- Email: [email protected]
Mullerian adenosarcoma of the uterus: Report of a rare case and review of the literature
GYNECOLOCIC
ONCOLOGY
30,
291-297 (1988)
Mullerian Adenosarcoma of the Uterus: Report of a Rare Case and Review of the Literature ARIE DEKEL, M.D., Dov DICKER, M.D., DANIEL KUGLER, M.D., MORDECHAI BEN DAVID, M.D., RIVKA GAL, M.D., AND JACK A. GOLDMAN, M.D. Department of Obstetrics-Gynecology and Pathology, Golda Meir Medical Center (Hasharon Hospital), Petah-Tikva, and Tel-Aviv University Medical School, Israel Received December 8. 1986 A rare case of Mullerian adenosarcoma of the uterus is described, found during diagnostic curettage. Panhysterectomy was performed. These rare tumors have a low potential for malignancy and are characterized by benign epithelial and malignant stromal elements. They should be distinguished from the highly malignant mixed Mullerian tumors which contain, by definition, both carcinomatous and sarcomatous elements. The literature on the subject has been reviewed. o 1988 Academic press. IW.
INTRODUCTION
Mullerian mixed tumors of the uterus are very malignant, often fatal, neoplasms containing both carcinomatous and sarcomatous elements. Recently Clement and Scully [l] described similar mixed tumors of the uterus in which the stromal component is malignant, but the epithelial elements benign. These neoplasms, designated Mullerian adenosarcoma, have a characteristically low malignant potential; they should be distinguished from the more aggressive classic form of mixed Mullerian tumor. In view of its scarcity, we report a case of Mullerian adenosarcoma and review the literature on the subject. CASE REPORT
E.R., a 52-year-old woman, G, P,, was admitted to the Gynecological department with postmenopausal bleeding and lower abdominal pain. Past history revealed that she had undergone left radical mastectomy for ductal adenocarcinoma of the breast, followed by external radiotherapy in 1973. On admission she was in satisfactory general condition. Pelvic examination revealed a moderately enlarged uterus. Xray of the chest, I.V.P., barium enema,
291 0090-8258188$1SO Copyright 0 1988 by Academic Press, Inc. All rights of reproduction in any form reserved.
292
DEKEL
FIG.
ET AL.
1. Large polypoid tumor fills the uterine cavity.
brain, liver, and bone scans were all negative for metastases. Fractional curettage was done, and histopathological examination showed the endometrium to be composed of a polypoid growth with benign glands and a sarcomatous stroma. The pathological diagnosis was Mullerian adenosarcoma of the uterus. Panhysterectomy was performed. The postoperative course was uneventful, and she left the hospital on the seventh postoperative day. She was referred to the Oncology department for further treatment. Macroscopic pathological examination: a polypoid mass, 6 x 5 x 3 cm, filled the uterine cavity and was attached to the fundus by a broad base (Fig. 1). The tumor was rubbery in consistency and showed a few areas of necrosis and hemorrhage. There was no gross invasion of the myometrium. Microscopic histopathological examination revealed the tumor to be composed of cystic, dilated glands surrounded by cellular stroma (Figs. 2 and 3). The stromal cells had plump or spindle-shaped nuclei, showing hyperchromatism and moderate pleomorphism (Fig. 4). There were an average of 10 mitotic figures per 10 highpower fields. The epithelial lining of the glands was usually similar to proliferative endometrium, but some areas were those of early secretory phase with basal vacuoles. There were no malignant changes in the glandular epithelial cells. The tumor was diagnosed as Mulletian adenosarcoma. There was no invasion of the adjacent endometrium, nor of the myometrium. One year after the operation the patient has no evidence of disease. Pelvic examination bone scan, abdominal and pelvic computerized tomography, and Xrays show no recurrence.
CASE
REPORTS
293
FIG. 2. Numerous glands, some of which are cystic, distributed uniformly throughout the sarcomatous stroma (HE x 50).
DISCUSSION
Mullerian adenosarcoma is a newly identified variety of uterine sarcoma. Clement and Scully [l] first described 10 cases in 1974. Roth ef al. [2] added one case and described the electron microscopic findings. Blythe et al. [3] reported another 3 cases in a 33-year review from the University of Iowa, which though unpublished is cited by Buchsbaum and Sciarra [4]. Ben-Baruch et al. [5], in a series of 31 uterine sarcomas collected in Israel, reported 2 cases with Mullerian adenosarcoma (Table 1). These are rare tumors indeed, often posing a problem in diagnosis and nomenclature. In view of their characteristically low-grade malignancy, Clement and Scully have chosen the term “Mullerian adenosarcoma” in order to emphasize the benign appearance of the epithelial component [l]. In fact, these neoplasms
294
DEKEL
ET AL.
FIG. 3. Regular columnar epithelial cells with basal vacuoles line a gland. Note a mitotic figure (arrow) in the cellular stroma.
form polypoid tumor growths and consist of an admixture of benign-appearing epithelial elements and a sarcomatous stroma. Thus, local recurrences often occur, and only exceptionally metastases are found. Electron microscopic studies by Roth ef al. [2] support the theory that these malignancies arise from undifferentiated multipotential Mullerian stem cells. In view of their sluggish course and histologic benignity these tumors must be distinguished from the more aggressive form of mixed Mullerian tumors characterized by carcinomatous epithelial and sarcomatous stromal elements. Furthermore, these tumors are also distinct from the malignant endometrial stromal tumors, including those designated as stromal sarcoma as well as those referred to as endolymphatic stromal myosis. Clement and Scully [l] reviewed several large series of neoplasms [6,7] but found none to be identical to those they reported; among these a large series of 53 endometrial stromal tumors were reviewed by Norris and Taylor [7], which they failed to identify as neoplasms belonging in the same category as their 10 cases. In a case reported by Teilum [8] the patient was alive and well without recurrence 10 years postoperatively. He described the tumor as “a differentiated and possibly benign variant of mixed mesodermal tumor.” Two series of tumors resembling those described by Clement and Scully [l] have been reported, by Abel1 [9] in the cervix, and by Vellios et al. [lo] in the cervix and endometrium. Both designated them “Papillary adenofibroma.” While
CASE REPORTS
295
FIG. 4. High-power view of the stroma. There are hyperchromatic and bizarre stromal cells (HE x looo).
the latter resembles microscopically the Mullerrian adenosarcoma, they should not be considered identical to them. The clinical features of these tumors are not distinctive. Elderly females are mainly affected, and postmenopausal bleeding and lower abdominal pain are the main presenting symptoms. The prognosis is rather difficult to interpret. Nevertheless these neoplasms reported are less fatal. Five of Clement and Scully’s [l] patients were living and well at 3 months, 1 year, 2 l/2 years, 6 years, and 7 l/2 years; one patient died at 4 years, clinically free of disease. Four patients had recurrent disease; 3 were local recurrences, and 1 was distant. The 3 patients reported from the University of Iowa had surgical removal of their disease. Patients died at 36 months and at 8 l/2 and 10 l/2 years with no evidence of disease. The activity of these three tumors supports Clement and Scully’s [l] original contention that these tumors are less malignant and should be classified accordingly. Nevertheless, in view of the malignant potential of these tumors, a total abdominal hysterectomy should be performed. In conclusion, the main practical point for which this case has been reported is that these malignant neoplasms do have a relatively favorable prognosis, a characteristic which serves to separate them from the treacherous prognosis of the mixed mesodermal tumors. Nevertheless, it may not contrast quite as much with the sluggish but evil behavior of the endometrial sarcoma of the stromatosis variety.
Year
1974
I976
1984
1985
1986
Author
Clement and Scully [I]
Roth er al. [2]
Ben-Baruch et al. [5]
Blythe et al. [3]
Dekel et al. Present case
1
I
52
mean-62
mean-54
14
mean-74
10
1
Age
OF THE UTERUS,
TABLE ADENOSARCOMA
No. of cases
MULLERIAN
abnormal vaginal bleeding, abdominal pain
vaginal discharge, bleeding, abdominal pain
vaginal bleeding
mucoid vaginal discharge, g-cm vaginal mass
abnormal vaginal bleeding
Clinical picture
17 CASES
I year post op. alive, free of disease.
All died 3, 8.5, and 10.5 years post op. with no evidence of disease.
Alive 2,7 years post op. No myometrial invasion.
3.5 years post op. alive. No. recurrence.
5 patients alive: 3 months, 1 year, 2.5 years, 6 years, and 7.5 years; I died at 4 years free of disease, 3 were local recurrences, and 1 was distant.
Outcome
CASE REPORTS
297
REFERENCES 1. Clement, P. B., and Scully, R. E. Mullerian adenosarcoma of the uterus: A clinicopathologic analysis of ten cases of a distinctive type of mullerian mixed tumor, Cancer 34, 1138-1149 (1974). 2. Roth, L. M., Pride, L. G., and Sharma, H. M. Mullerian adenosarcoma of the uterine cervix with heterologous elements. A light and electron microscopic study, Cancer 37, 1725-1736 (1976). 3. Blythe, J. G., Bari, W., and Buchsbaum, H. J. Uterine sarcoma-clinico pathologic study, unpublished data (cited by Buchsbaum [4]). 4. Buchsbaum, H. H., and Sciarra, J. J. Gynecologic oncology, in Gynecology and obstetrics (H. J. Buchsbaum and J. J. Sciarra, Eds.), Harper & Row, Philadelphia, pp. 6-8 (1985). 5. Ben-Baruch, G., Amir, G., Menczer, J., and Bubis, J. H. Uterine sarcoma in Israeli patients: A clinicopathological study, Zsr. J. Med. Sci. 20, 21l-215 (1984). 6. Hughesdon, P. E., and Cocks, D. P. Endometrial stroma complicating cystic hyperplasia with remarks on “carcino-sarcoma,” .I. Obstet. Gynecol. Brit. Commonw. 62, 567-571 (1955). 7. Norris, H. J., and Taylor, H. B. Mesenchymal tumors of the uterus. I. A clinical and pathological study of 53 endometrial stromal tumors, Cancer 19, 755-766 (1966). 8. Teilum, G. Special tumors of the ovary and testis, Lippincott, Philadelphia, pp. 286-87 (1971). 9. Abell, M. R. Papillary adenofibroma of the uterine cervix, Amer. J. Obstet. Gynecol. 110, 990993 (1971). 10. Vellios, F., Ng, A. B. P., and Reagan, J. W. Papillary adenofibroma of the uterus-a benign mesodermal mixed tumor of mullerian origin, Amer. J. Clin. P&o/. 60, 543-551 (1973).
ONCOLOGY
30,
291-297 (1988)
Mullerian Adenosarcoma of the Uterus: Report of a Rare Case and Review of the Literature ARIE DEKEL, M.D., Dov DICKER, M.D., DANIEL KUGLER, M.D., MORDECHAI BEN DAVID, M.D., RIVKA GAL, M.D., AND JACK A. GOLDMAN, M.D. Department of Obstetrics-Gynecology and Pathology, Golda Meir Medical Center (Hasharon Hospital), Petah-Tikva, and Tel-Aviv University Medical School, Israel Received December 8. 1986 A rare case of Mullerian adenosarcoma of the uterus is described, found during diagnostic curettage. Panhysterectomy was performed. These rare tumors have a low potential for malignancy and are characterized by benign epithelial and malignant stromal elements. They should be distinguished from the highly malignant mixed Mullerian tumors which contain, by definition, both carcinomatous and sarcomatous elements. The literature on the subject has been reviewed. o 1988 Academic press. IW.
INTRODUCTION
Mullerian mixed tumors of the uterus are very malignant, often fatal, neoplasms containing both carcinomatous and sarcomatous elements. Recently Clement and Scully [l] described similar mixed tumors of the uterus in which the stromal component is malignant, but the epithelial elements benign. These neoplasms, designated Mullerian adenosarcoma, have a characteristically low malignant potential; they should be distinguished from the more aggressive classic form of mixed Mullerian tumor. In view of its scarcity, we report a case of Mullerian adenosarcoma and review the literature on the subject. CASE REPORT
E.R., a 52-year-old woman, G, P,, was admitted to the Gynecological department with postmenopausal bleeding and lower abdominal pain. Past history revealed that she had undergone left radical mastectomy for ductal adenocarcinoma of the breast, followed by external radiotherapy in 1973. On admission she was in satisfactory general condition. Pelvic examination revealed a moderately enlarged uterus. Xray of the chest, I.V.P., barium enema,
291 0090-8258188$1SO Copyright 0 1988 by Academic Press, Inc. All rights of reproduction in any form reserved.
292
DEKEL
FIG.
ET AL.
1. Large polypoid tumor fills the uterine cavity.
brain, liver, and bone scans were all negative for metastases. Fractional curettage was done, and histopathological examination showed the endometrium to be composed of a polypoid growth with benign glands and a sarcomatous stroma. The pathological diagnosis was Mullerian adenosarcoma of the uterus. Panhysterectomy was performed. The postoperative course was uneventful, and she left the hospital on the seventh postoperative day. She was referred to the Oncology department for further treatment. Macroscopic pathological examination: a polypoid mass, 6 x 5 x 3 cm, filled the uterine cavity and was attached to the fundus by a broad base (Fig. 1). The tumor was rubbery in consistency and showed a few areas of necrosis and hemorrhage. There was no gross invasion of the myometrium. Microscopic histopathological examination revealed the tumor to be composed of cystic, dilated glands surrounded by cellular stroma (Figs. 2 and 3). The stromal cells had plump or spindle-shaped nuclei, showing hyperchromatism and moderate pleomorphism (Fig. 4). There were an average of 10 mitotic figures per 10 highpower fields. The epithelial lining of the glands was usually similar to proliferative endometrium, but some areas were those of early secretory phase with basal vacuoles. There were no malignant changes in the glandular epithelial cells. The tumor was diagnosed as Mulletian adenosarcoma. There was no invasion of the adjacent endometrium, nor of the myometrium. One year after the operation the patient has no evidence of disease. Pelvic examination bone scan, abdominal and pelvic computerized tomography, and Xrays show no recurrence.
CASE
REPORTS
293
FIG. 2. Numerous glands, some of which are cystic, distributed uniformly throughout the sarcomatous stroma (HE x 50).
DISCUSSION
Mullerian adenosarcoma is a newly identified variety of uterine sarcoma. Clement and Scully [l] first described 10 cases in 1974. Roth ef al. [2] added one case and described the electron microscopic findings. Blythe et al. [3] reported another 3 cases in a 33-year review from the University of Iowa, which though unpublished is cited by Buchsbaum and Sciarra [4]. Ben-Baruch et al. [5], in a series of 31 uterine sarcomas collected in Israel, reported 2 cases with Mullerian adenosarcoma (Table 1). These are rare tumors indeed, often posing a problem in diagnosis and nomenclature. In view of their characteristically low-grade malignancy, Clement and Scully have chosen the term “Mullerian adenosarcoma” in order to emphasize the benign appearance of the epithelial component [l]. In fact, these neoplasms
294
DEKEL
ET AL.
FIG. 3. Regular columnar epithelial cells with basal vacuoles line a gland. Note a mitotic figure (arrow) in the cellular stroma.
form polypoid tumor growths and consist of an admixture of benign-appearing epithelial elements and a sarcomatous stroma. Thus, local recurrences often occur, and only exceptionally metastases are found. Electron microscopic studies by Roth ef al. [2] support the theory that these malignancies arise from undifferentiated multipotential Mullerian stem cells. In view of their sluggish course and histologic benignity these tumors must be distinguished from the more aggressive form of mixed Mullerian tumors characterized by carcinomatous epithelial and sarcomatous stromal elements. Furthermore, these tumors are also distinct from the malignant endometrial stromal tumors, including those designated as stromal sarcoma as well as those referred to as endolymphatic stromal myosis. Clement and Scully [l] reviewed several large series of neoplasms [6,7] but found none to be identical to those they reported; among these a large series of 53 endometrial stromal tumors were reviewed by Norris and Taylor [7], which they failed to identify as neoplasms belonging in the same category as their 10 cases. In a case reported by Teilum [8] the patient was alive and well without recurrence 10 years postoperatively. He described the tumor as “a differentiated and possibly benign variant of mixed mesodermal tumor.” Two series of tumors resembling those described by Clement and Scully [l] have been reported, by Abel1 [9] in the cervix, and by Vellios et al. [lo] in the cervix and endometrium. Both designated them “Papillary adenofibroma.” While
CASE REPORTS
295
FIG. 4. High-power view of the stroma. There are hyperchromatic and bizarre stromal cells (HE x looo).
the latter resembles microscopically the Mullerrian adenosarcoma, they should not be considered identical to them. The clinical features of these tumors are not distinctive. Elderly females are mainly affected, and postmenopausal bleeding and lower abdominal pain are the main presenting symptoms. The prognosis is rather difficult to interpret. Nevertheless these neoplasms reported are less fatal. Five of Clement and Scully’s [l] patients were living and well at 3 months, 1 year, 2 l/2 years, 6 years, and 7 l/2 years; one patient died at 4 years, clinically free of disease. Four patients had recurrent disease; 3 were local recurrences, and 1 was distant. The 3 patients reported from the University of Iowa had surgical removal of their disease. Patients died at 36 months and at 8 l/2 and 10 l/2 years with no evidence of disease. The activity of these three tumors supports Clement and Scully’s [l] original contention that these tumors are less malignant and should be classified accordingly. Nevertheless, in view of the malignant potential of these tumors, a total abdominal hysterectomy should be performed. In conclusion, the main practical point for which this case has been reported is that these malignant neoplasms do have a relatively favorable prognosis, a characteristic which serves to separate them from the treacherous prognosis of the mixed mesodermal tumors. Nevertheless, it may not contrast quite as much with the sluggish but evil behavior of the endometrial sarcoma of the stromatosis variety.
Year
1974
I976
1984
1985
1986
Author
Clement and Scully [I]
Roth er al. [2]
Ben-Baruch et al. [5]
Blythe et al. [3]
Dekel et al. Present case
1
I
52
mean-62
mean-54
14
mean-74
10
1
Age
OF THE UTERUS,
TABLE ADENOSARCOMA
No. of cases
MULLERIAN
abnormal vaginal bleeding, abdominal pain
vaginal discharge, bleeding, abdominal pain
vaginal bleeding
mucoid vaginal discharge, g-cm vaginal mass
abnormal vaginal bleeding
Clinical picture
17 CASES
I year post op. alive, free of disease.
All died 3, 8.5, and 10.5 years post op. with no evidence of disease.
Alive 2,7 years post op. No myometrial invasion.
3.5 years post op. alive. No. recurrence.
5 patients alive: 3 months, 1 year, 2.5 years, 6 years, and 7.5 years; I died at 4 years free of disease, 3 were local recurrences, and 1 was distant.
Outcome
CASE REPORTS
297
REFERENCES 1. Clement, P. B., and Scully, R. E. Mullerian adenosarcoma of the uterus: A clinicopathologic analysis of ten cases of a distinctive type of mullerian mixed tumor, Cancer 34, 1138-1149 (1974). 2. Roth, L. M., Pride, L. G., and Sharma, H. M. Mullerian adenosarcoma of the uterine cervix with heterologous elements. A light and electron microscopic study, Cancer 37, 1725-1736 (1976). 3. Blythe, J. G., Bari, W., and Buchsbaum, H. J. Uterine sarcoma-clinico pathologic study, unpublished data (cited by Buchsbaum [4]). 4. Buchsbaum, H. H., and Sciarra, J. J. Gynecologic oncology, in Gynecology and obstetrics (H. J. Buchsbaum and J. J. Sciarra, Eds.), Harper & Row, Philadelphia, pp. 6-8 (1985). 5. Ben-Baruch, G., Amir, G., Menczer, J., and Bubis, J. H. Uterine sarcoma in Israeli patients: A clinicopathological study, Zsr. J. Med. Sci. 20, 21l-215 (1984). 6. Hughesdon, P. E., and Cocks, D. P. Endometrial stroma complicating cystic hyperplasia with remarks on “carcino-sarcoma,” .I. Obstet. Gynecol. Brit. Commonw. 62, 567-571 (1955). 7. Norris, H. J., and Taylor, H. B. Mesenchymal tumors of the uterus. I. A clinical and pathological study of 53 endometrial stromal tumors, Cancer 19, 755-766 (1966). 8. Teilum, G. Special tumors of the ovary and testis, Lippincott, Philadelphia, pp. 286-87 (1971). 9. Abell, M. R. Papillary adenofibroma of the uterine cervix, Amer. J. Obstet. Gynecol. 110, 990993 (1971). 10. Vellios, F., Ng, A. B. P., and Reagan, J. W. Papillary adenofibroma of the uterus-a benign mesodermal mixed tumor of mullerian origin, Amer. J. Clin. P&o/. 60, 543-551 (1973).