Clinicopathologic study of squamous cell carcinoma of the ovary

GYNECOLOGIC

ONCOLOGY

34,

75-79 (1989)

Clinicopathologic Study of Squamous Cell Carcinoma of the Ovary MASAMICHI KASHIMURA, M.D.,* MICHIOKI SHINOHARA, M.D.,* TOSHIO HIRAKAWA, TOSHIHARU KAMURA, M.D.,? AND KEITA MATSUKUMA, M.D.-t

M.D.,?

*Department of Obstetrics and Gynecology, University of Occupational and Environmental Health, and TDepartmentof Obstetricsand Gynecology, Kyushu University Faculty of Medicine, Japan Received February 2, 1988

Clinicopathologic study was performed on 10 squamous cell carcinomas of the ovary. All four patients with stage II or III lesions had deteriorated within 1 year after the operation, and four of six patients with stage I lesions had survived over 5 years. Clinical findings of the patients with ovarian SCC, including age, chief complaint, clinical stage, and outcome of the patients, were similar to those of common epithelial cancer. The effectiveness of chemotherapy was not shown in this study. Histopathologic study revealed that squamous cell carcinoma may arise not only from epidermis, but also from squamous metaplastic epithelium of respiratory gland. 0 1989 ~cadunic FW, w.

histogenesis of ovarian SCC. Histological evaluations were made on several findings, such as presence of squamous metaplasia, coexistence of benign cystic teratoma, and transition between malignant and benign squamous epithelium. Clinical findings of the patients with ovarian SCC were also investigated, including age, chief complaint, clinical stage, treatment, and outcome of the patients. RESULTS

1. Pathologic findings of SCC of the ovary. The tumor originated from the right side in six cases and the left side in four cases. The size of the tumor ranged from 7 cm to 22 cm in the longest diameter. All but two had a cystic tumor and contained a fatty material intermixed with hairs (Fig. 1). The remaining two cases showed a solid mass associated with severe peritoneal dissemination (Cases 3 and 5). All tumors had a partly solid area in the cystic wall, and squamous cell carcinoma was found in the solid area. A cut surface of this solid part revealed a gray, lees-like appearance with necrosis. Histologic findings of ovarian SCC are summarized in Table 1. Squamous metaplasia of glandular epithelium was noted in five cases, and these glandular epithelium consisted of respiratory gland in Cases 5, 6, and 7. Cystic teratoma was associated in seven cases. Atypia of the MATERIALS AND METHODS epidermis of benign cystic teratoma was observed in four The pathologic files of all ovarian neoplasms were re- cases of seven tumors. However, definite transition between squamous cell carcinoma and epidermis of cystic viewed during 23 years from 1961 to 1983 at Kyushu University Hospital and during 3 years from 1984 to 1986 teratoma was recognized in only one case (Case 8) (Fig. 2). In two other cases (Cases 6 and 7), squamous cell at University Hospital of Occupational and Environmental Health. A total of 1023 ovarian neoplasms, con- carcinoma was adjacent to the respiratory glandular epsisting of 676 benign neoplasms and 347 malignant neo- ithelium (Fig. 3). In the remaining four cases, transition plasms including borderline lesions, were listed in these between squamous cell carcinoma and benign cystic terfiles. Ten cases of ovarian SCC were collected, and all atoma was not obscure due to necrosis. Six tumors conhistologic slides were reevaluated in order to clarify the sisted of pure squamous cell carcinoma, but the remain-

Squamous cell carcinoma (SCC) is a rare entity in the malignant ovarian neoplasms. Several histogeneses of ovarian SCC were presented in past literature [l-14]. While many ovarian SCC developed in benign cystic teratoma, malignant transformation of Brenner tumor or endometrioid cystadenoma was also presented in the histogenesis of ovarian SCC. Some authors showed an unfavorable prognosis in the patients with ovarian SCC [10,15]. However, this observation was not fully accepted because the number of materials was limited. The purpose of this study is not only to clarify the histogenesis of ovarian SCC, but also to evaluate the clinical findings in the patients with ovarian SCC.

75 0090~8258/89$1.50

Copyright 0 1989 by Academic Press, Inc. All rights of reproduction in any form reserved.

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ET AL.

cobalt and 2000 mg of cyclophosphamide in Case 1,720O rad of cobalt and 4000 mg of cyclophosphamide in Case 2, 6000 rad of cobalt and 3000 mg of radium in Case 3, and 150 mg of bleomycin in Case 5). However, all patients with stage II and III lesions had deteriorated within 1 year after the operation. In the patients with stage I lesions, four underwent 150 mCi of intraperitoneal radiogold and two underwent a chemotherapy with 200 mg per day of oral 5-fluorouracil (Case 9) and 10 mg per day of oral melphalan (Case 10) after complete resection of the lesions. All four patients with intraperitoneal radiogold were alive over 5 years after surgery, and the remaining two patients with chemotherapy died within 1 year after surgery. DISCUSSION Benign cystic teratoma is a most frequent entity in the ovarian neoplasms, and malignant transformation of cys9). tic teratoma was relatively well documented in past literature [1,6,14-191. Peterson collected 147 malignancies ing four (Cases 2, 4, 5, and 7) had a component partly of 8038 cystic teratomas, and we thereafter collected 52 formed of adenosquamous cell carcinoma. The above malignancies of 2176 cystic teratomas in past literature. histologic findings suggest that the SCC of the ovary The frequency of malignant change of cystic teratoma originates not only from epidermis, but also from squa- ranged from 1.4 to 4.8% with an average of 2.4%. Squamous metaplastic epithelium of respiratory gland. mous cell carcinoma was the most frequent neoplasm in 2. Clinical findings. Clinical findings of the patients the malignancy of cystic teratoma (Table 3). By which pathogenesis does squamous cell carcinoma with ovarian SCC are summarized in Table 2. The age arise in the ovarian neoplasm? Many authors believe that of the patients ranged from 42 to 78 years, with an avthe SCC of the ovary may arise from epidermal tissue erage of 60.6 years. The chief complaints were lower of benign cystic teratoma [3,4,10-141. It has also been abdominal pain, abdominal mass, and fever. Eight pasuggested that the ovarian SCC may originate from Brentients had stage I and II lesions, and two had stage III ner tumor or endometrioid cystadenoma [5,7,9]. Other lesions. authors suggest that the ovarian SCC may arise from Several types of treatments were done for the patients metaplastic epithelium [2,6,8]. However, most authors with ovarian SCC. Complete resection of the tumor was do not show the distinct evidence of pathogenesis in not performed in the patients with stage II and III lesions. ovarian SCC. Several pathologic findings, such as stratThese patients underwent an external irradiation and intraperitoneal chemotherapy after surgery (5200 rad of ification of epidermis, cellular atypia, and presence of squamous metaplasia, were investigated in cases of 150 benign cystic teratomas. While squamous metaplasia of TABLE 1 the respiratory gland was frequently observed (5%), no Histologic Findings of XC of the Ovary evidence of direct malignant transformation of epidermis Squamous atypia was obtained by the review of benign cystic teratoma. Squamous of cystic Cystic Although finding cancer next to an epithelium doesn’t Case metaplasia teratoma teratoma Transition mean it arose from an epithelium, two cases showed the possibility of malignant transformation from metaplastic + epithelium of respiratory gland in present series. The question is raised whether clinical findings of ovar+ ian SCC are similar to those of common epithelial cancer or not. Takashina et al. [15] found that the average age Respiratory gland Respiratory gland of patients with cystic teratoma, malignant ovarian tu8 + + mor, and malignant cystic teratoma was 32.7, 44.8, and 9 + ? 50.8 years, respectively. They concluded that the age of 10 + ? patients with malignant cystic teratoma was higher than FIG. 1. The inner surface of ovarian SCC reveals a Rokitansky’s protuberance with hairs and a solid mass of carcinoma (arrow) (Case

+ --

7 -: +

:?

SQUAMOUS CELL CARCINOMA

OF THE OVARY

77

FIG. 2. Squamous cell carcinoma is next to the epidermis of benign cystic teratoma (Case 8, H.E., 100x).

that: of oti rer malignant tumors. On the contrary, Peterson et al. [193 revealed that the average age of 147 patien .ts wit1h malignant cystic teratoma was 45.4 years, this being younger than that of common epithelial cancer (55 years) [20]. However, the age distribution is considerec1 to be different in each histologic component of malign ant cy stic teratoma. It is still controversial whether the age 0Ir ovarian SCC is higher than that of common .helial cancer or not.

Most frequent presenting symptoms of ovarian cancer are an abdominal fullness, mass, and pain. Nine patients in our series presented the same symptoms, while 1:wo complained of fever which was considered to result fr ‘orn the necrosis of tumor. However, the symptom of fever was not frequently observed in the patients with ovarian SCC presented in past literature. FIG0 clinical stage and outcome of 95 ovarian Scc collected in past literature is shown in Table 4. Sij cty-

FIG. 3. Squamous cell carcinoma is next to the respiratory glandular epithelium of benign cystic teratoma (Case 6, H.E., 100x).

KASHIMURA

78

ET AL.

TABLE 2 Clinical Findings of SCC of the Ovary Case

Age

Complaint

Side

Longest diameter

Stage

1 2 3 4 5 6 7 8 9 10

66 61 42 50 60 74 49 62 64 78

Pain Pain Fever Pain Pain & mass Mass Pain Pain Mass Pain & fever

Right Right Left Right Left Right Right Right Left Left

15 cm 7 cm Unknown 13 cm 22 cm 20 cm 20 cm 16 cm 20 cm 21 cm

IIb IIb III Ia III Ia Ia Ia Ia Ia

Treatment RSO BSO LSO BSO LSO RSO BSO BSO BSO BSO

+ + + + + + + + + +

radiation + chemotherapy TAH + radiation + chemotherapy radiation TAH + radiogold TAH + chemotherapy radiogold radiogold TAH + radiogold TAH + chemotherapy TAH + chemotherapy

Outcome DOD DOD DOD Alive DOD Alive Alive DOD DOD DOD

(4 months) (9 months) (8 months) (14 years) (4 months) (11 years) (6 years) (10 years) (7 months) (4 months)

Note. RSO, LSO, BSO, right, left, bilateral salpingo-oophorectomy; TAH, total abdominal hysterectomy; DOD, died of disease; ( ), time after the operation. a Died of leukemia.

six percent of the patients had stage I and II lesions, and 34% had stage III and IV lesions. The stage distribution was similar to that of common epithelial cancer

POI. Management of malignant ovarian tumor is based on surgery followed by chemotherapy or radiotherapy. The effectiveness of chemotherapy or radiotherapy for ovarian SCC cannot be found in this series or past literature. Squamous cell carcinoma is originally a sensitive neoplasm for irradiation. In the present series, four patients TABLE 3 Malignant Change of Cystic Teratoma Author

Year

Marcial-Rojas Kelley caruso Krumerman Amerigo Yakushiji Takashina Present series

1958 1961 1971 1977 1978 1981 1981 1989

Number of cystic teratoma 268 462 305 143 349 145 184 320 2176

Total

Malignancy 6 8 10 4 5 7 4 8”

(2.2%) (1.7%) (3.3%) (2.8%) (1.4%) (4.8%) (2.2%) (2.5%)

52 (2.4%)

Squamous cell carcinoma 5 5 5 4 5 7 4 7

(1.9%) (1.1%) (1.6%) (2.8%) (1.4%) (4.8%) (2.2%) (2.2%)

42 (1.9%)

’ Including one case of adenocarcinoma.

TABLE 4 FIG0 Stage and Outcome of Ovarian SCC Number Stage I Stage II Stage III Stage IV

37 26 26 6 95

(39%) (27%) (27%) ( 7%)

2-Year survival

j-Year survival

22133 (67%) 10/22 (45%) 3/26 (12%) O/6 ( 0%)

15/30 5/20 3/26 O/6

(50%) (25%) (12%) ( 0%)

35/87 (40%)

23182 (28%)

with stage I lesions underwent an intraperitoneal radiogold after complete resection of the lesion, and were alive over 5 years after the operation. However, the effectiveness of radiogold for ovarian XC was not accepted due to limited materials. Some authors [10,1.5] presented the poor prognosis of ovarian SCC. However, Peterson et al. [I91 showed a 75% 5-year survival rate in the patients with unruptured tumor and without distant metastasis in the collected literature. We also collected 87 cases of ovarian SCC in which FIG0 clinical stage was precisely documented and over 2-years follow-up was performed (Table 4). The 5year survival rate of ovarian SCC was slightly lower than that of common epithelial cancer [20]. Consequently, it is still controversial whether the prognosis of patients with ovarian SCC is poor or not. REFERENCES 1. Amerigo, .I., Nogales, F. F., Jr., Fernandez-Sanz, J., Oliva, H., and Velasco, A. Squamous cell neoplasms arising from ovarian benign cystic teratoma, Gynecol. 0~01. 8, 277-283 (1979). 2. Fox, H. Bronchial carcinoma in an ovarian cystic teratoma (dermoid), J. Clin. Pnthol. 18, 164-168 (1965). 3. Gabrielli, M., Melissari, M., Caltabiano, M., and Mansani, F. E. Squamous cell carcinoma arising in a dermoid cyst of the ovary, Clinical and pathological report of a case, Eur. J. Gynaecol. Oncol. 2, 110-112 (1984). 4. Hanada, M., Tsujimura, T., and Shimizu, H. Multiple malignancies (squamous cell carcinoma and sarcoma) arising in a dermoid cyst of the ovary, Acta Pathol. Japan 31, 681-688 (1981). 5. Idelson, M. G. Malignancy in Brenner tumors of the ovary, with comments on histogenesis and possible estrogen production, Obstet. Gynecol. Surv. 18, 246-267 (1963). 6. 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). 7. Lele, S. B., Piver, M. S., Barlow, J. J., and Tsukada, Y. Case

SQUAMOUS CELL CARCINOMA report-Squamous cell carcinoma arising in ovarian endomefriosis, Gynecol. Oncol. 6, 290-293 (1978). 8. Maeyama, M., Miyazaki, K., Oka, M., Higashi, K., Nakayama, M., and Iwamasa, T. Malignant degeneration of benign cystic teratoma of the bilateral ovaries, Acru Obstet. Gynaecol. Japan 35, 331-334 (1983). 9. McCullough, K., Froats, E. R., and Falk, H. C. Epidermoid carcinoma arising in an endometrial cyst of the ovary, Arch. Pathol. 41, 335-337 (1946). 10. Peterson, W. F., and Prevost, E. C., Edmunds, F. T., Hundley, J. M., Jr., and Morris, F. K. Epidermoid carcinoma arising in a benign cystic teratoma-A report of 15 cases, Amer. J. Obstet. Gynecol. 71, 173-189 (1956). 11. Selim, M. A., Razi, A., and Lankerani, M. Squamous cell carcinoma arising from ovarian benign cystic teratoma, Amer. J. Obstet. Gynecol. 150, 790-792 (1984). 12. Shingleton, H. M., Middleton, F. F., and Gore, H. Squamous cell carcinoma in the ovary, Amer. J. Obstet. Gynecof. 120, 556-560 (1974). 13. Sivanesaratnam, V., and Lee, T. T. Squamous cell carcinoma arising in a dermoid cyst of the ovary, Aust. NZ J. Obstet. Gynaecol. 12, 269-272 (1972). 14. Yakushiji, M., Nishida, T., Sugiyama, T., Mitamura, T., Natsuaki,

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Y., Nagano, H., Tsunawaki, A., and Kato, T. Malignant degeneration of benign cystic teratomas of the ovary, Acta Obstet. Gynaecol. Japan 33, 1095-1098 (1981). 15. Takashina, T., Tamura, H., Kunizaki, A., Ito, E., Watanabe, W., Hori, Y., Hashimoto, M., Kawase, N., and Adachi, K. Malignant change of dermoid cyst, Obstet. Gynecol. Ther. 43,346-357 (1981) (in Japanese). 16 Caruso, P. A., Marsh, M. R., Minkowitz, S., and Karten, G. An intense clinicopathologic study of 305 teratomas of the ovary, Cancer 27, 343-348 (1971). 17. Kelley, R. R., and Scully, R. E. Cancer developing in dermoid cysts of the ovary-A report of 8 cases, including a carcinoid and a leiomyosarcoma, Cancer 14, 989-1000 (1961). 18. Martial-Rojas, R. A., and Medina, R. Cystic teratomas of the ovary-A clinical and pathological analysis of two hundred sixtyeight tumors, Arch. Pathol. 66, 577-589 (1958). 19. Peterson, W. F. Malignant degeneration of benign cystic teratomas of the ovary. A collective review of the literature, Obstet. Gynecol. Surv. 12, 793-830 (1957). 20. Swenerton, K. D., Hislop, T. G., Spinelli, J., LeRiche, J. C., Yang, N., and Boyes, D. A. Ovarian carcinoma: A multivariate analysis of prognostic factors, Obstet. Gynecol. 65,264-270 (1985).