Malignant tumors

Radiology residents have difficulty dealing with malignant bone tumors, and the difficulty gets worse in the years after residency. This is simply because malignant bone tumors, thankfully, are not very common. Nevertheless, every radiologist will encounter one or two a year in most practices and should be able to recognize them and provide a good differential diagnosis.

First, how do you recognize a malignant tumor and differentiate it from a benign process? This can be difficult and often even impossible. Recognizing that it is aggressive is usually easy, but saying that it is malignant is another matter altogether. Processes such as infection and eosinophilic granuloma can mimic malignant tumors and are, of course, benign. They will often be included in the differential diagnosis of an aggressive lesion along with malignant tumors.

Differentiation of malignant from benign

What radiologic criteria are useful for determining malignant versus benign? Standard textbooks and the literature give four aspects of a lesion to be examined: (1) cortical destruction, (2) periostitis, (3) orientation or axis of the lesion, and (4) zone of transition.

Let me expound on each of these criteria and show why only the last one—the zone of transition—is the most reliable, with an accuracy rate of 90%.

Cortical destruction

Often cortical bone is replaced by part of the noncalcified matrix (fibrous matrix or chondroid matrix) of benign fibro-osseous lesions and cartilaginous lesions. This can give the false impression of cortical destruction on plain films (Figure 3-1) or computed tomography (CT). Also, benign processes such as infection and eosinophilic granuloma can cause extensive cortical destruction and mimic a malignant tumor. Aneurysmal bone cysts are known to cause such thinning of the cortex as to make it radiographically undetectable (Figure 3-2). For these reasons I find cortical destruction to occasionally be misleading. Cortical destruction makes one think of a malignant lesion when using the Gestalt approach, but the lesion must also have other criteria for a malignant process, such as a wide zone of transition.

FIGURE 3-1 Apparent cortical destruction. This benign chondroblastoma has noncalcified chondroid tissue replacing cortical bone in the proximal femur, which gives the lesion a destructive appearance. This is an example of cortical replacement rather than of cortical destruction, which can be very confusing if one uses cortical destruction as an aggressive or malignant key in differential diagnosis. Note that the zone of transition is narrow, as one would expect in a benign lesion such as this.

FIGURE 3-2 A, Aneurysmal bone cyst. This benign lesion has thinned the cortex to such a degree as to make it imperceptible on a plain radiograph. As in Figure 3-1, this can be misconstrued as cortical destruction, giving the false impression of a malignant or very aggressive lesion. B, Giant cell tumor. This lesion in the proximal femur has expanded and thinned the cortex to such a degree that it is imperceptible on the plain film. C, On a CT scan through this region a very thin cortex that was greatly expanded was identified. This giant cell tumor originated from the greater trochanter, which is an epiphyseal equivalent. Note that it has a well-defined but nonsclerotic zone of transition, as all giant cell tumors in long bones do.

Periostitis

Periosteal reaction occurs in a nonspecific manner whenever the periosteum is irritated, whether it is irritated by a malignant tumor, a benign tumor, infection, or trauma. Callus formation in a fracture is actually just periosteal reaction of the most benign type. Periosteal reaction occurs in two types: benign (Figure 3-3, A and B) and aggressive (Figure 3–3, C and D). The difference between the two is based more on the timing of the growth of the irritation than on whether the process causing the periostitis is malignant or benign. For example, a slow-growing benign tumor will cause thick, wavy, uniform, or dense periostitis because it is a low-grade chronic irritation that gives the periosteum time to lay down thick new bone and remodel into more normal cortex. A malignant tumor causes a periosteal reaction that is high grade and more acute; hence, the periosteum does not have time to consolidate. It appears lamellated (onion skinned) or amorphous, or it may even appear sunburst. If the irritation stops or diminishes, the aggressive periostitis will solidify and appear benign. Therefore, when periostitis is seen, the radiologist should try to characterize it into either a benign (thick, dense, wavy) type or an aggressive (lamellated, amorphous, sunburst) type.

FIGURE 3-3 Benign periostitis. A, An osteoid osteoma in the midshaft of the tibia has caused thick, wavy, dense periostitis, which is classic for benign type of periostitis. Malignant lesions are incapable of forming this type of periostitis and should not be considered in the differential. This type of periostitis is basically indistinguishable from callus formation in a fracture. B, Thick, wavy periostitis (arrows) along the ilium in a child with a permeative lesion in the pelvis is characteristic for infection or eosinophilic granuloma. Ewing’s sarcoma was initially considered in the differential; however, the benign periostitis would make a malignant lesion very unlikely. Biopsy showed this lesion to be eosinophilic granuloma. C, Aggressive periostitis. Amorphous, sunburst periostitis with a Codman’s triangle (arrows) in a patient with a mixed lytic-sclerotic lesion of the humerus, which on biopsy was shown to be Ewing’s sarcoma. Although this type of periostitis is characteristic for a malignant lesion, it could also be seen with benign processes such as eosinophilic granuloma or infection. D, Lamellated, or onion-skinned, periostitis is characteristic of an aggressive process, such as in this patient with Ewing’s sarcoma of the femur. Again, this aggressive type of periostitis could conceivably occur in a benign process such as infection or eosinophilic granuloma.

Unfortunately, judging the lesion by its periostitis can be misleading. First, it takes considerable experience to accurately characterize periostitis because many times the reaction is not clearly benign or aggressive. Second, many benign lesions, such as infection, eosinophilic granuloma, aneurysmal bone cysts, osteoid osteomas, and even trauma, cause aggressive periostitis. Seeing benign periostitis, however, can be helpful because malignant lesions will not cause benign periostitis. Some investigators with great experience in dealing with malignant bone tumors state that the only way benign periostitis can occur in a malignant lesion is if there is a concomitant fracture or infection. I have seen a few exceptions, but overall I think it is a valid statement.

Orientation or axis of the lesion

The orientation or axis of the lesion is a poor determinant of benign versus aggressive and seldom helps me decide into which category the lesion should be placed. It has been said that if a lesion grows in the long axis of a long bone, rather than being circular, it is benign. Nonsense! Ewing’s sarcoma, an extremely malignant lesion, usually has its axis along the shaft of a long bone. Conversely, many fibrous cortical defects are circular yet totally benign. I see no reason to even consider the axis of a lesion as part of its radiologic evaluation.

Zone of transition

Without question the zone of transition is the most reliable indicator in determining benign versus malignant lesions. Unfortunately it also has some drawbacks, on which I will elaborate.

The zone of transition is the border between the lesion and the normal bone. It is said to be narrow if it is so well defined that it can be drawn with a fine-point pen (Figure 3-4). If it is imperceptible and cannot be clearly drawn, it is said to be wide (Figure 3-5). Obviously all shades of gray lie in between, but most lesions can be characterized as having either a narrow or a wide zone of transition. If the lesion has a sclerotic border, it, by definition, has a narrow zone of transition.

FIGURE 3-4 Narrow zone of transition. The border of normal bone with a lesion is known as the zone of transition. When, as in this example of a nonossifying fibroma, the border can be drawn with a fine-point pen it is said to be a narrow zone of transition, which is characteristic of a benign lesion. A narrow zone of transition may or may not have a sclerotic border.

FIGURE 3-5 Wide zone of transition. A lytic permeative process is seen in the midshaft of the femur in this patient. On biopsy it was found to be a malignant fibrous histiocytoma. The zone of transition in this lesion is said to be wide, because it cannot be easily drawn with a fine-point pen. A permeative lesion such as this, by definition, has a wide zone of transition.

If a lesion has a narrow zone of transition, it is a benign process. The exceptions to that are rare, and I’m willing to miss them. If a lesion has a wide zone of transition, it is aggressive. Notice that I said aggressive and not malignant. As with aggressive periostitis, many benign lesions can have a wide zone of transition. A few of the same processes that can cause aggressive periostitis, and thereby mimic a malignant tumor, can have a wide zone of transition (i.e., infection and eosinophilic granuloma). They are aggressive in their radiographic appearance because they are fast-acting, aggressive lesions. The zone of transition is usually easier to characterize than the periostitis, plus it is always there to evaluate (or you wouldn’t see a lesion), whereas many lesions, benign and malignant, have no periostitis. For these reasons the zone of transition is the most useful indicator of whether a lesion is benign or malignant.

A lesion that consists of multiple small holes is said to be permeative. It has no perceptible border and therefore has a wide zone of transition. Round cell tumors such as multiple myeloma, primary lymphoma of bone (formerly called reticulum cell sarcoma), and Ewing’s sarcoma are typical of this type of lesion. However, infection and eosinophilic granuloma (Figure 3-6) can have the same appearance.

FIGURE 3-6 Permeative pattern. A permeative pattern is defined as multiple, small, irregular holes in bone and indicates an aggressive process. Ewing’s sarcoma typically has a permeative pattern; however, infection and eosinophilic granuloma, as in this example, can also have a permeative pattern. This is a fine-detailed film of the same case shown in Figure 3–3, B.

The zone of transition applies only to lytic or predominantly lytic lesions. A blastic or sclerotic lesion will always appear to have a narrow zone of transition and may erroneously be included in the benign differential even if it is malignant.

It is critical to be aware that the zone of transition is a plain film finding and cannot be used with magnetic resonance imaging (MRI). Many malignant tumors will appear to have narrow zones of transition on MRI examinations and can mislead one into thinking a benign lesion is present (Figure 3-7). The zone of transition can be used only with lytic lesions and on plain films.

FIGURE 3-7 Zone of transition on MRI. A, A T2-weighted MRI scan of the knee in this child with knee pain shows a well-defined lesion (arrow) with a low signal border, suggesting a narrow zone of transition with a sclerotic border. Because the knee pain was described as probably related to the menisci, this lesion was believed to be an incidental, benign process, such as a nonossifying fibroma. However, the plain film (B), obtained later, shows a barely discernible lytic lesion with a wide zone of transition (arrow). This lesion was, in fact, painful, and the differential diagnosis, based solely on the plain film, would include osteosarcoma—the eventual histologic diagnosis. The zone of transition can be used only on plain films; it is invalid on MRI scans.

Differentiating types of tumors

Once it has been decided that a particular lesion is probably malignant, the differential is fairly straightforward. First, the list of malignant tumors is relatively short, and second, most tumors follow somewhat strict age groupings. Jack Edeiken, a famed skeletal radiologist, evaluated 4000 malignant bone tumors and found that they could be correctly diagnosed 80% of the time by using only the patient’s age! He basically divides the tumors into decades of when they will affect a patient; for example, osteosarcoma and Ewing’s sarcoma are the only childhood primary malignant tumors of bone, and after the age of 40, only metastatic disease (mets), myeloma, and chondrosarcoma are common (Table 3-1). Although there are certainly outliers that are uncommon, these age guidelines are extremely useful. It is inappropriate to mention Ewing’s sarcoma in a 40-year-old or mets in a 15-year-old. Obviously, if a 15-year-old has a known primary tumor, then mets must be considered—in fact, any bone lesion, regardless of its appearance, could be a met and would be suspicious in a patient with a known primary tumor.

TABLE 3-1

Malignant Tumors and Patient Age

Age (yr)	Tumor
1–30	Ewing’s sarcoma
	Osteosarcoma
30–40	Fibrosarcoma and malignant fibrous histiocytoma
	Malignant giant cell tumor
	Primary lymphoma of bone
	Parosteal sarcoma
40+	Mets
	Myeloma
	Chondrosarcoma