Journal of Neuro-Oncology 12: 121-124, 1992. © 1992 Kluwer Academic Publishers. Printed in the Netherlands.
Clinical Study
Intracerebral leukemic mass in acute myelogenous leukemia Kazuhiro Fukui, Ikuzo Iguchi, Akira Kito and Midori Ohba
Departments of Neurosurgery and Internal Medicine at Oogaki City Hospital, Oogaki, Japan
Key words." brain neoplasms, metastasis, leukemia, intracranial leukemic mass lesion, magnetic resonance imaging
Summary Leukemic intracranial space occupying lesions are rare. A 69 year old man with acute myelogenous leukemia was found to have an intracranial leukemic mass at the time of his remission period. Computed tomography and magnetic resonance imaging study demonstrated a large irregular mass in the right temporal lobe. After total removal of the tumor, the patient was treated with whole brain irradiation and intrathecal chemotherapy. After surviving for 7 months, the patient expired of hematologic relapse.
Introduction Central nervous system leukemia is seen in only 0.7% of all metastatic brain tumors [1] with the clinical manifestations generally attributed to diffuse infiltration of cranial and spinal nerves, brain parenchyma, and leptomeninges [2]. Leukemic intracranial space occupying lesions are rare, and in the literature, there are only 13 reported cases of intracranial leukemic mass lesions in the course of the disease [3-7]. Our patient developed left hemiparesis and leukemic mass was found and removed from the right temporal lobe. He made good neurological recovery and enjoyed a useful life until he had a hematologic relapse 7 months after the operation.
Case report A 69 year old man was diagnosed as having AML in September 1987. After induction of chemotherapy with enocitabine, daunorubicin, etoposide and vindesine, the patient had complete remission 4 months after the initial treatment. Then, he received 2 courses of consolidation and 3 courses of
maintenance chemotherapy with enocitabine, etoposide, vindesine, mitoxantrone and prednisolone. Intrathecal administration of methotrexate, cytosine arabinoside and prednisolone was undertaken twice, and the patient went into complete hematologic remission. In December 1989, 26 months after the initial treatment, the patient developed left hemiparesis and was readmitted to the hospital. A computed tomography (CT) scan demonstrated a large irregular mass in the right temporal lobe which was enhanced with contrast material (Fig. 1). Gadolinium-DTPA enhanced T~-weighted magnetic resonance (MR) images also demonstrated a large irregular enhanced tumor in that location (Fig. 2). Subsequently, a right temporal craniotomy was performed with total removal of the tumor which was located in the intracerebral parenchyma and not adhered to the dura mater nor to the leptomeninges. The mass was dark reddish with full of vascularity and had a definitely clear margin. Histological examination revealed an intracerebral mass of AML (Fig. 3) with negative leukocytic common antigen and a positive esterase reaction. After the operation, the patient was treated with 39.2 Gy of whole brain irradiation and intrathecal
122
Fig. 1. Computed tomography scans, precontrast (left) and postcontrast (right) CT scans, showing a large high density mass with irregular enhancement in right temporal lobe.
chemotherapy with methotrexate, cytosine arabinoside and prednisolone. Cerebrospinal fluid cytology became negative after 8 doses of intrathecal chemotherapy. CT scan demonstrated no recurrence of the tumor, and the patient was discharged without neurological deficit. However, in July 1990, the patient was readmitted to the Department of Internal Medicine because of hematologic relapse, and he expired two weeks later. An autopsy was not obtained.
Discussion
Leukemic intracerebral space occupying lesions are rare. Clinically verified central nervous system (CNS) leukemia has been seen in about 6.5-17% of AML and 40-58% of ALL [2, 8]. On autopsy study, 10-29% of AML [8--11] and 25-68% of ALL [9-11] cases showed CNS leukemia, but in most of the cases, there was diffuse leptomeningeal invasion, and microscopic parenchymal leukemic nodules were seen in only 7-12% [8, 10]. On CT study, only 4-7.5% of leukemic patients were diagnosed as having intracranial mass in the course of their disease [12, 13].
Fig. 2. Preoperative magnetic resonance images. Axial T~weighted (upper left) image showing isointense and T2-weighted image (upper right) showing hyperintense tumor in right temporal lobe. The Gd-DTPA enhanced T,-weighted images (lower left and right) showing marked enhancement of the tumor.
123
Fig. 3. Photomicrographof the tumorsectionshowingmyelogenousleukemiccellswithcleavedor ellipsenucleusand smallcytoplasms.
The nucleushas clear plasmosomeand corse chromatin. (H&E, x 1000). A search of the literature revealed only 13 reported cases of intracranial leukemic mass (9 cases of A L L , 4 cases of AML) were diagnosed in the course of their disease [3-7]. Of these cases, 9 cases had supratentorial and 4 cases had infratentorial lesions. Their ages were from 3 to 74 years, and all the patients under 15 years had ALL. The time of discovery of the leukemic mass in CNS following the initial diagnosis of leukemia is reported to be 5 months to 12 years, and all occurred after complete hematologic remission [3-7]. The standard therapy was removal of the tumor, whole brain irradiation from 23 to 42 Gy, and intrathecal administration of methotrexate, cytosine arabinoside and prednisolone [3-7]. Three patients expired after surviving for 2 weeks to 6 months [3, 5, 7]. Leukemic cells cannot invade brain parenchyma readily because of the dura meter and the bloodbrain barrier [14-16]. The mechanism of parenchymal invasion of leukemia cells is postulated in two reports [14, 15]. Azzarelli and Roessmann [14] indicated that leukemic cells infiltrate the leptomeninges by way of perivenous adventitial tissue connecting the dura mater and subarachnoid space.
Price and Johnson [15] pointed out that CNS leukemia is primarily an arachnoidal disease and that parenchymal involvement is due to perivascular extension along the Virchow-Robin spaces of the penetrating cerebral vessels through the pia-glial membrane and into the brain. Blasberg et al. [17] demonstrated that, at a distance of 2.5 mm from the brain surface, the concentration of methotrexate or cytosine arabinoside is less than 1% of that in the cerebrospinal fluid. Consequently, the tumor cells in brain parenchyma are in a pharmacologic sanctuary from the therapeutic agent thereby permitting progressive enlargement of the intracerebral mass. CT scan is an excellent tool for diagnosis of a CNS leukemic mass, demonstrating the lesion as isodense or slightly hyperdense when uniformly enhanced by contrast material [7, 12, 13]. Hemorrhage, abscess, methotrexate leukoencephalopathy, progressive multifocal leukoencephalopathy (thought to be an atypical central nervous system viral infection) may all be seen on CT of patients with leukemia, and must be considered in the differential diagnosis [7, 12, 13]. Primary and
124 metastatic malignant CNS tumors may also show CT findings resemble those of a leukemic mass and need to be differentiated. MR images of primary brain tumors commonly shows hypo- or isointensity on T~-weighted images and hyperintensity with surrounding edema on T2weighted images [18]. The size of the tumor is clearly delineated on Tt-weighted images by the administration of Gd-DTPA. Metastatic brain tumors also show essentially the same findings as primary brain tumor [18]. A search of the literature failed to reveal any report of MR images in the case of intracranial leukemic mass. This case showed isointensity on Tl-weighted image and hyperintensity with surrounding edema on T2-weighted image. The tumor was enhanced clearly by Gd-GTPA on T~-weighted images. The number of cases with central nervous leukemia is increasing as more patients have good remission as a result of improvements in chemotherapy [2, 8]. In the future, the incidence of CNS leukemia will likely be even higher so early diagnosis as well as prompt and adequate treatment will be essential in the management of these patients.
5.
6.
7.
8.
9.
10. 11.
12.
13.
14.
Acknowledgement 15.
The authors are grateful to Dr. William S. Fields for reviewing the manuscript.
16.
References
17.
1. The Committee of Brain Tumor Registry in Japan: Brain Tumor Registry in Japan, Vol 6. 1987, pp 41 2. Dawson DM, Rosenthal DS, Moloney WC: Neurological complications of acute leukemia in adults: changing rate. Ann Intern Med 79: 541-544, 1973 3. Moto A, Nakada J, Oka N, Endo S, Takaku A, Kitagawa M: Acute myeloid leukemia with intracranial tumor formation. No Shinkei Geka 13: 889-893, 1985 4. Nabors MW, Narayan RK, Poplack DG: Intracranial and
18.
otological presentation of acute lymphocytic leukemia. Neurosurgery 17: 309-312, 1985 Sadamori N, Tagawa M, Yamaguchi H, Ichimaru M, Taira Y, Fujii I, Miyagawa N, Miyazaki H, Mori K: A case of acute myelogenous leukemia and brain tumor formation in complete remission. Rinsho Ketsueki 18: 1349-1354, 1977 Shalev O, Slew F, Yaar I, Rachmilewitz EA: Intracerebral tumor and diffuse central nervous system infiltration complicating acute myelogenous leukemia. Cancer 44: 10661069, 1979 Wendling LR, Cromwell LD, Latchaw RE: Computed tomography of intracerebral leukemic masses. A JR 132: 217220, 1979 Wolk RW, Masse SR, Conklin R, Freireich EJ: The incidence of central nervous system leukemia in adults with acute leukemia. Cancer 33: 863-869, 1974 Moore EW, Thomas LB, Shaw RK, Freireich EJ: The central nervous system in acute leukemia. AMA Arch Int Med 105: 451-468, 1960 Phair JP, Anderson RE, Namiki H: The central nervous system in leukemia. Ann Intern Med 61: 863-875, 1964 Reske-Nielsen E, Petersen JH, Sogaard H, Jensen KB: Leukemia of the central nervous system. Lancet 1: 211-212, 1974 Gastaut JA, Gastaut JL, Carcassonne Y: Computerized axial tomography in the study of intracranial complications in hematology. Cancer 41: 487-501, 1978 Pagani JJ, Libshitz HI, Wallace S, Hayman LA: Central nervous system leukemia and lymphoma: Computed tomographic manifestations. AJNR 2: 397-403, 1981 Azzarelli B, Roessmann U: Pathogenesis of central nervous system infiltration in acute leukemia. Arch Pathol Lab Med 101: 203-205, 1977 Price RA, Johnson WW: The central nervous system in childhood leukemia: I. The arachnoid. Cancer 31: 520-533. Williams HM, Diamond HD, Graver LF: The pathogenesis and management of neurological complications in patients with malignant lymphomas and leukemia. Cancer 11: 7682, 1958 Blasberg RG, Patlak C, Fenstermacher JD: Intrathecal chemotherapy: Brain tissue profiles after ventriculo-cisternal perfusion. J Pharmacol Exp Ther 195: 73-83, 1975 Kazner E, Wende S, Grumme T, Stochdorph O, Felix R, Claussen C: CT and MR imaging of brain tumors. In: Computed tomography and magnetic resonance tomography of intracranial tumors, ed 2. Springer-Verlag, Berlin, Heidelberg, New York, London, Paris, Tokyo, Hong Kong 47-458, 1988
Address for offprints: K. Fukui, Department of Neurosurgery, Oogaki City Hospital Oogaki, Gifu Prefecture, 503 Japan
Clinical Study
Intracerebral leukemic mass in acute myelogenous leukemia Kazuhiro Fukui, Ikuzo Iguchi, Akira Kito and Midori Ohba
Departments of Neurosurgery and Internal Medicine at Oogaki City Hospital, Oogaki, Japan
Key words." brain neoplasms, metastasis, leukemia, intracranial leukemic mass lesion, magnetic resonance imaging
Summary Leukemic intracranial space occupying lesions are rare. A 69 year old man with acute myelogenous leukemia was found to have an intracranial leukemic mass at the time of his remission period. Computed tomography and magnetic resonance imaging study demonstrated a large irregular mass in the right temporal lobe. After total removal of the tumor, the patient was treated with whole brain irradiation and intrathecal chemotherapy. After surviving for 7 months, the patient expired of hematologic relapse.
Introduction Central nervous system leukemia is seen in only 0.7% of all metastatic brain tumors [1] with the clinical manifestations generally attributed to diffuse infiltration of cranial and spinal nerves, brain parenchyma, and leptomeninges [2]. Leukemic intracranial space occupying lesions are rare, and in the literature, there are only 13 reported cases of intracranial leukemic mass lesions in the course of the disease [3-7]. Our patient developed left hemiparesis and leukemic mass was found and removed from the right temporal lobe. He made good neurological recovery and enjoyed a useful life until he had a hematologic relapse 7 months after the operation.
Case report A 69 year old man was diagnosed as having AML in September 1987. After induction of chemotherapy with enocitabine, daunorubicin, etoposide and vindesine, the patient had complete remission 4 months after the initial treatment. Then, he received 2 courses of consolidation and 3 courses of
maintenance chemotherapy with enocitabine, etoposide, vindesine, mitoxantrone and prednisolone. Intrathecal administration of methotrexate, cytosine arabinoside and prednisolone was undertaken twice, and the patient went into complete hematologic remission. In December 1989, 26 months after the initial treatment, the patient developed left hemiparesis and was readmitted to the hospital. A computed tomography (CT) scan demonstrated a large irregular mass in the right temporal lobe which was enhanced with contrast material (Fig. 1). Gadolinium-DTPA enhanced T~-weighted magnetic resonance (MR) images also demonstrated a large irregular enhanced tumor in that location (Fig. 2). Subsequently, a right temporal craniotomy was performed with total removal of the tumor which was located in the intracerebral parenchyma and not adhered to the dura mater nor to the leptomeninges. The mass was dark reddish with full of vascularity and had a definitely clear margin. Histological examination revealed an intracerebral mass of AML (Fig. 3) with negative leukocytic common antigen and a positive esterase reaction. After the operation, the patient was treated with 39.2 Gy of whole brain irradiation and intrathecal
122
Fig. 1. Computed tomography scans, precontrast (left) and postcontrast (right) CT scans, showing a large high density mass with irregular enhancement in right temporal lobe.
chemotherapy with methotrexate, cytosine arabinoside and prednisolone. Cerebrospinal fluid cytology became negative after 8 doses of intrathecal chemotherapy. CT scan demonstrated no recurrence of the tumor, and the patient was discharged without neurological deficit. However, in July 1990, the patient was readmitted to the Department of Internal Medicine because of hematologic relapse, and he expired two weeks later. An autopsy was not obtained.
Discussion
Leukemic intracerebral space occupying lesions are rare. Clinically verified central nervous system (CNS) leukemia has been seen in about 6.5-17% of AML and 40-58% of ALL [2, 8]. On autopsy study, 10-29% of AML [8--11] and 25-68% of ALL [9-11] cases showed CNS leukemia, but in most of the cases, there was diffuse leptomeningeal invasion, and microscopic parenchymal leukemic nodules were seen in only 7-12% [8, 10]. On CT study, only 4-7.5% of leukemic patients were diagnosed as having intracranial mass in the course of their disease [12, 13].
Fig. 2. Preoperative magnetic resonance images. Axial T~weighted (upper left) image showing isointense and T2-weighted image (upper right) showing hyperintense tumor in right temporal lobe. The Gd-DTPA enhanced T,-weighted images (lower left and right) showing marked enhancement of the tumor.
123
Fig. 3. Photomicrographof the tumorsectionshowingmyelogenousleukemiccellswithcleavedor ellipsenucleusand smallcytoplasms.
The nucleushas clear plasmosomeand corse chromatin. (H&E, x 1000). A search of the literature revealed only 13 reported cases of intracranial leukemic mass (9 cases of A L L , 4 cases of AML) were diagnosed in the course of their disease [3-7]. Of these cases, 9 cases had supratentorial and 4 cases had infratentorial lesions. Their ages were from 3 to 74 years, and all the patients under 15 years had ALL. The time of discovery of the leukemic mass in CNS following the initial diagnosis of leukemia is reported to be 5 months to 12 years, and all occurred after complete hematologic remission [3-7]. The standard therapy was removal of the tumor, whole brain irradiation from 23 to 42 Gy, and intrathecal administration of methotrexate, cytosine arabinoside and prednisolone [3-7]. Three patients expired after surviving for 2 weeks to 6 months [3, 5, 7]. Leukemic cells cannot invade brain parenchyma readily because of the dura meter and the bloodbrain barrier [14-16]. The mechanism of parenchymal invasion of leukemia cells is postulated in two reports [14, 15]. Azzarelli and Roessmann [14] indicated that leukemic cells infiltrate the leptomeninges by way of perivenous adventitial tissue connecting the dura mater and subarachnoid space.
Price and Johnson [15] pointed out that CNS leukemia is primarily an arachnoidal disease and that parenchymal involvement is due to perivascular extension along the Virchow-Robin spaces of the penetrating cerebral vessels through the pia-glial membrane and into the brain. Blasberg et al. [17] demonstrated that, at a distance of 2.5 mm from the brain surface, the concentration of methotrexate or cytosine arabinoside is less than 1% of that in the cerebrospinal fluid. Consequently, the tumor cells in brain parenchyma are in a pharmacologic sanctuary from the therapeutic agent thereby permitting progressive enlargement of the intracerebral mass. CT scan is an excellent tool for diagnosis of a CNS leukemic mass, demonstrating the lesion as isodense or slightly hyperdense when uniformly enhanced by contrast material [7, 12, 13]. Hemorrhage, abscess, methotrexate leukoencephalopathy, progressive multifocal leukoencephalopathy (thought to be an atypical central nervous system viral infection) may all be seen on CT of patients with leukemia, and must be considered in the differential diagnosis [7, 12, 13]. Primary and
124 metastatic malignant CNS tumors may also show CT findings resemble those of a leukemic mass and need to be differentiated. MR images of primary brain tumors commonly shows hypo- or isointensity on T~-weighted images and hyperintensity with surrounding edema on T2weighted images [18]. The size of the tumor is clearly delineated on Tt-weighted images by the administration of Gd-DTPA. Metastatic brain tumors also show essentially the same findings as primary brain tumor [18]. A search of the literature failed to reveal any report of MR images in the case of intracranial leukemic mass. This case showed isointensity on Tl-weighted image and hyperintensity with surrounding edema on T2-weighted image. The tumor was enhanced clearly by Gd-GTPA on T~-weighted images. The number of cases with central nervous leukemia is increasing as more patients have good remission as a result of improvements in chemotherapy [2, 8]. In the future, the incidence of CNS leukemia will likely be even higher so early diagnosis as well as prompt and adequate treatment will be essential in the management of these patients.
5.
6.
7.
8.
9.
10. 11.
12.
13.
14.
Acknowledgement 15.
The authors are grateful to Dr. William S. Fields for reviewing the manuscript.
16.
References
17.
1. The Committee of Brain Tumor Registry in Japan: Brain Tumor Registry in Japan, Vol 6. 1987, pp 41 2. Dawson DM, Rosenthal DS, Moloney WC: Neurological complications of acute leukemia in adults: changing rate. Ann Intern Med 79: 541-544, 1973 3. Moto A, Nakada J, Oka N, Endo S, Takaku A, Kitagawa M: Acute myeloid leukemia with intracranial tumor formation. No Shinkei Geka 13: 889-893, 1985 4. Nabors MW, Narayan RK, Poplack DG: Intracranial and
18.
otological presentation of acute lymphocytic leukemia. Neurosurgery 17: 309-312, 1985 Sadamori N, Tagawa M, Yamaguchi H, Ichimaru M, Taira Y, Fujii I, Miyagawa N, Miyazaki H, Mori K: A case of acute myelogenous leukemia and brain tumor formation in complete remission. Rinsho Ketsueki 18: 1349-1354, 1977 Shalev O, Slew F, Yaar I, Rachmilewitz EA: Intracerebral tumor and diffuse central nervous system infiltration complicating acute myelogenous leukemia. Cancer 44: 10661069, 1979 Wendling LR, Cromwell LD, Latchaw RE: Computed tomography of intracerebral leukemic masses. A JR 132: 217220, 1979 Wolk RW, Masse SR, Conklin R, Freireich EJ: The incidence of central nervous system leukemia in adults with acute leukemia. Cancer 33: 863-869, 1974 Moore EW, Thomas LB, Shaw RK, Freireich EJ: The central nervous system in acute leukemia. AMA Arch Int Med 105: 451-468, 1960 Phair JP, Anderson RE, Namiki H: The central nervous system in leukemia. Ann Intern Med 61: 863-875, 1964 Reske-Nielsen E, Petersen JH, Sogaard H, Jensen KB: Leukemia of the central nervous system. Lancet 1: 211-212, 1974 Gastaut JA, Gastaut JL, Carcassonne Y: Computerized axial tomography in the study of intracranial complications in hematology. Cancer 41: 487-501, 1978 Pagani JJ, Libshitz HI, Wallace S, Hayman LA: Central nervous system leukemia and lymphoma: Computed tomographic manifestations. AJNR 2: 397-403, 1981 Azzarelli B, Roessmann U: Pathogenesis of central nervous system infiltration in acute leukemia. Arch Pathol Lab Med 101: 203-205, 1977 Price RA, Johnson WW: The central nervous system in childhood leukemia: I. The arachnoid. Cancer 31: 520-533. Williams HM, Diamond HD, Graver LF: The pathogenesis and management of neurological complications in patients with malignant lymphomas and leukemia. Cancer 11: 7682, 1958 Blasberg RG, Patlak C, Fenstermacher JD: Intrathecal chemotherapy: Brain tissue profiles after ventriculo-cisternal perfusion. J Pharmacol Exp Ther 195: 73-83, 1975 Kazner E, Wende S, Grumme T, Stochdorph O, Felix R, Claussen C: CT and MR imaging of brain tumors. In: Computed tomography and magnetic resonance tomography of intracranial tumors, ed 2. Springer-Verlag, Berlin, Heidelberg, New York, London, Paris, Tokyo, Hong Kong 47-458, 1988
Address for offprints: K. Fukui, Department of Neurosurgery, Oogaki City Hospital Oogaki, Gifu Prefecture, 503 Japan
