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Heterologous malignant mixed Müllerian tumor of the cervical stump
GYNECOLOGIC
ONCOLOGY
16, 422-428 (1983)
Heterologous Malignant Mixed Miillerian Tumor of the Cervical Stump MARIAN WAXMAN,
M.D.,’ JENNY S. WAXMAN, M.D., AND VICTOR ALINOVI, M.D.
Departments of Pathology and Obstetrics and Gynecology, Nassau Hospital, Mineola, New York, and Department of Pathology, Mount Sinai School of Medicine, Elmhurst General Hospital Center, Elmhurst, New York A 76-year-old woman presented with vaginal bleeding 37 years following supracervical hysterectomy for a benign disease. Extensive malignant mixed Mtillerian tumor was found in the remaining uterine cervix. This appears to be the first documented case of the malignant mixed Mtillerian tumor arising in a cervical stump. Possibility of derivation of this tumor from endometriosis notwithstanding, the cervical Mtillerian neoplastic potential parallels that of the endometrium because of the developmental kinship of the two. This potential has been fully retained and expressed as a tumor in the cervical stump in this case.
Malignant mixed Mtillerian tumors (MMMT) arise most commonly in the uterine body, while their origin in other organs, although well known, has been seldom reported. Very few cases of MMMT arising in the cervix have been described [l-3]. This neoplasm, occurring as a primary tumor of a cervical stump, has not been previously documented to the best of our knowledge. CASE REPORT
A 76-year-old woman, para O-O-O-O,was hospitalized for a bleeding cervical mass. She had a supracervical hysterectomy with left salpingo-oophorectomy for uterine myomas at age 39. Right hemicolectomy for cecal adenocarcinoma Dukes’ class B was done 9 years prior to this presentation. The patient had never received radiation treatment. Two months before the admission she complained of a watery vaginal discharge, but the examination disclosed an intact, smooth cervical stump with no abnormalities, and the cervical Pap smear was normal. She presented now because of spotty, intermittent vaginal bleeding of 4-weeks duration, which became brisk on the day of admission. The general physical examination was unremarkable. The external genitalia and vagina were normal. Seen protruding through the cervical OSwas an exophytic mass, about 3 cm in size, friable, and bleeding to touch. The cervical stump was palpated in the midline as a mass of about 5 cm in size. The uterine body was absent. ’ To whom requests for reprints should be addressed. Present address: Department of Pathology, St. Vincent’s Hospital, 153 West 11th Street, New York, N.Y. 10011. 422 0090~8258/83$1.50 Copyright All rights
Q 1983 by Academic Press, Inc. of reproduction in any form reserved.
CASE
REPORTS
423
No adnexa or other masses could be felt. Rectal examination was confirmatory of the above findings. Intravenous pyelogram demonstrated indentation of the posterior bladder wall by an extrinsic mass, which sonographically showed an irregular heterogeneous echo pattern. Laboratory values were normal except for a slight anemia. Chest X-ray films and barium enema showed no evidence of tumor. Following biopsy of the mass the patient underwent laparotomy. The stump was found to be enlarged, abnormally soft, and was adherent to the bladder. The uterus and left adnexa were absent, but the right ovary and tube were identified. The cul-de-sac appeared free of tumor. Except for extensive bowel adhesions the abdominal organs appeared normal, and there were no ascites. Resection of the complete cerival stump and right salpingo-oophorectomy were performed. Postoperatively, the patient received chemotherapy consisting of vincristine sulfate, Adriamycin, and Cytoxan. She was in good general condition and without evidence of recurrent or metastatic tumor 9 months after the operation. PATHOLOGIC EXAMINATION Gross. The cervical biopsy consisted of three greenish-brown and hemorrhagic pliable fragments measuring up to 6 x 3 cm in largest dimensions. The cervical stump was greatly thickened, measuring up to 5 cm in diameter and 5.5 cm in length. The exocervical OS was dilated and hemorrhagic, but the surrounding surface of the portio was pale whitish and smooth. The lumen was probe patent. Opening the cervix revealed a greatly thickened wall consisting almost entirely of soft, pliable, gray tumor tissue with hemorrhagic and necrotic areas (Fig. 1). Tumor deposits were readily seen on the surfaces of the ovary and fallopian tube, although there was no suggestion of tumor within these organs. Microscopic. The cervical biopsy disclosed a biphasic neoplasm consisting of malignant epithelial and mesenchymal components. The carcinoma showed mostly poorly differentiated glandular or solid patterns (Figs. 2 and 3). The sarcoma consisted predominantly of undifferentiated malignant mesenchymal spindle cells (Fig. 2). Occasional areas of chondrosarcoma were in evidence (Fig. 3), but no other differentiated homologous or heterologous elements were identified. The quantitative ratio of the sarcoma to carcinoma was roughly 1: 1. Carcinomatous elements predominated in the cervicectomy specimen. In addition to the patterns described above, there were prominent areas of papillary serous adenocarcinoma with psammoma bodies and areas in which the glands resembled endometrioid adenocarcinoma (Figs. 4A and B). The mesenchymal component showed an undifferentiated sarcoma only. The approximate ratio of sarcoma to carcinoma was 1: 19. The tumor displayed an aggressive growth pattern in that it had infiltrated throughout the entire thickness of the cervical wall and had invaded perineural and vascular spaces. Normal endocervical epithelium was identified in the uppermost part of the stump, but no endometrial tissue was found. The tubal and ovarian tumorous implants demonstrated identical histologic appearance. Otherwise, the tube and ovary were atrophic and showed no intrinsic metastases.
424
WAXMAN, WAXMAN, AND ALINOVI
FIG. 1. Bisected cervical stump showing almost complete tumor replacement of the walls and a vague outline of the endocervical lumen. The exocervix is relatively spared.
DISCUSSION
Contrary to previous opinions, the incidence of cervical cancer developing in a posthysterectomy stump has not been found to be increased, but is the same as that arising in the intact uterus [4]. Squamous cell carcinoma constitutes the majority (about 90%) of tumors originating from the cervical stump; adenocarcinoma is second in frequency (42 out of 402 cases or about 10%) [5-71. Only solitary cases of leiomyosarcoma [7,8], basal cell carcinoma [5], and mixed mesodermal tumor [5] have been mentioned in the literature, the latter without any documentation. The uterine cervix is an unusual site for a primary MMMT, and we could find only a handful of documented cases [l-3]. While MMMT of the ovary [9] and fallopian tube [IO] is distinct and easily diagnosable as primary tumors in these locations, caution is necessary in accepting the cervix as a primary site. Since the uterine body is a much more frequent seat of origin of this neoplasm than is the cervix, and there is often a tendency for the MMMT of the corpus to involve the cervix secondarily, as a polypoid intraluminal extension or as a mural infiltrate, a tumor involving both the body and cervix is presumed to have
CASE REPORTS
425
426
WAXMAN,
WAXMAN,
AND
ALINOVI
r;X . t%j
X
CASE REPORTS
427
F3~. 4. (A). An area showing papillary serous adenocarcinoma with psammoma bodie s. 0) Spi ndle cell sarcoma next to adenocarcinoma, the latter resembling endometrioid carcinoma. H&E (4 x 100; (B) x 100.
428
WAXMAN,
WAXMAN,
AND ALINOVI
originated in the body. A similar problem arises at times in distinguishing primary endocervical adenocarcinoma from a secondary cervical involvement of endometrial cancer [Ill. Abel1 and Ramirez [2] described criteria for accepting a uterine sarcoma or carcinosarcoma as a primary tumor of the cervix: (a) absence of involvement of the corpus in the hysterectomy specimen; (b) no enlargement of the corpus and no tumor in the endometrial curretings material; and (c) tumor of the cervical stump, and absence of similar tumor in the supracervical hysterectomy specimen. Our case fulfills the last criterion. Although material from the hysterectomy specimen was not available for review, the time interval of 37 years that had elapsed since the supracervical hysterectomy was performed, assures us that the patient did not have MMMT of the uterine body. To ensure that the tumor has indeed arisen from the cervical tissue, no endometrium should be found in the cervical stump. This consideration is important as reflected in the finding of residual endometrial tissue in as many as 19 (9%) out of 216 cervical stumps in one series [7]. It is likely, therefore, that some supracervical hysterectomies have been incomplete in that the lowermost part of the corpus with its endometrial lining remained in situ with the cervix, and that MMMT or other tumors can develop from such residual endometrium. Other possible sources of endometrium in the cervix include irregular extension of the endometrial lining into the endocervix, endometrial metaplasia of the endocervical crypt lining, and endometriosis. Careful examination failed to disclose any evidence of endometrial tissue in our case. The cervix may be a site of primary MMMT without necessarily harboring endometrial tissue. Since endocervical mucosa is Mtillerian-derived, its neoplastic potential is similar to that of the endometrium, the histogenetic considerations of the cervical tumor closely paralleling those pertaining to the origin of MMMT in the uterine corpus [12]. REFERENCES 1. Sternberg, W. H., Clark, W. H., and Smith, R. C. Malignant mixed mtillerian tumor. (Mixed mesodermal tumor of the uterus). A study of twenty-one cases, Cancer 7, 704-724 (1954). 2. Abell, M. R., and Ramirez, G. J. A. Sarcomas and carcinosarcomas of the uterine cervix, Cancer 31, 1176-l 192 (1973). 3. Hall-Craggs, M., Toker, C., and Nedwich, A. Carcinosarcoma of the uterine cervix: A light and electron microscopic study, Cancer 48, 161-169 (1981). 4. Dunn, M. R. Prevalence of carcinoma arising in cervical stumps, Amer. /. Obsret. Gynecol. 82, 83-87 (1961). 5. Creadick, R. N. Carcinoma of the cervical stump, Amer. J. Obsret. Gynecol. 75, 565-574 (1958). 6. Wolff, J. P., Lacour, J., Chassagne, D., Berend, M. Cancer of the cervical stump. A study of 173 patients, Obstet. Gynecol. 39, lo-16 (1972). 7. Pratt, J. H., Jefferies, J. A. The retained cervical stump. A 25-year experience, Obsfer. Gynecol. 48, 711-715 (1976).
8. Sturdy, D. E. Leiomyosarcoma of cervical stump following subtotal hysterectomy, Brir. J. Surg. 46, 369-370 (1959). 9. Hemandez, W., DiSaia, P. J., Morrow, C. P., and Townsend, D. E. Mixed mesodermal sarcoma of the ovary, Obster. Gynecol. 49, 59s-63s (1977). 10. Manes, J. L., and Taylor, H. B. Carcinosarcoma and mixed miillerian tumors of the fallopian tube. Report of four cases, Cancer 38, 1687-1693 (1976). 11. Haggard, J. L., Cotten, N., Dougherty, C. M., and Mickal, A. Primary adenocarcinoma of the cervix, Obstet. Gynecol. 24, 183-193 (1964). 12. Waxman, M., Boyce, J. G., Macasaet, M. M., and Lu, T. Concurrence of malignant and benign heterologous mixed tumors of the uterus, Amer. J. Clin. Puthol. 77, 631-637 (1982).
ONCOLOGY
16, 422-428 (1983)
Heterologous Malignant Mixed Miillerian Tumor of the Cervical Stump MARIAN WAXMAN,
M.D.,’ JENNY S. WAXMAN, M.D., AND VICTOR ALINOVI, M.D.
Departments of Pathology and Obstetrics and Gynecology, Nassau Hospital, Mineola, New York, and Department of Pathology, Mount Sinai School of Medicine, Elmhurst General Hospital Center, Elmhurst, New York A 76-year-old woman presented with vaginal bleeding 37 years following supracervical hysterectomy for a benign disease. Extensive malignant mixed Mtillerian tumor was found in the remaining uterine cervix. This appears to be the first documented case of the malignant mixed Mtillerian tumor arising in a cervical stump. Possibility of derivation of this tumor from endometriosis notwithstanding, the cervical Mtillerian neoplastic potential parallels that of the endometrium because of the developmental kinship of the two. This potential has been fully retained and expressed as a tumor in the cervical stump in this case.
Malignant mixed Mtillerian tumors (MMMT) arise most commonly in the uterine body, while their origin in other organs, although well known, has been seldom reported. Very few cases of MMMT arising in the cervix have been described [l-3]. This neoplasm, occurring as a primary tumor of a cervical stump, has not been previously documented to the best of our knowledge. CASE REPORT
A 76-year-old woman, para O-O-O-O,was hospitalized for a bleeding cervical mass. She had a supracervical hysterectomy with left salpingo-oophorectomy for uterine myomas at age 39. Right hemicolectomy for cecal adenocarcinoma Dukes’ class B was done 9 years prior to this presentation. The patient had never received radiation treatment. Two months before the admission she complained of a watery vaginal discharge, but the examination disclosed an intact, smooth cervical stump with no abnormalities, and the cervical Pap smear was normal. She presented now because of spotty, intermittent vaginal bleeding of 4-weeks duration, which became brisk on the day of admission. The general physical examination was unremarkable. The external genitalia and vagina were normal. Seen protruding through the cervical OSwas an exophytic mass, about 3 cm in size, friable, and bleeding to touch. The cervical stump was palpated in the midline as a mass of about 5 cm in size. The uterine body was absent. ’ To whom requests for reprints should be addressed. Present address: Department of Pathology, St. Vincent’s Hospital, 153 West 11th Street, New York, N.Y. 10011. 422 0090~8258/83$1.50 Copyright All rights
Q 1983 by Academic Press, Inc. of reproduction in any form reserved.
CASE
REPORTS
423
No adnexa or other masses could be felt. Rectal examination was confirmatory of the above findings. Intravenous pyelogram demonstrated indentation of the posterior bladder wall by an extrinsic mass, which sonographically showed an irregular heterogeneous echo pattern. Laboratory values were normal except for a slight anemia. Chest X-ray films and barium enema showed no evidence of tumor. Following biopsy of the mass the patient underwent laparotomy. The stump was found to be enlarged, abnormally soft, and was adherent to the bladder. The uterus and left adnexa were absent, but the right ovary and tube were identified. The cul-de-sac appeared free of tumor. Except for extensive bowel adhesions the abdominal organs appeared normal, and there were no ascites. Resection of the complete cerival stump and right salpingo-oophorectomy were performed. Postoperatively, the patient received chemotherapy consisting of vincristine sulfate, Adriamycin, and Cytoxan. She was in good general condition and without evidence of recurrent or metastatic tumor 9 months after the operation. PATHOLOGIC EXAMINATION Gross. The cervical biopsy consisted of three greenish-brown and hemorrhagic pliable fragments measuring up to 6 x 3 cm in largest dimensions. The cervical stump was greatly thickened, measuring up to 5 cm in diameter and 5.5 cm in length. The exocervical OS was dilated and hemorrhagic, but the surrounding surface of the portio was pale whitish and smooth. The lumen was probe patent. Opening the cervix revealed a greatly thickened wall consisting almost entirely of soft, pliable, gray tumor tissue with hemorrhagic and necrotic areas (Fig. 1). Tumor deposits were readily seen on the surfaces of the ovary and fallopian tube, although there was no suggestion of tumor within these organs. Microscopic. The cervical biopsy disclosed a biphasic neoplasm consisting of malignant epithelial and mesenchymal components. The carcinoma showed mostly poorly differentiated glandular or solid patterns (Figs. 2 and 3). The sarcoma consisted predominantly of undifferentiated malignant mesenchymal spindle cells (Fig. 2). Occasional areas of chondrosarcoma were in evidence (Fig. 3), but no other differentiated homologous or heterologous elements were identified. The quantitative ratio of the sarcoma to carcinoma was roughly 1: 1. Carcinomatous elements predominated in the cervicectomy specimen. In addition to the patterns described above, there were prominent areas of papillary serous adenocarcinoma with psammoma bodies and areas in which the glands resembled endometrioid adenocarcinoma (Figs. 4A and B). The mesenchymal component showed an undifferentiated sarcoma only. The approximate ratio of sarcoma to carcinoma was 1: 19. The tumor displayed an aggressive growth pattern in that it had infiltrated throughout the entire thickness of the cervical wall and had invaded perineural and vascular spaces. Normal endocervical epithelium was identified in the uppermost part of the stump, but no endometrial tissue was found. The tubal and ovarian tumorous implants demonstrated identical histologic appearance. Otherwise, the tube and ovary were atrophic and showed no intrinsic metastases.
424
WAXMAN, WAXMAN, AND ALINOVI
FIG. 1. Bisected cervical stump showing almost complete tumor replacement of the walls and a vague outline of the endocervical lumen. The exocervix is relatively spared.
DISCUSSION
Contrary to previous opinions, the incidence of cervical cancer developing in a posthysterectomy stump has not been found to be increased, but is the same as that arising in the intact uterus [4]. Squamous cell carcinoma constitutes the majority (about 90%) of tumors originating from the cervical stump; adenocarcinoma is second in frequency (42 out of 402 cases or about 10%) [5-71. Only solitary cases of leiomyosarcoma [7,8], basal cell carcinoma [5], and mixed mesodermal tumor [5] have been mentioned in the literature, the latter without any documentation. The uterine cervix is an unusual site for a primary MMMT, and we could find only a handful of documented cases [l-3]. While MMMT of the ovary [9] and fallopian tube [IO] is distinct and easily diagnosable as primary tumors in these locations, caution is necessary in accepting the cervix as a primary site. Since the uterine body is a much more frequent seat of origin of this neoplasm than is the cervix, and there is often a tendency for the MMMT of the corpus to involve the cervix secondarily, as a polypoid intraluminal extension or as a mural infiltrate, a tumor involving both the body and cervix is presumed to have
CASE REPORTS
425
426
WAXMAN,
WAXMAN,
AND
ALINOVI
r;X . t%j
X
CASE REPORTS
427
F3~. 4. (A). An area showing papillary serous adenocarcinoma with psammoma bodie s. 0) Spi ndle cell sarcoma next to adenocarcinoma, the latter resembling endometrioid carcinoma. H&E (4 x 100; (B) x 100.
428
WAXMAN,
WAXMAN,
AND ALINOVI
originated in the body. A similar problem arises at times in distinguishing primary endocervical adenocarcinoma from a secondary cervical involvement of endometrial cancer [Ill. Abel1 and Ramirez [2] described criteria for accepting a uterine sarcoma or carcinosarcoma as a primary tumor of the cervix: (a) absence of involvement of the corpus in the hysterectomy specimen; (b) no enlargement of the corpus and no tumor in the endometrial curretings material; and (c) tumor of the cervical stump, and absence of similar tumor in the supracervical hysterectomy specimen. Our case fulfills the last criterion. Although material from the hysterectomy specimen was not available for review, the time interval of 37 years that had elapsed since the supracervical hysterectomy was performed, assures us that the patient did not have MMMT of the uterine body. To ensure that the tumor has indeed arisen from the cervical tissue, no endometrium should be found in the cervical stump. This consideration is important as reflected in the finding of residual endometrial tissue in as many as 19 (9%) out of 216 cervical stumps in one series [7]. It is likely, therefore, that some supracervical hysterectomies have been incomplete in that the lowermost part of the corpus with its endometrial lining remained in situ with the cervix, and that MMMT or other tumors can develop from such residual endometrium. Other possible sources of endometrium in the cervix include irregular extension of the endometrial lining into the endocervix, endometrial metaplasia of the endocervical crypt lining, and endometriosis. Careful examination failed to disclose any evidence of endometrial tissue in our case. The cervix may be a site of primary MMMT without necessarily harboring endometrial tissue. Since endocervical mucosa is Mtillerian-derived, its neoplastic potential is similar to that of the endometrium, the histogenetic considerations of the cervical tumor closely paralleling those pertaining to the origin of MMMT in the uterine corpus [12]. REFERENCES 1. Sternberg, W. H., Clark, W. H., and Smith, R. C. Malignant mixed mtillerian tumor. (Mixed mesodermal tumor of the uterus). A study of twenty-one cases, Cancer 7, 704-724 (1954). 2. Abell, M. R., and Ramirez, G. J. A. Sarcomas and carcinosarcomas of the uterine cervix, Cancer 31, 1176-l 192 (1973). 3. Hall-Craggs, M., Toker, C., and Nedwich, A. Carcinosarcoma of the uterine cervix: A light and electron microscopic study, Cancer 48, 161-169 (1981). 4. Dunn, M. R. Prevalence of carcinoma arising in cervical stumps, Amer. /. Obsret. Gynecol. 82, 83-87 (1961). 5. Creadick, R. N. Carcinoma of the cervical stump, Amer. J. Obsret. Gynecol. 75, 565-574 (1958). 6. Wolff, J. P., Lacour, J., Chassagne, D., Berend, M. Cancer of the cervical stump. A study of 173 patients, Obstet. Gynecol. 39, lo-16 (1972). 7. Pratt, J. H., Jefferies, J. A. The retained cervical stump. A 25-year experience, Obsfer. Gynecol. 48, 711-715 (1976).
8. Sturdy, D. E. Leiomyosarcoma of cervical stump following subtotal hysterectomy, Brir. J. Surg. 46, 369-370 (1959). 9. Hemandez, W., DiSaia, P. J., Morrow, C. P., and Townsend, D. E. Mixed mesodermal sarcoma of the ovary, Obster. Gynecol. 49, 59s-63s (1977). 10. Manes, J. L., and Taylor, H. B. Carcinosarcoma and mixed miillerian tumors of the fallopian tube. Report of four cases, Cancer 38, 1687-1693 (1976). 11. Haggard, J. L., Cotten, N., Dougherty, C. M., and Mickal, A. Primary adenocarcinoma of the cervix, Obstet. Gynecol. 24, 183-193 (1964). 12. Waxman, M., Boyce, J. G., Macasaet, M. M., and Lu, T. Concurrence of malignant and benign heterologous mixed tumors of the uterus, Amer. J. Clin. Puthol. 77, 631-637 (1982).