Surg Neurol 1992;38:141-5
141
Central Neurocytoma Presenting with Gigantism: Case Report Yuzo Araki, M.D., Noboru Sakai, M.D., Takashi Andoh, M.D., Shin-ichi Yoshimura, M.D., and Hiromu Yamada, M.D. Department of Neurosurgery, Gifu University School of Medicine, 40 Tsukasa-machi, Gifu 500, Japan
Araki Y, Sakai N, Andoh T, Yoshimura S, Yamada H. Central neurocytoma presenting with gigantism: case report. Surg Neurol 1992;38:141-5.
We report a case of central neurocytoma presenting with gigantism. The patient was a 19-year-old man with a 2year history of rapid growth. Computed tomography revealed a round, slightly enhancing calcified tumor in the septal region. This lesion was resected, and postoperative radiotherapy was given. The preoperative serum growth hormone level was 20.7 ng/mL, and postoperatively this fell to 0.9 ng/mL. Pituitary dysfunction was not noted either before or after the operation. A low level of production of growth hormone releasing factor was detected when tumor cells obtained during surgery were cultured. WORDS: Central neurocytoma; Gigantism; Growth hormone; Growth hormone releasing factor (GRF)
KEY
after a minor head injury. Although he had no neurological signs, the scan showed a calcified mass in the interseptal region.
Examination On admission, his height was 190 cm (more than 2 SD above that of the average Japanese male) and his weight was 75 kg. Rapid growth had begun at the age o f 16 years (Figure 1). O n examination, glabellar protrusion and long fingers were noted (Figure 2, left). Figure 1. Growth chart in Japanese. B, Ht. (cm) 19C
18(
Central neurocytoma was first reported by Hassoun et al [4] in 1982, and is characterized by an intraventricular location, a predominant occurrence in young adults, a benign course, oligodendroglioma-like histology, and ultrastructural features of neuronal differentiation. T h e r e have been previous reports on 22 cases of central neurocytoma or intraventricular differentiated neuroblastoma, with electron microscopic diagnosis [ 2 , 4 - 6 , 1 0 ] , but none of these tumors were associated with gigantism. In this report, we present the first case of central neurocytoma associated with gigantism and discuss the possible causative mechanisms.
17[ 1GC 15C
B.Wt. (kg) 100
14C
90
13C
8O
12C
70
110
6O
100
5O
90
4O
80
30
7O
2O
GO
10
Case Report A 19-year-old man had noted a rapid increase in height for the previous 2 years. H e underwent computed tomographic (CT) scan examination on D e c e m b e r 22, 1989,
Address reprint requests to."Yuzo Araki, M.D., Department of Neurosurgery, Gifu University School of Medicine, 40 Tsukasa-machi, Gifu 500, Japan Received October 22, 1991; accepted January 23, 1992.
© 1992 by Elsevier Science Publishing Co., Inc.
50 0
1
2
3
4
5
6
7 8
9 10 11 12 13 14 15 16 17 18 19 20 0 Years
Growth Chart 0090-3019/92/$5.00
142
Surg Neurol 1992;38:141-5
Araki et al
Figure 2. Facial features and skull radiograph, indicating glabellar protrusion.
A plain x-ray film of the skull showed glabellar protrusion with no sellar enlargement (Figure 2, right). His heel pad thickness was 19 mm. CT scanning and magnetic resonance imaging (MRI) showed a partially calcified solid tumor (3 x 2 x 1.3 cm) that occupied the septum
pellucidum and lamina terminalis. No abnormalities of the pituitary gland were noted. Contrast enhancement of the lesion was only slight (Figures 3 and 4). Endocrinological examinations showed that the serum growth hormone (GH), luteinizing hormone, prolactin,
Figure 3. C T scans, showing an enhanced lesion at the septal region with some calcifications. P, plain; CE, contrast enhancement.
Central Neurocytoma with Gigantism
Surg Neurol 1992;38:141-5
143
j Figure 4. Tl-weighted MRI scans, showing intraventricular tumor developingfrom the septum pellucidum with positive gadolinium diethylenetriaminepentaacetic acia enhancement.
and cortisol levels were elevated to 20.7 ng/mL, 14.9 mIU/mL, 14.0 ng/mL, and 17.4 /a.g/dL, respectively, while the adrenocorticotropic hormone level was 60 pg/ mL. Follicle-stimulating hormone, thyrotropin, and antidiuretic hormone levels were within the normal range (Table 1). GH responded normally to glucose (75 g) and CB-154 (5 rag), and slightly increased in response to thyrotropin-releasing hormone (0.5 mg). Serum levels
Table 1.
i~i~ ~i~
of growth hormone-releasing factor (GRF) and somatostatin were not elevated.
Operation Subtotal resection of the tumor was performed via an anterior transcallosal approach on February 2, 1990. The tumor was located in the interseptal region and extended
EndocrinologicalData Hormone (normal range)
Growth hormone, ng/mL (0-5.0) Luteinizing hormone, mIU/mL (1.1-8.8) Follicle-stimulating hormone, ml U/mL ( 1.8-13.6) Prolactin, ng/mL (0-10.0) Thyrotropin,/~U/mL (0.4-4.4) Adrenocorticotropic hormone, pg/mL (30-60) Antidiuretic hormone, pg/mL (0.3-3.5) Cortisol, ~g/dL ( 3.7-13.0~ Triiodothyronine, ng/dL (100-170) Thyroxine,/a.g/dL (5.0-11.0) Free triiodothyronine, pg/dL (2.7-5.9) Free thyroxine, ng/dL (0.86-1.96) Growth hormone-releasing factor, pg/mL (10.3 ± 4,1) Somatomedin-C, U/mL (0-2.0) Somatostatin, pg/mL ( 1.0-12 ) Abnormal value.
Before surgery
After surgery
20.7 ~ 14.9 ~
0.9 4.7 4.6 7.5 1.1
12.0 14-0 ~ 1.2 60 a 0.6 17.4 ~ 135 8.4 4.8 1.33 5.1 0.80
100 6.8 2.8 1.04 6.6 0.74
--
24 ~
5.2
144
Surg Neurol 1992;38:141-5
Figure5. Photomicrographs of tumor histology. (A) Monotonous proliferation of tumor cells and anuclear fibrillated matrix (hematoxylin and eosin stain, original magnification × 100). (B) Positive reaction for glial fibrillary acidic protein (GFAP) is seen in reactive astrocytes (GFAP stain, original magnification × 200). (C) Positive reaction for neuron-specific enolase (NSE) is seen (NSE stain, original magnification x 200). (D) Electron microscopic features of tumor cells. Synapse-like structures and dense core vesicles are seen (original magnification × 15. 700).
into the hypothalamus. It was a generally soft, gray mass with some hard, calcified areas. There was little bleeding during the operation.
Postoperative
Course
After surgery, the patient received irradiation to a total dose of 39 Gy. Follow-up MRI examination demonstrated shrinking of the residual tumor mass, and no further increase in his height was noted after the operation. Postoperative endocrinological examinations showed that the basal serum G H level had fallen to 0.9 ng/dL (Table 1).
Araki et al
On histological examination, the tumor resembled an oligodendroglioma; the cells had predominantly round nuclei with a perinuclear halo, but broad rosettes were also present. Immunocytochemical studies showed no staining of the tumor cells by glial fibrillary acidic protein, except for a few astrocytes, but the tumor cells were positive for neuron-specific enolase (Figure 5 A - C ) . Electron microscopy revealed numerous 160-nm densecored vesicles, 70-nm clear vesicles, and some synaptic structures (Figure 5 D). These findings were characteristic of a central neurocytoma. In addition, tumor cells obtained at operation were cultured for 2 weeks in a medium of 18% fetal bovine serum and RPMI-1640 (5% CO2, 37°C). A low level o f GRF was detected (5.7 pg/mL), but G H production was not found.
Discussion Twenty-two cases o f central neurocytoma or differentiated neuroblastoma with electron microscopy data have been reported previously [ 2 - 1 1 ] . In addition, some tumors, with similar neuroradiological or pathological findings have been reported as oligodendrogliomas aris-
Central Neurocytoma with Gigantism
ing from the midline [10]. However, the association of gigantism or acromegaly with such tumors has not previously been noted. Our present patient was not so tall by Caucasian standards, but he was of abnormally tall stature for a Japanese and had an elevated serum G H level. In general, gigantism is caused by hypersecretion of G H from a pituitary adenoma or hyperplastic pituitary in a child or adolescent. Some pancreatic tumors or hypothalamic gangliocytomas produce GRF, which causes a secondary increase of the serum G H level and thus produces acromegaly [ 1] or gigantism. Our patient had neither a pituitary tumor nor a pancreatic tumor, and the presence of GRF in the tumor culture medium supports the possibility that he had a GRF-producing central neurocytoma that caused gigantism. We could not obtain an antibody for the immunohistochemical staining of GRF, so no examination of the operative specimen for GRF staining was performed. However, Deimling et al [2] have reported a case of central neurocytoma with gangliold cells, which have the potential to differentiate into mature neurons that could produce GRF. The other possibility is that gigantism may have been caused by hormonal imbalance due to compression of the hypothalamus by the tumor, since G H production is regulated by GRF and somatostatin, although the serum GRF level was not elevated in this patient.
Surg Neurol 1992;38:141-5
145
References 1. Asa SL, Scheithauer BW, Bilbao JM, Horvath E, Ryan N, Kovacs K, Randall RV, Law ER Jr, Singer W. Linfoot JA, Thorner MO, Vale W. A case for hypothalamic acromegaly: A clinicopathological study of six patients ~vith hypothalamic gangliocytomas producing growth hormone-releasing factor. J Clin Endocrinol Metab 1984;58:796-803. 2. Deimling A, Janzer R, Kleihues P, Wiestler OD. Patterns of differentiation in central neurocytoma. An immunohistochemical study of eleven biopsies. Acta Neuropathol 1990;79:473-9. 3. Grisoli F, Vincentelli F, Boudouresques G, Delpuech F, Hassoun J, Raybaud C. Primary cerebral neuroblastoma in an adult man. Surg Neurol 1981;16:266-70. 4. Hassoun J, Gambarelli D, Grisoli F, Pellet W, Salamon G, Pellissier JF, Toga M. Central neurocytoma. An electron-microscopic study of two cases. Acta Neuropathol (Berl) 1982;56:151-6. 5. Miyata M, Yamashita H, Shirakata S, Takeda Z. Central neurocytoma. Case report. Neurol Med Chir (Tokyo) 1989;29:1148-52. 6. Nishio S, TashimaT, Takeshita I, Fukui M. Intraventricular neurocytoma: clinicopathological features of six cases. J Neurosurg 1988;68:665-70. 7. Pearl GS, Mirra SS, Miles ML. Intracerebral ganglioneuroblastoma with intracytoplasmic microtubular aggregates: case report and ultrastructual study. Ultrastruct Pathol 1981;2:337-42. 8. Pearl GS, Takei Y, Bakay RAE, Davis P. Intraventricular primary cerebral neuroblastoma in adults: report of three cases. Neurosurgery 1985;16:847-9. 9. Townsend JJ, Seaman JP. Central neurocytoma--a rare benign intraventricular tumor. Acta Neuropathol (Berl) 1986;71: 167-70. 10. Tsujita Y, Nagashima K, Takakura K. A clinicopathological study of central neurocytoma. Neurol Surg 1989;41:547-58. 11. Wilson AJ, Leafier DH, Kohout ND. Differentiated cerebral neuroblastoma: a tumor in need of discovery. Hum Pathol 1985;16:647-9.
141
Central Neurocytoma Presenting with Gigantism: Case Report Yuzo Araki, M.D., Noboru Sakai, M.D., Takashi Andoh, M.D., Shin-ichi Yoshimura, M.D., and Hiromu Yamada, M.D. Department of Neurosurgery, Gifu University School of Medicine, 40 Tsukasa-machi, Gifu 500, Japan
Araki Y, Sakai N, Andoh T, Yoshimura S, Yamada H. Central neurocytoma presenting with gigantism: case report. Surg Neurol 1992;38:141-5.
We report a case of central neurocytoma presenting with gigantism. The patient was a 19-year-old man with a 2year history of rapid growth. Computed tomography revealed a round, slightly enhancing calcified tumor in the septal region. This lesion was resected, and postoperative radiotherapy was given. The preoperative serum growth hormone level was 20.7 ng/mL, and postoperatively this fell to 0.9 ng/mL. Pituitary dysfunction was not noted either before or after the operation. A low level of production of growth hormone releasing factor was detected when tumor cells obtained during surgery were cultured. WORDS: Central neurocytoma; Gigantism; Growth hormone; Growth hormone releasing factor (GRF)
KEY
after a minor head injury. Although he had no neurological signs, the scan showed a calcified mass in the interseptal region.
Examination On admission, his height was 190 cm (more than 2 SD above that of the average Japanese male) and his weight was 75 kg. Rapid growth had begun at the age o f 16 years (Figure 1). O n examination, glabellar protrusion and long fingers were noted (Figure 2, left). Figure 1. Growth chart in Japanese. B, Ht. (cm) 19C
18(
Central neurocytoma was first reported by Hassoun et al [4] in 1982, and is characterized by an intraventricular location, a predominant occurrence in young adults, a benign course, oligodendroglioma-like histology, and ultrastructural features of neuronal differentiation. T h e r e have been previous reports on 22 cases of central neurocytoma or intraventricular differentiated neuroblastoma, with electron microscopic diagnosis [ 2 , 4 - 6 , 1 0 ] , but none of these tumors were associated with gigantism. In this report, we present the first case of central neurocytoma associated with gigantism and discuss the possible causative mechanisms.
17[ 1GC 15C
B.Wt. (kg) 100
14C
90
13C
8O
12C
70
110
6O
100
5O
90
4O
80
30
7O
2O
GO
10
Case Report A 19-year-old man had noted a rapid increase in height for the previous 2 years. H e underwent computed tomographic (CT) scan examination on D e c e m b e r 22, 1989,
Address reprint requests to."Yuzo Araki, M.D., Department of Neurosurgery, Gifu University School of Medicine, 40 Tsukasa-machi, Gifu 500, Japan Received October 22, 1991; accepted January 23, 1992.
© 1992 by Elsevier Science Publishing Co., Inc.
50 0
1
2
3
4
5
6
7 8
9 10 11 12 13 14 15 16 17 18 19 20 0 Years
Growth Chart 0090-3019/92/$5.00
142
Surg Neurol 1992;38:141-5
Araki et al
Figure 2. Facial features and skull radiograph, indicating glabellar protrusion.
A plain x-ray film of the skull showed glabellar protrusion with no sellar enlargement (Figure 2, right). His heel pad thickness was 19 mm. CT scanning and magnetic resonance imaging (MRI) showed a partially calcified solid tumor (3 x 2 x 1.3 cm) that occupied the septum
pellucidum and lamina terminalis. No abnormalities of the pituitary gland were noted. Contrast enhancement of the lesion was only slight (Figures 3 and 4). Endocrinological examinations showed that the serum growth hormone (GH), luteinizing hormone, prolactin,
Figure 3. C T scans, showing an enhanced lesion at the septal region with some calcifications. P, plain; CE, contrast enhancement.
Central Neurocytoma with Gigantism
Surg Neurol 1992;38:141-5
143
j Figure 4. Tl-weighted MRI scans, showing intraventricular tumor developingfrom the septum pellucidum with positive gadolinium diethylenetriaminepentaacetic acia enhancement.
and cortisol levels were elevated to 20.7 ng/mL, 14.9 mIU/mL, 14.0 ng/mL, and 17.4 /a.g/dL, respectively, while the adrenocorticotropic hormone level was 60 pg/ mL. Follicle-stimulating hormone, thyrotropin, and antidiuretic hormone levels were within the normal range (Table 1). GH responded normally to glucose (75 g) and CB-154 (5 rag), and slightly increased in response to thyrotropin-releasing hormone (0.5 mg). Serum levels
Table 1.
i~i~ ~i~
of growth hormone-releasing factor (GRF) and somatostatin were not elevated.
Operation Subtotal resection of the tumor was performed via an anterior transcallosal approach on February 2, 1990. The tumor was located in the interseptal region and extended
EndocrinologicalData Hormone (normal range)
Growth hormone, ng/mL (0-5.0) Luteinizing hormone, mIU/mL (1.1-8.8) Follicle-stimulating hormone, ml U/mL ( 1.8-13.6) Prolactin, ng/mL (0-10.0) Thyrotropin,/~U/mL (0.4-4.4) Adrenocorticotropic hormone, pg/mL (30-60) Antidiuretic hormone, pg/mL (0.3-3.5) Cortisol, ~g/dL ( 3.7-13.0~ Triiodothyronine, ng/dL (100-170) Thyroxine,/a.g/dL (5.0-11.0) Free triiodothyronine, pg/dL (2.7-5.9) Free thyroxine, ng/dL (0.86-1.96) Growth hormone-releasing factor, pg/mL (10.3 ± 4,1) Somatomedin-C, U/mL (0-2.0) Somatostatin, pg/mL ( 1.0-12 ) Abnormal value.
Before surgery
After surgery
20.7 ~ 14.9 ~
0.9 4.7 4.6 7.5 1.1
12.0 14-0 ~ 1.2 60 a 0.6 17.4 ~ 135 8.4 4.8 1.33 5.1 0.80
100 6.8 2.8 1.04 6.6 0.74
--
24 ~
5.2
144
Surg Neurol 1992;38:141-5
Figure5. Photomicrographs of tumor histology. (A) Monotonous proliferation of tumor cells and anuclear fibrillated matrix (hematoxylin and eosin stain, original magnification × 100). (B) Positive reaction for glial fibrillary acidic protein (GFAP) is seen in reactive astrocytes (GFAP stain, original magnification × 200). (C) Positive reaction for neuron-specific enolase (NSE) is seen (NSE stain, original magnification x 200). (D) Electron microscopic features of tumor cells. Synapse-like structures and dense core vesicles are seen (original magnification × 15. 700).
into the hypothalamus. It was a generally soft, gray mass with some hard, calcified areas. There was little bleeding during the operation.
Postoperative
Course
After surgery, the patient received irradiation to a total dose of 39 Gy. Follow-up MRI examination demonstrated shrinking of the residual tumor mass, and no further increase in his height was noted after the operation. Postoperative endocrinological examinations showed that the basal serum G H level had fallen to 0.9 ng/dL (Table 1).
Araki et al
On histological examination, the tumor resembled an oligodendroglioma; the cells had predominantly round nuclei with a perinuclear halo, but broad rosettes were also present. Immunocytochemical studies showed no staining of the tumor cells by glial fibrillary acidic protein, except for a few astrocytes, but the tumor cells were positive for neuron-specific enolase (Figure 5 A - C ) . Electron microscopy revealed numerous 160-nm densecored vesicles, 70-nm clear vesicles, and some synaptic structures (Figure 5 D). These findings were characteristic of a central neurocytoma. In addition, tumor cells obtained at operation were cultured for 2 weeks in a medium of 18% fetal bovine serum and RPMI-1640 (5% CO2, 37°C). A low level o f GRF was detected (5.7 pg/mL), but G H production was not found.
Discussion Twenty-two cases o f central neurocytoma or differentiated neuroblastoma with electron microscopy data have been reported previously [ 2 - 1 1 ] . In addition, some tumors, with similar neuroradiological or pathological findings have been reported as oligodendrogliomas aris-
Central Neurocytoma with Gigantism
ing from the midline [10]. However, the association of gigantism or acromegaly with such tumors has not previously been noted. Our present patient was not so tall by Caucasian standards, but he was of abnormally tall stature for a Japanese and had an elevated serum G H level. In general, gigantism is caused by hypersecretion of G H from a pituitary adenoma or hyperplastic pituitary in a child or adolescent. Some pancreatic tumors or hypothalamic gangliocytomas produce GRF, which causes a secondary increase of the serum G H level and thus produces acromegaly [ 1] or gigantism. Our patient had neither a pituitary tumor nor a pancreatic tumor, and the presence of GRF in the tumor culture medium supports the possibility that he had a GRF-producing central neurocytoma that caused gigantism. We could not obtain an antibody for the immunohistochemical staining of GRF, so no examination of the operative specimen for GRF staining was performed. However, Deimling et al [2] have reported a case of central neurocytoma with gangliold cells, which have the potential to differentiate into mature neurons that could produce GRF. The other possibility is that gigantism may have been caused by hormonal imbalance due to compression of the hypothalamus by the tumor, since G H production is regulated by GRF and somatostatin, although the serum GRF level was not elevated in this patient.
Surg Neurol 1992;38:141-5
145
References 1. Asa SL, Scheithauer BW, Bilbao JM, Horvath E, Ryan N, Kovacs K, Randall RV, Law ER Jr, Singer W. Linfoot JA, Thorner MO, Vale W. A case for hypothalamic acromegaly: A clinicopathological study of six patients ~vith hypothalamic gangliocytomas producing growth hormone-releasing factor. J Clin Endocrinol Metab 1984;58:796-803. 2. Deimling A, Janzer R, Kleihues P, Wiestler OD. Patterns of differentiation in central neurocytoma. An immunohistochemical study of eleven biopsies. Acta Neuropathol 1990;79:473-9. 3. Grisoli F, Vincentelli F, Boudouresques G, Delpuech F, Hassoun J, Raybaud C. Primary cerebral neuroblastoma in an adult man. Surg Neurol 1981;16:266-70. 4. Hassoun J, Gambarelli D, Grisoli F, Pellet W, Salamon G, Pellissier JF, Toga M. Central neurocytoma. An electron-microscopic study of two cases. Acta Neuropathol (Berl) 1982;56:151-6. 5. Miyata M, Yamashita H, Shirakata S, Takeda Z. Central neurocytoma. Case report. Neurol Med Chir (Tokyo) 1989;29:1148-52. 6. Nishio S, TashimaT, Takeshita I, Fukui M. Intraventricular neurocytoma: clinicopathological features of six cases. J Neurosurg 1988;68:665-70. 7. Pearl GS, Mirra SS, Miles ML. Intracerebral ganglioneuroblastoma with intracytoplasmic microtubular aggregates: case report and ultrastructual study. Ultrastruct Pathol 1981;2:337-42. 8. Pearl GS, Takei Y, Bakay RAE, Davis P. Intraventricular primary cerebral neuroblastoma in adults: report of three cases. Neurosurgery 1985;16:847-9. 9. Townsend JJ, Seaman JP. Central neurocytoma--a rare benign intraventricular tumor. Acta Neuropathol (Berl) 1986;71: 167-70. 10. Tsujita Y, Nagashima K, Takakura K. A clinicopathological study of central neurocytoma. Neurol Surg 1989;41:547-58. 11. Wilson AJ, Leafier DH, Kohout ND. Differentiated cerebral neuroblastoma: a tumor in need of discovery. Hum Pathol 1985;16:647-9.
