29, 234-239 (1988)
Malignant Pericardial Effusion in Endometrial Adenocarcinoma YOSHINOBU HAYASHI, M.D.,’ TSUYOSHI IWASAKA, M,D., TOHRU HACHISUGA, M.D., TADAO KISHIKAWA, M.D., NORIBUMI IKEDA, AND HAJIME SUGIMORI, M.D. Department
of Obstetrics and Gynecology,
Saga Medical Saga 840-01, Japan
Received May 6, 1987 A case of endometrial adenocarcinoma in a 62-year-old woman with malignant pericardial effusion is presented. The patient underwent a total abdominal hysterectomy, bilateral salpingo-oophorectomy, pelvic node dissection, and paraaortic node biopsy. Postoperatively, she was placed on a combination chemotherapy regimen of cisplatin, doxorubicin, and cyclophosphamide. The patient developed cardiac tamponade during the course of chemotherapy. Although we first suspected cardiotoxic effect of doxorubicin, cytologic examination revealed adenocarcinoma cells in the pericardial fluid. A review of the literature revealed no other cases of cardiac metastasis from endometrial carcinoma diagnosed during life. 0 1988 Academic
Metastatic tumors of the heart are unusual. However, the incidence of all categories of metastatic cancer to the heart is increasing as antineoplastic treatment results in longer survival [l]. The primary cancers that most often spread to the heart are pulmonary and mammary carcinomas, lymphoma and leukemia, and malignant melanoma [2-81. Genital malignancies comprise an extremely small percentage of all secondary tumors of the heart [9-l 11. Particularly, so far as can be ascertained, there is no literature concerning cardiac metastasis from endometrial carcinoma diagnosed during life. The present paper describes a case of cardiac metastasis from endometrial adenocarconoma presenting cardiac tamponade. CASE REPORT
A 62-year-old woman, gravida 0, para 0, presented in June 1984 with lower abdominal discomfort. Pelvic examination revealed an enlarged, mobile uterus and bilateral adnexal masses. Endometrial biopsy revealed a serous papillary adenocarcinoma. Additional laboratory work-up was within normal limits and a ’ To whom reprint requests should be addressed. 234 0090-8258/88$150 Copyright All rights
0 1988 by Academic Press, Inc. of reproduction in any form reserved.
FIG. I. Section of serous papillary adenocarcinoma of the endometrium. Cells with prominent nucleoli cover librovascular stalks (hematoxylin and eosin. x 144).
chest X ray was negative for metastatic disease. She had FIG0 stage Ib endometrial carcinoma. The patient underwent a total abdominal hysterectomy, bilateral salpingo-oophorectomy, pelvic node dissection, and paraaortic node biopsy. Histologic examination of the surgical specimens demonstrated a serous papillary adenocarcinoma of the endometrium (Fig. I) with bilateral ovarian involvement and metastases to the pelvic and paraaortic nodes. She was considered to be surgical stage III. Postoperatively, the patient was placed on a combination chemotherapy regimen of cisplatin (40-50 mg/m’), doxorubicin (50 mg/m’), and cyclophosphamide (400-500 mg/m’). She was treated with 10 courses given at 4- to 6-week intervals until May 1985. At a second-look operation performed in July, neither ascites nor recurrent lesion was present in pelvic cavity. However, carcinoma dissemination was observed at the peritoneal surface of the diaphragm. Paraaortic nodes were also positive for metastasis. In order to avoid cardiotoxicity of doxorubicin which had been administered up to the maximum dose (500 mg/m’), the combination of chemotherapy was changed to that of cisplatin, methotrexate, 5-fluorouracil, and cyclophosphamide. An additional 2 courses were given in August and September. On October 23, a chest X ray revealed an enlarged cardiac shilhouette (Fig. 2). Electrocardiogram showed sinus tachycardia and low-voltage QRS complexes consistent with the findings of a pericardial effusion. Echocardiogram confirmed the presence of a large pericardial effusion. Ultrasonic scanning showed no ascites
HAYASHI ET AL.
FIG. 2. A chest X ray showing an enlarged cardiac shilhouette.
in the peritoneal cavity. Pericardiocenteses were performed seven times from November 5 to December 24, and a total of 1720 ml of pericardial fluid was removed. Adenocarcinoma cells were cytologically demonstrated in the pericardial effusion (Fig. 3). Cisplatin was instilled into the pericardial space on November 21 and 28. In addition, pleural effusion was first found on December 10 and thoracenteses were performed six times from December 12 to January 17, 1986. A total of 5470 ml of pleural fluid was removed. Adenocarcinoma cells were also found in the pleural effusion. Her general condition deteriorated gradually, and she died on January 18, 1986. DISCUSSION
Metastatic tumors of the heart are unusual, but more prevalent than primary cardiac tumors. The incidence of cardiac metastasis varies from 1.6 to 10% in autopsies of cancer patients [ 12,131.Carcinoma of the lung and breast, lymphoma and leukemia, and malignant melanoma are the primary neoplastic diseases that most often spread to the heart [2-81. Genital malignancies comprise an extremely small percentage of all secondary tumors of the heart. Autopsy data of patients
cells in clusters of three-dimensioned conFIG. 3. Smear of pericardial fluid. Adenocarcinoma figuration show hyperchromatic nuclei, finely-vacuolated cytoplasm, cytoplasmic vacuolation. and prominent nucleoli. Coarsely granular chromatin was irregularly distributed (Papanicolaou stain. x 280).
dying from cancer of the uterine cervix placed the incidence of cardiac metastases between 0.3 and 3.2% [9-l I], and probably even less common are cardiac metastases from endometrial carcinoma. Furthermore, manifestation of cardiac impairment during life is uncommon. Prolongation of the survival period following surgical excision and chemotherapy may be a crucial factor of unusual metastasis in this case. When papillary adenocarcinoma involves both endometrium and ovary, there are three possibilities: (i) a primary endometrial carcinoma metastatic to the ovary, (ii) a primary ovarian carcinoma metastatic to the endometrium, and (iii) endometrial and ovarian synchronous primary carcinomas. The patient was considered to be a primary endometrial carcinoma metastatic to the ovary, since the existence of transitional pattern from premalignant to malignant endometrial glands, the distinct tendency to invade the myometrium and to fill extensively the myometrial lymphatics, and the widespread involvement of the utrine cervix are the common manifestations of primary endometrial papillary adenocarcinoma 1141.
Metastatic tumors of the heart may involve the pericardium, myocardium, and endocardium via local extension, lymphatic spread, and/or hematogenous invasion. Lympatic circulation of the heart consists of an extensive subendocardial plexus which drains through the myocardial channels into the subepicardial plexus and then into the cardiac node and mediastinal system. In addition, the subepicardial
plexus interconnects with the lymphatic plexus of the aortic adventitia . It is therefore possible that retrograde lymphatic spread may be the mechanism of dissemination in this case, because paraaortic nodes in this patient were positive for metastasis at laparotomy. Alternatively, carcinoma might metastasize to the heart via direct extension through the diaphragma. Because a patient with cancer may develop a pericardial effusion for many different reasons, determination of the specific cause of an effusion is very important. When we found cardiac tamponade in this patient, we first suspected a cardiotoxic effect of doxorubicin. However, the cytologic examination of the pericardial fluid provided an immediate and accurate diagnosis. In such a case, pericardial fluid cytology is a very useful diagnostic procedure in determination of the mode of therapy and estimation of the prognosis. In patients with a limited life expectancy, the treatment of malignant pericardial effusion consists of pericardiocentesis with or without instillation of antineoplastic agents, tetracycline, or radioactive chromic phosphate. These treatments may control the effusion for short period of time [ 15,161.In patients with a reasonable life expectancy, the treatment may consist of creating a pericardial window which affords immediate and long-lasting relief. Hankins ef al. reported on a patient surviving more than 21 months after this treatment [ 171.Therefore, it is important that the clinician should keep in mind that the incidence of secondary tumors of the heart is increasing and that the patient can be relieved for significant periods of time if appropriate treatment is performed. REFERENCES 1. Lockwood, W. B., and Broghamer, W. L. The changing prevalence of secondary cardiac neoplasms as related to cancer therapy, Cancer 4.5, 2659-2662 (1980). 2. Berge, T., and Sievers, J. Myocardial metastasis, a pathological and electrocardiographic study, hit. Heart J. 30, 383-389 (1968). 3. Spindola-France, H, Bjork, L., and Berger, M. Intracavitary metastasis to the left ventricle: An angiocardiographic diagnosis, Bit. J. Radio/. 48, 649-651 (1975). 4. Fraser, R. S., Viloria, J. B., and Wang, N. S. Cardiac tamponade as a presentation of extracardiac malignancy, Cancer 4.5, 1697-1704 (1980). 5. Yazdi, H. M., Hajdu, S. I., and Melamed, M. R. Cytopathology of pericardial effusions, Acta Cytol. 24, 401-412 (1980).
6. Reyes, C. V., Strinden, C., and Banerji, M. The role of cytology in neoplastic cardiac tamponade, Acta Cytol. 26, 299-302 (1982).
7. McKenna, R. J., Ah, M. K., Ewer, M. S., and Frazier, 0. H. Pleural and pericardial effusions in cancer patients, Curr. Probi. Cancer 9, 1-44, (1985). 8. Pinto, M. M. Malignant pericardial effusion and cardiac tamponade, Acta Cytol. 30, 657-661 (1986). 9. Badib, A. O., Kurohara, S. S., Webster, J. H., and Pickren, J. W. Metastasis to organs in carcinoma of the uterine cervix, Cancer 21, 434-439 (1968). 10. Peeples, W. J., Amar, 1. C. H., Hazra, T. A., and Graft, D. The occurrence of metastasis outside the abdomen and retroperitoneal space in invasive carcinoma of the cervix, Gynecol. Oncol. 4, 307-310 (1976). 11. Ritcher, N., and Yon, J. L. Squamous cell carcinoma of the cervix metastatic to the heart, Gynecol.
Oncol. 7, 394-400 (1979).
12. Hanfling, S. M. Metastatic cancer to the heart: Review of the literature and report of 127 cases, Circulation 22, 474-483 (1960).
CASE REPORTS 13. Dibadj, A. Intracavitary
cardiac tumor secondary
to sqaumous cell carcinoma
.I. Clin. Pathol. 48, 58-61 (1967). 14. Hendrickson, M. R.. and Kempson, R. L. Endometrial carcinoma. in Surgical pathology of the uterine corpus, Saunders, Philadelphia, pp. 333-387 (1980). 15. Kefford, R. F., Woods, R. L.. Fox. R. M., and Tattersal, M. H. N. Intracavitary adriamycin nitrogen mustard and tetracycline in the control of malignant effusions. Mrid. J. A~sr. 2, 447448 (1980). 16. Martini, N., Freimann, A. H.. Watson, R. C.. and Hilaris, B. S. Intrapericardial instillation of radioactive chromic phospate in malignant pericardial effusion. Awwr-. J. Roentged. 128, 639-641 (1977). 17. Hankins. J. R., Satterfield. J. R.. Aisner. J., Wiernik. P. H. and McLaughlin, J. S. Pericardial window for malignant pericardial effusion. Ann. Thorrrcic~Surg. 30, 465-471 (1980).