THE JOURNAL OF UROLOGY
Copyright © 1977 by The Williams & Wilkins Co.
EARLY DETECTION BUT DELAYED APPEARANCE OF A TUMOR VICTOR F. MARSHALL
AND
JOHN F. SEYBOLT
From the Department of Surgery (Urology), James Bucahan Brady Foundation, and the Papanicolaou Cytology Laboratory, The New York Hospital-Cornell Medical Center, New York, New York
ABSTRACT
Herein is described a case of bladder cancer first detected by urinary cytology 20 years before a definite cystoscopic diagnosis could be established. To our knowledge, this represents the longest such interval on record. The case indicates the reliability of Papanicolaou studies of the especially when tumor cells are identified. Dr. Hugh J. Jewett has long been a cherished friend and colleague of the senior author. Doctor Jewett's Editorship of the Journal deserves a Festschrift. We are delighted to contribute to the celebration, and especially so since our contribution happens to be on the subject ofvesical neoplasia, in which field Doctor Jewett has particularly distinguished himself scientifically. This is a report of a case in which the late Dr. N. Papanicolaou demonstrated cancerous cells in a urine 20 years before convincing confirmation of invasive tumor of the bladder could be obtained. 1 Although an
uum was 2 cc. An excretory urogram indicated. a normal kidney and a non-hydronephrotic left kidney in the vis. On December 1, 1954 Dr. George N. Papanicolaou cancer cells in the urine. A prompt repetition of this examination again revealed neoplastic cells, the number of which was not affected by prostatic massage. The slides of the 1954 u.ri-· nary specimen have been lost but the abnormal cells found in this patient's urine in 1957 are illustrated in figure 1. Over the years the patient received numerous and varied drugs in treatment for the bladder condition. Seven years after the first cytologic examination (1961) he was seen in con-
FIG. 1. Malignant cells from patient's earliest available urinary specimen, also examined by Doctor Papanicolaou (December 3, 1957). Papanicolaou stain, x900.
carcinoma of the prostatic urethra was diagnosed pathologically at the time of a prostatic resection 9 years later, no visible tumor in the lower urinary tract was evident until a and a half before the patient succumbed. His death was uH,,m,ac,,ay caused by a transitional cell carcinoma of the bladder and renal pelvis. The interval between the initial cytologic detection and the subsequent demonstration of a full-blown, grossly evident cancer is the longest of which we know. We do have a similar case (J. M., NYH 398 542) in which the interval was 9 years. CASE REPORT
J\T. S., NYH 685 414, was a 57-year-old white man complaining of dysuria 1 year in duration. Cystoscopic examination disclosed a moderate patchy inflammation that seemed nonspecific, at the time not truly impressive. The vesical resid-
sultation at another hospital, having had several biopsies several urologists. One of these had been interpreted ally as carcinoma but the pathologist soon afterward retracted this malignant label and reduced it to mere change. The other biopsies were all considered neoplasm. At the time of the consultation mentioned ously the bladder showed areas of granularity and some white nonulcerated lesions rather like cystitis formal biopsy was reported as not showing ··--,...,-,,,., A transurethral resection of the prostate was ne>rtn,rrrwr1 elsewhere in 1963. 2 The pathologist found, "few situ transitional cell epithelioma, grade 3" in the nn~"'"n urethra, as well as an independent grade I adenocarcinoma of the prostate. These foci of in situ cancer were considered to have been excised completely. In 1965 further biopsies of the bladder and prostate revealed "cell atypism" but "no evidence
175
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176
MARSHALL AND SEYBOLT
firmed (fig. 1). Latent periods are known to occur in the development ofvesical carcinoma. Melamed and associates, at the Memorial Cancer Center, have reported, "During the latent period, cancer manifests itself at the cellular level and is detectable primarily by the cytological technique. Foci of in situ carcinoma from which abnormal cells are shed may escape cystoscopic detection and therefore biopsy for months or for years." 8 • 9 The case just presented is such an example and the interval between cytologic detection and definite cystoscopic confirmation is believed to be the longest on record. Utz and associates, at the Mayo Clinic, 10• 11 and others, 12• 13 have emphasized the occult nature ofin situ carcinoma of the bladder, actually naming it a "masquerade". REFERENCES
Fm. 2. Autopsy specimen, bladder (February 10, 1976). Moderately to poorly differentiated transitional cell carcinoma with transmural extension, right ureter. H & Estain, x400. Courtesy of Dr. Jack Lubin, Department of Pathology, Mt. Sinai Medical Center, Miami Beach, and the Papanicolaou Cancer Institute, Julius Schultz, PhD., President, Miami, Florida.
of carcinoma in either specimen". It was decided that the patient was suffering from a primary severe Proteus infection of the bladder. 3 In 1974 malignant cells were still being reported in the urinary sediment according to the patient's son. On January 10, 1975 a biopsy of the bladder was reported as showing a poorly differentiated transitional cell carcinoma with invasion of muscle and prostate. The patient's son, a physician, confirmed that this was "the first biopsy of the bladder which showed definite transitional cell carcinoma". The patient died at another institution about a year and a half later. At autopsy in 1976, 22 years after the onset of continuous symptoms, the patient was found to have an extensive transitional cell carcinoma of the bladder and the right renal pelvis and ureter (fig. 2). No prostatic adenocarcinoma was found. DISCUSSION
Although not infallible, the Papanicolaou method as applied to urinary sediment smears is recognized widely as highly reliable, particularly when neoplastic cells are identified. 4-7 It is regrettable that in this case the original cytologic smear has been lost but the cytologic report was unequivocally positive for malignant cells. Furthermore, it was repeatedly recon-
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. 2. Utz, D. C.: Personal communication. 3. Copy of letter from the late Dr. Abraham Hyman, Mt. Sinai Hospital, New York, New York. 4. Schmidlapp, C. J., II and Marshall, V. F.: The detection of cancer cells in the urine: a clinical appraisal of the Papanicolaou method. J. Urol., 59: 599, 1948. 5. Harrison, J. H., Botsford, T. W. and Tucker, M. R.: The use of the smear of the urinary sediment in the diagnosis and management of neoplasms of the kidney and bladder. Surg., Gynec. & Obst., 92: 129, 1951. 6. Roland, S. I. and Marshall, V. F.: The reliability of the Papanicolaou technique when cancer cells are found in the urine. Surg., Gynec. & Obst., 104: 41, 1957. 7. Brannan, W., Lucas, T. A. and Mitchell, W. T., Jr.: The accuracy of cytologic examination of urinary sediment in the detection of urothelial tumors. J. Urol., 109: 483, 1973. 8. Melamed, M. R., Koss, L. G., Ricci, A. and Whitmore, W. F.: Cytohistological observations on developing carcinoma of the urinary bladder in man. Cancer, 13: 67, 1960. 9. Melamed, M. R., Voutsa, N. G. and Grabstald, H.: Natural history and clinical behavior ofin situ carcinoma of the human urinary bladder. Cancer, 17: 1533, 1964. 10. 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. 11. Utz, D. C. and Zincke, H.: The masquerade of bladder cancer in situ as interstitial cystitis. J. Urol., 111: 160, 1974. 12. Moloney, P. J., Elliott, G. B., McLaughlin, M. and Sinclair, A. B.: In situ transitional cell carcinoma and the non-specifically inflamed contracting bladder. J. Urol., 111: 162, 1974. 13. 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.
Copyright © 1977 by The Williams & Wilkins Co.
EARLY DETECTION BUT DELAYED APPEARANCE OF A TUMOR VICTOR F. MARSHALL
AND
JOHN F. SEYBOLT
From the Department of Surgery (Urology), James Bucahan Brady Foundation, and the Papanicolaou Cytology Laboratory, The New York Hospital-Cornell Medical Center, New York, New York
ABSTRACT
Herein is described a case of bladder cancer first detected by urinary cytology 20 years before a definite cystoscopic diagnosis could be established. To our knowledge, this represents the longest such interval on record. The case indicates the reliability of Papanicolaou studies of the especially when tumor cells are identified. Dr. Hugh J. Jewett has long been a cherished friend and colleague of the senior author. Doctor Jewett's Editorship of the Journal deserves a Festschrift. We are delighted to contribute to the celebration, and especially so since our contribution happens to be on the subject ofvesical neoplasia, in which field Doctor Jewett has particularly distinguished himself scientifically. This is a report of a case in which the late Dr. N. Papanicolaou demonstrated cancerous cells in a urine 20 years before convincing confirmation of invasive tumor of the bladder could be obtained. 1 Although an
uum was 2 cc. An excretory urogram indicated. a normal kidney and a non-hydronephrotic left kidney in the vis. On December 1, 1954 Dr. George N. Papanicolaou cancer cells in the urine. A prompt repetition of this examination again revealed neoplastic cells, the number of which was not affected by prostatic massage. The slides of the 1954 u.ri-· nary specimen have been lost but the abnormal cells found in this patient's urine in 1957 are illustrated in figure 1. Over the years the patient received numerous and varied drugs in treatment for the bladder condition. Seven years after the first cytologic examination (1961) he was seen in con-
FIG. 1. Malignant cells from patient's earliest available urinary specimen, also examined by Doctor Papanicolaou (December 3, 1957). Papanicolaou stain, x900.
carcinoma of the prostatic urethra was diagnosed pathologically at the time of a prostatic resection 9 years later, no visible tumor in the lower urinary tract was evident until a and a half before the patient succumbed. His death was uH,,m,ac,,ay caused by a transitional cell carcinoma of the bladder and renal pelvis. The interval between the initial cytologic detection and the subsequent demonstration of a full-blown, grossly evident cancer is the longest of which we know. We do have a similar case (J. M., NYH 398 542) in which the interval was 9 years. CASE REPORT
J\T. S., NYH 685 414, was a 57-year-old white man complaining of dysuria 1 year in duration. Cystoscopic examination disclosed a moderate patchy inflammation that seemed nonspecific, at the time not truly impressive. The vesical resid-
sultation at another hospital, having had several biopsies several urologists. One of these had been interpreted ally as carcinoma but the pathologist soon afterward retracted this malignant label and reduced it to mere change. The other biopsies were all considered neoplasm. At the time of the consultation mentioned ously the bladder showed areas of granularity and some white nonulcerated lesions rather like cystitis formal biopsy was reported as not showing ··--,...,-,,,., A transurethral resection of the prostate was ne>rtn,rrrwr1 elsewhere in 1963. 2 The pathologist found, "few situ transitional cell epithelioma, grade 3" in the nn~"'"n urethra, as well as an independent grade I adenocarcinoma of the prostate. These foci of in situ cancer were considered to have been excised completely. In 1965 further biopsies of the bladder and prostate revealed "cell atypism" but "no evidence
175
LrnC,VCHHH~WL
176
MARSHALL AND SEYBOLT
firmed (fig. 1). Latent periods are known to occur in the development ofvesical carcinoma. Melamed and associates, at the Memorial Cancer Center, have reported, "During the latent period, cancer manifests itself at the cellular level and is detectable primarily by the cytological technique. Foci of in situ carcinoma from which abnormal cells are shed may escape cystoscopic detection and therefore biopsy for months or for years." 8 • 9 The case just presented is such an example and the interval between cytologic detection and definite cystoscopic confirmation is believed to be the longest on record. Utz and associates, at the Mayo Clinic, 10• 11 and others, 12• 13 have emphasized the occult nature ofin situ carcinoma of the bladder, actually naming it a "masquerade". REFERENCES
Fm. 2. Autopsy specimen, bladder (February 10, 1976). Moderately to poorly differentiated transitional cell carcinoma with transmural extension, right ureter. H & Estain, x400. Courtesy of Dr. Jack Lubin, Department of Pathology, Mt. Sinai Medical Center, Miami Beach, and the Papanicolaou Cancer Institute, Julius Schultz, PhD., President, Miami, Florida.
of carcinoma in either specimen". It was decided that the patient was suffering from a primary severe Proteus infection of the bladder. 3 In 1974 malignant cells were still being reported in the urinary sediment according to the patient's son. On January 10, 1975 a biopsy of the bladder was reported as showing a poorly differentiated transitional cell carcinoma with invasion of muscle and prostate. The patient's son, a physician, confirmed that this was "the first biopsy of the bladder which showed definite transitional cell carcinoma". The patient died at another institution about a year and a half later. At autopsy in 1976, 22 years after the onset of continuous symptoms, the patient was found to have an extensive transitional cell carcinoma of the bladder and the right renal pelvis and ureter (fig. 2). No prostatic adenocarcinoma was found. DISCUSSION
Although not infallible, the Papanicolaou method as applied to urinary sediment smears is recognized widely as highly reliable, particularly when neoplastic cells are identified. 4-7 It is regrettable that in this case the original cytologic smear has been lost but the cytologic report was unequivocally positive for malignant cells. Furthermore, it was repeatedly recon-
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. 2. Utz, D. C.: Personal communication. 3. Copy of letter from the late Dr. Abraham Hyman, Mt. Sinai Hospital, New York, New York. 4. Schmidlapp, C. J., II and Marshall, V. F.: The detection of cancer cells in the urine: a clinical appraisal of the Papanicolaou method. J. Urol., 59: 599, 1948. 5. Harrison, J. H., Botsford, T. W. and Tucker, M. R.: The use of the smear of the urinary sediment in the diagnosis and management of neoplasms of the kidney and bladder. Surg., Gynec. & Obst., 92: 129, 1951. 6. Roland, S. I. and Marshall, V. F.: The reliability of the Papanicolaou technique when cancer cells are found in the urine. Surg., Gynec. & Obst., 104: 41, 1957. 7. Brannan, W., Lucas, T. A. and Mitchell, W. T., Jr.: The accuracy of cytologic examination of urinary sediment in the detection of urothelial tumors. J. Urol., 109: 483, 1973. 8. Melamed, M. R., Koss, L. G., Ricci, A. and Whitmore, W. F.: Cytohistological observations on developing carcinoma of the urinary bladder in man. Cancer, 13: 67, 1960. 9. Melamed, M. R., Voutsa, N. G. and Grabstald, H.: Natural history and clinical behavior ofin situ carcinoma of the human urinary bladder. Cancer, 17: 1533, 1964. 10. 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. 11. Utz, D. C. and Zincke, H.: The masquerade of bladder cancer in situ as interstitial cystitis. J. Urol., 111: 160, 1974. 12. Moloney, P. J., Elliott, G. B., McLaughlin, M. and Sinclair, A. B.: In situ transitional cell carcinoma and the non-specifically inflamed contracting bladder. J. Urol., 111: 162, 1974. 13. 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.
