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Extragenital malignant mixed müllerian tumor
GYNECOLOGIC
ONCOLOGY
30,
422-426 (1988)
Extragenital Malignant Mixed Miiilerian Tumor KARL Departments
T. K. CHEN, M.D.*%‘,2AND RICHARD W. WOLK, M.D.t
of *Pathology
and tMedica1
Oncology, Frcsno Community Center, Fresno, California 93715
Hospital
and Medical
Received January 26, 1987 A case of extragenital malignant mixed mtillerian tumor that appeared to represent a second primary tumor in a patient previously treated for disseminated ovarian serous papillary carcinoma is reported and compared with other reported cases of extragenital malignant mixed miillerian tumor. 0 1988 Academic press. Inc.
Malignant mixed mtillerian tumors are observed most commonly in the endometrium, endocervix, vagina, ovaries, and fallopian tubes. Only six cases of malignant mixed mtillerian tumor have been reported to arise in extragenital sites [l-6]. We report a new case of extragenital malignant mixed mtillerian tumor which, unlike the previously reported cases, was preceded by ovarian serous papillary adenocarcinoma. CASE REPORT A 52-year-old, gravida II, para II woman underwent an exploratory laparotomy because of a pelvic mass. An 11 x 10 x 4-cm right ovarian tumor with diffuse intraabdominal tumor dissemination was found. Bilateral salpingo-oophorectomy, omentectomy, and appendectomy were performed. The right ovarian tumor was multicystic. Histologically the ovarian tumor showed features of papillary serous adenocarcinoma (Fig. 1). The omentum contained multiple nodules, up to 2 cm in diameter, of similar tumor tissue. The slightly enlarged left ovary also contained foci of tumor involvement. Postoperatively she received three courses of cyclophosphamide (CTX), doxorubicin (ADM), and diamminedichloroplatinum (CDDP) and six courses of CTX and ADM in a 9-month period. In the subsequent 2 years and 2 months she received 18 courses phenylalanine mustard (L-PAM). She refused a second-look laparotomy but had no clinical evidence of disease. Four years and 1 month after the initial operation, a recurrent pelvic tumor was found. A second laparotomy revealed a 11 x 10 x 3-cm cystic tumor. An incisional biopsy and drainage of tumor cysts were performed. The biopsy showed papillary carcinoma similar to the original ovarian tumor. After the operation ’ To whom reprint requests should be addressed. * Current address: Department of Pathology, Saint Agnes Medical Center, 1303 E. Hemdon, Fresno, California 93710. 0090-8258/88$1.50 Copyright All rights
0 1988 by Academic Press, Inc. of reproduction in any form reserved.
422
EXTRAGENITAL
FIG.
423
CARCINOSARCOMA
1. Ovarian serous papillary adenocarcinoma (H & E
x
100).
she received three courses of hexamethylmelamine (HXM), CDDP, and vinblastin (VLB) followed by three courses of HXM, CDDP, and VLB. Serial CT scans showed decreasing size of the pelvic tumor. A third laparotomy was done 6 months after the second operation. It revealed no residual tumor. Seven months after the third laparotomy (62 months after initial operation) a left pelvic mass developed. It led to the fourth laparotomy which revealed a locm pelvic tumor. The tumor and the uterus were resected. Histologically the tumor showed features of a malignant mixed mtillerian tumor, homologous type (carcinosarcoma) (Figs. 2 and 3). The carcinomatous component was composed of columnar hyperchromatic cells arranged in irregular tubules, glands, and scattered papilli. It was comparable to the original ovarian tumor. The sarcomatous component was composed of oval or spindle-shaped cells arranged in poorly defined bundles. The nuclei showed moderate pleomorphism. Scattered giant tumor cells with bizarre nuclei were seen. Rhabdomyoblasts, osteoid, and cartilage were not present. There were frequent mitotic figures. The uterus was adherent to the tumor, but uninvolved by tumor. Postoperatively, she received 4500 rads of pelvic irradiation. Nine months after
424
CHEN AND WOLK
FIG. 2. Pelvic carcinosarcoma (H & E X 100).
her fourth laparotomy, a fifth laparotomy revealed peritoneal tumor masses which were debulked. She died 2 months later (73 months after initial operation). DISCUSSION
Significant changes in the histologic appearance of ovarian tumors after therapy have been reported [7-111. In most cases, the changes consisted of “retroconversion” or “maturation” of malignant teratomas following chemotherapy [79,1 11.Hong er al. in 1980reported a case of benign transformation after multiagent chemotherapy of an ovarian cystadenocarcinoma [lo]. Recently Hernandez et al. reported significant changes of histologic appearance after chemotherapy of ovarian carcinomas in 9 of 34 patients [12]. Of their 9 cases, 4 changed from mixed differentiated epithelial types to undifferentiated type, 4 changed from low grade to high grade, and 1 changed from large cell undifferentiated to small cell undifferentiated. Of the 4 cases with low to high grade transformation, 2 also changed from serous to undifferentiated. They proposed four possible explanations for the observed changes: (1) modification of the tumor by cytotoxic therapy; (2) spontaneous dedifferentiation of the initial tumor; (3) tumor cell heterogeneity with preferential growth of one cell type over the other; and (4) the development of a second primary tumor. In the present case, we documented an extragenital malignant mixed miillerian tumor that developed after chemotherapy for an ovarian serous papillary adenocarcinoma. The primary ovarian tumor was adequately sampled (12 tissue
EXTRAGENITAL
CARCINOSARCOMA
425
FIG. 3. High-power view of the sarcomatous component showing moderate degree of nuclear pleomorphism (H & E x 250).
blocks from an 1l-cm tumor) for histologic study and no sarcomatous element was found. The possible relationships between the ovarian carcinoma and subsequent extragenital carcinosarcoma in our case include all four mechanisms proposed by Hernandez et al. [12]. However the sharp morphologic contrast between the initial and subsequent tumors, and the fact that the carcinosarcoma developed after a negative laparotomy, supported the possibility that the carcinosarcoma was a second primary tumor. Only six cases of extragenital malignant mixed mtillerian tumor have previously been reported [l-6]. The tumor in three cases was, as in the present case, homologous. The other three cases were heterologous tumors. One case was associated with endometriosis and the tumor developed after radiation therapy for the endometriosis [2]. Of the five cases with follow-up information, five died within 5 months after diagnosis, and one was alive with metastasis 6 months after diagnosis. Our case appears to be the seventh case of extragenital malignant mixed mtillerian tumor. The unique feature in our case is the development of
426
CHEN
AND
WOLK
the tumor after chemotherapy for ovarian carcinoma. With the recent advances in the treatment of ovarian carcinomas, and the resultant long survival in many patients, we expect to see more examples similar to our case in the future. REFERENCES 1. Ober, W. B., and Black, M. B. Neoplasm of the subcoelomic mesenchyme, Arch. Pnthol. Lab. Med. 59, 698-705 (1955). 2. De LaPava, S., Nigogosyan, G., and Pickren, J. W. Sarcomatous transformation of “true” endometriosis, N.Y. J. Med. 63, 2548-2553 (1963). 3. Ferric, R. K., and Ross, R. C. Retroperitoneal mullerian carcinosarcoma, Can. Med. Assoc. J. 18, 1290-1291 (1967). 4. Weisz-Canington, P., Biglow, B., and Schinella, R. A. Mixed heterologous tumor of mtillerian type arising in the cecal peritoneum, report of a case, Dis. Colon Rectum 20, 329-333 (1977). 5. Hasiuk, A. S., Petersen, R. O., Hanjani, P., and Griffin, T. D. Extragenital malignant mixed mtillerian tumor. Case report and review of the literature, Amer. J. C/in. Pathol. 81, 102-105 (1984). 6. Nguyen, G., and Berendt, R. C. Aspiration biopsy cytology of metastatic endometrial stromal sarcoma and extragenital mixed mesodermal tumor, Dug. Cytopathol. 2, 256-260 (1986). 7. Smith, J., Rutledge, F., and Sutow, W. Malignant gynecologic tumors in children: Current approaches to treatment, Amer. J. Obsret. Gynecol. 116, 261 (1973). 8. Piver, S., Sinks, L., Barlow, J., and Tsukada, Y. Five year remission of metastatic solid teratoma of the ovary, Cnncer 38, 987-993 (1976). 9. DiSaia, P., Saltz, F., Kagan, A., and Marrow, P. Chemotherapeutic retroconversion of immature teratoma of the ovary, Obstet. Gynecol. 49, 346-350 (1977). 10. Hong, S. J., Lurrain, J. R., Tsukada, Y., Piver, M. S., Humber, J. R., and Freeman, A. I. Cystadenocarcinoma of the ovary in a 4-year-old; benign transformation during therapy, Cancer 45, 2227-2230 (1980).
11. Dara, P., Rich, W. M., Hodel, K., and DiSaia, P. J. Long-term disease-free survival in immature teratoma of the ovary, Cancer 50, 159-162 (1982). 12. Hernandez, E., Rosenshein, N. B., Bhagavan, B. S., and Parmley, T. H. Tumor heterogeneity and histopathology in epithelial ovarian cancer, Obstet. Gynecol. 63, 330-334 (1984).
ONCOLOGY
30,
422-426 (1988)
Extragenital Malignant Mixed Miiilerian Tumor KARL Departments
T. K. CHEN, M.D.*%‘,2AND RICHARD W. WOLK, M.D.t
of *Pathology
and tMedica1
Oncology, Frcsno Community Center, Fresno, California 93715
Hospital
and Medical
Received January 26, 1987 A case of extragenital malignant mixed mtillerian tumor that appeared to represent a second primary tumor in a patient previously treated for disseminated ovarian serous papillary carcinoma is reported and compared with other reported cases of extragenital malignant mixed miillerian tumor. 0 1988 Academic press. Inc.
Malignant mixed mtillerian tumors are observed most commonly in the endometrium, endocervix, vagina, ovaries, and fallopian tubes. Only six cases of malignant mixed mtillerian tumor have been reported to arise in extragenital sites [l-6]. We report a new case of extragenital malignant mixed mtillerian tumor which, unlike the previously reported cases, was preceded by ovarian serous papillary adenocarcinoma. CASE REPORT A 52-year-old, gravida II, para II woman underwent an exploratory laparotomy because of a pelvic mass. An 11 x 10 x 4-cm right ovarian tumor with diffuse intraabdominal tumor dissemination was found. Bilateral salpingo-oophorectomy, omentectomy, and appendectomy were performed. The right ovarian tumor was multicystic. Histologically the ovarian tumor showed features of papillary serous adenocarcinoma (Fig. 1). The omentum contained multiple nodules, up to 2 cm in diameter, of similar tumor tissue. The slightly enlarged left ovary also contained foci of tumor involvement. Postoperatively she received three courses of cyclophosphamide (CTX), doxorubicin (ADM), and diamminedichloroplatinum (CDDP) and six courses of CTX and ADM in a 9-month period. In the subsequent 2 years and 2 months she received 18 courses phenylalanine mustard (L-PAM). She refused a second-look laparotomy but had no clinical evidence of disease. Four years and 1 month after the initial operation, a recurrent pelvic tumor was found. A second laparotomy revealed a 11 x 10 x 3-cm cystic tumor. An incisional biopsy and drainage of tumor cysts were performed. The biopsy showed papillary carcinoma similar to the original ovarian tumor. After the operation ’ To whom reprint requests should be addressed. * Current address: Department of Pathology, Saint Agnes Medical Center, 1303 E. Hemdon, Fresno, California 93710. 0090-8258/88$1.50 Copyright All rights
0 1988 by Academic Press, Inc. of reproduction in any form reserved.
422
EXTRAGENITAL
FIG.
423
CARCINOSARCOMA
1. Ovarian serous papillary adenocarcinoma (H & E
x
100).
she received three courses of hexamethylmelamine (HXM), CDDP, and vinblastin (VLB) followed by three courses of HXM, CDDP, and VLB. Serial CT scans showed decreasing size of the pelvic tumor. A third laparotomy was done 6 months after the second operation. It revealed no residual tumor. Seven months after the third laparotomy (62 months after initial operation) a left pelvic mass developed. It led to the fourth laparotomy which revealed a locm pelvic tumor. The tumor and the uterus were resected. Histologically the tumor showed features of a malignant mixed mtillerian tumor, homologous type (carcinosarcoma) (Figs. 2 and 3). The carcinomatous component was composed of columnar hyperchromatic cells arranged in irregular tubules, glands, and scattered papilli. It was comparable to the original ovarian tumor. The sarcomatous component was composed of oval or spindle-shaped cells arranged in poorly defined bundles. The nuclei showed moderate pleomorphism. Scattered giant tumor cells with bizarre nuclei were seen. Rhabdomyoblasts, osteoid, and cartilage were not present. There were frequent mitotic figures. The uterus was adherent to the tumor, but uninvolved by tumor. Postoperatively, she received 4500 rads of pelvic irradiation. Nine months after
424
CHEN AND WOLK
FIG. 2. Pelvic carcinosarcoma (H & E X 100).
her fourth laparotomy, a fifth laparotomy revealed peritoneal tumor masses which were debulked. She died 2 months later (73 months after initial operation). DISCUSSION
Significant changes in the histologic appearance of ovarian tumors after therapy have been reported [7-111. In most cases, the changes consisted of “retroconversion” or “maturation” of malignant teratomas following chemotherapy [79,1 11.Hong er al. in 1980reported a case of benign transformation after multiagent chemotherapy of an ovarian cystadenocarcinoma [lo]. Recently Hernandez et al. reported significant changes of histologic appearance after chemotherapy of ovarian carcinomas in 9 of 34 patients [12]. Of their 9 cases, 4 changed from mixed differentiated epithelial types to undifferentiated type, 4 changed from low grade to high grade, and 1 changed from large cell undifferentiated to small cell undifferentiated. Of the 4 cases with low to high grade transformation, 2 also changed from serous to undifferentiated. They proposed four possible explanations for the observed changes: (1) modification of the tumor by cytotoxic therapy; (2) spontaneous dedifferentiation of the initial tumor; (3) tumor cell heterogeneity with preferential growth of one cell type over the other; and (4) the development of a second primary tumor. In the present case, we documented an extragenital malignant mixed miillerian tumor that developed after chemotherapy for an ovarian serous papillary adenocarcinoma. The primary ovarian tumor was adequately sampled (12 tissue
EXTRAGENITAL
CARCINOSARCOMA
425
FIG. 3. High-power view of the sarcomatous component showing moderate degree of nuclear pleomorphism (H & E x 250).
blocks from an 1l-cm tumor) for histologic study and no sarcomatous element was found. The possible relationships between the ovarian carcinoma and subsequent extragenital carcinosarcoma in our case include all four mechanisms proposed by Hernandez et al. [12]. However the sharp morphologic contrast between the initial and subsequent tumors, and the fact that the carcinosarcoma developed after a negative laparotomy, supported the possibility that the carcinosarcoma was a second primary tumor. Only six cases of extragenital malignant mixed mtillerian tumor have previously been reported [l-6]. The tumor in three cases was, as in the present case, homologous. The other three cases were heterologous tumors. One case was associated with endometriosis and the tumor developed after radiation therapy for the endometriosis [2]. Of the five cases with follow-up information, five died within 5 months after diagnosis, and one was alive with metastasis 6 months after diagnosis. Our case appears to be the seventh case of extragenital malignant mixed mtillerian tumor. The unique feature in our case is the development of
426
CHEN
AND
WOLK
the tumor after chemotherapy for ovarian carcinoma. With the recent advances in the treatment of ovarian carcinomas, and the resultant long survival in many patients, we expect to see more examples similar to our case in the future. REFERENCES 1. Ober, W. B., and Black, M. B. Neoplasm of the subcoelomic mesenchyme, Arch. Pnthol. Lab. Med. 59, 698-705 (1955). 2. De LaPava, S., Nigogosyan, G., and Pickren, J. W. Sarcomatous transformation of “true” endometriosis, N.Y. J. Med. 63, 2548-2553 (1963). 3. Ferric, R. K., and Ross, R. C. Retroperitoneal mullerian carcinosarcoma, Can. Med. Assoc. J. 18, 1290-1291 (1967). 4. Weisz-Canington, P., Biglow, B., and Schinella, R. A. Mixed heterologous tumor of mtillerian type arising in the cecal peritoneum, report of a case, Dis. Colon Rectum 20, 329-333 (1977). 5. Hasiuk, A. S., Petersen, R. O., Hanjani, P., and Griffin, T. D. Extragenital malignant mixed mtillerian tumor. Case report and review of the literature, Amer. J. C/in. Pathol. 81, 102-105 (1984). 6. Nguyen, G., and Berendt, R. C. Aspiration biopsy cytology of metastatic endometrial stromal sarcoma and extragenital mixed mesodermal tumor, Dug. Cytopathol. 2, 256-260 (1986). 7. Smith, J., Rutledge, F., and Sutow, W. Malignant gynecologic tumors in children: Current approaches to treatment, Amer. J. Obsret. Gynecol. 116, 261 (1973). 8. Piver, S., Sinks, L., Barlow, J., and Tsukada, Y. Five year remission of metastatic solid teratoma of the ovary, Cnncer 38, 987-993 (1976). 9. DiSaia, P., Saltz, F., Kagan, A., and Marrow, P. Chemotherapeutic retroconversion of immature teratoma of the ovary, Obstet. Gynecol. 49, 346-350 (1977). 10. Hong, S. J., Lurrain, J. R., Tsukada, Y., Piver, M. S., Humber, J. R., and Freeman, A. I. Cystadenocarcinoma of the ovary in a 4-year-old; benign transformation during therapy, Cancer 45, 2227-2230 (1980).
11. Dara, P., Rich, W. M., Hodel, K., and DiSaia, P. J. Long-term disease-free survival in immature teratoma of the ovary, Cancer 50, 159-162 (1982). 12. Hernandez, E., Rosenshein, N. B., Bhagavan, B. S., and Parmley, T. H. Tumor heterogeneity and histopathology in epithelial ovarian cancer, Obstet. Gynecol. 63, 330-334 (1984).