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Healed Tuberculosis of the Kidney
HEALED TUBERCULOSIS OF THE KIDNEY ARCHIE H. BAGGENSTOSS Section on Pathologic Anatomy AND
LAURENCE F. GREENE Fellow in Urology, lvl ayo Clinic, Rochester, lvlinnesota
Reports of spontaneous healing of renal tuberculosis are not frequent. Most of these reports consist of apparent clinical cures based on the disappearance of urinary symptoms, the absence of pathologic elements in the urine, notably the tubercle bacillus and finally, the disappearance of tuberculous lesions from the bladder. Instances in which the kidney has been totally destroyed and excluded from the urinary tract have been offered as examples of the spontaneous healing of renal tuberculosis. Likewise the destruction and exclusion of a portion of the kidney resulting in an apparent cure have been described. Finally, spontaneous healing of the renal lesion with maintenance of normal renal function also has been reported. A clinical diagnosis of healed renal tuberculosis must be made with extreme reservation. The renal infection may pass into an inactive or latent phase with all outward manifestations of complete healing; at a later date, however, reactivation of the disease process may occur. In order to determine whether renal tuberculosis can heal, it is necessary to carry out careful studies of the pathologic changes of such kidneys. Reports of healed renal tuberculosis, verified by examination of the kidney, are rare. Ktimmell's report concerned a man who had undergone orchidectomy 13 years previously because of tuberculous orchitis. Because of frequency, dysuria and pain in the lumbar region, left nephrectomy was performed. The outstanding pathologic changes noted in the kidney were small cavities completely lined by epithelial tissue. Irregular scars and scattered epithelial cells were observed. A diagnosis of healed renal tuberculosis was made. Pechere reported the case of a patient who died of tuberculosis. In the kidney several hard, fibrous nodules were found and these were considered to be the scars of healed renal tuberculosis. Wildbolz described a case of healed renal tuberculosis in which the diagnosis was verified careful study of the kidney. Left nephrectomy 165
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had been performed for caseous cavernous tuberculosis with calcification, 20 years after the clinical diagnosis of tuberculous epididymitis had been made. Six years following nephrectomy the patient died of cholecystitis and pancreatitis. In the upper pole of the remaining kidney a caseous cavity with areas of calcification was found. The cavity measured 3 by 2 cm. and was not connected with the renal pelvis. After careful search Wildbolz was unable to detect the presence of any tuberculous tissue or tubercle bacilli. Wildbolz, nevertheless, reaffirmed his conviction that tuberculosis of the kidney almost never heals. He was able to find only 1 previously published case of healed renal tuberculosis which was verified by anatomic study. In this case, which was reported by Castaigne, the tuberculous lesion healed while the kidney retained its normal function. As evidence of the infrequency with which renal tuberculosis heals, Wildbolz pointed out that 20 years elapsed between the report of Castaigne and his own report. He interpreted the cases of healed renal tuberculosis reported by American urologists as instances of healing of tuberculous nephritis. Medlar examined the kidneys of 30 patients who died of active pulmonary tuberculosis but who exhibited no signs of renal phthisis during life. Of prime importance in this study was the search for scars of healed renal tuberculosis. Medlar noted that the incidence of scars in the kidneys from patients who died of pulmonary tuberculosis was much greater than in a group of nontuberculous patients. He believed that a goodly portion of these scars represented healed tuberculous lesions. The scars of healed tuberculosis of the kidney, as described by Medlar, were most frequently of microscopic size and scattered throughout the cortex and medulla. All scars showed destruction of the renal tissue in varying degrees with connective tissue replacement. In some lesions lymphocytes were numerous; in other lesions only occasional lymphocytes were present around the periphery of the scar. Cases of healed renal tuberculosis at the Mayo Clinic. Fifteen cases in which healed or regressing tubercles of the kidney were found incidentally at necropsy have been collected at the clinic over a period of 18 years from 1922 to May, 1940, inclusive. There were 13 men and 2 women in this group. The mean age of these patients at the time of death was 62.9 years; the youngest patient was 33 years of age and the oldest 81. Thirteen of them were more than SO years of age. The causes of death were as follows: heart disease in 4 cases; infections of
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various types and locations in 4; neoplastic disease in 3; arteriosclerosis in 2; duodenal ulcer in 1 case, and fracture of the femur in 1. In no instance was tuberculosis a primary or contributory cause of death. Associated lesions of tuberculosis. In each of the 15 cases in which healed or regressing tuberculous lesions were found in the kidney there was evidence of tuberculosis in the lung as well. In 11 cases, both components of the primary complex, consisting of a healed or regressing parenchymal lesion together with a similar lesion in the hilar lymph nodes, were present. In 4 cases, only one of the component parts of the primary complex was found. Apical scars either in one or both apices of the lungs were present in all but 3 cases. In addition to these evidences of tuberculous infection, lesions grossly similar to those of the kidney were present in the spleen and liver in 11 cases. No other evidence of tuberculosis was present in these cases. Macroscopic appearance of the lesions in the kidney. The tubercles appeared as small yellowish or grayish white, firm nodules, varying from 0.8 to 4 mm. in diameter. All lesions were in the cortex of the kidney. In 10 instances they were immediately beneath the capsule; in 5 they were 1 to 4 mm. beneath the surface of the cortex. Only 1 nodule was present in all cases but one, and in this case 3 were present. Only a single kidney was involved in each case. The cut surface of these nodules was white or yellow and in some instances granular, gritty material, thought to be calcium, was present. Histologic study of the renal lesions. In each case, histologic sections of the renal nodules were made and stained with hematoxylin and eosin. In 9 cases in which sufficient material was available, sections were stained for acid-fast bacilli also. In general these lesions were round or oval, circumscribed nodules, sharply demarcated from the surrounding renal cortex. Although each lesion is spoken of as a tubercle, it probably represents a number of conglomerate tubercles. On the basis of their histologic appearance, the lesions could be divided into 2 groups: (1) those that were completely healed and (2) those that were regressing but not completely inactive. In 9 cases, the renal tubercles appeared to be completely healed histologically (figs. 1 and 2, a and b). The ce.ntral portions of these tubercles contained calcium salts in four cases (fig. 2, a), loose fibrous connective tissue in 3 (fig. 2, b), and hyalinized connective tissue in 2. The calcium salts were embedded in a center of hyalinized connective
FIG. 1. Healed tubercle of the kidney. A caseous center with dust-like calcium deposits and a hyalinized connective tissue periphery (hematoxylin and eosin X 65).
FIG. 2. Healed renal tubercle; a, calcareous center with hyalinized connective tissue at periphery (hematoxylin and eosin, X 75); b, loose connective tissue in center with hyalinized connective tissue at periphery (hematoxylin and eosin, X 58).
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tissue in 2 instances, and in a caseous center in 2. The periphery of these lesions consisted of fibrous and hyalinized connective tissue fibers in all cases. There was no histologic evidence of activity such as proliferation of epithelioid cells, fibroblasts or giant cells. Occasional lymphocytes were present. In 5 cases of this group of histologically healed lesions, sufficient tissue was available to make sections which were stained for Mycobacterium tuberculosis. In none of these was Mycobacterium tuberculosis found. In 6 cases in the series the renal tubercles were regressing but were not entirely inactive or healed (figs. 3 and 4). The central portions of
FIG. 3. Regressing renal tubercle; caseous center with hyalinized connective tissue at periphery and numerous lymphocytes (hematoxylin and eosin, X 40).
these lesions were caseous in 4 cases (fig. 3), and composed of hyalinized fibrous tissue in 2 (fig. 4). The central portion of the lesion was surrounded by fibroblasts and numerous lymphocytes constituted the extreme periphery of the lesion (fig. 4). Giant cells were not observed. In 3 cases, sufficient tissue was present to make sections and stain them for Mycobacterium tuberculosis. In none of these were such organisms found. Histologic appearance of associated tubercles in spleen and liver. In 11 of the 15 cases in our series, tubercles were found in the spleen on macroscopic examination. Sections of the tubercles in the spleens were
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FIG. 4. Regressing renal tubercle; hyalinized fibrous connective tissue in center with numerous lymphocytes at extreme periphery (hematoxylin and eosin, X 45).
FIG. 5. Healed splenic tubercle; this lesion and the one depicted in figure 2b were found in the same case.
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available for histologic study in 8 of these 11 cases. In each of 5 cases the tubercles of the spleen and the healed tubercle of the kidney resembled each other in practically all respects (fig. 5). This similarity included not only the evidences of healing but also the degree and distribution of caseation, fibrosis and calcification. In 3 cases, however, the splenic tubercles were completely healed histologically whereas the corresponding renal tubercles although regressing, were not completely inactive. Sections of the hepatic tubercles were available for histologic study in six cases of the series. In 4 of these the appearances were practically
FIG. 6. Healed hepatic tubercle; this lesion and the one depicted in figure 4 were found in the same case (hematoxylin and eosin, X 55).
identical with those of the corresponding renal tubercles. In 2, the hepatic tubercles were completely healed histologically (fig. 6), whereas the corresponding renal tubercles were not completely inactive. Comment. Before discussing the results of this investigation, it is well to call attention to the nature of our material and compare it with that used by other workers. Most investigators who have studied the problem of healing in renal tuberculosis have used cases in which there was clinical evidence of renal tuberculosis at some time or otheL We are of the opinion that such cases are poorly adapted to the demonstration of healing. The use of such material is analogous to the use of cases of clinically apparent pulmonary tuberculosis for the demonstration
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of healing when it is well known that healing most readily and frequently takes place in cases in which the tuberculous process never becomes clinically apparent. From this standpoint, the material used by Medlar is much better adapted for the demonstration of healing in renal tuberculosis than that of most investigators. He used cases of pulmonary tuberculosis which had no clinically apparent renal tuberculosis. Unfortunately, however, the lesions described as healed by Medlar were admittedly not specifically recognizable as tuberculous. The type of renal lesion which he described has been considered to be tuberculous nephritis by Wildbolz. Our material on the other hand has been obtained from cases in which neither clinical renal nor clinical pulmonary tuberculosis was present. Both the renal lesions and the pulmonary lesions were subclinical and were incidental findings. In some instances they were not recognized even grossly at necropsy as tuberculosis. The renal lesions which we have described are examples of isolated miliary tubercles. The infection in these cases probably reached the kidney by way of the blood stream from the lesions of the primary complex in the lung shortly after the primary infection occurred. Our descriptions and photomicrographs should have made clear that we are not concerned with so-called tuberculous nephritis. This condition has been much discussed by urologists of the German school and although it may occur, the lesions admittedly have no characteristic appearance which would enable one to diagnose them as tuberculous. In any study of the problem of healed tuberculosis of the kidney, 2 questions must be answered: 1. Is the lesion really tuberculosis? 2. Is it healed? It sometimes has been said of renal tuberculosis that if the histologic diagnosis is possible, it is not healed, and on the other hand, if it is healed, it can no longer be recognized as tuberculosis. Stoerk stated that it would be of interest to be able to demonstrate the fate of miliary cortical tubercles but that concerning these, hypotheses only can be ventured. He assumed that in analogy to the behavior of tuberculous nodules in other parts of the body that at least the sparse formation of tubercles in the renal cortex may heal when the general somatic circumstances of the individual are favorable. That the healed residuals of the nodules are not recognizable as such, he thought, is not surprising; according to him, there would be nothing else to expect except circumscribed proliferation of connective tissue in the intertubular region, and as the most specific sign, residual caseation. He stated, moreover, that he has never seen the latter.
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We are aware of the possibility that other granulomatous diseases may conceivably give rise to lesions similar to those which we have described. If the nodules described were due to some infectious granuloma, other than tuberculosis, evidence of such a disease would be expected elsewhere in the body. This did not occur in the cases in our series, however. Other lesions in which the histologic appearance may resemble that described are medullary fibromasand so-called capsulomas. The former, however, occur only in the medulla and all of the renal lesions which we described are in the cortex. Capsulomas are intimately associated with the capsule and contain various elements such as adipose connective tissue and muscle in addition to fibrous connective tissue. Caseation, which was present in the healed tubercles in 2 cases and in the regressing tubercles in 4 cases is not a feature of capsulomas. Calcification, which occurred in the healed tubercles in 4 cases, is likewise not a feature of these tumors. On the other hand, caseation and calcification are accepted as characteristic processes of tuberculous lesions. The histologic appearance of the lesions which we have described is typical of miliary tubercles and the histologic evidence of healing and regression were very definite. The fact that similar healed tubercles were present in the liver and spleen in most cases is confirmatory evidence of the tuberculous nature of the renal lesions. We are aware that histologic evidence of healing is in itself not proof that tubercle bacilli may not have been present. Further evidence such as might be gained by the inoculation of the lesions into guinea-pigs would be desirable but was not possible in this study. It has been noted that, in some instances, the splenic and hepatic tubercles were completely healed while the renal tubercles in the same case, although obviously regressing, were not completely inactive. This may indicate that the processes of regression and healing in tuberculous lesions of the kidney go on at a slower rate than the similar processes in the liver and spleen. We believe that these 15 cases collected over a period of 18 years in which healed or healing tuberculous lesions were found, probably represent only a small proportion of the cases in which tubercle bacilli actually lodged in the kidney and gave rise to lesions. It is quite likely that in a significant number of cases tubercles of this size are overlooked altogether at necropsy, especially when they are located beneath the surface of the cortex. It is also likely that in many instances the lesions are not typical and are not recorded as tuberculosis. Finally, it is a well known fact that the lesions of tuberculosis may heal without leaving a trace.
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Although the evidence presented demonstrates conclusively that tuberculosis of the kidney does heal, we are in agreement with those who believe that when renal tuberculosis reaches the stage at which it gives rise to symptoms and clinically demonstrable changes, it rarely if ever heals. The question may well be asked: why did the tuberculous renal lesions heal in these cases? Probably the 2 most important factors were the comparatively small number of the infecting organisms and the high resistance of the individuals. That the number of bacilli in the blood stream were comparatively small is suggested not only by the small size of the lesions, but also by the fact that the lesions were single in all but one case, were found in only 1 kidney, and in some instances the kidney was the only site of the involvement other than the lungs. When tubercles occurred in the spleen and liver, they were generally single also. Indicative of active resistance to the infection is the fact that in each of these cases healing also occurred in tuberculous lesions in the lung, hilar lymph nodes, liver or spleen. It is interesting that all the healed or healing lesions in the kidney were in the cortex. Putschar pointed out that in all of the anatomically investigated cases of early renal tuberculosis, the lesion from which the chronic renal tuberculosis takes its origin was always in the papilla near the apex or in the region of the angle of the calyx. In any case, the lesion was always located in the medulla. He stated that a cortical lesion as the starting point for chronic renal tuberculosis has never been described. Putschar expressed the belief that this fact can best be explained on the assumption that the medullary portions are infected not by a single bacillus but by emboli which, because of their larger size, are unable to reach the glomeruli. In other words, only small doses of bacilli reach the cortex and because of the small size of the infecting dose, these lesions tend to heal. When the medulla is infected, however, the infection occurs because larger numbers of bacilli lodge there and give rise to a more severe and consequently progressive type of infection. Ulceration into the renal pelvis presumably also facilitates the spread and progression of such a lesion. SUMMARY AND CONCLUSIONS
Healed miliary tubercles of the kidney were found incidentally at necropsy in 9 cases. Similar miliary tubercles with definite evidence of regression but slight histologic evidence of activity were found in 6
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additional cases. In none of these cases was there any clinical evidence of either renal or pulmonary tuberculosis. These cases add to the evidence that renal tuberculosis heals when circumstances are favorable. It is probable that healed tubercles of this type occur more frequently than the small number of cases reported indicate. REFERENCES D'ABREU, A.: Closed renal tuberculosis; with special reference to the possibility of healing in this disease. Brit. M. J., 1: 605-606, 1933. BUGBEE, H. G.: Two cases representing unusual types of renal tuberculosis. Tr. Am. A. Genito-Urin. Surg., 17: 95-105, 1924. BUMPUS, H. C., JR., AND THOMPSON, G. J.: Renal tuberculosis; changing conceptions in the decade 1920-1930. Am. J. Surg., 9: 545-551, 1930. CASTAIGNE: Quoted by WILDBOLZ, HANS. EKEHORN, G.: Kann die Nierentuberkulose bisweilen spontan ausheilen? Folia urol., 4: 180-188, 1909. HARBITZ, FRANCIS: Uber spontane Heilbarkeit von Nierentuberkulose. Ztschr. f. urol. Chir., 1: 582-587, 1913. HARRIS, R. I.: Tuberculous bacilluria: its incidence and significance amongst patients suffering from surgical tuberculosis. Brit. J. Surg., 16: 464-484, 1929. HEYN, ARTHUR: Ueber disseminirte Nephritis bacillaris Tuberkuloser ohne Nierentuberkel. Virchows Arch. f. path. Anat., 165: 42-79, 1901. KEYES, E. L.: Concerning apparent cures of renal tuberculosis. Surg., Gynec. & Obst., 18: 214-217, 1914. KEYES, E. L.: The spontaneous healing of renal tuberculosis. J. A. M. A., 104: 13801383, 1935. KuMMELL, H.: Gibt es eine spontane oder nightoperative Heilung der Nierentuberkulose? Deutsche Ztschr. f. Chir., 203-204: 303-313, 1927. LIEBERMEISTER, GUSTAV: Studien tiber Komplikationen der Lungentuberkulose und tiber die Verbreitung der Tuberkelbazillen in den Organen und im Blut der Phthisiker. Virchows Arch. f. path. Anat., 197: 332-425, 1909. MEDLAR, E. M.: Cases of renal infection in pulmonary tuberculosis; evidence of healed tuberculous lesions. Am. J. Path., 2: 401-413, 1926. MINDER, Juuus: Zur Frage der sogenannten Spontanheilung der Nierentuberkulose. Ztschr. f. Urol., 31: 523-532, 1937. PECHERE: Quoted by Stenholm, Ture: Zur Frage der Spontanheilung bei der Nierentuberkulose, der tuberkulosen Bazillurie und der tuberkulosen Nephritis; unter besonderer Berticksichtigung der gesamten Literatur von 1920 an. Zentralbl. f. Chir., 62: 518, 1935. PETTAVEL, C. A.: Guerison apparente d'une tuberculose renale par exclusion renale (autonephrectomie). Schweiz med. Wchnschr., 59: 1264-1265, 1929. PuTSCHAR, WALTER: Die entztindlichen Erkrankungen der ableitenden Harnwege und der Nierenhtillen einschlieszlich der Pyelonephritis und der Pyonephrose. In Henke, F. and Lubarsch, 0.: Handbuch der speziellen pathologischen Anatomie und Histologie. Berlin, Julius Springer, 1934, vol. 6, pt. 2, pp. 486-501. REED, RONALD: Observations on the healing of renal tuberculosis. Brit. J. Urol., 11: 305-324, 1939. SCHAFFHAUSER, F.: Intrarenal ausgeschaltete chronische Nierentuberkulose, zugleich ein Beitrag zur Frage der Spontanheilung der Nierentuberkulose. Ztschr. f. urol. Chir., 40: 426-439, 1935. STOERK, 0.: Spezifische Infektionen. In Henke, F. and Lubarsch, 0.: Handbuch der speziellen pathologischen Anatomie und Histologie. Berlin, Julius Springer, 1925, vol. 6, pt. 1, pp. 494-499. THOMAS, G. J. AND KINSELLA, T. J.: Some data concerning the clinical course of renal tuberculosis. J. Urol., 19: 95-107, 1928. WILDBOLZ, HANS: Uber die Moglichkeit einer Spontanheilung der Nierentuberkulose. Ztschr. f. urol. Chir. u. Gynlik., 42: 257-267, 1936.
LAURENCE F. GREENE Fellow in Urology, lvl ayo Clinic, Rochester, lvlinnesota
Reports of spontaneous healing of renal tuberculosis are not frequent. Most of these reports consist of apparent clinical cures based on the disappearance of urinary symptoms, the absence of pathologic elements in the urine, notably the tubercle bacillus and finally, the disappearance of tuberculous lesions from the bladder. Instances in which the kidney has been totally destroyed and excluded from the urinary tract have been offered as examples of the spontaneous healing of renal tuberculosis. Likewise the destruction and exclusion of a portion of the kidney resulting in an apparent cure have been described. Finally, spontaneous healing of the renal lesion with maintenance of normal renal function also has been reported. A clinical diagnosis of healed renal tuberculosis must be made with extreme reservation. The renal infection may pass into an inactive or latent phase with all outward manifestations of complete healing; at a later date, however, reactivation of the disease process may occur. In order to determine whether renal tuberculosis can heal, it is necessary to carry out careful studies of the pathologic changes of such kidneys. Reports of healed renal tuberculosis, verified by examination of the kidney, are rare. Ktimmell's report concerned a man who had undergone orchidectomy 13 years previously because of tuberculous orchitis. Because of frequency, dysuria and pain in the lumbar region, left nephrectomy was performed. The outstanding pathologic changes noted in the kidney were small cavities completely lined by epithelial tissue. Irregular scars and scattered epithelial cells were observed. A diagnosis of healed renal tuberculosis was made. Pechere reported the case of a patient who died of tuberculosis. In the kidney several hard, fibrous nodules were found and these were considered to be the scars of healed renal tuberculosis. Wildbolz described a case of healed renal tuberculosis in which the diagnosis was verified careful study of the kidney. Left nephrectomy 165
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had been performed for caseous cavernous tuberculosis with calcification, 20 years after the clinical diagnosis of tuberculous epididymitis had been made. Six years following nephrectomy the patient died of cholecystitis and pancreatitis. In the upper pole of the remaining kidney a caseous cavity with areas of calcification was found. The cavity measured 3 by 2 cm. and was not connected with the renal pelvis. After careful search Wildbolz was unable to detect the presence of any tuberculous tissue or tubercle bacilli. Wildbolz, nevertheless, reaffirmed his conviction that tuberculosis of the kidney almost never heals. He was able to find only 1 previously published case of healed renal tuberculosis which was verified by anatomic study. In this case, which was reported by Castaigne, the tuberculous lesion healed while the kidney retained its normal function. As evidence of the infrequency with which renal tuberculosis heals, Wildbolz pointed out that 20 years elapsed between the report of Castaigne and his own report. He interpreted the cases of healed renal tuberculosis reported by American urologists as instances of healing of tuberculous nephritis. Medlar examined the kidneys of 30 patients who died of active pulmonary tuberculosis but who exhibited no signs of renal phthisis during life. Of prime importance in this study was the search for scars of healed renal tuberculosis. Medlar noted that the incidence of scars in the kidneys from patients who died of pulmonary tuberculosis was much greater than in a group of nontuberculous patients. He believed that a goodly portion of these scars represented healed tuberculous lesions. The scars of healed tuberculosis of the kidney, as described by Medlar, were most frequently of microscopic size and scattered throughout the cortex and medulla. All scars showed destruction of the renal tissue in varying degrees with connective tissue replacement. In some lesions lymphocytes were numerous; in other lesions only occasional lymphocytes were present around the periphery of the scar. Cases of healed renal tuberculosis at the Mayo Clinic. Fifteen cases in which healed or regressing tubercles of the kidney were found incidentally at necropsy have been collected at the clinic over a period of 18 years from 1922 to May, 1940, inclusive. There were 13 men and 2 women in this group. The mean age of these patients at the time of death was 62.9 years; the youngest patient was 33 years of age and the oldest 81. Thirteen of them were more than SO years of age. The causes of death were as follows: heart disease in 4 cases; infections of
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various types and locations in 4; neoplastic disease in 3; arteriosclerosis in 2; duodenal ulcer in 1 case, and fracture of the femur in 1. In no instance was tuberculosis a primary or contributory cause of death. Associated lesions of tuberculosis. In each of the 15 cases in which healed or regressing tuberculous lesions were found in the kidney there was evidence of tuberculosis in the lung as well. In 11 cases, both components of the primary complex, consisting of a healed or regressing parenchymal lesion together with a similar lesion in the hilar lymph nodes, were present. In 4 cases, only one of the component parts of the primary complex was found. Apical scars either in one or both apices of the lungs were present in all but 3 cases. In addition to these evidences of tuberculous infection, lesions grossly similar to those of the kidney were present in the spleen and liver in 11 cases. No other evidence of tuberculosis was present in these cases. Macroscopic appearance of the lesions in the kidney. The tubercles appeared as small yellowish or grayish white, firm nodules, varying from 0.8 to 4 mm. in diameter. All lesions were in the cortex of the kidney. In 10 instances they were immediately beneath the capsule; in 5 they were 1 to 4 mm. beneath the surface of the cortex. Only 1 nodule was present in all cases but one, and in this case 3 were present. Only a single kidney was involved in each case. The cut surface of these nodules was white or yellow and in some instances granular, gritty material, thought to be calcium, was present. Histologic study of the renal lesions. In each case, histologic sections of the renal nodules were made and stained with hematoxylin and eosin. In 9 cases in which sufficient material was available, sections were stained for acid-fast bacilli also. In general these lesions were round or oval, circumscribed nodules, sharply demarcated from the surrounding renal cortex. Although each lesion is spoken of as a tubercle, it probably represents a number of conglomerate tubercles. On the basis of their histologic appearance, the lesions could be divided into 2 groups: (1) those that were completely healed and (2) those that were regressing but not completely inactive. In 9 cases, the renal tubercles appeared to be completely healed histologically (figs. 1 and 2, a and b). The ce.ntral portions of these tubercles contained calcium salts in four cases (fig. 2, a), loose fibrous connective tissue in 3 (fig. 2, b), and hyalinized connective tissue in 2. The calcium salts were embedded in a center of hyalinized connective
FIG. 1. Healed tubercle of the kidney. A caseous center with dust-like calcium deposits and a hyalinized connective tissue periphery (hematoxylin and eosin X 65).
FIG. 2. Healed renal tubercle; a, calcareous center with hyalinized connective tissue at periphery (hematoxylin and eosin, X 75); b, loose connective tissue in center with hyalinized connective tissue at periphery (hematoxylin and eosin, X 58).
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tissue in 2 instances, and in a caseous center in 2. The periphery of these lesions consisted of fibrous and hyalinized connective tissue fibers in all cases. There was no histologic evidence of activity such as proliferation of epithelioid cells, fibroblasts or giant cells. Occasional lymphocytes were present. In 5 cases of this group of histologically healed lesions, sufficient tissue was available to make sections which were stained for Mycobacterium tuberculosis. In none of these was Mycobacterium tuberculosis found. In 6 cases in the series the renal tubercles were regressing but were not entirely inactive or healed (figs. 3 and 4). The central portions of
FIG. 3. Regressing renal tubercle; caseous center with hyalinized connective tissue at periphery and numerous lymphocytes (hematoxylin and eosin, X 40).
these lesions were caseous in 4 cases (fig. 3), and composed of hyalinized fibrous tissue in 2 (fig. 4). The central portion of the lesion was surrounded by fibroblasts and numerous lymphocytes constituted the extreme periphery of the lesion (fig. 4). Giant cells were not observed. In 3 cases, sufficient tissue was present to make sections and stain them for Mycobacterium tuberculosis. In none of these were such organisms found. Histologic appearance of associated tubercles in spleen and liver. In 11 of the 15 cases in our series, tubercles were found in the spleen on macroscopic examination. Sections of the tubercles in the spleens were
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FIG. 4. Regressing renal tubercle; hyalinized fibrous connective tissue in center with numerous lymphocytes at extreme periphery (hematoxylin and eosin, X 45).
FIG. 5. Healed splenic tubercle; this lesion and the one depicted in figure 2b were found in the same case.
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available for histologic study in 8 of these 11 cases. In each of 5 cases the tubercles of the spleen and the healed tubercle of the kidney resembled each other in practically all respects (fig. 5). This similarity included not only the evidences of healing but also the degree and distribution of caseation, fibrosis and calcification. In 3 cases, however, the splenic tubercles were completely healed histologically whereas the corresponding renal tubercles although regressing, were not completely inactive. Sections of the hepatic tubercles were available for histologic study in six cases of the series. In 4 of these the appearances were practically
FIG. 6. Healed hepatic tubercle; this lesion and the one depicted in figure 4 were found in the same case (hematoxylin and eosin, X 55).
identical with those of the corresponding renal tubercles. In 2, the hepatic tubercles were completely healed histologically (fig. 6), whereas the corresponding renal tubercles were not completely inactive. Comment. Before discussing the results of this investigation, it is well to call attention to the nature of our material and compare it with that used by other workers. Most investigators who have studied the problem of healing in renal tuberculosis have used cases in which there was clinical evidence of renal tuberculosis at some time or otheL We are of the opinion that such cases are poorly adapted to the demonstration of healing. The use of such material is analogous to the use of cases of clinically apparent pulmonary tuberculosis for the demonstration
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of healing when it is well known that healing most readily and frequently takes place in cases in which the tuberculous process never becomes clinically apparent. From this standpoint, the material used by Medlar is much better adapted for the demonstration of healing in renal tuberculosis than that of most investigators. He used cases of pulmonary tuberculosis which had no clinically apparent renal tuberculosis. Unfortunately, however, the lesions described as healed by Medlar were admittedly not specifically recognizable as tuberculous. The type of renal lesion which he described has been considered to be tuberculous nephritis by Wildbolz. Our material on the other hand has been obtained from cases in which neither clinical renal nor clinical pulmonary tuberculosis was present. Both the renal lesions and the pulmonary lesions were subclinical and were incidental findings. In some instances they were not recognized even grossly at necropsy as tuberculosis. The renal lesions which we have described are examples of isolated miliary tubercles. The infection in these cases probably reached the kidney by way of the blood stream from the lesions of the primary complex in the lung shortly after the primary infection occurred. Our descriptions and photomicrographs should have made clear that we are not concerned with so-called tuberculous nephritis. This condition has been much discussed by urologists of the German school and although it may occur, the lesions admittedly have no characteristic appearance which would enable one to diagnose them as tuberculous. In any study of the problem of healed tuberculosis of the kidney, 2 questions must be answered: 1. Is the lesion really tuberculosis? 2. Is it healed? It sometimes has been said of renal tuberculosis that if the histologic diagnosis is possible, it is not healed, and on the other hand, if it is healed, it can no longer be recognized as tuberculosis. Stoerk stated that it would be of interest to be able to demonstrate the fate of miliary cortical tubercles but that concerning these, hypotheses only can be ventured. He assumed that in analogy to the behavior of tuberculous nodules in other parts of the body that at least the sparse formation of tubercles in the renal cortex may heal when the general somatic circumstances of the individual are favorable. That the healed residuals of the nodules are not recognizable as such, he thought, is not surprising; according to him, there would be nothing else to expect except circumscribed proliferation of connective tissue in the intertubular region, and as the most specific sign, residual caseation. He stated, moreover, that he has never seen the latter.
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We are aware of the possibility that other granulomatous diseases may conceivably give rise to lesions similar to those which we have described. If the nodules described were due to some infectious granuloma, other than tuberculosis, evidence of such a disease would be expected elsewhere in the body. This did not occur in the cases in our series, however. Other lesions in which the histologic appearance may resemble that described are medullary fibromasand so-called capsulomas. The former, however, occur only in the medulla and all of the renal lesions which we described are in the cortex. Capsulomas are intimately associated with the capsule and contain various elements such as adipose connective tissue and muscle in addition to fibrous connective tissue. Caseation, which was present in the healed tubercles in 2 cases and in the regressing tubercles in 4 cases is not a feature of capsulomas. Calcification, which occurred in the healed tubercles in 4 cases, is likewise not a feature of these tumors. On the other hand, caseation and calcification are accepted as characteristic processes of tuberculous lesions. The histologic appearance of the lesions which we have described is typical of miliary tubercles and the histologic evidence of healing and regression were very definite. The fact that similar healed tubercles were present in the liver and spleen in most cases is confirmatory evidence of the tuberculous nature of the renal lesions. We are aware that histologic evidence of healing is in itself not proof that tubercle bacilli may not have been present. Further evidence such as might be gained by the inoculation of the lesions into guinea-pigs would be desirable but was not possible in this study. It has been noted that, in some instances, the splenic and hepatic tubercles were completely healed while the renal tubercles in the same case, although obviously regressing, were not completely inactive. This may indicate that the processes of regression and healing in tuberculous lesions of the kidney go on at a slower rate than the similar processes in the liver and spleen. We believe that these 15 cases collected over a period of 18 years in which healed or healing tuberculous lesions were found, probably represent only a small proportion of the cases in which tubercle bacilli actually lodged in the kidney and gave rise to lesions. It is quite likely that in a significant number of cases tubercles of this size are overlooked altogether at necropsy, especially when they are located beneath the surface of the cortex. It is also likely that in many instances the lesions are not typical and are not recorded as tuberculosis. Finally, it is a well known fact that the lesions of tuberculosis may heal without leaving a trace.
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Although the evidence presented demonstrates conclusively that tuberculosis of the kidney does heal, we are in agreement with those who believe that when renal tuberculosis reaches the stage at which it gives rise to symptoms and clinically demonstrable changes, it rarely if ever heals. The question may well be asked: why did the tuberculous renal lesions heal in these cases? Probably the 2 most important factors were the comparatively small number of the infecting organisms and the high resistance of the individuals. That the number of bacilli in the blood stream were comparatively small is suggested not only by the small size of the lesions, but also by the fact that the lesions were single in all but one case, were found in only 1 kidney, and in some instances the kidney was the only site of the involvement other than the lungs. When tubercles occurred in the spleen and liver, they were generally single also. Indicative of active resistance to the infection is the fact that in each of these cases healing also occurred in tuberculous lesions in the lung, hilar lymph nodes, liver or spleen. It is interesting that all the healed or healing lesions in the kidney were in the cortex. Putschar pointed out that in all of the anatomically investigated cases of early renal tuberculosis, the lesion from which the chronic renal tuberculosis takes its origin was always in the papilla near the apex or in the region of the angle of the calyx. In any case, the lesion was always located in the medulla. He stated that a cortical lesion as the starting point for chronic renal tuberculosis has never been described. Putschar expressed the belief that this fact can best be explained on the assumption that the medullary portions are infected not by a single bacillus but by emboli which, because of their larger size, are unable to reach the glomeruli. In other words, only small doses of bacilli reach the cortex and because of the small size of the infecting dose, these lesions tend to heal. When the medulla is infected, however, the infection occurs because larger numbers of bacilli lodge there and give rise to a more severe and consequently progressive type of infection. Ulceration into the renal pelvis presumably also facilitates the spread and progression of such a lesion. SUMMARY AND CONCLUSIONS
Healed miliary tubercles of the kidney were found incidentally at necropsy in 9 cases. Similar miliary tubercles with definite evidence of regression but slight histologic evidence of activity were found in 6
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additional cases. In none of these cases was there any clinical evidence of either renal or pulmonary tuberculosis. These cases add to the evidence that renal tuberculosis heals when circumstances are favorable. It is probable that healed tubercles of this type occur more frequently than the small number of cases reported indicate. REFERENCES D'ABREU, A.: Closed renal tuberculosis; with special reference to the possibility of healing in this disease. Brit. M. J., 1: 605-606, 1933. BUGBEE, H. G.: Two cases representing unusual types of renal tuberculosis. Tr. Am. A. Genito-Urin. Surg., 17: 95-105, 1924. BUMPUS, H. C., JR., AND THOMPSON, G. J.: Renal tuberculosis; changing conceptions in the decade 1920-1930. Am. J. Surg., 9: 545-551, 1930. CASTAIGNE: Quoted by WILDBOLZ, HANS. EKEHORN, G.: Kann die Nierentuberkulose bisweilen spontan ausheilen? Folia urol., 4: 180-188, 1909. HARBITZ, FRANCIS: Uber spontane Heilbarkeit von Nierentuberkulose. Ztschr. f. urol. Chir., 1: 582-587, 1913. HARRIS, R. I.: Tuberculous bacilluria: its incidence and significance amongst patients suffering from surgical tuberculosis. Brit. J. Surg., 16: 464-484, 1929. HEYN, ARTHUR: Ueber disseminirte Nephritis bacillaris Tuberkuloser ohne Nierentuberkel. Virchows Arch. f. path. Anat., 165: 42-79, 1901. KEYES, E. L.: Concerning apparent cures of renal tuberculosis. Surg., Gynec. & Obst., 18: 214-217, 1914. KEYES, E. L.: The spontaneous healing of renal tuberculosis. J. A. M. A., 104: 13801383, 1935. KuMMELL, H.: Gibt es eine spontane oder nightoperative Heilung der Nierentuberkulose? Deutsche Ztschr. f. Chir., 203-204: 303-313, 1927. LIEBERMEISTER, GUSTAV: Studien tiber Komplikationen der Lungentuberkulose und tiber die Verbreitung der Tuberkelbazillen in den Organen und im Blut der Phthisiker. Virchows Arch. f. path. Anat., 197: 332-425, 1909. MEDLAR, E. M.: Cases of renal infection in pulmonary tuberculosis; evidence of healed tuberculous lesions. Am. J. Path., 2: 401-413, 1926. MINDER, Juuus: Zur Frage der sogenannten Spontanheilung der Nierentuberkulose. Ztschr. f. Urol., 31: 523-532, 1937. PECHERE: Quoted by Stenholm, Ture: Zur Frage der Spontanheilung bei der Nierentuberkulose, der tuberkulosen Bazillurie und der tuberkulosen Nephritis; unter besonderer Berticksichtigung der gesamten Literatur von 1920 an. Zentralbl. f. Chir., 62: 518, 1935. PETTAVEL, C. A.: Guerison apparente d'une tuberculose renale par exclusion renale (autonephrectomie). Schweiz med. Wchnschr., 59: 1264-1265, 1929. PuTSCHAR, WALTER: Die entztindlichen Erkrankungen der ableitenden Harnwege und der Nierenhtillen einschlieszlich der Pyelonephritis und der Pyonephrose. In Henke, F. and Lubarsch, 0.: Handbuch der speziellen pathologischen Anatomie und Histologie. Berlin, Julius Springer, 1934, vol. 6, pt. 2, pp. 486-501. REED, RONALD: Observations on the healing of renal tuberculosis. Brit. J. Urol., 11: 305-324, 1939. SCHAFFHAUSER, F.: Intrarenal ausgeschaltete chronische Nierentuberkulose, zugleich ein Beitrag zur Frage der Spontanheilung der Nierentuberkulose. Ztschr. f. urol. Chir., 40: 426-439, 1935. STOERK, 0.: Spezifische Infektionen. In Henke, F. and Lubarsch, 0.: Handbuch der speziellen pathologischen Anatomie und Histologie. Berlin, Julius Springer, 1925, vol. 6, pt. 1, pp. 494-499. THOMAS, G. J. AND KINSELLA, T. J.: Some data concerning the clinical course of renal tuberculosis. J. Urol., 19: 95-107, 1928. WILDBOLZ, HANS: Uber die Moglichkeit einer Spontanheilung der Nierentuberkulose. Ztschr. f. urol. Chir. u. Gynlik., 42: 257-267, 1936.