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Hypernephroma arising in wall of simple renal cyst
HYPERNEPHROMA SIMPLE
G. SUFRIN,
RENAL
ARISING
IN WALL
OF
CYST
M.D.
W. ETRA,
M.D.
J. GAETA,
M.D.
C. E. MERRIN,
M.D.
From the Roswell Park Memorial Institute, New York State Department of Health, State University of New York at Buffalo, New York
ABSTRACT -An unusual case of hypernephroma arising from the wall of a simple renal cyst is presented. Despite prior controversy as to the existence of this entity continuity between normal and neoplastic cells lining the cyst wall was demonstrated thus confirming this lesion as a distinct entity. Furthermore, we wish to direct attention to the limitations of biochemical and cytologic analysis of renal cyst fluid in distinguishing benign and neoplastic lesions.
The coexistence of cyst and hypernephroma within the same kidney has been reported to be uncommon; Emmett, Levine, and Woolnerl observed only 10 examples of this in a series of 1,007 surgically documented cases. Gibson’ has classified the relationship between cysts and tumors arising from the same kidney as follows: (1) widely separated lesions of unrelated origin; (2) origin of a cyst within a tumor; (3) origin of a tumor within a cyst; (4) origin of a cyst distal to a tumor. That the occurrence of neoplasm within a cyst (type 3) is rare, is attested to by the large Mayo Clinic series in which no case was found of tumor in a simple serous cyst.3 Others, however, have called attention to this entity.4-‘3 Kropp et al. l4 noted a mortality of 1.6 per cent and a morbidity of 30 per cent associated with exploration of renal masses that subsequently proved to be benign cysts. Thus a diagnostic test that convincingly allowed one to exclude tumor would be of value. To increase confidence in the preoperative evaluation of renal mass lesions, techniques including nephrotomography, sonography, selective renal arteriography, and cyst puncture have been proposed. Recently, biochemical and cytologic study of aspirated cyst fluid has been stated to be a highly reliable
UROLOGY
/ OCTOBER
1975 / VOLUME
VI. NUMBER
method to evaluate the presence of neoplasm in an otherwise cystic-appearing renal mass.15 The following case report further documents the existence of tumor arising within a cyst and emphasizes that a normal cyst fluid analysis does not invariably exclude malignancy. Case Report This was the first admission at Roswell Park Memorial Institute of a fifty-seven-year-old white male entering for evaluation of a left renal mass. The patient was entirely well until the onset of mild left flank and low back pain six months prior to admission. The pain gradually progressed in severity, and three weeks prior to admission lumbosacral spine films showed a lytic lesion at second lumbar vertebra. A metastatic workup included an intravenous pyelogram which demonstrated a left renal mass. There was no history of hematuria, fever, or weight loss. Past medical history and review of symptoms were noncontributory. Physical examination was entirely normal and showed a well-developed, well-nourished male with normal vital signs. No abdominal masses or bruits were noted. Complete blood cell count,
507
FIGURE 1. (A) X-ray film of lumbar spine; note lytic lesion and collapsed second lumbar vertebra. (B) Selective left renal arteriogram; inferior displacement of kidney and renal artery by mass in upper pole of left kidney. Hypervascularity and abnormal vessels are seen corresponding to location of tumor in cyst wall.
urinalysis, SMA 12, serum enzymes, and electrocardiogram were normal. Chest x-ray film and liver scan were normal. Lumbosacral spine films showed a lytic lesion and a collapsed vertebral body at the second lumbar vertebra (Fig. 1A). Intravenous pyelogram revealed a normal right kidney. A large%ass was noted in theupppr pole of the left kidney with displacement of the renal axis and distortion of the collecting system. No calcification was noted within this mass. Selective left renal arteriography showed inferior displacement of the renal artery and a relatively avascular mass in the left upper pole (Fig. 1B). However, areas of increased vascularity and abnormal vessels suggesting a tumor were seen in the inferior portion of the mass. A preoperative diagnosis of left hypernephroma with vertebral metastasis was made and because of persistent flank pain, a left nephrectomy performed. Pathology Examination of the resected specimen showed that the upper pole of the kidney was replaced by a 12 by 12 cm. cystic lesion containing 425 ml. of clear yellow fluid. Except for several nodular areas occurring within the cyst, the peripheral wall of the cyst was translucent and measured an average of 0.5 mm. in thickness. On opening the cyst, the inner wall was noted to be smooth except for several (ten to twelve) irregular nodular areas measuring up to 5 mm. in thickness and 5 mm. in maximum diameter. The base of the cyst was also studded with similar nodules of firm white to yellow tissue interspersed by a smooth lining. On sectioning the kidney, the renal cortex appeared to be superficially infiltrated by these nodules although the medullary portion appeared intact. In those areas of the cyst wall which were grossly noted to be smooth, histologic examina-
508
tion showed a simple fibrous wall partially lined by a row of epithelial cells (Fig. 2A). In the nodular areas described however, both in the peripheral wall and in the base of the cyst, the epithelium became thicker (Fig. 2B) and became arranged in solid sheets which infiltrated the cyst wall and underlying renal cortex (Fig. 2C). As can be seen, these cells showed the cytologic features of a renal cell carcinoma. An additional important observation was the absence of any hemorrhage, calcification, or tumor necrosis which further argues against the occurrence of cystic degeneration within a tumor. Comment Previous reports of tumor occurring within the wall of a simple renal cyst indicate that 71 per cent of cases occurred in males, with an average age at the time of diagnosis of fifty-five years4*13 Hematuria was distinctly uncommon, whereas aspirated cyst fluid was grossly normal in 35 per cent of cases. Furthermore, of those cases in which cytopathologic study of the cyst fluid was reported, 50 per cent were normal. Since calcification within a renal mass suggests neoplasm, it is of interest that only 7 per cent of lesions showed calcification. Arteriography was positive in 60 per cent of cases. In the majority of reports the diagnosis of tumor within a cyst was not suspected preoperatively. Although the pathologic findings presented in Figure 2A and B indicate that tumor arose from the wall of a cyst, it must be noted that controversy surrounds this interpretation. Gibson2 based on the earlier work of Hepler,16 suggested that while tumors could arise from the wall of a solitary cyst it was more likely that the majority of these cases represented cyst distal to a tumor (type 4). He asserted that tumors arising in the kidney may, by causing tubular and vascular
UROLOGY
/ OCTOBER
1975 I
VOLUME
VI, NUMBER
4
FIGURE 2. (A) Peripheral portion of cyst wall uninvolved by tumor (reduced from X 200). (B) Detail of cyst wall with epithelial lining (reduced from x 160). (C) Wall of cyst injiltrated by sheets of neoplastic cells (reduced from x 160).
Cyst fluid analysis ____ Patient Cyst Fluid Serum
TABLE I.
study Color Blood urea nitrogen (mg. per 100 ml.) Glucose (mg. per 100 ml.) Total lipid
Clear yellow
.
Normal Serum Value .
.
25
21
< 20
85
90
Cl00
ml.)
70
689
470 to 750
(mg. per 100 ml.) Lactic dehydrogenase (I.U. per ml.) Total protein (Gm. per 100 ml.) Immunoglobulins (mf;;er 100 ml.)
54
133
120 to 250
68
126
90 to 200
5.6
6.4
6 to 8
628 52 125
800 to 1,800 90 to 450 60 to 250 . .
C;WP;;l100
745 IgA IgM Culture Cytology
;s No growth Negative for tumor
UROLOGY / OCTOBER 1975 / VOLUME VI, NUMBER 4
509
occlusion, result in cyst formation. Gibson believed that such cysts enlarge and eventually engulf the tumor giving the tumor the appearance of having originated from the cyst wall. In the case reported here, however, histologic evidence confirms the origin of tumor within a cyst. Biochemical and cytologic study of aspirated renal cyst fluid has been reported to be a highly reliable indicator of the presence of tumor.15 Based on an extensive experience with mass lesions of the kidney Lang” has stated that analysis of aspirated cyst fluid is a decisive diagnostic investigation. In general, the fluid contained in a benign cyst is clear, cytologically negative, has a normal total lipid and total protein content and a normal lactic dehydrogenase level.” In the case reported here, fluid from the cyst fulfilled these criteria although tumor was present in the cyst wall (Table I). Hence, although Lang has asserted that biochemical and cytologic assay of the cyst fluid is the crucial diagnostic investigation, claims as to the infallibility of cyst fluid analysis must be modified. Furthermore, since alterations in serum immunoglobulins have been observed in association with hypernephroma, it is instructive to compare the immunoglobulin pattern of cyst fluid to that of serum. I8 The reduction of IgM concentration is noteworthy although the ultimate significance of this finding awaits further study. In addition to the benign nature of the cyst fluid, this case is of further interest in that the arteriogram clearly demonstrated the malignant nature of the lesion and illustrated the intimate anatomic relationship between tumor and cyst wall (Fig. 1B). The paucity of radiographic findings in previously reported cases of tumor arising within a cyst has been alluded to.’ In a recent article a normal arteriogram was noted despite histologically proved evidence of tumor within a cyst. I2 Contrary to previous observations and although rare, hypernephroma may arise within the wall of a simple serous cyst as illustrated by the case presented. In addition, we direct attention to possible limitations of biochemical and cytologic analysis of cyst fluid as the sole diagnostic examination in presumed cystic lesions of the kidney.
510
666 Elm Street Buffalo, New York 14203 (DR. SUFRIN)
References 1. EMMETT, J. L., LEVINE, S. R., and WOOLNER, L. B.: Co-existence of renal cyst and tumour: incidence in 1,007cases, Br. J. Urol. 35: 403 (1963). 2. GIBSON, T. E.: Interrelationship of renal cysts and tumors: report of three cases, J. Urol. 71: 241 (1954). 3. LEVINE, S. It., EMMETT, J. L., and WOOLNER, L. B.: Cyst and tumor occurring in the same kidney, ibid. 91r 8 (1964). 4. EMANUEL, M. : Small renal cell carcinoma presenting as a solitary cyst, J. Maine Med. Assoc. 44: 192 (1953). 5. LOWSLEY, 0. S.: Malignant cyst of the kidney, J. Urol. 74: 586 (1955). 6. BRANNAN, W., MILLER, W., and CRISLER, M.: Coexistence of renal neoplasms and renal cysts, South. Med. J. 55: 749 (1962). 7. KHORSAND, D. : Carcinoma within solitary renal cysts, J. Urol. 93: 440 (1965). of asymptomatic 8. KAISER, T. F., et al. : Evaluation renal masses by selective renal angiography and percutaneous needle puncture: a preliminary report, ibid. 98: 436 (1967). 9. SILVERMAN, J. F., and KILHENNY, C.: Tumor in the wall of a simple renal cyst. Report of a case, Radiology 93: 95 (1969). 10. WEITZNER, S. : Clear cell carcinoma of the free wall of a simple renal cyst, J. Urol. 106: 515 (1971). of cyst and tumor in the 11. LANG, E. K.: Co-existence same kidney, Radiology 101: 7 (1971). 12. GELLMAN, A. C., SPORER, A., and SEEBODE, J.: Carcinoma of kidney. Benign-appearing calcified cyst, Urology 2: 556 (1973). 13. SRIMANNARAYANA,A., KELLY, D. G., and DUFF, F. A.: Renal cell carcinoma in the free wall of a simple renal cyst, Br. J. Urol. 47: 152 (1975). 14. KROPP, K. A., GRAYHACK, J. T., WENDEL, R. M., and DAHL, D. S.: Morbidity and mortality of renal exploration for cyst, Surg. Gynecol. Obstet. 125: 803 (1967). of avascular renal 15. LANG, E. K., et al. : Assessment mass lesions: the use of nephrotomography, arteriography, cyst puncture, double contrast study and histochemical and histopathologic examination of the aspirate, South. Med. J. 65: I (1972). 16. HEPLER, A. B. : Solitary cysts of the kidney. A report of seven cases and observations on the pathogenesis of these cysts, Surg. Gynecol. Obstet. 50: 668 (1930). Diagnosis of 17. LANG, E. K.: The Roentgenographic Renal Mass Lesions, St. Louis, Warren H. Green, Inc., 1971, p. 99. 18. RAVITZ, G., WATNE, A. L., and MILAM, D. F.: Autoantibodies to human renal cell carcinoma, J. Urol. 107: 26 (1972).
UROLOGY
/
OCTOBER 1975 /
VOLUME VI, NUMBER 4
G. SUFRIN,
RENAL
ARISING
IN WALL
OF
CYST
M.D.
W. ETRA,
M.D.
J. GAETA,
M.D.
C. E. MERRIN,
M.D.
From the Roswell Park Memorial Institute, New York State Department of Health, State University of New York at Buffalo, New York
ABSTRACT -An unusual case of hypernephroma arising from the wall of a simple renal cyst is presented. Despite prior controversy as to the existence of this entity continuity between normal and neoplastic cells lining the cyst wall was demonstrated thus confirming this lesion as a distinct entity. Furthermore, we wish to direct attention to the limitations of biochemical and cytologic analysis of renal cyst fluid in distinguishing benign and neoplastic lesions.
The coexistence of cyst and hypernephroma within the same kidney has been reported to be uncommon; Emmett, Levine, and Woolnerl observed only 10 examples of this in a series of 1,007 surgically documented cases. Gibson’ has classified the relationship between cysts and tumors arising from the same kidney as follows: (1) widely separated lesions of unrelated origin; (2) origin of a cyst within a tumor; (3) origin of a tumor within a cyst; (4) origin of a cyst distal to a tumor. That the occurrence of neoplasm within a cyst (type 3) is rare, is attested to by the large Mayo Clinic series in which no case was found of tumor in a simple serous cyst.3 Others, however, have called attention to this entity.4-‘3 Kropp et al. l4 noted a mortality of 1.6 per cent and a morbidity of 30 per cent associated with exploration of renal masses that subsequently proved to be benign cysts. Thus a diagnostic test that convincingly allowed one to exclude tumor would be of value. To increase confidence in the preoperative evaluation of renal mass lesions, techniques including nephrotomography, sonography, selective renal arteriography, and cyst puncture have been proposed. Recently, biochemical and cytologic study of aspirated cyst fluid has been stated to be a highly reliable
UROLOGY
/ OCTOBER
1975 / VOLUME
VI. NUMBER
method to evaluate the presence of neoplasm in an otherwise cystic-appearing renal mass.15 The following case report further documents the existence of tumor arising within a cyst and emphasizes that a normal cyst fluid analysis does not invariably exclude malignancy. Case Report This was the first admission at Roswell Park Memorial Institute of a fifty-seven-year-old white male entering for evaluation of a left renal mass. The patient was entirely well until the onset of mild left flank and low back pain six months prior to admission. The pain gradually progressed in severity, and three weeks prior to admission lumbosacral spine films showed a lytic lesion at second lumbar vertebra. A metastatic workup included an intravenous pyelogram which demonstrated a left renal mass. There was no history of hematuria, fever, or weight loss. Past medical history and review of symptoms were noncontributory. Physical examination was entirely normal and showed a well-developed, well-nourished male with normal vital signs. No abdominal masses or bruits were noted. Complete blood cell count,
507
FIGURE 1. (A) X-ray film of lumbar spine; note lytic lesion and collapsed second lumbar vertebra. (B) Selective left renal arteriogram; inferior displacement of kidney and renal artery by mass in upper pole of left kidney. Hypervascularity and abnormal vessels are seen corresponding to location of tumor in cyst wall.
urinalysis, SMA 12, serum enzymes, and electrocardiogram were normal. Chest x-ray film and liver scan were normal. Lumbosacral spine films showed a lytic lesion and a collapsed vertebral body at the second lumbar vertebra (Fig. 1A). Intravenous pyelogram revealed a normal right kidney. A large%ass was noted in theupppr pole of the left kidney with displacement of the renal axis and distortion of the collecting system. No calcification was noted within this mass. Selective left renal arteriography showed inferior displacement of the renal artery and a relatively avascular mass in the left upper pole (Fig. 1B). However, areas of increased vascularity and abnormal vessels suggesting a tumor were seen in the inferior portion of the mass. A preoperative diagnosis of left hypernephroma with vertebral metastasis was made and because of persistent flank pain, a left nephrectomy performed. Pathology Examination of the resected specimen showed that the upper pole of the kidney was replaced by a 12 by 12 cm. cystic lesion containing 425 ml. of clear yellow fluid. Except for several nodular areas occurring within the cyst, the peripheral wall of the cyst was translucent and measured an average of 0.5 mm. in thickness. On opening the cyst, the inner wall was noted to be smooth except for several (ten to twelve) irregular nodular areas measuring up to 5 mm. in thickness and 5 mm. in maximum diameter. The base of the cyst was also studded with similar nodules of firm white to yellow tissue interspersed by a smooth lining. On sectioning the kidney, the renal cortex appeared to be superficially infiltrated by these nodules although the medullary portion appeared intact. In those areas of the cyst wall which were grossly noted to be smooth, histologic examina-
508
tion showed a simple fibrous wall partially lined by a row of epithelial cells (Fig. 2A). In the nodular areas described however, both in the peripheral wall and in the base of the cyst, the epithelium became thicker (Fig. 2B) and became arranged in solid sheets which infiltrated the cyst wall and underlying renal cortex (Fig. 2C). As can be seen, these cells showed the cytologic features of a renal cell carcinoma. An additional important observation was the absence of any hemorrhage, calcification, or tumor necrosis which further argues against the occurrence of cystic degeneration within a tumor. Comment Previous reports of tumor occurring within the wall of a simple renal cyst indicate that 71 per cent of cases occurred in males, with an average age at the time of diagnosis of fifty-five years4*13 Hematuria was distinctly uncommon, whereas aspirated cyst fluid was grossly normal in 35 per cent of cases. Furthermore, of those cases in which cytopathologic study of the cyst fluid was reported, 50 per cent were normal. Since calcification within a renal mass suggests neoplasm, it is of interest that only 7 per cent of lesions showed calcification. Arteriography was positive in 60 per cent of cases. In the majority of reports the diagnosis of tumor within a cyst was not suspected preoperatively. Although the pathologic findings presented in Figure 2A and B indicate that tumor arose from the wall of a cyst, it must be noted that controversy surrounds this interpretation. Gibson2 based on the earlier work of Hepler,16 suggested that while tumors could arise from the wall of a solitary cyst it was more likely that the majority of these cases represented cyst distal to a tumor (type 4). He asserted that tumors arising in the kidney may, by causing tubular and vascular
UROLOGY
/ OCTOBER
1975 I
VOLUME
VI, NUMBER
4
FIGURE 2. (A) Peripheral portion of cyst wall uninvolved by tumor (reduced from X 200). (B) Detail of cyst wall with epithelial lining (reduced from x 160). (C) Wall of cyst injiltrated by sheets of neoplastic cells (reduced from x 160).
Cyst fluid analysis ____ Patient Cyst Fluid Serum
TABLE I.
study Color Blood urea nitrogen (mg. per 100 ml.) Glucose (mg. per 100 ml.) Total lipid
Clear yellow
.
Normal Serum Value .
.
25
21
< 20
85
90
Cl00
ml.)
70
689
470 to 750
(mg. per 100 ml.) Lactic dehydrogenase (I.U. per ml.) Total protein (Gm. per 100 ml.) Immunoglobulins (mf;;er 100 ml.)
54
133
120 to 250
68
126
90 to 200
5.6
6.4
6 to 8
628 52 125
800 to 1,800 90 to 450 60 to 250 . .
C;WP;;l100
745 IgA IgM Culture Cytology
;s No growth Negative for tumor
UROLOGY / OCTOBER 1975 / VOLUME VI, NUMBER 4
509
occlusion, result in cyst formation. Gibson believed that such cysts enlarge and eventually engulf the tumor giving the tumor the appearance of having originated from the cyst wall. In the case reported here, however, histologic evidence confirms the origin of tumor within a cyst. Biochemical and cytologic study of aspirated renal cyst fluid has been reported to be a highly reliable indicator of the presence of tumor.15 Based on an extensive experience with mass lesions of the kidney Lang” has stated that analysis of aspirated cyst fluid is a decisive diagnostic investigation. In general, the fluid contained in a benign cyst is clear, cytologically negative, has a normal total lipid and total protein content and a normal lactic dehydrogenase level.” In the case reported here, fluid from the cyst fulfilled these criteria although tumor was present in the cyst wall (Table I). Hence, although Lang has asserted that biochemical and cytologic assay of the cyst fluid is the crucial diagnostic investigation, claims as to the infallibility of cyst fluid analysis must be modified. Furthermore, since alterations in serum immunoglobulins have been observed in association with hypernephroma, it is instructive to compare the immunoglobulin pattern of cyst fluid to that of serum. I8 The reduction of IgM concentration is noteworthy although the ultimate significance of this finding awaits further study. In addition to the benign nature of the cyst fluid, this case is of further interest in that the arteriogram clearly demonstrated the malignant nature of the lesion and illustrated the intimate anatomic relationship between tumor and cyst wall (Fig. 1B). The paucity of radiographic findings in previously reported cases of tumor arising within a cyst has been alluded to.’ In a recent article a normal arteriogram was noted despite histologically proved evidence of tumor within a cyst. I2 Contrary to previous observations and although rare, hypernephroma may arise within the wall of a simple serous cyst as illustrated by the case presented. In addition, we direct attention to possible limitations of biochemical and cytologic analysis of cyst fluid as the sole diagnostic examination in presumed cystic lesions of the kidney.
510
666 Elm Street Buffalo, New York 14203 (DR. SUFRIN)
References 1. EMMETT, J. L., LEVINE, S. R., and WOOLNER, L. B.: Co-existence of renal cyst and tumour: incidence in 1,007cases, Br. J. Urol. 35: 403 (1963). 2. GIBSON, T. E.: Interrelationship of renal cysts and tumors: report of three cases, J. Urol. 71: 241 (1954). 3. LEVINE, S. It., EMMETT, J. L., and WOOLNER, L. B.: Cyst and tumor occurring in the same kidney, ibid. 91r 8 (1964). 4. EMANUEL, M. : Small renal cell carcinoma presenting as a solitary cyst, J. Maine Med. Assoc. 44: 192 (1953). 5. LOWSLEY, 0. S.: Malignant cyst of the kidney, J. Urol. 74: 586 (1955). 6. BRANNAN, W., MILLER, W., and CRISLER, M.: Coexistence of renal neoplasms and renal cysts, South. Med. J. 55: 749 (1962). 7. KHORSAND, D. : Carcinoma within solitary renal cysts, J. Urol. 93: 440 (1965). of asymptomatic 8. KAISER, T. F., et al. : Evaluation renal masses by selective renal angiography and percutaneous needle puncture: a preliminary report, ibid. 98: 436 (1967). 9. SILVERMAN, J. F., and KILHENNY, C.: Tumor in the wall of a simple renal cyst. Report of a case, Radiology 93: 95 (1969). 10. WEITZNER, S. : Clear cell carcinoma of the free wall of a simple renal cyst, J. Urol. 106: 515 (1971). of cyst and tumor in the 11. LANG, E. K.: Co-existence same kidney, Radiology 101: 7 (1971). 12. GELLMAN, A. C., SPORER, A., and SEEBODE, J.: Carcinoma of kidney. Benign-appearing calcified cyst, Urology 2: 556 (1973). 13. SRIMANNARAYANA,A., KELLY, D. G., and DUFF, F. A.: Renal cell carcinoma in the free wall of a simple renal cyst, Br. J. Urol. 47: 152 (1975). 14. KROPP, K. A., GRAYHACK, J. T., WENDEL, R. M., and DAHL, D. S.: Morbidity and mortality of renal exploration for cyst, Surg. Gynecol. Obstet. 125: 803 (1967). of avascular renal 15. LANG, E. K., et al. : Assessment mass lesions: the use of nephrotomography, arteriography, cyst puncture, double contrast study and histochemical and histopathologic examination of the aspirate, South. Med. J. 65: I (1972). 16. HEPLER, A. B. : Solitary cysts of the kidney. A report of seven cases and observations on the pathogenesis of these cysts, Surg. Gynecol. Obstet. 50: 668 (1930). Diagnosis of 17. LANG, E. K.: The Roentgenographic Renal Mass Lesions, St. Louis, Warren H. Green, Inc., 1971, p. 99. 18. RAVITZ, G., WATNE, A. L., and MILAM, D. F.: Autoantibodies to human renal cell carcinoma, J. Urol. 107: 26 (1972).
UROLOGY
/
OCTOBER 1975 /
VOLUME VI, NUMBER 4