Vol. 68, No. 4
309
Intracranial Germinomas A Case Report KUANG-JAW FAN, M.D., Assistant Professor of Pathology, and ANTHONY AGBATA, M.D., Resident in Pathology, Department of Pathology, Howard University, Washington, D.C.
pineal from arising T UMORS as rare rather are cells parenchymal cell of origin in germ compared to tumors literathe in reviewing that region. In fact, in the pineal of tumors ture, the great majority region have been of germ cell origin, namely all of germinomas.1 - In the old literature, tumors in this region, regardless of their origins, had been called "pinealoma" because of their histologic resemblance to the fetal pineal body.5 Not infrequently, tumors which are histologically identical to the "pinealoma" were also reportedly found in the suprasellar region, third ventricle and even in the intrasellar space.6-8 These tumors outside the pineal region had been collectively referred to as "ectopic pinealoma". Russell first pointed out the histologic similarity between the "pinealoma" or "ectopic pinealoma" and the seminoma of the testis or dysgerminoma of the ovary in a case report by Harris and Cairns.9 Subsequently, "germinoma" was proposed by Friedman to replace the old term "pinealoma" which is mostly of germ cell origin.10 Currently, this new designation seems to be widely accepted by most pathologists. When the germinoma occurs intracranially, it exclusively involves the midline structures, mostly in the pineal region and occasionally in the suprasellar region, third ventricle and intrasellar space.4 Multifocal intracranial germinomas, especially the simultaneous involvement of the pineal region and suprasellar region or the floor of the third ventricle, have been reported.11 This particular situation has been interpreted as multifocality (two primary foci) or metastasis (seeding of tumor cells along the posterior
wall of the third ventricle from the pineal region).4'12 However, their genesis has never been clarified. The present report of a pathological study of a case of multifocal intracranial germinomas may help elucidate the pathogenesis and biological behavior of this uncommon tumor. CASE REPORT
A 23 year old unmarried black female was admitted to Howard University Hospital in May, 1974 because of amenorrhea and polydypsia. In 1970, she first experienced weakness of both legs which became ataxic in the following years. Before this admission she was also found to have weight loss, impaired memory and occasional hallucinations. She was treated with Depomedrol and Vitamin B 12. The clinical impression was multiple sclerosis. The neurological examination on admission revealed a cachetic female with ataxia and horizontal nystagmus. No visual field defect was disclosed. Laboratory data showed hyperglycemia (265 mg%), hypernatremia (169 mEq/l) and anemia (Hct 29.7%, hemoglobulin 9.3 Gm%). The other tests, including C. S.F., were within normal limits. After admission, she developed streptococcal meningitis which was treated with intravenous antibiotics. Her condition improved. However, hypernatremia persisted and diabetes insipiduus became prominent. Further investigations revealed hypofunction of the thyroid and a suggestive calcification in the suprasellar region. Fifteen weeks after admission, she began to have varying periods of hypothemia and fever. She subsequently became unconscious. A gastrostomy was performed for feeding. Her condition deteriorated rapidly and she expired four months after admission. A complete autopsy was performed. Acute hemorrhagic pancreatitis and confluent bronchopneumonia, which were regarded as the immediate causes of death, were found. There were also marked fatty change of liver and atrophy of thyroid and adrenal glands. Lesions in the intracranial cavity were rather conspicuous. There was a large infiltrative suprasellar tumor (Fig. 1) involving the optic chiasm, the floor of third ventricle and the hypothalamic areas. The fornix and the adja-
310
JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION
cent brain tissue were also noticed to be infiltrated by the tumor. The intrasellar space appeared to be intact. No gross tumor mass could be identified in the pineal region. Microscopically, the suprasellar tumor was identical to testicular seminoma (Fig. 2 left). It was composed of two types of cells: large polygonal or epitheloid tumor cells which were divided into lobules by a fibrovascular stroma and small lymphocytic cells which were confined in the stroma. Some of the large tumor cells were rather anaplastic and contained some diastase resistant PAS positive granules in the cytoplasm. The lymphocytic cells in the stroma were most-
Fig. 1. Sagittal view of the brain showing the tumor in the suprasellar region. The optic chiasm, 3rd ventricle and adjacent brain tissue are infiltrated by tumor. No gross tumor can be recognized in the pineal region (arrow). seen in the perivascular area. Many of them were identified as plasma cells electronmicroscopical ly. No transitional cell type between large tumor cells and small lymphocytic cells was observed. The Masson' s trichrome and PTAH stains disclosed a fibrous and non-glial nature of the tumor stroma. Multiple sections of the pineal region revealed degenerative fibrocollagenous tissue which was infiltrated by lymphocytic cells. Among the degenerative tissue stroma, there were several small foci of tumor cells which were observed to
ly
Fig. 2. Microscopic features of the suprasellar tumor showing large epitheloid tumor cells in a lobule and small lymphocytic cells in the stroma. X 400. (left). Microscopic features of tissue from the pineal region. Note large epitheloid tumor cells among the degenerated tissue which is infiltrated by lymphocytic cells. X 400. (Right). two types of cells:
be identical to the large epitheloid tumor cells of the suprasellar tumor (Fig. 2 right). No normal pineal tissue could be identified in series of sections from the
pineal region.
JULY, 1976
DISCUSSION
The intracranial germinoma has been demonstrated to be identical with the seminoma of the testis and dysgerminoma of the ovary microscopically and at the fine structure level.13' 4 Their histochemical similarity was also reported.15 In fact, some primitive germ cells were observed to migrate to the intracranial cavity in an embryo.15 The coexistence of typical teratoma and germinoma in the intracranial cavity is also frequently reported. 17-23 All of these evidences support the theory of teratogenicity of intracranial germinoma. A germinoma found in the suprasellar region could be primary or metastatic (seeding of tumor cells along the posterior wall of the third ventricle) from the pineal region. The controversy of multifocality or metastasis in previously reported cases of multiple intracranial germinomas is by no means clarified by the present case report. However, the unique situation of this case, the coexistence of a large suprasellar germinoma and a microscopic germinoma in the degenerated pineal region, may cast some light on the pathogenesis and the biological behavior of this tumor. Since the presence of lymphocytic cells in the seminoma or intracranial germinoma has been recognized as a phenomenon of immune response to tumor cells,24 the degenerative process with lymphocytic infiltration in the pineal region observed probably represents a successful immune response which is able to destroy most of the tumor tissue. The significance of this case report is twofold. First, since pineal bodies have not been examined histologically in many routine autopsies, it is conceivable that some grossly unrecognizable small germinomas or other tumors in the pineal region have been overlooked. A careful histologic examination of the pineal region should be recommended. Second, if the degenerated tissue observed in the pineal region is truly due to a successful immune response, as authors have suggested, the possibility of immunotherapy for seminoma or intracranial germinoma could be feasible clinically.
Intracranial Germinomas
Vol. 68, No. 4
SUMMARY
The literature on intracranial germinomas is reviewed and a case of suprasellar germinoma, associated with a microscopic tumor in the pineal region, is reported. An attempt has been made to discuss the pathogenesis and biological behaviour of this uncommon tumor.
12.
13. 14. 15.
LITERATURE CITED
1. MAIER, J. G. and D. DEJONG. Pineal Body Tumors. Am. J. Roentgen., 99:826-832, 1967. .2. DEGIROLAMI, U. and H. SCHMIDEK. Clinicopathological Study of 53 Tumors of the Pineal Region. J. Neurosurg., 39:455-462, 1973. 3. RUSSELL, D. S. and L. J. RUBINSTEIN. Pathology of Tumors of the Nervous System, 3rd Edition. Baltimore: The Williams and Wilkins Company. 1971. pp. 209-217. 4. RUBINSTEIN, L. J. Tumors of the Central Nervous System, Atlas of Tumor Pathology, 2nd series, Fascicle 6. Washington, D.C.: Armed Forces Institute of Pathology, pp. 269-284. 5. GLOBUS, J. H. and S. SILBERT. Pinealomas. Arch. Neurol., 25:937-984, 1931. 6. SIMSON, L. R. and I. LAMPE and M. R. AB ELL. Suprasellar Germinomas. Cancer, 22:533-544, 1968. 7. GHATAK, N. R. and A. HIRANO and H. M. ZIMMERMAN. Intrasellar Germinomas: A Form of Ectopic Pinealoma. J. Neurosurg., 31:670-675, 1969. 8. CUNEO, H. M. Ectopic Pinealomas. J. Neurosurg., 17:161-165, 1960. 9. HARRIS, W. and H. CAIRNS. Diagnosis and Treatment of Pineal Tumors: with Report of a Case. Lancet, 1:3-9, 1932. 10. FRIEDMAN, N. B. Germinoma of the Pineal: Its Identity with Germinoma ("Seminoma") of the Testis. Cancer Res., 7:363-368, 1947. 11. DAYAN, A. D. and A. H. E. MARSHALL, A.
16.
17.
18. 19. 20. 21. 22. 23.
24.
311
A. MILLER, F. J. PICK and N. E. RANKIN. Atypical Teratomas of the Pineal and Hypothalamus. J. Path. Bact., 92:1-28, 1966. KAGEYAMA, N. and R. BELSKY. Ectopic Pinealoma in the Chiasma Region. Neurology (Minneap.), 1:318-327, 1961. RAMSEY, H. J. Ultrastructure of a Pineal Tumor. Cancer, 18:1014-1025, 1965. PIERCE, G. B. Ultrastructure of Human Testicular Tumors. Cancer, 19:1963-1983, 1966. BEELEY, J. M. and J. J. DALY, W. R. TIMPERLEY and J. WARNER. Ectopic Pinealoma: An Unusual Clinical Presentation and a Histochemical Comparison with a Seminoma of the Testis. J. Neurol. Neurosurg. and Psychiat., 36:864-873, 1973. MINTZ, B. Formation and Early Development of Germ Cells. Symposium on the Germ Cells and Earliest Stages of Development. Milan, Fondazione A. Baselli, Instituto Lombardo, 1961. BOCHNER, S. J. and J. E. Scarff. Teratomas of the Pineal Body: Classification of Embryonal Tumors of the Pineal Body; Report of a Case of Teratoma of the Pineal Body Presenting with Formed Teeth. Arch. Surg., 36:303, 1938. BAGGENSTOSS, A. H. and J. G. Love. Pinealomas. Arch. Neurol. Psychiat., 41:1187, 1939. RUSSELL, D. S. Pinealoma: Its Relationship to Teratoma. J. Path. Bact., 56:145-150, 1944. RUSSELL, D. S. "Ectopic Pinealoma": Its Kinship to Atypical Teratoma of Pineal Gland; Report of a Case. J. Path. Bact., 68:125-129, 1954. BORIT, A. Embryonal Carcinoma of the Pineal Region. J. Path., 97:165-168, 1969. WALTON, K. Teratomas of the Pineal Region and Their Relationshp to Pinealomas. J. Path. Bact., 61:11-21, 1949. JAMES, W. and H. R. DUDLEY. Teratoma in the Region of the Pineal Body (Report of a Case). J. Neurosurg., 14:235-241, 1957. MARSHALL, A. H. E. and A. D. DAYAN. An Immune Reaction in Man Against Seminomas, Dysgerminomas, Pinealomas and the Mediastinal Tumours of Similar Histological Appearance. Lancet, 2:1102-1104, 1964.
p
(Sampson & Braxton, from page 280) 17. U. S. Public Health Service. The Health. Consequences of Smoking. A Public Health Service Review: 1967. U. S. Government Printing Office, Washington, D. C. 1968. 18. U.S. Department of Health, Education and Welfare. Progress Against Cancer 1970. U.S. Government Printing Office, Washington, D.C. 1970, pp. 58-59. 19. SEBRANEK, J. G. and R. G. CASSENS. Ni-
trosamines: A Review. J. Milk Food Technol., 36:76-91, 1973. 20. MILLER, J. A. and E. C. MILLER. Natural and Synthetic Chemical Carcinogens in the Etiology of Cancer. Cancer Res., 25:1292-1304, 1965. 21. BERG, J. W. and W. HAENSZEL and S. S. DEVESA. Epidemiology of Gastrointestinal Cancer. Seventh National Cancer Conference Proceedings. 1973, pp. 459-464.
309
Intracranial Germinomas A Case Report KUANG-JAW FAN, M.D., Assistant Professor of Pathology, and ANTHONY AGBATA, M.D., Resident in Pathology, Department of Pathology, Howard University, Washington, D.C.
pineal from arising T UMORS as rare rather are cells parenchymal cell of origin in germ compared to tumors literathe in reviewing that region. In fact, in the pineal of tumors ture, the great majority region have been of germ cell origin, namely all of germinomas.1 - In the old literature, tumors in this region, regardless of their origins, had been called "pinealoma" because of their histologic resemblance to the fetal pineal body.5 Not infrequently, tumors which are histologically identical to the "pinealoma" were also reportedly found in the suprasellar region, third ventricle and even in the intrasellar space.6-8 These tumors outside the pineal region had been collectively referred to as "ectopic pinealoma". Russell first pointed out the histologic similarity between the "pinealoma" or "ectopic pinealoma" and the seminoma of the testis or dysgerminoma of the ovary in a case report by Harris and Cairns.9 Subsequently, "germinoma" was proposed by Friedman to replace the old term "pinealoma" which is mostly of germ cell origin.10 Currently, this new designation seems to be widely accepted by most pathologists. When the germinoma occurs intracranially, it exclusively involves the midline structures, mostly in the pineal region and occasionally in the suprasellar region, third ventricle and intrasellar space.4 Multifocal intracranial germinomas, especially the simultaneous involvement of the pineal region and suprasellar region or the floor of the third ventricle, have been reported.11 This particular situation has been interpreted as multifocality (two primary foci) or metastasis (seeding of tumor cells along the posterior
wall of the third ventricle from the pineal region).4'12 However, their genesis has never been clarified. The present report of a pathological study of a case of multifocal intracranial germinomas may help elucidate the pathogenesis and biological behavior of this uncommon tumor. CASE REPORT
A 23 year old unmarried black female was admitted to Howard University Hospital in May, 1974 because of amenorrhea and polydypsia. In 1970, she first experienced weakness of both legs which became ataxic in the following years. Before this admission she was also found to have weight loss, impaired memory and occasional hallucinations. She was treated with Depomedrol and Vitamin B 12. The clinical impression was multiple sclerosis. The neurological examination on admission revealed a cachetic female with ataxia and horizontal nystagmus. No visual field defect was disclosed. Laboratory data showed hyperglycemia (265 mg%), hypernatremia (169 mEq/l) and anemia (Hct 29.7%, hemoglobulin 9.3 Gm%). The other tests, including C. S.F., were within normal limits. After admission, she developed streptococcal meningitis which was treated with intravenous antibiotics. Her condition improved. However, hypernatremia persisted and diabetes insipiduus became prominent. Further investigations revealed hypofunction of the thyroid and a suggestive calcification in the suprasellar region. Fifteen weeks after admission, she began to have varying periods of hypothemia and fever. She subsequently became unconscious. A gastrostomy was performed for feeding. Her condition deteriorated rapidly and she expired four months after admission. A complete autopsy was performed. Acute hemorrhagic pancreatitis and confluent bronchopneumonia, which were regarded as the immediate causes of death, were found. There were also marked fatty change of liver and atrophy of thyroid and adrenal glands. Lesions in the intracranial cavity were rather conspicuous. There was a large infiltrative suprasellar tumor (Fig. 1) involving the optic chiasm, the floor of third ventricle and the hypothalamic areas. The fornix and the adja-
310
JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION
cent brain tissue were also noticed to be infiltrated by the tumor. The intrasellar space appeared to be intact. No gross tumor mass could be identified in the pineal region. Microscopically, the suprasellar tumor was identical to testicular seminoma (Fig. 2 left). It was composed of two types of cells: large polygonal or epitheloid tumor cells which were divided into lobules by a fibrovascular stroma and small lymphocytic cells which were confined in the stroma. Some of the large tumor cells were rather anaplastic and contained some diastase resistant PAS positive granules in the cytoplasm. The lymphocytic cells in the stroma were most-
Fig. 1. Sagittal view of the brain showing the tumor in the suprasellar region. The optic chiasm, 3rd ventricle and adjacent brain tissue are infiltrated by tumor. No gross tumor can be recognized in the pineal region (arrow). seen in the perivascular area. Many of them were identified as plasma cells electronmicroscopical ly. No transitional cell type between large tumor cells and small lymphocytic cells was observed. The Masson' s trichrome and PTAH stains disclosed a fibrous and non-glial nature of the tumor stroma. Multiple sections of the pineal region revealed degenerative fibrocollagenous tissue which was infiltrated by lymphocytic cells. Among the degenerative tissue stroma, there were several small foci of tumor cells which were observed to
ly
Fig. 2. Microscopic features of the suprasellar tumor showing large epitheloid tumor cells in a lobule and small lymphocytic cells in the stroma. X 400. (left). Microscopic features of tissue from the pineal region. Note large epitheloid tumor cells among the degenerated tissue which is infiltrated by lymphocytic cells. X 400. (Right). two types of cells:
be identical to the large epitheloid tumor cells of the suprasellar tumor (Fig. 2 right). No normal pineal tissue could be identified in series of sections from the
pineal region.
JULY, 1976
DISCUSSION
The intracranial germinoma has been demonstrated to be identical with the seminoma of the testis and dysgerminoma of the ovary microscopically and at the fine structure level.13' 4 Their histochemical similarity was also reported.15 In fact, some primitive germ cells were observed to migrate to the intracranial cavity in an embryo.15 The coexistence of typical teratoma and germinoma in the intracranial cavity is also frequently reported. 17-23 All of these evidences support the theory of teratogenicity of intracranial germinoma. A germinoma found in the suprasellar region could be primary or metastatic (seeding of tumor cells along the posterior wall of the third ventricle) from the pineal region. The controversy of multifocality or metastasis in previously reported cases of multiple intracranial germinomas is by no means clarified by the present case report. However, the unique situation of this case, the coexistence of a large suprasellar germinoma and a microscopic germinoma in the degenerated pineal region, may cast some light on the pathogenesis and the biological behavior of this tumor. Since the presence of lymphocytic cells in the seminoma or intracranial germinoma has been recognized as a phenomenon of immune response to tumor cells,24 the degenerative process with lymphocytic infiltration in the pineal region observed probably represents a successful immune response which is able to destroy most of the tumor tissue. The significance of this case report is twofold. First, since pineal bodies have not been examined histologically in many routine autopsies, it is conceivable that some grossly unrecognizable small germinomas or other tumors in the pineal region have been overlooked. A careful histologic examination of the pineal region should be recommended. Second, if the degenerated tissue observed in the pineal region is truly due to a successful immune response, as authors have suggested, the possibility of immunotherapy for seminoma or intracranial germinoma could be feasible clinically.
Intracranial Germinomas
Vol. 68, No. 4
SUMMARY
The literature on intracranial germinomas is reviewed and a case of suprasellar germinoma, associated with a microscopic tumor in the pineal region, is reported. An attempt has been made to discuss the pathogenesis and biological behaviour of this uncommon tumor.
12.
13. 14. 15.
LITERATURE CITED
1. MAIER, J. G. and D. DEJONG. Pineal Body Tumors. Am. J. Roentgen., 99:826-832, 1967. .2. DEGIROLAMI, U. and H. SCHMIDEK. Clinicopathological Study of 53 Tumors of the Pineal Region. J. Neurosurg., 39:455-462, 1973. 3. RUSSELL, D. S. and L. J. RUBINSTEIN. Pathology of Tumors of the Nervous System, 3rd Edition. Baltimore: The Williams and Wilkins Company. 1971. pp. 209-217. 4. RUBINSTEIN, L. J. Tumors of the Central Nervous System, Atlas of Tumor Pathology, 2nd series, Fascicle 6. Washington, D.C.: Armed Forces Institute of Pathology, pp. 269-284. 5. GLOBUS, J. H. and S. SILBERT. Pinealomas. Arch. Neurol., 25:937-984, 1931. 6. SIMSON, L. R. and I. LAMPE and M. R. AB ELL. Suprasellar Germinomas. Cancer, 22:533-544, 1968. 7. GHATAK, N. R. and A. HIRANO and H. M. ZIMMERMAN. Intrasellar Germinomas: A Form of Ectopic Pinealoma. J. Neurosurg., 31:670-675, 1969. 8. CUNEO, H. M. Ectopic Pinealomas. J. Neurosurg., 17:161-165, 1960. 9. HARRIS, W. and H. CAIRNS. Diagnosis and Treatment of Pineal Tumors: with Report of a Case. Lancet, 1:3-9, 1932. 10. FRIEDMAN, N. B. Germinoma of the Pineal: Its Identity with Germinoma ("Seminoma") of the Testis. Cancer Res., 7:363-368, 1947. 11. DAYAN, A. D. and A. H. E. MARSHALL, A.
16.
17.
18. 19. 20. 21. 22. 23.
24.
311
A. MILLER, F. J. PICK and N. E. RANKIN. Atypical Teratomas of the Pineal and Hypothalamus. J. Path. Bact., 92:1-28, 1966. KAGEYAMA, N. and R. BELSKY. Ectopic Pinealoma in the Chiasma Region. Neurology (Minneap.), 1:318-327, 1961. RAMSEY, H. J. Ultrastructure of a Pineal Tumor. Cancer, 18:1014-1025, 1965. PIERCE, G. B. Ultrastructure of Human Testicular Tumors. Cancer, 19:1963-1983, 1966. BEELEY, J. M. and J. J. DALY, W. R. TIMPERLEY and J. WARNER. Ectopic Pinealoma: An Unusual Clinical Presentation and a Histochemical Comparison with a Seminoma of the Testis. J. Neurol. Neurosurg. and Psychiat., 36:864-873, 1973. MINTZ, B. Formation and Early Development of Germ Cells. Symposium on the Germ Cells and Earliest Stages of Development. Milan, Fondazione A. Baselli, Instituto Lombardo, 1961. BOCHNER, S. J. and J. E. Scarff. Teratomas of the Pineal Body: Classification of Embryonal Tumors of the Pineal Body; Report of a Case of Teratoma of the Pineal Body Presenting with Formed Teeth. Arch. Surg., 36:303, 1938. BAGGENSTOSS, A. H. and J. G. Love. Pinealomas. Arch. Neurol. Psychiat., 41:1187, 1939. RUSSELL, D. S. Pinealoma: Its Relationship to Teratoma. J. Path. Bact., 56:145-150, 1944. RUSSELL, D. S. "Ectopic Pinealoma": Its Kinship to Atypical Teratoma of Pineal Gland; Report of a Case. J. Path. Bact., 68:125-129, 1954. BORIT, A. Embryonal Carcinoma of the Pineal Region. J. Path., 97:165-168, 1969. WALTON, K. Teratomas of the Pineal Region and Their Relationshp to Pinealomas. J. Path. Bact., 61:11-21, 1949. JAMES, W. and H. R. DUDLEY. Teratoma in the Region of the Pineal Body (Report of a Case). J. Neurosurg., 14:235-241, 1957. MARSHALL, A. H. E. and A. D. DAYAN. An Immune Reaction in Man Against Seminomas, Dysgerminomas, Pinealomas and the Mediastinal Tumours of Similar Histological Appearance. Lancet, 2:1102-1104, 1964.
p
(Sampson & Braxton, from page 280) 17. U. S. Public Health Service. The Health. Consequences of Smoking. A Public Health Service Review: 1967. U. S. Government Printing Office, Washington, D. C. 1968. 18. U.S. Department of Health, Education and Welfare. Progress Against Cancer 1970. U.S. Government Printing Office, Washington, D.C. 1970, pp. 58-59. 19. SEBRANEK, J. G. and R. G. CASSENS. Ni-
trosamines: A Review. J. Milk Food Technol., 36:76-91, 1973. 20. MILLER, J. A. and E. C. MILLER. Natural and Synthetic Chemical Carcinogens in the Etiology of Cancer. Cancer Res., 25:1292-1304, 1965. 21. BERG, J. W. and W. HAENSZEL and S. S. DEVESA. Epidemiology of Gastrointestinal Cancer. Seventh National Cancer Conference Proceedings. 1973, pp. 459-464.
