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Malignant struma ovarii
GYNECOLOGIC ONCOLOGY32, 224-227 (1989)
Malignant Struma Ovarii NORMAN G. ROSENBLUM, PH.D., M.D., *'1 VIRGINIA A. L I V o L s I , M.D.,? PAMELA R. EDMONDS, M . D . , t AND JOHN J. MIKUTA, M.D.* *Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, and the ?Section of Surgical Pathology, Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania 19104 Received July 6, 1987
Malignant struma ovarii is a very rare tumor, with considerable disagreement concerning the necessary histologic features for malignancy. The prognosis with patients with a malignant struma ovarii is difficult to make because of inadequate follow-up of the reported cases and long clinical courses. In most cases the patients responded well to surgical treatment but sometimes patients have died from malignant struma ovarii, in particular, if there is metastasis. There is evidence that radioactive iodine is effective in treating metastatic struma. The present case reports the use of intraperitoneal chromic phosphate for metastatic intraperitoneal disease, with thyroid suppression. Long-term follow-up will be necessary to properly evaluate this therapy. Prophylactic administration of thyroid hormone should be considered in cases of malignant struma ovarii. © 1989AcademicPress,Inc. INTRODUCTION Malignant struma ovarii is a term which has been used in the literature to describe histologically malignant tumor, arising in association with thyroid tissue in teratomas of the ovary. The diagnosis is difficult and there is no agreement in the literature concerning the necessary histologic features for malignancy. Although 5 to 10% of struma have been stated to be malignant and approximately 50 cases of malignant struma have been reported; most of the latter were diagnosed on histologic grounds alone. The approximately 20 cases that belong in the clinically malignant category have been associated with peritoneal implants, intraabdominal spread or metastasis in lymph nodes, bone, liver, lung, mediastinum, and brain. Because of the rarity of this tumor, there is considerable confusion concerning proper management [1]. Presented is a case of papillary thyroid carcinoma arising within a struma ovarii; with metastasis to the contralateral :Fo whom correspondence should be addressed at Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, The Lankenau Hospital, Philadelphia, PA 19151. 224 0090-8258/89 $1.50 Copyright © 1989 by Academic Press, Inc. All rights of reproduction in any form reserved.
ovary, and malignant peritoneal cytology. This was treated successfully with surgery, intraperitoneal chromic phosphate 32p, and thyroid suppression. A review of the literature is also presented. CASEREPORT A.M.Z. is a 37-year-old, white female, gravida 3, para 2, SAB 1, whose last menstrual period was December 14, 1983. In October of 1983 the patient had a sudden onset of left lower quadrant pelvic pain. On evaluation the patient was found to have a tender left adnexal mass; this was confirmed by ultrasound. The patient was taken to the operating room with a diagnosis of torsion of a left adnexal mass. At laparotomy there was no free fluid, no evidence of intraperitoneal disease, and what appeared to be a torsion of a dermoid cyst. The contralateral ovary appeared grossly normal. The patient underwent a left salpingo-oophorectomy and her postoperative recovery was unremarkable. On pathologic review of this left adnexal mass the patient appeared to have a struma ovarii with a focus of papillary adenocarcinoma within the struma ovarii. The patient was referred to the Hospital of the University of Pennsylvania for further evaluation. Workup was negative; thyroid scan and thyroid function tests were normal. The patient was taken to the operating room on January 3, 1984, where she underwent an examination under anesthesia, cystoscopy, proctoscopy, exploratory laparotomy, peritoneal washings, total abdominal hysterectomy, right salpingo-oophorectomy, omentectomy, common iliac and paraaortic lymphadenectomy, and multiple peritoneal biopsies. At laparotomy there was no free fluid and no gross evidence of metastatic disease. H e r postoperative course was essentially unremarkable and she was discharged on the ninth postoperative day. The final pathology demonstrated two subcapsular metastasis of papillary ad-
MALIGNANT STRUMA OVARII
enocarcinoma to the right ovary consistent with the previous primary tumor. In addition, the peritoneal washings from the left hemidiaphragm and left paracolic gutter contained clusters of cells consistent with metastatic papillary adenocarcinoma. The patient subsequently received 15 mCi of intraperitoneal chromic phosphate 32p and was placed on oral thyroid suppression and estrogen-progesterone replacement. The patient remains clinically free of disease 4½ years after initial diagnosis. PATHOLOGY The first specimen, which was a tube and ovary, consisted of an 11 x 8.5 x 6-cm cystic ovarian mass with a smooth outer surface. The cyst appeared to be occupied by hairs, yellow gritty sebaceous material, and a portion of tooth. In one area of the cyst the lesion consisted of a soft, friable tissue with occasional cystic spaces filled with mucoid material. Microscopically, the gross impression was supported by the presence of a cystic teratoma containing skin, nerve, cartilage, and upper respiratory epithelium as well as benign thyroid tissue. Large portions of the thyroid tissue were associated with a papillary tumor containing numerous psammoma bodies. The tumor was composed predominantly of papillae as well as a few follicular structures, and these were lined by epithelium containing enlarged overlapping nuclei with clear nucleoplasm (Fig. 1), The tumor did not extend to the surface of the ovary which was intact. The second operative procedure yielded numerous abdominal biopsies as well as the uterus and right ovary and tube. Of significance was the finding of two tiny subcapsular tumor metastases in the right ovary. These were predominantly follicular in pattern but contained the same nuclei as in the primary lesion. In addition, immunoperoxidase staining for thyroglobulin was markedly positive within the epithelium of these follicular structures as well as in the centrally contained colloid (Fig. 2) [2]. Peritoneal fluid cytology showed papillary clusters consistent with papillary carcinoma in the peritoneal fluid. DISCUSSION Struma ovarii is a teratoma in which thyroid tissue is present exclusively or forms a grossly recognizable component of a more complex teratoma [3]. Struma ovarii was first described by Von Kalden in 1895, and Gottschalk in 1899 [4]. It comprises less than 2% of ovarian teratomas with peak frequency during the fifth decade of life. Bilaterality is present in 6% of cases, the left ovary is more frequently involved, and less than 5% of struma ovarii have thyroid function [3]. Theoretically, any type of malignant tumor may arise in one of the elements of a benign cystic teratoma. Ma-
225
lignant change of a struma ovarii has been reported in approximately 5% of cases. It is characterized by embryonal, follicular, and papillary patterns similar to those in malignant tumors of the thyroid gland [1]. Over 50 cases of malignant struma ovarii have been reported but in 60% of these the diagnosis has been based solely on the histologic features of the neoplasm and there has been no other evidence of malignancy [4,5]. In some of these cases the true diagnosis was strumal carcinoid rather than a thyroid adenocarcinoma, which appears to be clinically benign and more frequent [6]. The true incidence of carcinoma arising in struma ovarii is probably well below 1%, with a 15-year review from the state of Colorado revealing a frequency of 0.3% [7]. As stated above, malignant degeneration of a struma ovarii is very rare. Rotton and Tovell reported one case of their own and 16 cases from the literature [8]. GonzalesAngulo et al. observed 2 cases and in a review of the literature they revealed 37 previously reported cases [5]. Pardo-Mindan and Vazquez reported 1 case of malignant struma ovarii with metastasis and they noted 45 cases of histologically malignant struma ovarii that had been reported; but only 17 were associated with metastasis [9]. Pardo-Mindan et al. believe that struma ovarii is only malignant if the tumor shows clearly invasive signs and/or metastatis while nuclear alterations are not enough to diagnose malignancy. We agree with this interpretation. Follicular carcinomas are the most commonly reported, whereas, papillary carcinomas are seldom described. From the pathologic point of view, sometimes predominantly follicular or mixed papillary-follicular carcinomas may have been diagnosed as pure follicular carcinomas. Five cases of papillary carcinoma have been described and the present case represents the sixth papillary carcinoma arising in a struma [7,9-11]. Metastatic spread mostly hematogenous to liver, mediastinum, and other organs have been noted [10,11]. The evidence of malignancy in these cases seem beyond doubt. Sometimes these metastasis may become apparent 10 to 20 years after surgery. The last previously reported case of malignant struma was from Gould et al. in a 15year review of cystic teratomas in the state of Colorado [7]. A women developed a papillary adenocarcinoma in a struma ovarii found at laparotomy for a pelvic mass. A left salpingo-oophorectomy was performed and the patient has subsequently become pregnant. Because of the rarity of malignant struma ovarii, there is considerable confusion concerning management. Therapy has ranged from radical surgery (TAH BSO) and chemotherapy, with and without thyroidectomy, to conservative surgery with preservation of reproductive function, when no evidence of disease progression is noted at the time of surgery. Recurrent or metastatic struma ovarii has been successively treated with radioiodine. Radioisotope uptake in metastatic struma ovarii may be
FIG. 1. Papillary tumor in ovary is seen. Note presence of fibrous cores of tissue lined by neoplastic cells which contain large overlapping "ground-glass" nuclei characteristic of thyroid papillary carcinoma (hematoxylin-eosin, x 300).
FIG. 2. Metastasis to right ovary is shown. Note ovarian stroma on right and darkly staining tumor cells on left. Immunoperoxidase staining localized thyroglobnlin to these tumor nests (immunoperoxidase thyroglobulin-hematoxylin counterstain, × 350). 226
MALIGNANT STRUMA OVARII
enhanced by thyroidectomy followed by complete ablation of any remaining cervical tissue with radioiodine [11]. Kempers e t al. described five malignant tumors of lowgrade malignancy treated with ~31Iand carried a favorable prognosis [11]. Survival of 8. 15. 16, and 20 years, respectively, were reported. One woman died 7½ years postoperatively with liver and bone metastasis. PardonMindan et al. reported a case of metastatic struma ovarii with intraabdominal metastasis treated with TAH BSO and chemotherapy [6]. The patient developed progressive disease, was treated with palliative irradiation, and died 3 years after initial diagnosis prior to initiation of ~3~I irradiation. The patient in the present report was treated with TAH BSO and intraabdominal chromic phosphate. and continues on thyroid suppression. The only other patient treated in the literature with intraperitoneal therapy was a patient described by Woodruff et al. with evidence of metastasis to the liver El0]. The patient received intraperitoneal radioactive gold but developed a subsequent recurrent pelvic mass which was treated with external cobalt therapy.
227
2. LiVolsi, V. A., Logerfo, P., and Feind, C. R. Thyroglobulin in struma ovarii, J. Surg. Res. 25, 12-14 (1978). 3. Scully, R. E. Recent progress in ovarian cancer, Hum. Pathol. 1, 73-79 (1970). 4. Yannopoulos, D., Yannopoulos, K., and Ossowski, R. Malignant struma ovarii, in Pathology annual (S. C. Sommer, Ed.), AppletonCentury-Crofts, New York, pp. 403-413 (1976). 5. Gonzalez-Angulo, A., Kaufman, R. H., Braungardt, C. D., Chapman, F. C., and Hinshaw, A. S. Adenocarcinoma of thyroid arising in struma ovarii (malignant struma ovarii): A report of two cases and review of the literature, Obstet. Gynecol, 21, 567-576 (1963). 6. Robby, S. J., and Scully, R. E. Strumal carcinoid of the ovary: An analysis of 50 cases of a distinctive tumor composed of thyroid tissue and carcinoid, Cancer 46, 2019-2034 (1980). 7. Gould, S. F., Lopez, R. L., and Speers, W. C. Malignant struma ovarii: A"case report and literature review, J. Reprod. Med. 28, 415-419 (1983). 8. Rotton, W. N., and Tovell, H. M. M. Malignant struma ovarii: A case report, Bull. Sloane Hosp. Women 2, 121-127 (1956). 9. Pardo-Mindan, F. J., and Vasquez, J. J. Malignant struma ovarii: Light and electron microscopic study, Cancer 51, 337-343 (1983).
REFERENCES
10. Woodruff, J. D., Rauh, J. T., and Markley, R. L. Ovarian struma, Obstet. Gynecol. 27, 194-202 (1966).
1. Fox. H.. and Langley, F. A. Tumours o f the ovary; monophyletic germ cell tumours. Heinemann Medical Books. London. Chap. 16. pp. 231-248 c 1976).
11. Kempers, R. D., Dockerty, M. B., Hoffman, D. L., and Bartholomen, L. G. Struma ovarii: Ascitic, hyperthyroid, and asymptomatic syndromes, Ann. Intern. Med. 72, 883-893 (1970).
Malignant Struma Ovarii NORMAN G. ROSENBLUM, PH.D., M.D., *'1 VIRGINIA A. L I V o L s I , M.D.,? PAMELA R. EDMONDS, M . D . , t AND JOHN J. MIKUTA, M.D.* *Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, and the ?Section of Surgical Pathology, Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania 19104 Received July 6, 1987
Malignant struma ovarii is a very rare tumor, with considerable disagreement concerning the necessary histologic features for malignancy. The prognosis with patients with a malignant struma ovarii is difficult to make because of inadequate follow-up of the reported cases and long clinical courses. In most cases the patients responded well to surgical treatment but sometimes patients have died from malignant struma ovarii, in particular, if there is metastasis. There is evidence that radioactive iodine is effective in treating metastatic struma. The present case reports the use of intraperitoneal chromic phosphate for metastatic intraperitoneal disease, with thyroid suppression. Long-term follow-up will be necessary to properly evaluate this therapy. Prophylactic administration of thyroid hormone should be considered in cases of malignant struma ovarii. © 1989AcademicPress,Inc. INTRODUCTION Malignant struma ovarii is a term which has been used in the literature to describe histologically malignant tumor, arising in association with thyroid tissue in teratomas of the ovary. The diagnosis is difficult and there is no agreement in the literature concerning the necessary histologic features for malignancy. Although 5 to 10% of struma have been stated to be malignant and approximately 50 cases of malignant struma have been reported; most of the latter were diagnosed on histologic grounds alone. The approximately 20 cases that belong in the clinically malignant category have been associated with peritoneal implants, intraabdominal spread or metastasis in lymph nodes, bone, liver, lung, mediastinum, and brain. Because of the rarity of this tumor, there is considerable confusion concerning proper management [1]. Presented is a case of papillary thyroid carcinoma arising within a struma ovarii; with metastasis to the contralateral :Fo whom correspondence should be addressed at Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, The Lankenau Hospital, Philadelphia, PA 19151. 224 0090-8258/89 $1.50 Copyright © 1989 by Academic Press, Inc. All rights of reproduction in any form reserved.
ovary, and malignant peritoneal cytology. This was treated successfully with surgery, intraperitoneal chromic phosphate 32p, and thyroid suppression. A review of the literature is also presented. CASEREPORT A.M.Z. is a 37-year-old, white female, gravida 3, para 2, SAB 1, whose last menstrual period was December 14, 1983. In October of 1983 the patient had a sudden onset of left lower quadrant pelvic pain. On evaluation the patient was found to have a tender left adnexal mass; this was confirmed by ultrasound. The patient was taken to the operating room with a diagnosis of torsion of a left adnexal mass. At laparotomy there was no free fluid, no evidence of intraperitoneal disease, and what appeared to be a torsion of a dermoid cyst. The contralateral ovary appeared grossly normal. The patient underwent a left salpingo-oophorectomy and her postoperative recovery was unremarkable. On pathologic review of this left adnexal mass the patient appeared to have a struma ovarii with a focus of papillary adenocarcinoma within the struma ovarii. The patient was referred to the Hospital of the University of Pennsylvania for further evaluation. Workup was negative; thyroid scan and thyroid function tests were normal. The patient was taken to the operating room on January 3, 1984, where she underwent an examination under anesthesia, cystoscopy, proctoscopy, exploratory laparotomy, peritoneal washings, total abdominal hysterectomy, right salpingo-oophorectomy, omentectomy, common iliac and paraaortic lymphadenectomy, and multiple peritoneal biopsies. At laparotomy there was no free fluid and no gross evidence of metastatic disease. H e r postoperative course was essentially unremarkable and she was discharged on the ninth postoperative day. The final pathology demonstrated two subcapsular metastasis of papillary ad-
MALIGNANT STRUMA OVARII
enocarcinoma to the right ovary consistent with the previous primary tumor. In addition, the peritoneal washings from the left hemidiaphragm and left paracolic gutter contained clusters of cells consistent with metastatic papillary adenocarcinoma. The patient subsequently received 15 mCi of intraperitoneal chromic phosphate 32p and was placed on oral thyroid suppression and estrogen-progesterone replacement. The patient remains clinically free of disease 4½ years after initial diagnosis. PATHOLOGY The first specimen, which was a tube and ovary, consisted of an 11 x 8.5 x 6-cm cystic ovarian mass with a smooth outer surface. The cyst appeared to be occupied by hairs, yellow gritty sebaceous material, and a portion of tooth. In one area of the cyst the lesion consisted of a soft, friable tissue with occasional cystic spaces filled with mucoid material. Microscopically, the gross impression was supported by the presence of a cystic teratoma containing skin, nerve, cartilage, and upper respiratory epithelium as well as benign thyroid tissue. Large portions of the thyroid tissue were associated with a papillary tumor containing numerous psammoma bodies. The tumor was composed predominantly of papillae as well as a few follicular structures, and these were lined by epithelium containing enlarged overlapping nuclei with clear nucleoplasm (Fig. 1), The tumor did not extend to the surface of the ovary which was intact. The second operative procedure yielded numerous abdominal biopsies as well as the uterus and right ovary and tube. Of significance was the finding of two tiny subcapsular tumor metastases in the right ovary. These were predominantly follicular in pattern but contained the same nuclei as in the primary lesion. In addition, immunoperoxidase staining for thyroglobulin was markedly positive within the epithelium of these follicular structures as well as in the centrally contained colloid (Fig. 2) [2]. Peritoneal fluid cytology showed papillary clusters consistent with papillary carcinoma in the peritoneal fluid. DISCUSSION Struma ovarii is a teratoma in which thyroid tissue is present exclusively or forms a grossly recognizable component of a more complex teratoma [3]. Struma ovarii was first described by Von Kalden in 1895, and Gottschalk in 1899 [4]. It comprises less than 2% of ovarian teratomas with peak frequency during the fifth decade of life. Bilaterality is present in 6% of cases, the left ovary is more frequently involved, and less than 5% of struma ovarii have thyroid function [3]. Theoretically, any type of malignant tumor may arise in one of the elements of a benign cystic teratoma. Ma-
225
lignant change of a struma ovarii has been reported in approximately 5% of cases. It is characterized by embryonal, follicular, and papillary patterns similar to those in malignant tumors of the thyroid gland [1]. Over 50 cases of malignant struma ovarii have been reported but in 60% of these the diagnosis has been based solely on the histologic features of the neoplasm and there has been no other evidence of malignancy [4,5]. In some of these cases the true diagnosis was strumal carcinoid rather than a thyroid adenocarcinoma, which appears to be clinically benign and more frequent [6]. The true incidence of carcinoma arising in struma ovarii is probably well below 1%, with a 15-year review from the state of Colorado revealing a frequency of 0.3% [7]. As stated above, malignant degeneration of a struma ovarii is very rare. Rotton and Tovell reported one case of their own and 16 cases from the literature [8]. GonzalesAngulo et al. observed 2 cases and in a review of the literature they revealed 37 previously reported cases [5]. Pardo-Mindan and Vazquez reported 1 case of malignant struma ovarii with metastasis and they noted 45 cases of histologically malignant struma ovarii that had been reported; but only 17 were associated with metastasis [9]. Pardo-Mindan et al. believe that struma ovarii is only malignant if the tumor shows clearly invasive signs and/or metastatis while nuclear alterations are not enough to diagnose malignancy. We agree with this interpretation. Follicular carcinomas are the most commonly reported, whereas, papillary carcinomas are seldom described. From the pathologic point of view, sometimes predominantly follicular or mixed papillary-follicular carcinomas may have been diagnosed as pure follicular carcinomas. Five cases of papillary carcinoma have been described and the present case represents the sixth papillary carcinoma arising in a struma [7,9-11]. Metastatic spread mostly hematogenous to liver, mediastinum, and other organs have been noted [10,11]. The evidence of malignancy in these cases seem beyond doubt. Sometimes these metastasis may become apparent 10 to 20 years after surgery. The last previously reported case of malignant struma was from Gould et al. in a 15year review of cystic teratomas in the state of Colorado [7]. A women developed a papillary adenocarcinoma in a struma ovarii found at laparotomy for a pelvic mass. A left salpingo-oophorectomy was performed and the patient has subsequently become pregnant. Because of the rarity of malignant struma ovarii, there is considerable confusion concerning management. Therapy has ranged from radical surgery (TAH BSO) and chemotherapy, with and without thyroidectomy, to conservative surgery with preservation of reproductive function, when no evidence of disease progression is noted at the time of surgery. Recurrent or metastatic struma ovarii has been successively treated with radioiodine. Radioisotope uptake in metastatic struma ovarii may be
FIG. 1. Papillary tumor in ovary is seen. Note presence of fibrous cores of tissue lined by neoplastic cells which contain large overlapping "ground-glass" nuclei characteristic of thyroid papillary carcinoma (hematoxylin-eosin, x 300).
FIG. 2. Metastasis to right ovary is shown. Note ovarian stroma on right and darkly staining tumor cells on left. Immunoperoxidase staining localized thyroglobnlin to these tumor nests (immunoperoxidase thyroglobulin-hematoxylin counterstain, × 350). 226
MALIGNANT STRUMA OVARII
enhanced by thyroidectomy followed by complete ablation of any remaining cervical tissue with radioiodine [11]. Kempers e t al. described five malignant tumors of lowgrade malignancy treated with ~31Iand carried a favorable prognosis [11]. Survival of 8. 15. 16, and 20 years, respectively, were reported. One woman died 7½ years postoperatively with liver and bone metastasis. PardonMindan et al. reported a case of metastatic struma ovarii with intraabdominal metastasis treated with TAH BSO and chemotherapy [6]. The patient developed progressive disease, was treated with palliative irradiation, and died 3 years after initial diagnosis prior to initiation of ~3~I irradiation. The patient in the present report was treated with TAH BSO and intraabdominal chromic phosphate. and continues on thyroid suppression. The only other patient treated in the literature with intraperitoneal therapy was a patient described by Woodruff et al. with evidence of metastasis to the liver El0]. The patient received intraperitoneal radioactive gold but developed a subsequent recurrent pelvic mass which was treated with external cobalt therapy.
227
2. LiVolsi, V. A., Logerfo, P., and Feind, C. R. Thyroglobulin in struma ovarii, J. Surg. Res. 25, 12-14 (1978). 3. Scully, R. E. Recent progress in ovarian cancer, Hum. Pathol. 1, 73-79 (1970). 4. Yannopoulos, D., Yannopoulos, K., and Ossowski, R. Malignant struma ovarii, in Pathology annual (S. C. Sommer, Ed.), AppletonCentury-Crofts, New York, pp. 403-413 (1976). 5. Gonzalez-Angulo, A., Kaufman, R. H., Braungardt, C. D., Chapman, F. C., and Hinshaw, A. S. Adenocarcinoma of thyroid arising in struma ovarii (malignant struma ovarii): A report of two cases and review of the literature, Obstet. Gynecol, 21, 567-576 (1963). 6. Robby, S. J., and Scully, R. E. Strumal carcinoid of the ovary: An analysis of 50 cases of a distinctive tumor composed of thyroid tissue and carcinoid, Cancer 46, 2019-2034 (1980). 7. Gould, S. F., Lopez, R. L., and Speers, W. C. Malignant struma ovarii: A"case report and literature review, J. Reprod. Med. 28, 415-419 (1983). 8. Rotton, W. N., and Tovell, H. M. M. Malignant struma ovarii: A case report, Bull. Sloane Hosp. Women 2, 121-127 (1956). 9. Pardo-Mindan, F. J., and Vasquez, J. J. Malignant struma ovarii: Light and electron microscopic study, Cancer 51, 337-343 (1983).
REFERENCES
10. Woodruff, J. D., Rauh, J. T., and Markley, R. L. Ovarian struma, Obstet. Gynecol. 27, 194-202 (1966).
1. Fox. H.. and Langley, F. A. Tumours o f the ovary; monophyletic germ cell tumours. Heinemann Medical Books. London. Chap. 16. pp. 231-248 c 1976).
11. Kempers, R. D., Dockerty, M. B., Hoffman, D. L., and Bartholomen, L. G. Struma ovarii: Ascitic, hyperthyroid, and asymptomatic syndromes, Ann. Intern. Med. 72, 883-893 (1970).