J. Endocrinol. Invest. 15: 387-391, 1992
CASE REPORT
Intracranial dissemination of an ACTH secreting pituitary neoplasm - Acase report and review of the literature D. Tonner*, P. Belding**, S.A. Moore**, and J.A. Schlechte* Departments of Internal Medieine* and Pathology** University of lowa College of Medieine, lowa City, lowa, USA ABSTRACT. A 52-year-old woman developed recurrent hypercortisolism 3 yr after successful surgical treatment of Cushing's disease. At postmortem, eosinophilic pituitary tissue showing positive ACTH immunohistochemical staining was present in the frontal lobe and cerebellum but there was no tumor in the sella. In the absence of a pituitary tumor, extrasellar ACTH producing tissue could arise from
seeding of the cerebrospinal fluid with tumor ceUs at the time of operation or from an atypical pituitary carcinoma. In this report we review the mechanisms of intracranial dissemination of pituitary tissue and ACTH-secreting pituitary carcinomas, including parasellar invasion, meningeal seeding, and cerebrospinal and hematogenous spread.
INTRODUCTION
of pleomorphie nuelei (Fig. 1a). One yr later, thyroid hormone therapy was instituted but symptoms of glueoeortieoid exeess had resolved and urinary free eortisol exeretion was normal (Table 1), Sella CT seans obtained between 1985 and 1988 revealed only postoperative ehanges, Three yr after surgery, she developed headaehe, hirsutism, eonfusion, ineontinenee, hypertension, truneal obesity, violaeeous striae and proximal museie weakness. Twenty-four h urinary free eortisol exeretion, morning serum eortisol and ACTH levels were elevated and an 8 mg dexamethasone suppression test revealed >50% suppression of urinary free eortisol from baseline levels (Table 1) suggesting the presenee of an ACTH-seereting pituitary adenoma. T2-weighted MRI images revealed a gadolinium-enhaneing mass in the left cerebellum and old bifrontal infarets (Fig, 2), A CT sean also showed the left eerebellar mass with surrounding edema, Neither radiographie study demonstrated a pituitary mass, Cytologie analysis of the eerebrospinal fluid was negative, Beeause of the diserepaney between the dexamethasone suppression test (wh ich suggested reeurrent pituitary tumor) and the negative radiographie findings, we performed petrosal sinus sampling (2), We simultaneously sampled ACTH levels in the pituitary and systemie eireulations and the inferior petrosal sinus/peripheral ratio was 200 to 75 fl9/9r creatinine without improvement in her symptoms. She died nine months after the symptoms of glucocorticoid excess appeared. At postmortem, the brain showed bifrontal atrophy and a mildly thickened dura mater adherent to the calvarium. A 3.5x2.0x1.8 cm mass was located within the superolateral aspect of the left cerebellar hemisphere and the adjacent parenchyma was indented, soft, and
Fig 2 - Gadolinium-enhanced MRI (T-2 welghted image)
hemorrhagic. There was also a 1.0x1.0xO.5 cm nodule in the anterior fossa, adherent to the left cribiform plate with a corresponding defect in the left gyrus rec-
Fig. 1 - (A) Pitwtary adenoma resected in 1985 composed of polygonal cells with round nuclel exhlbltmg milcl pleomorphism (H & E x400). (8) Posterior fossa tumor found at autopsy revealing features similar to original pituitary adenoma with slightly larger nuclei exhibiting more pleomorphism (H & E x400).
388
Pituitary carcinoma
Fig. 4 - Posterior lossa tumor lound at autopsy demonstratlflg immunoreactivity for ACTH (immunoperoxidase with 3-amino-9ethylcarbazole as chromagen x 300).
Fig . 3 -Mlcroscopic subaraehnold !oeus 01 p'tUitary adenoma on lateral surface of the medulla (H & E x 100).
tus. Serial decalcified sections of the skull base revealed no tumor in the sella or adjacent sinuses. Microscopic examination of the cerebellar and anterior fossa masses revealed uniform cells arranged in irregular lobules, trabeculae, and sheets. The neoplastic cells were polygonal with abundant eosinophilic cytoplasm , and contained round to oval nuclei with peripheral chromatin and occasional nucleoli (Fig. 1B). No mitotic activity was noted, but there were occasional large cells with irregular, hyperchromatic nuclei and mild nuclear pleomorphism. The tumor resected in 1985 showed less prominent vascularity and less nuclear pleomorphism (Fig. 1A). Two microscopic foci of neoplasm were also noted in the subarachnoid space on the lateral and ventral surfaces of the medulla, but the neoplasm did not invade surrounding brain tissue or vascular structures (Fig. 3) . To elucidate the origin of the metastatic lesions, we performed immunoperoxidase staining on paraffin embedded formalin fixed tissue from the autopsy using the avidin-biotin method (3). Tissue blocks from the original resection were no longer available making immunohistochemical evaluation impossible. Human chromogranin A, ACTH , neuron specific enolase, growth hormone, prolactin, factor VIII, Ulex europaeus lectin, S-100, vimentin, epithelial membrane antigen, and high and low molecular weight cytokeratins were tested. The neoplastic tissue exhibited positive staining for neuron specific enolase, ACTH, and chromogranin consistent with pituitary origin (Fig. 4).
itary tissue is metastasis from a pituitary carcinoma. Intracranial metastases from hormonally active pituitary tumors constitute over half of the reported cases (4-19), but only three have been associated with ACTH hypersecretion (17-19) (Table 2). Intracranial metastases are typically composed of large, spindie shaped and polygonal cells with necrotic changes, hyperchromatic nuclei and mitotic figures. All areas of the CNS may harbor metastatic lesions and cytoplasmic staining may reveal acidophilic, basophilic or chromophobic characteristics (20). Hepatic metastases have also been associated with ACTH hypersecretion (2125). All reported ACTH-secreting pituitary carcinomas have demonstrated a prominent sellar mass (1719). Our case is unique in that cerebellar and frontal lobe ACTH producing tissue appeared in the absence of intrasellar pituitary tissue. Zafar et al. reported extensive central nervous system metastases from an ACTH-secreting pituitary carcinoma which appeared after clinical remission but postmortem examination revealed prominent tumor in the sella (19). Surgery preceded the appearance of metastases in 12 of the reported cases and is probably responsible for the intracranial dissemination of tumor in our patient. All of the tumors described in Table 2 were re sec ted via open craniotomy and extensive surgical manipulation could lead to seeding of the cerebrospinal fluid with tumor cells (10, 12, 16). It is possible that the transsphenoidal surgical approach will be associated with a decreased incidence of such intracranial seeding. The mechanism of pituitary tissue dissemination with-
DISCUSSION The most obvious explanation for extrasellar pitu-
389
D. Tonner, P. Be/ding, S.A. Moore, et al.
Table 2 - Pituitary carcinomas with central nervous system metastases. Author year
Age sex
Hormone secreted
Site(s) of metastasis
Feiring 1953
38M
ACTH (probable)
frontal lobe
+
+
+
Salassa 1959
46M
ACTH (probable)
spinal cord
+
+
+
Zafar 1984
60M
ACTH
pons spinal cord
+
+
+
Newton 1962
27F
GH
temporal lobe
?
Ogilvy 1973
49F
GH
temporal lobe olfactory tract
+
+
+
Hashimoto 1986
48F
GH
occipital lobe pons, spinal cord
+
+
+
+
+
+
+
Alive at report
Cellular anaplasia
U 1984
62M
PRL
occipital lobe
Cohen 1982
70M
PRL
cerebello-pontine angle
Martin 1981
31F
PRL
cerebellum
+
Cairns 1931
25F
none
spinal cord
?
7F
none
frontal lobe
+
Graf 1962
Radiatio'l/ surgery
Residual tumor (sellar)
+
+
+ +
Madonick 1963
75M
none
frontal, temporal lobes
Epstein 1964
29M
none
cauda equina
+
+
Alive at report
Solitare 1967
66F
none
frontal lobe
?
+
?
Fleischer 1972
50M
none
pons
+
+
+
Ogilvy 1973
58M
none
spinal cord parietal lobe
+
+
+
+~present
-~absent. ?~unknown.
in the central nervous system is likely multifactorial. Besides invasion of parasellar structures, a pituitary tumor may spread along the meninges, through the cerebrospinal fluid, or via a hematogenous route. Ogilvy and Jakubowski found neoplastic celis in the cerebrospinal fluid in two patients with nonfunctioning pituitary tumors (10, 12) and Hashimoto et al. reported subarachnoid dissemination of a growth hormone secreting pituitary tumor (13). Subarachnoid metastases have also been noted with medulioblastomas, oligodendrogliomas, ependymomas, astrocytomas and glioblastoma multiforme (6, 26). Even though cerebrospinal fluid cytology was negative at the time the Cushing's disease recurred in the present case, cerebrospinal fluid dissemination of the neoplasm cannot be excluded as the source of the cerebellum and frontal lobe implants. Even though radiation therapy is effective and wideIy used it could alter the behavior of a benign neoplasm and lead to intracranial dissemination of tumor. The tissue obtained at postmortem in our patient, however, showed no anaplastic change. It is unlikely that radiation therapy was responsible for the pituitary tissue in the cerebellum, but may ex-
plain minor histological differences between the original neoplasm and the meningeal-based lesions found at autopsy. In addition, there was no direct invasion of the brain or sinuses, and no evidence of vascular invasion to suggest malignant transformation. The tumor was basically pushing away brain tissue with a mass effect similar to a meningioma. How or whether hypothalamic stimulation of extrapituitary tissue occurs is unclear. Whether the implants found in the cerebellum and frontal lobe of our patient were autonomous sites of ACTH production or whether the metastases were stimulated by hypothalamic or tumor-related corticotropin releasing factor (CRF) cannot be elucidated. CRFproducing tumors have been reported and may be difficult to distinguish from ectopic ACTH-producing lesions (27, 28). CRF immunoflourescent staining was not performed on our sampies.
RE FE REN CES 1. Lloyd R.V. Endocrine pathology. Springer-Verlag. New York, 1990, p. 17.
390
Pituitary carcinoma
2. Findling J.w., Aron D.C., Tyrrell J.B., Shinsako J.H., Fitzgerald PA, Norman 0., Wilson C.B., Forsham P.H. Selective venous sampling for ACTH in Cushing's syndrome. Differentiation between Cushing's disease and the ectopic ACTH syndrome. Ann. Intern. Med. 94. 647, 1981. 3. Hsu S-M., Raine L., Fangen H. Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: A comparison between ABC and unlabeled antibody (PAP) procedures. J. Histochem. Cytochem. 29. 577, 1981. 4. Cairns H, Russel D.S. Intracranial and spine metastases in gliomas of the brain. Brain54. 377, 1931. 5. Graf C.J., Blinderman E.E., Terplan K.L. Pituitary carcinoma in a child with distant metastases. J. Neurosurg. 19: 254, 1962. 6. Madonick M.J., Rubinstein L.J., Dacso M.R., Ribner H. Chromophobe adenoma of pituitary gland with subarachnoid metastases. Neurology 13. 836, 1963. 7. Epstein JA, Epstein B.S., Molho L., Zimmerman H.M. Carcinoma of the pituitary gland with metastases to the spinal cord and roots of the cauda equina. J. Neurosurg. 21: 844, 1964.
16.
17.
18.
19.
20.
21.
22. D'Abrera V.S.E., Burke W.J., Blessel K.F, Bader L. Carcinoma of the pituitary gland. J. Pathol. 109: 335, 1973. 23. Sheldon W.H., Golden A, Bondy P.K. Cushing's syndrome produced by a pituitary basophilic carcinoma with hepatic metastasis. Am. J. Med. 17: 134,1954. 24. Forbes W. Carcinoma of the pituitary gland with metastasis to the liver in a case of Cushing's syndrome. J. Pathol. Bact. 59: 137,1947. 25. Queiroz L.S., Facure N.O., Facure J.J., Modesto N.P., deFaria J.L. Pituitary carcinoma with liver metastases and Cushing's syndrome. Arch. Pathol. 99: 32,1975. 26. Scheithauer B.w., Kovacs K.T., Laws E.R., Randall R.V. Pathology of invasive pituitary tumors with special reference to functional classification. J. Neurosurg. 65: 733,1986. 27. Belsky J.L., Cuello B., Swanson L.w., Simmons D.M., Jarrett R.M., Braza F. Cushing's syndrome due to ectopic production of corticotropin-releasing factor. J. Clin. Endocrinol. Metab. 60.496,1985.
8. Solitare G.B., Jatlow P. Adenohypophyseal carcinoma. Case report. J. Neurosurg. 26:624,1967. 9. Fleischer AS., Reagan T., Ransohoff J. Primary carcinoma of the pituitary with metastasis to the brain stem. J. Neurosurg. 36: 781, 1972. 10. Ogilvy K.M., Jakubowski J, Shortland J.R. Spinal subarachnoid spread of pituitary adenoma. J. Neurol. Neurosurg. Psychiatry 37: 1186,1974. 11. Newton T.H., Burhenne H.J., Palubinskas AJ. Primary carcinoma of the pituitary. Am. J. Roentgenol. 87: 110,1962. 12. Ogilvy K.M., Jakubowski J. Intracranial dissemination of pituitary adenomas. J. Neurol. Neurosurg. Psychiatry 36: 199,1973. 13. Hashimoto N, Handa J., Nishi S. Intracranial and intraspinal dissemination from a growth hormone-secreting pituitary tumor. J. Neurosurg. 64: 140,1986. 14. Hoi Sang U., Johnson C. Metastatic prolactin-secreting pituitary adenoma. Hum. Pathol. 15:94,1984. 15. Cohen
D.L.,
Diengdoh
J.V.,
Thomas
Himsworth R.L. An intracranial metastasis from a PRL secreting pituitary tumour. Clin. Endocrinol. (Oxt.) 18: 259, 1983. Martin NA, Haies M., Wilson C.B. Cerebellar metastasis from a prolactinoma during treatment with bromocriptine. J. Neurosurg. 55.615,1981. Feiring E.H., Davidoff L.M., Zimmerman H.M. Primary carcinoma of the pituitary. J. Neuropathol. Exp. Neurol. 12: 205, 1953. Salassa R.M., Kearns T.P., Kernohan J.U., Sprague R.G., MacCarty C.S. Pituitary tumors in patients with Cushing's syndrome. J. Clin. Endocrinol. Metab. 19.· 1523,1959. Zafar M.S., Mellinger R.C, Chason J.L. Cushing's disease due to pituitary carcinoma. Henry Ford Hosp. Med. J. 32: 61, 1984. McCarty K.S. Jr, Bredesen OE, Vogel F.S. Neoplasms of the anterior pituitary. Neurosurgery 3: 96, 1978. Scholz DA, Gastineau CF, Harrison E.G. Jr. Cushing's syndrome with malignant chromophobe tumor of the pituitary and extracranial metastasis. Am. J. Med. 17· 134,1962.
28. Carey R.M., Varma SK, Drake C.R. Jr. Ectopic secretion of corticotropin-releasing factor as a cause of Cushing's syndrome.
D.G.T.,
N. Engl. J. Med. 311.13, 1984.
391
CASE REPORT
Intracranial dissemination of an ACTH secreting pituitary neoplasm - Acase report and review of the literature D. Tonner*, P. Belding**, S.A. Moore**, and J.A. Schlechte* Departments of Internal Medieine* and Pathology** University of lowa College of Medieine, lowa City, lowa, USA ABSTRACT. A 52-year-old woman developed recurrent hypercortisolism 3 yr after successful surgical treatment of Cushing's disease. At postmortem, eosinophilic pituitary tissue showing positive ACTH immunohistochemical staining was present in the frontal lobe and cerebellum but there was no tumor in the sella. In the absence of a pituitary tumor, extrasellar ACTH producing tissue could arise from
seeding of the cerebrospinal fluid with tumor ceUs at the time of operation or from an atypical pituitary carcinoma. In this report we review the mechanisms of intracranial dissemination of pituitary tissue and ACTH-secreting pituitary carcinomas, including parasellar invasion, meningeal seeding, and cerebrospinal and hematogenous spread.
INTRODUCTION
of pleomorphie nuelei (Fig. 1a). One yr later, thyroid hormone therapy was instituted but symptoms of glueoeortieoid exeess had resolved and urinary free eortisol exeretion was normal (Table 1), Sella CT seans obtained between 1985 and 1988 revealed only postoperative ehanges, Three yr after surgery, she developed headaehe, hirsutism, eonfusion, ineontinenee, hypertension, truneal obesity, violaeeous striae and proximal museie weakness. Twenty-four h urinary free eortisol exeretion, morning serum eortisol and ACTH levels were elevated and an 8 mg dexamethasone suppression test revealed >50% suppression of urinary free eortisol from baseline levels (Table 1) suggesting the presenee of an ACTH-seereting pituitary adenoma. T2-weighted MRI images revealed a gadolinium-enhaneing mass in the left cerebellum and old bifrontal infarets (Fig, 2), A CT sean also showed the left eerebellar mass with surrounding edema, Neither radiographie study demonstrated a pituitary mass, Cytologie analysis of the eerebrospinal fluid was negative, Beeause of the diserepaney between the dexamethasone suppression test (wh ich suggested reeurrent pituitary tumor) and the negative radiographie findings, we performed petrosal sinus sampling (2), We simultaneously sampled ACTH levels in the pituitary and systemie eireulations and the inferior petrosal sinus/peripheral ratio was 200 to 75 fl9/9r creatinine without improvement in her symptoms. She died nine months after the symptoms of glucocorticoid excess appeared. At postmortem, the brain showed bifrontal atrophy and a mildly thickened dura mater adherent to the calvarium. A 3.5x2.0x1.8 cm mass was located within the superolateral aspect of the left cerebellar hemisphere and the adjacent parenchyma was indented, soft, and
Fig 2 - Gadolinium-enhanced MRI (T-2 welghted image)
hemorrhagic. There was also a 1.0x1.0xO.5 cm nodule in the anterior fossa, adherent to the left cribiform plate with a corresponding defect in the left gyrus rec-
Fig. 1 - (A) Pitwtary adenoma resected in 1985 composed of polygonal cells with round nuclel exhlbltmg milcl pleomorphism (H & E x400). (8) Posterior fossa tumor found at autopsy revealing features similar to original pituitary adenoma with slightly larger nuclei exhibiting more pleomorphism (H & E x400).
388
Pituitary carcinoma
Fig. 4 - Posterior lossa tumor lound at autopsy demonstratlflg immunoreactivity for ACTH (immunoperoxidase with 3-amino-9ethylcarbazole as chromagen x 300).
Fig . 3 -Mlcroscopic subaraehnold !oeus 01 p'tUitary adenoma on lateral surface of the medulla (H & E x 100).
tus. Serial decalcified sections of the skull base revealed no tumor in the sella or adjacent sinuses. Microscopic examination of the cerebellar and anterior fossa masses revealed uniform cells arranged in irregular lobules, trabeculae, and sheets. The neoplastic cells were polygonal with abundant eosinophilic cytoplasm , and contained round to oval nuclei with peripheral chromatin and occasional nucleoli (Fig. 1B). No mitotic activity was noted, but there were occasional large cells with irregular, hyperchromatic nuclei and mild nuclear pleomorphism. The tumor resected in 1985 showed less prominent vascularity and less nuclear pleomorphism (Fig. 1A). Two microscopic foci of neoplasm were also noted in the subarachnoid space on the lateral and ventral surfaces of the medulla, but the neoplasm did not invade surrounding brain tissue or vascular structures (Fig. 3) . To elucidate the origin of the metastatic lesions, we performed immunoperoxidase staining on paraffin embedded formalin fixed tissue from the autopsy using the avidin-biotin method (3). Tissue blocks from the original resection were no longer available making immunohistochemical evaluation impossible. Human chromogranin A, ACTH , neuron specific enolase, growth hormone, prolactin, factor VIII, Ulex europaeus lectin, S-100, vimentin, epithelial membrane antigen, and high and low molecular weight cytokeratins were tested. The neoplastic tissue exhibited positive staining for neuron specific enolase, ACTH, and chromogranin consistent with pituitary origin (Fig. 4).
itary tissue is metastasis from a pituitary carcinoma. Intracranial metastases from hormonally active pituitary tumors constitute over half of the reported cases (4-19), but only three have been associated with ACTH hypersecretion (17-19) (Table 2). Intracranial metastases are typically composed of large, spindie shaped and polygonal cells with necrotic changes, hyperchromatic nuclei and mitotic figures. All areas of the CNS may harbor metastatic lesions and cytoplasmic staining may reveal acidophilic, basophilic or chromophobic characteristics (20). Hepatic metastases have also been associated with ACTH hypersecretion (2125). All reported ACTH-secreting pituitary carcinomas have demonstrated a prominent sellar mass (1719). Our case is unique in that cerebellar and frontal lobe ACTH producing tissue appeared in the absence of intrasellar pituitary tissue. Zafar et al. reported extensive central nervous system metastases from an ACTH-secreting pituitary carcinoma which appeared after clinical remission but postmortem examination revealed prominent tumor in the sella (19). Surgery preceded the appearance of metastases in 12 of the reported cases and is probably responsible for the intracranial dissemination of tumor in our patient. All of the tumors described in Table 2 were re sec ted via open craniotomy and extensive surgical manipulation could lead to seeding of the cerebrospinal fluid with tumor cells (10, 12, 16). It is possible that the transsphenoidal surgical approach will be associated with a decreased incidence of such intracranial seeding. The mechanism of pituitary tissue dissemination with-
DISCUSSION The most obvious explanation for extrasellar pitu-
389
D. Tonner, P. Be/ding, S.A. Moore, et al.
Table 2 - Pituitary carcinomas with central nervous system metastases. Author year
Age sex
Hormone secreted
Site(s) of metastasis
Feiring 1953
38M
ACTH (probable)
frontal lobe
+
+
+
Salassa 1959
46M
ACTH (probable)
spinal cord
+
+
+
Zafar 1984
60M
ACTH
pons spinal cord
+
+
+
Newton 1962
27F
GH
temporal lobe
?
Ogilvy 1973
49F
GH
temporal lobe olfactory tract
+
+
+
Hashimoto 1986
48F
GH
occipital lobe pons, spinal cord
+
+
+
+
+
+
+
Alive at report
Cellular anaplasia
U 1984
62M
PRL
occipital lobe
Cohen 1982
70M
PRL
cerebello-pontine angle
Martin 1981
31F
PRL
cerebellum
+
Cairns 1931
25F
none
spinal cord
?
7F
none
frontal lobe
+
Graf 1962
Radiatio'l/ surgery
Residual tumor (sellar)
+
+
+ +
Madonick 1963
75M
none
frontal, temporal lobes
Epstein 1964
29M
none
cauda equina
+
+
Alive at report
Solitare 1967
66F
none
frontal lobe
?
+
?
Fleischer 1972
50M
none
pons
+
+
+
Ogilvy 1973
58M
none
spinal cord parietal lobe
+
+
+
+~present
-~absent. ?~unknown.
in the central nervous system is likely multifactorial. Besides invasion of parasellar structures, a pituitary tumor may spread along the meninges, through the cerebrospinal fluid, or via a hematogenous route. Ogilvy and Jakubowski found neoplastic celis in the cerebrospinal fluid in two patients with nonfunctioning pituitary tumors (10, 12) and Hashimoto et al. reported subarachnoid dissemination of a growth hormone secreting pituitary tumor (13). Subarachnoid metastases have also been noted with medulioblastomas, oligodendrogliomas, ependymomas, astrocytomas and glioblastoma multiforme (6, 26). Even though cerebrospinal fluid cytology was negative at the time the Cushing's disease recurred in the present case, cerebrospinal fluid dissemination of the neoplasm cannot be excluded as the source of the cerebellum and frontal lobe implants. Even though radiation therapy is effective and wideIy used it could alter the behavior of a benign neoplasm and lead to intracranial dissemination of tumor. The tissue obtained at postmortem in our patient, however, showed no anaplastic change. It is unlikely that radiation therapy was responsible for the pituitary tissue in the cerebellum, but may ex-
plain minor histological differences between the original neoplasm and the meningeal-based lesions found at autopsy. In addition, there was no direct invasion of the brain or sinuses, and no evidence of vascular invasion to suggest malignant transformation. The tumor was basically pushing away brain tissue with a mass effect similar to a meningioma. How or whether hypothalamic stimulation of extrapituitary tissue occurs is unclear. Whether the implants found in the cerebellum and frontal lobe of our patient were autonomous sites of ACTH production or whether the metastases were stimulated by hypothalamic or tumor-related corticotropin releasing factor (CRF) cannot be elucidated. CRFproducing tumors have been reported and may be difficult to distinguish from ectopic ACTH-producing lesions (27, 28). CRF immunoflourescent staining was not performed on our sampies.
RE FE REN CES 1. Lloyd R.V. Endocrine pathology. Springer-Verlag. New York, 1990, p. 17.
390
Pituitary carcinoma
2. Findling J.w., Aron D.C., Tyrrell J.B., Shinsako J.H., Fitzgerald PA, Norman 0., Wilson C.B., Forsham P.H. Selective venous sampling for ACTH in Cushing's syndrome. Differentiation between Cushing's disease and the ectopic ACTH syndrome. Ann. Intern. Med. 94. 647, 1981. 3. Hsu S-M., Raine L., Fangen H. Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: A comparison between ABC and unlabeled antibody (PAP) procedures. J. Histochem. Cytochem. 29. 577, 1981. 4. Cairns H, Russel D.S. Intracranial and spine metastases in gliomas of the brain. Brain54. 377, 1931. 5. Graf C.J., Blinderman E.E., Terplan K.L. Pituitary carcinoma in a child with distant metastases. J. Neurosurg. 19: 254, 1962. 6. Madonick M.J., Rubinstein L.J., Dacso M.R., Ribner H. Chromophobe adenoma of pituitary gland with subarachnoid metastases. Neurology 13. 836, 1963. 7. Epstein JA, Epstein B.S., Molho L., Zimmerman H.M. Carcinoma of the pituitary gland with metastases to the spinal cord and roots of the cauda equina. J. Neurosurg. 21: 844, 1964.
16.
17.
18.
19.
20.
21.
22. D'Abrera V.S.E., Burke W.J., Blessel K.F, Bader L. Carcinoma of the pituitary gland. J. Pathol. 109: 335, 1973. 23. Sheldon W.H., Golden A, Bondy P.K. Cushing's syndrome produced by a pituitary basophilic carcinoma with hepatic metastasis. Am. J. Med. 17: 134,1954. 24. Forbes W. Carcinoma of the pituitary gland with metastasis to the liver in a case of Cushing's syndrome. J. Pathol. Bact. 59: 137,1947. 25. Queiroz L.S., Facure N.O., Facure J.J., Modesto N.P., deFaria J.L. Pituitary carcinoma with liver metastases and Cushing's syndrome. Arch. Pathol. 99: 32,1975. 26. Scheithauer B.w., Kovacs K.T., Laws E.R., Randall R.V. Pathology of invasive pituitary tumors with special reference to functional classification. J. Neurosurg. 65: 733,1986. 27. Belsky J.L., Cuello B., Swanson L.w., Simmons D.M., Jarrett R.M., Braza F. Cushing's syndrome due to ectopic production of corticotropin-releasing factor. J. Clin. Endocrinol. Metab. 60.496,1985.
8. Solitare G.B., Jatlow P. Adenohypophyseal carcinoma. Case report. J. Neurosurg. 26:624,1967. 9. Fleischer AS., Reagan T., Ransohoff J. Primary carcinoma of the pituitary with metastasis to the brain stem. J. Neurosurg. 36: 781, 1972. 10. Ogilvy K.M., Jakubowski J, Shortland J.R. Spinal subarachnoid spread of pituitary adenoma. J. Neurol. Neurosurg. Psychiatry 37: 1186,1974. 11. Newton T.H., Burhenne H.J., Palubinskas AJ. Primary carcinoma of the pituitary. Am. J. Roentgenol. 87: 110,1962. 12. Ogilvy K.M., Jakubowski J. Intracranial dissemination of pituitary adenomas. J. Neurol. Neurosurg. Psychiatry 36: 199,1973. 13. Hashimoto N, Handa J., Nishi S. Intracranial and intraspinal dissemination from a growth hormone-secreting pituitary tumor. J. Neurosurg. 64: 140,1986. 14. Hoi Sang U., Johnson C. Metastatic prolactin-secreting pituitary adenoma. Hum. Pathol. 15:94,1984. 15. Cohen
D.L.,
Diengdoh
J.V.,
Thomas
Himsworth R.L. An intracranial metastasis from a PRL secreting pituitary tumour. Clin. Endocrinol. (Oxt.) 18: 259, 1983. Martin NA, Haies M., Wilson C.B. Cerebellar metastasis from a prolactinoma during treatment with bromocriptine. J. Neurosurg. 55.615,1981. Feiring E.H., Davidoff L.M., Zimmerman H.M. Primary carcinoma of the pituitary. J. Neuropathol. Exp. Neurol. 12: 205, 1953. Salassa R.M., Kearns T.P., Kernohan J.U., Sprague R.G., MacCarty C.S. Pituitary tumors in patients with Cushing's syndrome. J. Clin. Endocrinol. Metab. 19.· 1523,1959. Zafar M.S., Mellinger R.C, Chason J.L. Cushing's disease due to pituitary carcinoma. Henry Ford Hosp. Med. J. 32: 61, 1984. McCarty K.S. Jr, Bredesen OE, Vogel F.S. Neoplasms of the anterior pituitary. Neurosurgery 3: 96, 1978. Scholz DA, Gastineau CF, Harrison E.G. Jr. Cushing's syndrome with malignant chromophobe tumor of the pituitary and extracranial metastasis. Am. J. Med. 17· 134,1962.
28. Carey R.M., Varma SK, Drake C.R. Jr. Ectopic secretion of corticotropin-releasing factor as a cause of Cushing's syndrome.
D.G.T.,
N. Engl. J. Med. 311.13, 1984.
391
