GYNECOLOGIC
ONCOLOGY
‘d‘t,
195-197 (1992)
CASE REPORT lntramedullary Spinal Cord Metastases from Epithelial Ovarian Carcinoma ANDREW W. THOMAS, Department
M.D.,
of Medicine,
SHERYL R. SIMON, M.D. ,I AND CAROL EVANS, Allegheny
General
Received
May
A patient with poorly differentiatedserouscystadenocarcinoma of both ovarieswho had undergoneextensivemedicaltreatment presentedwith nonspecificneurologiccomplaints.With the aid of magneticresonanceimaging, a metastaticlesionin the intramedullary area of the spinal cord wasdiagnosed.Rapidly instituted high-dosesteroidsand radiotherapy resultedin resolution of her symptoms, Intramedullary spinal cord metastasisis an unusualmetastaticsite. This isthe first reportedcaseof epithelial ovarian carcinomametastaticto the intramedullary spinal cord. 0 1992 Academic
Press, Inc.
Central nervous system metastases are rare in patients with epithelial ovarian cancer (l-3). In one autopsy series, 11 of 381 (3%) patients had metastases to the cerebrum, cerebellum, pons, medulla, and leptomeninges [l]. In a retrospective epidemiologic review, the frequency was only 0.29% [2]. Ovarian cancer is the fourth leading cause of cancer death in women. Most patients die as a result of massive intraabdominal disease. As advances in therapy have prolonged disease-free interval and median survival [4], patterns of metastases may change and spread to unusual sites may become more common [3]. A case of ovarian cancer with symptomatic intramedullary spinal cord metastasis is reported to document a metastatic site that has not been previously recognized. CASE REPORT A 49-year-old woman underwent exploratory laparotomy and debulking procedure at an outside health facility ’ To whom reprint requests should be addressed at Allegheny Hospital, 320 East North Ave., Pittsburgh, PA 15212.
Hospital,
General
Pittsburgh,
Pennsylvania
M.D.
15212
3, 1991
for poorly differentiated serous cystadenocarcinoma of both ovaries. Postoperatively she received 12 cycles of chemotherapy consisting of cyclophosphamide, doxorubicin, and cisplatin. A second-look laparotomy approximately 1 year later was negative for tumor. One year later a 1.5cm peritoneal nodule was discovered on CT scan. The patient underwent a third laparotomy. The nodule was resected. The remainder of the abdomen and pelvis were free of disease. Chemotherapy was restarted with cyclophosphamide and cisplatin. After 5 months, CA-125 level rose and chemotherapy was changed to melphalan, but after 1 year, CA-125 level, which had stabilized, began rising. The CT scan of the abdomen and pelvis was normal. Chemotherapy was changed to carboplatin and the CA125 level decreased. Six months later CA-125 level rose and chemotherapy was changed to etoposide and the CA-125 level dropped. Two months later, the patient reported recurrent headaches, dizziness, and right-sided weakness. A magnetic resonance image (MRI) of the brain showed multiple small lesions in the left cerebral hemisphere consistent with metastatic carcinoma. The patient was treated with steroids and received radiotherapy to the brain. A repeat CT scan of the brain revealed resolution of the lesions and her strength gradually improved. Three months after the discovery of the brain metastases, the patient reported a 2-week history of bilateral lower extremity weakness, clumsiness of the left hand, and paresthesias in the ankles and toes. She was referred to Allegheny General Hospital. Physical examination was remarkable for bilateral lower-extremity weakness, 3/5 proximal muscle strength, 4/5 distal muscle strength, and decreased left hand grip. She had bilateral Babinski signs.
195 oo90-8258/92 $1 SO Copyright 0 1992 by Academic Press, Inc. All rights of reproduction in any form reserved.
196
THOMAS,
FIG. 1. MRI scan of the cervkal-thoracic
SIMON, AND EVANS
spine demonstrates signal enhancement within the spinal cord (Tl image).
Evaluation included a normal MRI of the lumbar spine. MRI of the cervicothoracic spine revealed an abnormalfusiform dilitation of the cervical spinal cord from C3 through the cervicothoracic junction. Following infusion of intravenous contrast, an area of ovoid enhancement was seen (Fig. 1). On the basis of the clinical presentation and characteristic MRI findings, intramedullary spinal cord metastasis was diagnosed. High-dose steroids were begun and the patient received radiotherapy (30 Gy) to the cervical spine. Her strength improved over the next few weeks. A CT scan of the abdomen and pelvis revealed a questionable hepatic mass. An ultrasound of the liver confirmed the metastatic involvement of the liver that was suggested by the CT scan, A bone scan was normal. A CT scan of the chest revealed metastatic spread to the right lung. The patient was restarted on chemotherapy with ifosfamide and mesna. The liver and lung metastases progressed and she developed bone and skin metastases. She expired 6 months after the discovery of the intramedullary spinal cord metastasis.
DISCUSSION The intramedullary spinal cord is an unusual site of metastatic cancer [5-121. Of 3359 patients studied at autopsy, 29% had metastases to the central nervous system (CNS). Only 5% had intramedullary spinal cord metastases [19]. Less than 200 cases of intramedullary spinal cord metastases have been recorded [8]. Lung and breast were the most commonly associated primary cancers, accounting for approximately 50% and 15% of cases, respectively. Lymphoma, colorectal cancer, head and neck tumors, renal cell cancer, and melanoma have also been associated with intramedullary spinal cord metastases [9]. We could find no reported cases of epithelial ovarian cancer with metastatic spread to the intramedullary spinal cord. Intramedullary spinal cord metastasis occurs at any time during the course of cancer. Usually it is associated with widespread CNS and systemic metastases [9], as in our case. The clinical presentation of intramedullary spinal cord
197
CASE REPORT
metastases is often very subtle and nonspecific. Grem et al. found that back or radicular pain was the presenting symptom in 61% of the patients reviewed while weakness and parathesias were present in 64 and 27% of patients, respectively [9]. If left untreated neurologic deficits usually evolve rapidly. They may progress within 1 week but more commonly over 1 month. Less commonly deficits develop over 1 to 6 months. Patients experience paraparesis or tetraparesis, pain, paresthesias, and a sensory level deficit, as well as urinary and bowel symptoms [6,9,10]. Since the symptoms of intramedullary spinal cord metastases are often very subtle, diagnosis can be very difficult. MRI provides an easy and noninvasive technique for studying the spinal cord and is more sensitive and specific than a myelogram or postmyelogram CT scan [13,14]. Metastatic tumor and reactive edema within the cord appear hypointense relative to normal cord tissue on Tl-weighted images and hyperintense on T2-weighted images. Metastatic tumors enhance with contrast administration and appear well-circumscribed (13). Myelography was previously the most important radiographic study, characteristically revealing a fusiform expansion of the spinal cord. Myelograms have been reported to be negative in about 40% of cases (14). Other diagnostic tests including cerebrospinal fluid examination and plain spine films, are of little value in the diagnosis of intramedullary spinal cord metastases [9,14]. Cerebrospinal fluid analyses usually reveal elevation of protein levels, normal cell counts, and a negative cytological examination
[lOI*
Intramedullary spinal cord metastasis is considered a neurological emergency. Patients are treated with steroids and radiotherapy to the spinal cord. Response depends on neurological status at diagnosis. Neurosurgical procedures may be of benefit in selected patients, particularly if the tumor is well-encapsulated, the systemic disease is under control, and the tumor type is radioresistant [7,8,15,16]. Despite these measures, the prognosis of patients with intramedullary spinal cord metastases is poor, and most patients succumb to widespread metastatic disease within weeks [9]. In conclusion, as therapy of ovarian cancer improves and intraabdominal disease is controlled with aggressive surgery and chemotherapy, systemic metastases, especially in unusual sites, may become more common. Intramedullary spinal cord metastasis is an unusual complication of cancer that can present as progressive myelopathy in a patient with disseminated disease.
Awareness of intramedullary important as clinical suspicion make this diagnosis. Although if patients are treated rapidly, be avoided and quality of life
spinal cord metastases is must be high in order to life expectancy is limited, neurological sequelae may may be improved.
REFERENCES 1. Rose, P. G., Piver, M. S., Tsukada, Y., and Lau, T. S. Metastatic patterns in histologic variants of ovarian cancer: An autopsy study, Cancer 64, 1508-1513 (1989). 2. Larson, D. M., Copeland, L. J., Moser, R. P., Malone, J. M., Jr. Gershenson, D. M., and Wharton, J. T. Central nervous system metastases in epithelial ovarian carcinoma, Obsret. Gynecol. 68, 746-750 (1986). 3. Plaxe, S. C., Dottino, P. R., Lipsztein, R., Dalton, J., and Cohen, C. J. Clinical features and treatment outcome of patients with epithehal carcinoma of the ovary metastatic to the central nervous system, Obstet. Gynecol. 75, 278-281 (1990). 4. Ozols, R. F. Ovarian cancer, Semin. Surg. Oncol. 6, 328-338 (1990). 5. Edelson, R. N., Deck, M. D. F., and Posner, J. B. Intramedullary spinal cord metastases. Clinical and radiographic findings in nine cases, Neurology 22, 122221231 (1972). 6. Costigan, D. A., and Winkelman, M. D. Intramedullary spinal cord metastasis. A chnicopathological study of 13 cases, J. Neurosurg. 62, 227-233 (1985). 7. Winkelman, M. D., Adelstein, D. J., and Karlins, N. L. Intramedullary spinal cord metastasis: Diagnostic and therapeutic considerations, Arch. Neural. 44, 526-531 (1987). 8. Choucair, A. K. Myelopathies in the cancer patient: Incidence, presentation, diagnosis and management, Oncology 5,25-31(1991). 9. Grem, J. L., Burgess, J., and Trump, D. L. Clinical features and natural history of intramedullary spinal cord metastasis, Cancer 56, 2305-2314 (1985). 10. Jellinger, K., Kothbauer, P., Sunder-Plassmann, E., and Weiss, R. Intramedullary spinal cord metastases, J. Neural. 220,31-41(1979). 11. Benson, D. F. Intramedullary spinal cord metastasis, Neurology 10, 281-287 (1960). 12. Takakura, K., Sano, K., Hojo, S., and Hirano, A. Metastatic tumors of the central nervous system, Igaku-Shoin, New York (1982). Kamholtz, R., and Sze, G. Current imaging in spinal metastatic 13. disease, Semirz. Oncol. 18, 158-169 (1991). 14. Post, M. J. D., Quencer, R. M., Green, B. A., Montalvo, B. M., Tobias, J. A., Sowers, J. J., and Levin, I. H. Intramedullary spinal cord metastases, mainly of nonneurogenic origin. Am. J. Roentgenol. 148, 1015-1022 (1987). 15. Decker, R. E., Sundrani, S., Citron, M. L., and Herrschaft, D. S. Intramedullary spinal cord metastases treated by complete resection of tumor prior to radiotherapy and chemotherapy. Case report and review, Spine l2, 393-395 (1987). 16. Findlay, J. M., Bernstein, M., Vanderlinden, R. G., and Resch, L. Microsurgical resection of solitary intramedullary spinal cord metastases, Neurosurgery 21, 911-915 (1987).
ONCOLOGY
‘d‘t,
195-197 (1992)
CASE REPORT lntramedullary Spinal Cord Metastases from Epithelial Ovarian Carcinoma ANDREW W. THOMAS, Department
M.D.,
of Medicine,
SHERYL R. SIMON, M.D. ,I AND CAROL EVANS, Allegheny
General
Received
May
A patient with poorly differentiatedserouscystadenocarcinoma of both ovarieswho had undergoneextensivemedicaltreatment presentedwith nonspecificneurologiccomplaints.With the aid of magneticresonanceimaging, a metastaticlesionin the intramedullary area of the spinal cord wasdiagnosed.Rapidly instituted high-dosesteroidsand radiotherapy resultedin resolution of her symptoms, Intramedullary spinal cord metastasisis an unusualmetastaticsite. This isthe first reportedcaseof epithelial ovarian carcinomametastaticto the intramedullary spinal cord. 0 1992 Academic
Press, Inc.
Central nervous system metastases are rare in patients with epithelial ovarian cancer (l-3). In one autopsy series, 11 of 381 (3%) patients had metastases to the cerebrum, cerebellum, pons, medulla, and leptomeninges [l]. In a retrospective epidemiologic review, the frequency was only 0.29% [2]. Ovarian cancer is the fourth leading cause of cancer death in women. Most patients die as a result of massive intraabdominal disease. As advances in therapy have prolonged disease-free interval and median survival [4], patterns of metastases may change and spread to unusual sites may become more common [3]. A case of ovarian cancer with symptomatic intramedullary spinal cord metastasis is reported to document a metastatic site that has not been previously recognized. CASE REPORT A 49-year-old woman underwent exploratory laparotomy and debulking procedure at an outside health facility ’ To whom reprint requests should be addressed at Allegheny Hospital, 320 East North Ave., Pittsburgh, PA 15212.
Hospital,
General
Pittsburgh,
Pennsylvania
M.D.
15212
3, 1991
for poorly differentiated serous cystadenocarcinoma of both ovaries. Postoperatively she received 12 cycles of chemotherapy consisting of cyclophosphamide, doxorubicin, and cisplatin. A second-look laparotomy approximately 1 year later was negative for tumor. One year later a 1.5cm peritoneal nodule was discovered on CT scan. The patient underwent a third laparotomy. The nodule was resected. The remainder of the abdomen and pelvis were free of disease. Chemotherapy was restarted with cyclophosphamide and cisplatin. After 5 months, CA-125 level rose and chemotherapy was changed to melphalan, but after 1 year, CA-125 level, which had stabilized, began rising. The CT scan of the abdomen and pelvis was normal. Chemotherapy was changed to carboplatin and the CA125 level decreased. Six months later CA-125 level rose and chemotherapy was changed to etoposide and the CA-125 level dropped. Two months later, the patient reported recurrent headaches, dizziness, and right-sided weakness. A magnetic resonance image (MRI) of the brain showed multiple small lesions in the left cerebral hemisphere consistent with metastatic carcinoma. The patient was treated with steroids and received radiotherapy to the brain. A repeat CT scan of the brain revealed resolution of the lesions and her strength gradually improved. Three months after the discovery of the brain metastases, the patient reported a 2-week history of bilateral lower extremity weakness, clumsiness of the left hand, and paresthesias in the ankles and toes. She was referred to Allegheny General Hospital. Physical examination was remarkable for bilateral lower-extremity weakness, 3/5 proximal muscle strength, 4/5 distal muscle strength, and decreased left hand grip. She had bilateral Babinski signs.
195 oo90-8258/92 $1 SO Copyright 0 1992 by Academic Press, Inc. All rights of reproduction in any form reserved.
196
THOMAS,
FIG. 1. MRI scan of the cervkal-thoracic
SIMON, AND EVANS
spine demonstrates signal enhancement within the spinal cord (Tl image).
Evaluation included a normal MRI of the lumbar spine. MRI of the cervicothoracic spine revealed an abnormalfusiform dilitation of the cervical spinal cord from C3 through the cervicothoracic junction. Following infusion of intravenous contrast, an area of ovoid enhancement was seen (Fig. 1). On the basis of the clinical presentation and characteristic MRI findings, intramedullary spinal cord metastasis was diagnosed. High-dose steroids were begun and the patient received radiotherapy (30 Gy) to the cervical spine. Her strength improved over the next few weeks. A CT scan of the abdomen and pelvis revealed a questionable hepatic mass. An ultrasound of the liver confirmed the metastatic involvement of the liver that was suggested by the CT scan, A bone scan was normal. A CT scan of the chest revealed metastatic spread to the right lung. The patient was restarted on chemotherapy with ifosfamide and mesna. The liver and lung metastases progressed and she developed bone and skin metastases. She expired 6 months after the discovery of the intramedullary spinal cord metastasis.
DISCUSSION The intramedullary spinal cord is an unusual site of metastatic cancer [5-121. Of 3359 patients studied at autopsy, 29% had metastases to the central nervous system (CNS). Only 5% had intramedullary spinal cord metastases [19]. Less than 200 cases of intramedullary spinal cord metastases have been recorded [8]. Lung and breast were the most commonly associated primary cancers, accounting for approximately 50% and 15% of cases, respectively. Lymphoma, colorectal cancer, head and neck tumors, renal cell cancer, and melanoma have also been associated with intramedullary spinal cord metastases [9]. We could find no reported cases of epithelial ovarian cancer with metastatic spread to the intramedullary spinal cord. Intramedullary spinal cord metastasis occurs at any time during the course of cancer. Usually it is associated with widespread CNS and systemic metastases [9], as in our case. The clinical presentation of intramedullary spinal cord
197
CASE REPORT
metastases is often very subtle and nonspecific. Grem et al. found that back or radicular pain was the presenting symptom in 61% of the patients reviewed while weakness and parathesias were present in 64 and 27% of patients, respectively [9]. If left untreated neurologic deficits usually evolve rapidly. They may progress within 1 week but more commonly over 1 month. Less commonly deficits develop over 1 to 6 months. Patients experience paraparesis or tetraparesis, pain, paresthesias, and a sensory level deficit, as well as urinary and bowel symptoms [6,9,10]. Since the symptoms of intramedullary spinal cord metastases are often very subtle, diagnosis can be very difficult. MRI provides an easy and noninvasive technique for studying the spinal cord and is more sensitive and specific than a myelogram or postmyelogram CT scan [13,14]. Metastatic tumor and reactive edema within the cord appear hypointense relative to normal cord tissue on Tl-weighted images and hyperintense on T2-weighted images. Metastatic tumors enhance with contrast administration and appear well-circumscribed (13). Myelography was previously the most important radiographic study, characteristically revealing a fusiform expansion of the spinal cord. Myelograms have been reported to be negative in about 40% of cases (14). Other diagnostic tests including cerebrospinal fluid examination and plain spine films, are of little value in the diagnosis of intramedullary spinal cord metastases [9,14]. Cerebrospinal fluid analyses usually reveal elevation of protein levels, normal cell counts, and a negative cytological examination
[lOI*
Intramedullary spinal cord metastasis is considered a neurological emergency. Patients are treated with steroids and radiotherapy to the spinal cord. Response depends on neurological status at diagnosis. Neurosurgical procedures may be of benefit in selected patients, particularly if the tumor is well-encapsulated, the systemic disease is under control, and the tumor type is radioresistant [7,8,15,16]. Despite these measures, the prognosis of patients with intramedullary spinal cord metastases is poor, and most patients succumb to widespread metastatic disease within weeks [9]. In conclusion, as therapy of ovarian cancer improves and intraabdominal disease is controlled with aggressive surgery and chemotherapy, systemic metastases, especially in unusual sites, may become more common. Intramedullary spinal cord metastasis is an unusual complication of cancer that can present as progressive myelopathy in a patient with disseminated disease.
Awareness of intramedullary important as clinical suspicion make this diagnosis. Although if patients are treated rapidly, be avoided and quality of life
spinal cord metastases is must be high in order to life expectancy is limited, neurological sequelae may may be improved.
REFERENCES 1. Rose, P. G., Piver, M. S., Tsukada, Y., and Lau, T. S. Metastatic patterns in histologic variants of ovarian cancer: An autopsy study, Cancer 64, 1508-1513 (1989). 2. Larson, D. M., Copeland, L. J., Moser, R. P., Malone, J. M., Jr. Gershenson, D. M., and Wharton, J. T. Central nervous system metastases in epithelial ovarian carcinoma, Obsret. Gynecol. 68, 746-750 (1986). 3. Plaxe, S. C., Dottino, P. R., Lipsztein, R., Dalton, J., and Cohen, C. J. Clinical features and treatment outcome of patients with epithehal carcinoma of the ovary metastatic to the central nervous system, Obstet. Gynecol. 75, 278-281 (1990). 4. Ozols, R. F. Ovarian cancer, Semin. Surg. Oncol. 6, 328-338 (1990). 5. Edelson, R. N., Deck, M. D. F., and Posner, J. B. Intramedullary spinal cord metastases. Clinical and radiographic findings in nine cases, Neurology 22, 122221231 (1972). 6. Costigan, D. A., and Winkelman, M. D. Intramedullary spinal cord metastasis. A chnicopathological study of 13 cases, J. Neurosurg. 62, 227-233 (1985). 7. Winkelman, M. D., Adelstein, D. J., and Karlins, N. L. Intramedullary spinal cord metastasis: Diagnostic and therapeutic considerations, Arch. Neural. 44, 526-531 (1987). 8. Choucair, A. K. Myelopathies in the cancer patient: Incidence, presentation, diagnosis and management, Oncology 5,25-31(1991). 9. Grem, J. L., Burgess, J., and Trump, D. L. Clinical features and natural history of intramedullary spinal cord metastasis, Cancer 56, 2305-2314 (1985). 10. Jellinger, K., Kothbauer, P., Sunder-Plassmann, E., and Weiss, R. Intramedullary spinal cord metastases, J. Neural. 220,31-41(1979). 11. Benson, D. F. Intramedullary spinal cord metastasis, Neurology 10, 281-287 (1960). 12. Takakura, K., Sano, K., Hojo, S., and Hirano, A. Metastatic tumors of the central nervous system, Igaku-Shoin, New York (1982). Kamholtz, R., and Sze, G. Current imaging in spinal metastatic 13. disease, Semirz. Oncol. 18, 158-169 (1991). 14. Post, M. J. D., Quencer, R. M., Green, B. A., Montalvo, B. M., Tobias, J. A., Sowers, J. J., and Levin, I. H. Intramedullary spinal cord metastases, mainly of nonneurogenic origin. Am. J. Roentgenol. 148, 1015-1022 (1987). 15. Decker, R. E., Sundrani, S., Citron, M. L., and Herrschaft, D. S. Intramedullary spinal cord metastases treated by complete resection of tumor prior to radiotherapy and chemotherapy. Case report and review, Spine l2, 393-395 (1987). 16. Findlay, J. M., Bernstein, M., Vanderlinden, R. G., and Resch, L. Microsurgical resection of solitary intramedullary spinal cord metastases, Neurosurgery 21, 911-915 (1987).
