384
Surg Neurol 1992;37:384-7
Medulla Oblongata Germinoma in Association with Klinefelter Syndrome Masaaki Hashimoto, M.D., Madoka Hatasa, M.D., Souji Shinoda, M.D., and Toshio Masuzawa, M.D. Department of Surgical Neurology, Jichi Medical School, Yakushiji, Japan
Hashimoto M, Hatasa M, Shinoda S, Masuzawa T. Medulla oblongata germinoma in association with Klinefelter syndrome. Surg Neurol 1992;37:384-7.
A rare case of medulla oblongata germinoma in a 19-yearold Japanese man with Klinefelter syndrome is presented. Light microscopic examination of the resected specimen showed very few lymphocytes, a n d a n immunohistochemical study for placental alkaline phosphatase was of great diagnostic value. Up to now there have been only five cases of intracranial germ cell tumors in association with Klinefelter syndrome. These tumors were situated along in the midline structure. It is emphasized that endocrinological factors at the time of embryogenesis as well as a genetic malignant potential are important in the pathogenesis of extragonadal germ cell tumors associated with Klinefelter syndrome. KEYWORDS: Klinefelter syndr°me; Medulla °bl°ngata germinoma; Placental alkaline phosphatase; Endocrinological factor
Klinefelter syndrome is a well-documented condition of male primary hypogonadism associated with an abnormality of the sex chromosomes [8]. Sandberg [15] has reviewed the implications of X chromosome anomalies in neoplasm. It is recognized that patients with Klinefelter syndrome have a greater incidence of breast cancer [7], extragonadal germ cell tumors [ 1,2,4,12,14,17 ], and other malignancies [3,6]. Most of the extragonadal tumors have been in the mediastinum [12,17], only four cases having been reported in the central nervous system [1,2,4,14]. We report a rare case of a medulla oblongata germinoma occurring in association with Klinefelter syndrome and discuss the genesis of extragonadal germ cell tumors.
Address reprint requests to: Masaaki Hashimoto, M.D., Department of Surgical Neurology, Jichi Medical School, 3311-1 Yakushiji, Minamikawachi-machi, Kawachi-gun, Tochigi-ken, 329-04, Japan. Received August 19, 1991; accepted October 31, 1991.
© 1992 by Elsevier Science Publishing Co., Inc.
Case Report A 19-year-old Japanese man was referred to our hospital in February 1990, because of swallowing disturbance and sleep apnea. H e was o f somewhat more slender stature than normal. The pubic and axillary hair were scanty. H e had previously been diagnosed as having Klinefelter syndrome on the basis of clinical findings and a chromosomal karyotype o f 47,XXY. In May 1989 he had suffered from autonomic nervous disorder including orthostatic hypotension and difficulty in urination. Five months later he gradually became aware o f the swallowing disturbance and sleep apnea was observed. Therefore he was transferred to our hospital. A neurological examination showed paralysis o f the left ninth and tenth nerves, dysmetria, and bilateral Babinski sign. Blood gas analyses showed an oxygen saturation of 9 5 % - 9 8 % , oxygen partial pressure of 9 3 - 9 6 mm Hg, carbon dioxide partial pressure o f 4 4 - 4 6 mm Hg, and p H of 7.40-7.43 when he was awake. During sleep the oxygen saturation was 6 3 - 8 5 mm Hg, oxygen partial pressure 3 8 - 5 5 mm Hg, carbon dioxide partial pressure 8 1 - 9 0 mm Hg, and p H 7.29-7.34. Because of his sleep apnea the patient required a respirator during sleep. Serum testosterone was 3.1 ng/mL (normal, 4 - 1 2 ng/mL), luteinizing h o r m o n e was 17.4 mIU/mL (normal, 7 - 2 0 mIU/mL), and follicle-stimulating hormone was 37.1 mIU/mL (normal, 5 - 2 2 mIU/ mL). Alpha-fetoprotein, human chorionic gonadotropin, and carcinoembryonic antigen were all within the normal ranges. A chest x-ray film showed no abnormalities in the mediastinum. A plain computed tomography scan demonstrated an isodense mass with homogeneous enhancement in the fourth ventricle. On magnetic resonance imaging (MRI) the Tl-weighted SE image revealed an area of low signal intensity in the dorsal part o f the medulla extending to the fourth ventricle (Figure 1 A). After the administration of gadolinium diethylene-triamine-pentaacidic acid (Gd-DTPA), the mass showed intense, uniform enhancement. The pineal gland was free of tumor (Figure 1 B). 0090-3019/92/$5.00
Medulla Oblongata Germinoma
Figure 1. (A) Tl-weighted SE image (500/38) shows an area of low signal intensity in the dorsal part of the medulla oblongata extending to the fourth ventricle. (By After the administration of Gd-DTPA. the mass lesion shows intense, uniform enhancement. The pineal gland is free of tumor.
At surgery, performed through a midline suboccipital approach, apparent swelling of the medulla was observed. Between the cerebellar tonsils we observed a grayish-red tumor extending to the fourth ventricle through Magendie's foramen (Figure 2). The tumor borders were poorly defined in the dorsal region of the medulla oblongata. Since a frozen section of a biopsy specimen obtained from the fourth ventricle suggested germinoma, no further extirpation was carried out.
Figure 2. The tumor mass (arrowJ was visualized between the cerebellar tonsils through a midline suboccipital approach.
Surg Neurol 1992;3v:384-7
385
Postoperative Course The brain was irradiated with 30 cGy, and the tumor site received an additional 30 cGy. The spinal cord was irradiated with 35 cGy. MRI performed 2 months after the operation revealed no abnormal lesion in the medulla oblongata (Figure 3).
Figure 3. MRI performed after surgery and radiotherapy reveals no abnormal lesion in the medulla oblongata or fourth ventricle.
386
Surg Neurol 1992;37:384-7
Figure 4. (A) Large spheroid cells have well-defined cell membranes and large, irregular nuclei with coarselygranular chromatin. Small lymphocytes are very few among the large cells (hematoxylin and eosin stain × 230). (B) Some of these cells show mitotic figures (arrows) (hematoxylin and eosin stain x 450;. (C) Positive staining for PLAP is demonstrated in the cell membranes of large cells (PLAP stain x 450).
Preparation of Specimens
The tumor specimens were fixed in 6% formalin, embedded in paraffin, and stained with hematoxylin and eosin. For immunoperoxidase study, sections were stained by the peroxidase-antiperoxidase method with placental alkaline phosphatase (PLAP) (DAKO) and Leu7 (Becton Dickinson) as monoclonal antibedies. We used PLAP diluted at 100 : 1 and Leu7 at 10 : 1.
Pathological Findings
Light microscopy examination showed the presence of two distinct cell types. One consisted of large spheroid cells with well-defined cell membranes and large, irregular vesicular nuclei with coarsely granular chromatin. Some of these cells showed mitotic figures. The other type consisted of small, darkly stained cells with large nuclei. There were very few of them and they were interspersed among the large cells (Figure 4 A and B). A positive immunoperoxidase reaction for PLAP was demonstrated in the cell membranes of large cells (Figure 4 C). The cytoplasm of some large cells was also stained with Leu7.
Discussion Klinefelter syndrome has been estimated to occur at a rate of approximately 0.06% in the general population
Hashimoto et al
[5]. In 1942, Klinefelter became the first to describe the syndrome of gynecomastia, azoospermia, and small, firm testis [8]. In 1965 Jackson et al [7] reported a high incidence of breast cancer in patients with Klinefelter syndrome. Other studies have shown that patients with Klinefelter syndrome seem to be at increased risk of certain malignancies including leukemia [6], lymphoma [3], Leydig cell tumor [13], and extragonadal germ cell tumors [1,2,4,12,14,17]. Sogge et al [ 17] reviewed the literature on 24 cases of primary mediastinal germ cell tumors and found two cases of Klinefelter syndrome. T h e r e f o r e he emphasized that Klinefelter patients may be predisposed to the development of germ cell tumors. Rubinstein [14] was the first to describe extragonadal germ cell tumors in the central nervous system in association with Klinefelter syndrome. Up to now there have been only five cases (including this one) ofintracranial germ cell tumors associated with Klinefelter syndrome [1,2,4,14] (Table 1). The tumors in all five cases were situated along the midline structure: two in the pineal region, one in the suprasellar region, one in the hypothalamus, and in this case, in the medulla oblongata. All tumors were histologically diagnosed as germinoma; there were no seminomas in the mediastinum [12]. The most common sites for intracranial germinoma are the pineal and suprasellar regions [18]. A search of the literature revealed no reports of tumor in the region of the medulla oblongata, even in association with Klinefelter syndrome. The pathogenesis of the association o f malignancies and Klinefelter syndrome remains conjectural. Mukerjee et al [11] reported that fibroblasts from patients with Klinefelter syndrome were transformed to malignancy three to ten times more frequently by simian papovavirus 40 in patients so afflicted than in a normal
Medulla Oblongata Germinoma
Surg N e u r o l 1992;37:384-7
T a b l e 1. Cases of Klinefelter Syndrome with Cerebral Germ
Cell Tumors Reference
Age (yr)
Site of tumor
Histology
Rubinstein [14] Aphagon et al [1] Ellis et al [4] Arens et al [2] Present case
16 20 12 15 19
Pineal region Suprasellar region Posterior hypothalamus Pineal region Medulla oblongata
Germinoma Germinoma Germinoma Germinoma Germinoma
control population. With respect to the pathogenesis of extragonadal germ cell tumor, Arens et al [2] speculated that in Klinefelter syndrome there is an alteration in gonadal ridge differentiation that leads to malinduction and dyssynchronization of migration of the primordial germ cells. As a result primordial germ cells continue to advance toward the midline structure [2]. These ectopic cells differentiate into one of the extragonadal germ cell tumors because of some unknown carcinogenic trigger, which we consider to be an endocrinological factor, and because of their genetic malignant potential, as Mukerjee indicated. Hypergonadotropic stimulation during embryogenesis is believed to elicit malignant change that gives rise to male breast cancer and germ cell tumors [19]. In fact estimates suggest that the incidence of breast cancer in patients with Klinefelter syndrome is up to 20 times greater than that in males with a normal karyotype [7]. Light microscopy examination of germinoma shows a distinct histological feature known as the "two-cell pattern." In our case only a few of the small cells were observed among the large cells, and we could not be certain of a definite diagnosis with hematoxylin and eosin staining alone. Therefore, immunoperoxidase studies for PLAP and Leu7 were of great diagnostic value. About 90% ofgerminoma cases are positive for PLAP, making this the most effective test for its diagnosis [9]. Leu7, which is known to cross-react with myelin-associated protein and to be positive in oligodendroglioma [16], was noted in the cytoplasm of some large cells. Motoi et al [10] reported that Leu7 was positive for astrocytoma, glioblastoma, and choroid plexus papilloma, in addition to oligodendroglioma, and was negative for germinoma. More cases of germinoma must be examined to determine whether Leu7 is positive or not. At present, the 5-year survival rate for cerebral germinoma is more than 80% because of effective chemotherapy (including cis-platinum) and radiotherapy. In our case, we have detected no recurrence of the tumor after radiotherapy. A definite diagnosis for germinoma and effective therapies are necessary for a good prognosis. To obtain a definite diagnosis, it is important to evaluate the pathological findings by immunohistochemical studies for PLAP and Leu7. Patients should undergo chemo-
387
therapy and/or radiotherapy as soon as the pathological diagnosis has been made.
References 1. Aphagon, A, Yoshida Y, Kusuno K, Uno T. Suprasellar germinoma in association with Klinefelter's syndrome. Case report. J Neurosurg 1983;58:136-8. 2. Arens R, Marcus D, Engelberg S, Findler G, Goodman RM, Passwelt JH. Cerebral germinomas and Klinefelter syndrome. Cancer 1988;61:1228-31. 3. Becher R. Klinefetter's syndrome and malignant lymphoma. Cancer Genet Cytogenet 1986;21:271-3. 4. Ellis SJ, Crockard A, Barnard RO. Klinefelter's syndrome, cerebral germinoma, Chiari malformation, and syrinx: a case report. Neurosurgery 1986;18:220-2. 5. Gerald PS. Current concepts in genetics: sex chromosome disorder. N Engl J Med 1976;294:706-8. 6. Horsman DE, Pantzar JT, Dill FJ, Kalousek DK. Klinefelter's syndrome and acute leukemia. Cancer Genet Cytogenet 1987;26:375-6. 7. Jackson AW, Muldal S, Ockey CH, O'connor PJ. Carcinoma of male breast in association with Klinefelter syndrome. Br Med J 1965;1:223-7. 8. Klinefelter HFJr, Reifenstein EC Jr, Albright F. Syndrome characterized by gynecomastia, aspermatogenesis without c~-leydigism and increased excretion of follicle-stimulating hormone. J Clin Endocrinol 1942;2:615-27. 9. Kurisaka M. Germ cell tumor. In: Kurisaka M, Nakazato Y, eds. lmmunohistochemical diagnosis of brain tumors. Tokyo: Asakura Publishing Company, 1986:113-29. 10. Motoi M, Yoshino T, Hayashi K, Nose S, Horie Y, Ogawa K. Immunohistochemical studies on human brain tumor using antiLeu7 monoclonal antibody in paraffin-embedded specimens. Acta Neuropathol (Berl) 1985;66:75-77. 11. Mukerjee D, Bowen J, Anderson DE. Simian papovavirus 40 transformation of cells from cancer patient with XY/XXY mosaic Klinefelter's syndrome. Cancer Res 1970;30:176972.
12. Nichols CR, Heerema NA, Palmer C, Loehrer PJ, Williams SD, Einhorn LH. Klinefelter's syndrome associated with mediastinal germ cell neoplasms. J Clin Oncol 1987;5:1290-4. 13. Oda Y, Kawahara E, Nakanishi I, Nakamura H. A case of Leydig cell tumor of the testis in a patient with Klinefelter's syndrome. J Jpn Soc Clin Cytol 1987;26:664-9. 14. Rubinstein LJ. Tumors of the central nervous system. In Rubinstein LJ, ed. Atlas of tumor pathology. Washington DC: Armed Forces Institute of Pathology, 1972:270. 15. Sandberg AA. The X chromosome in human neoplasia, including sex chromatin and congenital conditions with X chromosome anomalies, ln: Sandberg AA, ed. Cytogenetics of the mammalian X chromosome. N e w York: Alan R. Liss, 1983:459-98. 16. Schuller-Petrovics S, Gebhalrt W, Lassmann H, Rumpold H, Kraft D. A shared antigenic determinant between natural killer cells and nervous tissue. Nature 1983;306:179-81. 17. Sogge MR, McDonald SD, Cofold PB. Malignant potential of the dysplastic germ cell in Klinefelter's syndrome. Am J Med 1979;66:515-8. 18. Takeuchi J, Handa H, Nagata I. Suprasellar germinoma. J Neurosurg 1978~49:41-8. 19. Wan SP, Uechi MD. Seminoma in atrophic testis. Urology 1980; 16:183-5.
Surg Neurol 1992;37:384-7
Medulla Oblongata Germinoma in Association with Klinefelter Syndrome Masaaki Hashimoto, M.D., Madoka Hatasa, M.D., Souji Shinoda, M.D., and Toshio Masuzawa, M.D. Department of Surgical Neurology, Jichi Medical School, Yakushiji, Japan
Hashimoto M, Hatasa M, Shinoda S, Masuzawa T. Medulla oblongata germinoma in association with Klinefelter syndrome. Surg Neurol 1992;37:384-7.
A rare case of medulla oblongata germinoma in a 19-yearold Japanese man with Klinefelter syndrome is presented. Light microscopic examination of the resected specimen showed very few lymphocytes, a n d a n immunohistochemical study for placental alkaline phosphatase was of great diagnostic value. Up to now there have been only five cases of intracranial germ cell tumors in association with Klinefelter syndrome. These tumors were situated along in the midline structure. It is emphasized that endocrinological factors at the time of embryogenesis as well as a genetic malignant potential are important in the pathogenesis of extragonadal germ cell tumors associated with Klinefelter syndrome. KEYWORDS: Klinefelter syndr°me; Medulla °bl°ngata germinoma; Placental alkaline phosphatase; Endocrinological factor
Klinefelter syndrome is a well-documented condition of male primary hypogonadism associated with an abnormality of the sex chromosomes [8]. Sandberg [15] has reviewed the implications of X chromosome anomalies in neoplasm. It is recognized that patients with Klinefelter syndrome have a greater incidence of breast cancer [7], extragonadal germ cell tumors [ 1,2,4,12,14,17 ], and other malignancies [3,6]. Most of the extragonadal tumors have been in the mediastinum [12,17], only four cases having been reported in the central nervous system [1,2,4,14]. We report a rare case of a medulla oblongata germinoma occurring in association with Klinefelter syndrome and discuss the genesis of extragonadal germ cell tumors.
Address reprint requests to: Masaaki Hashimoto, M.D., Department of Surgical Neurology, Jichi Medical School, 3311-1 Yakushiji, Minamikawachi-machi, Kawachi-gun, Tochigi-ken, 329-04, Japan. Received August 19, 1991; accepted October 31, 1991.
© 1992 by Elsevier Science Publishing Co., Inc.
Case Report A 19-year-old Japanese man was referred to our hospital in February 1990, because of swallowing disturbance and sleep apnea. H e was o f somewhat more slender stature than normal. The pubic and axillary hair were scanty. H e had previously been diagnosed as having Klinefelter syndrome on the basis of clinical findings and a chromosomal karyotype o f 47,XXY. In May 1989 he had suffered from autonomic nervous disorder including orthostatic hypotension and difficulty in urination. Five months later he gradually became aware o f the swallowing disturbance and sleep apnea was observed. Therefore he was transferred to our hospital. A neurological examination showed paralysis o f the left ninth and tenth nerves, dysmetria, and bilateral Babinski sign. Blood gas analyses showed an oxygen saturation of 9 5 % - 9 8 % , oxygen partial pressure of 9 3 - 9 6 mm Hg, carbon dioxide partial pressure o f 4 4 - 4 6 mm Hg, and p H of 7.40-7.43 when he was awake. During sleep the oxygen saturation was 6 3 - 8 5 mm Hg, oxygen partial pressure 3 8 - 5 5 mm Hg, carbon dioxide partial pressure 8 1 - 9 0 mm Hg, and p H 7.29-7.34. Because of his sleep apnea the patient required a respirator during sleep. Serum testosterone was 3.1 ng/mL (normal, 4 - 1 2 ng/mL), luteinizing h o r m o n e was 17.4 mIU/mL (normal, 7 - 2 0 mIU/mL), and follicle-stimulating hormone was 37.1 mIU/mL (normal, 5 - 2 2 mIU/ mL). Alpha-fetoprotein, human chorionic gonadotropin, and carcinoembryonic antigen were all within the normal ranges. A chest x-ray film showed no abnormalities in the mediastinum. A plain computed tomography scan demonstrated an isodense mass with homogeneous enhancement in the fourth ventricle. On magnetic resonance imaging (MRI) the Tl-weighted SE image revealed an area of low signal intensity in the dorsal part o f the medulla extending to the fourth ventricle (Figure 1 A). After the administration of gadolinium diethylene-triamine-pentaacidic acid (Gd-DTPA), the mass showed intense, uniform enhancement. The pineal gland was free of tumor (Figure 1 B). 0090-3019/92/$5.00
Medulla Oblongata Germinoma
Figure 1. (A) Tl-weighted SE image (500/38) shows an area of low signal intensity in the dorsal part of the medulla oblongata extending to the fourth ventricle. (By After the administration of Gd-DTPA. the mass lesion shows intense, uniform enhancement. The pineal gland is free of tumor.
At surgery, performed through a midline suboccipital approach, apparent swelling of the medulla was observed. Between the cerebellar tonsils we observed a grayish-red tumor extending to the fourth ventricle through Magendie's foramen (Figure 2). The tumor borders were poorly defined in the dorsal region of the medulla oblongata. Since a frozen section of a biopsy specimen obtained from the fourth ventricle suggested germinoma, no further extirpation was carried out.
Figure 2. The tumor mass (arrowJ was visualized between the cerebellar tonsils through a midline suboccipital approach.
Surg Neurol 1992;3v:384-7
385
Postoperative Course The brain was irradiated with 30 cGy, and the tumor site received an additional 30 cGy. The spinal cord was irradiated with 35 cGy. MRI performed 2 months after the operation revealed no abnormal lesion in the medulla oblongata (Figure 3).
Figure 3. MRI performed after surgery and radiotherapy reveals no abnormal lesion in the medulla oblongata or fourth ventricle.
386
Surg Neurol 1992;37:384-7
Figure 4. (A) Large spheroid cells have well-defined cell membranes and large, irregular nuclei with coarselygranular chromatin. Small lymphocytes are very few among the large cells (hematoxylin and eosin stain × 230). (B) Some of these cells show mitotic figures (arrows) (hematoxylin and eosin stain x 450;. (C) Positive staining for PLAP is demonstrated in the cell membranes of large cells (PLAP stain x 450).
Preparation of Specimens
The tumor specimens were fixed in 6% formalin, embedded in paraffin, and stained with hematoxylin and eosin. For immunoperoxidase study, sections were stained by the peroxidase-antiperoxidase method with placental alkaline phosphatase (PLAP) (DAKO) and Leu7 (Becton Dickinson) as monoclonal antibedies. We used PLAP diluted at 100 : 1 and Leu7 at 10 : 1.
Pathological Findings
Light microscopy examination showed the presence of two distinct cell types. One consisted of large spheroid cells with well-defined cell membranes and large, irregular vesicular nuclei with coarsely granular chromatin. Some of these cells showed mitotic figures. The other type consisted of small, darkly stained cells with large nuclei. There were very few of them and they were interspersed among the large cells (Figure 4 A and B). A positive immunoperoxidase reaction for PLAP was demonstrated in the cell membranes of large cells (Figure 4 C). The cytoplasm of some large cells was also stained with Leu7.
Discussion Klinefelter syndrome has been estimated to occur at a rate of approximately 0.06% in the general population
Hashimoto et al
[5]. In 1942, Klinefelter became the first to describe the syndrome of gynecomastia, azoospermia, and small, firm testis [8]. In 1965 Jackson et al [7] reported a high incidence of breast cancer in patients with Klinefelter syndrome. Other studies have shown that patients with Klinefelter syndrome seem to be at increased risk of certain malignancies including leukemia [6], lymphoma [3], Leydig cell tumor [13], and extragonadal germ cell tumors [1,2,4,12,14,17]. Sogge et al [ 17] reviewed the literature on 24 cases of primary mediastinal germ cell tumors and found two cases of Klinefelter syndrome. T h e r e f o r e he emphasized that Klinefelter patients may be predisposed to the development of germ cell tumors. Rubinstein [14] was the first to describe extragonadal germ cell tumors in the central nervous system in association with Klinefelter syndrome. Up to now there have been only five cases (including this one) ofintracranial germ cell tumors associated with Klinefelter syndrome [1,2,4,14] (Table 1). The tumors in all five cases were situated along the midline structure: two in the pineal region, one in the suprasellar region, one in the hypothalamus, and in this case, in the medulla oblongata. All tumors were histologically diagnosed as germinoma; there were no seminomas in the mediastinum [12]. The most common sites for intracranial germinoma are the pineal and suprasellar regions [18]. A search of the literature revealed no reports of tumor in the region of the medulla oblongata, even in association with Klinefelter syndrome. The pathogenesis of the association o f malignancies and Klinefelter syndrome remains conjectural. Mukerjee et al [11] reported that fibroblasts from patients with Klinefelter syndrome were transformed to malignancy three to ten times more frequently by simian papovavirus 40 in patients so afflicted than in a normal
Medulla Oblongata Germinoma
Surg N e u r o l 1992;37:384-7
T a b l e 1. Cases of Klinefelter Syndrome with Cerebral Germ
Cell Tumors Reference
Age (yr)
Site of tumor
Histology
Rubinstein [14] Aphagon et al [1] Ellis et al [4] Arens et al [2] Present case
16 20 12 15 19
Pineal region Suprasellar region Posterior hypothalamus Pineal region Medulla oblongata
Germinoma Germinoma Germinoma Germinoma Germinoma
control population. With respect to the pathogenesis of extragonadal germ cell tumor, Arens et al [2] speculated that in Klinefelter syndrome there is an alteration in gonadal ridge differentiation that leads to malinduction and dyssynchronization of migration of the primordial germ cells. As a result primordial germ cells continue to advance toward the midline structure [2]. These ectopic cells differentiate into one of the extragonadal germ cell tumors because of some unknown carcinogenic trigger, which we consider to be an endocrinological factor, and because of their genetic malignant potential, as Mukerjee indicated. Hypergonadotropic stimulation during embryogenesis is believed to elicit malignant change that gives rise to male breast cancer and germ cell tumors [19]. In fact estimates suggest that the incidence of breast cancer in patients with Klinefelter syndrome is up to 20 times greater than that in males with a normal karyotype [7]. Light microscopy examination of germinoma shows a distinct histological feature known as the "two-cell pattern." In our case only a few of the small cells were observed among the large cells, and we could not be certain of a definite diagnosis with hematoxylin and eosin staining alone. Therefore, immunoperoxidase studies for PLAP and Leu7 were of great diagnostic value. About 90% ofgerminoma cases are positive for PLAP, making this the most effective test for its diagnosis [9]. Leu7, which is known to cross-react with myelin-associated protein and to be positive in oligodendroglioma [16], was noted in the cytoplasm of some large cells. Motoi et al [10] reported that Leu7 was positive for astrocytoma, glioblastoma, and choroid plexus papilloma, in addition to oligodendroglioma, and was negative for germinoma. More cases of germinoma must be examined to determine whether Leu7 is positive or not. At present, the 5-year survival rate for cerebral germinoma is more than 80% because of effective chemotherapy (including cis-platinum) and radiotherapy. In our case, we have detected no recurrence of the tumor after radiotherapy. A definite diagnosis for germinoma and effective therapies are necessary for a good prognosis. To obtain a definite diagnosis, it is important to evaluate the pathological findings by immunohistochemical studies for PLAP and Leu7. Patients should undergo chemo-
387
therapy and/or radiotherapy as soon as the pathological diagnosis has been made.
References 1. Aphagon, A, Yoshida Y, Kusuno K, Uno T. Suprasellar germinoma in association with Klinefelter's syndrome. Case report. J Neurosurg 1983;58:136-8. 2. Arens R, Marcus D, Engelberg S, Findler G, Goodman RM, Passwelt JH. Cerebral germinomas and Klinefelter syndrome. Cancer 1988;61:1228-31. 3. Becher R. Klinefetter's syndrome and malignant lymphoma. Cancer Genet Cytogenet 1986;21:271-3. 4. Ellis SJ, Crockard A, Barnard RO. Klinefelter's syndrome, cerebral germinoma, Chiari malformation, and syrinx: a case report. Neurosurgery 1986;18:220-2. 5. Gerald PS. Current concepts in genetics: sex chromosome disorder. N Engl J Med 1976;294:706-8. 6. Horsman DE, Pantzar JT, Dill FJ, Kalousek DK. Klinefelter's syndrome and acute leukemia. Cancer Genet Cytogenet 1987;26:375-6. 7. Jackson AW, Muldal S, Ockey CH, O'connor PJ. Carcinoma of male breast in association with Klinefelter syndrome. Br Med J 1965;1:223-7. 8. Klinefelter HFJr, Reifenstein EC Jr, Albright F. Syndrome characterized by gynecomastia, aspermatogenesis without c~-leydigism and increased excretion of follicle-stimulating hormone. J Clin Endocrinol 1942;2:615-27. 9. Kurisaka M. Germ cell tumor. In: Kurisaka M, Nakazato Y, eds. lmmunohistochemical diagnosis of brain tumors. Tokyo: Asakura Publishing Company, 1986:113-29. 10. Motoi M, Yoshino T, Hayashi K, Nose S, Horie Y, Ogawa K. Immunohistochemical studies on human brain tumor using antiLeu7 monoclonal antibody in paraffin-embedded specimens. Acta Neuropathol (Berl) 1985;66:75-77. 11. Mukerjee D, Bowen J, Anderson DE. Simian papovavirus 40 transformation of cells from cancer patient with XY/XXY mosaic Klinefelter's syndrome. Cancer Res 1970;30:176972.
12. Nichols CR, Heerema NA, Palmer C, Loehrer PJ, Williams SD, Einhorn LH. Klinefelter's syndrome associated with mediastinal germ cell neoplasms. J Clin Oncol 1987;5:1290-4. 13. Oda Y, Kawahara E, Nakanishi I, Nakamura H. A case of Leydig cell tumor of the testis in a patient with Klinefelter's syndrome. J Jpn Soc Clin Cytol 1987;26:664-9. 14. Rubinstein LJ. Tumors of the central nervous system. In Rubinstein LJ, ed. Atlas of tumor pathology. Washington DC: Armed Forces Institute of Pathology, 1972:270. 15. Sandberg AA. The X chromosome in human neoplasia, including sex chromatin and congenital conditions with X chromosome anomalies, ln: Sandberg AA, ed. Cytogenetics of the mammalian X chromosome. N e w York: Alan R. Liss, 1983:459-98. 16. Schuller-Petrovics S, Gebhalrt W, Lassmann H, Rumpold H, Kraft D. A shared antigenic determinant between natural killer cells and nervous tissue. Nature 1983;306:179-81. 17. Sogge MR, McDonald SD, Cofold PB. Malignant potential of the dysplastic germ cell in Klinefelter's syndrome. Am J Med 1979;66:515-8. 18. Takeuchi J, Handa H, Nagata I. Suprasellar germinoma. J Neurosurg 1978~49:41-8. 19. Wan SP, Uechi MD. Seminoma in atrophic testis. Urology 1980; 16:183-5.
