GYNECOLOGIC
ONCOLOGY
46,
246-250 (1992)
CASE REPORT Small Cell Carcinoma with Neurosecretory Granules Arising in an Ovarian Dermoid Cyst DAVID HORNG-CHYI CHANG, M.D.,* SWEI HSUEH, M.D.,* AND YUNG-KUEI Departments of Obstetrics and Gynecology
and *Pathology,
Chang Gung Memorial
Hospital,
SOONG,
M.D.
Chang Gung Medical College, Taipei, Taiwan
Received November 25, 1991
A rare small cell carcinoma with neurosecretory granules arising in an ovarian dermoid cyst with 7 years survival after conservative surgery and adjuvant chemotherapy with cisplatin, adriamycin, and cyclophosphamide is described. Light microscopy showed the typical uniformly small cells with hyperchromic nuclei and scanty basophilic cytoplasm within the mature cystic teratoma. Although none of the immunohistochemical stains were reactive, electron microscopy demonstrated the membrane-bound neurosecretory granules in sometumor cells. The related literature is reviewed and the issues concerning treatment options in this unusual malignancy are discussed. 0 WEhdemic PEW, IN.
INTRODUCTION Mature cystic teratoma is a common neoplasm in the second and third decades of life, and accounts for about lo-20% of all ovarian tumors. However, it rarely undergoes malignant transformation, with a reported incidence of l-2% [l-4]. The vast majority of transformations are squamous cell carcinomas [l-lo], followed less frequently by adenocarcinoma and other even rarer malignancies, such as melanoma [ll-141 or malignant neural tumor [15]. It is exceptional to encounter a small cell undifferentiated carcinoma arising in a dermoid cyst, as described in this case. Malignancy developing in one of the elements of a benign cystic teratoma is thought to be associated with a poor prognosis [2,4,6]. We present a successfully treated case of small cell carcinoma with neurosecretory granules ’ To whom correspondence and reprint requests should be addressed at Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Chang Gung Medical College, 199, Tun-Hwa North Road, Taipei, 10591, Taiwan. Fax: 886-3-3285294.
arising in a mature cystic teratoma, with the patient currently alive without evidence of recurrence, 7 years after conservative surgery and adjuvant chemotherapy. CASE REPORT A 22-year-old, gravida 0 para 0, female patient suffered from periodic low abdominal pain for 2 months. She herself palpated a rapidly growing tumor mass. She visited our outpatient clinic where a huge pelvic mass with firm consistency was found by rectal examination. Gynecological ultrasound revealed bilateral adnexal masses,measuring 18.0 x 15.2 and 5.6 x 8.0 cm, respectively. There was scanty ascites and the outlines of both masses were irregular. She was admitted for further evaluation and management under the impression of possible ovarian malignancy. Her past history was reviewed and no major systemic medical diseases were found. She was a virgin with irregular menstruation but the menstrual amount and duration were quite normal. She had an appendectomy at 12 years of age due to acute appendicitis. Physical examination revealed a normal female with a firm, fixed massup to the level of umbilicus without shifting dullness. The external genitalia were normal in appearance. An intravenous pyelography showed a huge pelvic mass with nodular and patchy calcified densities compressing the lower parts of both ureters with slight stasis of contrast medium in the collecting system. The mass was compatible with an ovarian tumor, such as dermoid cyst or cystadenoma. Barium enema revealed upward and lateral displacement of the sigmoid colon and backward displacement of the rectum. Numerous calcified nodules could be seen in the pelvic cavity. Liver-spleen scan showed no evidence of a space-occupying lesion. The
246 0090-8258/92 $4.00
Copyright 0 1992by AcademicPress,Inc. All rights of reproductionin any form reserved.
CASE REPORT
electrocardiogram was normal. Gynecologic sonography revealed a heteroechogenic mass, about 18.0 x 15.2 cm in size, with irregular contours in the left adnexa and a cystic mass with solid parts measuring about 5.6 x 8.0 cm in the right adnexa. The tumor markers including (Yfetoprotein, carcinoembryonic antigen, and P-HCG were all within normal range. Exploratory laparotomy was undertaken through a midline incision extending above the umbilicus. A huge wellencapsulated mass measuring 20 x 18 x 16 cm arising from the left ovary was found. The right adnexa also had a cystic mass with smooth capsule, measuring 6 x 5 x 4 cm. There was no ascites. No tumor implants were found in the peritoneal cavity. A left salpingo-oophorectomy and enucleation of the right ovarian tumor were done. Both were sent for frozen section. The pathology showed a small cell undifferentiated carcinoma arising in the left ovarian dermoid cyst. The right ovarian tumor was a benign cystic teratoma. Peritoneal washings were sent for cytologic examination.
247
After recovery, eight courses of combination chemotherapy with cisplatin (60 mg/m’), adriamycin (50 mg/m2), and cyclophosphamide (500 mg/m’) were given in 3-week intervals. After completion of chemotherapy, oncological investigations including chest X ray, abdominopelvic computerized axial tomography, intravenous pyelography, and barium enema all revealed no evidence of recurrence. The complete blood count and blood chemistries were all normal. Regular menstruation had resumed soon after the cessation of chemotherapy. She was followed-up regularly on an outpatient basis. She married 5 years after completion of chemotherapy. An ovulatory pattern of basal body temperature has been noted. Hysterosalpingogram revealed a patent right fallopian tube and normal uterine cavity contour. The left tube was absent due to the previous operation. However, she has not become pregnant, possibly due to the severe oligospermia of her husband. She is currently well, without evidence of recurrence, 7 years after the primary diagnosis.
FIG. 1. The mature squamous cell epithelium lining the cystic area is covered with laminated keratin. In the solid area, there are sheets of undifferentiated small tumor cells (H&E, x34).
248
HORNG-CHYI
CHANG, HSUEH. AND SOONG
PATHOLOGIC FINDINGS Gross description. The specimens submitted consisted of a left ovarian tumor which measured 20 x 18 x 16 cm and a right ovarian tumor measuring 5.5 x 4.5 x 4.5 cm. Both were well encapsulated. Upon opening the tumors, both were found to contain hair, greasy materials, and cartilaginous parts. Microscopic @dings. The left ovarian tumor was a teratoma with mature elements of skin, skin appendages, areas of calcification, soft tissue, and epithelium-lined spaces. There were solid masses within the teratoma which were composed of solid sheets of undifferentiated cells (Fig. 1). The undifferentiated tumor cells were mostly small with round to oval or spindle-shaped hyperchromatic nuclei and scanty basophilic cytoplasm. Multiple foci of necrosis and a high mitotic rate were prominent features (Fig. 2). Studies with special stains for the presence of cytoplasmic granules (Grimelius and Masson-Fontana silver stain) were negative. Immunohistochemically, the tumor cells were negative for Vimentin (Biogenex, 1: loO), S-100 (Dako, 1: 250), epithelial membrane antigen (Dako, 1: NO), synaptophysin (Boehringer, 1:2), chromogranin (Biogenex, 1: lOO),
AEl/AE3 (Hybritech, 1: 50), and neuron-specific enolase (Dako , 1: 100). Electron microscopy, however, revealed membrane-bound neurosecretory granules in some tumor cells (Fig. 3) and confirmed the diagnosis of small cell undifferentiated carcinoma. Structures resembling the fallopian tube were seen nearby. The right ovarian tumor was a benign cystic teratoma with elements of skin, skin appendages, soft tissue, brain, and cartilage. The pelvic soft tissue had marked mesothelial cell hyperplasia but was benign. The washing cytology was negative for malignancy. DISCUSSION Mature teratomas are usually cystic and contain mature tissues of ectodermal, mesodermal, and endodermal origin [16]. Although the majority of dermoid cysts are benign, the possibility of malignant transformation should always be kept in mind to ensure the careful histologic examination of the entire neoplasm, especially the solid areas, lest the concomitant malignancy be overlooked. Malignant change theoretically may arise from all elements of benign teratoma. Almost every conceivable carcinoma and sarcoma derived from mature human tissues
FIG. 2. High-power view showing the aggregates of small cells with hyperchromic round and spindle-shaped nuclei and scanty cytoplasm. Mitoses and focal necrosis are seen (H&E, x 340).
CASE REPORT
FIG. 3.
249
Electron microscopy shows the membrane-bound neurosecretory granules (arrow) in some tumor cells (x24,000)
has been reported [l-19]. The ectoderm is thought to be the commonest to undergo malignant change [3]. Squamous cell carcinoma is by far the most common malignancy encountered [l-lo] and accounts for 75 [4] to 88% [6] in large reported series. Adenocarcinoma and carcinoid are much less frequent [4,6,9]. Other rarer cases reported included choriocarcinoma [6], leiomyosarcoma [9], spindle-cell sarcomas [9,18], malignant melanomas [ 1l-141, multiple neuroectodermal tumors [ 151, and mutinous ovarian carcinoma with “sarcoma-like” mural nodules [ 171. Undifferentiated or anaplastic carcinomas arising in ovarian dermoid cyst are extremely rare, with only three cases reported in the collective series of Curling et al. [2] and Stamp et al. [4]. All patients died within 12 months of diagnosis. There were no detailed immunohistochemical nor ultrastructural descriptions in these cases. Our patient may be the first such case to have a detailed study with a panel of immunohistochemical stains and ultrastructural studies. Though negative for all of the immuno-
histochemical stains, the neoplasm did demonstrate membrane-bound neurosecretory granules in some tumor cells. The average age of the patients with malignant degeneration in ovarian dermoid cysts tended to be higher (4556 years of age [3,4,6]) than patients with benign cystic teratomas, which have a peak incidence during the second and third decades of life [3]. It is noteworthy that those reported cases with undifferentiated or anaplastic carcinoma in dermoid cysts were younger, 30 to 33 years of age [2,4]. The present case was even younger, 22 years old at the time of diagnosis. Since malignant dermoid cysts tend to spread, the survival rate in reported cases is very poor [4-61. The corrected 5-year survival among patients with adequate follow-up was 15% in Peterson’s series [6]. However, patients without apparent metastases or rupture of the cyst had a corrected 5-year survival of 75%. Among patients with adenocarcinoma, sarcoma, malignant melanoma [ 1l-141, or anaplastic carcinoma, no 5-year survival has been reported [4,6]. The single most important prog-
250
HORNG-CHYI
CHANG, HSUEH, AND SOONG
2. Curling, 0. M., Potsides, P. N., and Hudson, C. N. Malignant nosticator in patient survival is confinement of the neochange in benign cystic teratoma of the ovary, Br. J. Obstet. Gyplasm within the ovarian tunica. Extracapsular extension naecol. 86, 399-402 (1979). and high degree of anaplasia convey a grave prognosis, 3. Ribeiro, G., Hughesdon, P., and Wiltshaw, E. Squamous carcinoma with most patients dying of disease within 2 years of arising in dermoid cyst and associated with hypercalcemia: A clinprimary diagnosis [l]. The long-term survival without reicopathologic study of six cases, Gynecol. Oncol. 29, 222-230 currence in our case may be the result of the neoplasm (1988). being encapsulated and removed intact without rupture 4. Stamp,G. W. H., and McConnell, E. M. Malignancy arising in at operation. cystic ovarian teratomas. A report of 24 cases, Br. J. Obstet. Gynaecof. 90, 671-675 (1983). The rarity of cases with malignant degeneration within an ovarian dermoid cyst precludes a final conclusion about 5. Selim, M. A., Razi, A., and Lankerani, M. Squamous cell carcinoma arising from ovarian benign cystic teratoma, Am. 1. Obstet. the optimal management of these kinds of neoplasm. The Gynecol. #O(6), 790-792 (1984). main therapeutic approach of patients with a high-grade 6. Peterson, W. F. Malignant degeneration of benign cystic teratomas malignant tumor arising from a dermoid cyst remains surof the ovary. A collective review of the literature, Obstet. Gynecol. gical, although the extent of surgery has varied from cysSurv. 12, 793-830 (1957). tectomy to total abdominal hysterectomy and bilateral 7. Peterson, W. F., Frevost, E. C., Edmunds, F. T., Hundley, J. M., salpingo-oophorectomy [18]. When the lesion occurs in a Jr., and Morris, F. K. Epidermoid carcinoma arising in a benign woman late in, or past, the reproductive years, total recystic teratoma. A report of 15 cases, Am. J. Obstet. Gynecol. 71(l), 173-189 (1956). moval of the pelvic organs would seem to be the pro8. Tang, L. C. H., So, K. F., and Wong, R. L. C. Squamous cell cedure of choice [6]. Many of these neoplasms, however, carcinoma in a cystic teratoma of the ovary, Arch. Gynecol. 236, are discovered during the early or middle reproductive 55-59 (1984). years, in which the preservation of fertility is of ultimate 9. Kelley, R. R., and Scully, R. E. Cancer developing in dermoid importance. Thus, conservative measures should be critcysts of the ovary. A report of 8 cases, including a carcinoid and ically considered, if possible, even when malignant transa leiomyosarcoma, Cancer 14(5), 989-1000 (1961). formation has occurred. Preservation of the contralateral 10. Gabrielli, M., Melissa& M., Caltabiano, M., and Mansani, F. E. Squamous cell carcinoma arising in a dermoid cyst of the ovary. ovary and the uterus seems justifiable in younger women Clinical and pathological report of a case, Eur. .l, Gynaecol. Oncol. with stage I neoplasms [8], as in our patient. 2, 110-112 (1984). The role of chemotherapy or radiotherapy remains un11. Gregg, R. H. Primary malignant melanoma arising in an ovarian clear. None of the earlier reports support the use of radermoid cyst. Am. J. Obstet. Gynecol. 143(l), 25-28 (1982). diotherapy in these neoplasms. Neither postoperative ra- 12. Tham, K. T., Ma, P. H., and Kung, T. M. Malignant melanoma diation nor adjuvant chemotherapy in patients with in an ovarian cystic teratoma. Hum. Pathol. l2(6), 577-579 (1981). extracapsular disease appears to improve the survival time 13. Tsukamoto, N., Matsukuma, K., Matsumura, M., Kamura, T., Matsuyama, T., and Kinjo, M. Primary malignant melanoma arising [1,4]. The role or optimal combination of adjuvant chemin a cystic teratoma of the ovary, Gynecol. Oncol. 23, 395-400 otherapy is still unknown, because of the limited number (1986). in each reported series [2,3]. Stage I patients have a 14. Ueda, Y., Kimura, A., Kawahara, E., Kitagawa, H., and Nakchance of survival with surgery alone [3]. Although our anishi, I. Malignant melanoma arising in a dermoid cyst of the case had a stage IA tumor, the use of chemotherapy was ovary, Cancer 67, 3141-3145 (1991). in the hope of improving survival, in view of the grave 15. Olah, K. S., Needham, P. G., and Jones, B. Multiple neuroectodermal tumors arising in a mature cystic teratoma of the ovary. outcome in reported patients [2,4]. However, whether Case report, Gynecol. Oncol. 34, 222-225 (1989). there was additive benefit remains speculative. Further 16. Christopherson, W. A., and Councell, R. B. Malignant degenerstudies are needed before a definitive conclusion can be ation of a mature ovarian teratoma, J. Gynecol. Obstet. 30, 379drawn. 384 (1989).
REFERENCES 1. Krumerman, M. S., and Chung, A. Squamous carcinoma arising in benign cystic teratoma of the ovary. A report of four cases and review of the literature, Cancer 39, 1237-1242 (1977).
17. Escoffery, C. T., and Kulkami, S. K. An unusual malignancy arising in a benign cystic teratoma of the ovary, Aust. N.Z. J. Obstet. Gynecol. 29, 85-87 (1989). 18. Richardson, G., Robertson, D. I., O’Connor, M. E., Nation, J. G., and Stuart, G. C. E. Malignant transformation occurring in mature cystic teratomas of the ovary. CJS 33(6), 499-503 (1990).
ONCOLOGY
46,
246-250 (1992)
CASE REPORT Small Cell Carcinoma with Neurosecretory Granules Arising in an Ovarian Dermoid Cyst DAVID HORNG-CHYI CHANG, M.D.,* SWEI HSUEH, M.D.,* AND YUNG-KUEI Departments of Obstetrics and Gynecology
and *Pathology,
Chang Gung Memorial
Hospital,
SOONG,
M.D.
Chang Gung Medical College, Taipei, Taiwan
Received November 25, 1991
A rare small cell carcinoma with neurosecretory granules arising in an ovarian dermoid cyst with 7 years survival after conservative surgery and adjuvant chemotherapy with cisplatin, adriamycin, and cyclophosphamide is described. Light microscopy showed the typical uniformly small cells with hyperchromic nuclei and scanty basophilic cytoplasm within the mature cystic teratoma. Although none of the immunohistochemical stains were reactive, electron microscopy demonstrated the membrane-bound neurosecretory granules in sometumor cells. The related literature is reviewed and the issues concerning treatment options in this unusual malignancy are discussed. 0 WEhdemic PEW, IN.
INTRODUCTION Mature cystic teratoma is a common neoplasm in the second and third decades of life, and accounts for about lo-20% of all ovarian tumors. However, it rarely undergoes malignant transformation, with a reported incidence of l-2% [l-4]. The vast majority of transformations are squamous cell carcinomas [l-lo], followed less frequently by adenocarcinoma and other even rarer malignancies, such as melanoma [ll-141 or malignant neural tumor [15]. It is exceptional to encounter a small cell undifferentiated carcinoma arising in a dermoid cyst, as described in this case. Malignancy developing in one of the elements of a benign cystic teratoma is thought to be associated with a poor prognosis [2,4,6]. We present a successfully treated case of small cell carcinoma with neurosecretory granules ’ To whom correspondence and reprint requests should be addressed at Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Chang Gung Medical College, 199, Tun-Hwa North Road, Taipei, 10591, Taiwan. Fax: 886-3-3285294.
arising in a mature cystic teratoma, with the patient currently alive without evidence of recurrence, 7 years after conservative surgery and adjuvant chemotherapy. CASE REPORT A 22-year-old, gravida 0 para 0, female patient suffered from periodic low abdominal pain for 2 months. She herself palpated a rapidly growing tumor mass. She visited our outpatient clinic where a huge pelvic mass with firm consistency was found by rectal examination. Gynecological ultrasound revealed bilateral adnexal masses,measuring 18.0 x 15.2 and 5.6 x 8.0 cm, respectively. There was scanty ascites and the outlines of both masses were irregular. She was admitted for further evaluation and management under the impression of possible ovarian malignancy. Her past history was reviewed and no major systemic medical diseases were found. She was a virgin with irregular menstruation but the menstrual amount and duration were quite normal. She had an appendectomy at 12 years of age due to acute appendicitis. Physical examination revealed a normal female with a firm, fixed massup to the level of umbilicus without shifting dullness. The external genitalia were normal in appearance. An intravenous pyelography showed a huge pelvic mass with nodular and patchy calcified densities compressing the lower parts of both ureters with slight stasis of contrast medium in the collecting system. The mass was compatible with an ovarian tumor, such as dermoid cyst or cystadenoma. Barium enema revealed upward and lateral displacement of the sigmoid colon and backward displacement of the rectum. Numerous calcified nodules could be seen in the pelvic cavity. Liver-spleen scan showed no evidence of a space-occupying lesion. The
246 0090-8258/92 $4.00
Copyright 0 1992by AcademicPress,Inc. All rights of reproductionin any form reserved.
CASE REPORT
electrocardiogram was normal. Gynecologic sonography revealed a heteroechogenic mass, about 18.0 x 15.2 cm in size, with irregular contours in the left adnexa and a cystic mass with solid parts measuring about 5.6 x 8.0 cm in the right adnexa. The tumor markers including (Yfetoprotein, carcinoembryonic antigen, and P-HCG were all within normal range. Exploratory laparotomy was undertaken through a midline incision extending above the umbilicus. A huge wellencapsulated mass measuring 20 x 18 x 16 cm arising from the left ovary was found. The right adnexa also had a cystic mass with smooth capsule, measuring 6 x 5 x 4 cm. There was no ascites. No tumor implants were found in the peritoneal cavity. A left salpingo-oophorectomy and enucleation of the right ovarian tumor were done. Both were sent for frozen section. The pathology showed a small cell undifferentiated carcinoma arising in the left ovarian dermoid cyst. The right ovarian tumor was a benign cystic teratoma. Peritoneal washings were sent for cytologic examination.
247
After recovery, eight courses of combination chemotherapy with cisplatin (60 mg/m’), adriamycin (50 mg/m2), and cyclophosphamide (500 mg/m’) were given in 3-week intervals. After completion of chemotherapy, oncological investigations including chest X ray, abdominopelvic computerized axial tomography, intravenous pyelography, and barium enema all revealed no evidence of recurrence. The complete blood count and blood chemistries were all normal. Regular menstruation had resumed soon after the cessation of chemotherapy. She was followed-up regularly on an outpatient basis. She married 5 years after completion of chemotherapy. An ovulatory pattern of basal body temperature has been noted. Hysterosalpingogram revealed a patent right fallopian tube and normal uterine cavity contour. The left tube was absent due to the previous operation. However, she has not become pregnant, possibly due to the severe oligospermia of her husband. She is currently well, without evidence of recurrence, 7 years after the primary diagnosis.
FIG. 1. The mature squamous cell epithelium lining the cystic area is covered with laminated keratin. In the solid area, there are sheets of undifferentiated small tumor cells (H&E, x34).
248
HORNG-CHYI
CHANG, HSUEH. AND SOONG
PATHOLOGIC FINDINGS Gross description. The specimens submitted consisted of a left ovarian tumor which measured 20 x 18 x 16 cm and a right ovarian tumor measuring 5.5 x 4.5 x 4.5 cm. Both were well encapsulated. Upon opening the tumors, both were found to contain hair, greasy materials, and cartilaginous parts. Microscopic @dings. The left ovarian tumor was a teratoma with mature elements of skin, skin appendages, areas of calcification, soft tissue, and epithelium-lined spaces. There were solid masses within the teratoma which were composed of solid sheets of undifferentiated cells (Fig. 1). The undifferentiated tumor cells were mostly small with round to oval or spindle-shaped hyperchromatic nuclei and scanty basophilic cytoplasm. Multiple foci of necrosis and a high mitotic rate were prominent features (Fig. 2). Studies with special stains for the presence of cytoplasmic granules (Grimelius and Masson-Fontana silver stain) were negative. Immunohistochemically, the tumor cells were negative for Vimentin (Biogenex, 1: loO), S-100 (Dako, 1: 250), epithelial membrane antigen (Dako, 1: NO), synaptophysin (Boehringer, 1:2), chromogranin (Biogenex, 1: lOO),
AEl/AE3 (Hybritech, 1: 50), and neuron-specific enolase (Dako , 1: 100). Electron microscopy, however, revealed membrane-bound neurosecretory granules in some tumor cells (Fig. 3) and confirmed the diagnosis of small cell undifferentiated carcinoma. Structures resembling the fallopian tube were seen nearby. The right ovarian tumor was a benign cystic teratoma with elements of skin, skin appendages, soft tissue, brain, and cartilage. The pelvic soft tissue had marked mesothelial cell hyperplasia but was benign. The washing cytology was negative for malignancy. DISCUSSION Mature teratomas are usually cystic and contain mature tissues of ectodermal, mesodermal, and endodermal origin [16]. Although the majority of dermoid cysts are benign, the possibility of malignant transformation should always be kept in mind to ensure the careful histologic examination of the entire neoplasm, especially the solid areas, lest the concomitant malignancy be overlooked. Malignant change theoretically may arise from all elements of benign teratoma. Almost every conceivable carcinoma and sarcoma derived from mature human tissues
FIG. 2. High-power view showing the aggregates of small cells with hyperchromic round and spindle-shaped nuclei and scanty cytoplasm. Mitoses and focal necrosis are seen (H&E, x 340).
CASE REPORT
FIG. 3.
249
Electron microscopy shows the membrane-bound neurosecretory granules (arrow) in some tumor cells (x24,000)
has been reported [l-19]. The ectoderm is thought to be the commonest to undergo malignant change [3]. Squamous cell carcinoma is by far the most common malignancy encountered [l-lo] and accounts for 75 [4] to 88% [6] in large reported series. Adenocarcinoma and carcinoid are much less frequent [4,6,9]. Other rarer cases reported included choriocarcinoma [6], leiomyosarcoma [9], spindle-cell sarcomas [9,18], malignant melanomas [ 1l-141, multiple neuroectodermal tumors [ 151, and mutinous ovarian carcinoma with “sarcoma-like” mural nodules [ 171. Undifferentiated or anaplastic carcinomas arising in ovarian dermoid cyst are extremely rare, with only three cases reported in the collective series of Curling et al. [2] and Stamp et al. [4]. All patients died within 12 months of diagnosis. There were no detailed immunohistochemical nor ultrastructural descriptions in these cases. Our patient may be the first such case to have a detailed study with a panel of immunohistochemical stains and ultrastructural studies. Though negative for all of the immuno-
histochemical stains, the neoplasm did demonstrate membrane-bound neurosecretory granules in some tumor cells. The average age of the patients with malignant degeneration in ovarian dermoid cysts tended to be higher (4556 years of age [3,4,6]) than patients with benign cystic teratomas, which have a peak incidence during the second and third decades of life [3]. It is noteworthy that those reported cases with undifferentiated or anaplastic carcinoma in dermoid cysts were younger, 30 to 33 years of age [2,4]. The present case was even younger, 22 years old at the time of diagnosis. Since malignant dermoid cysts tend to spread, the survival rate in reported cases is very poor [4-61. The corrected 5-year survival among patients with adequate follow-up was 15% in Peterson’s series [6]. However, patients without apparent metastases or rupture of the cyst had a corrected 5-year survival of 75%. Among patients with adenocarcinoma, sarcoma, malignant melanoma [ 1l-141, or anaplastic carcinoma, no 5-year survival has been reported [4,6]. The single most important prog-
250
HORNG-CHYI
CHANG, HSUEH, AND SOONG
2. Curling, 0. M., Potsides, P. N., and Hudson, C. N. Malignant nosticator in patient survival is confinement of the neochange in benign cystic teratoma of the ovary, Br. J. Obstet. Gyplasm within the ovarian tunica. Extracapsular extension naecol. 86, 399-402 (1979). and high degree of anaplasia convey a grave prognosis, 3. Ribeiro, G., Hughesdon, P., and Wiltshaw, E. Squamous carcinoma with most patients dying of disease within 2 years of arising in dermoid cyst and associated with hypercalcemia: A clinprimary diagnosis [l]. The long-term survival without reicopathologic study of six cases, Gynecol. Oncol. 29, 222-230 currence in our case may be the result of the neoplasm (1988). being encapsulated and removed intact without rupture 4. Stamp,G. W. H., and McConnell, E. M. Malignancy arising in at operation. cystic ovarian teratomas. A report of 24 cases, Br. J. Obstet. Gynaecof. 90, 671-675 (1983). The rarity of cases with malignant degeneration within an ovarian dermoid cyst precludes a final conclusion about 5. Selim, M. A., Razi, A., and Lankerani, M. Squamous cell carcinoma arising from ovarian benign cystic teratoma, Am. 1. Obstet. the optimal management of these kinds of neoplasm. The Gynecol. #O(6), 790-792 (1984). main therapeutic approach of patients with a high-grade 6. Peterson, W. F. Malignant degeneration of benign cystic teratomas malignant tumor arising from a dermoid cyst remains surof the ovary. A collective review of the literature, Obstet. Gynecol. gical, although the extent of surgery has varied from cysSurv. 12, 793-830 (1957). tectomy to total abdominal hysterectomy and bilateral 7. Peterson, W. F., Frevost, E. C., Edmunds, F. T., Hundley, J. M., salpingo-oophorectomy [18]. When the lesion occurs in a Jr., and Morris, F. K. Epidermoid carcinoma arising in a benign woman late in, or past, the reproductive years, total recystic teratoma. A report of 15 cases, Am. J. Obstet. Gynecol. 71(l), 173-189 (1956). moval of the pelvic organs would seem to be the pro8. Tang, L. C. H., So, K. F., and Wong, R. L. C. Squamous cell cedure of choice [6]. Many of these neoplasms, however, carcinoma in a cystic teratoma of the ovary, Arch. Gynecol. 236, are discovered during the early or middle reproductive 55-59 (1984). years, in which the preservation of fertility is of ultimate 9. Kelley, R. R., and Scully, R. E. Cancer developing in dermoid importance. Thus, conservative measures should be critcysts of the ovary. A report of 8 cases, including a carcinoid and ically considered, if possible, even when malignant transa leiomyosarcoma, Cancer 14(5), 989-1000 (1961). formation has occurred. Preservation of the contralateral 10. Gabrielli, M., Melissa& M., Caltabiano, M., and Mansani, F. E. Squamous cell carcinoma arising in a dermoid cyst of the ovary. ovary and the uterus seems justifiable in younger women Clinical and pathological report of a case, Eur. .l, Gynaecol. Oncol. with stage I neoplasms [8], as in our patient. 2, 110-112 (1984). The role of chemotherapy or radiotherapy remains un11. Gregg, R. H. Primary malignant melanoma arising in an ovarian clear. None of the earlier reports support the use of radermoid cyst. Am. J. Obstet. Gynecol. 143(l), 25-28 (1982). diotherapy in these neoplasms. Neither postoperative ra- 12. Tham, K. T., Ma, P. H., and Kung, T. M. Malignant melanoma diation nor adjuvant chemotherapy in patients with in an ovarian cystic teratoma. Hum. Pathol. l2(6), 577-579 (1981). extracapsular disease appears to improve the survival time 13. Tsukamoto, N., Matsukuma, K., Matsumura, M., Kamura, T., Matsuyama, T., and Kinjo, M. Primary malignant melanoma arising [1,4]. The role or optimal combination of adjuvant chemin a cystic teratoma of the ovary, Gynecol. Oncol. 23, 395-400 otherapy is still unknown, because of the limited number (1986). in each reported series [2,3]. Stage I patients have a 14. Ueda, Y., Kimura, A., Kawahara, E., Kitagawa, H., and Nakchance of survival with surgery alone [3]. Although our anishi, I. Malignant melanoma arising in a dermoid cyst of the case had a stage IA tumor, the use of chemotherapy was ovary, Cancer 67, 3141-3145 (1991). in the hope of improving survival, in view of the grave 15. Olah, K. S., Needham, P. G., and Jones, B. Multiple neuroectodermal tumors arising in a mature cystic teratoma of the ovary. outcome in reported patients [2,4]. However, whether Case report, Gynecol. Oncol. 34, 222-225 (1989). there was additive benefit remains speculative. Further 16. Christopherson, W. A., and Councell, R. B. Malignant degenerstudies are needed before a definitive conclusion can be ation of a mature ovarian teratoma, J. Gynecol. Obstet. 30, 379drawn. 384 (1989).
REFERENCES 1. Krumerman, M. S., and Chung, A. Squamous carcinoma arising in benign cystic teratoma of the ovary. A report of four cases and review of the literature, Cancer 39, 1237-1242 (1977).
17. Escoffery, C. T., and Kulkami, S. K. An unusual malignancy arising in a benign cystic teratoma of the ovary, Aust. N.Z. J. Obstet. Gynecol. 29, 85-87 (1989). 18. Richardson, G., Robertson, D. I., O’Connor, M. E., Nation, J. G., and Stuart, G. C. E. Malignant transformation occurring in mature cystic teratomas of the ovary. CJS 33(6), 499-503 (1990).
