GYNECOLOGIC
ONCOLOGY
4,
314-323 (1976)
Papillary Serous Tumors of the Ovary: An Electron Microscopic Study ANCEL BLAUSTEIN, M.D. Department of Pathology, New York University School of Medicine and Department Pathology, Booth Memorial Medical Center, Flushing, New York 11355
of
Received March 19, 1976 Fifteen papillary cystic tumors of the ovary were studied by electron microscopy. These consisted of eight serous cystadenocarcinomas, one recurrent cystadenocarcinoma, one borderline tumor, and five benign cystadenomata. Multiple samples were studied both by light and electron microscopy. Electron microscopic criteria previously described as useful in distinguishing between benign and malignant lesions were not found to be sufficiently consistent to be useful.
Previous studies [ 11have suggested that certain electron microscopic observations were useful in studying papillary serous tumors of the ovary; in particular tumors with borderline malignant changes. This presentation consists of an electron microscopic study of 15 cases of papillary serous tumors of the ovary applying the criteria suggested in the above study. MATERIALS
AND METHODS
Fifteen papillary cystic tumors of the ovary were studied by both light and electron microscopic examination. These consisted of eight serous cystadenocarcinomata, one recurrent pelvic mass in a previous case of serous cystadenocarcinema, and five cases of serous cystadenoma. There was one borderline tumor. Tissue samples were taken from the tumors immediately upon removal. These were processed so that half of each sample was used for light microscopy and half for electron microscopy. Sections used for electron microscopy were placed in a drop of 5% cacodylate buffered glutaraldehyde (pH 7.2). They were transferred to 1% osmium tetroxide (ice cold), dehydrated in graded alcohols, and embedded in eponaraldite mixture. Sections were cut with a Porter-Blum Microtome, stained with lead citrate and uranyl acetate, and examined with an RCA EMU4 microscope. Tumors were classified according to the WHO classification as benign cystadenoma, cystadenocarcinoma, and borderline malignant. The electron Aicrographs were reviewed using the criteria of Gondos [ll. These were: (1) shape of the nucleus; (2) cell membrane interdigitation; and (3) presence or absence of cilia. OBSERVATIONS Cystadenoma. Nuclear borders were both smooth as well as showing nuclear indentations of the same magnitude as seen in cystadenocarcinoma (Fig. 1). Nucleoli were prominent in cystadenoma (Fig. 2). Membrane interdigitations were prominent. Nuclear chromatin showed both central clumping as well as condensation along the nuclear membrane, and nuclear bodies were present in 314 Copyright @ 1976 by Academic Press. Inc. All rights of reproduction in any form reserved.
PAPILLARY
SEROUS TUMORS OF THE OVARY
315
FIG. 1. Serous cystadenoma. Nuclear indentations and enfolding is prominent (3000x).
two cases. Both electron-dense and light bodies, mitochondria, and rough endoplasmic reticulum were seen in the cytoplasm. Microvilh and cilia appeared along the luminal borders. Cell attachments consisting of desmosomes, terminal bars, and complex interdigitations were seen. Cell budding was present in two of five cases (Fig. 3). Serous cystadenocarcinoma. Numerous samples were taken from each of the eight cases of serous cystadenocarcinoma. While some nuclear pleomorphism was seen, a greater number of nuclei showed no indentations or irregularities (Figs. 4 and 5). Nuclear bodies (Figs. 6 and 7) were present in six of the eight cases. Nucleoli were not more prominent than in cystadenoma, but in all cases of carcinoma they were fenestrated (Fig. S), where present. In carcinoma, we did find cytoplasmic budding in five cases, however this feature was also found in the benign counterpart. In carcinoma many more mitochondria (Fig. 9) and much more rough endoplasmic reticulum are present. The configuration of the mito-
316
ANCEL BLAUSTEIN
FIG. 2. Serous cystadenoma. Nucleoli are prominent (1700x).
chondria appeared to be no different than in cystadenoma. We observed, as Gondos [ 11did, that cell interdigitations along lateral borders were less prominent in carcinoma than in cystadenoma, but of eight cases of carcinoma, this feature was not a distinguishing characteristic in three. In one case of recurrent carcinoma, where the tumor by light microscopy was poorly differentiated, electron microscopy demonstrated striking interdigitation (Fig. 10). Cilia were a prominent feature of cystadenoma, but in two of our eight cases of carcinoma, cilia were present (Figs. 11 and 12). In both these cases there was extensive pelvic extension of the tumor. Borderline tumors. Only one case of borderline tumor was studied by electron microscopy. Nuclear irregularity was minimal, nucleoli were prominent, and cilia were present. Desmosomes and terminal bars were similar to those found in cystadenoma and carcinoma. Lateral borders were flattened, and interdigitations were less prominent.
FIG. 3. Serous cystadenoma; cytoplasmic budding is present (6000x).
FIG. 4. Serous cystadenocarcinoma. Nuclei are regular in appearance (6000x).
317
FIG. 5. Serous cystadenocarcinoma. Nuclei are regular, mitochondria are abundant, and nuclear bodies (arrows) are present (6000x).
FIG. 6. Serous cystadenocarcinoma. Nuclear body (arrow) showing an electron-dense central core (15,000x). 318
FIG. 7. Serous cystadenocarcinoma. Nuclear body (arrow) showing a lamellated pattern (11,000x).
FIG. 8. Serous cystadenocarcinoma. Fenestration of the nucleolus (1800x).
319
320
ANCEL
BLAUSTEIN
FIG. 9. Serous cystadenocarcinoma. Rough endoplasmic reticulum is prominent and mitochrondria are abundant and normal in appearance (6000x).
DISCUSSION
We were unable to confirm that increased nuclear irregularity paralleled increased potential for malignancy. Nuclear irregularity was found as often in cystadenomata as in carcinoma, and nuclear regularity was prominent in tumors in which extensive metastases already existed. Nucleoli were seen as often in cystadenomata as in carcinoma. The only difference we noted was fenestration of the nucleoli in carcinoma. Nuclear bodies were a prominent feature of carcinoma but were also found in cystadenomata. In general, there appears to be a decreased degree of membrane interdigitation, although this was not a useful distinction in three of our eight cases of carcinoma. In a case of recurrent serous cystadenocarcinema the membrane interdigitations were exaggerated. This phenomenon has been described by Bernard [2] in other tumors. We found cilia in two cases of serous cystadenocarcinoma, and this observation [3] has been made in renal carcinoma in hamsters. It is therefore doubtful that the presence of cilia is a reliable indicator of benignity. Since only one borderline tumor was examined, no conclusions can be drawn.
PAPILLARY
SEROUS
TUMORS
OF
THE
OVARY
321
FIG. 10. Serous cystadenocarcinoma (recurrent). There are numerous intercellular interdigitations (8400x).
SUMMARY Electron microscopy has helped to confirm that these tumors represent Mullerian differentiation from celomic epithelium [4,5]. Fine structure criteria that have thus far been suggested as being helpful in distinguishing between cystadenoma, borderline tumors, and serous cystadenocarcinoma are not consistent.
322
ANCEL BLAUSTEIN
FIG. 11. Serous cystadenocarcinoma. There are numerous cilia on the cell surfaces (6600x).
FIG. 12. Serous cystadenocarcinoma. Cilia (arrow; insert for Fig. 11) (12,500x).
PAPILLARY
SEROUS TUMORS
OF THE
OVARY
323
REFERENCES 1. Gondos, B. Electron microscopic study of papillary setous tumors of the ovary, Cancer 27, 1455 (1971). 2. Bernhard, W. Some problems of fine structure in tumor cells, Progr. Exp. Tumor Res. 3, l-34 (1%3). 3. Mannweiler, K., and Bernhard, W. Recherches ultrastrurales sor une tumeur renale experimentale du hamster, J. Ultrastruct. Res. 1, 158-189 (1957). 4. Luisi, A. Malignant ovarian tumors of Mullerian origin, in Ovarian Cancer (F. Gentil and A. C. Junqueira, Eds.), Springer-Verlag, Berlin/Heidelberg/New York, pp. 9-22 (1968). 5. Stemberg, W. H. Non-functioning ovarian neoplasms, in The Ovary (H. G. Grady and D. E. Smith, Eds.), Williams & Wilkins, Baltimore, pp. 209-254 (1%3).
ONCOLOGY
4,
314-323 (1976)
Papillary Serous Tumors of the Ovary: An Electron Microscopic Study ANCEL BLAUSTEIN, M.D. Department of Pathology, New York University School of Medicine and Department Pathology, Booth Memorial Medical Center, Flushing, New York 11355
of
Received March 19, 1976 Fifteen papillary cystic tumors of the ovary were studied by electron microscopy. These consisted of eight serous cystadenocarcinomas, one recurrent cystadenocarcinoma, one borderline tumor, and five benign cystadenomata. Multiple samples were studied both by light and electron microscopy. Electron microscopic criteria previously described as useful in distinguishing between benign and malignant lesions were not found to be sufficiently consistent to be useful.
Previous studies [ 11have suggested that certain electron microscopic observations were useful in studying papillary serous tumors of the ovary; in particular tumors with borderline malignant changes. This presentation consists of an electron microscopic study of 15 cases of papillary serous tumors of the ovary applying the criteria suggested in the above study. MATERIALS
AND METHODS
Fifteen papillary cystic tumors of the ovary were studied by both light and electron microscopic examination. These consisted of eight serous cystadenocarcinomata, one recurrent pelvic mass in a previous case of serous cystadenocarcinema, and five cases of serous cystadenoma. There was one borderline tumor. Tissue samples were taken from the tumors immediately upon removal. These were processed so that half of each sample was used for light microscopy and half for electron microscopy. Sections used for electron microscopy were placed in a drop of 5% cacodylate buffered glutaraldehyde (pH 7.2). They were transferred to 1% osmium tetroxide (ice cold), dehydrated in graded alcohols, and embedded in eponaraldite mixture. Sections were cut with a Porter-Blum Microtome, stained with lead citrate and uranyl acetate, and examined with an RCA EMU4 microscope. Tumors were classified according to the WHO classification as benign cystadenoma, cystadenocarcinoma, and borderline malignant. The electron Aicrographs were reviewed using the criteria of Gondos [ll. These were: (1) shape of the nucleus; (2) cell membrane interdigitation; and (3) presence or absence of cilia. OBSERVATIONS Cystadenoma. Nuclear borders were both smooth as well as showing nuclear indentations of the same magnitude as seen in cystadenocarcinoma (Fig. 1). Nucleoli were prominent in cystadenoma (Fig. 2). Membrane interdigitations were prominent. Nuclear chromatin showed both central clumping as well as condensation along the nuclear membrane, and nuclear bodies were present in 314 Copyright @ 1976 by Academic Press. Inc. All rights of reproduction in any form reserved.
PAPILLARY
SEROUS TUMORS OF THE OVARY
315
FIG. 1. Serous cystadenoma. Nuclear indentations and enfolding is prominent (3000x).
two cases. Both electron-dense and light bodies, mitochondria, and rough endoplasmic reticulum were seen in the cytoplasm. Microvilh and cilia appeared along the luminal borders. Cell attachments consisting of desmosomes, terminal bars, and complex interdigitations were seen. Cell budding was present in two of five cases (Fig. 3). Serous cystadenocarcinoma. Numerous samples were taken from each of the eight cases of serous cystadenocarcinoma. While some nuclear pleomorphism was seen, a greater number of nuclei showed no indentations or irregularities (Figs. 4 and 5). Nuclear bodies (Figs. 6 and 7) were present in six of the eight cases. Nucleoli were not more prominent than in cystadenoma, but in all cases of carcinoma they were fenestrated (Fig. S), where present. In carcinoma, we did find cytoplasmic budding in five cases, however this feature was also found in the benign counterpart. In carcinoma many more mitochondria (Fig. 9) and much more rough endoplasmic reticulum are present. The configuration of the mito-
316
ANCEL BLAUSTEIN
FIG. 2. Serous cystadenoma. Nucleoli are prominent (1700x).
chondria appeared to be no different than in cystadenoma. We observed, as Gondos [ 11did, that cell interdigitations along lateral borders were less prominent in carcinoma than in cystadenoma, but of eight cases of carcinoma, this feature was not a distinguishing characteristic in three. In one case of recurrent carcinoma, where the tumor by light microscopy was poorly differentiated, electron microscopy demonstrated striking interdigitation (Fig. 10). Cilia were a prominent feature of cystadenoma, but in two of our eight cases of carcinoma, cilia were present (Figs. 11 and 12). In both these cases there was extensive pelvic extension of the tumor. Borderline tumors. Only one case of borderline tumor was studied by electron microscopy. Nuclear irregularity was minimal, nucleoli were prominent, and cilia were present. Desmosomes and terminal bars were similar to those found in cystadenoma and carcinoma. Lateral borders were flattened, and interdigitations were less prominent.
FIG. 3. Serous cystadenoma; cytoplasmic budding is present (6000x).
FIG. 4. Serous cystadenocarcinoma. Nuclei are regular in appearance (6000x).
317
FIG. 5. Serous cystadenocarcinoma. Nuclei are regular, mitochondria are abundant, and nuclear bodies (arrows) are present (6000x).
FIG. 6. Serous cystadenocarcinoma. Nuclear body (arrow) showing an electron-dense central core (15,000x). 318
FIG. 7. Serous cystadenocarcinoma. Nuclear body (arrow) showing a lamellated pattern (11,000x).
FIG. 8. Serous cystadenocarcinoma. Fenestration of the nucleolus (1800x).
319
320
ANCEL
BLAUSTEIN
FIG. 9. Serous cystadenocarcinoma. Rough endoplasmic reticulum is prominent and mitochrondria are abundant and normal in appearance (6000x).
DISCUSSION
We were unable to confirm that increased nuclear irregularity paralleled increased potential for malignancy. Nuclear irregularity was found as often in cystadenomata as in carcinoma, and nuclear regularity was prominent in tumors in which extensive metastases already existed. Nucleoli were seen as often in cystadenomata as in carcinoma. The only difference we noted was fenestration of the nucleoli in carcinoma. Nuclear bodies were a prominent feature of carcinoma but were also found in cystadenomata. In general, there appears to be a decreased degree of membrane interdigitation, although this was not a useful distinction in three of our eight cases of carcinoma. In a case of recurrent serous cystadenocarcinema the membrane interdigitations were exaggerated. This phenomenon has been described by Bernard [2] in other tumors. We found cilia in two cases of serous cystadenocarcinoma, and this observation [3] has been made in renal carcinoma in hamsters. It is therefore doubtful that the presence of cilia is a reliable indicator of benignity. Since only one borderline tumor was examined, no conclusions can be drawn.
PAPILLARY
SEROUS
TUMORS
OF
THE
OVARY
321
FIG. 10. Serous cystadenocarcinoma (recurrent). There are numerous intercellular interdigitations (8400x).
SUMMARY Electron microscopy has helped to confirm that these tumors represent Mullerian differentiation from celomic epithelium [4,5]. Fine structure criteria that have thus far been suggested as being helpful in distinguishing between cystadenoma, borderline tumors, and serous cystadenocarcinoma are not consistent.
322
ANCEL BLAUSTEIN
FIG. 11. Serous cystadenocarcinoma. There are numerous cilia on the cell surfaces (6600x).
FIG. 12. Serous cystadenocarcinoma. Cilia (arrow; insert for Fig. 11) (12,500x).
PAPILLARY
SEROUS TUMORS
OF THE
OVARY
323
REFERENCES 1. Gondos, B. Electron microscopic study of papillary setous tumors of the ovary, Cancer 27, 1455 (1971). 2. Bernhard, W. Some problems of fine structure in tumor cells, Progr. Exp. Tumor Res. 3, l-34 (1%3). 3. Mannweiler, K., and Bernhard, W. Recherches ultrastrurales sor une tumeur renale experimentale du hamster, J. Ultrastruct. Res. 1, 158-189 (1957). 4. Luisi, A. Malignant ovarian tumors of Mullerian origin, in Ovarian Cancer (F. Gentil and A. C. Junqueira, Eds.), Springer-Verlag, Berlin/Heidelberg/New York, pp. 9-22 (1968). 5. Stemberg, W. H. Non-functioning ovarian neoplasms, in The Ovary (H. G. Grady and D. E. Smith, Eds.), Williams & Wilkins, Baltimore, pp. 209-254 (1%3).
