©1990 S. Karger AG. Basel 0302-2838/90/0186-0017$2 75/0
Eur Urol 1990; 18(suppl 2):17-21
Renal Oncocytoma: Prognosis and Treatment
1608101
Michael M. Lieber Department of Urology, Mayo Clinic, Rochester, Minn., USA
Histopathology
‘Oncocytes’ by definition are large neoplastic cells with an intensely eosinophilic granular cytoplasm. By definition, ‘oncocytomas’ are tumors composed only of oncocytes. Oncocytomas are not uncommon throughout the body and are not limited to the kidneys. Numerous histochemical and ultrastructural studies have demon strated that the brightly eosinophilic cytoplasmic granu larity of oncocytes results from the fact that the cyto plasm of oncocytes is packed with mitochondria. The exact cell type that gives rise to an oncocytoma in the kidney or in other organs is unknown. However, several recent histochemical and immunohistochemical studies using monoclonal antibodies suggest that oncocytomas in animals and man probably arise from the distal renal tubules, in particular from the intercalated cells of the collecting tubules [2, 3],
Many renal cell carcinomas which behave as typical aggressive cancers also contain eosinophilic granular cells, either alone or in combination with clear-cell neo plastic elements. Such renal cell carcinomas generally have been called granular-cell or dark-cell renal carcino mas. But it is important to recognize that renal cell car cinomas made up of eosinophilic granular cells are not typical oncocytomas. Rather, the specific term ‘renal oncocytoma’ has come by selected usage to apply to a renocortical neoplasm made up of only a pure popula tion of very best differentiated eosinophilic granular cells or oncocytes. Since renocortical tumors which are composed strictly of very well differentiated oncocytes behave in a generally benign fashion, this fine-tuning of histological variables appears to have a practical end point. However, it is most important to remember that malignantly behaving renal neoplasms often have onco cytic features. Therefore, the differentiation of a typical renal oncocytoma from an oncocytic renal-cell carci noma can be a somewhat difficult pathological task based on nuclear morphology. Specific color illustrations of histopathology can be found in reference 4.
Gross Appearance
Renal oncocytomas often have a typical macroscopic appearance which differs substantially from the typical gross appearance of most renal cell carcinomas. Renal oncocytomas are generally well encapsulated with a well-
Downloaded by: University of Exeter 144.173.6.94 - 6/7/2020 11:51:47 PM
It is now certain that renal oncocytoma is a fairly common clinicopathologic entity. Current series suggest that 3-7% of solid renocortical tumors previously classi fied as renal cell carcinomas are in fact typical renal oncocytomas. Thus, renal oncocytoma is an unusual, but not rare, renocortical neoplasm which most urologists, radiologists and pathologists will come upon from time to time. The start of the renal oncocytoma era can be dated exactly to the publication of Klein and Valensi in 1976 [1]. Prior to 1975 there had been only 6 individual case reports describing renal oncocytomas.
Lieber
defined, thick, fibrous capsule, and the tumor tissue itself rarely penetrates the renal capsule or invades other structures. Because of this expansile growth, renal onco cytomas are almost always spherical without the types of invasive pseudopod-like growth seen with some renal cell carcinomas. The renal pelvis, the intrarenal collect ing system and the perinephric fat generally are not invaded by the tumor. On fresh cross-section, renal oncocytoma tissue is generally tannish-brown or ma hogany-brown in color. This characteristic brown col oring is usually different from the bright yellow or yellow-and-white cut surface seen with typical renal cell car cinomas. The cross-section of small renal oncocytomas generally has a homogeneous appearance with no hemor rhage or necrosis within the tumor. Medium- and large sized oncocytomas commonly show a prominent, stel late, central, fibrous scar which gives them an almost pathognomic cross appearance [1, 4], The characteristic central scar is often imaged preoperatively by CT or magnetic resonance imaging (MRI) examination of the tumor, sometimes even by ultrasound examination, and can serve to suggest the diagnosis of oncocytoma preoperatively.
Clinical Presentation
As might be expected from their slow, well-encapsu lated, spherical, expansile growth, renal oncocytomas usually are not symptomatic. Indeed, the vast majority of such tumors has been discovered incidentally during the course of evaluation for some unrelated symptom or at postmortem examination. This important feature was originally pointed out by Klein and Valensi [1], In every large series reported, the majority of typical onco cytomas was in fact discovered incidentally, and in some series none of the patients with oncocytomas had any symptoms at all. Indeed, the incidence of gross hematuria, abdominal pain, flank mass and micro scopic hematuria has been remarkably low [5], New techniques to image the kidneys and the retroperitoneum have come into widespread use in the past de cade. These new techniques include ultrasound imag ing, CT imaging of the abdomen and now MRI. In most large medical centers commonly carrying out these new techniques, many more renocortical neoplasms, both renal cell carcinomas and renal oncocytomas, are being discovered in a small and asymptomatic stage than ever before [6],
Incidence of Renal Oncocytoma Multifocal Occurrence and Bilaterality
Current collected literature series do not suggest a preference for right or left kidney or site within the kid ney for renal oncocytomas. Rather, they occur uniformly throughout the renal cortex. Ninety-four percent of tu mors have been unilateral, but it is most important to remember that approximately 6% of reported cases of oncocytoma had bilateral tumors [5]. Both synchronous and asynchronous bilateral renal oncocytomas have been reported and, in addition, bilateral solid renal tumors with a renal oncocytoma on one side and a typical renal cell carcinoma on the other side have also been reported. Multifocal renal oncocytomas occurring in multiple lo cations within one kidney or in both kidneys have also been described. The specific term ‘oncocytomatosis’ has been used to describe this typical entity [7], As tumor enucleation or partial nephrectomy becomes a more common treatment for renal oncocytoma, the fact that multifocal renal oncocytomas or oncocytomatosis may occur in the same kidney must be borne in mind, and a careful search by radiological imaging techniques and by direct examination at the time of surgery must be em ployed to look for multifocal oncocytomas which could
Downloaded by: University of Exeter 144.173.6.94 - 6/7/2020 11:51:47 PM
The last time that I collected large series of renal oncocytomas was approximately 5 years ago [5], At that time 11 large series of renocortical tumors were pooled, making up a total of 4,304 individual tumors studied from around the world. In this group, 149 instances of typical renal oncocytoma were identified. Such figures suggest an overall incidence of about 3-4% for renal oncocytomas among tumors previously classified as re nal cell carcinomas or sometimes as renal adenomas. If the large, perhaps somewhat selective, Mayo Clinic se ries’ numbers are excluded [4], the frequency of renal oncocytomas in tumors previously classified as renal cell carcinomas rises to 87/1,587 or 5.4%. For patients described in the English-language uro logie literature, the ratio of renal oncocytomas among males and females has been 2.2:1, very similar to the sex distribution of typical renal cell carcinomas. Ages of patients with renal oncocytoma have varied from 15 to 94 years. The median age for patients with renal onco cytoma has been 62-63 years, which is a somewhat older median age than for patients with typical renal cell carcinoma, which in many large series is around 55 years.
Renal Oncocytoma: Prognosis and Treatment
Tumor Size
Renal oncocytomas in reported clinical series have not been small incidentally discovered renocortical neo plasms found at the time of autopsy. Rather, in collected series, the median size of reported oncocytomas was 6 cm in diameter. This means that half the tumors were 6 cm in size or larger and quite a few were indeed larger than 10 cm in diameter. Renal oncocytomas are not pathological curiosities but rather substantial renal mass lesions.
Radiological Findings
The majority of renal oncocytomas have been discov ered and continue to be discovered because an excretory urogram, ultrasound examination or CT scan of the abdomen is performed for some unrelated reason. By excretory urography, by ultrasound examination or by CT scanning, most oncocytomas simply have the typical appearance of a solid renal mass lesion. For certain larger tumors, the prominent, central, stellate, scar re gion is imaged and can suggest preoperatively the diag nosis of a renal oncocytoma. This imaging result has not been specific. We have suggested from our own institu tion that renal oncocytomas may give a relatively spe cific pattern by MRI which may be useful for diagnosis [8], but further experience with MRI of renal oncocyto mas will be necessary at many centers to see if these pre liminary observations can be substantiated. To date, renal angiography has been the test which has most likely suggested the presence of renal oncocy toma preoperatively. A number of typical angiographic signs that suggest the presence of a renal oncocytoma have been described [9]. These include a lucent rim sign, a homogeneous capillary nephrogram phase, the absence of wild, neoplastic vessels, and most usually the spoke wheeled appearance of the feeding arteries. In a group of oncocytomas seen at the Mayo Clinic which had had angiography performed, approximately one half of the tumors had typical angiographic appearances suggesting preoperatively the possibility of an oncocytoma. The other half of the tumors were either hypovascular or had an otherwise nonspecific angiographic pattern that could
not be differentiated from standard renal cell carcino mas. There have also been some suggestions in the urologie literature that specific radionucleide scanning tech niques might be useful for detecting renal oncocytomas preoperatively or that skinny needle aspiration biopsy might be useful for preoperative diagnosis as well [5], As yet, these specific techniques have not come into wide clinical use and must be regarded as areas for further clinical investigation at this time.
Treatment
Up until recent years nearly all renal oncocytomas were considered to be typical renal cell carcinomas and therefore most patients were treated by typical radical nephrectomy. Therefore, for almost all of the patients reported in the urologie literature, treatment by nephrec tomy was carried out. For renal oncocytomas, nephrec tomy has been a particularly good treatment and vir tually always has been curative. This fact must be remembered for the patient with a large solid renal mass lesion which destroys most of the kidney and for whom a good contralateral kidney is present. Whether the patient has a renal cell carcinoma or a renal oncocytoma, radical (total) nephrectomy will be the treatment of choice and agonizing over the possible presence of a renal oncocy toma is not rewarding. The real treatment dilemma occurs for the common clinical situation when a small asymptomatic solid renal mass lesion is discovered when a CT examination of the abdomen is performed for gen eral diagnostic purposes [10]. Many small, low-stage renal cell carcinomas are now being discovered by such a related clinical scenario [6]. Many solid renocortical lesions discovered by this technique also turn out to be renal oncocytomas. If such small ‘solid’ tumors are found in an anatomi cal or functional solitary kidney, extensive efforts should be made to salvage the remaining renal parenchyma by carring out tumor enucleation or partial nephrectomy by conventional techniques. But, there remains an area of active controversy and one for which no clear data are available now: that is, when patients with a contralateral normal kidney are found to have a small solitary mass lesion in the other kidney. For a relatively young, other wise healthy patient, our general approach has been for a tumor 4 cm in diameter or smaller, well-encapsulated by CT and confined to one of the poles of the kidney, to
Downloaded by: University of Exeter 144.173.6.94 - 6/7/2020 11:51:47 PM
be treated at the same operative exposure or might require total nephrectomy.
19
Lieber
20
Prognosis
Typical very well differentiated, pure, eosinophilic, granular-cell, renocortical tumors (typical renal oncocy tomas) appear almost invariably to have a benign clini cal behavior [5], Virtually none of the patients reported with typical renal oncocytomas have shown progressive disease or died from metastatic renal oncocytoma. In deed, typical renal oncocytomas behave like benign rather than malignant tumors. There have been a few case reports in the literature in which patients with a renal oncocytoma have been reported in which the tu mor was thought to be metastatic or in which the patient died of metastatic renal cancer. It is virtually impossible to know whether patients really had classic renal oncocy tomas. Higher-grade oncocytic or dark-cell renal cancers occur, metastasize and cause patients’ deaths. Whatever the ‘final determination’ in this regard, at this point it seems safe and reasonably conservative to state that the vast majority of typical renal oncocytomas have shown benign behavior, even when the primary tumor has been very large.
DNA Ploidy Analysis
Nuclear DNA ploidy analysis has been reported for a number of renal oncocytomas. Somewhat unexpectedly, certain typical oncocytomas have had abnormal ploidy patterns, showing either DNA tetraploidy or DNA aneuploidy [11], For this reason, DNA ploidy pattern alone cannot be used to distinguish between benign and malig nant neoplasms in the kidney.
Future Directions
Renal oncocytoma cells are different from the cells making up the vast majority of renal cell carcinomas or from the normal renocortical parenchyma. Some immu nologic or biochemical difference which can be exploited by new radiological, immunologic or nuclear medicine imaging techniques will no doubt be found in the future which will make preoperative diagnosis of renal oncocy toma much more definite. Such techniques may indeed be on the horizon [12], However, because renal oncocy tomas are relatively rare, definitive documentation that new techniques are reliable and practically useful will take a while to demonstrate since, even in very busy large medical centers, only a few typical renal oncocytomas are seen in a given year. Until the day arrives when confident preoperative diagnosis of renal oncocytoma is possible, urologists and radiologists must live with uncertainty in the treatment of a number of solid renal masses. They must adapt their clinical approach to the certain empirical truth that renal oncocytomas do exist. Removing a basically normal kid ney for a small, polar, well-encapsulated, typical renal oncocytoma is not now a great triumph of the urologist’s skill and art.
References 1 Klein, M. J.; Valensi, Q. J.: Proximal tubular adenomas of kidney
with so-called oncocytic features: a clinicopathological study of 13 cases of a rarely reported neoplasm. Cancer 38: 906-914 (1976). Nogueira, E.; Bannasch, P.: Cellular origin of rat renal oncocy toma. Lab. Invest. 59: 337-343 (1988). 3 Zerban, H.; Nogueira, E.; Riedasch, G.; Bannasch, P.: Renal oncocytoma: origin from the collecting duct. Virchows Arch. 52: 375-387 (1987). 4 Lieber. M.M.; Tornerà, K.M.; Farrow, G.M.: Renal oncocytoma. J. Urol. 125' 481-485. (1981).
Downloaded by: University of Exeter 144.173.6.94 - 6/7/2020 11:51:47 PM
recommend renal exploration and attempt partial ne phrectomy for these patients, with frozen-section control of the margins of resection [10]. Many 1-, 2- and 3-cmdiameter renal oncocytomas located in the poles of the kidneys are being discovered by CT scanning of the abdomen. To carry out radical nephrectomy for such patients, when such tumors can be technically removed with a safe margin and with a large fraction of a normal kidney thereby preserved, seems unnecessary. ‘Reflex’ radical nephrectomy for every solid renocortical lesion must be avoided now since tumors commonly are being picked up at such an early stage. Radical nephrectomy is not entirely appropriate in every case. Conversely, in the markedly elderly patients with a large renal tumor in which the possibility of an oncocy toma might be entertained, needle biopsy of the tumor, perhaps in multiple areas to demonstrate the presence of oncocytes, might be helpful. There are cases reported in the literature in which patients with bilateral large and unresectable renal oncocytomas have been followed for many years without showing distinct progression of the tumors. Such ‘observation treatment’ of oncocytomas might be entirely appropriate for the very elderly patient or patients who are otherwise at very poor operative risk because of extensive medical problems.
21
Renal Oncocytoma: Prognosis and Treatment
11 Rainwater, L.M.; Farrow, G.M.; Lieber, M.M.: Flow cytometry of renal oncocytoma: common occurrence of deoxyribonucleic acid polyploidy and aneuploidy. J. Urol. 135: 1167-1171 (1986). 12 Lee, V.W.; Allard, J.; Foster, J.; Sheahan, K.; Franklin, P.: Func tional oncocytoma of the kidney: evaluation by dual tracer scin tigraphy. J. nucl. Med. 28- 1911-1914 (1987).
Michael M. Lieber, MD Department of Urology Mayo Clinic Rochester, MN 55905 (USA)
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5 Lieber, M.M.; Tsukamoto, T.: Renal oncocytoma: in deKermon, Pavone-Macaluso, Tumors of the kidney, pp 257-273 (Williams & Wilkins, Baltimore 1986). 6 Konnak, J.W.; Grossman, H.B.: Renal cell carcinoma as an inci dental finding. J. Urol. 134. 1094-1096 (1985). 7 Warfel, K.A.; Eble, J.N.: Renal oncocytomatosis. J. Urol. 127 1179-1180 (1982). 8 Remark, R.R.; Berquist, T.FL: Lieber, M.M.: Charboneau. J.W.; Hartman, G.W.: Magnetic resonance imaging of renal oncocyto ma. Urology if 176-179 (1988). 9 Ambos, M.A.; Bosniak, M.A.; Valensi. Q.J.; Madayag, M.A.; Lefleur, S.S.: Angiographic patterns in renal oncocytomas. Radi ology 129: 615-622 (1978). 10 Lieber. M.M.: Renal cell carcinoma: new developments (Edito rial). Mayo Clin. Proc. 6O' 715-716 (1985).
Eur Urol 1990; 18(suppl 2):17-21
Renal Oncocytoma: Prognosis and Treatment
1608101
Michael M. Lieber Department of Urology, Mayo Clinic, Rochester, Minn., USA
Histopathology
‘Oncocytes’ by definition are large neoplastic cells with an intensely eosinophilic granular cytoplasm. By definition, ‘oncocytomas’ are tumors composed only of oncocytes. Oncocytomas are not uncommon throughout the body and are not limited to the kidneys. Numerous histochemical and ultrastructural studies have demon strated that the brightly eosinophilic cytoplasmic granu larity of oncocytes results from the fact that the cyto plasm of oncocytes is packed with mitochondria. The exact cell type that gives rise to an oncocytoma in the kidney or in other organs is unknown. However, several recent histochemical and immunohistochemical studies using monoclonal antibodies suggest that oncocytomas in animals and man probably arise from the distal renal tubules, in particular from the intercalated cells of the collecting tubules [2, 3],
Many renal cell carcinomas which behave as typical aggressive cancers also contain eosinophilic granular cells, either alone or in combination with clear-cell neo plastic elements. Such renal cell carcinomas generally have been called granular-cell or dark-cell renal carcino mas. But it is important to recognize that renal cell car cinomas made up of eosinophilic granular cells are not typical oncocytomas. Rather, the specific term ‘renal oncocytoma’ has come by selected usage to apply to a renocortical neoplasm made up of only a pure popula tion of very best differentiated eosinophilic granular cells or oncocytes. Since renocortical tumors which are composed strictly of very well differentiated oncocytes behave in a generally benign fashion, this fine-tuning of histological variables appears to have a practical end point. However, it is most important to remember that malignantly behaving renal neoplasms often have onco cytic features. Therefore, the differentiation of a typical renal oncocytoma from an oncocytic renal-cell carci noma can be a somewhat difficult pathological task based on nuclear morphology. Specific color illustrations of histopathology can be found in reference 4.
Gross Appearance
Renal oncocytomas often have a typical macroscopic appearance which differs substantially from the typical gross appearance of most renal cell carcinomas. Renal oncocytomas are generally well encapsulated with a well-
Downloaded by: University of Exeter 144.173.6.94 - 6/7/2020 11:51:47 PM
It is now certain that renal oncocytoma is a fairly common clinicopathologic entity. Current series suggest that 3-7% of solid renocortical tumors previously classi fied as renal cell carcinomas are in fact typical renal oncocytomas. Thus, renal oncocytoma is an unusual, but not rare, renocortical neoplasm which most urologists, radiologists and pathologists will come upon from time to time. The start of the renal oncocytoma era can be dated exactly to the publication of Klein and Valensi in 1976 [1]. Prior to 1975 there had been only 6 individual case reports describing renal oncocytomas.
Lieber
defined, thick, fibrous capsule, and the tumor tissue itself rarely penetrates the renal capsule or invades other structures. Because of this expansile growth, renal onco cytomas are almost always spherical without the types of invasive pseudopod-like growth seen with some renal cell carcinomas. The renal pelvis, the intrarenal collect ing system and the perinephric fat generally are not invaded by the tumor. On fresh cross-section, renal oncocytoma tissue is generally tannish-brown or ma hogany-brown in color. This characteristic brown col oring is usually different from the bright yellow or yellow-and-white cut surface seen with typical renal cell car cinomas. The cross-section of small renal oncocytomas generally has a homogeneous appearance with no hemor rhage or necrosis within the tumor. Medium- and large sized oncocytomas commonly show a prominent, stel late, central, fibrous scar which gives them an almost pathognomic cross appearance [1, 4], The characteristic central scar is often imaged preoperatively by CT or magnetic resonance imaging (MRI) examination of the tumor, sometimes even by ultrasound examination, and can serve to suggest the diagnosis of oncocytoma preoperatively.
Clinical Presentation
As might be expected from their slow, well-encapsu lated, spherical, expansile growth, renal oncocytomas usually are not symptomatic. Indeed, the vast majority of such tumors has been discovered incidentally during the course of evaluation for some unrelated symptom or at postmortem examination. This important feature was originally pointed out by Klein and Valensi [1], In every large series reported, the majority of typical onco cytomas was in fact discovered incidentally, and in some series none of the patients with oncocytomas had any symptoms at all. Indeed, the incidence of gross hematuria, abdominal pain, flank mass and micro scopic hematuria has been remarkably low [5], New techniques to image the kidneys and the retroperitoneum have come into widespread use in the past de cade. These new techniques include ultrasound imag ing, CT imaging of the abdomen and now MRI. In most large medical centers commonly carrying out these new techniques, many more renocortical neoplasms, both renal cell carcinomas and renal oncocytomas, are being discovered in a small and asymptomatic stage than ever before [6],
Incidence of Renal Oncocytoma Multifocal Occurrence and Bilaterality
Current collected literature series do not suggest a preference for right or left kidney or site within the kid ney for renal oncocytomas. Rather, they occur uniformly throughout the renal cortex. Ninety-four percent of tu mors have been unilateral, but it is most important to remember that approximately 6% of reported cases of oncocytoma had bilateral tumors [5]. Both synchronous and asynchronous bilateral renal oncocytomas have been reported and, in addition, bilateral solid renal tumors with a renal oncocytoma on one side and a typical renal cell carcinoma on the other side have also been reported. Multifocal renal oncocytomas occurring in multiple lo cations within one kidney or in both kidneys have also been described. The specific term ‘oncocytomatosis’ has been used to describe this typical entity [7], As tumor enucleation or partial nephrectomy becomes a more common treatment for renal oncocytoma, the fact that multifocal renal oncocytomas or oncocytomatosis may occur in the same kidney must be borne in mind, and a careful search by radiological imaging techniques and by direct examination at the time of surgery must be em ployed to look for multifocal oncocytomas which could
Downloaded by: University of Exeter 144.173.6.94 - 6/7/2020 11:51:47 PM
The last time that I collected large series of renal oncocytomas was approximately 5 years ago [5], At that time 11 large series of renocortical tumors were pooled, making up a total of 4,304 individual tumors studied from around the world. In this group, 149 instances of typical renal oncocytoma were identified. Such figures suggest an overall incidence of about 3-4% for renal oncocytomas among tumors previously classified as re nal cell carcinomas or sometimes as renal adenomas. If the large, perhaps somewhat selective, Mayo Clinic se ries’ numbers are excluded [4], the frequency of renal oncocytomas in tumors previously classified as renal cell carcinomas rises to 87/1,587 or 5.4%. For patients described in the English-language uro logie literature, the ratio of renal oncocytomas among males and females has been 2.2:1, very similar to the sex distribution of typical renal cell carcinomas. Ages of patients with renal oncocytoma have varied from 15 to 94 years. The median age for patients with renal onco cytoma has been 62-63 years, which is a somewhat older median age than for patients with typical renal cell carcinoma, which in many large series is around 55 years.
Renal Oncocytoma: Prognosis and Treatment
Tumor Size
Renal oncocytomas in reported clinical series have not been small incidentally discovered renocortical neo plasms found at the time of autopsy. Rather, in collected series, the median size of reported oncocytomas was 6 cm in diameter. This means that half the tumors were 6 cm in size or larger and quite a few were indeed larger than 10 cm in diameter. Renal oncocytomas are not pathological curiosities but rather substantial renal mass lesions.
Radiological Findings
The majority of renal oncocytomas have been discov ered and continue to be discovered because an excretory urogram, ultrasound examination or CT scan of the abdomen is performed for some unrelated reason. By excretory urography, by ultrasound examination or by CT scanning, most oncocytomas simply have the typical appearance of a solid renal mass lesion. For certain larger tumors, the prominent, central, stellate, scar re gion is imaged and can suggest preoperatively the diag nosis of a renal oncocytoma. This imaging result has not been specific. We have suggested from our own institu tion that renal oncocytomas may give a relatively spe cific pattern by MRI which may be useful for diagnosis [8], but further experience with MRI of renal oncocyto mas will be necessary at many centers to see if these pre liminary observations can be substantiated. To date, renal angiography has been the test which has most likely suggested the presence of renal oncocy toma preoperatively. A number of typical angiographic signs that suggest the presence of a renal oncocytoma have been described [9]. These include a lucent rim sign, a homogeneous capillary nephrogram phase, the absence of wild, neoplastic vessels, and most usually the spoke wheeled appearance of the feeding arteries. In a group of oncocytomas seen at the Mayo Clinic which had had angiography performed, approximately one half of the tumors had typical angiographic appearances suggesting preoperatively the possibility of an oncocytoma. The other half of the tumors were either hypovascular or had an otherwise nonspecific angiographic pattern that could
not be differentiated from standard renal cell carcino mas. There have also been some suggestions in the urologie literature that specific radionucleide scanning tech niques might be useful for detecting renal oncocytomas preoperatively or that skinny needle aspiration biopsy might be useful for preoperative diagnosis as well [5], As yet, these specific techniques have not come into wide clinical use and must be regarded as areas for further clinical investigation at this time.
Treatment
Up until recent years nearly all renal oncocytomas were considered to be typical renal cell carcinomas and therefore most patients were treated by typical radical nephrectomy. Therefore, for almost all of the patients reported in the urologie literature, treatment by nephrec tomy was carried out. For renal oncocytomas, nephrec tomy has been a particularly good treatment and vir tually always has been curative. This fact must be remembered for the patient with a large solid renal mass lesion which destroys most of the kidney and for whom a good contralateral kidney is present. Whether the patient has a renal cell carcinoma or a renal oncocytoma, radical (total) nephrectomy will be the treatment of choice and agonizing over the possible presence of a renal oncocy toma is not rewarding. The real treatment dilemma occurs for the common clinical situation when a small asymptomatic solid renal mass lesion is discovered when a CT examination of the abdomen is performed for gen eral diagnostic purposes [10]. Many small, low-stage renal cell carcinomas are now being discovered by such a related clinical scenario [6]. Many solid renocortical lesions discovered by this technique also turn out to be renal oncocytomas. If such small ‘solid’ tumors are found in an anatomi cal or functional solitary kidney, extensive efforts should be made to salvage the remaining renal parenchyma by carring out tumor enucleation or partial nephrectomy by conventional techniques. But, there remains an area of active controversy and one for which no clear data are available now: that is, when patients with a contralateral normal kidney are found to have a small solitary mass lesion in the other kidney. For a relatively young, other wise healthy patient, our general approach has been for a tumor 4 cm in diameter or smaller, well-encapsulated by CT and confined to one of the poles of the kidney, to
Downloaded by: University of Exeter 144.173.6.94 - 6/7/2020 11:51:47 PM
be treated at the same operative exposure or might require total nephrectomy.
19
Lieber
20
Prognosis
Typical very well differentiated, pure, eosinophilic, granular-cell, renocortical tumors (typical renal oncocy tomas) appear almost invariably to have a benign clini cal behavior [5], Virtually none of the patients reported with typical renal oncocytomas have shown progressive disease or died from metastatic renal oncocytoma. In deed, typical renal oncocytomas behave like benign rather than malignant tumors. There have been a few case reports in the literature in which patients with a renal oncocytoma have been reported in which the tu mor was thought to be metastatic or in which the patient died of metastatic renal cancer. It is virtually impossible to know whether patients really had classic renal oncocy tomas. Higher-grade oncocytic or dark-cell renal cancers occur, metastasize and cause patients’ deaths. Whatever the ‘final determination’ in this regard, at this point it seems safe and reasonably conservative to state that the vast majority of typical renal oncocytomas have shown benign behavior, even when the primary tumor has been very large.
DNA Ploidy Analysis
Nuclear DNA ploidy analysis has been reported for a number of renal oncocytomas. Somewhat unexpectedly, certain typical oncocytomas have had abnormal ploidy patterns, showing either DNA tetraploidy or DNA aneuploidy [11], For this reason, DNA ploidy pattern alone cannot be used to distinguish between benign and malig nant neoplasms in the kidney.
Future Directions
Renal oncocytoma cells are different from the cells making up the vast majority of renal cell carcinomas or from the normal renocortical parenchyma. Some immu nologic or biochemical difference which can be exploited by new radiological, immunologic or nuclear medicine imaging techniques will no doubt be found in the future which will make preoperative diagnosis of renal oncocy toma much more definite. Such techniques may indeed be on the horizon [12], However, because renal oncocy tomas are relatively rare, definitive documentation that new techniques are reliable and practically useful will take a while to demonstrate since, even in very busy large medical centers, only a few typical renal oncocytomas are seen in a given year. Until the day arrives when confident preoperative diagnosis of renal oncocytoma is possible, urologists and radiologists must live with uncertainty in the treatment of a number of solid renal masses. They must adapt their clinical approach to the certain empirical truth that renal oncocytomas do exist. Removing a basically normal kid ney for a small, polar, well-encapsulated, typical renal oncocytoma is not now a great triumph of the urologist’s skill and art.
References 1 Klein, M. J.; Valensi, Q. J.: Proximal tubular adenomas of kidney
with so-called oncocytic features: a clinicopathological study of 13 cases of a rarely reported neoplasm. Cancer 38: 906-914 (1976). Nogueira, E.; Bannasch, P.: Cellular origin of rat renal oncocy toma. Lab. Invest. 59: 337-343 (1988). 3 Zerban, H.; Nogueira, E.; Riedasch, G.; Bannasch, P.: Renal oncocytoma: origin from the collecting duct. Virchows Arch. 52: 375-387 (1987). 4 Lieber. M.M.; Tornerà, K.M.; Farrow, G.M.: Renal oncocytoma. J. Urol. 125' 481-485. (1981).
Downloaded by: University of Exeter 144.173.6.94 - 6/7/2020 11:51:47 PM
recommend renal exploration and attempt partial ne phrectomy for these patients, with frozen-section control of the margins of resection [10]. Many 1-, 2- and 3-cmdiameter renal oncocytomas located in the poles of the kidneys are being discovered by CT scanning of the abdomen. To carry out radical nephrectomy for such patients, when such tumors can be technically removed with a safe margin and with a large fraction of a normal kidney thereby preserved, seems unnecessary. ‘Reflex’ radical nephrectomy for every solid renocortical lesion must be avoided now since tumors commonly are being picked up at such an early stage. Radical nephrectomy is not entirely appropriate in every case. Conversely, in the markedly elderly patients with a large renal tumor in which the possibility of an oncocy toma might be entertained, needle biopsy of the tumor, perhaps in multiple areas to demonstrate the presence of oncocytes, might be helpful. There are cases reported in the literature in which patients with bilateral large and unresectable renal oncocytomas have been followed for many years without showing distinct progression of the tumors. Such ‘observation treatment’ of oncocytomas might be entirely appropriate for the very elderly patient or patients who are otherwise at very poor operative risk because of extensive medical problems.
21
Renal Oncocytoma: Prognosis and Treatment
11 Rainwater, L.M.; Farrow, G.M.; Lieber, M.M.: Flow cytometry of renal oncocytoma: common occurrence of deoxyribonucleic acid polyploidy and aneuploidy. J. Urol. 135: 1167-1171 (1986). 12 Lee, V.W.; Allard, J.; Foster, J.; Sheahan, K.; Franklin, P.: Func tional oncocytoma of the kidney: evaluation by dual tracer scin tigraphy. J. nucl. Med. 28- 1911-1914 (1987).
Michael M. Lieber, MD Department of Urology Mayo Clinic Rochester, MN 55905 (USA)
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