised
with the lesion and may complicate or compromise the definitive surgery. Furthermore, a biopsy may reach
only the periphery of a lesion and may not be representative of the entire process. Even if a diagnosis
of metastatic carcinoma is made, the primary site may not be specifiable. Since this was a small,
clinically solitary lesion in a non-vital area, the surgeon simply removed the entire lesion with a cuff
of surrounding normal tissue (a marginal excision which turns out to be a small radical excision).
The real problem, then, rests with the pathologist who has to interpret what is a very unusual
histopathology for a rib lesion. When one of us was consulted for this case, all of the radiographic
differential diagnoses listed above were considered prior to looking at the histologic section. The
section demonstrates a space-occupying lesion composed of spindle cells, but the pattern of these cells
and their cytologic features do not make sense in the context of either a metastatic epithelial tumor or
a primary bone tumor. First, while the lesion is very definitely hypercellular, the spindle cells are
bland and the mitotic rate is exceptionally low. Metastatic carcinomas that show spindle cell
differentiation are usually composed of bizarre cells with hyperchromatic nuclei and show high mitotic
rates. Primary fibrous lesions of bone that are benign are usually less cellular than this lesion.
Some, like fibrous dysplasia, usually demonstrate evidence of immature bone formation or show
cartilaginous differentiation (see case 5). Although fibrous dysplasia has been described as having a
slightly whorled pattern, this lesion is more storiform than even most fibrohistiocytic lesions and
contains whorls that resemble the stars in Van Gogh's "The
Starry Night." Benign fibrous lesions that approach the cellularity and pattern of this
lesion would include non-ossifying fibroma (see Case 1) and benign fibrous histiocytoma. The former has
a different radiographic appearance, age range, and skeletal distribution than the process in these
sections. The latter may be a larger and atypical adult variant of non-ossifying fibroma. Both lesions
are thought to be fibrohistiocytic and often contain histiocytes and/or foamy macrophages; this lesion
does not. To the referring pathologist, this was thought to be a benign lesion, but one that could not
easily be classified.
The key to the diagnosis of this case is having either a really thorough history or absolutely
divergent thinking when looking at the histologic sections. Since a very thorough history was not
available, the way this diagnosis was initially arrived at was to throw away every preconceived notion
about tumors and their behavior and look at the tissue by its morphology alone---ignoring its site of
origin and the known patient history. Histologically, this lesion shows indolent though locally
aggressive behavior. There is replacement of the marrow cavity and destruction of the overlying cortex.
The spindle cell stroma is not only storiform but also shows separation of tumor cells by long, thin
collagen fibers and contains whorls that in some places appear almost epithelial. Some of the whorls
consist of large groups of plump cells with indistinct borders; others comprise a very few cells and are
reminiscent of squamous pearls. The nuclei are bland and vesicular. A very few nuclei have distinct
intranuclear clear vacuoles. These characteristics are typical for both the fibrous and transitional
forms of meningioma, but because this lesion
arises in a rib and because there is no pertinent past medical history one's mind-set is not immediately
led toward this diagnosis. To test this hypothesis, the lesion was shown without history to the senior
neurosurgical pathologist at Mt. Sinai. The neuropathologist immediately pronounced the lesion a
meningioma of fibrous or transitional type and asked whether the skeletal muscle in the sections was from
the temporalis muscle. He was informed that the skeletal muscle was, in fact, intercostal muscle and asked if this would change his diagnosis. He said that if
he had been told that the lesion came from a rib, he might never have considered the diagnosis of
meningioma at all! The diagnosis of metastatic meningioma was conveyed, rather trepidaciously, to the
referring pathologist who questioned the consultant's sanity. Upon careful questioning by the referring
pathologist, the thoracic surgeon later revealed that the patient had had a craniotomy 12 years prior to
the rib resection ("But it was for a benign meningioma," the surgeon said, "and how could that be
relevant to his present problem?"). The original sections were obtained from the hospital where the
patient had his craniotomy, and the histology of the original meningioma and that of the rib lesion were
virtually identical. Immunohistochemistry on the sections derived from the rib mass is weakly positive
for cytokeratin, strongly positive for epithelial membrane antigen and vimentin, and negative for S-100
protein, giving even more credence to the diagnosis. At last contact the patient was 79 years old and
remained tumor free seven years after the resection.
Meningioma, which is a tumor arising from the leptomeninges, is almost always a benign tumor, and it
has a metastatic incidence of less than one per thousand [72]. Many of the reports that have described
metastasis associated with this tumor have included cases of hemangiopericytoma , which have been
confused with angioblastic meningioma [67]. Still other cases of metastatic meningioma have included
those of atypical or frankly malignant cytology
[66,
67,
73]
, those which have recurred locally following
initial surgery
[68,
69,
74]
, papillary meningiomas [70]. Meningioma occuring at a distant site has also
been reported as a result of unintentional iatrogenic implantation [71]. Virtually all reported cases
have presented only after surgery on the primary tumor and not as metastases from an occult primary
tumor, hence underscoring the importance of an accurate history.
While this case illustrates a somewhat challenging diagnosis, its take-home lesson is that even
solitary radiolucent lesions in the elderly should be considered metastatic until proven otherwise.
Points to Remember:
| Holes in bones occurring in patients over 40 are metastases until proven otherwise. Multiple holes in bones are more likely metastatic than solitary holes. |
| 80% of skeletal metastases come from one of five primary sites: Breast, lung, thyroid, kidney, and prostate (mnemonic: B.L.T. with Kosher Pickle). |
| Making the diagnosis of the correct primary is a matter of getting a good history, having the right immunohistochemistry, or often, from sheer luck. |
| Meningioma metastasizing outside the C.N.S. is very unusual in the absence of highly atypical histology or previous surgeries. |
|
|
References
General Considerations
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- Gilkey, F., Sweet, D.E., and Mirra, J.: Radiologic/Pathologic Correlation of Bone Tumors. in Bone Tumors, Clinical, Radiologic, and Pathologic Correlations, 2nd Edition, Chapter 27, p 1803-1831, Ed. Mirra,J.,J.B. Lippincott Co., Philadelphia,PA, 1989.
- Greenspan, A., and Klein, M.J.: Radiology and Pathology of Bone Tumors (In Musculoskeletal Oncology: An Interdisciplinary Approach. (Philadelphia: W.B. Saunders Co., 1992),13-72.
- Kahn, L.B., Wood, F.W., and Ackerman, L.V.: Fracture Callus Associated with Benign and Malignant Bone Lesions and Mimicking Osteosarcoma. Amer.J. Clin. Path. 52:14-24, 1969.
- Lodwick, G.S.: Predictor Variables in Bone Tumors. Seminars in Radiology 1:293, 1966.
- Madewell, J.E., Ragsdale, B.D., Sweet, D.E. Radiologic and Pathologic Analysis of Solitary Bone Lesions. Part I. Internal Margins. Radiol. Clin. North Am..19: 715-48, 1981.
- McLeod, R.A., and Berquist, T.H.: Bone Tumor Imaging: Contribution of C.T. and M.R.I. In Bone Tumors, K.K. Unni, Ed. (1988: Churchill Livingstone, New York), 1-34.
- Milch, R.A. and Changus, G.W.: Response of Bone to Tumor Invasion. Cancer 9:340-351, 1956
- Olendorf, W., and Olendorf, W.Jr.: MRI Primer (New York: Raven Press), 1991.
- Ragsdale, B.D., Madewell, J.E., Sweet, D.E. Radiologic and Pathologic Analysis of Solitary Bone Lesions. Part II: Periosteal Reactions. Radiol. Clin. North Am. 19:749-83, 1981.
- Spjut, H.J., Dorfman, H.D., Fechner, R.E., and Ackerman, L.V.: Tumors of Bone and Cartilage (In: Atlas of Tumor Pathology, Fascicle 5, Series 2, Armed Forces Institute of Pathology, Washington, D.C.), 1971.
- Sprawls, Perry The Physical Principles of Diagnostic Radiolggy (Baltimore: University Park Press), 1977.
- Sprawls, Perry The Physical Principles of Diagnostic Imaging (Baltimore: University Park Press), 1987.
- Squire, L. F.: Fundamentals of Roentgenology , Fourth Edition (Boston: Harvard Press), 1988.
- Sweet, D.E., Madewell, J.E., Ragsdale, B.D. Radiologic and Pathologic Analysis of Solitary Bone Lesions. Part III: Matrix Patterns. Radiol. Clin. North Am. 19:785-814, 1981.
Case 1
- Caffey, J.: On Fibrous Defects in Cortical Walls of Growing Tubular Bone: Their Radiologic Appearances, Structures, Prevalence, Natural Course and Diagnostic Significance. Adv. Pediatr. 7:13-51, 1955.
- Hoeffel,C., Panuel, M., Plenat, F., Mainard, L.. Hoeffel, J.C.: Pathological Fracture in Non-ossifying Fibroma with Histological Features of Aneurysmal Bone Cyst. Eur. Radiology 9(4):669-71, 1999.
- Kotzot, D., Stoss, H., Wagner, H., Ulmer, R.: Jaffe-Campanacci Syndrome: Case Report and Review of Literature. Clin. Dysmorphol. Oct;3(4):328-334, 1994.
- Matsuo,M., Ehara, S., Tamakawa,Y., Kitagawa, Y., Abe, M., Sakuma, T.: Aggressive Appearance of Non-ossifying Fibroma with Pathologic Fracture: A Case Report. Radiat. Med. Mar-Apr;15(2):113-115, 1997.
- Mirra, J.M., Bone Tumors, Clinical, Radiologic, and Pathologic Correlations (Philadelphia, Lea and Febiger), 1989.
- Toriello, H.V., Bultman, R., Panek, R.W. et.al., Non-ossifying Fibromas and Giant Cell Reparative Granulomas in a Child with Oculo-ectodermal Syndrome. Clin. Dysmorphol. Oct;8(4):265-268, 1999.
Case 2
- Birch, M.A., Taylor, W., Frazer, W.D. et.al.: Absence of Paramyxovirus RNA in Cultures of Pagetic Bone Cells and in Pagetic Bone. J.Bone Mineral Res. Jan; 9 (1):11-16, 1994.
- Bullough P.G.: Bullough and Vigorita's Orthopedic Pathology. Mosby- Wolfe Press. pp156-167, 1997.
- Cody, J.D., Singer, Roodman, G.D. et.al.: Genetic Linkage of Paget Disease of the Bone to Chromosome 18q. Am.J.Hum.Genet. Nov; 6(5):1117-22, 1997.
- Dorfman, H.D, Czerniak. B ; Bone Tumors. Mosby Press; 1195-1206, 1998.
- Halbach H, Farrel C, Ditrich F.J. Neoplasms arising in Paget's disease of bone: a study of 82 cases. J.Clin.Pathol 83:594-600, 1985.
- Helfrich, M.H., Hobson, R.P., Grabowski,P.S., et.al.: A Negative Search for a Paramyxoviral Etiology of Paget's Disease of Bone: Molecular, Immunological, and Ultrastructural Studies in UK Patients. J.Bone Mineral Res. Dec; 15 (12):2315-29, 2000.
- Kurihara, N., Reddy, S.V., Menan, C., et.al.: Osteoclasts Expressing the Measles Virus Nucleocapsid Gene Display a Pagetic Phenotype. J. Clin. Invest Mar.; 105(5)607-614, 2000.
- Mirra J.M, Brien E.W, Tehranzadeh J. Paget's disease of bone; review with emphasis on radiological features. Part II: Skeletal Radiol; 24:175-184, 1995.
- Paget J; On a form of chronic inflammation of bones (Osteitis Deformans). Med.Chr.Trans. 60; 37, 1877.
- Rebel A, Basle M, Pouplard A, Kouyoumdjan S, Filmon R, Lepatezour A; Viral antigens in osteoclasts from Paget's disease of bone contained viral antigenic material: ultrastructural and immunological studies suggested that measles or measles related virus was the agent involved. Lancet 16:344-346, 1980.
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Case 3
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Case 5
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Case 6
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Case 7
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Case 8
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Case 9
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Case 10
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