SQUAMOUS CELL CARCINOMA OF URETER EXTENDING INTO RENAL VEIN Positive Immunohistochemical Carcinoembryonic Antigen
Staining for
KAORU NAKAMURA, M.D. MIKI SHIRAMIZU, M.D. YOJI KATSUOKA, M.D. SHIRO BABA, M.D.
From the Department of Urology, Isehara Kyodo Hospital, Isehara, Kanagawa, Japan
ABSTRACT-A case of squamous cell carcinoma of the ureter with extension into the renal vein is presented. Zmmunoperoxidase method revealed positive staining for carcinoembryonic antigen. The literature on ureteral tumors is reviewed with special reference to renal vein involvement and carcinoembryonic antigen.
Primary ureteral carcinoma is not rare, and most of these tumors are histologically transitional cell carcinoma (TCC). Only about 1 percent of primary ureteral carcinomas are reported to be squamous cell carcinoma (SCC).l Extension of tumor thrombus into the main renal vein is rare in renal pelvic or ureteral tumors, although occasionally observed in renal cell carcinoma. There have been only 6 cases of TCC of the kidney invading the main renal vein and/or the inferior vena cava.2 To the best of our knowledge there have been no previous reports of squamous cell carcinoma of the ureter invading the main renal vein. Fulks and Falace3 reported the first case of ureteral carcinoma with extensive squamous differentiation and positive immunoperoxidase staining for carcinoembryonic antigen (CEA). Herein we present a case of SCC of the ureter which extended into the main renal vein and revealed positive CEA staining in tumor sections . Case Report A sixty-eight-year-old woman was referred from the gynecologic department of our hospital in February 1988 for further evaluation of
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abdominal mass in left lower quadrant. She had noticed the mass about four months before but left it untreated. Her previous medical history was noncontributory. She had no history of urolithiasis nor recurrent urinary tract infections. Physical examination revealed a large solid mass in the left side of the abdomen. No supraclavicular mass was noted. Admission laboratory data showed: hematocrit 38.5, serum creatinine 0.9 mg/lOO mL, and total protein 6.6 g/100 mL with albumin-globulin ratio of 0.98. The serum CEA level was 1.0 ng/mL (reference interval in nonsmokers 0 to 2.5 ng/mL). Urinalysis showed no protein, no glucose, and no red or white blood cells. Urine culture was sterile. Urine cytology was rated class I. Chest x-ray film was normal. Excretory urography showed nonvisualized left kidney. Retrograde pyelogram revealed complete obstruction of left lower ureter. There was no tumor in the bladder. Computerized tomography (CT) scan showed left atrophic kidney with hydronephrosis and left ureter with thick wall which had irregular interface and multilocular parenchyma (Fig. 1). Angiogram revealed the mass was mainly supplied by the inferior
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/ NOVEMBER1992
/ VOLUME40,NUMBER5
I
CAT scan shows left ureter with wall surrounding aorta.
FIGURE 1.
irregular
thick,
mesenteric artery and hypovascularity. A selective left renal angiogram showed stretched intrarenal arteries and occlusion of left renal vein. No cavogram was obtained. Bone scintigram was negative. At the time of surgery, the tumor expanded partly into the intraperitoneum, and the mesocolon was fixed on the surface of the tumor. Aorta was surrounded by the tumor but was able to be dissected sharply from the surrounding tumor. Tumor thrombus was felt within the left renal vein. The renal vein was excised at the inlet of the vena cava. There was no tumor thrombus into the vena cava. On gross examination, the tumor around the ureteral lumen measured 7.5 cm in length and 3.5 cm in thickness (Fig. 2A). Tumor was very
FIGURE 2. (A) Resected specimen showing tumor around left ureteral lumen, and (I?) tumor thrombus occluding lumen of left main renal vein (arrows).
FIGURE 3.
(hematoxylin
UROLOGY
Histologic section of ureteral and eosin).
/ NOVEMBER1992
carcinoma
/ VOLUME40,NUMBERS
fragile and some part of it was necrotic. The lumen of the main renal vein was occluded by tumor thrombus (Fig. 2B). Pathologic diagnosis was squamous cell carcinoma with invasion into the adjacent fat (Fig. 3). The renal vein contained tumor thrombus consisting of squamous cell carcinoma. Immunoperoxidase staining for CEA was done on thin sections of formalin-fixed, paraffin-embedded tissue. There were positive stainings in the cytoplasm or cell membrane region of squamous cell carcinoma (Fig. 4). Postoperatively the patient was given chemotherapy with pepleomycin and cis-platinum. However, she died of local disease recurrence in August 1988. Autopsy was not done.
459
FIGURE uteteral antigen staining
4. Immunoperoridase-stained section of carcinoma: with anti-carcinoembryonic serum (Dako), cells demonstrate positive in cytoplasm or cell membrane.
Comment Extension of urothelial carcinoma into the main renal vein and/or vena cava is rare, although extension of renal cell carcinoma into the vena cava is not rare with a reported incidence of approximately 5 percent.4 Review of the literature to date indicated only 6 cases of transitional cell carcinoma of the renal pelvis invading the main renal vein and vena cava have been published.2 Such renal vein obstruction was added to the causes of nonvisualization on excretory urogram in patients with TCC, in addition to the main cause of extensive destruction of the renal substance.5 We believe there are no previous reports of squamous cell carcinoma of the ureter which extended into the main renal vein. Squamous cell carcinoma of the ureter is reported to consist of only 1 percent of primary ureteral carcinoma.’ Chronic irritation of the uroepithelium has been usually associated *with the development of SCC, but in our case the patient had no previous history of urolithiasis nor urinary tract infection. The possible pathway of left main renal vein thrombus with ureteral carcinoma is thought to be through left gonadal vein which drains into the main renal vein. Carcinoembryonic antigen is present in the tumor cells of patients with bladder malignancies with immunoperoxidase staining techniques. A proportion of urothelial tumors (35 to
460
57 % ) were found to be positive for carcinoembryonic antigen.s,7 Bladder epithelium is of entodermal origin like digestive system epithelium; however ureteral epithelium is of mesodermal origin8 Therefore, data on carcinoembryonic antigen in bladder carcinoma do not always apply to ureteral carcinoma.3 There is only one report by Fulks and Falace3 that showed carcinoembryonic antigen in ureteral tumor tissue. In their case, ureteral tumor was histologically transitional cell carcinoma with extensive squamous differentiation. Our case revealed only squamous cell carcinoma without any focus of transitional cell carcinoma. As they3 pointed out, on embryologic grounds the positive immunohistochemical staining observed in ureteral malignancies may be due to cross-reacting substances rather than Gold and Freedman’9 carcinoembryonic antigen. The clinical significance of carcinoembryonic antigen in ureteral malignancies is not determined because of paucity of cases. More studies on this topic will be of interest. Isehara Kyodo Hospital 2-17-1 Sakuradai, Isehara Kanagawa 259-l 1 Japan (DR. NAKAMURA) References 1. Droller MJ: Transitional cell cancer: upper tracts and bladder, in Walsh PC, Gittes RF, Perlmutter AD, and Stamey TA (Eds): Campbell’s Urology, Baltimore, Williams & Wilkins, ~012, 1986, p 1423. 2. Chang SY and Ma CP: Transitional cell carcinoma of the kidney with extension into the inferior vena cava, Eur Urol 13: 287 (1987). 3. Fulks RM, and Falace PB: Carcinoma of the ureter with extensive squamous differentiation and positive immunoperoxidase staining for carcinoembryonic antigen, J Urol 133: 92 (1985). 4. Clayman RV, Gonzalez R, and Fraley EE: Renal cell cancer invading the inferior vena cava: clinical review and anatomical approach, J Urol 123: 157 (1980). 5. Jitsukawa S, et al: Transitional cell carcinoma of kidney extending into renal vein and inferior vena cava, Urology 25: 310 (1985). 6. Jautzke G, and Altenaehr E: Immunohistochemical demonstration of carcinoembryonic antigen (CEA) and its correlation with grading and staging on tissue sections of urinary bladder carcinoma, Cancer 50: 2052 (1982). 7. Jakse G, Rauschmeirer H, Rosmanith P and Hofstadter F: Determination of carcinoembryonic antigen in tissue, serum and urine in patients with transitional cell carcinoma of the urinary bladder, Urol Int 38: 121 (1983). 8. Arey LB: Developmental Anatomy: A Textbook and Laboratory Manual of Embryology, ed 7, Philadelphia, W.B. Saunders Co., 1965, p 83. 9. Gold P and Freedman SO: Specific carcinoembryonic antigen of the human digestive system, J Exp Med 122: 467 (1965).
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Staining for
KAORU NAKAMURA, M.D. MIKI SHIRAMIZU, M.D. YOJI KATSUOKA, M.D. SHIRO BABA, M.D.
From the Department of Urology, Isehara Kyodo Hospital, Isehara, Kanagawa, Japan
ABSTRACT-A case of squamous cell carcinoma of the ureter with extension into the renal vein is presented. Zmmunoperoxidase method revealed positive staining for carcinoembryonic antigen. The literature on ureteral tumors is reviewed with special reference to renal vein involvement and carcinoembryonic antigen.
Primary ureteral carcinoma is not rare, and most of these tumors are histologically transitional cell carcinoma (TCC). Only about 1 percent of primary ureteral carcinomas are reported to be squamous cell carcinoma (SCC).l Extension of tumor thrombus into the main renal vein is rare in renal pelvic or ureteral tumors, although occasionally observed in renal cell carcinoma. There have been only 6 cases of TCC of the kidney invading the main renal vein and/or the inferior vena cava.2 To the best of our knowledge there have been no previous reports of squamous cell carcinoma of the ureter invading the main renal vein. Fulks and Falace3 reported the first case of ureteral carcinoma with extensive squamous differentiation and positive immunoperoxidase staining for carcinoembryonic antigen (CEA). Herein we present a case of SCC of the ureter which extended into the main renal vein and revealed positive CEA staining in tumor sections . Case Report A sixty-eight-year-old woman was referred from the gynecologic department of our hospital in February 1988 for further evaluation of
458
abdominal mass in left lower quadrant. She had noticed the mass about four months before but left it untreated. Her previous medical history was noncontributory. She had no history of urolithiasis nor recurrent urinary tract infections. Physical examination revealed a large solid mass in the left side of the abdomen. No supraclavicular mass was noted. Admission laboratory data showed: hematocrit 38.5, serum creatinine 0.9 mg/lOO mL, and total protein 6.6 g/100 mL with albumin-globulin ratio of 0.98. The serum CEA level was 1.0 ng/mL (reference interval in nonsmokers 0 to 2.5 ng/mL). Urinalysis showed no protein, no glucose, and no red or white blood cells. Urine culture was sterile. Urine cytology was rated class I. Chest x-ray film was normal. Excretory urography showed nonvisualized left kidney. Retrograde pyelogram revealed complete obstruction of left lower ureter. There was no tumor in the bladder. Computerized tomography (CT) scan showed left atrophic kidney with hydronephrosis and left ureter with thick wall which had irregular interface and multilocular parenchyma (Fig. 1). Angiogram revealed the mass was mainly supplied by the inferior
UROLOGY
/ NOVEMBER1992
/ VOLUME40,NUMBER5
I
CAT scan shows left ureter with wall surrounding aorta.
FIGURE 1.
irregular
thick,
mesenteric artery and hypovascularity. A selective left renal angiogram showed stretched intrarenal arteries and occlusion of left renal vein. No cavogram was obtained. Bone scintigram was negative. At the time of surgery, the tumor expanded partly into the intraperitoneum, and the mesocolon was fixed on the surface of the tumor. Aorta was surrounded by the tumor but was able to be dissected sharply from the surrounding tumor. Tumor thrombus was felt within the left renal vein. The renal vein was excised at the inlet of the vena cava. There was no tumor thrombus into the vena cava. On gross examination, the tumor around the ureteral lumen measured 7.5 cm in length and 3.5 cm in thickness (Fig. 2A). Tumor was very
FIGURE 2. (A) Resected specimen showing tumor around left ureteral lumen, and (I?) tumor thrombus occluding lumen of left main renal vein (arrows).
FIGURE 3.
(hematoxylin
UROLOGY
Histologic section of ureteral and eosin).
/ NOVEMBER1992
carcinoma
/ VOLUME40,NUMBERS
fragile and some part of it was necrotic. The lumen of the main renal vein was occluded by tumor thrombus (Fig. 2B). Pathologic diagnosis was squamous cell carcinoma with invasion into the adjacent fat (Fig. 3). The renal vein contained tumor thrombus consisting of squamous cell carcinoma. Immunoperoxidase staining for CEA was done on thin sections of formalin-fixed, paraffin-embedded tissue. There were positive stainings in the cytoplasm or cell membrane region of squamous cell carcinoma (Fig. 4). Postoperatively the patient was given chemotherapy with pepleomycin and cis-platinum. However, she died of local disease recurrence in August 1988. Autopsy was not done.
459
FIGURE uteteral antigen staining
4. Immunoperoridase-stained section of carcinoma: with anti-carcinoembryonic serum (Dako), cells demonstrate positive in cytoplasm or cell membrane.
Comment Extension of urothelial carcinoma into the main renal vein and/or vena cava is rare, although extension of renal cell carcinoma into the vena cava is not rare with a reported incidence of approximately 5 percent.4 Review of the literature to date indicated only 6 cases of transitional cell carcinoma of the renal pelvis invading the main renal vein and vena cava have been published.2 Such renal vein obstruction was added to the causes of nonvisualization on excretory urogram in patients with TCC, in addition to the main cause of extensive destruction of the renal substance.5 We believe there are no previous reports of squamous cell carcinoma of the ureter which extended into the main renal vein. Squamous cell carcinoma of the ureter is reported to consist of only 1 percent of primary ureteral carcinoma.’ Chronic irritation of the uroepithelium has been usually associated *with the development of SCC, but in our case the patient had no previous history of urolithiasis nor urinary tract infection. The possible pathway of left main renal vein thrombus with ureteral carcinoma is thought to be through left gonadal vein which drains into the main renal vein. Carcinoembryonic antigen is present in the tumor cells of patients with bladder malignancies with immunoperoxidase staining techniques. A proportion of urothelial tumors (35 to
460
57 % ) were found to be positive for carcinoembryonic antigen.s,7 Bladder epithelium is of entodermal origin like digestive system epithelium; however ureteral epithelium is of mesodermal origin8 Therefore, data on carcinoembryonic antigen in bladder carcinoma do not always apply to ureteral carcinoma.3 There is only one report by Fulks and Falace3 that showed carcinoembryonic antigen in ureteral tumor tissue. In their case, ureteral tumor was histologically transitional cell carcinoma with extensive squamous differentiation. Our case revealed only squamous cell carcinoma without any focus of transitional cell carcinoma. As they3 pointed out, on embryologic grounds the positive immunohistochemical staining observed in ureteral malignancies may be due to cross-reacting substances rather than Gold and Freedman’9 carcinoembryonic antigen. The clinical significance of carcinoembryonic antigen in ureteral malignancies is not determined because of paucity of cases. More studies on this topic will be of interest. Isehara Kyodo Hospital 2-17-1 Sakuradai, Isehara Kanagawa 259-l 1 Japan (DR. NAKAMURA) References 1. Droller MJ: Transitional cell cancer: upper tracts and bladder, in Walsh PC, Gittes RF, Perlmutter AD, and Stamey TA (Eds): Campbell’s Urology, Baltimore, Williams & Wilkins, ~012, 1986, p 1423. 2. Chang SY and Ma CP: Transitional cell carcinoma of the kidney with extension into the inferior vena cava, Eur Urol 13: 287 (1987). 3. Fulks RM, and Falace PB: Carcinoma of the ureter with extensive squamous differentiation and positive immunoperoxidase staining for carcinoembryonic antigen, J Urol 133: 92 (1985). 4. Clayman RV, Gonzalez R, and Fraley EE: Renal cell cancer invading the inferior vena cava: clinical review and anatomical approach, J Urol 123: 157 (1980). 5. Jitsukawa S, et al: Transitional cell carcinoma of kidney extending into renal vein and inferior vena cava, Urology 25: 310 (1985). 6. Jautzke G, and Altenaehr E: Immunohistochemical demonstration of carcinoembryonic antigen (CEA) and its correlation with grading and staging on tissue sections of urinary bladder carcinoma, Cancer 50: 2052 (1982). 7. Jakse G, Rauschmeirer H, Rosmanith P and Hofstadter F: Determination of carcinoembryonic antigen in tissue, serum and urine in patients with transitional cell carcinoma of the urinary bladder, Urol Int 38: 121 (1983). 8. Arey LB: Developmental Anatomy: A Textbook and Laboratory Manual of Embryology, ed 7, Philadelphia, W.B. Saunders Co., 1965, p 83. 9. Gold P and Freedman SO: Specific carcinoembryonic antigen of the human digestive system, J Exp Med 122: 467 (1965).
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