P RIMARY carcinoma of the ureter, once considered rare, makes up about I per
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1 JANUARY, 1973 TUMORS OF THE URETER PROBLEMS IN DIAGNOSIS By J. J. CANCELMO, JR., M.D., R. C. UHLMAN, M.D., J. L. ESHLEMAN, M.D., andn. F. V1EK, M.D. WAYNE, P RIMARY carcinoma of the ureter, once considered rare, makes up about I per cent of all neoplasms of the upper urinary tract.6 To date there have been about I,2oo tumors of the ureter reported in the literature. 4 The purpose of this paper is to present our experience with tumors of the ureter and the problems encountered in their diagnosis. PATHOLOGY Benign tumors of the ureter are rare. Of the malignant neoplasms, those of transitional cell origin make up per cent;7 4 the remainder include squamous cell carcinom as, adenocarci nom as, and sarcom as. The term papillary refers not only to the gross villous frondlike projections characteristic of the tumor type, but is also used to describe the microscopic appearance. \Vhile some Grade I papillomas have been described as benign, most authorities treat this lesion as potentially malignant. These tumors may demonstrate a multicentric origin with concomitant lesions being found in the renal pelvis and/or bladder, as well as multiple ureteral sites. #{176} 2 Bilateral ureteral tumors are rare, and simultaneous bilateral ureteral tumors extremely rare.2 8 A working classification presented by McDonald and Priestlyil includes: A. Papillary carcinoma Grade i, 2, and 3 B. Papillary and infiltrating carcinoma Grade 2, 3, and 4 C. Nonpapillary infiltrating carcinoma Grade 2, 3, and 4. Over-all evaluation then includes: the structure type (papillary or nonpapillary); the cell type (transitional or squamous); PENNSYLVANIA the degree of anaplasia (Broder s classification) ; as well as absence or presence of local infiltration and regional or distant metastases. ETIOLOGY The etiology of transitional cell carcinoma of the urinary tract, like that of other malignancies, is by no means settled. However, there is significant evidence that there are several chemical agents which may cause these tumors. There is good reason to believe that the metabolites of the parent aromatic amines, 2-naphthylamine, and 4-amino-diphenyl are carcinogenic in the urinary tract. There is also evidence to incriminate cigarette smoking as a cause. The mechanism is probably by way of enzymatic disturbances of tryptophan metabolism. Chronic infection and stone disease have also been implicated. CLINICAL AND UROLOGIC FINDINGS Ureteral carcinoma is more common in men than women (3:1)6 and is usually seen in patients over 50. The lower one-third of the ureter is the most frequent location. 7 Hematuria is usually the chief complaint, although flank pain does occur when there are obstructive manifestations. Given the patient in whom the clinical and roentgenologic findings are suspicious of pathology, cystoscopy with retrograde pyelography has been the most fruitful examination. Cystoscopy may disclose a concomitant bladder tumor or ureteral tumor protruding from an orifice. Simple biopsy of these lesions may be diagnostic. Attempt at ureteral catheterization is the subsequent examination performed, and it the operator is fortunate enough to be able to traverse the obstruction, invaluable information may be gained. Two signs have 132
2 \TOL 117, No. Tumors of the Ureter I 33 been considered diagnostic of tumor: (a) the Chevassu-Mock sign-increased ureteral bleeding following manipulation at the site of the tumor; and (b) Marion s sign -drainage of clear or clearing urine after passage of the ureteral catheter above or beyond the tumor. 9 Once the catheter has passed into the renal pelvis, collection of urine for culture and cytology, followed by routine pyelography with appropriate films, is accomplished. After this, some authorities have suggested the passage of a stone basket in an attempt to secure biopsy material. In those patients in whom the catheter cannot be negotiated past the site of obstruction, the coiling of the catheter below the obstruction may demonstrate the -, - -.,,..,., r - 2 papillary transitional cell carcinoma. The intravenous pyelogram demonstrated a right hydronephrosis and hydroureter with poor delineation ofthe tumor. FIG. 2. Left retrograde pyelogram demcnstrating the goblet sign. This is due to the contrast material extending around the edge of the tumor and dilatation of the ureter. Note dilatation of the ureter below the tumor. Histologic examination showed Grade I papillary transitional cell carcinoma. characteristic sign described by Bergman et al.4 Ureteropyelography done by means of the occluding tip technique with the patient in a Trendelenburg position may give additional imormation. The use of the newly developed ureteroscope as well as the brush technique with cytologv ma facilitate diagnosis. ROENTGEN DIAGNOSIS Accurate diagnosis of these tumors is difficult and probably the least precise of any urologic lesion.7 Filling defects in the ureter are frequently difficult or impossible to demonstrate on intravenous pyelogra-
3 34 J. J. Cancelmo, Jr., R. C. Uhlman, J. L. Eshleman and N. F. Viek JANUARY, 1973 :.. is, FIG. 3. Bergman s sign(s). (A) Left occluding tip pyelogram demonstrating a complete obstruction due to a large tumor. Note marked dilatation of the ureter below the tumor. (B) Left retrograde pyelogram demonstrating coiling of the catheter below and around the tumor. Histologic examination revealed Grade 2 papillary transitional cell carcinoma. ph)-. This may be due to a nonfunctioning kidney, incomplete filling of the ureter, or failure of the ureter to dilate proximal to the tumor. There is a nonfunctioning kidnev on the intravenous pvelogram in close to 50 per cent of the reported series The occluding tip pyelogram is still probably the best method of demonstrating filling defects in the ureter (Fig. ). One sign frequently mentioned in the literature is the goblet-shaped halo ofopaque medium around the neoplasm (Fig. 2). When this is seen on an intravenous pyelogram, the deformity is reversed (the opaque medium is going over the top of the tumor), and it is referred to as an inverted goblet sign. 4 In 1961, Bergman et al.4 observed that the ureter is dilated immediately below a neoplasm in contradistinction to a mechanical obstruction from a stone where the ureter is collapsed below the stone (Fig. 31). These authors also call attention to the frequency with which the ureteral catheter tends to coil in the dilated area below the tumor. This occurred in approximately halfof their 7 cases and in i out of6 in our own personal experience (Fig. 3B). Emmett and Witten7 have referred to this characteristic coiling of the catheter as Bergman s sign.7 DIFFERENTIAL DIAGNOSIS Small defects in the ureter are extremely difficult to evaluate (Fig., 4-C). A tumor should be suspected in zi because of slight dilatation of the ureter below the filling defect. In C, there is also slight dilatation of the ureter below the defect, but this patient had a stone. Larger filling defects that cause a slight bulge in the contour of the
4 VOL. 117, No. I Tumors of the Ureter 135 FIG. 4. Three small filling defects in the distal right ureter with similar appearance. (A) Defect (arrow) due to Grade 2 papillary transitional cell carcinoma. Note slight dilatation ofthe ureter below the filling defect. ( B) Defect (arrow) due to nonopaque stone. (C) Defect (arrow) due to stone. There is a suggestion of slight dilatation of the ureter below the filling defect. ureter are not as difficult to differentiate from nonopaque calculi, although the task is still not an easy one (Fig., A and B). Pyelitis and uretenitis cystica (Fig. 6) in most cases should not cause difficulty in diagnosis from tumor. The lesions are multiple and usually involve the upper third of the ureter. These defects are more apt to be confused with blood clots or nonopaque stones. However, their fixed position, relative uniformity in size, and characteristic notching in the contour of the ureter all help to differentiate these lesions. Solid nonpapillary infiltrating tumors of the ureter present an even more formidable diagnostic problem. The lesion may suggest a benign stricture or retropenitoneal fibrosis, but any obstructing lesion of this type, particularly in a male over 40 years of age, should be looked upon with suspicion (Fig. 7). To go a step further, Figure 8, A and B shows an almost identical appearance; yet in 8A we have a primary tumor and in 8B we are dealing with a secondary tumor. Rarely, benign tumors have to be considered. Endometniosis can cause filling defects similar to papillary tumor and/or result in strictures similar to nonpapillarv infiltrating tumor. Benign strictures, penureteral fibrosis, vanicosi ties, secondary carcinoma (direct extension or metastatic) and rarely malacoplakia 6 have to be differentiated from a primary nonpapillary infiltrating ureteral tumor. TREATMENT Treatment of these tumors is based on the patient s general condition and the status of both upper urinary tracts. No papillary tumor of the upper urinary tract should be treated until both kidneys and ureters have been completely and adequately visualized roentgenographically7
5 136 j. j. Cancelrno, Jr., R. C. Uhlman, j. L. Eshleman and N. F. Viek JANUARY, 1973 FIG. 5. (A) Large oval filling defect due to Grade 2 papillary transitional cell carcinoma. Note slight bulge in contour of the ureter at the tumor site, but no dilatation of the ureter below the tumor. (B) Two defects (one round and one oval) due to nonopaque calculi. Note slight dilatation of the ureter about both defects. and the patient cystoscoped. For unilateral growths with a normal contralateral side, a nephroureterectomy with excision of a cuff of bladder has found the most favor among authorities.8 Where this cannot be logically accomplished, a local excision with primary anastomosis or excision with urinary diversion has been employed. Survival rates depend on the tumor cell type, grade, stage, and extent of the disease. SUMMARY The various manifestations of carcinoma of the ureter are presented including the FIG. 6. Multiple small relatively uniform filling defects secondary to ureteritis cystica.
6 \ ol.. 117, No. Tumors of the Ureter I 37 ureteral stricture at first believed to represent a benign process. On opening the specimen, the pathologist thought that the stricture was due to carci noma. Microscopically, the stricture was benign, there being no evidence of neoplasm. The filling defect (arrow) just proximal to the stricture represents a nonopaque stone. etiologic, pathologic, clinical, urographic, and roentgen findings. Many entities have to be considered in the differential diagnosis, although nonopaque calculi appear to be the most common. FIG. 8. Secondary ureteral involvement from extension ofa primary carcinoma ofthe sigmoid. The management of this disease is briefly J. J. Cancelmo, Jr., M.D. 337 West Lancaster Avenue Wayne, Pennsylvania ABESHOUSE, B. S. Malignant tumors of ureter. Am. 7. Surg., 1956, 9!, I. BARROSO, C. W., JR., FLORENCE, T. S., and Scorr, C., JR. Bilateral papillary carcinomas of ureters: presentation of case and two year follow-up report. 7. Urol., 1966, 96, BECK, A. D., HESLIN, J. E., MILNER, W. A., and GARLICK, W. B. Primary tumors of ureter: diagnosis and management. 7. Urol, 1969, 102, BERGMAN, H., FRIEDENBERG, R. M., and SAYEGH, V. New roentgenologic signs of carcinoma of ureter. AM. J. ROENTGENOL., RAD. THERAPY & NUCLEAR MED., 1961, 86, 707-7I7. 5. BERLIN, L., WALDMAN, I., WHITE, F. H., and MCLAIN, C. R., JR. Endometriosis of ureter; rare manifestation of common disease. AM. J.
7 138 J. J. Cancelmo, Jr., R. C. Uhiman, J. L. Eshleman and N. F. Viek JANUARY, 1973 ROENTGENOL., RAD. THERAPY & NUCLEAR MED., 1964, 92, BLOOM, N. A., VIDONE, R. A., and LYTTON, B. Primary carcinoma of ureter: report of 102 new cases. 7. Urol., 1970, 103, EMMETT, J. L., and WITTEN, D. M. Clinical Urography. Third edition. W. B. Saunders Company, Philadelphia, 1971, 2, i 145-I GREENE, L. B., HAYLLAR, B. L., and BOGASH, M. Epithelial tumors of renal pelvis and ureter. 7. Urol., 1958, 79, JoNssoN, G. Primary tumors of ureter, report of 17 cases. Acta chir. scandinav., 1963, 126, KAPLAN, J. H., MCDONALD, J. R., and THOMP- SON, G. J. Multicentric origin of papillary tumors of urinary tract. 7. Urol., 1951, 66, II. MALTRY, E. Benign and Malignant Tumors of the Urinary Bladder. Medical Examination Publishing Co., Inc., MCDONALD, J., and PRIESTLY, J. T. Carcinoma of renal pelvis: histologic study of seventyfive cases with special reference to prognosis. 7. Urol., 944,5!, OCHSNER, S., and BURNS, E. Pyelitis cystica and ureterltis cystica. South. M. 7., 1958, 5!, ROBARDS, V. L., JR., THOMPSON, I. M., and Ross, G., JR. Primary tumors of ureter. 7.A.M.A., 1964, 187, Is. SAVIGNAC, E. M. Primary carcinoma of ureter. AM. J. ROENTGENOL., RAD. THERAPY & Nu- CLEAR MED., 1955, 74, SCHNEIDERMAN, L., and SIMON, M. A. Malacoplakia of urinary tract. 7. Urol., 1968, zoo, SENGER, F. L., and FUREY, C. A., JR. Primary ureteral tumors with review of literature since Urol., 953, 69, i8. VIEK, N. F., UHLMAN, R. C., and VERILLI, R. Simultaneous bilateral transi tional cell carcinoma of ureters. 7. Urol., :963, 89,
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