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Squamous cell neoplasms arising from ovarian benign cystic teratoma
GYNECOLOGIC
ONCOLOGY
8, 277-283 (1979)
Squamous
Cell Neoplasms Arising from Ovarian Benign Cystic Teratoma
JOAQUIN AM~RIGO, FRANCISCO F. NOGALES, JR.,’ JUAN FERNANDEZ~ANZ, HORACIO OLIVA, AND ANGEL VELASCO Department
of Pathology, Madrid.
Seville Medical Scguridad Swiul.
School, Burgos,
Uni\~rrsidad Spain
Autcjnomn
Received October 9. 1978 Five cases of squamous cell carcinoma arising in benign cystic teratomas found in postmenopausal patients are presented. Exhaustive tissue sampling is necessary for the discovering of malignancy in this age group. Carcinogenesis is thought to be due to local factors. Carcinoma in situ of a bowenoid type was present in two cases, which suggests an epidermal origin; however, squamous clear-cell carcinoma similar to that of the respiratory tract was also found. Prognostic parameters are discussed attaching special importance to tumor stage and the presence of tumor emboli in capsular vessels.
INTRODUCTION
As all the tissues of the benign cystic teratoma (BCT) are present in the well-differentiated, adult form, they lack the intrinsic malignant potential found in the embryonic tissues of the immature teratoma; however, they are subjected to the malignant degeneration common to all mature tissues. This phenomenon is seen to occur in 1.8% of BCTs [I]. As there is a great variety of tissues reproduced in this type of tumor, it can be said that almost any type of neoplasm may arise in BCT. Cases have been described of carcinoid [2], strumal carcinoid [3], thyroid carcinoma [4], adenncarcinema [l], basocellular carcinoma [I], diverse sarcomas [2, 51, melanoma [63, melanotic progonoma [7], and many others. However, 88% of all neoplasms that originated in BCT are squamous carcinomas [I]. Until now, only 58 cases of squamous degeneration of BCT with fully documented clinicopathologic data have been reported in the English- and Frenchspeaking literature [2, 8, 141. The present report communicates 5 such cases and outlines some clinicopathologic features of this tumor. MATERIAL
AND METHODS
Among 349 BCTS studied, five cases of squamous cell carcinoma were found, representing 1.4% of the total number of cases. The number of blocks made for I Address for reprints: Dr. Francisco F. Nogales, Departamento de Anatomia Patologica, Hospital Universitario, Avda. Dr. Fedriani, sin, Seville, Spain. 277 0090-82X3/79/060277-07$01.0010 Copyright @ 1979 by Academic Press. Inc. All rights of reproduction in any form reserved.
278
AMkRIGO
ET AL.
each tumor varied between 5 and 25. In each case detailed follow-up data were available.
clinical
history and
RESULTS
Clinical
Findings
All the patients were postmenopausal, the average age being 51 years. All complained of vague abdominal pain at some stage of their illness and on examination palpable abdominal masses were found in all instances. Two of the tumors were found to be in International Federation of Obstetrics and Gynecology (F.I.G.O.) stage I, two in stage III, and the remainder in stage IV. Four of the tumors occurred in the right ovary and the other in the left ovary. A BCT without any evidence of malignant change was found in the contralateral ovary in cases 2 and 3. Surgical treatment consisted of unilateral salpingo-oophorectomy in cases 1 and 5 and total abdominal hysterectomy with bilateral salpingo-oophorectomy in the other three cases. Only one of the patients received postoperative chemotherapy (Melphalan and Adriamycin) with no apparent beneficial effect. In only case 3 was postoperative radiotherapy used. Two of the patients, cases 2 and 5, survived 9 months and 9 years, respectively, with no evidence of disease; however, the rest died with widespread metastases 1 to 14 months postoperatively. Pathologic
Findings
The neoplasm varied in size between 9 and 2.5 cm, all had a cystic appearance and contained sebaceous material intermixed with numerous hairs. All except cases 2 and 5 showed capsular adhesions. In cases 1 and 4, firm, white areas of parietal thickening were evident (Fig. I) ranging from 4 cm to a few mm. Although no parietal thickening was found in case 5, there were small papillary areas (Fig. 2A). The contralateral BCTs found in cases 2 and 3 did not show any remarkable features. Histologically, a squamous cell carcinoma was evident in all cases,. with invasive cellular cords and evident foci of dyskeratosis. Cases 2 and 4 showed in some areas a cellularity consisting of abundant polygonal clear cells (Fig. 3). Case 5 had a papillomatous pattern with exophytic growth in the central cavity (Fig. 2B), but was easily differentiated from a malignant Brenner tumor. In all instances except case 5, the fibrous capsular material had been microscopically invaded. Tumor emboli were found in the blood vessels in cases 1,2, and 4 (Fig. 4). In cases 1 and 5, carcinoma in situ was found, showing transition towards areas of invasion (Fig. 5A). In no case was it possible to directly elucidate the epithelial cell type which had given rise to the neoplasm, although the areas of carcinoma in situ of cases 1 and 5 had a pattern similar to Bowen’s disease (Fig. 5B). In all cases other tissues originating from the three germ layers were present. Foreign body granulomas were also found. The clinicopathological findings are summarized in Table I.
SQUAMOUS
FIG.
right
1. tumor.
Bilateral
cystic
teratomas:
CELL
279
NEOPLASMS
an area of squamous
cell carcinoma
(arrow)
is present
FIG. 2. (A) Papillary excrescences present in the inner surface of an otherwise benign teratoma. (B) Low magnification of the same area, showing a squamous cell carcinoma papillomatous pattern, H & E X IO.
in the
cystic with a
280
AMeRIC
ET AL.
FIG. 3. Squamous cell carcinoma with a cleai-cell anaplastic pattern reminiscent of some neoplasms of the respiratory tract, H & E x 140.
FIG. 4. Squamous cell carcinoma emboli found in the capsular blood vessels, H & E X 180.
SQUAMOUS
CELL
281
NEOPLASMS
FIG. 5. (A) A cyst predominantly lined by carcinoma in situ. An area of initial capsular is present (arrows), H & E x 14. (B) Squared-off area from (A). Noninvasive squamous cinoma with a Bowen disease-like pattern. H & E X 140.
TABLE SQUAMOUS
CELL
Age
FIG0 stage
I
59
IV
2
47
3
52
4
45
5
52
Case
‘l Carcinoma
CARCINOMA DEVELOPING CLINICOPATHOLOGIC
Side and size of tumor Left,
1
IO cm
Right,
25 cm
III
Right,
9 cm
III
Right.
I2 cm
Right,
20 cm
I
in situ.
invasion cell car-
I IN DERMOID RESULTS
Histologic features Invaded capsule. CIS” foci Tumor emboli Invaded capsule Invaded capsule Tumor emboli Invaded capsule Tumor emboli Intact capsule CIS foci
CYST
OF THE
Treatment
Survival
LSO
Died of tumor (I month)
TAH-BSO TAH-BSO Radiotherapy TAH-BSO Chemotherapy RSO
OVARY,
+ +
Alive (N.E.D. 9 years) Died of tumor (14 months) Died of tumor (8 months) Alive (N.E.D. 9 months)
282
AMBRIG
ET
AL.
DISCUSSION
The percentage of squamous cell carcinomas originating in BCTs is relatively constant in most series, and rarely exceeds 2% [l, 2, 8, 11, 141. The majority of reported cases occur in postmenopausal patients, being found very exceptionally in younger age groups [5]. For this reason, the tissue sampling of BTCs obtained from patients above 40 years of age must be exhaustive since the malignant degenerative change in some cases may not be grossly evident; they frequently present as foci of carcinoma in situ which may not be visible to the naked eye [ 121. Moreover, the tumor may remain masked by the extensive granulomatous reaction that represents a constant feature in this age group [15]. It has been argued that the bilateral forms of BCT show a higher index of malignancy [ 161, however, this has now been disregarded [ 11. Malignancy in these cases is only present in one of the tumors, a fact which strongly suggests that exclusively local factors determine carcinogenesis since any general influence would affect both sides. It has been proposed that squamous cell malignancy in BCT arises due to a continued carcinogenic effect by the cyst contents themselves, especially the sebum [ 10, 171 but this has not been confirmed in experimental models [18]. The teratoid tissues from which the squamous cell carcinoma arise may have various origins. An epidermal origin is the most likely, as epidermis is always found in BCT. This is indirectly confirmed by finding Bowen’s disease-like patterns typical of carcinomas of the skin [ 12, 14, 191; this was observed in two of our cases. On other occasions it has been suggested that they may arise from respiratory epithelium by metaplasia [ 10, 111. In the present series two of the cases corresponded to squamous carcinoma with areas of clear cells, a pattern which has often been observed in the respiratory tract [201. From the clinicopathological point of view, the most important prognostic indicator, as confirmed in the present series, is the degree of extension of the tumor. Stage I tumors show a good survival while those in stages III and IV have a uniformly bad outlook. Another important parameter is the capsular involvement which was evident in all our cases except one. However, case 2 showed a prolonged survival despite focal invasion of the capsule. Some authors 121, also consider the degree of anaplasia as an important feature regarding prognosis, however, in three of our cases, despite good cellular differentiation clinical course was very poor. One microscopic aspect we believe of great importance prognostitally is the presence of tumor emboli in blood vessels. Blood-borne metastases from BCT with malignant squamous degeneration has been described elsewhere [13], and in our study the three patients with the poorest clinical outcome all demonstrated such emboli, a finding hitherto unreported, although these are rare in squamous cell carcinomas of other locations. In the small number of cases reported to date, neither radiotherapy or chemotherapy had any effect [13]. Our untreated cases showed survival rates similar to those which had received radiotherapy or chemotherapy [ 11, 131. It appears that the more effective type of therapy is a radical surgical approach, which may include block resection of the cyst and adherent viscera. Removal of lymph nodes is not indicated as in practically none of the published cases have lymphatic metastases been observed [ 131.
SQUAMOUS
CELL
283
NEOPLASMS
REFERENCES 1. Peterson, W. F. Malignant degeneration of benign cystic teratomas of the ovary. review of the literature, Obsret. G~necol. Sun,. 12, 793-830 (1957). 2. Kelley, R. R., and Scully, R. E. Cancer developing in dermoid cysts of the ovary. 989-1000 (1961). 3. Scully, R. E. Recent progress in ovarian cancer, Human Putho/. 1, 73-98 (1970). 4. Mayberger, H. W. Adenocarcinoma of thyroid origin in a benign cystic teratoma,Amrr. Gynrcd.
78,
817-820
A collective Crrncer
14,
J. Ohstet.
(1959).
5. Climie. A. R. W., and Leonard, P. H. Malignant degeneration of benign cystic teratomas of the ovary, Cancer 22, 824-832 (1968). 6. Bruning, E. G. H. Malignant melanomas originating in a dermoid cyst of the ovary, Amer. J. Ohstet. G.vnecol. 85, 131-132 (1963). 7. Hameed, K., and Burslem, M. R. G. A melanotic ovarian neoplasm resembling the “Retinal Anlage” tumor, Cancer 25, 561-567 (1970). 8. Caruso, P. A., March, M. R., Minkowitz, S., and Karten. G. An intense clinicopathologic study of 305 teratomas of the ovary, Cuncrr 27, 343-348 (1971). 9. Czernobilsky, B., Rotenstreich, L., and Lancet, M. Ovarian dermoid with squamous carcinomapseudosarcoma, Arch. Patho/. 93, 141-144 (1972). 10. Fox, H. Bronchial carcinoma in an ovarian cystic teratoma (dermoid).J. C/in. Pa/ho/. 18, 164-168 (1965).
I I. Krumerman, M. S., and Chung, A. Squamous carcinoma arising in benign cystic teratoma of the ovary, Cunccr 39, 1237-1242 (1977). 12. Klionsky, B. L., Nikens, 0. J., and Amortegui, A. J. Squamous cell carcinoma in situ arising in adult cystic teratoma of the ovary, Arch. Parhol. 93, 161-163 (1972). 13. Pantoja, E., Rodriguez-Ibanez, I., Axtmayer, R. W., Noy. M. A., and Pelegrina. I. Complications of dermoid tumors of the ovary,.Ohster. G~necol. 45, 89-94 (197.5). 14. Philippe, E., Laedlein-Greilsammer, E. de Mot, R., Ritter, J., Mandard, J. C., Muller, G., and Gandar. R. Cancerisation secondaire des dysembryones benins de I’ovaire, Arch. Anuf. Putho/. 19,
283-288
(1971).
15. Nogales, F. F., Jr. Los teratomas ovaricos: Estudio clinic0 patologico de 265 cases, Tesis doctoral, pp. 40-41, Madrid (1974). 16. Eisenstadter, D. Karzinomatose dermoid zysten des ovariums, Monutschr. Grhurtsh Gyniik 54, 360-371 (1921). 17. Counseller, V. S., and Wellbrock, W. L. A. Squamous cell epitheliomas in dermoid cysts of the ovary, Amer. J. Obstet. Gynec~ol. 28, 40-47 (1934). 18. Willis, R. A. The borderland of embryology and pathology, Butterworth, London (1968). 19. Marcial-Rojas, R. A., and Medina, R. Cystic teratomas of the ovary: Clinical and pathological analysis of 268 tumors, Arch. Purhol. 66, 577-589 (1958). 20. Morgan, A. D., and McKenzie, D. H. Clear-cell carcinoma of the lung. J. Puthol. Bactrriol. 87, 25-27
(1964).
ONCOLOGY
8, 277-283 (1979)
Squamous
Cell Neoplasms Arising from Ovarian Benign Cystic Teratoma
JOAQUIN AM~RIGO, FRANCISCO F. NOGALES, JR.,’ JUAN FERNANDEZ~ANZ, HORACIO OLIVA, AND ANGEL VELASCO Department
of Pathology, Madrid.
Seville Medical Scguridad Swiul.
School, Burgos,
Uni\~rrsidad Spain
Autcjnomn
Received October 9. 1978 Five cases of squamous cell carcinoma arising in benign cystic teratomas found in postmenopausal patients are presented. Exhaustive tissue sampling is necessary for the discovering of malignancy in this age group. Carcinogenesis is thought to be due to local factors. Carcinoma in situ of a bowenoid type was present in two cases, which suggests an epidermal origin; however, squamous clear-cell carcinoma similar to that of the respiratory tract was also found. Prognostic parameters are discussed attaching special importance to tumor stage and the presence of tumor emboli in capsular vessels.
INTRODUCTION
As all the tissues of the benign cystic teratoma (BCT) are present in the well-differentiated, adult form, they lack the intrinsic malignant potential found in the embryonic tissues of the immature teratoma; however, they are subjected to the malignant degeneration common to all mature tissues. This phenomenon is seen to occur in 1.8% of BCTs [I]. As there is a great variety of tissues reproduced in this type of tumor, it can be said that almost any type of neoplasm may arise in BCT. Cases have been described of carcinoid [2], strumal carcinoid [3], thyroid carcinoma [4], adenncarcinema [l], basocellular carcinoma [I], diverse sarcomas [2, 51, melanoma [63, melanotic progonoma [7], and many others. However, 88% of all neoplasms that originated in BCT are squamous carcinomas [I]. Until now, only 58 cases of squamous degeneration of BCT with fully documented clinicopathologic data have been reported in the English- and Frenchspeaking literature [2, 8, 141. The present report communicates 5 such cases and outlines some clinicopathologic features of this tumor. MATERIAL
AND METHODS
Among 349 BCTS studied, five cases of squamous cell carcinoma were found, representing 1.4% of the total number of cases. The number of blocks made for I Address for reprints: Dr. Francisco F. Nogales, Departamento de Anatomia Patologica, Hospital Universitario, Avda. Dr. Fedriani, sin, Seville, Spain. 277 0090-82X3/79/060277-07$01.0010 Copyright @ 1979 by Academic Press. Inc. All rights of reproduction in any form reserved.
278
AMkRIGO
ET AL.
each tumor varied between 5 and 25. In each case detailed follow-up data were available.
clinical
history and
RESULTS
Clinical
Findings
All the patients were postmenopausal, the average age being 51 years. All complained of vague abdominal pain at some stage of their illness and on examination palpable abdominal masses were found in all instances. Two of the tumors were found to be in International Federation of Obstetrics and Gynecology (F.I.G.O.) stage I, two in stage III, and the remainder in stage IV. Four of the tumors occurred in the right ovary and the other in the left ovary. A BCT without any evidence of malignant change was found in the contralateral ovary in cases 2 and 3. Surgical treatment consisted of unilateral salpingo-oophorectomy in cases 1 and 5 and total abdominal hysterectomy with bilateral salpingo-oophorectomy in the other three cases. Only one of the patients received postoperative chemotherapy (Melphalan and Adriamycin) with no apparent beneficial effect. In only case 3 was postoperative radiotherapy used. Two of the patients, cases 2 and 5, survived 9 months and 9 years, respectively, with no evidence of disease; however, the rest died with widespread metastases 1 to 14 months postoperatively. Pathologic
Findings
The neoplasm varied in size between 9 and 2.5 cm, all had a cystic appearance and contained sebaceous material intermixed with numerous hairs. All except cases 2 and 5 showed capsular adhesions. In cases 1 and 4, firm, white areas of parietal thickening were evident (Fig. I) ranging from 4 cm to a few mm. Although no parietal thickening was found in case 5, there were small papillary areas (Fig. 2A). The contralateral BCTs found in cases 2 and 3 did not show any remarkable features. Histologically, a squamous cell carcinoma was evident in all cases,. with invasive cellular cords and evident foci of dyskeratosis. Cases 2 and 4 showed in some areas a cellularity consisting of abundant polygonal clear cells (Fig. 3). Case 5 had a papillomatous pattern with exophytic growth in the central cavity (Fig. 2B), but was easily differentiated from a malignant Brenner tumor. In all instances except case 5, the fibrous capsular material had been microscopically invaded. Tumor emboli were found in the blood vessels in cases 1,2, and 4 (Fig. 4). In cases 1 and 5, carcinoma in situ was found, showing transition towards areas of invasion (Fig. 5A). In no case was it possible to directly elucidate the epithelial cell type which had given rise to the neoplasm, although the areas of carcinoma in situ of cases 1 and 5 had a pattern similar to Bowen’s disease (Fig. 5B). In all cases other tissues originating from the three germ layers were present. Foreign body granulomas were also found. The clinicopathological findings are summarized in Table I.
SQUAMOUS
FIG.
right
1. tumor.
Bilateral
cystic
teratomas:
CELL
279
NEOPLASMS
an area of squamous
cell carcinoma
(arrow)
is present
FIG. 2. (A) Papillary excrescences present in the inner surface of an otherwise benign teratoma. (B) Low magnification of the same area, showing a squamous cell carcinoma papillomatous pattern, H & E X IO.
in the
cystic with a
280
AMeRIC
ET AL.
FIG. 3. Squamous cell carcinoma with a cleai-cell anaplastic pattern reminiscent of some neoplasms of the respiratory tract, H & E x 140.
FIG. 4. Squamous cell carcinoma emboli found in the capsular blood vessels, H & E X 180.
SQUAMOUS
CELL
281
NEOPLASMS
FIG. 5. (A) A cyst predominantly lined by carcinoma in situ. An area of initial capsular is present (arrows), H & E x 14. (B) Squared-off area from (A). Noninvasive squamous cinoma with a Bowen disease-like pattern. H & E X 140.
TABLE SQUAMOUS
CELL
Age
FIG0 stage
I
59
IV
2
47
3
52
4
45
5
52
Case
‘l Carcinoma
CARCINOMA DEVELOPING CLINICOPATHOLOGIC
Side and size of tumor Left,
1
IO cm
Right,
25 cm
III
Right,
9 cm
III
Right.
I2 cm
Right,
20 cm
I
in situ.
invasion cell car-
I IN DERMOID RESULTS
Histologic features Invaded capsule. CIS” foci Tumor emboli Invaded capsule Invaded capsule Tumor emboli Invaded capsule Tumor emboli Intact capsule CIS foci
CYST
OF THE
Treatment
Survival
LSO
Died of tumor (I month)
TAH-BSO TAH-BSO Radiotherapy TAH-BSO Chemotherapy RSO
OVARY,
+ +
Alive (N.E.D. 9 years) Died of tumor (14 months) Died of tumor (8 months) Alive (N.E.D. 9 months)
282
AMBRIG
ET
AL.
DISCUSSION
The percentage of squamous cell carcinomas originating in BCTs is relatively constant in most series, and rarely exceeds 2% [l, 2, 8, 11, 141. The majority of reported cases occur in postmenopausal patients, being found very exceptionally in younger age groups [5]. For this reason, the tissue sampling of BTCs obtained from patients above 40 years of age must be exhaustive since the malignant degenerative change in some cases may not be grossly evident; they frequently present as foci of carcinoma in situ which may not be visible to the naked eye [ 121. Moreover, the tumor may remain masked by the extensive granulomatous reaction that represents a constant feature in this age group [15]. It has been argued that the bilateral forms of BCT show a higher index of malignancy [ 161, however, this has now been disregarded [ 11. Malignancy in these cases is only present in one of the tumors, a fact which strongly suggests that exclusively local factors determine carcinogenesis since any general influence would affect both sides. It has been proposed that squamous cell malignancy in BCT arises due to a continued carcinogenic effect by the cyst contents themselves, especially the sebum [ 10, 171 but this has not been confirmed in experimental models [18]. The teratoid tissues from which the squamous cell carcinoma arise may have various origins. An epidermal origin is the most likely, as epidermis is always found in BCT. This is indirectly confirmed by finding Bowen’s disease-like patterns typical of carcinomas of the skin [ 12, 14, 191; this was observed in two of our cases. On other occasions it has been suggested that they may arise from respiratory epithelium by metaplasia [ 10, 111. In the present series two of the cases corresponded to squamous carcinoma with areas of clear cells, a pattern which has often been observed in the respiratory tract [201. From the clinicopathological point of view, the most important prognostic indicator, as confirmed in the present series, is the degree of extension of the tumor. Stage I tumors show a good survival while those in stages III and IV have a uniformly bad outlook. Another important parameter is the capsular involvement which was evident in all our cases except one. However, case 2 showed a prolonged survival despite focal invasion of the capsule. Some authors 121, also consider the degree of anaplasia as an important feature regarding prognosis, however, in three of our cases, despite good cellular differentiation clinical course was very poor. One microscopic aspect we believe of great importance prognostitally is the presence of tumor emboli in blood vessels. Blood-borne metastases from BCT with malignant squamous degeneration has been described elsewhere [13], and in our study the three patients with the poorest clinical outcome all demonstrated such emboli, a finding hitherto unreported, although these are rare in squamous cell carcinomas of other locations. In the small number of cases reported to date, neither radiotherapy or chemotherapy had any effect [13]. Our untreated cases showed survival rates similar to those which had received radiotherapy or chemotherapy [ 11, 131. It appears that the more effective type of therapy is a radical surgical approach, which may include block resection of the cyst and adherent viscera. Removal of lymph nodes is not indicated as in practically none of the published cases have lymphatic metastases been observed [ 131.
SQUAMOUS
CELL
283
NEOPLASMS
REFERENCES 1. Peterson, W. F. Malignant degeneration of benign cystic teratomas of the ovary. review of the literature, Obsret. G~necol. Sun,. 12, 793-830 (1957). 2. Kelley, R. R., and Scully, R. E. Cancer developing in dermoid cysts of the ovary. 989-1000 (1961). 3. Scully, R. E. Recent progress in ovarian cancer, Human Putho/. 1, 73-98 (1970). 4. Mayberger, H. W. Adenocarcinoma of thyroid origin in a benign cystic teratoma,Amrr. Gynrcd.
78,
817-820
A collective Crrncer
14,
J. Ohstet.
(1959).
5. Climie. A. R. W., and Leonard, P. H. Malignant degeneration of benign cystic teratomas of the ovary, Cancer 22, 824-832 (1968). 6. Bruning, E. G. H. Malignant melanomas originating in a dermoid cyst of the ovary, Amer. J. Ohstet. G.vnecol. 85, 131-132 (1963). 7. Hameed, K., and Burslem, M. R. G. A melanotic ovarian neoplasm resembling the “Retinal Anlage” tumor, Cancer 25, 561-567 (1970). 8. Caruso, P. A., March, M. R., Minkowitz, S., and Karten. G. An intense clinicopathologic study of 305 teratomas of the ovary, Cuncrr 27, 343-348 (1971). 9. Czernobilsky, B., Rotenstreich, L., and Lancet, M. Ovarian dermoid with squamous carcinomapseudosarcoma, Arch. Patho/. 93, 141-144 (1972). 10. Fox, H. Bronchial carcinoma in an ovarian cystic teratoma (dermoid).J. C/in. Pa/ho/. 18, 164-168 (1965).
I I. Krumerman, M. S., and Chung, A. Squamous carcinoma arising in benign cystic teratoma of the ovary, Cunccr 39, 1237-1242 (1977). 12. Klionsky, B. L., Nikens, 0. J., and Amortegui, A. J. Squamous cell carcinoma in situ arising in adult cystic teratoma of the ovary, Arch. Parhol. 93, 161-163 (1972). 13. Pantoja, E., Rodriguez-Ibanez, I., Axtmayer, R. W., Noy. M. A., and Pelegrina. I. Complications of dermoid tumors of the ovary,.Ohster. G~necol. 45, 89-94 (197.5). 14. Philippe, E., Laedlein-Greilsammer, E. de Mot, R., Ritter, J., Mandard, J. C., Muller, G., and Gandar. R. Cancerisation secondaire des dysembryones benins de I’ovaire, Arch. Anuf. Putho/. 19,
283-288
(1971).
15. Nogales, F. F., Jr. Los teratomas ovaricos: Estudio clinic0 patologico de 265 cases, Tesis doctoral, pp. 40-41, Madrid (1974). 16. Eisenstadter, D. Karzinomatose dermoid zysten des ovariums, Monutschr. Grhurtsh Gyniik 54, 360-371 (1921). 17. Counseller, V. S., and Wellbrock, W. L. A. Squamous cell epitheliomas in dermoid cysts of the ovary, Amer. J. Obstet. Gynec~ol. 28, 40-47 (1934). 18. Willis, R. A. The borderland of embryology and pathology, Butterworth, London (1968). 19. Marcial-Rojas, R. A., and Medina, R. Cystic teratomas of the ovary: Clinical and pathological analysis of 268 tumors, Arch. Purhol. 66, 577-589 (1958). 20. Morgan, A. D., and McKenzie, D. H. Clear-cell carcinoma of the lung. J. Puthol. Bactrriol. 87, 25-27
(1964).