J Neurosurg 47:771-775, 1977
A metastasizing ependymoma of the cauda equina Case report
CONSTANTINE MAVROUDIS, M . D . , JEANNETTE J. TOWNSEND, M . D . , AND CHARLES B. WILSON, M . D .
Departments of Sargery, Pathology, and Neurological Surgery, University of California Medical Center, San Francisco, California A case is described in which a metastatic ependymoma of the cauda equina recurred after prolonged remission. Similarities to five previously reported cases are discussed, with emphasis on the mode of metastasis. Factors most closely associated with distant metastases include early onset, numerous local operations, long survival, and massive local recurrence at the time of distant metastases. KEY WORDS 9 metastasizing ependymoma extraneural metastases 9 intraspinal tumor
9 blepharoblast
9
This 37-year-old man first complained of low-back pain with radiation to the back of his legs in 1947, at 7 years of age. A
myelogram demonstrated a block in the lumbosacral region, and at operation an elongated pinkish flesh-like t u m o r was thought to be entirely removed. His symptoms disappeared and he did well until 1949, when a myelogram showed a recurrent block and he was re-explored. Only scar tissue was found at this time and there was no evidence of recurrent tumor. H e was free of symptoms after the operation and was able to participate actively in sports during his enlistment in the A r m e d Forces from 1957 to 1961. In 1969, he developed transient back and bilateral posterior thigh pain, followed in 1971 by decreased sensation in the posterior thighs, weakness of gastrocnemius muscles, and difficulty in emptying his bladder, Reexploration of the spine from L-2 to the sacrum revealed a papillary mass of recurrent ependymoma that was partially resected. Postoperatively he received radiotherapy.
J. Neurosurg. / Volume 47 / November, 1977
771
E
XTRANEURAL metastases developing from primary intracranial glioblastomas and gliomas are well documented 2,5-7 but uncommon, while those arising from intraspinal t u m o r s are rare. 11 Although e p e n d y m o m a s constituted approximately 63% of spinal cord gliomas, only five well documented cases o f extraneural metastases from the cauda equina have been recorded. 9,1~ All were characterized by early onset of disease, numerous operations, and long survival. This report documents another case of extraneural metastasis 29 years after the original resection of a cauda equina ependymoma. Case Report
C. Mavroudis, J. J. Townsend and C. B. Wilson
FIG. 1. Chest film taken in June, 1976, showing metastatic nodules. The patient did well until August, 1972, when he noted loss of movement of the left fifth toe, although sensation was intact. A myelogram showed regrowth of the tumor. He then experienced a rapid progression of symptoms with increasing numbness of the
side of the feet and posterolateral aspect of the thighs, and weakness of the toes. He lost sensation of bowel movements and control of flatus, and developed numbness of the penis. When first admitted to this institution in December, 1973, cerebrospinal fluid cytology showed enlarged cells consistent with recurrent tumor, and radiographs revealed erosion and possible invasion of L-4 and L-5 vertebral bodies. During the next 7 months, he received seven courses of 1,3 bis (2chloroethyl)- 1-nitrosourea (BCNU). The patient developed back pain related to stress on the spine in November, 1974, and reexploration in January, 1975, disclosed tumor invading through the sacrum. In February, 1975, a bilateral posterior L4-S1 fusion with left Harrington rod placement was performed. This was followed by radiotherapy that relieved his pain temporarily. Because of recurrent pain, another course of BCNU was given. In April, 1976, because of increased pain but stable neurological symptoms, he was considered for a right Harrington rod fixation. A routine chest film in June, 1976 (Fig. 1), revealed multiple bilateral asymptomatic pulmonary densities not present on a chest film performed 16 months previously. A lung biopsy was performed on the left. At operation numerous nodules were palpated throughout the lung parenchyma, and diaphragmatic implants were seen. The patient has had an uneventful recovery and has been started on chemotherapy.
Neuropathological Findings
FIG. 2. Photomicrograph of section from the cauda equlna demonstrating the perivascular arrangement of the ependymal cells. H & E, • 187.
The tissue sections taken in 1947 and 1971 could not be obtained for review. Sections from the tissue removed in January, 1975, revealed a moderately cellular tumor composed of cuboidal to columnar cells forming a perivascular pattern (Fig. 2). The nuclei were oval to round with fine stippled chromatin, and neither pleomorphism nor mitotic activity was seen. The nuclei were arranged in a ring-like fashion around blood vessels, and their processes, radiating toward the vessel wall, formed typical perivascular pseudorosettes. No ependymal rosettes were found. Sections from the lung biopsy performed in June, 1976, demonstrated numerous solid trabecular or columnar cells with frequent perivascular pseudorosettes (Fig. 3). Special
772
J. Neurosurg. / Volume 47 / November, 1977
Metastasizing ependymoma of the cauda equina
FIG. 3. Photomicrograph of section of a pulmonary nodule showing the perivascular arrangement of the columnar cells and the myxomatous degeneration between the vessel wall and tumor cells. H & E, • 298. stains revealed only rare groups of blepharoblasts in these cells. In many areas a myxomatous type of degeneration was present between the ependymal cells and the vessel wails. The nuclei were round to oval, but displayed more irregular nuclear membranes and coarser chromatin than was evident in the cauda equina biopsy. Mitoses were frequent in contrast to the 1975 cauda equina biopsy. In several areas small spaces ringed by tumor cells were found, suggesting true ependymal rosettes (Fig. 3). Dr. Lucien J. Rubinstein kindly reviewed the slides from 1975 and 1976 and concluded that the lung nodules represented metastases from an ependymoma of the cauda equina. Discussion Ependymomas of the cauda equina are considered benign, but may recur locally after incomplete removal. Survival of patients has been lengthened in recent years by improved care of paraplegics, which provides an increased period for the development of metastases. A review of the five reported cauda equina ependymomas with distant metastases shows a mean age of onset for the original tumor of J. Neurosurg. / Volume 47 / November, 1977
24.8 years with a range of 17 to 29. There were three men and two women, and each had at least two operations related to the ependymoma. All had a favorable response to radiotherapy, and the mean survival after diagnosis was 18.2 years with a range of 4 to 31 years. Metastases were discovered before death in three of the patients (Table 1). The age of onset for our patient was 7 years, the earliest recorded presentation, yet the evolution of his disease has resembled that in the previously reported cases as shown in Table 1. The factors most closely associated with distant metastases are: 1) early onset of disease; 2) numerous local operations; 3) long survival; and 4) massive local recurrence at the time of distant metastases. The pathway of distant metastasis is presumably related to the number of operations and seeding of ependymal cells into the bloodstream during operation. The generally accepted postulate is that glial cells do not invade intact blood vessels. In support of this, Zimmerman 15 demonstrated that gliomas produced experimentally in mice will not invade or metastasize unless homogenized and directly injected into the bloodstream, favoring growth in the liver, kidneys, spleen, and lungs. Tumor cells are exposed to open venous channels at surgery, and with multiple operations, as performed in these patients, the opportunities for metastasis are greatly enhanced. More recently there have been reports of extradural metastases from glioblastomas in the absence of previous surgery. 3,~,8 Anzil' reviewed the reported cases and noted that tumor cells were found in the venous channels, which made it likely that the glioblastoma spreads outside the skull through the venous system after having gained entrance into it either at the dural or intracerebral level. The clinical evidence and Zimmerman's work 15 suggest that the blood is a pathway for extradural metastases, but by no means answer questions related to hostresponse reactions and parent-cell interaction with the now presumably blood-borne metastatic cell. Such questions will have to be answered at a cellular and immunological level and are beyond the scope of this communication. Weiss TM described the four criteria for proof of extraneural metastases from a central nervous system tumor: 1) the microscopic demonstration of a single histologically 773
C. Mavroudis, J. J. Townsend and C. B. Wilson TABLE 1 Reported cases of extraneural metastases of ependymomas o f the cauda equina
No. of Operations
Courses of Radiotherapy
M
5
2
29
M
3
1
pulmonary: mediastinum, subcutaneous over chest film sternum, lungs, pleura, liver, renal vein
4
Patterson, et aL, 1961
28
F
3
2
17
Rubinstein & Logan, 1970
17
F
3
5
pulmonary: mediastinum, pleura, lungs, hilar lymph node, chest film para-aortic lymph nodes lungs, pleura, para-aortic lymph node, wall of IV ventricle
29
Wight, et al., 1973
28
M
2
2
bone and chest wall
31
Mavroudis, et al., 1977
7
M
5
2*
pulmonary: still alive chest film
Age at Onset (yrs)
Sex
Weiss, 1955
22
Sharma, 1956
Author, Year
Metastatic Sites Premortem
Survival (yrs)
Postmortem retroperitoneum, liver, chest wall, pleura, lungs, mediastinum, tracheobronchial lymph nodes
retroperitoneum pleura, para-aortic nodes, humerus
10
29
*This patient also had eight courses of chemotherapy. characteristic neoplasm of the central nervous system; 2) evidence that the initial symptoms were due to the tumor; 3) a complete necropsy conducted in sufficient detail to rule out the possibility of another site; and 4) identical morphological features in the central nervous system t u m o r and distant deposits. We have been able to meet all of the criteria except for a p o s t m o r t e m examination. Careful systemic studies in our patient at the time of this comm u n i c a t i o n have not revealed a n o t h e r primary tumor. In 1955, Weiss xa stated that the development of metastases from ependymomas of the cauda equina would become more frequent because of lengthening survival. The majority of the extraneural metastases in these case reports were clinically asymptomatic and histologically benign. With early detection, radiation therapy or surgical removal could be offered with potentially significant palliation of disease. References
1. Anzil AP: Glioblastoma multiforme with extracranial metastases in the absence of 774
previous
craniotomy.
Neurosurg 33:88-94, 1970
Case
report.
J
2. Barone BM, Elvidge AR: Ependymomas. A clinical survey. J Neurosurg 33:428-438, 1970 3. Brander WL, Turner DR: Extracranial metastases from a glioma in the absence of surgical intervention. J Neurosurg Psychiatry 38: 1133-1135, 1975 4. Dolman CL: Lymph node metastasis as first manifestation of glioblastoma. Case report. J Neurosurg 41:607-609, 1974 5. Fokes EC Jr, Earle KM: Ependymomas: clinical and pathological aspects. J Neurosurg 30:585-594, 1969 6. Fragoyannis S, Yalcin S: Ependymomas with distant metastases. Report of two cases and review of the literature. Cancer 19:246-256, 1966 7. Glasauer FE, Yuan RHP: Intracranial tumors with extracranial metastases. Case report and review of the literature. J Neurosurg 20: 474-493, 1963 8. Henriquez AS, Robertson DM, Marshall WJS: Primary neuroblastoma of the central nervous system with spontaneous extracranial metastases. Case report. J Neurosurg 38: 226-231, 1973 9. Patterson RH Jr, Campbell WG Jr, Parsons H: Ependymoma of the cauda equina with J. Neurosurg. / Volume 47 / November, 1977
Metastasizing ependymoma of the cauda equina 10.
11. 12. 13.
multiple visceral metastases. Report of a case. J Neurosurg 18:145-150, 1961 Rubinstein LJ, Logan W J: Extraneural metastases in ependymoma of the cauda equina. J Neurol Neurosurg Psychiatry 33:763-770, 1970 Russell DS, Rubinstein L J: Pathology of Tumors of the Nervous System, ed 3. London: Edward Arnold, 1971 Sharma KD: A metastasizing ependymoma of the cauda equina. Indian J Med Sci 10: 639-641, 1956 Weiss L: A metastasizing ependymoma of the cauda equina. Cancer 8:161-171, 1955
J. Neurosurg. / Volume 47 / November, 1977
14. Wight DGD, Holley K J, Finbow JAH: Metastasizing ependymoma of the cauda equina. J Clin Pathoi 26:929-935, 1973 15. Zimmerman HM: The nature of gliomas as revealed by animal experimentation. Am J Pathol 31:1-29, 1955
This work was supported in part by USPHS Grant GM-01474-11. Address reprint requests to: Charles B. Wilson, M.D., Department of Neurosurgery, University of California, San Francisco, California 94143.
775
A metastasizing ependymoma of the cauda equina Case report
CONSTANTINE MAVROUDIS, M . D . , JEANNETTE J. TOWNSEND, M . D . , AND CHARLES B. WILSON, M . D .
Departments of Sargery, Pathology, and Neurological Surgery, University of California Medical Center, San Francisco, California A case is described in which a metastatic ependymoma of the cauda equina recurred after prolonged remission. Similarities to five previously reported cases are discussed, with emphasis on the mode of metastasis. Factors most closely associated with distant metastases include early onset, numerous local operations, long survival, and massive local recurrence at the time of distant metastases. KEY WORDS 9 metastasizing ependymoma extraneural metastases 9 intraspinal tumor
9 blepharoblast
9
This 37-year-old man first complained of low-back pain with radiation to the back of his legs in 1947, at 7 years of age. A
myelogram demonstrated a block in the lumbosacral region, and at operation an elongated pinkish flesh-like t u m o r was thought to be entirely removed. His symptoms disappeared and he did well until 1949, when a myelogram showed a recurrent block and he was re-explored. Only scar tissue was found at this time and there was no evidence of recurrent tumor. H e was free of symptoms after the operation and was able to participate actively in sports during his enlistment in the A r m e d Forces from 1957 to 1961. In 1969, he developed transient back and bilateral posterior thigh pain, followed in 1971 by decreased sensation in the posterior thighs, weakness of gastrocnemius muscles, and difficulty in emptying his bladder, Reexploration of the spine from L-2 to the sacrum revealed a papillary mass of recurrent ependymoma that was partially resected. Postoperatively he received radiotherapy.
J. Neurosurg. / Volume 47 / November, 1977
771
E
XTRANEURAL metastases developing from primary intracranial glioblastomas and gliomas are well documented 2,5-7 but uncommon, while those arising from intraspinal t u m o r s are rare. 11 Although e p e n d y m o m a s constituted approximately 63% of spinal cord gliomas, only five well documented cases o f extraneural metastases from the cauda equina have been recorded. 9,1~ All were characterized by early onset of disease, numerous operations, and long survival. This report documents another case of extraneural metastasis 29 years after the original resection of a cauda equina ependymoma. Case Report
C. Mavroudis, J. J. Townsend and C. B. Wilson
FIG. 1. Chest film taken in June, 1976, showing metastatic nodules. The patient did well until August, 1972, when he noted loss of movement of the left fifth toe, although sensation was intact. A myelogram showed regrowth of the tumor. He then experienced a rapid progression of symptoms with increasing numbness of the
side of the feet and posterolateral aspect of the thighs, and weakness of the toes. He lost sensation of bowel movements and control of flatus, and developed numbness of the penis. When first admitted to this institution in December, 1973, cerebrospinal fluid cytology showed enlarged cells consistent with recurrent tumor, and radiographs revealed erosion and possible invasion of L-4 and L-5 vertebral bodies. During the next 7 months, he received seven courses of 1,3 bis (2chloroethyl)- 1-nitrosourea (BCNU). The patient developed back pain related to stress on the spine in November, 1974, and reexploration in January, 1975, disclosed tumor invading through the sacrum. In February, 1975, a bilateral posterior L4-S1 fusion with left Harrington rod placement was performed. This was followed by radiotherapy that relieved his pain temporarily. Because of recurrent pain, another course of BCNU was given. In April, 1976, because of increased pain but stable neurological symptoms, he was considered for a right Harrington rod fixation. A routine chest film in June, 1976 (Fig. 1), revealed multiple bilateral asymptomatic pulmonary densities not present on a chest film performed 16 months previously. A lung biopsy was performed on the left. At operation numerous nodules were palpated throughout the lung parenchyma, and diaphragmatic implants were seen. The patient has had an uneventful recovery and has been started on chemotherapy.
Neuropathological Findings
FIG. 2. Photomicrograph of section from the cauda equlna demonstrating the perivascular arrangement of the ependymal cells. H & E, • 187.
The tissue sections taken in 1947 and 1971 could not be obtained for review. Sections from the tissue removed in January, 1975, revealed a moderately cellular tumor composed of cuboidal to columnar cells forming a perivascular pattern (Fig. 2). The nuclei were oval to round with fine stippled chromatin, and neither pleomorphism nor mitotic activity was seen. The nuclei were arranged in a ring-like fashion around blood vessels, and their processes, radiating toward the vessel wall, formed typical perivascular pseudorosettes. No ependymal rosettes were found. Sections from the lung biopsy performed in June, 1976, demonstrated numerous solid trabecular or columnar cells with frequent perivascular pseudorosettes (Fig. 3). Special
772
J. Neurosurg. / Volume 47 / November, 1977
Metastasizing ependymoma of the cauda equina
FIG. 3. Photomicrograph of section of a pulmonary nodule showing the perivascular arrangement of the columnar cells and the myxomatous degeneration between the vessel wall and tumor cells. H & E, • 298. stains revealed only rare groups of blepharoblasts in these cells. In many areas a myxomatous type of degeneration was present between the ependymal cells and the vessel wails. The nuclei were round to oval, but displayed more irregular nuclear membranes and coarser chromatin than was evident in the cauda equina biopsy. Mitoses were frequent in contrast to the 1975 cauda equina biopsy. In several areas small spaces ringed by tumor cells were found, suggesting true ependymal rosettes (Fig. 3). Dr. Lucien J. Rubinstein kindly reviewed the slides from 1975 and 1976 and concluded that the lung nodules represented metastases from an ependymoma of the cauda equina. Discussion Ependymomas of the cauda equina are considered benign, but may recur locally after incomplete removal. Survival of patients has been lengthened in recent years by improved care of paraplegics, which provides an increased period for the development of metastases. A review of the five reported cauda equina ependymomas with distant metastases shows a mean age of onset for the original tumor of J. Neurosurg. / Volume 47 / November, 1977
24.8 years with a range of 17 to 29. There were three men and two women, and each had at least two operations related to the ependymoma. All had a favorable response to radiotherapy, and the mean survival after diagnosis was 18.2 years with a range of 4 to 31 years. Metastases were discovered before death in three of the patients (Table 1). The age of onset for our patient was 7 years, the earliest recorded presentation, yet the evolution of his disease has resembled that in the previously reported cases as shown in Table 1. The factors most closely associated with distant metastases are: 1) early onset of disease; 2) numerous local operations; 3) long survival; and 4) massive local recurrence at the time of distant metastases. The pathway of distant metastasis is presumably related to the number of operations and seeding of ependymal cells into the bloodstream during operation. The generally accepted postulate is that glial cells do not invade intact blood vessels. In support of this, Zimmerman 15 demonstrated that gliomas produced experimentally in mice will not invade or metastasize unless homogenized and directly injected into the bloodstream, favoring growth in the liver, kidneys, spleen, and lungs. Tumor cells are exposed to open venous channels at surgery, and with multiple operations, as performed in these patients, the opportunities for metastasis are greatly enhanced. More recently there have been reports of extradural metastases from glioblastomas in the absence of previous surgery. 3,~,8 Anzil' reviewed the reported cases and noted that tumor cells were found in the venous channels, which made it likely that the glioblastoma spreads outside the skull through the venous system after having gained entrance into it either at the dural or intracerebral level. The clinical evidence and Zimmerman's work 15 suggest that the blood is a pathway for extradural metastases, but by no means answer questions related to hostresponse reactions and parent-cell interaction with the now presumably blood-borne metastatic cell. Such questions will have to be answered at a cellular and immunological level and are beyond the scope of this communication. Weiss TM described the four criteria for proof of extraneural metastases from a central nervous system tumor: 1) the microscopic demonstration of a single histologically 773
C. Mavroudis, J. J. Townsend and C. B. Wilson TABLE 1 Reported cases of extraneural metastases of ependymomas o f the cauda equina
No. of Operations
Courses of Radiotherapy
M
5
2
29
M
3
1
pulmonary: mediastinum, subcutaneous over chest film sternum, lungs, pleura, liver, renal vein
4
Patterson, et aL, 1961
28
F
3
2
17
Rubinstein & Logan, 1970
17
F
3
5
pulmonary: mediastinum, pleura, lungs, hilar lymph node, chest film para-aortic lymph nodes lungs, pleura, para-aortic lymph node, wall of IV ventricle
29
Wight, et al., 1973
28
M
2
2
bone and chest wall
31
Mavroudis, et al., 1977
7
M
5
2*
pulmonary: still alive chest film
Age at Onset (yrs)
Sex
Weiss, 1955
22
Sharma, 1956
Author, Year
Metastatic Sites Premortem
Survival (yrs)
Postmortem retroperitoneum, liver, chest wall, pleura, lungs, mediastinum, tracheobronchial lymph nodes
retroperitoneum pleura, para-aortic nodes, humerus
10
29
*This patient also had eight courses of chemotherapy. characteristic neoplasm of the central nervous system; 2) evidence that the initial symptoms were due to the tumor; 3) a complete necropsy conducted in sufficient detail to rule out the possibility of another site; and 4) identical morphological features in the central nervous system t u m o r and distant deposits. We have been able to meet all of the criteria except for a p o s t m o r t e m examination. Careful systemic studies in our patient at the time of this comm u n i c a t i o n have not revealed a n o t h e r primary tumor. In 1955, Weiss xa stated that the development of metastases from ependymomas of the cauda equina would become more frequent because of lengthening survival. The majority of the extraneural metastases in these case reports were clinically asymptomatic and histologically benign. With early detection, radiation therapy or surgical removal could be offered with potentially significant palliation of disease. References
1. Anzil AP: Glioblastoma multiforme with extracranial metastases in the absence of 774
previous
craniotomy.
Neurosurg 33:88-94, 1970
Case
report.
J
2. Barone BM, Elvidge AR: Ependymomas. A clinical survey. J Neurosurg 33:428-438, 1970 3. Brander WL, Turner DR: Extracranial metastases from a glioma in the absence of surgical intervention. J Neurosurg Psychiatry 38: 1133-1135, 1975 4. Dolman CL: Lymph node metastasis as first manifestation of glioblastoma. Case report. J Neurosurg 41:607-609, 1974 5. Fokes EC Jr, Earle KM: Ependymomas: clinical and pathological aspects. J Neurosurg 30:585-594, 1969 6. Fragoyannis S, Yalcin S: Ependymomas with distant metastases. Report of two cases and review of the literature. Cancer 19:246-256, 1966 7. Glasauer FE, Yuan RHP: Intracranial tumors with extracranial metastases. Case report and review of the literature. J Neurosurg 20: 474-493, 1963 8. Henriquez AS, Robertson DM, Marshall WJS: Primary neuroblastoma of the central nervous system with spontaneous extracranial metastases. Case report. J Neurosurg 38: 226-231, 1973 9. Patterson RH Jr, Campbell WG Jr, Parsons H: Ependymoma of the cauda equina with J. Neurosurg. / Volume 47 / November, 1977
Metastasizing ependymoma of the cauda equina 10.
11. 12. 13.
multiple visceral metastases. Report of a case. J Neurosurg 18:145-150, 1961 Rubinstein LJ, Logan W J: Extraneural metastases in ependymoma of the cauda equina. J Neurol Neurosurg Psychiatry 33:763-770, 1970 Russell DS, Rubinstein L J: Pathology of Tumors of the Nervous System, ed 3. London: Edward Arnold, 1971 Sharma KD: A metastasizing ependymoma of the cauda equina. Indian J Med Sci 10: 639-641, 1956 Weiss L: A metastasizing ependymoma of the cauda equina. Cancer 8:161-171, 1955
J. Neurosurg. / Volume 47 / November, 1977
14. Wight DGD, Holley K J, Finbow JAH: Metastasizing ependymoma of the cauda equina. J Clin Pathoi 26:929-935, 1973 15. Zimmerman HM: The nature of gliomas as revealed by animal experimentation. Am J Pathol 31:1-29, 1955
This work was supported in part by USPHS Grant GM-01474-11. Address reprint requests to: Charles B. Wilson, M.D., Department of Neurosurgery, University of California, San Francisco, California 94143.
775
