D URING the course of our routine work

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1 THE ROENTGENOGRAPHIC APPEARANCE OF RENAL CANCER METASTASIS IN BONE ROBERT S. SHERMAN, M.D., and T. ARTHUR PEARSON, M.D.* D URING the course of our routine work it occurred to us that renal cancer metastatic to bone might occasionally present certain unique characteristics in the roentgenogram. To test the value of this impression we have studied the material available at Memorial Hospital from the standpoint of roentgen-ray diagnosis. This consists of thirty-six proved cases of renal cancer metastases in bone that have adequate roentgenographic coverage. Each case had at least one pathological report indicating renal cancer origin, based on tissue from the primary tumor, from the metastasis, or in certain instances from both. The pathological diagnosis might have come from the surgical specimen or biopsy, aspiration biopsy, or post-mortem specimen. If biopsy of a metastasis were reported as cancer, indicative of renal origin, and if, in addition, pyelographic evidence of renal tumor were conclusive, the case was accepted. Similarly, if a renal cancer were removed and metastases were subsequently rewaled in the bones, the case was included. In no instance does diagnbis rest on roentgenographic cvidence alone. Early studies on metastases to hone from renal cancer were made by Scudder and Gibson and Bloodgood. The latter, in commenting on radiographic appearance, stated that the lesion was always destructive without any element of production, and that there were no roentgenographic findings that diff erentiated hypernephroma from any othcr form of skeletal carcinomatous metastases. More recent reports were made by Copeland, Fort, Gillies, Turner and Jaffe, Herger and Sauer, and Abeshouse. When the radiographic appearance was commented upon, From the Department of Diagnostic Roentgenology, Memorial Hospital, New York, N. Y. * Assistant Radiologist, New York Hospital, New York, N. Y. Received for publication, February 10, I 948. renal cancer metastases in bone were held to be generally osteolytic and to show no specific features. Recently Fried collected eighty-seven cases of renal cancer from the files of Montefiore Hospital: 45 per cent, or thirty-nine cases, had metastasized to bone. In 43 per cent of these thirty-nine, the involvement was solitary. Fried stated that the osscous lesions were always destructive, rarely produced new bone. He was chiefly interested in roentgen-ray treatment and reported little if any local symptomatic improvement, and occasionally growth continued in spite of radiation. CLINICAL FEATURES Twenty-three of our thirty-six cases were in men, thirteen in women. The age range of the patients was from 27 to 70 years. In twenty-eight, the first symptom that was responsible for the initial visit to the physician was the disease in bone. Pain was the outstanding complaint in thirty-two cases. In twenty-one, localized swelling was revealed. Four patients had pulsating tumors. Ten patients had had a renal cancer removed previously. The time interval between the nephrectomy and the appearance of the metastasis varied as follows: one, one month; four, one year; one, two and one-half years; one, three years; two, six years; one, ten years. The Pathological Laboratories of Memorial Hospital made the following diagnoses : adenocarcinoma, renal type, twentyfive cases; renal carcinoma, six; hypernephroma, three ; embryonal carcinoma, two. No correlation between the cell type and the roentgenographic appearance of the metastases was evident. A primary bone tumor was diagnosed clinically in thirteen patients, osteogenic sarcoma being the most frequently suspected. Other clinical diagnoses were endothelioma,

2 THE ROENTGENOGRAM OF RENAL CANCER METASTASIS IN BONE Pearson 77 angioma, cancer of the lung, parotid tumor, Brodie s abscess, myeloma, and cyst. Fourteen cases were diagnosed as metastases. Some patients came to the hospital with the correct diagnosis previously established. In a number no clinical diagnosis was offered. Eighteen cases were diagnosed roentgenologically as metastatic. An additional four were described simply as bone destruction while some were called malignant tumor. There were four cases, however, in which the roentgenographic diagnosis was osteogenic sarcoma. There were instances in which diagnoscs of myeloma, hemangioma, and even giant-cell tumor and bone cyst were offered. In no instance was the diagnosis of renal cancer metastasis made on the basis of the roentgenographic appearance alone. The number of incorrect diagnoses, both rlinical and roentgenographic, and even the occasional indeterminate pathological report, emphasizes a difficulty that, in our experience, is not usually encountered in metastases secondary to primary cancer in breast, lung, prostate, or less common sources (Fig. I). In fact, amputation has becp done on a mistaken diagnosis of primary bone tumor. This difficulty is probably due not only to our failure, in the past, to appreciate the varied appearance of renal cancer in bone, but also to the tendency of this form of primary growth to remain silent, the relatively slow rate of growth of some renal cancers, and the rather high percentage of solitary mrtastases. It is hoped that the present study will improve our roentgenographic diagnoses in the future. ROENTGENOGRAPHIC DIAGNOSIS In attempting to determine the roentgeno- FIG. I. Cancer metastasis in an unusual site diagnosed clinically and radiographically as carcinoma of the antrum. A qualified pathological report of angiosarcoma of bone on biopsy was given. Autopsy proof of renal primary tumor followed.

3 CANCER July 1948 FIG. 2. A, Lytic type cancer metastasis in the shaft of the humerus with pathological fracture. B, After roentgen-ray treatment the fracture healed. The metastasis now resembles the septate form. This is an instance of exceptional response to roentgen-ray treatment. graphic appearance of renal cancer metastatic to bone, we intend to follow the more or less standard plan that we pursue in making a roentgenographic diagnosis in any case of bone tumor. This system recognizes, as the logical and productive approach, the need to analyze each of the basic features that may be encountered. The following information derives from an examination of the earliest roentgenogram available in each instance. Later on, subsequent negatives were studied to note the effects of growth and of treatment as the case might be. Based upon roentgenographic evidence, twenty-one of the thirty-six cases were solitary, i.e., only a single metastasis was revealed in the roentgenograms. In the fifteen instances where two or more tumors were seen, the largest or most significant tumor was described, because it had been found that all the metastases in any one case were fundamentally alike. Location in Skeleton. The twenty-one instances of solitary metastases were distributed as follows: humerus 4 maxilla I pelvis 4 skull I femur 3 rib I spine 2 scapula I mandible 2 tibia I fibula I In the fifteen patients showing two or more areas of metastases an equally diffuse distribution in the skeleton was encountered. It is

4 THE ROENTGENOGRAM OF RENAL CANCER METASTASIS IN BONE Sherman t3 Pearson [279 differentiated in two tumors arising in the maxilla. There was no instance of subperiosteal cancer metastasis noted in this material. Symmetry in Bone, This term refers to the position of the tumor relative to the long axis of the bone in both sagittal and lateral projections and applies specifically to tumors in the tubular bones. There were nineteen in which symmetry could not be determined. Of the remainder, fifteen were symmetrically FIG. 3. Patchy type of cancer metastasis showing an unusual degree of periosteal reaction for kidney cancer metastasis. evident that there is no significant site of predilection for renal tumor metastases to bone in this series. Location in Bone. By this we refer to the part of bone involved, i.e., epiphysis, metaphysis, or diaphysis. Application of this feature is limited to the tubular bones. There were fifteen cases in which the lesion was in a long bone. Of these, three were in midshaft, ten toward the ends, and two at the ends, i.e., in the former epiphyseal areas. Site of Origin. It is usually possible to determine whether a tumor arises from the cortical or the medullary portion of a bone. In thirty-four of the thirty-six cases, the medulla was thought to be the site of origin. Cortical and medullary origin could not be FIG. 4. Septate type of cancer metastasis in the distal portion of the shaft of the femur.

5 2801 CANCER July 1948 positioned and two were not. In the tubular bones, therefore, symmetry is to be expected in renal tumor metastases. Direction of Growth. Many times it is possible to postulate the growth direction of tumors occurring in bones. Some tend to travel and extend within the bone itself, while others may break out of the bone relatively early and expand in the periosseous structures. There were twenty tumors in which no clear distinction between these two different courses of growth could be discerned. In twelve, growth seemed to occur principally within the bone, and in four there was an early or pronounced tendency to grow outward, beyond the bone. General Configuration. The over-all shape of a bone tumor may be one of its important romtgenographic characteristics. In determining shape, both the osseous and the peri- OSS~OUS part of the lesion must be considered and both sagittal and lateral views are necessary to reconstruct three dimensional aspects. Only a general statement pertaining to shape is indicated; terms such as spherical, oval, and fusiform are sufficiently informative. There were three cases with spherical metastases, three with fusiform, and twenty-seven with oval metastases. There were three instances in which the general configuration could not be determined with assurance. It seems that an oval shape is the one to be expected in renal cancer metastases in bone. Destruction and Production in Medullary Bone, In judging the degree of destruction and production, the density of the normal neighboring bone was used as the basis of comparison. Calcification and the formation of normal or abnormal bone were considered productive changes. Destruction of medul- FIG. 5. An unusually large metastasis of the septate type in the ilium. This is to be differentiated from the lrsolitaryj form of myeloma.

6 THE ROENTGENOGRAM OF RENAL CANCER METASTASIS IN BONE Sherman G? Pearson [28 I FIG. 6. Septate form in the distal portion of the shaft of the femur. lary bone was present to some degree in each of the thirty-six cases. In seventeen, it was unaccompanied by any productive change; in sixteen, destruction predominated over varying degrees of productive change, while in three destruction and production were considered to be about equal in degree. In no tumor did production predominate. Destruction of bone is thus seen to be a constant finding in renal cancer metastases. In thirty-three of the thirty-six cases it was present to a greater degree than productive change. In no case was production the outstanding feature. Pattern. Eighteen tumors had no internal pattern whatsoever (Fig. 2 A). In an additional nine there were either a few scattered indefinite calcific flecks or a few sketchy incomplete septa within the area of destruction. These twenty-seven cases were designated the lytic-pattern tumors. In three cases, the pattern of the tumor showed fine patchy areas of destruction around which there seemed to be nearly normal-appearing bone. While these were predominantly drstructive lesions, the total amount of destruction was relatively small compared to the tumor area (Fig. 3). This pattern was called the patchy type. There were six tumors in which the structure was unusual. These were characterized by large, well-formed, coarse, heavy septa running through the area of destruction. These six cases were designated as the septate type (Figs. 4, 5, and 6). Boundary. The boundary of a tumor includes all portions, both osseous and periosseous. The border in these tumors varied from indistinct to clear-cut. Except for the fact that the periphery of these lesions was generally more apparent than is the case for metastases in general, no further significance could be attached to this feature. Cortex. Destruction of the cortex was found in varying degrees in thirty-five of the cases. In one there was evidence indicating slight cortical expansion. The destruction varied from a tiny area of erosion to large areas of cortical bone loss. Cortical destruction appears to be another rather constant feature for this type of cancer metastasis. Periosteum. In thirty-one instances in this series there was no periosteal reaction evident on the initial roentgenograms. In several of these thirty-one, however, periosteal reaction would not be expected to show, for instance, in those lesions in the vertebrae or in the maxilla. A reaction of the periosteum did occur five times, in three of which the change was graded as moderate and in two as minimal. In these five cases there was a perpendicular type of reaction twice and a parallel type four times, the two forms being recognized simultaneously in one instance. Periosseous Mass. A mass extrinsic to the bone was formed in twenty-nine cases. In seven the mass was small, in fifteen it was moderate in size, and in seven it was described as large. In general, the size of the soft-tissue mass was related to the size of the osseous part of the tumor, so that in those called moderate periosseous mass the area

7 2821 CANCER July 1948 of bone involvement and the size of the softtissue mass were approximately equal. Joint Changes. Occasionally tumors occurring at or near a joint can cause changes in the joint that may be of value in formulating a roentgenographic diagnosis. Synovitis and growth into or even across a joint are examples of such findings. There was no evidence of synovitis in this group. None of the large body joints showed any significant effect. Pathological Fracture. There were fourteen pathological fractures in this series. In several tumors the bone was so destroyed that any semblance of continuity had vanished, but the general alignment did not seem essentially disturbed. The fractures were found in the spine and in the tubular bones. In one case several fractures were present. There was a single instance in which a patho- logical fracture had healed well under roentgen-ray treatment (Fig. 2 B). Rate of Growth. In eleven cases it was possible to make some estimate of the rate of growth. All had received varying amounts of roentgen-ray treatment, so that there is no case in which growth uncomplicated by any outside factor can be judged. Observation periods varied from several months to two years in one instance, the average time being around eight months. There was only one tumor in this group that did not seem to have grown during the observation period, in spite of the fact that all had received roentgen-ray treatment. One seemed to enlarge by about 10 per cent in two years, and there were two others that appeared to grow at about this rate. One of the most rapidly enlarging lesions became five times larger in an eight-month period. FIG. 7. Predominantly lytic type of metastasis but with sufficient septa formation to warrant suggesting renal origin.

8 THE ROENTGENOGRAM OF RENAL CANCER METASTASIS IN BONE Pearson [283 The average rate would seem to be a 50 per cent growth in five to seven months in spite of roentgcn-ray treatment. In all cases the treatment was in moderate amounts, averaging about 1500 r (air dose) to each of two fields. No significant alteration in the character of the tumor in the roentgenogram could be attributed to the growth effect alone. BBect of Iriadiation. The general effect of roentgen-ray treatment on the growth of the tumor has been mentioned in connection with the size of the lesion revealed in the roentgenogram. There are certain smaller changes that have been seen occasionally in the roentgenogram. In four cases more septa appeared as a result of roentgen-ray treatnient. Onc pathological fracture healed after trcatmcnt. In five no effect was evident on production or destruction nor on the pattern of the tumor. As noted before, nine continued to enlarge in spite of treatment. These findings indicate renal cancer metastatic to bone shows somewhat varying growth rates; that moderate amounts of rocntgcn-ray therapy exert little if any effect on the growth of this lesion; and finally, that a few cases may show slight treatment re- 5ponSe in the roentgenogram, in the form of more septa. growth rate seemed to vary considerably, and most metastases showed little or no effect roentgenographically following moderate amounts of roentgen-ray treatment. There was no significant predilection for any bone nor for any particular part of a bone. It seems possible to divide bone metastases from renal cancer into three roentgenographic types: the lytic, the septate, and the patchy. The lytic was the most common, being found in twenty-seven cases; the septate, in six; and the patchy, in three. The lytic form is characterized by a predominance of medullary and cortical destruction over productive change; the septate, by approximately equal degrees of production and destruction with an internal pattern made up of dense septa forming loculations ; the patchy form is evidenced by fine patchy areas of medullary bone destruction. Generally speaking, the lytic and the patchy types constitute the roentgenographic appearance expected in the majority of cancer metastases in bone, while the septate form was sufficiently dis- Size. The smallest metastasis to bone measured about I cm. in diameter and reprewnted one of many similar areas of cancer metastases. The largest tumor was 22 by 18 cm., and the average about 10 cm. SUMMARY This study indicates that metastases in bone from renal cancer show practically con- \tant features of medullary origin, oval configuration, destruction of medullary and cortical bone, and the formation of a periosseous mas. There were no metastases in which production exceeded destruction in degree. When occurring in tubular bones, the position of the metastasis was always symmetrical or nearly so. The boundary of the metastasis can best be described as being fairly apparent in many cases. Pathological fractures occurred in about half the cases. A periosteal reaction was infrequent. The FIG. 8. Lytic type of metastasis containing a few septa.

9 CANCER ]uly 1948 FIG. 9. Lytic type of metastasis in unusual location. A little periosteal reaction and a few septa are present. tinctive to warrant assuming renal cancer to be the primary tumor. Five of the twenty-seven lytic cases showed septa formation in a minor degree (Figs. 7, 8, 9). True, the septa were delicate, indistinct, and incomplete, and the prominence of medullary and cortical bone destruction meant that these five cases had to be classified in the lytic group. However, their resemblance to the septate form suggests that it might be justifiable to relate their origin to renal cancer. DIFFERENTIAL DIAGNOSIS The purely lytic types of renal cancer metastases have nothing specific in their roentgenographic appearance to distinguish them from metastases of other origin. The differential diagnosis in this group must therefore distinguish them from the primary bone tumors, certain infections in bone, or the histi- ocytoses. Generally speaking, differentiation from the primary bone tumors is the most important and in most cases a knowledge of the roentgenographic characteristics of a metastasis is sufficient in itself to make differentiation possible. The important points are knowledge of the existence of a primary malignant tumor, multiplicity, the ill-defined edges, the predominance of destruction over production, the scarcity of periosteal reaction, the oval shape, the lack of internal pattern, and the symmetrical tendency. What has been said for the lytic form holds for the most part for the lrss common patchy type. There is, however, a somewhat greater tendency for the patchy type to resemble Ewing s tumor, primary reticulum-cell sarcoma of bone, and certain infections. The differential diagnosis of the srptate form deserves special emphasis. We believe it is probably this form that has been responsible for the variety of roentgenographic diagnoses offered in renal cancer metastatic to bone. The resemblance to benign giant cell tumor of bone seems but a superficial one to us. Its asymmetrical position, absence of periosteal reaction, epiphyseal relationship, lack of soft-parts extension, frequency of fracture into the joint, the distinct periphery, and above all the internal pattern with its fine regular septation will differentiatc giant-cell tumor. The roentgenographic characteristics of osteogenic sarcoma should enable one to differentiate it in most instances, for it is pear-shaped, shows a prominent soft-parts mass, and has plentiful periosteal reaction. Its borders are indistinct and often production predominates. The essential feature is the disorganization of the internal pattern with amorphous productive areas. Angioma of bone is an uncommon tumor in our experience. Its regular internal pattern, distinct periphery, absence of softparts mass, and absence of cortical destruction are some of the features that should distinguish it from the septate form of renal cancer metastatic to bone. In our experience there are two conditions that somewhat resemble the septate form of metastasis. These are the large, partially loculated type of myeloma which occurs oc-

10 THE ROENTGENOGRAM OF RENAL CANCER METASTASIS IN BONE Sherman LY Pearson [285 casionally and which has been reported as solitary, and a few of the metastases of thyroid origin, especially the metastasizing struma. The former has been seen in the flat bones. In both conditions the septa are less well developed, scanty, and incomplete with scalloping at the periphery of the tumor. SUMMARY AND CONCLUSIONS I. Thirty-six proved cases of bone metas tasis from kidney cancer have been studied roentgenographically. Three forms of bone involvement have been noted: the lytic, the patchy, and the septate. Recognition of the septate form in the roentgenogram offers the possibility of diagnosing the lesion as cancer metastasis of renal origin. REFERENCES ABESHOUSE, B. S., and WEINBERG, T.: Akkilignant renal neoplasms; clinical and pathologic study. Arch. Surg. 50: 46-55, COPELAND, M. M.: Bone metastases. Radiology 16: , I FRIED, J. R.: Skeletal and pulmonary metastases from cancer of the kidney, prostate and bladder. Am. J. Roentgenol. 55: , FORT, W. A,: Cancer metastatic to bone. Radiology 24: 96-98, a GIBSON, A,, and BLOODGOOD, J. C.: Metastatic hypernephroma with special reference to bone metastasis. Surg., Gynec. d Obst. 37: , GILLIES, C. L.: Malignant tumors of kidney in adults. Am. 1. Roentgenol. 43: , HERGER, C. C., and SAUER, H. R.: Cortical kidney tumor-analysis of loo consecutive cases. Surg., Gynec. B Obst. 78: , SCUDDER, C. L.: Bone metastases of hypernephroma. Ann. Surg. 44: , TURNER, J. W., and JAFFE, H. L.: Metastatic neoplasms. Am. J. Roentgenol. 43: , 1940.