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Primary Benign Neoplasm of the Ureter
THE JOURNAL OF UROLOGY
Vol. 61, No. 3, September 1948 Printed in U.S.A.
PRIMARY BENIGN NEOPLASM OF THE URETER JOSEPH M. EDELSTEIN
AND
SAUL M. MARCUS
From the Departments of Pathology and Surgery, Tufts College Medical School, Boston, Massachusetts
It is the object of this report to record a case of benign primary neoplasm of the ureter and to review the English literature on the subject of benign primary ureteral neoplasms. The rarity of this type of neoplasm is shown by the fact that Renner in reviewing 130,000 autopsies at the Vienna Pathological Institute in 1931 found only 3 examples of ureteral tumors. The first report of benign neoplasm of the ureter was given by Lebert in 1861, a polypoid fibroma, according to the pathologic report. Lancereaux reported a second in 1865, a papilloma of the ureter. Extensive reviews of the literature have been made by Melicow and Findlay in 1932, and by Rusche and Bacon in 1938. The report of Melicow and Findlay included a total of 28 cases from the literature; however, in view of the fact that 12 of those cases had no histologic study, it was felt that they should not be considered as valid case reports in tabulating a total. The review of Rusche and Bacon in 1938 included in a total of 11 cases, 2 granulomata which were not true neoplasms, and a third case which was apparently not benign in view of the statement: "Islets of epithelial cells were noted in lymphatic channels in the submucosal tissue"; thus 24 incidences of benign ureteral neoplasm have been published through 1938. An unusual neoplasm was a cavernous hemangioma ,vhich encircled the ureter and was adherent to the adventitia in several places but had not constricted the ureter or produced any obstruction. Ewing cites a pure myoma of the ureter, reported by Buttner. A neurofibroma was reported, apparently arising from the ureter and encircling it. An unusual finding was that of an endometrioma of the ureter, intraureteral, which, however, showed no cyclic bleeding and apparently was not functioning as true endometrial tissue. The author pointed out that the cyclic occurrence of intensified symptoms, especially hematuria in a female, should always raise the suspicion of a ureteral endometrioma. A report of 1944 brought out a total of 27 cases of benign ureteral neoplasms in which the diagnosis was verified by 1) inspection of the interior of the renal pelvis and entire ureter and 2) microscopic examination of the tumor. Sixteen other reported cases were rejected by the author because they failed to satisfy one or both of these criteria. Reports of benign ureteral neoplasms in recent years have all been confirmed by microscopic studies. CASE REPORT
A married, 60 year old white man complained of hematuria of 3 years' duration. The present illness began 3 years previoi:1sly with an attack of painless hematuria lasting a few days. The second attack occurred 1 year later with a 409
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week's duration of bleeding. Intravenous pyelogram at that time demonstrated no disease. From that time, until shortly before his visit to my office, he had mild attacks of hematuria at intervals of about 6 months. The last attack was 1 week previously with hematuria lasting about 4 days, followed by cystoscopy and pyelogram at a hospital by another physician but results ·were inconclusive. Occasional frequency and nocturia were present off and on. The stream was normal. There was no loss of weight elicited. He complained of some dull pain in right lower quadrant. The family and past histories were essentially negative. Physical examination disclosed no significant abnormality. The blood pressure was 140/85. Urinalysis showed nothing abnormal, but the urinary sediment contained a few pus cells and 8 to 10 red blood cells. The prostatic secretion was normal. A diagnosis of probable tumor of the genito-urinary tract was made. While making arrangements for cystoscopy and pyelography, the patient had another attack of severe bleeding, felt faint, and had recurrent pain in the left lower quadrant and flank 1 week after examination. Six days later examination with a No. 24 McCarthy cysto-urethroscope was negative. Indigo carmine returned from both sides in good concentration in 6 minutes. Because of previous x-rays and cystoscopy elsewhere, add the normal function from the right kidney by indigo carmine, the right orifice was not catheterized. The left ureteral orifice was catheterized with a No. 10 Woodruff terminal eye catheter, and a uretero-pyelogram was performed with 20 per cent diodrast solution. The ureter filled only about one-half its length, and no dye would go above it into the kidney. Because of this, the Woodruff catheter was removed and a No. 5 x-ray catheter was passed to the renal pelvis which filled with dye and then a ureteropyelogram taken. There was a large filling defect in the ureter about 2 cm. in diameter opposite the fourth lumbar vertebra (fig. 1). The patient left the table in good condition. After the retrograde pyelogram was taken a diagnosis of primary tumor of the ureter was made, and hospitalization advised. Complete laboratory studies were carried out before the operation. Urinalysis showed urine to be strawcolored, slightly turbid, pH 4.5, specific gravity 1.015, slight trace of albumin, no sugar or acetone, 2-4 white blood cells per high power field, 1-3 red blood cells with occasional renal cells seen to high power field. Urine culture negative. Red blood count 4,700,000; hemoglobin 92 per cent. White blood count: 5,400, polymorphonuclears 58 per cent, lymphocytes 40 per cent, eosinophiles 2 per cent. Smear normal. Blood chemistry: nonprotein nitrogen 44 mg. per 100 cc of blood, sugar 85 mg. per 100 cc of blood, prothrombin time normal, Hinton negative, blood type B, Rh positive. On May 1, 1946, four days after admission, a left nephroureterectomy was performed under spinal anesthesia. An incision was made over the left loin parallel to the twelfth rib, about 7 inches in length. This was carried through the skin, fascia and muscles. The perirenal space was opened, and the kidney delivered. The ureter was freed downward for a considerable length where it widened perceptibly, dilating to about 3 cm. in diameter at the site of the tumor.
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The latter was found about 7 cm. from the ureterovesical junction. At the site of the tumor there were numerous telangiectatic vessels coursing over the ureter surrounding the tumor. The tumor could be felt as a firm, flat, mobile mass in the ureteL Below it the ureter resumed its normal caliber. The incision of the loin was enlarged anteriorly and the ureter -Yrns dissected down almost to the bladder. At this point two large clamps ,rnre placed on the renal pedicle and the kidney ,vas cut away. The pedicle was tied with a circular tie of J\T o. 2 double chromic catgut, and a transfixation suture of the same material was placed between the 2 clamps. The kidney and ureter were then held in 1 piece and stripped down as low as possible at the site of the normal ureter lmY down
FIG. 1. Ureteropyelogram.
Note filling defect in ureter (left)
near the bladder. Two clamps were placed on it and it was cu(off between the clamps. A tie of No. 1 chromic catgut was placed around the stump of the ureter, the latter carbolized and allowed to recede. A Penrose drain was placed at the stump of the ureter, another in the renal fossa, and the wound sutured in layers with No. 1 chromic catgut. Black silk, interrupted, was used for the skin. Patient stood operation ·well; no shock or hemorrhage. The patient made an uneventful recovery. The patient was out, of bed on the second postoperative day; the drains were removed on the seventh day, and sutures on the ninth day. The patient was discharged on the tenth day. After discharge the patient continued to have a serous discharge from the drain site for a few weeks, the latter then healing completely. Subsequent examinations demonstrated a solid scar with no hernia. The patient returned to work 2 months after the operation. Urinalysis repeatedly since then has been
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JOSEPH M. EDELSTEIN AND SAUL M. MARCUS
negative chemically and microscopically. Fifteen months since the operation, there has been no recurrence of hematuria and the patient is working and well. PATHOLOGY
The specimen consisted of a left kidney with attached ureter, the kidney measuring 10 by 5 by 2.5 cm. and the ureter 10 cm. in length and 0.7 cm. in circumference in its first 7 cm. (fig. 2, A). Beyond this point the circumference widened to 2.8 cm. and narrowed to 1.7 cm. at the distal resected margin. The
Fm. 2. A, Kidney and ureter. Note dilatation and distortion of lower ureter. Kidney and ureter opened, to demonstrate papilloma of ureter.
B,
kidney weighed 115 gm. The surface of the kidney was smooth and brown pink. The cortex ·1Yas well delineated and measured 0.6 cm. in width. The calyces and pelvis were slightly dilated. The mucosa of the pelvis presented a fe-w pin point petechial hemorrhages but was otherwise smooth, glistening and not thickened. The proximal 7 cm. of the ureter revealed 2 small, focal areas of hemorrhage just beneath the pelvis. Otherwise the mucosa was smooth and not thickened. At a point 7 cm. from the origin of the ureter, and projecting into the lumen, was a papilliferous structure which measured 2 by 1.4 by O.8 cm., and was attached by a slender pedicle to the mucosa. This pedicle measured 1.1 cm. in length and 0.2 cm. in diameter. The polypoid structure was pink and moist, freely movable, and of doughy consistence (fig. 2, B). The remainder of the ureter was dilated and was thinned out and smooth in the region where it surrounded the polyp. There was no gross evidence of a recent or healed inflammatory process in any portion of
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the ureter. The distal 2 cm. of the ureter presented a corrugated gray mucosa. The gross diagnosis was papilloma of the ureter; minimal dilation of pelvis and calyces of kidney. Microscopic examination of sections from the kidney: The overall pattern was normal, with a cortex of normal width and containing a normal number of glomeruli. All the tubules of the kidney were slightly dilated. The capsule was not thickened and there was no evidence of an inflammatory process in the kidney. The glomeruli revealed slight but definite increase in thickening of the parietal layer of Bowman's capsule; the basement membrane of the tuft capillaries was swollen, focally, and thickened by a translucent, pale, pink substance. Arterioles showed no significant reduction in lumen width; the walls were minimally thickened.
FIG. 3. Papilloma of ureter. Note transitional cell pattern, palisade arrangement, and intact basement membrane. X 190, Microphotograph.
Ureteral tumor: The histological sections demonstrated clearly the delicate papillary nature of the tumor. It was composed of a core of vascularized connertive tissue with branching processes of transitional epithelium (fig. 3). Depmding upon the plane in which the section was cut, the epithelium had the form of elongated cells or polyhedral cells. There was a distinct basement men-½rane in all processes of the tumor and the line of junction between epithelium and connective tissue stalk was sharp. The cells of the tumor proper were of approximately the same size and shape, being polyhedral in outline with pink cytoplasm. They had an oval or round nucleus in which the chromatin was finely dispersed at the periphery of the nucleus. Some nuclei contained small, acidophilic nucleoli. A rare mitotic figure was seen. Hyperchromatic nuclei were not noted and there was no invasion of the stalk in the sections examined. Ureter: Sections taken at various levels above and below the tumor revealed a mucosa of normal transitional epithelium. The wall, however, above the tumor, was thickened due to an hypertrophy of the musculature. Diagnosis: Papilloma
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of ureter, transitional cell type; no evidence of malignancy; minimal hydronephrosis and slight hypertrophy of ureteral wall. DISCUSSION
It has been stressed by numerous observers that the outstanding symptoms are pain, hematuria and a palpably enlarged kidney. The pain may be severe and of the quality of colic due to the passage of clots of blood; this pain may also be referred to the groin, scrotum and penis. Another type of pain, dull and aching, may be felt in the flank; this is due to the hydronephrosis; or a dragging sensation may be experienced by the patient because of the hydronephrosis. In some instances a palpably enlarged kidney may be present due to the obstruction and if a superimposed infection occurs the clinical picture may be that of a renal bacterial infection or even sepsis. Hematuria, profuse, spontaneous and intermittent, gross or microscopic, was noted in about 70 to 75 per cent of the cases. This is both the most prominent and earliest symptom. The finding of an enlarged and palpable kidney was reported in 40 per cent of cases, almost always due to hydronephrosis. The tumor itself is rarely palpable. Urinary frequency has been noted, more marked in tumors in the lower third of the ureter. A persistence or recurrence of hematuria after nephrectomy for hydronephrosis has been noted and then the real diagnosis of ureteral neoplasm has been made. As pointed out above, the cyclic occurrence of intensified symptoms especially hematuria in a female should bring to mind the possibility of endometrioma of the ureter. A rather unusual situation was encountered in the report of a pulsating cavernous hemangioma of the ureter simulating an inoperable carcinoma of the bladder. The angioma of the ureter made its impression beneath the mucous membrane of the bladder in two places, eroding it with the production of hemorrhage, so that it gave every appearance of a vesical growth. The diagnosis of ureteral neoplasms depends upon history and physical examination, cystoscopic findings, and x-ray examination. Cystoscopic examination may reveal pouting at the ureterovesical orifice or the tumor may actually protrude through and be visualized directly. Dilatation and injection of the ureteral orifice on cystoscopy are suggestive of the possibility of ureteral disease and call for further investigation with the object of ruling in or out the presence of neoplasm. The passage of a ureteral catheter and meeting obstruction is very suggestive. Further attempts with the passage of blood is also suggestive of the possibility of ureteral tumor. Other diagnostic procedures are the intravenous phthalein test, as a differential for the 2 ureters. A most important procedure is the ureterogram. Conditions to be differentiated in ureterograms are malignancy, tuberculosis, inflammatory strictures and calculi. The treatment of ureteral neoplasm has been total ureteronephrectomy, particularly since papilloma is found more commonly than the other rarer conditions and because of the potential malignancy of benign transitional cell neoplasms. The operation has been that of Beer who states that the added risk of removing the whole ureter through the second pararectus incision is negligible.
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It has been recommended that an ounce of 1: 20,000 bichloricle solution be used in the bladder to destroy any tumor cells thrown down because of manipulations from above. More conservative treatment has been asked for, particularly when one is dealing with neoplasms such as fibroma or myoma or lipoma, and the kidney can be spared as well as a portion of the ureteL The treatment in these cases depends upon a rapid diagnosis at the time of surgery by the pathologist, It has been stressed also that in dealing with ureteral granuloma which may be bilateral, there is clanger in performing radical surgery, such as ureteronephrectomy. One may discover at a later date that the remaining kidney is impaired. The authors point out the importance of biopsy by means of rapid diagnosis at the time of surgery and thus the course of action is more rational. Chronic irritation by calculi seems to precede a very small number of benign ureteral neoplasms. The significance of ureteritis cystica is open to much question in attempting to link it as a possible cause of ureteral neoplasm. Leukoplakia, according to Aschner, may precede the formation of calculi in some instances and be a factor in the development of a ureteral tumor. It has been suggested but not proved that the etiological factor in ureteral tumors is some carcinogenic substance eliminated through the kidneys. There is circumstantial evidence that certain dyes by inhalation may lead to the appearance of tumors of the kidney and ureter. There is direct evidence that a parasite will cause these tumors. Arsenic has been thought to be of some importance in the production of ureteral neoplasm, particularly those people who have been treated for other conditions with the chemicals. The tumor of the ureter in this case report was apparently present for 3 years and possibly longer inasmuch as the patient was known to have complained of attacks of hematuria during a 3 year period. Although it cannot be proved absolutely that the ureteral papilloma was the sole cause of the hematuria in this man's case, the evidence points strongly to it as the etiologic factor. An interesting point is the almost negligible dilatation of the pelvis and calyces of the kidney above the ureteral obstruction. There was probably a degree of obstruction but not sufficient over a period of 3 years to have produced significant hydronephrosis. The histologic study of the tumor confirmed the clinical course of its benign nature. There was an orderly arrangement to the palisade architecture of the tumor and the cells ,vere of about the same size and shape with a rare mitosis. There was no breaking through the basement membrane. The richly vascularized connective tissue stalks of the tumor explain the hematuria. The consensus of opinion was that this represented a benign neoplasm and showed none of the features which are seen in carcinoma, such as variation in size and shape of cells, invasion of the stalk, hyperchromatic nuclei, and many mitotic figures. The potential malignancy of benign ureteral neoplasm, particularly the transitional cell papilloma, has been stressed by many. Some have used a terminology and classification in which benign papillomata of the transitional cell type have been called grade I carcinoma. There are histologic criteria of carcinoma which a benign papilloma does not have and this case report utilizes the classification
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of "benign papilloma" and reserves the diagnosis of carcinoma ·when there is invasion of the stalk of the neoplasm or base, or when the malignancy characteristics of the cells are such as to warrant such a diagnosis. The study of numerous microscopic sections in dealing with urinary tract neoplasms cannot be emphasized enough in diagnosis. Benign neoplasms of the ureter may be classified into : A) Epithelial: papilloma; and B) non-epithelial: myoma, lipoma, fibroma, hemangioma, etc. Cases of mixed tumor have been reported; in 1 a tumor of the ureter was found at autopsy, which was composed of smooth muscle, epithelium, connective tissue and bone. The second ·was classed as a fibromyoma. The papilloma may be pedunculated or may be sessile; in the former instance, the complication of intussusception should be kept in mind. Also, due to obstruction, hydrometer and hydronephrosis may develop. The nonepithelial neoplasms may arise in the wall and compress the ureter or may arise from the outer coats and encircle the ureter. The transitional cell papilloma shows numerous branching and stalked processes with a palisade arrangement to the cells which are of the same size and shape, shmY few or no mitoses and no hyperchromatism. There is no invasion of the stalk or base of the neoplasm. SUMMARY AND CONCLUSIONS
A report of a primary, benign, ureteral transitional cell papilloma is added to the literature, and the symptoms, diagnosis and treatment discussed. A total number of 32 cases, including this case report, of benign ureteral neoplasms, primary, which have been confirmed by microscopic examination, is recorded. The separation of benign papilloma from carcinoma is made in this report, and the criteria for such a diagnosis listed. A suggestion for more conservative surgery in treatment when one is dealing with connective tissue tumors such as lipoma, myomas, etc., is made; this will often result from consultation with the pathologist at the time of operation. The importance of accurate investigation of the ureter as ·well as the kidney and bladder in cases of hematuria is emphasized. This is accomplished by ureteropyelogram. The authors thank Dr. H. Edward MacMahon, Tufts College Medical School, for his aid in preparing this report. REFERENCES AscHNER, P. W.: Surg., Gynec. & Obst., 35: 749, 1922. BARNES, R. W., AND KAWAICHI, G. K.: Urol. and Cutan. Rev., 48: 430, 1944. BEER, E.: J. A. M.A., 77: 1176, 1921; J. Urol., 29: 135, 1933. BINDER, A.: Ziegler's Beitr., p.69, 1921. Quoted by Kleinschmidt. BRIDGE, R., AND KIRKLAND, K.: M. J. Australia, 1: 160, 1934. Brit. J. Urol., 5: 323, 1933: Fifth Triennial Congress of Internat. Society of Urology. BUTTNER: Ztschr. f. Geburtschulfe u. Gynakologie, 28: 136, 1894. CAULK, J. R.: Surg., Gynec. & Obst., 41: 49, 1925. CooNEY, C. J.: J. Urol., 47: 651, 1942. DEAN, A. L. JR.: Bull. N. Y. Acad. Med., 14: 128, 1938. DJEAH-Y AN (Watjen), Central bl. f. Allg. Path. u. path. Anat., 35: 549, 1924-25. EPSTEIN, G. S.: Ztschr. f. urol. Chir., 39: 63, 1934.
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FERGUSON, J. D.: Brit. J. Urol., 17: 59, 1945. HAMER, H. G., MERTZ, H. 0., AND WISHARD, W. N., JR.: J. Urol., 29: 43, 1933. HuNNER, G. L.: J. Urol., 40: 752, 1938. LANCEREAux: Dictionaire Dechambra, Article Rein, 3c Series, III, 247. LEBERT: Anat. Path., 1: 269, 1861; 2: 372, 1861. McMAHON, S.: J. Urol., 51: 616, 1944. MELrcow, M. M., AND FINDLAY, H. V., Surg., Gynec. & Obst., 54: 680, 1932. MooRE, T.: Brit. J. Surg., 29: 371, 1941-42. OTTLEY, C. M.: Brit. J. Surg., 32: 531, 1944-45. PNrcH, F. S.: Urol. & Cutan. Rev., 42: 625, 1938. RAMSEY, E. M.: J. Urol., 42: 341, 1939. RANDALL, A.: J. Urol., 46: 419, 1941. RAYICH, A.: Arch. Surg., 30: 442, 1935. RENNER, JVI. J.: Surg., Gynec. AND OBST., 52: 793, 1931. RuscHE, C., AND BACON, S. K.: .T. Urol., 39: 319, 1938. TAKAHASHI, A.: Urol. & Cutan. Rev., 32: 78, 1928. WILSON, W. E.: Brit. J. Urol., 17: 62, EJ45.
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Vol. 61, No. 3, September 1948 Printed in U.S.A.
PRIMARY BENIGN NEOPLASM OF THE URETER JOSEPH M. EDELSTEIN
AND
SAUL M. MARCUS
From the Departments of Pathology and Surgery, Tufts College Medical School, Boston, Massachusetts
It is the object of this report to record a case of benign primary neoplasm of the ureter and to review the English literature on the subject of benign primary ureteral neoplasms. The rarity of this type of neoplasm is shown by the fact that Renner in reviewing 130,000 autopsies at the Vienna Pathological Institute in 1931 found only 3 examples of ureteral tumors. The first report of benign neoplasm of the ureter was given by Lebert in 1861, a polypoid fibroma, according to the pathologic report. Lancereaux reported a second in 1865, a papilloma of the ureter. Extensive reviews of the literature have been made by Melicow and Findlay in 1932, and by Rusche and Bacon in 1938. The report of Melicow and Findlay included a total of 28 cases from the literature; however, in view of the fact that 12 of those cases had no histologic study, it was felt that they should not be considered as valid case reports in tabulating a total. The review of Rusche and Bacon in 1938 included in a total of 11 cases, 2 granulomata which were not true neoplasms, and a third case which was apparently not benign in view of the statement: "Islets of epithelial cells were noted in lymphatic channels in the submucosal tissue"; thus 24 incidences of benign ureteral neoplasm have been published through 1938. An unusual neoplasm was a cavernous hemangioma ,vhich encircled the ureter and was adherent to the adventitia in several places but had not constricted the ureter or produced any obstruction. Ewing cites a pure myoma of the ureter, reported by Buttner. A neurofibroma was reported, apparently arising from the ureter and encircling it. An unusual finding was that of an endometrioma of the ureter, intraureteral, which, however, showed no cyclic bleeding and apparently was not functioning as true endometrial tissue. The author pointed out that the cyclic occurrence of intensified symptoms, especially hematuria in a female, should always raise the suspicion of a ureteral endometrioma. A report of 1944 brought out a total of 27 cases of benign ureteral neoplasms in which the diagnosis was verified by 1) inspection of the interior of the renal pelvis and entire ureter and 2) microscopic examination of the tumor. Sixteen other reported cases were rejected by the author because they failed to satisfy one or both of these criteria. Reports of benign ureteral neoplasms in recent years have all been confirmed by microscopic studies. CASE REPORT
A married, 60 year old white man complained of hematuria of 3 years' duration. The present illness began 3 years previoi:1sly with an attack of painless hematuria lasting a few days. The second attack occurred 1 year later with a 409
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JOSEPH M. EDELSTEIN AND SAUL M, MARCUS
week's duration of bleeding. Intravenous pyelogram at that time demonstrated no disease. From that time, until shortly before his visit to my office, he had mild attacks of hematuria at intervals of about 6 months. The last attack was 1 week previously with hematuria lasting about 4 days, followed by cystoscopy and pyelogram at a hospital by another physician but results ·were inconclusive. Occasional frequency and nocturia were present off and on. The stream was normal. There was no loss of weight elicited. He complained of some dull pain in right lower quadrant. The family and past histories were essentially negative. Physical examination disclosed no significant abnormality. The blood pressure was 140/85. Urinalysis showed nothing abnormal, but the urinary sediment contained a few pus cells and 8 to 10 red blood cells. The prostatic secretion was normal. A diagnosis of probable tumor of the genito-urinary tract was made. While making arrangements for cystoscopy and pyelography, the patient had another attack of severe bleeding, felt faint, and had recurrent pain in the left lower quadrant and flank 1 week after examination. Six days later examination with a No. 24 McCarthy cysto-urethroscope was negative. Indigo carmine returned from both sides in good concentration in 6 minutes. Because of previous x-rays and cystoscopy elsewhere, add the normal function from the right kidney by indigo carmine, the right orifice was not catheterized. The left ureteral orifice was catheterized with a No. 10 Woodruff terminal eye catheter, and a uretero-pyelogram was performed with 20 per cent diodrast solution. The ureter filled only about one-half its length, and no dye would go above it into the kidney. Because of this, the Woodruff catheter was removed and a No. 5 x-ray catheter was passed to the renal pelvis which filled with dye and then a ureteropyelogram taken. There was a large filling defect in the ureter about 2 cm. in diameter opposite the fourth lumbar vertebra (fig. 1). The patient left the table in good condition. After the retrograde pyelogram was taken a diagnosis of primary tumor of the ureter was made, and hospitalization advised. Complete laboratory studies were carried out before the operation. Urinalysis showed urine to be strawcolored, slightly turbid, pH 4.5, specific gravity 1.015, slight trace of albumin, no sugar or acetone, 2-4 white blood cells per high power field, 1-3 red blood cells with occasional renal cells seen to high power field. Urine culture negative. Red blood count 4,700,000; hemoglobin 92 per cent. White blood count: 5,400, polymorphonuclears 58 per cent, lymphocytes 40 per cent, eosinophiles 2 per cent. Smear normal. Blood chemistry: nonprotein nitrogen 44 mg. per 100 cc of blood, sugar 85 mg. per 100 cc of blood, prothrombin time normal, Hinton negative, blood type B, Rh positive. On May 1, 1946, four days after admission, a left nephroureterectomy was performed under spinal anesthesia. An incision was made over the left loin parallel to the twelfth rib, about 7 inches in length. This was carried through the skin, fascia and muscles. The perirenal space was opened, and the kidney delivered. The ureter was freed downward for a considerable length where it widened perceptibly, dilating to about 3 cm. in diameter at the site of the tumor.
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The latter was found about 7 cm. from the ureterovesical junction. At the site of the tumor there were numerous telangiectatic vessels coursing over the ureter surrounding the tumor. The tumor could be felt as a firm, flat, mobile mass in the ureteL Below it the ureter resumed its normal caliber. The incision of the loin was enlarged anteriorly and the ureter -Yrns dissected down almost to the bladder. At this point two large clamps ,rnre placed on the renal pedicle and the kidney ,vas cut away. The pedicle was tied with a circular tie of J\T o. 2 double chromic catgut, and a transfixation suture of the same material was placed between the 2 clamps. The kidney and ureter were then held in 1 piece and stripped down as low as possible at the site of the normal ureter lmY down
FIG. 1. Ureteropyelogram.
Note filling defect in ureter (left)
near the bladder. Two clamps were placed on it and it was cu(off between the clamps. A tie of No. 1 chromic catgut was placed around the stump of the ureter, the latter carbolized and allowed to recede. A Penrose drain was placed at the stump of the ureter, another in the renal fossa, and the wound sutured in layers with No. 1 chromic catgut. Black silk, interrupted, was used for the skin. Patient stood operation ·well; no shock or hemorrhage. The patient made an uneventful recovery. The patient was out, of bed on the second postoperative day; the drains were removed on the seventh day, and sutures on the ninth day. The patient was discharged on the tenth day. After discharge the patient continued to have a serous discharge from the drain site for a few weeks, the latter then healing completely. Subsequent examinations demonstrated a solid scar with no hernia. The patient returned to work 2 months after the operation. Urinalysis repeatedly since then has been
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negative chemically and microscopically. Fifteen months since the operation, there has been no recurrence of hematuria and the patient is working and well. PATHOLOGY
The specimen consisted of a left kidney with attached ureter, the kidney measuring 10 by 5 by 2.5 cm. and the ureter 10 cm. in length and 0.7 cm. in circumference in its first 7 cm. (fig. 2, A). Beyond this point the circumference widened to 2.8 cm. and narrowed to 1.7 cm. at the distal resected margin. The
Fm. 2. A, Kidney and ureter. Note dilatation and distortion of lower ureter. Kidney and ureter opened, to demonstrate papilloma of ureter.
B,
kidney weighed 115 gm. The surface of the kidney was smooth and brown pink. The cortex ·1Yas well delineated and measured 0.6 cm. in width. The calyces and pelvis were slightly dilated. The mucosa of the pelvis presented a fe-w pin point petechial hemorrhages but was otherwise smooth, glistening and not thickened. The proximal 7 cm. of the ureter revealed 2 small, focal areas of hemorrhage just beneath the pelvis. Otherwise the mucosa was smooth and not thickened. At a point 7 cm. from the origin of the ureter, and projecting into the lumen, was a papilliferous structure which measured 2 by 1.4 by O.8 cm., and was attached by a slender pedicle to the mucosa. This pedicle measured 1.1 cm. in length and 0.2 cm. in diameter. The polypoid structure was pink and moist, freely movable, and of doughy consistence (fig. 2, B). The remainder of the ureter was dilated and was thinned out and smooth in the region where it surrounded the polyp. There was no gross evidence of a recent or healed inflammatory process in any portion of
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the ureter. The distal 2 cm. of the ureter presented a corrugated gray mucosa. The gross diagnosis was papilloma of the ureter; minimal dilation of pelvis and calyces of kidney. Microscopic examination of sections from the kidney: The overall pattern was normal, with a cortex of normal width and containing a normal number of glomeruli. All the tubules of the kidney were slightly dilated. The capsule was not thickened and there was no evidence of an inflammatory process in the kidney. The glomeruli revealed slight but definite increase in thickening of the parietal layer of Bowman's capsule; the basement membrane of the tuft capillaries was swollen, focally, and thickened by a translucent, pale, pink substance. Arterioles showed no significant reduction in lumen width; the walls were minimally thickened.
FIG. 3. Papilloma of ureter. Note transitional cell pattern, palisade arrangement, and intact basement membrane. X 190, Microphotograph.
Ureteral tumor: The histological sections demonstrated clearly the delicate papillary nature of the tumor. It was composed of a core of vascularized connertive tissue with branching processes of transitional epithelium (fig. 3). Depmding upon the plane in which the section was cut, the epithelium had the form of elongated cells or polyhedral cells. There was a distinct basement men-½rane in all processes of the tumor and the line of junction between epithelium and connective tissue stalk was sharp. The cells of the tumor proper were of approximately the same size and shape, being polyhedral in outline with pink cytoplasm. They had an oval or round nucleus in which the chromatin was finely dispersed at the periphery of the nucleus. Some nuclei contained small, acidophilic nucleoli. A rare mitotic figure was seen. Hyperchromatic nuclei were not noted and there was no invasion of the stalk in the sections examined. Ureter: Sections taken at various levels above and below the tumor revealed a mucosa of normal transitional epithelium. The wall, however, above the tumor, was thickened due to an hypertrophy of the musculature. Diagnosis: Papilloma
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of ureter, transitional cell type; no evidence of malignancy; minimal hydronephrosis and slight hypertrophy of ureteral wall. DISCUSSION
It has been stressed by numerous observers that the outstanding symptoms are pain, hematuria and a palpably enlarged kidney. The pain may be severe and of the quality of colic due to the passage of clots of blood; this pain may also be referred to the groin, scrotum and penis. Another type of pain, dull and aching, may be felt in the flank; this is due to the hydronephrosis; or a dragging sensation may be experienced by the patient because of the hydronephrosis. In some instances a palpably enlarged kidney may be present due to the obstruction and if a superimposed infection occurs the clinical picture may be that of a renal bacterial infection or even sepsis. Hematuria, profuse, spontaneous and intermittent, gross or microscopic, was noted in about 70 to 75 per cent of the cases. This is both the most prominent and earliest symptom. The finding of an enlarged and palpable kidney was reported in 40 per cent of cases, almost always due to hydronephrosis. The tumor itself is rarely palpable. Urinary frequency has been noted, more marked in tumors in the lower third of the ureter. A persistence or recurrence of hematuria after nephrectomy for hydronephrosis has been noted and then the real diagnosis of ureteral neoplasm has been made. As pointed out above, the cyclic occurrence of intensified symptoms especially hematuria in a female should bring to mind the possibility of endometrioma of the ureter. A rather unusual situation was encountered in the report of a pulsating cavernous hemangioma of the ureter simulating an inoperable carcinoma of the bladder. The angioma of the ureter made its impression beneath the mucous membrane of the bladder in two places, eroding it with the production of hemorrhage, so that it gave every appearance of a vesical growth. The diagnosis of ureteral neoplasms depends upon history and physical examination, cystoscopic findings, and x-ray examination. Cystoscopic examination may reveal pouting at the ureterovesical orifice or the tumor may actually protrude through and be visualized directly. Dilatation and injection of the ureteral orifice on cystoscopy are suggestive of the possibility of ureteral disease and call for further investigation with the object of ruling in or out the presence of neoplasm. The passage of a ureteral catheter and meeting obstruction is very suggestive. Further attempts with the passage of blood is also suggestive of the possibility of ureteral tumor. Other diagnostic procedures are the intravenous phthalein test, as a differential for the 2 ureters. A most important procedure is the ureterogram. Conditions to be differentiated in ureterograms are malignancy, tuberculosis, inflammatory strictures and calculi. The treatment of ureteral neoplasm has been total ureteronephrectomy, particularly since papilloma is found more commonly than the other rarer conditions and because of the potential malignancy of benign transitional cell neoplasms. The operation has been that of Beer who states that the added risk of removing the whole ureter through the second pararectus incision is negligible.
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It has been recommended that an ounce of 1: 20,000 bichloricle solution be used in the bladder to destroy any tumor cells thrown down because of manipulations from above. More conservative treatment has been asked for, particularly when one is dealing with neoplasms such as fibroma or myoma or lipoma, and the kidney can be spared as well as a portion of the ureteL The treatment in these cases depends upon a rapid diagnosis at the time of surgery by the pathologist, It has been stressed also that in dealing with ureteral granuloma which may be bilateral, there is clanger in performing radical surgery, such as ureteronephrectomy. One may discover at a later date that the remaining kidney is impaired. The authors point out the importance of biopsy by means of rapid diagnosis at the time of surgery and thus the course of action is more rational. Chronic irritation by calculi seems to precede a very small number of benign ureteral neoplasms. The significance of ureteritis cystica is open to much question in attempting to link it as a possible cause of ureteral neoplasm. Leukoplakia, according to Aschner, may precede the formation of calculi in some instances and be a factor in the development of a ureteral tumor. It has been suggested but not proved that the etiological factor in ureteral tumors is some carcinogenic substance eliminated through the kidneys. There is circumstantial evidence that certain dyes by inhalation may lead to the appearance of tumors of the kidney and ureter. There is direct evidence that a parasite will cause these tumors. Arsenic has been thought to be of some importance in the production of ureteral neoplasm, particularly those people who have been treated for other conditions with the chemicals. The tumor of the ureter in this case report was apparently present for 3 years and possibly longer inasmuch as the patient was known to have complained of attacks of hematuria during a 3 year period. Although it cannot be proved absolutely that the ureteral papilloma was the sole cause of the hematuria in this man's case, the evidence points strongly to it as the etiologic factor. An interesting point is the almost negligible dilatation of the pelvis and calyces of the kidney above the ureteral obstruction. There was probably a degree of obstruction but not sufficient over a period of 3 years to have produced significant hydronephrosis. The histologic study of the tumor confirmed the clinical course of its benign nature. There was an orderly arrangement to the palisade architecture of the tumor and the cells ,vere of about the same size and shape with a rare mitosis. There was no breaking through the basement membrane. The richly vascularized connective tissue stalks of the tumor explain the hematuria. The consensus of opinion was that this represented a benign neoplasm and showed none of the features which are seen in carcinoma, such as variation in size and shape of cells, invasion of the stalk, hyperchromatic nuclei, and many mitotic figures. The potential malignancy of benign ureteral neoplasm, particularly the transitional cell papilloma, has been stressed by many. Some have used a terminology and classification in which benign papillomata of the transitional cell type have been called grade I carcinoma. There are histologic criteria of carcinoma which a benign papilloma does not have and this case report utilizes the classification
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JOSEPH M. EDELSTEIN AND SAUL M. MARCUS
of "benign papilloma" and reserves the diagnosis of carcinoma ·when there is invasion of the stalk of the neoplasm or base, or when the malignancy characteristics of the cells are such as to warrant such a diagnosis. The study of numerous microscopic sections in dealing with urinary tract neoplasms cannot be emphasized enough in diagnosis. Benign neoplasms of the ureter may be classified into : A) Epithelial: papilloma; and B) non-epithelial: myoma, lipoma, fibroma, hemangioma, etc. Cases of mixed tumor have been reported; in 1 a tumor of the ureter was found at autopsy, which was composed of smooth muscle, epithelium, connective tissue and bone. The second ·was classed as a fibromyoma. The papilloma may be pedunculated or may be sessile; in the former instance, the complication of intussusception should be kept in mind. Also, due to obstruction, hydrometer and hydronephrosis may develop. The nonepithelial neoplasms may arise in the wall and compress the ureter or may arise from the outer coats and encircle the ureter. The transitional cell papilloma shows numerous branching and stalked processes with a palisade arrangement to the cells which are of the same size and shape, shmY few or no mitoses and no hyperchromatism. There is no invasion of the stalk or base of the neoplasm. SUMMARY AND CONCLUSIONS
A report of a primary, benign, ureteral transitional cell papilloma is added to the literature, and the symptoms, diagnosis and treatment discussed. A total number of 32 cases, including this case report, of benign ureteral neoplasms, primary, which have been confirmed by microscopic examination, is recorded. The separation of benign papilloma from carcinoma is made in this report, and the criteria for such a diagnosis listed. A suggestion for more conservative surgery in treatment when one is dealing with connective tissue tumors such as lipoma, myomas, etc., is made; this will often result from consultation with the pathologist at the time of operation. The importance of accurate investigation of the ureter as ·well as the kidney and bladder in cases of hematuria is emphasized. This is accomplished by ureteropyelogram. The authors thank Dr. H. Edward MacMahon, Tufts College Medical School, for his aid in preparing this report. REFERENCES AscHNER, P. W.: Surg., Gynec. & Obst., 35: 749, 1922. BARNES, R. W., AND KAWAICHI, G. K.: Urol. and Cutan. Rev., 48: 430, 1944. BEER, E.: J. A. M.A., 77: 1176, 1921; J. Urol., 29: 135, 1933. BINDER, A.: Ziegler's Beitr., p.69, 1921. Quoted by Kleinschmidt. BRIDGE, R., AND KIRKLAND, K.: M. J. Australia, 1: 160, 1934. Brit. J. Urol., 5: 323, 1933: Fifth Triennial Congress of Internat. Society of Urology. BUTTNER: Ztschr. f. Geburtschulfe u. Gynakologie, 28: 136, 1894. CAULK, J. R.: Surg., Gynec. & Obst., 41: 49, 1925. CooNEY, C. J.: J. Urol., 47: 651, 1942. DEAN, A. L. JR.: Bull. N. Y. Acad. Med., 14: 128, 1938. DJEAH-Y AN (Watjen), Central bl. f. Allg. Path. u. path. Anat., 35: 549, 1924-25. EPSTEIN, G. S.: Ztschr. f. urol. Chir., 39: 63, 1934.
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FERGUSON, J. D.: Brit. J. Urol., 17: 59, 1945. HAMER, H. G., MERTZ, H. 0., AND WISHARD, W. N., JR.: J. Urol., 29: 43, 1933. HuNNER, G. L.: J. Urol., 40: 752, 1938. LANCEREAux: Dictionaire Dechambra, Article Rein, 3c Series, III, 247. LEBERT: Anat. Path., 1: 269, 1861; 2: 372, 1861. McMAHON, S.: J. Urol., 51: 616, 1944. MELrcow, M. M., AND FINDLAY, H. V., Surg., Gynec. & Obst., 54: 680, 1932. MooRE, T.: Brit. J. Surg., 29: 371, 1941-42. OTTLEY, C. M.: Brit. J. Surg., 32: 531, 1944-45. PNrcH, F. S.: Urol. & Cutan. Rev., 42: 625, 1938. RAMSEY, E. M.: J. Urol., 42: 341, 1939. RANDALL, A.: J. Urol., 46: 419, 1941. RAYICH, A.: Arch. Surg., 30: 442, 1935. RENNER, JVI. J.: Surg., Gynec. AND OBST., 52: 793, 1931. RuscHE, C., AND BACON, S. K.: .T. Urol., 39: 319, 1938. TAKAHASHI, A.: Urol. & Cutan. Rev., 32: 78, 1928. WILSON, W. E.: Brit. J. Urol., 17: 62, EJ45.
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