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Choriocarcinoma and bilateral renal metastases
CHORIOCARCINOMA
AND BILATERAL
RENAL METASTASES
LARRY B. NEWMAN, THOMAS JAMES LESLIE
E. MORGAN,
M.D. M.D.
G. BUCY, M.D. WISE,
M.D.
From the Departments of Surgery, Division of Urology, and Obstetrics and Gynecology, St. Louis County Hospital and Washington University School of Medicine, St. Louis, Missouri
ABSTRACT - A case of choriocarcinomu presenting with metastases to both kidneys is reported. The epio%miologic and pathologic aspects of gestational choriocarcinoma are briejly discussed. Prior reports of renal metastases with choriocarcinoma are reviewed, and the fairly typical clinical presentation of this entity is emphasized.
Choriocarcinoma or chorioepithelioma is a trophoblastic neoplasm which begins in the fetal chorion and represents a derangement of trophoblastic growth. 1 This tumor is characteristically a disease of young women of child-bearing age. It metastasizes early to various sites and can present with bizarre clinical signs and symptoms.’ This report is of a patient with choriocarcinoma who had clinical features of bilateral renal metastases. The clinical, epidemiologic, and pathologic aspects of this tumor are reviewed. Case Report A twenty-four-year-old white woman was admitted to the St. Louis County Hospital on December 6, 1973, with a three-hour history of pain on the left side of her abdomen. The patient pulmonary or urologic no previous had symptoms or disease. Her past history included a spontaneous abortion five years prior to admission, followed by a dilatation and curettage. Four years prior to admission, the patient underwent a right salpingo-oophorectomy for an ectopic Subsequent normal intubal pregnancy. trauterine pregnancies and deliveries occurred three years and two years prior to this admission.
On physical examination the patient had a blood pressure of 120/80 mm. Hg and a pulse rate of 86. There was tenderness in the left upper abdomen associated with a questionable mass. Bowel sounds were normal. Laboratory data on admission included a hematocrit of 34 and a white blood cell count of 7,500. Urinalysis showed 5 to 6 white blood cells and 14 to 18 red blood cells per high-power field. Routine biochemical profile including serum electrolytes, blood urea nitrogen, and creatinine were within normal limits. Chest roentgenogram demonstrated a 6 cm.mass in the left lung field (Fig. 1A). Intravenous pyelography revealed a nonfunctioning left kidney with the bowel shadow displaced medially and some distortion of the upper pole collecting system on the right side (Fig. 1B). Midstream arteriogram demonstrated a mass in the lower pole of the left kidney measuring 4 to 5 cm., with outward displacement of capsular vessels (Fig. 1C). In addition a 7 by g-cm. irregular mass in the upper pole was noted in the right kidney. These observations were confirmed on selective renal arteriography. During this procedure, the patient’s blood pressure dropped to 90/60 mm. Hg, and her pulse rate rose to 110 per minute.
UROLOGY
/ MAY 1975 / VOLUME
V. NUMBER 5
FIGURE 1. (A) Chest roentgenogram demonstrating &cm. lesion in left lung. (B) Intravenous pyelogram showing nonfunctioning left kidney and distortion of upper pole calyces of right kidney. (C) Midstream arteriogram with left lower pole and right upper pole tumor blush.
On repeat physical examination a definite mass was palpated in the left abdomen associated with increasing tenderness in that area. A repeat hematocrit at this point revealed a drop from the previous reading of 34 to 28. After failure of stabilization of her blood pressure with fluid and 2 units of whole blood over a period of forty-five minutes, the patient was taken to the operating room; and a left retroperitoneal exploration was performed through a twelfth rib incision. A tense blue mass was noted in the retroperitoneum completely filling Gerota’s fascia. On opening Gerota’s fascia, numerous clots were evacuated. A 4 by 5cm. mass was visualized in the lower pole of the left kidney, and a heminephrectomy was performed. The patient’s postoperative course was uneventful, and the pathologic diagnosis was
UROLOGY
/ MAY 1975 / VOLUME
V, NUMBER 5
choriocarcinoma of the lower pole of the left kidney (Fig. 2A). Intravenous pyelogram obtained on the sixth postoperative day demonstrated prompt function bilaterally without evidence of urinary extravasation (Fig. 2B). On the seventh postoperative day the patient underwent dilatation and curettage, and laparoscopy. No significant pathologic findings were noted either grossly or microscopically. Postoperatively, the patient’s twenty-four-hour urine for human chorionic gonadtropins was positive qualitatively on two occasions. On quantitative estimation, a value of 76,100 I. U. (normal is less than 20 I.U.) and positive readings in dilutions of 1 to 64 were made. Thirteen days postoperatively the patient was placed on a five-day course of triple chemotherapy, consisting of methotrexate 15
FIGURE 2. (A) Photomicrograph showing cytotrophoblastic and syncytiotrophoblastic tumor cells. (B) Postoperative intravenous pyelogram demonstrating bilateral renal visualization (dressings in place).
mg. intramuscularly per day, chlorambucil 10 mg. orally per day, and actinomycin-D 600 micrograms intravenously per day. Initially her condition deteriorated; the platelet count fell to 35 x lo3 per cubic millimeter, and the white blood cell count dropped to 1.6 x lo3 per cubic millimeter. Massive hematuria developed, requiring multiple transfusions and continuous bladder irrigation. Her general condition, however, improved gradually; the twenty-four-hour urine chorionic gonadotropin titer dropped to after her first course of 4,250 I.U. chemotherapy. During the next two months, the patient underwent two repeat courses of triple chemotherapy, each attended by marked toxicity and hematuria. Her serum and urinary gonadotropin levels are now within normal range. Findings on chest x-ray films and intravenous pyelograms have shown some improvement, but roentgenologic evidence of tumor as well as significant hematuria persist. Comment Choriocarcinoma may be divided into two large categories: gestational and nongestational. Gestational choriocarcinoma is by far the more common, and arises in placental tissue or in a hydatidiform mole. Nongestational choriocarcinema most commonly arises in the ovaries, but rarely it may be primary in the retroperitoneum,
660
pineal body, or the mediastinum.3 Histologically, the primary tumor may present as a mixed germ cell tumor but, interestingly, often metastasizes as pure choriocarcinoma. 4 Gestational choriocarcinoma most commonly occurs in the period of maximum fecundity, the third decade of life. About 40 per cent of gestational choriocarcinoma is preceded by hydatidiform moles and 20 per cent by normal term pregnancy. 5-10The remaining 40 per cent of gestational trophoblastic disease arises from tubal or ovarian ectopic pregnancies. 8~11 Choriocarcinoma is a rapidly growing tumor which characteristically outgrows its blood supply with ensuing necrosis and hemorrhage. Besides tissue diagnosis the most common means of diagnosis is by elevated urinary or serum levels of human chorionic gonadotropin. Prior to the era of modern chemotherapy, large autopsy series frequently reported an incidence of pulmonary metastases of over 95 per cent. 6,‘,12 Hence, a fairly typical presenting complaint of a patient with metastatic choriocarcinoma was gross hemoptysis. The actual incidence of renal metastases in gestational choriocarcinoma is difficult to establish, but it is quite unusual as a presenting symptom. In several series of choriocarcinoma, in which all or most of the compiled before effective cases were chemotherapy was introduced, the reported incidence of metastatic disease in the kidneys
UROLOGY
/ MAY1975
/ VOLUMEV,
NUMBER5
varied from 10 to 50 per cent, with 40 per cent are being the average. 6,7*12 Renal metastases generally a sign of far advanced disease. In a series of 32 cases there was no instance in which the kidneys were the primary site of metastases; but in 25 per cent the kidneys were involved at autopsy. r2 The case reported here is most unusual in its presentation, but by no means unique. In a series of 40 cases of choriocarcinoma, 1 case was mistakenly diagnosed on admission as renal cell carcinoma.6 An isolated case has been reported in which vaginal and renal metastases simultaneously developed in a forty-seven-year-old woman three months after hysterectomy. Massive hematuria developed, and nephrectomy was required. s In a review of 24 cases compiled in 1956, it was noted that in 2 of the cases the diagnosis on admission was hypernephroma, and in 1 of these cases, nephrectomy was performed and the correct diagnosis made only after histopathologic examination of the surgical specimen. lo In 1967 a case was reported as metastatic choriocarcinoma which presented as a right renal mass associated with hematuria, fever, and leukocytosis. l3 In some of the cases mentioned previously, details regarding presenting symptoms and signs are scanty, but in others, there is sufficient information to conclude that patients with choriocarcinoma metastatic to the kidney present in a fairly characteristic fashion. She is a woman of child-bearing age who has previously been pregnant. Costovertebral angle pain develops on the involved side(s), usually associated with gross, even massive, hematuria or perirenal bleeding. Radiologic studies suggest a tumor in one or both kidneys. If the physician sees such a case, a chorionic gonadotropin assay may help establish the diagnosis so that nephrectomy may possibly be avoided and appropriate chemotherapy be promptly initiated. Any unexpected bizarre illness in women of reproductive age should always be regarded as possibly due to choriocarcinoma. Because of its rapid growth rate and hemorrhagic tendency, this neoplasm can produce an illness of rapid onset and relatively short duration. l4 Therefore, the importance of consideration of metastatic gestational choriocarcinoma in the differential
UROLOGY
/ MAY 1975 I VOLUME V, NUMBER 5
diagnosis of women of child-bearing age who present with hematuria or perirenal bleeding and evidence of renal neoplasm should be emphasized. Department of Surgery 601 South Brentwood St. Louis, Missouri 63105 (DR. WISE) References neoplasms, 1. LEWIS, J,, JR. : Gestational trophoblastic Bull. Sloane Hosp. Women 14: 121 (1968). 2. MARCUSE, P. M. : Puhnonary syncytial giant cell embolism: report of a maternal death, Obstet. Gynecol. 3: 210 (1954). disease: natural history, 3. Lr, M. D.: Trophoblastic diagnosis, and treatment, Ann. Int. Med. 74: 102 (1971). 4. GOLDSTEIN, D. P., and PIRO, A. J.: Combination chemotherapy in the treatment of germ cell tumors containing choriocarcinoma in males and females, Surg. Gynecol. Obstet. 134: 61 (1972). 5. MATALON, M., PAZ, B., MODAN, M., and MODAN, B.: Malignant trophoblastic disorders, Am. J. Obstet. Gynecol. 112: 101 (1972). 6. MARQUEZ-MOUTER, H., DELAVEGA, G. A., RIDAURA, in C., and ROBLES, M. : Gestational choriocarcinoma the General Hospital of Mexico. Analysis of 40 cases, Cancer 22: 91 (1968). of the 7. NOVAK, E., and SEAH, C. S.: Choriocarcinoma uterus: a study of 74 cases from the Mathieu Memorial Chorioepithelioma Registry, Am. J. Obstet. Gynecol. 67: 933 (1954). 8. GOLDSTEIX, P., WINIG, P., and SHIRLEY, R. L.: Actinomycin-D as initial therapy of gestational trophoblastic disease: a re-evaluation, Obstet. Gynecol. 39: 341 (1972). 9. OBER, W. B., EDGCOURB, J. H., and PRICE, E. B., JR.: The pathology of choriocarcinoma, Ann. N. Y. Acad. Sci. 173: 299 (1971). 10. HOU, P. C., and PANG, S. C.: Chorioepithelioma: an analytical study of 28 necropsied cases with special reference to the possibility of spontaneous retrogression, J. Pathol. Bacterial. 72: 95 (1956). 11. PATTON, G. W., JR., and GOLDSTEIN, D. P.: Gestational choriocarcinoma of the tube and ovary, Surg. Gynecol. Obstet. 137: 608 (1973). 12. ACOSTA-SISON, H.: The relative frequency of various anatomic sites as the point of first metastasis in 32 cases of chorioepithelioma, Am. J. Obstet. Gynecol. 75: 1149 (1958). 13. PATRICK, C. E., NORTON, J. H., and DACSO, M. in the kidney: a case report, J. R.: Choriocarcinoma Ural. 97: 444 (1967). 14. KITTREDGE, R. D.: Choriocarcinoma: aspects of the clinical pathology, Am. J. Roentgenol. Radium. Ther. Nucl. Med. 117: 637 (1973).
661
AND BILATERAL
RENAL METASTASES
LARRY B. NEWMAN, THOMAS JAMES LESLIE
E. MORGAN,
M.D. M.D.
G. BUCY, M.D. WISE,
M.D.
From the Departments of Surgery, Division of Urology, and Obstetrics and Gynecology, St. Louis County Hospital and Washington University School of Medicine, St. Louis, Missouri
ABSTRACT - A case of choriocarcinomu presenting with metastases to both kidneys is reported. The epio%miologic and pathologic aspects of gestational choriocarcinoma are briejly discussed. Prior reports of renal metastases with choriocarcinoma are reviewed, and the fairly typical clinical presentation of this entity is emphasized.
Choriocarcinoma or chorioepithelioma is a trophoblastic neoplasm which begins in the fetal chorion and represents a derangement of trophoblastic growth. 1 This tumor is characteristically a disease of young women of child-bearing age. It metastasizes early to various sites and can present with bizarre clinical signs and symptoms.’ This report is of a patient with choriocarcinoma who had clinical features of bilateral renal metastases. The clinical, epidemiologic, and pathologic aspects of this tumor are reviewed. Case Report A twenty-four-year-old white woman was admitted to the St. Louis County Hospital on December 6, 1973, with a three-hour history of pain on the left side of her abdomen. The patient pulmonary or urologic no previous had symptoms or disease. Her past history included a spontaneous abortion five years prior to admission, followed by a dilatation and curettage. Four years prior to admission, the patient underwent a right salpingo-oophorectomy for an ectopic Subsequent normal intubal pregnancy. trauterine pregnancies and deliveries occurred three years and two years prior to this admission.
On physical examination the patient had a blood pressure of 120/80 mm. Hg and a pulse rate of 86. There was tenderness in the left upper abdomen associated with a questionable mass. Bowel sounds were normal. Laboratory data on admission included a hematocrit of 34 and a white blood cell count of 7,500. Urinalysis showed 5 to 6 white blood cells and 14 to 18 red blood cells per high-power field. Routine biochemical profile including serum electrolytes, blood urea nitrogen, and creatinine were within normal limits. Chest roentgenogram demonstrated a 6 cm.mass in the left lung field (Fig. 1A). Intravenous pyelography revealed a nonfunctioning left kidney with the bowel shadow displaced medially and some distortion of the upper pole collecting system on the right side (Fig. 1B). Midstream arteriogram demonstrated a mass in the lower pole of the left kidney measuring 4 to 5 cm., with outward displacement of capsular vessels (Fig. 1C). In addition a 7 by g-cm. irregular mass in the upper pole was noted in the right kidney. These observations were confirmed on selective renal arteriography. During this procedure, the patient’s blood pressure dropped to 90/60 mm. Hg, and her pulse rate rose to 110 per minute.
UROLOGY
/ MAY 1975 / VOLUME
V. NUMBER 5
FIGURE 1. (A) Chest roentgenogram demonstrating &cm. lesion in left lung. (B) Intravenous pyelogram showing nonfunctioning left kidney and distortion of upper pole calyces of right kidney. (C) Midstream arteriogram with left lower pole and right upper pole tumor blush.
On repeat physical examination a definite mass was palpated in the left abdomen associated with increasing tenderness in that area. A repeat hematocrit at this point revealed a drop from the previous reading of 34 to 28. After failure of stabilization of her blood pressure with fluid and 2 units of whole blood over a period of forty-five minutes, the patient was taken to the operating room; and a left retroperitoneal exploration was performed through a twelfth rib incision. A tense blue mass was noted in the retroperitoneum completely filling Gerota’s fascia. On opening Gerota’s fascia, numerous clots were evacuated. A 4 by 5cm. mass was visualized in the lower pole of the left kidney, and a heminephrectomy was performed. The patient’s postoperative course was uneventful, and the pathologic diagnosis was
UROLOGY
/ MAY 1975 / VOLUME
V, NUMBER 5
choriocarcinoma of the lower pole of the left kidney (Fig. 2A). Intravenous pyelogram obtained on the sixth postoperative day demonstrated prompt function bilaterally without evidence of urinary extravasation (Fig. 2B). On the seventh postoperative day the patient underwent dilatation and curettage, and laparoscopy. No significant pathologic findings were noted either grossly or microscopically. Postoperatively, the patient’s twenty-four-hour urine for human chorionic gonadtropins was positive qualitatively on two occasions. On quantitative estimation, a value of 76,100 I. U. (normal is less than 20 I.U.) and positive readings in dilutions of 1 to 64 were made. Thirteen days postoperatively the patient was placed on a five-day course of triple chemotherapy, consisting of methotrexate 15
FIGURE 2. (A) Photomicrograph showing cytotrophoblastic and syncytiotrophoblastic tumor cells. (B) Postoperative intravenous pyelogram demonstrating bilateral renal visualization (dressings in place).
mg. intramuscularly per day, chlorambucil 10 mg. orally per day, and actinomycin-D 600 micrograms intravenously per day. Initially her condition deteriorated; the platelet count fell to 35 x lo3 per cubic millimeter, and the white blood cell count dropped to 1.6 x lo3 per cubic millimeter. Massive hematuria developed, requiring multiple transfusions and continuous bladder irrigation. Her general condition, however, improved gradually; the twenty-four-hour urine chorionic gonadotropin titer dropped to after her first course of 4,250 I.U. chemotherapy. During the next two months, the patient underwent two repeat courses of triple chemotherapy, each attended by marked toxicity and hematuria. Her serum and urinary gonadotropin levels are now within normal range. Findings on chest x-ray films and intravenous pyelograms have shown some improvement, but roentgenologic evidence of tumor as well as significant hematuria persist. Comment Choriocarcinoma may be divided into two large categories: gestational and nongestational. Gestational choriocarcinoma is by far the more common, and arises in placental tissue or in a hydatidiform mole. Nongestational choriocarcinema most commonly arises in the ovaries, but rarely it may be primary in the retroperitoneum,
660
pineal body, or the mediastinum.3 Histologically, the primary tumor may present as a mixed germ cell tumor but, interestingly, often metastasizes as pure choriocarcinoma. 4 Gestational choriocarcinoma most commonly occurs in the period of maximum fecundity, the third decade of life. About 40 per cent of gestational choriocarcinoma is preceded by hydatidiform moles and 20 per cent by normal term pregnancy. 5-10The remaining 40 per cent of gestational trophoblastic disease arises from tubal or ovarian ectopic pregnancies. 8~11 Choriocarcinoma is a rapidly growing tumor which characteristically outgrows its blood supply with ensuing necrosis and hemorrhage. Besides tissue diagnosis the most common means of diagnosis is by elevated urinary or serum levels of human chorionic gonadotropin. Prior to the era of modern chemotherapy, large autopsy series frequently reported an incidence of pulmonary metastases of over 95 per cent. 6,‘,12 Hence, a fairly typical presenting complaint of a patient with metastatic choriocarcinoma was gross hemoptysis. The actual incidence of renal metastases in gestational choriocarcinoma is difficult to establish, but it is quite unusual as a presenting symptom. In several series of choriocarcinoma, in which all or most of the compiled before effective cases were chemotherapy was introduced, the reported incidence of metastatic disease in the kidneys
UROLOGY
/ MAY1975
/ VOLUMEV,
NUMBER5
varied from 10 to 50 per cent, with 40 per cent are being the average. 6,7*12 Renal metastases generally a sign of far advanced disease. In a series of 32 cases there was no instance in which the kidneys were the primary site of metastases; but in 25 per cent the kidneys were involved at autopsy. r2 The case reported here is most unusual in its presentation, but by no means unique. In a series of 40 cases of choriocarcinoma, 1 case was mistakenly diagnosed on admission as renal cell carcinoma.6 An isolated case has been reported in which vaginal and renal metastases simultaneously developed in a forty-seven-year-old woman three months after hysterectomy. Massive hematuria developed, and nephrectomy was required. s In a review of 24 cases compiled in 1956, it was noted that in 2 of the cases the diagnosis on admission was hypernephroma, and in 1 of these cases, nephrectomy was performed and the correct diagnosis made only after histopathologic examination of the surgical specimen. lo In 1967 a case was reported as metastatic choriocarcinoma which presented as a right renal mass associated with hematuria, fever, and leukocytosis. l3 In some of the cases mentioned previously, details regarding presenting symptoms and signs are scanty, but in others, there is sufficient information to conclude that patients with choriocarcinoma metastatic to the kidney present in a fairly characteristic fashion. She is a woman of child-bearing age who has previously been pregnant. Costovertebral angle pain develops on the involved side(s), usually associated with gross, even massive, hematuria or perirenal bleeding. Radiologic studies suggest a tumor in one or both kidneys. If the physician sees such a case, a chorionic gonadotropin assay may help establish the diagnosis so that nephrectomy may possibly be avoided and appropriate chemotherapy be promptly initiated. Any unexpected bizarre illness in women of reproductive age should always be regarded as possibly due to choriocarcinoma. Because of its rapid growth rate and hemorrhagic tendency, this neoplasm can produce an illness of rapid onset and relatively short duration. l4 Therefore, the importance of consideration of metastatic gestational choriocarcinoma in the differential
UROLOGY
/ MAY 1975 I VOLUME V, NUMBER 5
diagnosis of women of child-bearing age who present with hematuria or perirenal bleeding and evidence of renal neoplasm should be emphasized. Department of Surgery 601 South Brentwood St. Louis, Missouri 63105 (DR. WISE) References neoplasms, 1. LEWIS, J,, JR. : Gestational trophoblastic Bull. Sloane Hosp. Women 14: 121 (1968). 2. MARCUSE, P. M. : Puhnonary syncytial giant cell embolism: report of a maternal death, Obstet. Gynecol. 3: 210 (1954). disease: natural history, 3. Lr, M. D.: Trophoblastic diagnosis, and treatment, Ann. Int. Med. 74: 102 (1971). 4. GOLDSTEIN, D. P., and PIRO, A. J.: Combination chemotherapy in the treatment of germ cell tumors containing choriocarcinoma in males and females, Surg. Gynecol. Obstet. 134: 61 (1972). 5. MATALON, M., PAZ, B., MODAN, M., and MODAN, B.: Malignant trophoblastic disorders, Am. J. Obstet. Gynecol. 112: 101 (1972). 6. MARQUEZ-MOUTER, H., DELAVEGA, G. A., RIDAURA, in C., and ROBLES, M. : Gestational choriocarcinoma the General Hospital of Mexico. Analysis of 40 cases, Cancer 22: 91 (1968). of the 7. NOVAK, E., and SEAH, C. S.: Choriocarcinoma uterus: a study of 74 cases from the Mathieu Memorial Chorioepithelioma Registry, Am. J. Obstet. Gynecol. 67: 933 (1954). 8. GOLDSTEIX, P., WINIG, P., and SHIRLEY, R. L.: Actinomycin-D as initial therapy of gestational trophoblastic disease: a re-evaluation, Obstet. Gynecol. 39: 341 (1972). 9. OBER, W. B., EDGCOURB, J. H., and PRICE, E. B., JR.: The pathology of choriocarcinoma, Ann. N. Y. Acad. Sci. 173: 299 (1971). 10. HOU, P. C., and PANG, S. C.: Chorioepithelioma: an analytical study of 28 necropsied cases with special reference to the possibility of spontaneous retrogression, J. Pathol. Bacterial. 72: 95 (1956). 11. PATTON, G. W., JR., and GOLDSTEIN, D. P.: Gestational choriocarcinoma of the tube and ovary, Surg. Gynecol. Obstet. 137: 608 (1973). 12. ACOSTA-SISON, H.: The relative frequency of various anatomic sites as the point of first metastasis in 32 cases of chorioepithelioma, Am. J. Obstet. Gynecol. 75: 1149 (1958). 13. PATRICK, C. E., NORTON, J. H., and DACSO, M. in the kidney: a case report, J. R.: Choriocarcinoma Ural. 97: 444 (1967). 14. KITTREDGE, R. D.: Choriocarcinoma: aspects of the clinical pathology, Am. J. Roentgenol. Radium. Ther. Nucl. Med. 117: 637 (1973).
661