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Squamous Cell Carcinoma Occurring in the Stump of a Chronically Infected Ureter Many Years After Nephrectomy
THE JOURNAL OF UROLOGY
Vol. 67, No. 2, February 1952 Printed in U.S.A.
SQUAMOUS CELL CARCINOMA OCCURRING IN THE STUMP OF A CHRONICALLY INFECTED URETER MANY YEARS AFTER NEPHRECTOMY JOHN A. LOEF
AND
PHILIP A. CASELLA
From the Department of Urology, St. Elizabeth's Hospital, Chicago, Ill.
Carcinoma of the ureter is no longer considered a rare or uncommon condition, due to its increased frequency and recognition during the last decade. In this article we wish to present a case of squamous cell carcinoma occurring in the stump of a chronically infected ureter many years after nephrectomy, and which we believe to be the first of its type. Recently Scott reported on 182 cases of carcinoma of the ureter, 23 of which were squamous cell type. Additional cases of squamous cell carcinoma of the ureter have been reported by Brooks, Pilcher, and Glazier. However, all of these cases have been associated with malignancy in the pelvis or kidney parenchyma. The case history that follows will show how a metaplastic process can change the nature of a cell in the course of time from benign to malignant by irritation due to the presence of chronically infected tissue. CASE REPORT
Sixteen years ago, our 66 year old patient first complained of urinary symptoms at which time she was treated for right ureteral calculi, right infected hydronephrosis, and hydro-ureters with chronic cystitis. Therapy at first was medical management, followed by nephrostomy; then the medical regimen was continued for two more years. Not responding to this type of therapy, the patient underwent nephrectomy 14 years ago for the infected hydronephrosis and hydroureter. The following year she required three additional hospitalizations for the continued urinary symptoms caused by the right pyo-ureter. These urinary symptoms persisted and returned periodically during the following years. Six months ago, the backaches, pain in the right abdominal region and burning on urination returned, persisting to date. When first examined by us in December 1949, she complained of burning, frequency, and a dull aching pain in the right lower quadrant which was increasing in intensity for over two weeks. Her past history revealed only symptoms referrable to her kidney disorder. Cystoscopic examination revealed a dilated and inflamed right ureteral orifice from which a purulent exudate was emitted. A No. 5 ureteral catheter was passed about eight centimeters into the right ureteral orifice. Ten cubic centimeters of skiodan was injected and a roentgenogram of the right lower quadrant developed (fig. 1). This ureterogram demonstrated a very irregular dilatation and filling defect involving the right ureteral stump. Physical examination disclosed a well developed, well nourished, white female who did not appear acutely ill. The positive findings were: enlarged heart to the left, dull weak tones, but no murmurs; abdomen revealed no rigidity, no masses but tenderness over the suprapubic and right lower quadrant area; postoperative scars on the abdomen and lumbar region. 159
160
JOHN A. LOEF AND PHILIP A. CASELLA
Laboratory reports before surgery disclosed 4.3 million red blood cells per cu. mm. of blood; 11.7 gm. hemoglobin per 100 cc of blood; 6,900 white blood cells per cu. mm. of blood, with 5 per cent eosinophils, 64 per cent neutrophils and 31 per cent lymphocytes; nonprotein nitrogen 22 mg. per cent. Catheterized specimen of urine: specific gravity of 1.027, amber, cloudy, acid, albumin 100 mg. per 100 cc, many pus cells, and 3 red blood cells per high powered field. The second cystoscopic examination the day prior to surgery revealed the bladder mucosa moderately congested, right ureteral orifice reddened, ulcerated and edematous, with an inability to pass the ureteral catheter beyond 1 cm. With a preoperative diagnosis of a mass in the right ureteral stump, the patient was scheduled for surgery. Through a right Gibson incision, a large mass 12 by 7 by 4 cm. adherent to bladder, peritoneum and renal fossa was exposed and
Fro. 1
resected. The patient had a satisfactory postoperative course except for a left saphenous thrombosis successfully treated with anticoagulant therapy. The patient was discharged on her eighteenth postoperative day in apparently good condition. The specimen consisted of an indurated, in places at its periphery, friable mass 3 by 2 cm. which was attached in a linear direction to a mass of semifirm tissue 12 by 7 by 4 cm. Microscopic examination (fig. 2) revealed the indurated and friable tissue consisted of edematous ureter' and adventitious tissue. "The normal mucosa is replaced by anaplastic epithelial cells which form papillae and also infiltrate the subepithelial connective tissue circular muscle bundles to the level of the longitudinal muscle bundles. The anaplastic epithelial cells have a varied morphology and resemble transitional cells, squamous cells, and spindle cells. The wall of the ureter is edematous and also infiltrated with plasma cells,
SQU.~J\/IOUS CELL CARC:I~OMA
1(-\l
round cells and epithelioid cells." The gross and microscopic diagnosis wa,:; squamous cell carcinoma of the ureter. On returning home, the patient continued to have pain in the operative area and hip region. This area became more tense, distended and tender in the following weeks. She was readmitted to the hospital seven weeks after her last discharge with complaints of severe right lower quadrant pain, tenderness in the abdomen and a distended, fluctuating mass in this area. Incision and drainage of this mass disclosed a large retroperitoneal abscess in the old operative region. For the next 2 Yrneks, this infected sinus tract drained profusely emitting a green tinged, foui odored pus. After draining for one week, an x-ray of the tract with an opaque oil revealed only a large, dilated, blind pocket apparently not connected to any loop of bowel. On her sixteenth hospital day, the patient
started to hemorrhage spontaneously through the sinus tract and expired t,rn hours later from an erosion of one of the larger pelvic blood vessels. Autopsy permit was denied. DISCUSSION
Carcinoma of the pelvis and ureter comprises about 7 per cent of all cancers of the uriuary tract, according to Herbut. The mucous membrane of the calyces, ihe pelvis, the ureter and the bladder all have similar lining of transitional epithelium. Thomas and Regnier reported that tumors in the renal pelvis are seen more frequently than those of the meter. In the 253 cases that they reported of tumors of the pelvis and ureter, only 15 per cent involved the ureter al011e. 11any cases of carcinoma of the ureter arise after nephrectomy from tumors of the kidney pelvis, as reported by Bailey, Howarth, and Mombaerts, the
162
,JOHN A. LOEF AND PHILIP A. CASELLA
reason being that renal pelvic neoplasms metastasize frequently by direct extension or drop metastasis to the ureter and even to the bladder mucosa. Carcinoma of the renal pelvis and ureter may take origin from another source as this case illustrates. When metastatic carcinoma of the ureter follows a case of malignancy in the pelvis or kidney parenchyma, the pathology and etiology can be demonstrated (Bailey, Fort and Harlin; Howarth; Mombaerts). However, when a kidney is removed for reasons other than a tumor, such as an infection or calculi, and many years later the ureteral stump that remains becomes the seat of a malignancy, an entirely different process is demonstrated. According to Herbut, the direct cause of carcinoma of the ureter is unknown but the most common theories are: leukoplakia, epithelial inclusions, mechanical or inflammatory irritation, carcinomatous rest, and excretions of carcinogens in the urine. Therefore, this is an example of origin by metaplasia or leukoplakia. Boyd remarks that leukoplakia is a rare accompaniment of chronic inflammation. The mucosa in these cases is an epidermoid change, a metaplasia of the transitional type of epithelium to a squamous stratified type. This may be regarded as a precursor of the nonpapillary type of carcinoma. In this case the squamous cell metaplasia produced by the infection later developed into squamous cell carcinoma. McCrea showed how the repeated insults to the tissues over extended periods by exacerbations, followed by low grade, continued infection, most probably induce this type of metaplasia. COMMENT
The case presented illustrates some of the known facts of carcinoma of the ureter. The etiology was evidently chronic infection and irritation. Fifteen years ago the patient had a right ureteral calculus, infected hydronephrosis and, after nephrectomy, developed pyo-ureter. The pyo-ureter was so extensive that three hospitalizations were required in the year following her nephrectomy. The pyo-ureter was never completely controlled but the patient developed a tolerance and immunity to her infection and remained relatively asymptomatic subjectively. Periodically the patient did experience episodes of abdominal pain, backache and urinary distress. The inflammatory process and possibly the malignant changes became evident 6 months prior to the time she sought medical treatment again. \Vhen she presented herself for further study, the findings were presumed to be those of an infected ureteral stump. Gross and microscopic examination of the excised mass revealed infected necrotic tissue and squamous cell carcinomatous degeneration in one area, produced by a squamous cell metaplastic process of the chronically infected tissue. We have learned from this case and the review of the literature that total ureterectomy should be done as the procedure of choice in treatment of chronically infected kidneys, tumors of the renal pelvis, polyposis, and pyo-ureters where surgical treatment is indicated. Only by this radical procedure can chronic pyo-ureter and possibly carcinoma of the ureteral stump be eliminated. However, because of the rarity of carcinoma of the ureter, in uncomplicated cases one should remove only that portion of the ureter reached without additional trauma or incision.
SQUAMOUS CELL CARCINOMA
163,
SUMMARY
1. A case has been presented of carcinoma occurring in the ureteral stump· many years after nephrectomy for a chronically infected kidney and ureter. 2. This illustrates how squamous cell metaplasia, in the presence of chronic· infection and irritation develops into squamous cell carcinoma. 3. A total ureterectomy should be the treatment of choice in cases of chronically infected kidney, tumors of the renal pelvis, polyposis and pyo-ureters, when surgery is indicated.
3600 W. Fullerton Ave., Chicago (F. G. M.) 400 S. Laramie Ave., Chicago (M. L. M.) REFERENCES BAILEY, M. K., FoRT, C. A., AND HARLIN, H. C.: J. Urol., 62: 44, 1949. Boyd, W.: Textbook of Pathology. Philadelphia: Lea & Febiger, 1940, 3rd ed., p. 681. BROOKS, W. H.: J. Urol., 61: 29, 1949. GLAZIER, M.: Urol. & Cutan. Rev., 53: 595, 1949. HERBUT, P.A.: Surgical Pathology. Philadelphia: Lea & Febiger, 1948, 1st ed., p. 523. HINMAN, F.: The Principles and Practice of Urology, Philadelphia: W. B. Saunders Co., 1936, 1st ed., p. 1005. HowARTH, V. S.: Med. J. Australia 2, 746, 1949. McCREA, L. E.: J.A.M.A., 142: 631, 1950. MoMBAERTs, J.: J. Belge d'urol., 4: 153, 1948. PILCHER, F.: Canad. Med. Assoc. J., 57: 3, 1947. SCOTT, W.W.: J. Urol., 50: 45, 1943.
Vol. 67, No. 2, February 1952 Printed in U.S.A.
SQUAMOUS CELL CARCINOMA OCCURRING IN THE STUMP OF A CHRONICALLY INFECTED URETER MANY YEARS AFTER NEPHRECTOMY JOHN A. LOEF
AND
PHILIP A. CASELLA
From the Department of Urology, St. Elizabeth's Hospital, Chicago, Ill.
Carcinoma of the ureter is no longer considered a rare or uncommon condition, due to its increased frequency and recognition during the last decade. In this article we wish to present a case of squamous cell carcinoma occurring in the stump of a chronically infected ureter many years after nephrectomy, and which we believe to be the first of its type. Recently Scott reported on 182 cases of carcinoma of the ureter, 23 of which were squamous cell type. Additional cases of squamous cell carcinoma of the ureter have been reported by Brooks, Pilcher, and Glazier. However, all of these cases have been associated with malignancy in the pelvis or kidney parenchyma. The case history that follows will show how a metaplastic process can change the nature of a cell in the course of time from benign to malignant by irritation due to the presence of chronically infected tissue. CASE REPORT
Sixteen years ago, our 66 year old patient first complained of urinary symptoms at which time she was treated for right ureteral calculi, right infected hydronephrosis, and hydro-ureters with chronic cystitis. Therapy at first was medical management, followed by nephrostomy; then the medical regimen was continued for two more years. Not responding to this type of therapy, the patient underwent nephrectomy 14 years ago for the infected hydronephrosis and hydroureter. The following year she required three additional hospitalizations for the continued urinary symptoms caused by the right pyo-ureter. These urinary symptoms persisted and returned periodically during the following years. Six months ago, the backaches, pain in the right abdominal region and burning on urination returned, persisting to date. When first examined by us in December 1949, she complained of burning, frequency, and a dull aching pain in the right lower quadrant which was increasing in intensity for over two weeks. Her past history revealed only symptoms referrable to her kidney disorder. Cystoscopic examination revealed a dilated and inflamed right ureteral orifice from which a purulent exudate was emitted. A No. 5 ureteral catheter was passed about eight centimeters into the right ureteral orifice. Ten cubic centimeters of skiodan was injected and a roentgenogram of the right lower quadrant developed (fig. 1). This ureterogram demonstrated a very irregular dilatation and filling defect involving the right ureteral stump. Physical examination disclosed a well developed, well nourished, white female who did not appear acutely ill. The positive findings were: enlarged heart to the left, dull weak tones, but no murmurs; abdomen revealed no rigidity, no masses but tenderness over the suprapubic and right lower quadrant area; postoperative scars on the abdomen and lumbar region. 159
160
JOHN A. LOEF AND PHILIP A. CASELLA
Laboratory reports before surgery disclosed 4.3 million red blood cells per cu. mm. of blood; 11.7 gm. hemoglobin per 100 cc of blood; 6,900 white blood cells per cu. mm. of blood, with 5 per cent eosinophils, 64 per cent neutrophils and 31 per cent lymphocytes; nonprotein nitrogen 22 mg. per cent. Catheterized specimen of urine: specific gravity of 1.027, amber, cloudy, acid, albumin 100 mg. per 100 cc, many pus cells, and 3 red blood cells per high powered field. The second cystoscopic examination the day prior to surgery revealed the bladder mucosa moderately congested, right ureteral orifice reddened, ulcerated and edematous, with an inability to pass the ureteral catheter beyond 1 cm. With a preoperative diagnosis of a mass in the right ureteral stump, the patient was scheduled for surgery. Through a right Gibson incision, a large mass 12 by 7 by 4 cm. adherent to bladder, peritoneum and renal fossa was exposed and
Fro. 1
resected. The patient had a satisfactory postoperative course except for a left saphenous thrombosis successfully treated with anticoagulant therapy. The patient was discharged on her eighteenth postoperative day in apparently good condition. The specimen consisted of an indurated, in places at its periphery, friable mass 3 by 2 cm. which was attached in a linear direction to a mass of semifirm tissue 12 by 7 by 4 cm. Microscopic examination (fig. 2) revealed the indurated and friable tissue consisted of edematous ureter' and adventitious tissue. "The normal mucosa is replaced by anaplastic epithelial cells which form papillae and also infiltrate the subepithelial connective tissue circular muscle bundles to the level of the longitudinal muscle bundles. The anaplastic epithelial cells have a varied morphology and resemble transitional cells, squamous cells, and spindle cells. The wall of the ureter is edematous and also infiltrated with plasma cells,
SQU.~J\/IOUS CELL CARC:I~OMA
1(-\l
round cells and epithelioid cells." The gross and microscopic diagnosis wa,:; squamous cell carcinoma of the ureter. On returning home, the patient continued to have pain in the operative area and hip region. This area became more tense, distended and tender in the following weeks. She was readmitted to the hospital seven weeks after her last discharge with complaints of severe right lower quadrant pain, tenderness in the abdomen and a distended, fluctuating mass in this area. Incision and drainage of this mass disclosed a large retroperitoneal abscess in the old operative region. For the next 2 Yrneks, this infected sinus tract drained profusely emitting a green tinged, foui odored pus. After draining for one week, an x-ray of the tract with an opaque oil revealed only a large, dilated, blind pocket apparently not connected to any loop of bowel. On her sixteenth hospital day, the patient
started to hemorrhage spontaneously through the sinus tract and expired t,rn hours later from an erosion of one of the larger pelvic blood vessels. Autopsy permit was denied. DISCUSSION
Carcinoma of the pelvis and ureter comprises about 7 per cent of all cancers of the uriuary tract, according to Herbut. The mucous membrane of the calyces, ihe pelvis, the ureter and the bladder all have similar lining of transitional epithelium. Thomas and Regnier reported that tumors in the renal pelvis are seen more frequently than those of the meter. In the 253 cases that they reported of tumors of the pelvis and ureter, only 15 per cent involved the ureter al011e. 11any cases of carcinoma of the ureter arise after nephrectomy from tumors of the kidney pelvis, as reported by Bailey, Howarth, and Mombaerts, the
162
,JOHN A. LOEF AND PHILIP A. CASELLA
reason being that renal pelvic neoplasms metastasize frequently by direct extension or drop metastasis to the ureter and even to the bladder mucosa. Carcinoma of the renal pelvis and ureter may take origin from another source as this case illustrates. When metastatic carcinoma of the ureter follows a case of malignancy in the pelvis or kidney parenchyma, the pathology and etiology can be demonstrated (Bailey, Fort and Harlin; Howarth; Mombaerts). However, when a kidney is removed for reasons other than a tumor, such as an infection or calculi, and many years later the ureteral stump that remains becomes the seat of a malignancy, an entirely different process is demonstrated. According to Herbut, the direct cause of carcinoma of the ureter is unknown but the most common theories are: leukoplakia, epithelial inclusions, mechanical or inflammatory irritation, carcinomatous rest, and excretions of carcinogens in the urine. Therefore, this is an example of origin by metaplasia or leukoplakia. Boyd remarks that leukoplakia is a rare accompaniment of chronic inflammation. The mucosa in these cases is an epidermoid change, a metaplasia of the transitional type of epithelium to a squamous stratified type. This may be regarded as a precursor of the nonpapillary type of carcinoma. In this case the squamous cell metaplasia produced by the infection later developed into squamous cell carcinoma. McCrea showed how the repeated insults to the tissues over extended periods by exacerbations, followed by low grade, continued infection, most probably induce this type of metaplasia. COMMENT
The case presented illustrates some of the known facts of carcinoma of the ureter. The etiology was evidently chronic infection and irritation. Fifteen years ago the patient had a right ureteral calculus, infected hydronephrosis and, after nephrectomy, developed pyo-ureter. The pyo-ureter was so extensive that three hospitalizations were required in the year following her nephrectomy. The pyo-ureter was never completely controlled but the patient developed a tolerance and immunity to her infection and remained relatively asymptomatic subjectively. Periodically the patient did experience episodes of abdominal pain, backache and urinary distress. The inflammatory process and possibly the malignant changes became evident 6 months prior to the time she sought medical treatment again. \Vhen she presented herself for further study, the findings were presumed to be those of an infected ureteral stump. Gross and microscopic examination of the excised mass revealed infected necrotic tissue and squamous cell carcinomatous degeneration in one area, produced by a squamous cell metaplastic process of the chronically infected tissue. We have learned from this case and the review of the literature that total ureterectomy should be done as the procedure of choice in treatment of chronically infected kidneys, tumors of the renal pelvis, polyposis, and pyo-ureters where surgical treatment is indicated. Only by this radical procedure can chronic pyo-ureter and possibly carcinoma of the ureteral stump be eliminated. However, because of the rarity of carcinoma of the ureter, in uncomplicated cases one should remove only that portion of the ureter reached without additional trauma or incision.
SQUAMOUS CELL CARCINOMA
163,
SUMMARY
1. A case has been presented of carcinoma occurring in the ureteral stump· many years after nephrectomy for a chronically infected kidney and ureter. 2. This illustrates how squamous cell metaplasia, in the presence of chronic· infection and irritation develops into squamous cell carcinoma. 3. A total ureterectomy should be the treatment of choice in cases of chronically infected kidney, tumors of the renal pelvis, polyposis and pyo-ureters, when surgery is indicated.
3600 W. Fullerton Ave., Chicago (F. G. M.) 400 S. Laramie Ave., Chicago (M. L. M.) REFERENCES BAILEY, M. K., FoRT, C. A., AND HARLIN, H. C.: J. Urol., 62: 44, 1949. Boyd, W.: Textbook of Pathology. Philadelphia: Lea & Febiger, 1940, 3rd ed., p. 681. BROOKS, W. H.: J. Urol., 61: 29, 1949. GLAZIER, M.: Urol. & Cutan. Rev., 53: 595, 1949. HERBUT, P.A.: Surgical Pathology. Philadelphia: Lea & Febiger, 1948, 1st ed., p. 523. HINMAN, F.: The Principles and Practice of Urology, Philadelphia: W. B. Saunders Co., 1936, 1st ed., p. 1005. HowARTH, V. S.: Med. J. Australia 2, 746, 1949. McCREA, L. E.: J.A.M.A., 142: 631, 1950. MoMBAERTs, J.: J. Belge d'urol., 4: 153, 1948. PILCHER, F.: Canad. Med. Assoc. J., 57: 3, 1947. SCOTT, W.W.: J. Urol., 50: 45, 1943.