0022-534 7 /79/1215-0681$02.00/0
Vol. 121, May Printed in U.S.A.
'fiIE JOURNAL OF UROLOGY
Copyright © 1979 by The Williams & Wilkins Co.
PRIMARY CARCINOMA IN SITU OF THE URETER AND RENAL PELVIS ANSAR U. KHAN, GEORGE M. FARROW, HORST ZINCKE,* DAVID C. UTZ
AND
LAURENCE F. GREENE
From the Mayo Clinic and Mayo Foundation, Rochester, Minnesota
ABSTRACT
Primary carcinoma in situ of the ureter or renal pelvis is rare. We describe 3 patients, each of whom had a different mode of presentation. When malignant cells in the urine from the upper urinary tract are associated with urographic evidence of an appropriate lesion, aggressive surgical therapy is indicated. In the absence of such a urographic abnormality patients with positive cytologic examinations should be followed closely because the exfoliated cells usually are from poorly differentiated neoplasms. Primary transitional cell carcinoma of the upper urinary tract constitutes about 5 per cent of all urothelial cancer. 1 Although, conceptually, urothelial carcinomas must pass through an in situ stage before becoming papillary or invasive 2 reports of primary in situ cancer of the renal pelvis or ureter without synchronous vesical neoplasia are extremely rare.:i-,; Herein we report on 3 patients with such in situ cancer who were seen at the Mayo Clinic during the last 6 years. The modes of presentation, the difficulties in diagnosis and the problems of management when this lesion presents only in the upper urinary tract are discussed. CASE REPORTS
Case 1 . A 70-year-old man was referred to us for urologic evaluation because of gross hematuria. The hematuria had occurred 3 months previously and had been associated with fracture of the lower right ribs. The excretory urogram (IVP) was interpreted as being within normal limits (fig. 1, A) but cytologic study of the urine revealed malignant cells. Cystoscopic examination revealed a normal-appearing bladder mucosa but a moderately obstructive prostate. The patient underwent transurethral prostatic resection. The source of the malignant cells in the urine was not determined and he was seen regularly at 3-month intervals until 9 months later when an episode of gross hematuria occurred. Cystoscopy revealed localization of the bleeding to the right ureteral orifice. After retrograde pyelography ureteral brushings from the lower third of the right ureter were done (fig. 1, B). The ureteral brushings were positive for poorly differentiated transitional cell carcinoma and, through an extended incision of the right flank, a nephroureterectomy was done and a cuff of the bladder was removed. The middle third of the ureter showed mucosal atypia, while a small area in the lower ureter, about 4 cm. away from the ureterovesical junction, showed changes of carcinoma in situ (fig. 1, C). Random sections of the renal pelvis and upper ureter showed no evidence of malignancy. Postoperatively, cytologic study of a voided urine specimen showed no abnormality but 6 months later voided urine showed carcinoma cells. Overt urothelial carcinoma was still not apparent 2 years later, findings on random bladder biopsy specimens were normal and the voided urine and urine from the left ureter contained malignant cells. Case 2. A 72-year-old woman was examined because of vague aches and pain, which for many years had affected the entire body. She also had a history of recurrent urinary infections and chronic urethrotrigonitis for which she had Accepted for publication July 21, 1978. Read at annual meeting of North Central Section, American Urological Association, San Diego, California, November 6-12, 1977. * Requests for reprints: Mayo Clinic, 200 First St. S.W., Rochester, Minnesota 55901.
received several urethral dilations and multiple courses of antibiotics. The patient denied any history of gross hematuria. An IVP revealed an obstructed left ureteropelvic junction with associated pyelocaliectasis and cortical atrophy (fig. 2). Cytologic study of voided and ureteral urine was positive for malignant cells and a left retrograde ureteropyelogram showed a normal left ureter except for an obstruction at the ureteropelvic junction. A left nephroureterectomy was done and a cuff of the bladder was removed. The specimen showed diffuse in situ grade 4 transitional cell carcinoma of the renal pelvis, extending into the infundibulum and minor calices. The ureteropelvic junction was obstructed by a fibrous stricture but it was not involved in the epithelial malignant change. Postoperatively, cytologic study of voided urine showed no malignant cells. Followup examinations during the last 6 years have shown no recurrent urothelial malignancy. Case 3. A 65-year-old woman, with a 10-year history of stress incontinence and occasional dysuria, had persistent microhematuria and pyuria. An IVP showed persistent narrowing of the distal portion of the left ureter and minimal ureterectasis proximal to the narrowing. Results of cystoscopic examination were normal and a left retrograde pyeloureterogram confirmed the stricture in the lower portion of the ureter (fig. 3, A). Urine cultures were negative but cytologic study of voided urine and of urine obtained from the left ureter revealed malignant cells. Through an extended incision in the left flank a nephroureterectomy was done and a cuff of the bladder was removed. Postoperatively, cytologic study of a voided urine specimen showed no abnormality. Histologic examination of the ureteral stricture showed in situ grade 3 transitional cell carcinoma in the lower third of the ureter, extending distally to about 1.4 cm. from the ureterovesical junction (fig. 3, B). Followup examinations have been normal for the last 4 years but, recently, cytologic study of a voided urine specimen was positive for malignant cells, while study of a right ureteral urine specimen showed no abnormality. No overt urothelial malignancy is as yet apparent and findings on a random bladder biopsy specimen showed no carcinoma. PATHOLOGIC FINDINGS
The concept of carcinoma in situ is not new, dating back several decades to the early work on carcinoma of the uterine cervix, and is in keeping with modern ideas of carcinogenesis that a progressive neoplastic alteration of the cells of an epithelial surface occurs before a grossly visible or an invasive neoplasm develops. The realization that carcinoma in situ is a stage in the development of urothelial malignancy has been delayed because urine cytologic study is generally not done early when the urothelial tumor is suspected or when the patient is asymptomatic. Carcinoma in situ may be defined as 681
682
KHAN AND ASSOCIATES
Fm. 1. Case 1. A, IVP findings are within normal limits. B, retrograde pyelogram 9 months later shows suspicious narrowing of distal third of ureter. C, nephroureterectomy-note carcinoma in situ in lower ureter.
Fm. 2. Case 2. IVP shows obstructed left ureteropelvic junction, pyelocaliectasis and cortical atrophy.
attention to the lesion may be drawn by urologic investigation for related symptoms, such as gross hematuria and renal colic (cases 1 and 2), or serendipitously (case 3). Diagnosis of the tumor also may present difficulties when the tumor is not apparent on the IVP and when malignant cells are present in the ureteral urine. These patients should be observed closely with urograms being taken regularly until a suspicious area becomes apparent, after which ureteral or renal pelvic brushing should be done to obtain tissue for histologic examination.12 Knowledge of the natural history of in situ urothelial carcinoma unassociated with concurrent invasive tumor is still scant and has been gained mainly from the studies of this lesion in the bladder. 7· 10· 13· 14 Recent articles7· 10 • 15 suggest that the natural evolution ofurothelial cancer from the in situ stage to invasion may span a longer period than previously reported. 14 · 16 Whether carcinoma in situ of the upper urinary tract behaves in a similar manner is not known, although in the single case report by Murphy and associates 3 it appeared that the lesion was present for 4 years and had not yet become invasive. In situ carcinoma of the ureter normally has been described in association with invasive bladder cancer7· 17· 18 and the poor prognosis associated with this condition probably should be ascribed to the invasive bladder tumor and the widespread urothelial abnormality that accompanies it. The keystone to
a full thickness carcinomatous alteration in the morphologic appearance of the transitional cell mucosa but without architectural alteration of the mucosa, such as papillary formation or invasion (fig. 3, B). This alteration occurs over a field of mucosal cells rather than in a single cell and, thus, when an invasive tumor eventually evolves it is usually within a moreor-less widespread zone of in situ carcinoma. 7 DISCUSSION
More reliable diagnostic techniques and the increasing use of urine cytology have facilitated the early diagnosis ofurothelial cancer at the in situ stage. 8• 0 Early diagnosis also has created a problem in the management of patients whose results of urinary cytology are positive and who have no overt evidence of tumor. 8• 10• 11 The problem is compounded further when random biopsy specimens of the bladder show no abnormalities and the malignant cells in the urine can be localized to the upper urinary tracts with no evidence of tumor on urographic studies. In most patients with positive urinary findings and occult tumors the lesion eventually develops in the bladder. 7· 11 Rarely, does the lesion become manifest only in the upper urinary tract. 7 There are various modes of presentation of this tumor and
Fm. 3. Case 3. A, left retrograde ureteropyelogram shows stricture of distal ureter. B, carcinoma in situ. There is increase in cell layers with individual cytologic features of malignancy and disordered maturation. H & E, reduced from xl60.
683
PRIMARY CARCINOMA IN SITU
the diagnosis of in situ carcinoma of the upper urinary tract is the presence of malignant cells in the ureteral urine, which occurs predominantly when the tumors are in the more malignant zones of the biologic spectrum. 19 Detection of a well differentiated tumor in the in situ stages is difficult because the incidence of positive findings on urine cell studies in well differentiated ureteral or pelvic tumors is low. 19 In our 3 patients the cytologic study of ureteral urine was positive and the tumors were either Broders' grade 3 or 4. Thus, a reasonably aggressive surgical approach for this lesion seems to be indicated. In our experience nephroureterectomy with removal of a bladder cuff was done in each instance through an extended flank incision. The incidence of subsequent bladder tumors in patients with transitional cell carcinoma of the upper urinary tract is high 20 and in 2 of our patients positive findings on voided urine were noted in a period of 6 and 48 months after nephroureterectomy. The incidence of a tumor developing in the contralateral upper urinary tracts is about 1.5 per cent. 21 Study of urine from the contralateral ureter of each of our 2 patients showed no malignant cells. In the patient described by Murphy and associates epithelial atypia was noted on bladder biopsy 11 weeks after the removal of the primary lesion and 1 year later cytologic study of urine from the contralateral ureter also was positive. 3 REFERENCES
1. Batata, M.A., Whitmore, W. F., Jr., Hilaris, B. S., Tokita, N. and Grabstald, H.: Primary carcinoma of the ureter: a prognostic study. Cancer, 35: 1626, 1975. 2. Melicow, M. M.: Carcinoma in situ: an historical perspective. Urol. Clin. N. Amer., 3: 5, 1976. 3. Murphy, W. M., von Buedingen, R. P. and Poley, R. W.: Primary carcinoma in situ of renal pelvis and ureter. Cancer, 34: 1126, 1974. 4. Foot, N. C. and Papanicolaou, G. N.: Early renal carcinoma in situ. Detected by means of smears of fixed urinary sediment. J.A.M.A., 139: 356, 1949. 5. Grabstald, H., Whitmore, W. F. and Melamed, M. R.: Renal pelvic tumors. J.A.M.A., 218: 845, 1971. 6. Melicow, M. M. and Hollowell, J. W.: Intra-urothelial cancer: carcinoma in situ, Bowen's disease of the urinary system: discussion of thirty cases. J. Urol., 68: 763, 1952. 7. Farrow, G. M., Utz, D. C. and Rife, C. C.: Morphological and clinical observations of patients with early bladder cancer treated with total cystectomy. Cancer Res., 36: 2495, 1976. 8. Utz, D. C. and Farrow, G. M.: In situ carcinoma of the bladder. J.C. E. Urol., 16: 19, 1977. 9. Utz, D. C. and Zincke, H.: The masquerade of bladder cancer in situ as interstitial cystitis. J. Urol., 111: 160, 1974. 10. Farrow, G. M., Utz, D. C., Rife, C. C. and Greene, L. F.: Clinical observations on sixty-nine cases of in situ carcinoma of the urinary bladder. Cancer Res., 37: 2794, 1977.
11. Heney, N. M., Szyfelbein, W. M., Daly, J. J., Prout, G. R. and Bredin, H. C.: Positive urinary cytology in patients without evident tumor. J. Urol., 117: 223, 1977. 12. Gill, W. B., Lu, C. T. and Thomsen, S.: Retrograde brushing: a new technique for obtaining histologic and cytologic material from ureteral, renal pelvic and renal caliceal lesions. J. Urol., l09: 573, 1973. 13. Koss, L. G.: Tumors of the urinary bladder. In: Atlas of Tumor Pathology. Washington, D.C.: Armed Forces Institute of Pathology, fasc. 11, p. 68, 1975. 14. Melamed, M. R., Voutsa, N. G. and Grabstald, H.: Natural history and clinical behavior of in situ carcinoma of the human urinary bladder. Cancer, 17: 1533, 1964. 15. Marshall, V. F. and Seybolt, J. F.: Early detection but delayed appearance ofa bladder tumor. J. Urol., 118: 175, 1977. 16. Utz, D. C., Hanash, K. A. and Farrow, G. M.: The plight of the patient with carcinoma in situ of the bladder. J. Urol., 103: 160, 1970. 17. Culp, 0. S., Utz, D. C. and Harrison, E. G., Jr.: Experiences with ureteral carcinoma in situ detected during operations for vesical neoplasm. J. Urol., 97: 679, 1967. 18. Sharma, T. C., Melamed, M. R. and Whitmore, W. F., Jr.: Carcinoma in-situ of the ureter in patients with bladder carcinoma treated by cystectomy. Cancer, 26: 583, 1970. 19. Zincke, H., Aguilo, J. J., Farrow, G. M., Utz, D. C. and Khan, A. U.: Significance of urinary cytology in the early detection of transitional cell cancer of the upper urinary tract. J. Urol., 116: 781, 1976. 20. Strong, D. W. and Pearse, H. D.: Recurrent urothelial tumors following surgery for transitional cell carcinoma of the upper urinary tract. Cancer, 38: 2178, 1976. 21. Lathan, H. S. and Kay, S.: Malignant tumors of the renal pelvis. Surg., Gynec. & Obst., 138: 613, 1974. EDITORIAL COMMENT Early detection of ureteral carcinomas has been elusive compared to those in the bladder, which can be biopsied readily as well as studied by the Papanicolaou method. Since currently available ureteroscopes are barely useful and only in grossly dilated structures Papanicolaou smears are usually the only preoperative objective evidence when there is not a simultaneous vesical growth. The authors are to be commended for presenting 3 authenticated cases that emphasize the need for good cytologists (as those at the Mayo Clinic obviously are). The reliable Papanicolaou smears, when read as showing carcinoma by adequate cytologists, are 98 per cent sound and should apply to ureteral as well as vesical carcinomas. I coauthored with Doctor Papanicolaou the first publication on his method as applied to urine 1 and the applications seem to be growing. Victor F. Marshall Department of Urology New York Hospital New York, New York 1. Papanicolaou, G. N. and Marshall, V. F.: Urine sediment smears as a diagnostic procedure in cancers of the urinary tract. Science, 101: 519, 1945.
Vol. 121, May Printed in U.S.A.
'fiIE JOURNAL OF UROLOGY
Copyright © 1979 by The Williams & Wilkins Co.
PRIMARY CARCINOMA IN SITU OF THE URETER AND RENAL PELVIS ANSAR U. KHAN, GEORGE M. FARROW, HORST ZINCKE,* DAVID C. UTZ
AND
LAURENCE F. GREENE
From the Mayo Clinic and Mayo Foundation, Rochester, Minnesota
ABSTRACT
Primary carcinoma in situ of the ureter or renal pelvis is rare. We describe 3 patients, each of whom had a different mode of presentation. When malignant cells in the urine from the upper urinary tract are associated with urographic evidence of an appropriate lesion, aggressive surgical therapy is indicated. In the absence of such a urographic abnormality patients with positive cytologic examinations should be followed closely because the exfoliated cells usually are from poorly differentiated neoplasms. Primary transitional cell carcinoma of the upper urinary tract constitutes about 5 per cent of all urothelial cancer. 1 Although, conceptually, urothelial carcinomas must pass through an in situ stage before becoming papillary or invasive 2 reports of primary in situ cancer of the renal pelvis or ureter without synchronous vesical neoplasia are extremely rare.:i-,; Herein we report on 3 patients with such in situ cancer who were seen at the Mayo Clinic during the last 6 years. The modes of presentation, the difficulties in diagnosis and the problems of management when this lesion presents only in the upper urinary tract are discussed. CASE REPORTS
Case 1 . A 70-year-old man was referred to us for urologic evaluation because of gross hematuria. The hematuria had occurred 3 months previously and had been associated with fracture of the lower right ribs. The excretory urogram (IVP) was interpreted as being within normal limits (fig. 1, A) but cytologic study of the urine revealed malignant cells. Cystoscopic examination revealed a normal-appearing bladder mucosa but a moderately obstructive prostate. The patient underwent transurethral prostatic resection. The source of the malignant cells in the urine was not determined and he was seen regularly at 3-month intervals until 9 months later when an episode of gross hematuria occurred. Cystoscopy revealed localization of the bleeding to the right ureteral orifice. After retrograde pyelography ureteral brushings from the lower third of the right ureter were done (fig. 1, B). The ureteral brushings were positive for poorly differentiated transitional cell carcinoma and, through an extended incision of the right flank, a nephroureterectomy was done and a cuff of the bladder was removed. The middle third of the ureter showed mucosal atypia, while a small area in the lower ureter, about 4 cm. away from the ureterovesical junction, showed changes of carcinoma in situ (fig. 1, C). Random sections of the renal pelvis and upper ureter showed no evidence of malignancy. Postoperatively, cytologic study of a voided urine specimen showed no abnormality but 6 months later voided urine showed carcinoma cells. Overt urothelial carcinoma was still not apparent 2 years later, findings on random bladder biopsy specimens were normal and the voided urine and urine from the left ureter contained malignant cells. Case 2. A 72-year-old woman was examined because of vague aches and pain, which for many years had affected the entire body. She also had a history of recurrent urinary infections and chronic urethrotrigonitis for which she had Accepted for publication July 21, 1978. Read at annual meeting of North Central Section, American Urological Association, San Diego, California, November 6-12, 1977. * Requests for reprints: Mayo Clinic, 200 First St. S.W., Rochester, Minnesota 55901.
received several urethral dilations and multiple courses of antibiotics. The patient denied any history of gross hematuria. An IVP revealed an obstructed left ureteropelvic junction with associated pyelocaliectasis and cortical atrophy (fig. 2). Cytologic study of voided and ureteral urine was positive for malignant cells and a left retrograde ureteropyelogram showed a normal left ureter except for an obstruction at the ureteropelvic junction. A left nephroureterectomy was done and a cuff of the bladder was removed. The specimen showed diffuse in situ grade 4 transitional cell carcinoma of the renal pelvis, extending into the infundibulum and minor calices. The ureteropelvic junction was obstructed by a fibrous stricture but it was not involved in the epithelial malignant change. Postoperatively, cytologic study of voided urine showed no malignant cells. Followup examinations during the last 6 years have shown no recurrent urothelial malignancy. Case 3. A 65-year-old woman, with a 10-year history of stress incontinence and occasional dysuria, had persistent microhematuria and pyuria. An IVP showed persistent narrowing of the distal portion of the left ureter and minimal ureterectasis proximal to the narrowing. Results of cystoscopic examination were normal and a left retrograde pyeloureterogram confirmed the stricture in the lower portion of the ureter (fig. 3, A). Urine cultures were negative but cytologic study of voided urine and of urine obtained from the left ureter revealed malignant cells. Through an extended incision in the left flank a nephroureterectomy was done and a cuff of the bladder was removed. Postoperatively, cytologic study of a voided urine specimen showed no abnormality. Histologic examination of the ureteral stricture showed in situ grade 3 transitional cell carcinoma in the lower third of the ureter, extending distally to about 1.4 cm. from the ureterovesical junction (fig. 3, B). Followup examinations have been normal for the last 4 years but, recently, cytologic study of a voided urine specimen was positive for malignant cells, while study of a right ureteral urine specimen showed no abnormality. No overt urothelial malignancy is as yet apparent and findings on a random bladder biopsy specimen showed no carcinoma. PATHOLOGIC FINDINGS
The concept of carcinoma in situ is not new, dating back several decades to the early work on carcinoma of the uterine cervix, and is in keeping with modern ideas of carcinogenesis that a progressive neoplastic alteration of the cells of an epithelial surface occurs before a grossly visible or an invasive neoplasm develops. The realization that carcinoma in situ is a stage in the development of urothelial malignancy has been delayed because urine cytologic study is generally not done early when the urothelial tumor is suspected or when the patient is asymptomatic. Carcinoma in situ may be defined as 681
682
KHAN AND ASSOCIATES
Fm. 1. Case 1. A, IVP findings are within normal limits. B, retrograde pyelogram 9 months later shows suspicious narrowing of distal third of ureter. C, nephroureterectomy-note carcinoma in situ in lower ureter.
Fm. 2. Case 2. IVP shows obstructed left ureteropelvic junction, pyelocaliectasis and cortical atrophy.
attention to the lesion may be drawn by urologic investigation for related symptoms, such as gross hematuria and renal colic (cases 1 and 2), or serendipitously (case 3). Diagnosis of the tumor also may present difficulties when the tumor is not apparent on the IVP and when malignant cells are present in the ureteral urine. These patients should be observed closely with urograms being taken regularly until a suspicious area becomes apparent, after which ureteral or renal pelvic brushing should be done to obtain tissue for histologic examination.12 Knowledge of the natural history of in situ urothelial carcinoma unassociated with concurrent invasive tumor is still scant and has been gained mainly from the studies of this lesion in the bladder. 7· 10· 13· 14 Recent articles7· 10 • 15 suggest that the natural evolution ofurothelial cancer from the in situ stage to invasion may span a longer period than previously reported. 14 · 16 Whether carcinoma in situ of the upper urinary tract behaves in a similar manner is not known, although in the single case report by Murphy and associates 3 it appeared that the lesion was present for 4 years and had not yet become invasive. In situ carcinoma of the ureter normally has been described in association with invasive bladder cancer7· 17· 18 and the poor prognosis associated with this condition probably should be ascribed to the invasive bladder tumor and the widespread urothelial abnormality that accompanies it. The keystone to
a full thickness carcinomatous alteration in the morphologic appearance of the transitional cell mucosa but without architectural alteration of the mucosa, such as papillary formation or invasion (fig. 3, B). This alteration occurs over a field of mucosal cells rather than in a single cell and, thus, when an invasive tumor eventually evolves it is usually within a moreor-less widespread zone of in situ carcinoma. 7 DISCUSSION
More reliable diagnostic techniques and the increasing use of urine cytology have facilitated the early diagnosis ofurothelial cancer at the in situ stage. 8• 0 Early diagnosis also has created a problem in the management of patients whose results of urinary cytology are positive and who have no overt evidence of tumor. 8• 10• 11 The problem is compounded further when random biopsy specimens of the bladder show no abnormalities and the malignant cells in the urine can be localized to the upper urinary tracts with no evidence of tumor on urographic studies. In most patients with positive urinary findings and occult tumors the lesion eventually develops in the bladder. 7· 11 Rarely, does the lesion become manifest only in the upper urinary tract. 7 There are various modes of presentation of this tumor and
Fm. 3. Case 3. A, left retrograde ureteropyelogram shows stricture of distal ureter. B, carcinoma in situ. There is increase in cell layers with individual cytologic features of malignancy and disordered maturation. H & E, reduced from xl60.
683
PRIMARY CARCINOMA IN SITU
the diagnosis of in situ carcinoma of the upper urinary tract is the presence of malignant cells in the ureteral urine, which occurs predominantly when the tumors are in the more malignant zones of the biologic spectrum. 19 Detection of a well differentiated tumor in the in situ stages is difficult because the incidence of positive findings on urine cell studies in well differentiated ureteral or pelvic tumors is low. 19 In our 3 patients the cytologic study of ureteral urine was positive and the tumors were either Broders' grade 3 or 4. Thus, a reasonably aggressive surgical approach for this lesion seems to be indicated. In our experience nephroureterectomy with removal of a bladder cuff was done in each instance through an extended flank incision. The incidence of subsequent bladder tumors in patients with transitional cell carcinoma of the upper urinary tract is high 20 and in 2 of our patients positive findings on voided urine were noted in a period of 6 and 48 months after nephroureterectomy. The incidence of a tumor developing in the contralateral upper urinary tracts is about 1.5 per cent. 21 Study of urine from the contralateral ureter of each of our 2 patients showed no malignant cells. In the patient described by Murphy and associates epithelial atypia was noted on bladder biopsy 11 weeks after the removal of the primary lesion and 1 year later cytologic study of urine from the contralateral ureter also was positive. 3 REFERENCES
1. Batata, M.A., Whitmore, W. F., Jr., Hilaris, B. S., Tokita, N. and Grabstald, H.: Primary carcinoma of the ureter: a prognostic study. Cancer, 35: 1626, 1975. 2. Melicow, M. M.: Carcinoma in situ: an historical perspective. Urol. Clin. N. Amer., 3: 5, 1976. 3. Murphy, W. M., von Buedingen, R. P. and Poley, R. W.: Primary carcinoma in situ of renal pelvis and ureter. Cancer, 34: 1126, 1974. 4. Foot, N. C. and Papanicolaou, G. N.: Early renal carcinoma in situ. Detected by means of smears of fixed urinary sediment. J.A.M.A., 139: 356, 1949. 5. Grabstald, H., Whitmore, W. F. and Melamed, M. R.: Renal pelvic tumors. J.A.M.A., 218: 845, 1971. 6. Melicow, M. M. and Hollowell, J. W.: Intra-urothelial cancer: carcinoma in situ, Bowen's disease of the urinary system: discussion of thirty cases. J. Urol., 68: 763, 1952. 7. Farrow, G. M., Utz, D. C. and Rife, C. C.: Morphological and clinical observations of patients with early bladder cancer treated with total cystectomy. Cancer Res., 36: 2495, 1976. 8. Utz, D. C. and Farrow, G. M.: In situ carcinoma of the bladder. J.C. E. Urol., 16: 19, 1977. 9. Utz, D. C. and Zincke, H.: The masquerade of bladder cancer in situ as interstitial cystitis. J. Urol., 111: 160, 1974. 10. Farrow, G. M., Utz, D. C., Rife, C. C. and Greene, L. F.: Clinical observations on sixty-nine cases of in situ carcinoma of the urinary bladder. Cancer Res., 37: 2794, 1977.
11. Heney, N. M., Szyfelbein, W. M., Daly, J. J., Prout, G. R. and Bredin, H. C.: Positive urinary cytology in patients without evident tumor. J. Urol., 117: 223, 1977. 12. Gill, W. B., Lu, C. T. and Thomsen, S.: Retrograde brushing: a new technique for obtaining histologic and cytologic material from ureteral, renal pelvic and renal caliceal lesions. J. Urol., l09: 573, 1973. 13. Koss, L. G.: Tumors of the urinary bladder. In: Atlas of Tumor Pathology. Washington, D.C.: Armed Forces Institute of Pathology, fasc. 11, p. 68, 1975. 14. Melamed, M. R., Voutsa, N. G. and Grabstald, H.: Natural history and clinical behavior of in situ carcinoma of the human urinary bladder. Cancer, 17: 1533, 1964. 15. Marshall, V. F. and Seybolt, J. F.: Early detection but delayed appearance ofa bladder tumor. J. Urol., 118: 175, 1977. 16. Utz, D. C., Hanash, K. A. and Farrow, G. M.: The plight of the patient with carcinoma in situ of the bladder. J. Urol., 103: 160, 1970. 17. Culp, 0. S., Utz, D. C. and Harrison, E. G., Jr.: Experiences with ureteral carcinoma in situ detected during operations for vesical neoplasm. J. Urol., 97: 679, 1967. 18. Sharma, T. C., Melamed, M. R. and Whitmore, W. F., Jr.: Carcinoma in-situ of the ureter in patients with bladder carcinoma treated by cystectomy. Cancer, 26: 583, 1970. 19. Zincke, H., Aguilo, J. J., Farrow, G. M., Utz, D. C. and Khan, A. U.: Significance of urinary cytology in the early detection of transitional cell cancer of the upper urinary tract. J. Urol., 116: 781, 1976. 20. Strong, D. W. and Pearse, H. D.: Recurrent urothelial tumors following surgery for transitional cell carcinoma of the upper urinary tract. Cancer, 38: 2178, 1976. 21. Lathan, H. S. and Kay, S.: Malignant tumors of the renal pelvis. Surg., Gynec. & Obst., 138: 613, 1974. EDITORIAL COMMENT Early detection of ureteral carcinomas has been elusive compared to those in the bladder, which can be biopsied readily as well as studied by the Papanicolaou method. Since currently available ureteroscopes are barely useful and only in grossly dilated structures Papanicolaou smears are usually the only preoperative objective evidence when there is not a simultaneous vesical growth. The authors are to be commended for presenting 3 authenticated cases that emphasize the need for good cytologists (as those at the Mayo Clinic obviously are). The reliable Papanicolaou smears, when read as showing carcinoma by adequate cytologists, are 98 per cent sound and should apply to ureteral as well as vesical carcinomas. I coauthored with Doctor Papanicolaou the first publication on his method as applied to urine 1 and the applications seem to be growing. Victor F. Marshall Department of Urology New York Hospital New York, New York 1. Papanicolaou, G. N. and Marshall, V. F.: Urine sediment smears as a diagnostic procedure in cancers of the urinary tract. Science, 101: 519, 1945.
