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Cholangiocarcinoma presenting as a cerebellar metastasis: Case report and review of the literature
CT: THE JOURNAL OF COMPUTED TOMOGRAPHY
1984; 8:191-195
CHOLANGIOCARCINOMA PRESENTING AS A CEREBELLAR METASTASIS: CASE REPORT AND REVIEW OF THE LITERATURE MARK S. GUDESBLATT, CHARLES F. LANZIERI,
MD, WALTER SENCER, MD, MICHAEL MD, AND SUN K. SONG, MD
Cholangiocarcinoma is an uncommon tumor that presents with hepatobiliary dysfunction. We report a patient with a chronic progressive organic mental syndrome, diffuse weakness, and gait disturbance who was discovered to have obstructive hydrocephalus due to a neoplasm. Pathologic examination revealed primary cholangiocarcinoma metastatic to the cerebellum. This tumor has not been previously reported to present with neurologic involvement.
KEY WORDS:
Cholangiocarcinoma; Cerebellar metastases
One of the most common complications of cancer is intracranial metastatic disease. Neurologic manifestations of metastatic disease are often the presenting complaint of many patients (1). Tumors of hepatobiliary origin most commonly present with signs and symptoms referable to the gastrointestinal tract (2). Central nervous system metastases of hepatobiliary cancers are extremely rare, and have only occasionally been seen with widely disseminated disease (3,4).The following is the first case report of cholangiocarcinoma presenting with complaints referable to the central nervous system and not the gastrointestinal tract.
From the Departments of Neurology, Neuroradiology, and Neuropathology, The Mount Sinai Medical Center and School of Medicine of the City University of New York. Address reprint requests to: Mark S. Gudesblatt, MD, Department of Neurology, Mount Sinai Hospital, One Gustave Levy Place, New York, New York 10029. Received September 1983. 0 1984 by Elsevier Science Publishing Co., Inc. 52 Vanderbilt Ave., New York, NY 10017 0149-936X3/841$3.00
SACHER,
MD,
CASE REPORT
A %-year-old woman was admitted to the neurology service in 1982 for evaluation of a change in mental status of 6 months’ duration. The patient was well until sustaining a traumatic hip fracture in 1981. After internal fixation was performed, she was discharged in good condition. Within a few months, her family noticed a personality change. She became withdrawn and had a decrease in appetite associated with weight loss and several episodes of nausea and vomiting. Subsequently progressive gait difficulty, confusion, and intermittent lethargy became apparent. On admission, the general medical examination revealed a very thin woman with no abnormalities of the lungs, abdomen, cardiovascular or lymphatic systems. The mental status examination revealed the patient to be mildly lethargic but easily arousable with a marked organic mental syndrome. The results of the cranial nerve examination were entirely normal, except for a slow speech pattern. unilateral and bilateral cold-water calories produced Motor examination revealed abnormal responses. diffuse paratonia, mild general limb weakness, and hyperactive deep tendon reflexes. Bilateral ankle clonus, Babinski signs, and frontal release reflexes were present. Rapid alternating movements were slow with slight dysmetria. Gait could not be tested. Significant laboratory data included only mild abnormalities of liver function: serum glutamic pyruvic transaminase, 165 units (normal, 8 to 40 units); serum glutamic oxaloacetic transaminase, 64 units (normal, 8 to 42 units); alkaline phosphatase, 112 units (normal, 30 to 85 units); lactic dehydrogenase, 309 units (normal, 90 to 200 units); and yglutamyl transpeptidase triphosphate, 245 units
192
GUDESBLATT ET AL.
CT: THE JOURNAL OF COMPUTED TOMOGRAPHY VOL. 8 NO. 3
(normal, 4 to 28 units). The following laboratory data was normal: complete blood cell count, coagulation parameters, erythrocyte sedimentation rate, serum electrolytes, bilirubin, thyroid functions, and anti-nuclear antibody (ANA). The hepatitis surface antigen was negative. Carcinoembryonic antigen (CEA) and alpha-fetoprotein were not measured. The computed tomography (CT) scan (Figure 1) revealed a large, irregular, peripherally enhancing mass predominantly in the right cerebellar hemisphere, but involving the vermis as well. Obstructive hydrocephalus was present. The vertebral angiogram (Figure 2) showed a mass with arteriovenous shunting consistent with a vascular intraaxial tumor, most likely metastatic in nature. A liver scan demonstrated a large discrete cold area about 7 cm in size in the inferior portion of the right lobe of the liver. Ultrasonography revealed a 4.5cm mass involving the anterior aspect of the right lobe of the liver. The retroperitoneum and kidneys appeared normal. The chest x-ray was normal. A bone scan showed no bony metastases. A laparoscopic-directed biopsy was performed, which revealed gross replacement of the right lobe of the liver by tumor. There was no evidence of ascites or peritoneal carcinomatoses. The preliminary 1. A post-contrast-enhanced CT scan showing evidence of an enhancing mass with central lucency, involving the left cerebeller hemisphere. Obstructive hydrocephalus with enlargement of the fourth and lateral ventricles is noted. FIGURE
biopsy report was well-differentiated epithelial tumor. The patient and family refused further diagnostic or therapeutic measures. The patient died 4 days later.
PATHOLOGY An autopsy was performed approximately 16 hours after death. The postmortem examination of the liver disclosed a large yellow-white lobulated noncapsulated firm tumor nodule in the anterior part of the right lobe that measured 8 x 6 x 4 cm. The gallbladder was in contact with the undersurface of the tumor but was easily separated. The histologic diagnosis was cholangiocarcinoma, intrahepatic peripheral type, moderately to well differentiated (Figure 3). The lungs showed severe bilateral aspiration pneumonia. There was no metastases to any part of the body except for the cerebellum. The examination of the central nervous system disclosed a large, well-circumscribed tumor mass in the posterior-superior aspect of the cerebellum (Figure 4) involving the midline structures of the cerebellar cortex and both sides of the central white matter. It measured 4.5 x 2.5 x 2 cm. The cut surface of the tumor was finely granular and tan-white and showed large areas of necrotic change that were associated with one large collection of cystic fluid. The microscopic diagnosis was metastatic carcinoma with histologic features consistent with cholangiocarcinoma (Figure 3). DISCUSSION The clinical presentation of the patient was remarkable for signs and symptoms of neurologic and not hepatobiliary dysfunction. Central nervous system metastases are predominantly supratentorial, and those that are infratentorial generally exhibit a variety of cranial-nerve and long-tract abnormalities without a change in mental status (1,~). The long course and nonlocalizing examination seen in this case were very unusual for metastatic disease to the posterior fossa. The lack of any cranial nerve abnormality was attributed to a slow process. The initial complaints of nausea, vomiting, and anorexia may be attributable in many cases to gastrointestinal pathology, but in this situation might also be explained by central nervous system dysfunction. Cholangiocarcinoma is an uncommon primary liver tumor originating in the intrahepatic bile duct system. In one large series of over 7000 autopsies performed over a IO-year period, less than 300 (4%) had a primary malignancy of the liver (6). Of these, only 57 cases (0.7%) of all autopsies demonstrated
JULY 1984
view of FK XJRE 2. (A) Anteroposterior the selective injection of the left vertebral artcxy, revealing a highly vascular mass wit :h arteriovenous shunting involving the left vertebral angiogram. (B) Lateral view of 1:he left vertebral angiogram.
CHOLANGIOCARCINOMAiCEREBELLAR
METASTASIS
193
194
GUDESBLATT ET AL.
FIGURE 3. Cholangiocarcinoma tion approximately X 525.
CT: THE JOURNAL OF COMPUTED TOMOGRAPHY VOL. 8 NO. 3
in the liver. Magnifica-
intrahepatic bile duct cancer. This corresponds to 17.6% of all primary liver cancers. Other authors have reported an even lower incidence (2). The clinical presentation of cholangiocarcinoma is well described in the literature. Commonly reported early signs and symptoms are abdominal pain malaise (30%) jaundice (60%), fever (38%) (17.5%), and an abdominal mass (4%) (6). Jaundice was commonly noted to constitute an early sign 30 times more often in cholangiocarcinoma than in hepatocellular carcinoma. In no series were neurologic complaints part of the presenting picture (2,3,6-g). The most recent large review reports that the physical examination at initial presentation revealed evidence of hepatomegally (62%), ascites (27%), and jaundice (24%) (7). No neurological abnormalities were noted in the physical examination in that series. FIGURE 4. Transverse
section of cerebellum showing tumor occupying the superior-posterior region affecting midline structures and parts of the central white matter and the nuclear groups. Macrophotograph.
The metastatic pattern of cholangiocarcinoma is most noted for intrahepatic and regional lymph node metastases, with regional lymph node and pancreatic metastases being the most common extrahepatic sites (6). Antemortem diagnosis of extrahepatic metastases is rarely made (6). Autopsy examination revealed a variable frequency of extrahepatic metastases from 21 to 69% (6,8). Peripheral cholangiocarcinoma is noted to have metastases twice as often as the hilar type (6). The second most common extrahepatic site is lung, in one series accounting for 23% (6). In only one series was metastatic involvement of the brain noted in 4 of 137 patients (less than 4%) (3). This series does not distinguish between hepatocellular or cholangiocarcinoma type of primary liver tumors. Other large series, including almost 5OOO autopsies of patients with primary liver cancer (almost 1000 cases of cholangiocarcinoma), report no central nervous system metastases (2,6,7,9). The diagnosis of cholangiocarcinoma metastases to the cerebellum was made on postmortem examination. The route of spread was presumably hematogenous. The reasons for the usual sparing of the brain by this tumor are not known.
REFERENCES 1. Posner JB, Chernik NL: Intracranial
metastases from systemic cancer. In: Schoenberg BS (ed). Advances in Neurology. New York, Raven, 1978, pp 579-92.
2. Inouye AA, Whelan TJ: Primary live cancer: cases in Hawaii. Am J Surg 1978; 138:53-61.
A review of 205
3. El-Domeiri AA, Huvos AG, Goldsmith HS, et al: Primary malignant tumors of the liver. Cancer 1971;27:7-11. 4. Brunner DR, Dunne MG, Rao KL: Hepatoma cerebellar metastases. CT 1982;6:65-8. 5. Adams RD, Victor M: Principles York, McGraw-Hill, 1981.
presenting
of Neurology,
as a
2nd ed. New
6. Okuda K, Kubo Y, Okazaki N, et al: Clinical aspects of intrahepatic bile duct carcinoma including hilar carcinoma: A study of 57 autopsy-proven cases. Cancer 1977; 39:232-46. 7. Okuda K: Primary 1980;45:2663-9.
liver
cancers
8. Yarbrough DR: Primary carcinoma ducts. Am J Surg 1973;125:723-5.
in
Japan.
of the extrahepatic
Cancer bile
9. Schiff L, Schiff EF (eds): Diseases of the Liver, 5th ed. Philadelphia, Lippincott, 1982, pp 1128-36.
CONTINUING MEDICAL EDUCATION QUESTIONS 1. Neurologic
complaints system metastasis toms of malignancy. a. Often. b. Rarely. c. Never.
secondary to central nervous are the presenting symp-
JULY
CHOLANGIOCARCINOMNCEREBELLAR
1984
2. Hepatobiliary carcinomas nervous system. a. Often. b. Rarely. c. Never. 3. Cholangiocarcinoma a. Hematogenously.
usually
metastasize
metastasizes:
to the central
METASTASIS
195
b. By direct invasion. c. Via lymphatics. 4. Metastasis to the central nervous commonly: a. In the hemispheres. b. In the cerebellum. c. In the spinal cord.
system are seen most
1984; 8:191-195
CHOLANGIOCARCINOMA PRESENTING AS A CEREBELLAR METASTASIS: CASE REPORT AND REVIEW OF THE LITERATURE MARK S. GUDESBLATT, CHARLES F. LANZIERI,
MD, WALTER SENCER, MD, MICHAEL MD, AND SUN K. SONG, MD
Cholangiocarcinoma is an uncommon tumor that presents with hepatobiliary dysfunction. We report a patient with a chronic progressive organic mental syndrome, diffuse weakness, and gait disturbance who was discovered to have obstructive hydrocephalus due to a neoplasm. Pathologic examination revealed primary cholangiocarcinoma metastatic to the cerebellum. This tumor has not been previously reported to present with neurologic involvement.
KEY WORDS:
Cholangiocarcinoma; Cerebellar metastases
One of the most common complications of cancer is intracranial metastatic disease. Neurologic manifestations of metastatic disease are often the presenting complaint of many patients (1). Tumors of hepatobiliary origin most commonly present with signs and symptoms referable to the gastrointestinal tract (2). Central nervous system metastases of hepatobiliary cancers are extremely rare, and have only occasionally been seen with widely disseminated disease (3,4).The following is the first case report of cholangiocarcinoma presenting with complaints referable to the central nervous system and not the gastrointestinal tract.
From the Departments of Neurology, Neuroradiology, and Neuropathology, The Mount Sinai Medical Center and School of Medicine of the City University of New York. Address reprint requests to: Mark S. Gudesblatt, MD, Department of Neurology, Mount Sinai Hospital, One Gustave Levy Place, New York, New York 10029. Received September 1983. 0 1984 by Elsevier Science Publishing Co., Inc. 52 Vanderbilt Ave., New York, NY 10017 0149-936X3/841$3.00
SACHER,
MD,
CASE REPORT
A %-year-old woman was admitted to the neurology service in 1982 for evaluation of a change in mental status of 6 months’ duration. The patient was well until sustaining a traumatic hip fracture in 1981. After internal fixation was performed, she was discharged in good condition. Within a few months, her family noticed a personality change. She became withdrawn and had a decrease in appetite associated with weight loss and several episodes of nausea and vomiting. Subsequently progressive gait difficulty, confusion, and intermittent lethargy became apparent. On admission, the general medical examination revealed a very thin woman with no abnormalities of the lungs, abdomen, cardiovascular or lymphatic systems. The mental status examination revealed the patient to be mildly lethargic but easily arousable with a marked organic mental syndrome. The results of the cranial nerve examination were entirely normal, except for a slow speech pattern. unilateral and bilateral cold-water calories produced Motor examination revealed abnormal responses. diffuse paratonia, mild general limb weakness, and hyperactive deep tendon reflexes. Bilateral ankle clonus, Babinski signs, and frontal release reflexes were present. Rapid alternating movements were slow with slight dysmetria. Gait could not be tested. Significant laboratory data included only mild abnormalities of liver function: serum glutamic pyruvic transaminase, 165 units (normal, 8 to 40 units); serum glutamic oxaloacetic transaminase, 64 units (normal, 8 to 42 units); alkaline phosphatase, 112 units (normal, 30 to 85 units); lactic dehydrogenase, 309 units (normal, 90 to 200 units); and yglutamyl transpeptidase triphosphate, 245 units
192
GUDESBLATT ET AL.
CT: THE JOURNAL OF COMPUTED TOMOGRAPHY VOL. 8 NO. 3
(normal, 4 to 28 units). The following laboratory data was normal: complete blood cell count, coagulation parameters, erythrocyte sedimentation rate, serum electrolytes, bilirubin, thyroid functions, and anti-nuclear antibody (ANA). The hepatitis surface antigen was negative. Carcinoembryonic antigen (CEA) and alpha-fetoprotein were not measured. The computed tomography (CT) scan (Figure 1) revealed a large, irregular, peripherally enhancing mass predominantly in the right cerebellar hemisphere, but involving the vermis as well. Obstructive hydrocephalus was present. The vertebral angiogram (Figure 2) showed a mass with arteriovenous shunting consistent with a vascular intraaxial tumor, most likely metastatic in nature. A liver scan demonstrated a large discrete cold area about 7 cm in size in the inferior portion of the right lobe of the liver. Ultrasonography revealed a 4.5cm mass involving the anterior aspect of the right lobe of the liver. The retroperitoneum and kidneys appeared normal. The chest x-ray was normal. A bone scan showed no bony metastases. A laparoscopic-directed biopsy was performed, which revealed gross replacement of the right lobe of the liver by tumor. There was no evidence of ascites or peritoneal carcinomatoses. The preliminary 1. A post-contrast-enhanced CT scan showing evidence of an enhancing mass with central lucency, involving the left cerebeller hemisphere. Obstructive hydrocephalus with enlargement of the fourth and lateral ventricles is noted. FIGURE
biopsy report was well-differentiated epithelial tumor. The patient and family refused further diagnostic or therapeutic measures. The patient died 4 days later.
PATHOLOGY An autopsy was performed approximately 16 hours after death. The postmortem examination of the liver disclosed a large yellow-white lobulated noncapsulated firm tumor nodule in the anterior part of the right lobe that measured 8 x 6 x 4 cm. The gallbladder was in contact with the undersurface of the tumor but was easily separated. The histologic diagnosis was cholangiocarcinoma, intrahepatic peripheral type, moderately to well differentiated (Figure 3). The lungs showed severe bilateral aspiration pneumonia. There was no metastases to any part of the body except for the cerebellum. The examination of the central nervous system disclosed a large, well-circumscribed tumor mass in the posterior-superior aspect of the cerebellum (Figure 4) involving the midline structures of the cerebellar cortex and both sides of the central white matter. It measured 4.5 x 2.5 x 2 cm. The cut surface of the tumor was finely granular and tan-white and showed large areas of necrotic change that were associated with one large collection of cystic fluid. The microscopic diagnosis was metastatic carcinoma with histologic features consistent with cholangiocarcinoma (Figure 3). DISCUSSION The clinical presentation of the patient was remarkable for signs and symptoms of neurologic and not hepatobiliary dysfunction. Central nervous system metastases are predominantly supratentorial, and those that are infratentorial generally exhibit a variety of cranial-nerve and long-tract abnormalities without a change in mental status (1,~). The long course and nonlocalizing examination seen in this case were very unusual for metastatic disease to the posterior fossa. The lack of any cranial nerve abnormality was attributed to a slow process. The initial complaints of nausea, vomiting, and anorexia may be attributable in many cases to gastrointestinal pathology, but in this situation might also be explained by central nervous system dysfunction. Cholangiocarcinoma is an uncommon primary liver tumor originating in the intrahepatic bile duct system. In one large series of over 7000 autopsies performed over a IO-year period, less than 300 (4%) had a primary malignancy of the liver (6). Of these, only 57 cases (0.7%) of all autopsies demonstrated
JULY 1984
view of FK XJRE 2. (A) Anteroposterior the selective injection of the left vertebral artcxy, revealing a highly vascular mass wit :h arteriovenous shunting involving the left vertebral angiogram. (B) Lateral view of 1:he left vertebral angiogram.
CHOLANGIOCARCINOMAiCEREBELLAR
METASTASIS
193
194
GUDESBLATT ET AL.
FIGURE 3. Cholangiocarcinoma tion approximately X 525.
CT: THE JOURNAL OF COMPUTED TOMOGRAPHY VOL. 8 NO. 3
in the liver. Magnifica-
intrahepatic bile duct cancer. This corresponds to 17.6% of all primary liver cancers. Other authors have reported an even lower incidence (2). The clinical presentation of cholangiocarcinoma is well described in the literature. Commonly reported early signs and symptoms are abdominal pain malaise (30%) jaundice (60%), fever (38%) (17.5%), and an abdominal mass (4%) (6). Jaundice was commonly noted to constitute an early sign 30 times more often in cholangiocarcinoma than in hepatocellular carcinoma. In no series were neurologic complaints part of the presenting picture (2,3,6-g). The most recent large review reports that the physical examination at initial presentation revealed evidence of hepatomegally (62%), ascites (27%), and jaundice (24%) (7). No neurological abnormalities were noted in the physical examination in that series. FIGURE 4. Transverse
section of cerebellum showing tumor occupying the superior-posterior region affecting midline structures and parts of the central white matter and the nuclear groups. Macrophotograph.
The metastatic pattern of cholangiocarcinoma is most noted for intrahepatic and regional lymph node metastases, with regional lymph node and pancreatic metastases being the most common extrahepatic sites (6). Antemortem diagnosis of extrahepatic metastases is rarely made (6). Autopsy examination revealed a variable frequency of extrahepatic metastases from 21 to 69% (6,8). Peripheral cholangiocarcinoma is noted to have metastases twice as often as the hilar type (6). The second most common extrahepatic site is lung, in one series accounting for 23% (6). In only one series was metastatic involvement of the brain noted in 4 of 137 patients (less than 4%) (3). This series does not distinguish between hepatocellular or cholangiocarcinoma type of primary liver tumors. Other large series, including almost 5OOO autopsies of patients with primary liver cancer (almost 1000 cases of cholangiocarcinoma), report no central nervous system metastases (2,6,7,9). The diagnosis of cholangiocarcinoma metastases to the cerebellum was made on postmortem examination. The route of spread was presumably hematogenous. The reasons for the usual sparing of the brain by this tumor are not known.
REFERENCES 1. Posner JB, Chernik NL: Intracranial
metastases from systemic cancer. In: Schoenberg BS (ed). Advances in Neurology. New York, Raven, 1978, pp 579-92.
2. Inouye AA, Whelan TJ: Primary live cancer: cases in Hawaii. Am J Surg 1978; 138:53-61.
A review of 205
3. El-Domeiri AA, Huvos AG, Goldsmith HS, et al: Primary malignant tumors of the liver. Cancer 1971;27:7-11. 4. Brunner DR, Dunne MG, Rao KL: Hepatoma cerebellar metastases. CT 1982;6:65-8. 5. Adams RD, Victor M: Principles York, McGraw-Hill, 1981.
presenting
of Neurology,
as a
2nd ed. New
6. Okuda K, Kubo Y, Okazaki N, et al: Clinical aspects of intrahepatic bile duct carcinoma including hilar carcinoma: A study of 57 autopsy-proven cases. Cancer 1977; 39:232-46. 7. Okuda K: Primary 1980;45:2663-9.
liver
cancers
8. Yarbrough DR: Primary carcinoma ducts. Am J Surg 1973;125:723-5.
in
Japan.
of the extrahepatic
Cancer bile
9. Schiff L, Schiff EF (eds): Diseases of the Liver, 5th ed. Philadelphia, Lippincott, 1982, pp 1128-36.
CONTINUING MEDICAL EDUCATION QUESTIONS 1. Neurologic
complaints system metastasis toms of malignancy. a. Often. b. Rarely. c. Never.
secondary to central nervous are the presenting symp-
JULY
CHOLANGIOCARCINOMNCEREBELLAR
1984
2. Hepatobiliary carcinomas nervous system. a. Often. b. Rarely. c. Never. 3. Cholangiocarcinoma a. Hematogenously.
usually
metastasize
metastasizes:
to the central
METASTASIS
195
b. By direct invasion. c. Via lymphatics. 4. Metastasis to the central nervous commonly: a. In the hemispheres. b. In the cerebellum. c. In the spinal cord.
system are seen most