311
CLINEU
00213
Case report
Angiotropi~ ~ymphoma (intravascular large cell ~ym~homa) presenting with cauda equina syndrome David Lacomis”‘b, Thomas W. Smith”.b and Randall R. Longb
Key ~cords:
Angiotropic
lymphoma;
Peripheral
neuropathy;
Cauda
equina
Summary A 50-year-old
man
developed
cauda
equina
syndrome
of unknown
etiology
that was stable
for 20 months.
Two
months prior to sudden death. he experienced new back pain. confusion, seizures, and multiple cranial nerve palsies. Neuropathologic examination revealed angiotropic lymphoma without p~~renchynlal involvement or infarcts in the brain, spinal cord, and muscle. In addition, nerve roots in the cauda equina contained angiotropic lymphoma and infarcts of various ages. Angiotropic lymphoma should be considered as a cause of cauda equina syndrome and of disorders
that affect the central
and peripheral
nervous
Introduction
We report
Angiotropic lymphoma (intravascular large cell iymphoma) is a rare condition characterized by proliferation of neoplastic lymphoid cells within the lumina of blood vessels [1,2]. The disease has an affinity for the skin and central nervous system (CNS), often leading to cerebral infarction or dementia [I]. Spinal cord involvement, occasionally in isolation, has also been reported [3,4]. Peripheral nerves mononeuropathy
are less likely to be involved. [5] and a clinical presentation
ing the Guillain-Barre
Corre.spon&nw ment,
systems concurrently.
syndrome
fo: Dr. David
LJniv. of Mass.
Medical
01655, USA. Tel.: (508) 856-4147;
[6] have been described.
Lacomis.
Center,
but acute mimick-
MD,
Neurology
Depart-
55 Lake Ave., Worcester,
Fax: (508) 856-6778.
MA
an unusual
case of ~lngiotropic
lymphoma
with relatively long survival, symptomatic involvement of both the CNS and the peripheral nervous system (PNS), and with infarction of nerve roots of the cauda equina.
Case report A 50-year-old man developed progressive central and peripheral nervous system signs and symptoms over a 2-year period. Initially, the patient noted left leg, groin, and bilateral buttock numbness along with partial impotence and urinary urgency without incontinence. The general and neurologic examinations were normal except for loss of ankle jerks and hypesthesia in the left L5---S3 and right Sl- 3 dermatomes. Magnetic resonance imaging (MRI) of the craniospinai axis and myelography
I. A blood vessel in the frontal cortex contains malignant lymphoid cells. Immunoperoxidase magnification, I X0x.
were normal. Tibia1 somatosensory evoked potentials were consistent with a delay in large-fiber sensory conduction at or proximal to the cauda equina. The CSF was acellular, but protein was elevated at 93 mg/dl. A routine metabolic screen including vitamin B,?, ANA and ESR was normal. Over the ensuing 20 months. symptoms were stable. Serial thoracolumbar MR scans were unchanged. Cerebrospinal fluid protein gradually rose to 150 mg/dl. The patient then developed acute back and right radicular leg pain. Over the next month, right L5 paresis evolved, and the right plantar response became extensor. There was intermittent confusion, dysarthria, generalized and focal seizures, and night sweats. A left carotid angiogram was normal. An EEG revealed left temporo-parietal and bifrontal slowing. Spinal imaging was again normal. Nerve conduction studies revealed absent H-reflexes and slowed motor conduction velocities of 35537 m/set in the lower extremities. On needle examination, there was acute denervation in the right L5 myotome. Contrast enhanced cranial CT and MR scans revealed two areas of
cortical
enhancement
mononuclear cells, cose. Cytology did Muscle and sural frontal stereotactic enhancement “nonspecific
L26 (B-cell marker); originnal
(bilateral).
The CSF contained
3
291 mg/dl protein and 41 mg/dl glunot reveal malignant cells. nerve biopsies were normal. A right brain biopsy of an area of cortical
performed perivascular
at another institution revealed inflammation without vasculi-
tis”. Prednisone (80 mg/day) was administered with dramatic improvement in mental status and back pain. The right L-5 weakness improved, but lower extremity numbness was unchanged. For 2 months, there were no new symptoms, but then a new right CN VI palsy occurred. The CSF contained 9 mononuclear cells with a protein content of 153 mg/dl, and the IgG was now elevated to 18.0 mg!dl (0.5-6.1). Cough, shortness of breath, hemoptysis, pleural effusions, and right CN XII, and left CN VII (peripheral) palsies occurred. A mediastinal mass was detected on CT scan, and biopsy revealed a B-cell lymphoma. Two days later, the patient had a sudden cardiac arrest. Attempted resuscitation failed.
Fig 2. A: cauda equina nerve root showing extensive infarction. A blood vessel (bottom of field) contains malignant lymphoid c:ells. He] matoxylin ~ eosin; original magnification, 30x. B: higher magnification of another nerve root showing recent infarction and lemorrhage. A thrombosed blood vessel is present in the center of the field. Hematoxylin - eosin: original magnification. 60:
Pathologic
was observed in the sacral spinal cord. The mottled regions of the brain showed intravascular tumor cells and
findings
The brain weighed 1275 g. Aside from the presence of the biopsy site, the only gross abnormalities of the nervous system were areas of mottled discoloration in the superficial gray matter of the cerebrum a few nerve roots in the cauda equina. Microscopic
examination
revealed
bilaterally intravascular
and in neo-
petechial hemorrhages but no infarcts. Review of the slides from the previous brain biopsy disclosed one cortical vessel containing neoplastic lymphoid cells. The general
postmortem
examination
revealed
malig-
nant B-cell lymphoma within the blood vessels and parenchyma of the heart. Angiotropic lymphoma was also
plastic lymphoid cells in the cauda equina, epineurium of the left femoral and right posterior tibia1 nerves, iliopsoas muscle, spinal cord, brainstem, and leptomeninges and perforating vessels of the cerebral cortical gray matter. The tumor cells stained with leukocyte common anti-
present in the pancreas, parathyroid glands, sigmoid colon, and rectum. Parenchymal tumor cells were noted in the liver, spleen. kidneys. lungs, adrenal glands, right
gen (Dako) and B-cell markers (L26 (Dako, Fig. I), LN 1 (ICN Biomedicals)), but did not stain with macrophage
ers, of the parenchymal
(KPl (Dako)) or T-cell (Leu 22 (Becton and Dickinson), UCHLl (Dako)) markers. Blood vessels, but not tumor cells, stained with factor VIII (Dako). Many of the cauda equina nerve roots showed infarcts of various ages (Fig. 2A.B). The blood vessels in these areas showed marked intimal proliferation and also contained neoplastic lymphoid cells. Central chromatolysis of anterior horn cells
ureter, mediastinal lymph nodes and bone marrow. The cytologic characteristics, including positive B-cell markand
intravascular
were indistinguishable. Pulmonary fusions were also noted.
tumor
cells
edema and pleural ef-
Discussion Although our case is unique, it is somewhat similar to the cases recently described by Hamada et al. [3] in which
Fig. 2B
angiotropic lymphoma was confined to the spinal cord for 10---l2 months before cerebral involvement was clinically evident. Dubas and colleagues also reported a patient with angiotropic lymphoma confined to the lumbosacral spinal cord and nerve roots who died one month after the onset of symptoms [4]. In our case, the disease was initially clinically confined to either the cauda equina or conus medullaris for a much longer period of time (20 months) prior to the onset of cerebral symptoms. Until a mediastinal mass appeared just prior to death, a malignancy was not highly suspected. A vasculitic process had been the leading diagnostic candidate. Pathologic examination revealed infarction of multiple nerve roots in the cauda equina. The infarcts could be directly attributed to vascular occlusion by the malignant lymphoid cells. Infarcts in peripheral nerve related to angiotropic lymphoma have been described only once previously [7]. Krieger et al. described nerve and spinal cord infarcts from a similar process, namely intravascular malignant histiocytosis [8].
The clinical course and histopathologic studies suggest that the tumor began intravascularly in the region of the cauda equina and terminally spread throughout the nervous system and into other organs. Parenchymal involvement in angiotropic lymphoma is atypical. but it has been described, especially in the adrenal gland 191. Extravascular extravasation of tumor cells is a likely mechanism of spread to the parenchyma. We agree with Hamada et al. 131that angiotropic lymphoma should be considered as a rare. nonstructural cause of myelopathy or, as in our case, of cauda equina syndrome. Concurrent central and peripheral nervous system involvement with CSF protein elevation or meningeal inflammation should also raise this diagnostic possibility. Acknowledgement
We appreciate Dr. Allan Ropper’s assistance in the care of this patient.
315
References
5 Vital, C., Heraud. A., Vital, A., Coquet, M., Julien, M. and Maupetit, J. (1989) Acute monoeuropathy with angiotropic
1 Fredericks. R.K., Walker, F.O., Elster, A. and Challa, V. (1991) Angiotropic intravascular large-cell lymphoma (malignant angioendotheliomatosis). Report of a case and review
lymphoma. Acta Neuropathol. (Berl.), 78: 105-107. 6 Dolman, C.L., Sweeney, V.P. and Magil, L.A. (1979) Neoplastic angioendotheliosis. The case of the missed primary? Arch. Neurol., 36: 5-7. 7 Petito, C.K., Gottlieb, G.J., Doughterty, J.H. and Petito, F.A. (1978) Neoplastic angioendotheliosis: ultrastructural study and review of the literature. Neurology, 3: 3933399. 8 Krieger, C., Robitaille, Y., Jothy, S. and Elleker, G. (1982) Intravascular malignant histiocytosis mimicking central nervous system vasculitis: an immunopathological diagnostic
of the literature. Surg. Nemo]., 35: 218-223. 2 Clark. W.C., Dohan, C., Moss, T. and Schweitzer,
J.B.
( 199 I ) Immunocytochemical
evidence of lymphocytic derivation of neoplastic cells in malignant angioendotheliomatosis. J. Neurosurg., 74: 7577162. 3 Hamada, K., Hamada, T., Satoh. M., Tashiro, K., Katoh. I., Naganuma,
M.. Shima,
K., Ogata, A. and Nagashima, K. angioendothelioatosis presenting with myelopathy. Neurology, 4 I : I 13991140. 4 Dubas, F.. Saint-Andre, J.P.. Pouplard-Barthelaix, A., Delestre. F. and Emile, J. (1990) Intravascular malignant lymphomatosis (so-called malignant angioendotheliomatosis): a case confined to the lumbosacral spinal cord and nerve roots. Clin. Neuropathol.. 9: 115~120.
( 1991) Two cases of neoplastic
approach. Ann. Neural., 12: 489492. 9 Fulling, K.H. and Gersell D.J. (1983) Neoplastic angioendotheliomatosis. Histologic, immunohistochemical, and ultrastructural findings in 2 cases. Cancer. 5 I: 1107-l I 18.
CLINEU
00213
Case report
Angiotropi~ ~ymphoma (intravascular large cell ~ym~homa) presenting with cauda equina syndrome David Lacomis”‘b, Thomas W. Smith”.b and Randall R. Longb
Key ~cords:
Angiotropic
lymphoma;
Peripheral
neuropathy;
Cauda
equina
Summary A 50-year-old
man
developed
cauda
equina
syndrome
of unknown
etiology
that was stable
for 20 months.
Two
months prior to sudden death. he experienced new back pain. confusion, seizures, and multiple cranial nerve palsies. Neuropathologic examination revealed angiotropic lymphoma without p~~renchynlal involvement or infarcts in the brain, spinal cord, and muscle. In addition, nerve roots in the cauda equina contained angiotropic lymphoma and infarcts of various ages. Angiotropic lymphoma should be considered as a cause of cauda equina syndrome and of disorders
that affect the central
and peripheral
nervous
Introduction
We report
Angiotropic lymphoma (intravascular large cell iymphoma) is a rare condition characterized by proliferation of neoplastic lymphoid cells within the lumina of blood vessels [1,2]. The disease has an affinity for the skin and central nervous system (CNS), often leading to cerebral infarction or dementia [I]. Spinal cord involvement, occasionally in isolation, has also been reported [3,4]. Peripheral nerves mononeuropathy
are less likely to be involved. [5] and a clinical presentation
ing the Guillain-Barre
Corre.spon&nw ment,
systems concurrently.
syndrome
fo: Dr. David
LJniv. of Mass.
Medical
01655, USA. Tel.: (508) 856-4147;
[6] have been described.
Lacomis.
Center,
but acute mimick-
MD,
Neurology
Depart-
55 Lake Ave., Worcester,
Fax: (508) 856-6778.
MA
an unusual
case of ~lngiotropic
lymphoma
with relatively long survival, symptomatic involvement of both the CNS and the peripheral nervous system (PNS), and with infarction of nerve roots of the cauda equina.
Case report A 50-year-old man developed progressive central and peripheral nervous system signs and symptoms over a 2-year period. Initially, the patient noted left leg, groin, and bilateral buttock numbness along with partial impotence and urinary urgency without incontinence. The general and neurologic examinations were normal except for loss of ankle jerks and hypesthesia in the left L5---S3 and right Sl- 3 dermatomes. Magnetic resonance imaging (MRI) of the craniospinai axis and myelography
I. A blood vessel in the frontal cortex contains malignant lymphoid cells. Immunoperoxidase magnification, I X0x.
were normal. Tibia1 somatosensory evoked potentials were consistent with a delay in large-fiber sensory conduction at or proximal to the cauda equina. The CSF was acellular, but protein was elevated at 93 mg/dl. A routine metabolic screen including vitamin B,?, ANA and ESR was normal. Over the ensuing 20 months. symptoms were stable. Serial thoracolumbar MR scans were unchanged. Cerebrospinal fluid protein gradually rose to 150 mg/dl. The patient then developed acute back and right radicular leg pain. Over the next month, right L5 paresis evolved, and the right plantar response became extensor. There was intermittent confusion, dysarthria, generalized and focal seizures, and night sweats. A left carotid angiogram was normal. An EEG revealed left temporo-parietal and bifrontal slowing. Spinal imaging was again normal. Nerve conduction studies revealed absent H-reflexes and slowed motor conduction velocities of 35537 m/set in the lower extremities. On needle examination, there was acute denervation in the right L5 myotome. Contrast enhanced cranial CT and MR scans revealed two areas of
cortical
enhancement
mononuclear cells, cose. Cytology did Muscle and sural frontal stereotactic enhancement “nonspecific
L26 (B-cell marker); originnal
(bilateral).
The CSF contained
3
291 mg/dl protein and 41 mg/dl glunot reveal malignant cells. nerve biopsies were normal. A right brain biopsy of an area of cortical
performed perivascular
at another institution revealed inflammation without vasculi-
tis”. Prednisone (80 mg/day) was administered with dramatic improvement in mental status and back pain. The right L-5 weakness improved, but lower extremity numbness was unchanged. For 2 months, there were no new symptoms, but then a new right CN VI palsy occurred. The CSF contained 9 mononuclear cells with a protein content of 153 mg/dl, and the IgG was now elevated to 18.0 mg!dl (0.5-6.1). Cough, shortness of breath, hemoptysis, pleural effusions, and right CN XII, and left CN VII (peripheral) palsies occurred. A mediastinal mass was detected on CT scan, and biopsy revealed a B-cell lymphoma. Two days later, the patient had a sudden cardiac arrest. Attempted resuscitation failed.
Fig 2. A: cauda equina nerve root showing extensive infarction. A blood vessel (bottom of field) contains malignant lymphoid c:ells. He] matoxylin ~ eosin; original magnification, 30x. B: higher magnification of another nerve root showing recent infarction and lemorrhage. A thrombosed blood vessel is present in the center of the field. Hematoxylin - eosin: original magnification. 60:
Pathologic
was observed in the sacral spinal cord. The mottled regions of the brain showed intravascular tumor cells and
findings
The brain weighed 1275 g. Aside from the presence of the biopsy site, the only gross abnormalities of the nervous system were areas of mottled discoloration in the superficial gray matter of the cerebrum a few nerve roots in the cauda equina. Microscopic
examination
revealed
bilaterally intravascular
and in neo-
petechial hemorrhages but no infarcts. Review of the slides from the previous brain biopsy disclosed one cortical vessel containing neoplastic lymphoid cells. The general
postmortem
examination
revealed
malig-
nant B-cell lymphoma within the blood vessels and parenchyma of the heart. Angiotropic lymphoma was also
plastic lymphoid cells in the cauda equina, epineurium of the left femoral and right posterior tibia1 nerves, iliopsoas muscle, spinal cord, brainstem, and leptomeninges and perforating vessels of the cerebral cortical gray matter. The tumor cells stained with leukocyte common anti-
present in the pancreas, parathyroid glands, sigmoid colon, and rectum. Parenchymal tumor cells were noted in the liver, spleen. kidneys. lungs, adrenal glands, right
gen (Dako) and B-cell markers (L26 (Dako, Fig. I), LN 1 (ICN Biomedicals)), but did not stain with macrophage
ers, of the parenchymal
(KPl (Dako)) or T-cell (Leu 22 (Becton and Dickinson), UCHLl (Dako)) markers. Blood vessels, but not tumor cells, stained with factor VIII (Dako). Many of the cauda equina nerve roots showed infarcts of various ages (Fig. 2A.B). The blood vessels in these areas showed marked intimal proliferation and also contained neoplastic lymphoid cells. Central chromatolysis of anterior horn cells
ureter, mediastinal lymph nodes and bone marrow. The cytologic characteristics, including positive B-cell markand
intravascular
were indistinguishable. Pulmonary fusions were also noted.
tumor
cells
edema and pleural ef-
Discussion Although our case is unique, it is somewhat similar to the cases recently described by Hamada et al. [3] in which
Fig. 2B
angiotropic lymphoma was confined to the spinal cord for 10---l2 months before cerebral involvement was clinically evident. Dubas and colleagues also reported a patient with angiotropic lymphoma confined to the lumbosacral spinal cord and nerve roots who died one month after the onset of symptoms [4]. In our case, the disease was initially clinically confined to either the cauda equina or conus medullaris for a much longer period of time (20 months) prior to the onset of cerebral symptoms. Until a mediastinal mass appeared just prior to death, a malignancy was not highly suspected. A vasculitic process had been the leading diagnostic candidate. Pathologic examination revealed infarction of multiple nerve roots in the cauda equina. The infarcts could be directly attributed to vascular occlusion by the malignant lymphoid cells. Infarcts in peripheral nerve related to angiotropic lymphoma have been described only once previously [7]. Krieger et al. described nerve and spinal cord infarcts from a similar process, namely intravascular malignant histiocytosis [8].
The clinical course and histopathologic studies suggest that the tumor began intravascularly in the region of the cauda equina and terminally spread throughout the nervous system and into other organs. Parenchymal involvement in angiotropic lymphoma is atypical. but it has been described, especially in the adrenal gland 191. Extravascular extravasation of tumor cells is a likely mechanism of spread to the parenchyma. We agree with Hamada et al. 131that angiotropic lymphoma should be considered as a rare. nonstructural cause of myelopathy or, as in our case, of cauda equina syndrome. Concurrent central and peripheral nervous system involvement with CSF protein elevation or meningeal inflammation should also raise this diagnostic possibility. Acknowledgement
We appreciate Dr. Allan Ropper’s assistance in the care of this patient.
315
References
5 Vital, C., Heraud. A., Vital, A., Coquet, M., Julien, M. and Maupetit, J. (1989) Acute monoeuropathy with angiotropic
1 Fredericks. R.K., Walker, F.O., Elster, A. and Challa, V. (1991) Angiotropic intravascular large-cell lymphoma (malignant angioendotheliomatosis). Report of a case and review
lymphoma. Acta Neuropathol. (Berl.), 78: 105-107. 6 Dolman, C.L., Sweeney, V.P. and Magil, L.A. (1979) Neoplastic angioendotheliosis. The case of the missed primary? Arch. Neurol., 36: 5-7. 7 Petito, C.K., Gottlieb, G.J., Doughterty, J.H. and Petito, F.A. (1978) Neoplastic angioendotheliosis: ultrastructural study and review of the literature. Neurology, 3: 3933399. 8 Krieger, C., Robitaille, Y., Jothy, S. and Elleker, G. (1982) Intravascular malignant histiocytosis mimicking central nervous system vasculitis: an immunopathological diagnostic
of the literature. Surg. Nemo]., 35: 218-223. 2 Clark. W.C., Dohan, C., Moss, T. and Schweitzer,
J.B.
( 199 I ) Immunocytochemical
evidence of lymphocytic derivation of neoplastic cells in malignant angioendotheliomatosis. J. Neurosurg., 74: 7577162. 3 Hamada, K., Hamada, T., Satoh. M., Tashiro, K., Katoh. I., Naganuma,
M.. Shima,
K., Ogata, A. and Nagashima, K. angioendothelioatosis presenting with myelopathy. Neurology, 4 I : I 13991140. 4 Dubas, F.. Saint-Andre, J.P.. Pouplard-Barthelaix, A., Delestre. F. and Emile, J. (1990) Intravascular malignant lymphomatosis (so-called malignant angioendotheliomatosis): a case confined to the lumbosacral spinal cord and nerve roots. Clin. Neuropathol.. 9: 115~120.
( 1991) Two cases of neoplastic
approach. Ann. Neural., 12: 489492. 9 Fulling, K.H. and Gersell D.J. (1983) Neoplastic angioendotheliomatosis. Histologic, immunohistochemical, and ultrastructural findings in 2 cases. Cancer. 5 I: 1107-l I 18.
