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Carcinosarcoma of the uterus
Carcinosarcoma of the Uterus J A REVIEW OF THE LITERATURE AND REPORT OF FOUR NEW CASES HERMANCBARACHE, M.D.,Brooklyn, New York From tbe Tumor Service, Jewisb Chronic Disease Hospital, New York, New York.
and mesodermal tissue (striated muscle, osteoid tissue, cartilage and fat) ; composition tumors, in which a sarcomatous change has taken place in the stroma of a carcinoma, or the reverse; and collision tumors, a coalescence of separate and independent carcinoma and sarcoma. Almost all of the patients reported on in the literature had passed the menopause and were over fifty years of age before the development of symptoms. A great number of them were between fifty-five and sixty-five years old. Sternberg et al. reported three such tumors in children. The youngest was one year oId. Seventeen of their twenty-one patients were Negroes, including the three children. (The ratio of Negro to white patients admitted to the gynecological service at Charity Hospital was approximateIy 2 : I.) A number of the patients had received intrauterine radium for functional vaginal bleeding or some benign condition, usuahy ten or more years before the diagnosis of carcinosarcoma was made. In fact, some doctors still use intrauterine radium for vaginal bleeding as a routine, with and without diagnostic curettage, before the maIignancy has been histologically proven. Some authors find a causal relationship between the development of carcinosarcoma and the previous intrauterine radiation for a non-malignant condition. According to Hi11and Miller [7], “ If there is a direct relationship, as suggested by the high percentage of these patients having received irradiation, the frequency of carcinosarcoma may be expected to show an increase in the next several years as a result of the widespread use of radiotherapy during the rg3o’s for presumed functiona uterine bIeeding.” Ten cases of carcinosarcoma of the uterus were associated with uterine fibroids. Carpas and Speer [S]reported a case of carcinosarcoma of the endometrium in a patient who had received estrogen therapy for eleven years.
ARCINOSARCOMA of the uterus is a rare containing both carcinomatous and sarcomatous elements. (Figs. 2 and 3.) Not only does the medical profession generally lack knowledge of such tumors, but also some have doubted their existence. The exact number of cases reported has never been definitely determined. Many of the cases have not been reported, and the authenticity of some that have been reported has been questioned. According to Piquand [I], one in every 7,500 malignant tumors of the body of the uterus is a mixed tumor. Sternberg et al. [2] found twenty-one cases of carcinosarcoma among 26,I 14 patients with gynecologic problems admitted to the Charity Hospital of Louisiana during a period of six years, a frequency of 0.08 per cent. In a comprehensive review of the literature, Hoffstatter [3] (rgg3) found more than sixty “certain cases” of carcinosarcoma of the uterus. However, Symmonds and Dockerty [4], as recently as 1955, recorded seven cases from the literature and reported nine from the Mayo Clinic. They made the following statement, “No longer is it justifiable to question the existence of malignant uterine tumors containing tissues with the characteristics of both carcinoma and sarcoma.” The last report of sixteen additiona “proven” cases of carcinosarcoma of the uterus was made by Wolfe and Pedowitz [5] in rg58. In order to stimulate further the study and understanding of the subject of carcinosarcoma of the uterus, the literature is briefly summarized, and four new authentic cases are reported from the Jewish Chronic Disease Hospital. Meyer [6l cIassilied carcinosarcoma of the uterus as combination tumors, true teratomas with mahgnant transformation of both epithelial
C malignant tumor of the endometrium
American
Journal
01 Surgery,
Volume IOO, October 1960
522
Carcinosarcoma The symptoms and signs of carcinosarcoma of the uterus, as summarized from the literature, are characterized by irreguIar vagina1 bIeeding preceded by vaginal discharge, either purulent or otherwise. The bleeding may become so profuse that the patient requires blood transfusions. The source of the bleeding is muItiple polypoid masses attached to the anterior or posterior waI1 of the endometrium, protruding in many instances from the externa1 OSof the cervix into the vagina, or protruding outside of the vagina. (Fig. I.) Of thirty-six cases of uterine carcinosarcoma collected from the Iiterature by Saphir and Vas [9], nineteen had pedunculated tumors projecting either from the endometrium into the uterine cavity or from the cervix into the vagina. They consist of fragile, necrotic tissue which bleeds profuseIy at the Ieast manipuIation. The cervix may be equaIIy fragiIe and necrotic. Liza et al. [ ro] reported a case of carcinosarcoma of the uterus in which the cervix was so friable that it tore loose from the uterusduring hysterectomy. Before Iong the peIvis becomes fiIIed to the brim with muItipIe tumor masses which extend above the symphysis pubis. Pressure symptoms of pain, urinary and recta1 disturbances, and edema of the Iower extremities may ensue. EventuaIIy the whoIe abdomen is fiIIed with multipIe tumor masses and ascitic ffuid. A nodular liver may be paIpated severa fingers beIow the Costa1 margin. Metastasis, usuaIIy hematogenous, is either a pure carcinoma or pure sarcoma. OnIy four cases of combined metastasis are reported in the Iiterature. Local recurrence and regiona metastasis, infiltrating the bIadder, parametrium, vagina and perineum are frequent. (Case I, Fig. I.) Metastasis to Iymph nodes is infrequent. However, metastasis to the peritoneum, mesentery, Iiver, Iungs and pIeura is not uncommon. PIeuraI and pulmonary metastasis is usually associated with pIeura1 effusion. SkeIetaI and brain invoIvement are extremeIy rare. Dixon and Dockerty [II] reported a case of widespread skeIeta1 metastasis in which a tumor mass in the thoracic spine, compressing the spina cord, resuIted in transverse myeIitis. One of our patients (Case II) had metastasis to the brain. The treatment of choice for carcinosarcoma of the uterus is earIy tota hysterectomy and biIateraI saIpingo-oophorectomy. The tumor is radioresistant. However, one wouId hesitate to deprive a patient with carcinosarcoma of postoperative radiotherapy when the metastasis
of Uterus might be a pure carcinoma, since the Iatter is radiosensitive. According to Hi11 and MiIIer [7] “therapy is restricted to radica1 hysterectomy, since no cases have shown any significant response even to heavy irradiation.” UnfortunateIy, the disease is resistant to any form of treatment. The prognosis is so poor that the average surviva1 is from six to tweIve months after the diagnosis is estabIished. Hi11 and Miller and others report that there is no five-year surviva1; however, exceptions in the surviva1 rate may be found in any maIignancy, no matter how fatal, depending on the host resistance or immune reaction to cancer [r2]. Chesky et al. [I?] reported a case of nine years’ surviva1 and cited another by Camporo that survived four and a haIf years. Boschann [r4] reported a case of ten years’ surviva1 in 1954. CASE REPORTS CASE I. I. D., a fifty-eight year oId Negro woman, was admitted to the Jewish Chronic Disease HospitaI on August 14, 1958, with a diagnosis of carcinosarcoma of the uterus with general abdomina1 and pulmonary metastasis. The diagnosis was based on muItipIe biopsy specimens taken from the uterine fundus, cervix and vagina at the New York HospitaI. The slides were examined by Dr. F. W. Stewart and Dr. F. W. Foote of MemoriaI HospitaI, New York City. The patient first menstruated at the age of thirteen. Periods were aIways regular with a cycle of twenty-eight days and Iasted four days. She was Para VIII, gravida IX. Her menopause occurred at the age of forty. About six months previous to admission she had a sudden gush of dark red bIood from the vagina. She was treated by a Iocal physician with “injections“ and a vagina1 examination had not been performed. The bIeeding subsided in three to four days. She then received another series of “injections to kill her appetite” and was placed on a very strict diet. In a very short time the patient Iost 40 pounds. When suprapubic pain and urinary disturbance developed, the patient was brought to the hospita1 for admission. After a complete study, she was transferred to our institution for supportive treatment. PhysicaI findings on admission reveaIed that the peIvis was fiIIed by a Iarge, firm, fixed mass extending to about two fingers beIow the umbilicus. A fungating, bIeeding necrotic mass protruded from the cervix and vagina. The vagina1 waI1 was indurated and nodular. The fundus was fixed and “frozen ” within the peIvis. Her hemogIobin was 5.7 gm. per cent. Roentgenograms of the chest
523
Charache
FIG. 2. Case II. Photomicrograph showing carcinomatous and sarcomatous elements in carcinosarcoma of the endometrium. OriginaI magnification X 250.
FIG. I. Case I. Carcinosarcoma of the uterus with protrusion of poIypoid mass from the cervix outside of the
ease Hospital on January 25, 1957, with a diagnosis of carcinosarcoma of the uterus. The diagnosis was confirmed at our institution. In November 1955 she had a yeIIowish, fou1 vagina1 discharge. By February 1956 the discharge had become sanguineous, and she had Iower abdominal pain with distention. She was admitted to a hospita1 on JuIy 24, 1956, where a diagnostic curettage reveaIed the presence of carcinosarcoma of the uterus of the mixed mesenchyma1 type. She received 6,000 mg. hours of intrauterine radium, foIlowed by a total hysterectomy and biIatera1 salpingo-oophorectomy on August I, 1956. The pathological report was carcinosarcoma, mixed mesenchyma1 type, with necrosis of the endometrium and endocervica1 mucosa, and metastasis to the ovaries and omentum. (Fig. 2.) She did we11 until the middle of December when diplopia, aphasia, disturbed speech, convuIsive seizures and vomiting occurred. She became bedridden and Iost the use of her limbs. She was then transferred to our institution. Her abdomen was enIarged, with paIpabIe intraabdomina1 tumors and fluid. The Iiver extended to two fingers beIow the Costa1 margin. Roentgenogram reveaIed right pleura1 effusion and Ieft pulmonary metastasis. Pneumoencephalogram and eIectroencephaIogram were interpreted as showing signs of metastasis to the brain. A skeIeta1 survey faiIed to revea1 metastasis to the bone. She received a course of radiation, bIood transfusions, and other supportive measures, but became progressiveIy worse and died on June 24, 1957. nineteen months after the onset of symptoms. Consent for autopsy couId not be obtained.
vagina, and metastatic invoIvement of the vagina and perineum is shown. reveaIed puImonary metastasis. SkeletaI survey was pathoIogicaIIy negative. The patient was given bIood transfusions foIIowed by x-ray therapy and radium was inserted into the vagina. Vaginal bIeeding stopped. She was discharged as improved, after a fifty-five-day stay in the hospita1. She was readmitted a month Iater with recurring vagina1 bIeeding. At this time the vagina1 mass had increased greatly and invoIved the bladder, urethra and perineum. (Fig. I .) Intravenous pyeIogram showed a non-functioning Ieft kidney, hydronephrosis and hydroureter on the right side. Both Iungs were invoIved with metastasis. She was given severa bIood transfusions and another course of x-ray therapy to arrest the bIeeding. On the twentyfifth day of her second admission a high, spiking temperature deveIoped. Her respirations became Iabored and she died of bronchopneumonia the next day (November 19, Ig58), nine months after the onset of symptoms. Summary of the findings at autopsy: Gross and microscopic examination showed primary anaplastic carcinosarcoma of the uterus with metastasis to the Iungs, mediastinum, pleura, peritoneum, diaphragm, smaI1 and Iarge intestines, omentum, mesentery, peIvis, vagina, vuIva, Iymph nodes, Ieft adrena and gaIIbIadder. Examination of both kidneys reveaIed acute suppurative pyelonephritis, biIatera1 pyonephrosis and pyoureters. The examination of the Iungs showed bronchopneumonia. The other findings were fatty metamorphosis, ChoIeIithiasis, chronic ChoIecystitis, fibrosis of the myocardium and toxic spIenitis.
CASE III. I. Y., a sixty-four year oId Jewish woman, was admitted to the Jewish Chronic Disease HospitaI on November I, 1956, with a diagnosis of carcinosarcoma of the uterus. The diagnosis was confirmed at our institution.
CASE II. F. L., a sixty-nine year oId Jewish woman, was admitted to the Jewish Chronic Dis-
524
Carcinosarcoma The woman was Para v, gravida VII. Her menstrua1 history was uneventfu1 until she was forty-nine years of age when excessive vaginal bleeding developed, for which she had a dilatation and curettage and insertion of radium. The bIeeding subsided for fifteen years until her first admission to a hospital on August zg, 1956, for postmenopausal bleeding, abdominal pain and distention. A diagnostic diIatation and curettage and Iaparotomy revealed a malignant tumor of the uterus with a “frozen” pelvis and a partia1 intestinal obstruction. A segment of the smaI1 intestine had to be resected and a transverse coIostomy performed. The uterine curettings proved to be carcinosarcoma. (Fig. 3.) The patient was subsequently transferred to our institution after receiving 5,000 mg. hours of intrauterine radium. Examination reveaIed an undernourished, pale woman. She complained of abdominal pain. The abdomen was enIarged, with a large, firm mass extending from the pelvis toward the umbiIicus. This was further confirmed by vagina1 and rectal examination. The cervix was smaI1 and friabIe. The liver and spIeen were not enlarged. Both Iower extremities were markedIy edematous. A skeIeta1 survey revealed no evidence of metastasis to the bones. Roentgenograms of the chest were negative for metastasis, A gastrointestina1 series showed fixation of loops of intestine to the pelvic mass and angulation of jejuna1 Ioops by external pressure of abdominal masses. Intra-abdominal fluid was visuaIized. The intravenous pyeIogram was reported to be negative for metastasis. The patient received bIood transfusions, radiotherapy to the peIvis and other supportive treatment. She died on July 8, 1957, eIeven months after the onset of symptoms. Consent for autopsy couId not be obtained.
of Uterus
FIG. 3. Case III. Photomicrograph showing carcinomatous and sarcomatous elements in carcinosarcoma of the endometrium. OriginaI magnification X 250. admitted to a hospita1 and tota abdominal hysterectomy with biIatera1 saIpingo-oophorectomy was performed. The pathoIogica1 diagnosis was carcinosarcoma. Six weeks Iater she had a sanguineous, fou1 vagina1 discharge, foIIowed by intermittent vaginal bleeding. Recurrence of the malignancy was found in the vagina1 vauIt. On June I 2,Ig58, she was admitted to a municipa1 hospita1 where she received fifty x-ray treatments foIIowed by an expIoratory Iaparotomy which reveaIed abdomina1 metastasis and aIso metastasis to the urinary bIadder. A partia1 exenteration of the bladder was performed and an ilea bIadder created. The patient was subsequentIy transferred to our institution. Examination of the patient at the Jewish Chronic Disease HospitaI reveaIed a chronicaIIy III, emaciated, anemic woman. Her abdomen was distended with fluid, and multipIe tumor masses couId be paIpated throughout the abdomen. The Iiver was enIarged to about four fingers below the Costa1 margin. The vagina, which was fiIIed with bIood and necrotic tissue, admitted onIy one finger and bIed at the Ieast manipuIation. The Iower extremities were edematous. A gastrointestina1 series showed multiple intra-abdomina1 tumors dispIacing the stomach and intestines. A roentgenogram of the chest reveaIed puImonary metastasis with pLeuraI effusion. PyeIogram showed bilatera1 hydronephrosis. The skeIeta1 survey was negative for metastasis. The patient was given supportive treatment consisting of btood transfusions, intravenous ffuid, high caIoric and high vitamin diet and sedatives. She died on February 22, 1959, one year after the onset of symptoms. Autopsy consent couId not be obtained.
CASE IV. R. F., a frfty-two year old Jewish woman, was admitted to the Jewish Chronic Disease HospitaI on JuIy 14, 1958, with a postoperative diagnosis of carcinosarcoma of the uterus with genera1 metastasis. Through the courtesy of Dr. SamueI Weiner of St. John’s HospitaI, BrookIyn, New York, the diagnosis of carcinosarcoma (collision tumor) was confirmed by Dr. SamueI A. Wolfe of the State University of New York, Downstate MedicaI Center and Dr. Arthur Hertig of Harvard MedicaI School. The patient had a norma menstrual history. She was married at the age of twenty-four, had two norma1 pregnancies and deliveries and one incomplete abortion. She had an uneventfu1 menopause in 1953. In February 1958 she had her first episode of postmenopausal bIeeding associated with suprapubic pain. Her uterus was enIarged to the level of the umbilicus. BIeeding, necrotic, polypoid-Iike tissue protruded from the cervix. The patient was
SUMMARY
Carcinosarcoma of the uterus is a rare maIignant tumor of the endometrium containing both carcinomatous and sarcomatous eIements. AImost a11 the patients had passed their meno525
Charache pause and their fiftieth birthday. A number of them had received intrauterine radium for functiona vagina1 bIeeding or benign neopIasm ten or more years previousIy. A causa1 reIationship may exist between the deveIopment of carcinosarcoma and previous intrauterine irradiation for a non-maIignant condition. Physica1 findings, treatment and prognosis are discussed brieffy. Four new cases of carcinosarcoma of the uterus are reported from the Jewish Chronic Disease HospitaI.
2. STERNBERG,W. H., CLARK, W. H. and SMITH, R. C. MaIignant mixed MtiIIerian tumor (mixed mesodermaI tumor of the uterus). Cancer, 7: 704. 1954. 3. HOFSTKTTER, R. Carcinoma of the uterus. Wien. med. Wcbnscbr., 103: 649, 1953. 4. SYMMONDS, R. E. and DOCKERTY, M. B. Carcinosarcoma. Surg., Gynec. & Obst., IOO: 322, 1955. 5. WOLFE. S. A. and PEDOWITZ, P. Carcinosarcoma of the uterus: report of sixteen cases. Obst. ti Gynec., 12: 54, ig58. 6. MEYER. R. Beitrae zur Verst&ndiauna tiber die Namkngebung invder GeschuIstIehTe. Centralbl. f. allg. Patb. u. patb. Anat., 30: 291, 1920. 7. HILL, R. P. and MILLER, F. N. Carcinosarcoma of the uterus. Cancer, 4: 803, 1951. 8. CARPAS, C. M. and SPEER, F. D. Carcinosarcoma of an unusua1 case receiving the endometrium: estrogen therapy for eIeven years. Arch. Patb., 63: 17. 1957. Am. J. 9. SAPHI& 0. and VAS, A. Carcinosarcoma. CanCer, 33: 331, 1938. IO. LIZA, J. R., HARTMANN, H., BAYER, I. and BONAR, L. D. Carcinosarcoma of the uterus. Ann. Surg., 127: 338, 1948. II. DIXON, C. F. and DOCKERTY, M. B. Carcinosarcoma of the uterus. Am. J. Obst. &+Gynec., 39: 128, 1940. 12. CHARACHE, H. Longevity in cancer. Am. J. Surg., 88: 521, 1954. 13. CHESKY, V. E., DREESSE, W. C. and HELLWIG, C. A. Uterine mixed tumor of nine gears’ duration. Am. J. Surg., 84: 721, 1952. 14. BOSCHANN, H. W. Karzinosarkom des Uterus mit zehnjahrigen VerIauf. Geburtsb. u. Frauenb., 14:
CONCLUSION
Carcinosarcoma shouId be considered in postmenopausa1 bIeeding, especiaIIy when there is a protrusion of poIypoid tissue from the cervix or vagina. Radiation therapy shouId be restricted to maIignant conditions of the uterus when indicated. EarIy tota hysterectomy and biIatera1 salpingo-oophorectomy is the treatment of choice in operabIe cases of carcinosarcoma of the uterus. It is hoped that this paper wiI1 further stimuIate the study of carcinosarcoma of the uterus and thus improve the prognosis. REFERENCES I. PIQUAND, cited by CHESKY, V. C., DRESSE, W. C.
and HELLWIG, C. A. Uterine mixed tumors of nine years’ duration. Am. J. Surg.. 84: 721, 1952.
846
526
1954.
and mesodermal tissue (striated muscle, osteoid tissue, cartilage and fat) ; composition tumors, in which a sarcomatous change has taken place in the stroma of a carcinoma, or the reverse; and collision tumors, a coalescence of separate and independent carcinoma and sarcoma. Almost all of the patients reported on in the literature had passed the menopause and were over fifty years of age before the development of symptoms. A great number of them were between fifty-five and sixty-five years old. Sternberg et al. reported three such tumors in children. The youngest was one year oId. Seventeen of their twenty-one patients were Negroes, including the three children. (The ratio of Negro to white patients admitted to the gynecological service at Charity Hospital was approximateIy 2 : I.) A number of the patients had received intrauterine radium for functional vaginal bleeding or some benign condition, usuahy ten or more years before the diagnosis of carcinosarcoma was made. In fact, some doctors still use intrauterine radium for vaginal bleeding as a routine, with and without diagnostic curettage, before the maIignancy has been histologically proven. Some authors find a causal relationship between the development of carcinosarcoma and the previous intrauterine radiation for a non-malignant condition. According to Hi11and Miller [7], “ If there is a direct relationship, as suggested by the high percentage of these patients having received irradiation, the frequency of carcinosarcoma may be expected to show an increase in the next several years as a result of the widespread use of radiotherapy during the rg3o’s for presumed functiona uterine bIeeding.” Ten cases of carcinosarcoma of the uterus were associated with uterine fibroids. Carpas and Speer [S]reported a case of carcinosarcoma of the endometrium in a patient who had received estrogen therapy for eleven years.
ARCINOSARCOMA of the uterus is a rare containing both carcinomatous and sarcomatous elements. (Figs. 2 and 3.) Not only does the medical profession generally lack knowledge of such tumors, but also some have doubted their existence. The exact number of cases reported has never been definitely determined. Many of the cases have not been reported, and the authenticity of some that have been reported has been questioned. According to Piquand [I], one in every 7,500 malignant tumors of the body of the uterus is a mixed tumor. Sternberg et al. [2] found twenty-one cases of carcinosarcoma among 26,I 14 patients with gynecologic problems admitted to the Charity Hospital of Louisiana during a period of six years, a frequency of 0.08 per cent. In a comprehensive review of the literature, Hoffstatter [3] (rgg3) found more than sixty “certain cases” of carcinosarcoma of the uterus. However, Symmonds and Dockerty [4], as recently as 1955, recorded seven cases from the literature and reported nine from the Mayo Clinic. They made the following statement, “No longer is it justifiable to question the existence of malignant uterine tumors containing tissues with the characteristics of both carcinoma and sarcoma.” The last report of sixteen additiona “proven” cases of carcinosarcoma of the uterus was made by Wolfe and Pedowitz [5] in rg58. In order to stimulate further the study and understanding of the subject of carcinosarcoma of the uterus, the literature is briefly summarized, and four new authentic cases are reported from the Jewish Chronic Disease Hospital. Meyer [6l cIassilied carcinosarcoma of the uterus as combination tumors, true teratomas with mahgnant transformation of both epithelial
C malignant tumor of the endometrium
American
Journal
01 Surgery,
Volume IOO, October 1960
522
Carcinosarcoma The symptoms and signs of carcinosarcoma of the uterus, as summarized from the literature, are characterized by irreguIar vagina1 bIeeding preceded by vaginal discharge, either purulent or otherwise. The bleeding may become so profuse that the patient requires blood transfusions. The source of the bleeding is muItiple polypoid masses attached to the anterior or posterior waI1 of the endometrium, protruding in many instances from the externa1 OSof the cervix into the vagina, or protruding outside of the vagina. (Fig. I.) Of thirty-six cases of uterine carcinosarcoma collected from the Iiterature by Saphir and Vas [9], nineteen had pedunculated tumors projecting either from the endometrium into the uterine cavity or from the cervix into the vagina. They consist of fragile, necrotic tissue which bleeds profuseIy at the Ieast manipuIation. The cervix may be equaIIy fragiIe and necrotic. Liza et al. [ ro] reported a case of carcinosarcoma of the uterus in which the cervix was so friable that it tore loose from the uterusduring hysterectomy. Before Iong the peIvis becomes fiIIed to the brim with muItipIe tumor masses which extend above the symphysis pubis. Pressure symptoms of pain, urinary and recta1 disturbances, and edema of the Iower extremities may ensue. EventuaIIy the whoIe abdomen is fiIIed with multipIe tumor masses and ascitic ffuid. A nodular liver may be paIpated severa fingers beIow the Costa1 margin. Metastasis, usuaIIy hematogenous, is either a pure carcinoma or pure sarcoma. OnIy four cases of combined metastasis are reported in the Iiterature. Local recurrence and regiona metastasis, infiltrating the bIadder, parametrium, vagina and perineum are frequent. (Case I, Fig. I.) Metastasis to Iymph nodes is infrequent. However, metastasis to the peritoneum, mesentery, Iiver, Iungs and pIeura is not uncommon. PIeuraI and pulmonary metastasis is usually associated with pIeura1 effusion. SkeIetaI and brain invoIvement are extremeIy rare. Dixon and Dockerty [II] reported a case of widespread skeIeta1 metastasis in which a tumor mass in the thoracic spine, compressing the spina cord, resuIted in transverse myeIitis. One of our patients (Case II) had metastasis to the brain. The treatment of choice for carcinosarcoma of the uterus is earIy tota hysterectomy and biIateraI saIpingo-oophorectomy. The tumor is radioresistant. However, one wouId hesitate to deprive a patient with carcinosarcoma of postoperative radiotherapy when the metastasis
of Uterus might be a pure carcinoma, since the Iatter is radiosensitive. According to Hi11 and MiIIer [7] “therapy is restricted to radica1 hysterectomy, since no cases have shown any significant response even to heavy irradiation.” UnfortunateIy, the disease is resistant to any form of treatment. The prognosis is so poor that the average surviva1 is from six to tweIve months after the diagnosis is estabIished. Hi11 and Miller and others report that there is no five-year surviva1; however, exceptions in the surviva1 rate may be found in any maIignancy, no matter how fatal, depending on the host resistance or immune reaction to cancer [r2]. Chesky et al. [I?] reported a case of nine years’ surviva1 and cited another by Camporo that survived four and a haIf years. Boschann [r4] reported a case of ten years’ surviva1 in 1954. CASE REPORTS CASE I. I. D., a fifty-eight year oId Negro woman, was admitted to the Jewish Chronic Disease HospitaI on August 14, 1958, with a diagnosis of carcinosarcoma of the uterus with general abdomina1 and pulmonary metastasis. The diagnosis was based on muItipIe biopsy specimens taken from the uterine fundus, cervix and vagina at the New York HospitaI. The slides were examined by Dr. F. W. Stewart and Dr. F. W. Foote of MemoriaI HospitaI, New York City. The patient first menstruated at the age of thirteen. Periods were aIways regular with a cycle of twenty-eight days and Iasted four days. She was Para VIII, gravida IX. Her menopause occurred at the age of forty. About six months previous to admission she had a sudden gush of dark red bIood from the vagina. She was treated by a Iocal physician with “injections“ and a vagina1 examination had not been performed. The bIeeding subsided in three to four days. She then received another series of “injections to kill her appetite” and was placed on a very strict diet. In a very short time the patient Iost 40 pounds. When suprapubic pain and urinary disturbance developed, the patient was brought to the hospita1 for admission. After a complete study, she was transferred to our institution for supportive treatment. PhysicaI findings on admission reveaIed that the peIvis was fiIIed by a Iarge, firm, fixed mass extending to about two fingers beIow the umbilicus. A fungating, bIeeding necrotic mass protruded from the cervix and vagina. The vagina1 waI1 was indurated and nodular. The fundus was fixed and “frozen ” within the peIvis. Her hemogIobin was 5.7 gm. per cent. Roentgenograms of the chest
523
Charache
FIG. 2. Case II. Photomicrograph showing carcinomatous and sarcomatous elements in carcinosarcoma of the endometrium. OriginaI magnification X 250.
FIG. I. Case I. Carcinosarcoma of the uterus with protrusion of poIypoid mass from the cervix outside of the
ease Hospital on January 25, 1957, with a diagnosis of carcinosarcoma of the uterus. The diagnosis was confirmed at our institution. In November 1955 she had a yeIIowish, fou1 vagina1 discharge. By February 1956 the discharge had become sanguineous, and she had Iower abdominal pain with distention. She was admitted to a hospita1 on JuIy 24, 1956, where a diagnostic curettage reveaIed the presence of carcinosarcoma of the uterus of the mixed mesenchyma1 type. She received 6,000 mg. hours of intrauterine radium, foIlowed by a total hysterectomy and biIatera1 salpingo-oophorectomy on August I, 1956. The pathological report was carcinosarcoma, mixed mesenchyma1 type, with necrosis of the endometrium and endocervica1 mucosa, and metastasis to the ovaries and omentum. (Fig. 2.) She did we11 until the middle of December when diplopia, aphasia, disturbed speech, convuIsive seizures and vomiting occurred. She became bedridden and Iost the use of her limbs. She was then transferred to our institution. Her abdomen was enIarged, with paIpabIe intraabdomina1 tumors and fluid. The Iiver extended to two fingers beIow the Costa1 margin. Roentgenogram reveaIed right pleura1 effusion and Ieft pulmonary metastasis. Pneumoencephalogram and eIectroencephaIogram were interpreted as showing signs of metastasis to the brain. A skeIeta1 survey faiIed to revea1 metastasis to the bone. She received a course of radiation, bIood transfusions, and other supportive measures, but became progressiveIy worse and died on June 24, 1957. nineteen months after the onset of symptoms. Consent for autopsy couId not be obtained.
vagina, and metastatic invoIvement of the vagina and perineum is shown. reveaIed puImonary metastasis. SkeletaI survey was pathoIogicaIIy negative. The patient was given bIood transfusions foIIowed by x-ray therapy and radium was inserted into the vagina. Vaginal bIeeding stopped. She was discharged as improved, after a fifty-five-day stay in the hospita1. She was readmitted a month Iater with recurring vagina1 bIeeding. At this time the vagina1 mass had increased greatly and invoIved the bladder, urethra and perineum. (Fig. I .) Intravenous pyeIogram showed a non-functioning Ieft kidney, hydronephrosis and hydroureter on the right side. Both Iungs were invoIved with metastasis. She was given severa bIood transfusions and another course of x-ray therapy to arrest the bIeeding. On the twentyfifth day of her second admission a high, spiking temperature deveIoped. Her respirations became Iabored and she died of bronchopneumonia the next day (November 19, Ig58), nine months after the onset of symptoms. Summary of the findings at autopsy: Gross and microscopic examination showed primary anaplastic carcinosarcoma of the uterus with metastasis to the Iungs, mediastinum, pleura, peritoneum, diaphragm, smaI1 and Iarge intestines, omentum, mesentery, peIvis, vagina, vuIva, Iymph nodes, Ieft adrena and gaIIbIadder. Examination of both kidneys reveaIed acute suppurative pyelonephritis, biIatera1 pyonephrosis and pyoureters. The examination of the Iungs showed bronchopneumonia. The other findings were fatty metamorphosis, ChoIeIithiasis, chronic ChoIecystitis, fibrosis of the myocardium and toxic spIenitis.
CASE III. I. Y., a sixty-four year oId Jewish woman, was admitted to the Jewish Chronic Disease HospitaI on November I, 1956, with a diagnosis of carcinosarcoma of the uterus. The diagnosis was confirmed at our institution.
CASE II. F. L., a sixty-nine year oId Jewish woman, was admitted to the Jewish Chronic Dis-
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Carcinosarcoma The woman was Para v, gravida VII. Her menstrua1 history was uneventfu1 until she was forty-nine years of age when excessive vaginal bleeding developed, for which she had a dilatation and curettage and insertion of radium. The bIeeding subsided for fifteen years until her first admission to a hospital on August zg, 1956, for postmenopausal bleeding, abdominal pain and distention. A diagnostic diIatation and curettage and Iaparotomy revealed a malignant tumor of the uterus with a “frozen” pelvis and a partia1 intestinal obstruction. A segment of the smaI1 intestine had to be resected and a transverse coIostomy performed. The uterine curettings proved to be carcinosarcoma. (Fig. 3.) The patient was subsequently transferred to our institution after receiving 5,000 mg. hours of intrauterine radium. Examination reveaIed an undernourished, pale woman. She complained of abdominal pain. The abdomen was enIarged, with a large, firm mass extending from the pelvis toward the umbiIicus. This was further confirmed by vagina1 and rectal examination. The cervix was smaI1 and friabIe. The liver and spIeen were not enlarged. Both Iower extremities were markedIy edematous. A skeIeta1 survey revealed no evidence of metastasis to the bones. Roentgenograms of the chest were negative for metastasis, A gastrointestina1 series showed fixation of loops of intestine to the pelvic mass and angulation of jejuna1 Ioops by external pressure of abdominal masses. Intra-abdominal fluid was visuaIized. The intravenous pyeIogram was reported to be negative for metastasis. The patient received bIood transfusions, radiotherapy to the peIvis and other supportive treatment. She died on July 8, 1957, eIeven months after the onset of symptoms. Consent for autopsy couId not be obtained.
of Uterus
FIG. 3. Case III. Photomicrograph showing carcinomatous and sarcomatous elements in carcinosarcoma of the endometrium. OriginaI magnification X 250. admitted to a hospita1 and tota abdominal hysterectomy with biIatera1 saIpingo-oophorectomy was performed. The pathoIogica1 diagnosis was carcinosarcoma. Six weeks Iater she had a sanguineous, fou1 vagina1 discharge, foIIowed by intermittent vaginal bleeding. Recurrence of the malignancy was found in the vagina1 vauIt. On June I 2,Ig58, she was admitted to a municipa1 hospita1 where she received fifty x-ray treatments foIIowed by an expIoratory Iaparotomy which reveaIed abdomina1 metastasis and aIso metastasis to the urinary bIadder. A partia1 exenteration of the bladder was performed and an ilea bIadder created. The patient was subsequentIy transferred to our institution. Examination of the patient at the Jewish Chronic Disease HospitaI reveaIed a chronicaIIy III, emaciated, anemic woman. Her abdomen was distended with fluid, and multipIe tumor masses couId be paIpated throughout the abdomen. The Iiver was enIarged to about four fingers below the Costa1 margin. The vagina, which was fiIIed with bIood and necrotic tissue, admitted onIy one finger and bIed at the Ieast manipuIation. The Iower extremities were edematous. A gastrointestina1 series showed multiple intra-abdomina1 tumors dispIacing the stomach and intestines. A roentgenogram of the chest reveaIed puImonary metastasis with pLeuraI effusion. PyeIogram showed bilatera1 hydronephrosis. The skeIeta1 survey was negative for metastasis. The patient was given supportive treatment consisting of btood transfusions, intravenous ffuid, high caIoric and high vitamin diet and sedatives. She died on February 22, 1959, one year after the onset of symptoms. Autopsy consent couId not be obtained.
CASE IV. R. F., a frfty-two year old Jewish woman, was admitted to the Jewish Chronic Disease HospitaI on JuIy 14, 1958, with a postoperative diagnosis of carcinosarcoma of the uterus with genera1 metastasis. Through the courtesy of Dr. SamueI Weiner of St. John’s HospitaI, BrookIyn, New York, the diagnosis of carcinosarcoma (collision tumor) was confirmed by Dr. SamueI A. Wolfe of the State University of New York, Downstate MedicaI Center and Dr. Arthur Hertig of Harvard MedicaI School. The patient had a norma menstrual history. She was married at the age of twenty-four, had two norma1 pregnancies and deliveries and one incomplete abortion. She had an uneventfu1 menopause in 1953. In February 1958 she had her first episode of postmenopausal bIeeding associated with suprapubic pain. Her uterus was enIarged to the level of the umbilicus. BIeeding, necrotic, polypoid-Iike tissue protruded from the cervix. The patient was
SUMMARY
Carcinosarcoma of the uterus is a rare maIignant tumor of the endometrium containing both carcinomatous and sarcomatous eIements. AImost a11 the patients had passed their meno525
Charache pause and their fiftieth birthday. A number of them had received intrauterine radium for functiona vagina1 bIeeding or benign neopIasm ten or more years previousIy. A causa1 reIationship may exist between the deveIopment of carcinosarcoma and previous intrauterine irradiation for a non-maIignant condition. Physica1 findings, treatment and prognosis are discussed brieffy. Four new cases of carcinosarcoma of the uterus are reported from the Jewish Chronic Disease HospitaI.
2. STERNBERG,W. H., CLARK, W. H. and SMITH, R. C. MaIignant mixed MtiIIerian tumor (mixed mesodermaI tumor of the uterus). Cancer, 7: 704. 1954. 3. HOFSTKTTER, R. Carcinoma of the uterus. Wien. med. Wcbnscbr., 103: 649, 1953. 4. SYMMONDS, R. E. and DOCKERTY, M. B. Carcinosarcoma. Surg., Gynec. & Obst., IOO: 322, 1955. 5. WOLFE. S. A. and PEDOWITZ, P. Carcinosarcoma of the uterus: report of sixteen cases. Obst. ti Gynec., 12: 54, ig58. 6. MEYER. R. Beitrae zur Verst&ndiauna tiber die Namkngebung invder GeschuIstIehTe. Centralbl. f. allg. Patb. u. patb. Anat., 30: 291, 1920. 7. HILL, R. P. and MILLER, F. N. Carcinosarcoma of the uterus. Cancer, 4: 803, 1951. 8. CARPAS, C. M. and SPEER, F. D. Carcinosarcoma of an unusua1 case receiving the endometrium: estrogen therapy for eIeven years. Arch. Patb., 63: 17. 1957. Am. J. 9. SAPHI& 0. and VAS, A. Carcinosarcoma. CanCer, 33: 331, 1938. IO. LIZA, J. R., HARTMANN, H., BAYER, I. and BONAR, L. D. Carcinosarcoma of the uterus. Ann. Surg., 127: 338, 1948. II. DIXON, C. F. and DOCKERTY, M. B. Carcinosarcoma of the uterus. Am. J. Obst. &+Gynec., 39: 128, 1940. 12. CHARACHE, H. Longevity in cancer. Am. J. Surg., 88: 521, 1954. 13. CHESKY, V. E., DREESSE, W. C. and HELLWIG, C. A. Uterine mixed tumor of nine gears’ duration. Am. J. Surg., 84: 721, 1952. 14. BOSCHANN, H. W. Karzinosarkom des Uterus mit zehnjahrigen VerIauf. Geburtsb. u. Frauenb., 14:
CONCLUSION
Carcinosarcoma shouId be considered in postmenopausa1 bIeeding, especiaIIy when there is a protrusion of poIypoid tissue from the cervix or vagina. Radiation therapy shouId be restricted to maIignant conditions of the uterus when indicated. EarIy tota hysterectomy and biIatera1 salpingo-oophorectomy is the treatment of choice in operabIe cases of carcinosarcoma of the uterus. It is hoped that this paper wiI1 further stimuIate the study of carcinosarcoma of the uterus and thus improve the prognosis. REFERENCES I. PIQUAND, cited by CHESKY, V. C., DRESSE, W. C.
and HELLWIG, C. A. Uterine mixed tumors of nine years’ duration. Am. J. Surg.. 84: 721, 1952.
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1954.