Clinical Neurology and Neurosurgery 120 (2014) 99–102
Contents lists available at ScienceDirect
Clinical Neurology and Neurosurgery journal homepage: www.elsevier.com/locate/clineuro
Case report
Multifocal myeloid sarcoma in the central nervous system without leukemia Chenlong Yang a , Yuanbo Liu b , Guang Li c , Jiwei Bai a , Jun Qian b , Yulun Xu a,∗ a b c
Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, No. 6, Tiantan Xili, Chongwen District, Beijing 100050, China Department of Hematology, Beijing Tiantan Hospital, Capital Medical University, No. 6, Tiantan Xili, Chongwen District, Beijing 100050, China Department of Pathology, Beijing Tiantan Hospital, Capital Medical University, No. 6, Tiantan Xili, Chongwen District, Beijing 100050, China
a r t i c l e
i n f o
Article history: Received 16 October 2013 Received in revised form 18 February 2014 Accepted 23 February 2014 Available online 3 March 2014 Keywords: Myeloid sarcoma Chloroma Leukemia Chemotherapy CNS
1. Introduction Myeloid sarcoma is a localized tumor composed of primitive myeloid cells at an extramedullary site, which has often been described in association with leukemia or myeloid proliferative disorders. It is previously known as granulocytic sarcoma, chloroma, or extra-medullary myeloid tumor, and the 2008 World Health Organization classification adopted the term “myeloid sarcomas” as a subgroup of “acute myeloid leukemias, not otherwise categorized” [1]. Myeloid sarcoma most commonly occurs in the soft tissues of the head and neck, bone, and skin, while rarely in the central nervous system (CNS), especially spinal cord [2]. Herein, we describe a patient with multifocal myeloid sarcoma in the CNS. In particular, no leukemic manifestations were detected in bone marrow and peripheral blood examinations. 2. Case report In April 2012, a previously healthy 27-year-old man presented to us with a 6-month history of intermittent headache and a 3-month history of bilateral visual field defects. He was a radiology technician who had operated X-ray equipment for the previous 5 years. Physical examination revealed a homonymous
∗ Corresponding author. E-mail addresses: [email protected] (C. Yang), [email protected] (Y. Xu). http://dx.doi.org/10.1016/j.clineuro.2014.02.020 0303-8467/© 2014 Elsevier B.V. All rights reserved.
right lower quadrant visual field defect. Brain MRI showed a parasagittal mass involving the occipital lobes bilaterally. The lesion was isointense on T1-weighted images with homogeneous contrast enhancement, and mildly hyperintense on T2-weighted images (Fig. 1). Baseline laboratory data were normal: leukocyte count 8910/L with a normal differential, hemoglobin 132 g/L, and platelet count 204,000/L. A presumptive diagnosis of parasagittal meningioma was made, and subsequently a corresponding en-bloc tumorectomy was designed, not including a frozensection examination. Microscopically, gross total resection was performed of the intradural grayish mass with a well-defined cleavage plane. Immunohistological examination showed myeloid sarcoma (Fig. 2A) with positive staining for myeloperoxidase (MPO, Fig. 2B), CD34, CD45, CD68, CD99, and lysozyme. Postoperatively, his headaches resolved but the visual field defects remained. The postoperative MRI confirmed gross total resection. Subsequently, further cytogenetic examinations, bone marrow aspirates and adjuvant chemotherapy was recommended, nevertheless in vain due to the patient refusal. Five months after discharge, without any related intervention in the interim, the patient was readmitted with a 2-month history of pain and numbness in his right thigh, sphincter dysfunction, and occasional pain in the right flank. Neurological examination revealed a loss of sensation below the L2 dermatome on the right, and grade 4/5 right lower extremity weakness. Spinal MRI showed a giant mass in the spinal canal at L2–L3 that extended through the right L2–L3 intervertebral foramen, and a smaller mass at
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Fig. 1. The cranial MR images show a parasagittal mass involving bilateral occipital lobes (arrowheads). The lesion is isointense on axial T1-weighted images (A), and mildly hyperintense on axial T2-weighted images (B). After Gd-DTPA administration, the axial (C) and sagittal (D) images show homogeneous contrast enhancement. The corresponding MR images in the last follow-up (E–H) show tumor-free patterns.
S2–S3 (Fig. 3). The masses were suspected as myeloid sarcoma because of multiple occurrence or CSF dissemination. Cerebrospinal fluid smear examination was performed, identifying several typical immature cells with distinctive Auer rods (Fig. 2C). Resection of
the intra-spinal portion of the larger mass for local decompression and biopsy combined with six-cycle chemotherapy was scheduled. Intraoperatively, the larger mass was found epidural, and diffusely infiltrating into the right psoas muscle. Pathological examination
Fig. 2. H&E stain of the center of the resected brain tissue reveals myeloid sarcoma (A, ×200). Immunohistochemical stain shows positivity for myeloperoxidase (B, ×400). High-power views of cerebrospinal fluid smears show sporadic immature cells with Auer rods (C, ×1000). H&E stain of spinal tumor also reveals myeloid sarcoma (D, ×400).
C. Yang et al. / Clinical Neurology and Neurosurgery 120 (2014) 99–102
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Fig. 3. The spinal MR images. (A) sagittal T1-weighted, (B) sagittal T2-weighted, (C) coronal T1-weighted with contrast, and (D) axial T1-weighted images with contrast show a giant mass in the spinal canal at L2–L3 that extended through the right L2–L3 intervertebral foramen (asterisks), and a smaller mass at S2–S3 (arrowhead). The corresponding MR images in the last follow-up confirm the elimination of the masses (E–H).
of the resected specimen revealed myeloid sarcoma (Fig. 2D). The extra-spinal portion and the sacral mass were not surgically intervened. The repeated complete blood counts, peripheral blood smears and bone marrow aspirates with flow cytometry analysis showed no abnormalities. The patient was referred to the hematology department for further chemotherapy. Repeat bone marrow aspirates were normal. Cytogenetic analysis revealed the AML1/ETO fusion gene. The patient initially underwent two courses of an AMLtype induction chemotherapy regimen using idarubicin 10 mg/day for 3 days and medium-dose cytarabine (1.5 g/day) for 3 days. Because of severe myelosuppression, the subsequent courses were changed to daunorubicin 60 mg/day for 3 days, cytosine arabinoside 150 mg/day for 7 days, and etoposide 100 mg/day for 4 days. Intrathecal cytarabine 50 mg or methotrexate 10 mg was administered twice a week during the treatment period. At discharge after 3 cycles of chemotherapy, no immature cells were detected in the cerebrospinal fluid, and his symptoms had improved, spinal MRI showing significant regression of the tumor. A total of 6 cycles of chemotherapy was performed, and then MRI showed total elimination of the masses (Fig. 3). At the last follow-up, 13 months postoperatively, no new onset neurological dysfunction or leukemia manifestation was noted. 3. Discussion Myeloid sarcoma is a rare neoplasm of primitive myeloid cell origin, most commonly found in association with an acute or chronic leukemia or myeloproliferative disorder, while it may
rarely occur de novo with no apparent sign or symptom of concomitant hematological disease [3]. Central nervous system involvement is extremely rare, with a reported incidence of 3.25% in patients with myeloid sarcoma [4]. The causes and natural history of this rare entity are unclear, and it is not known whether this patient’s radiation exposure increased his risk of tumorigenesis or even the future risk of progression to leukemia. The neurological symptoms and MRI manifestations of myeloid sarcoma in CNS may be nonspecific, and the differential diagnosis should include meningioma, lymphoma, and neurofibromatosis. Preoperative diagnosis is challenging, and elaborative cerebrospinal fluid cytological examinations, chromosome analysis and molecular methods may be helpful. The accurate diagnosis of myeloid sarcoma depends on pathological criteria and immunohistochemical staining, especially monoclonal antibodies against MPO [5]. Treatment of this condition may include surgical decompression, together with comprehensive assessment and treatment for underlying systemic disorder [6]. The optimal surgical scheme of myeloid sarcoma may differ from that with respect to other intrinsic tumor in CNS, in which case intraoperative frozen biopsy or stereotactic biopsy is of great value. From the surgical point of view, aggressive total resection may not be necessary, as myeloid sarcomas respond well to chemotherapy with which complete elimination of the residual lesion could be achieved. In this case, the visual functional sequelae may be associated with the surgical approach for the occipital mass. Auer rods in the cerebrospinal fluid smear and identification of
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the AML1/ETO fusion gene provided important diagnostic clues, suggesting potential or delayed AML, and induction chemotherapy was administered in the hope of achieving complete remission. Low-dose chemotherapy may be ineffective because of the blood-brain barrier, and medium- or high-dose chemotherapy may lead to myelosuppression and an increased risk of infection. Eventually, bone marrow or stem cell transplantation can be considered. According to the published literatures, very few cases of myeloid sarcoma in CNS without leukemia were reported [1,7]. The age at onset and tumor location varied considerably, without obvious sex predominance. While most of them are inclined to adhere to the dura mater resembling meningioma or hematoma, and the mass could be found intradural or epidural. To releasing the neurological symptoms, local surgical decompression could be attempted as to the brain or spinal myeloid sarcoma [8]. Additionally, myeloid sarcomas could respond well to chemotherapy, but there is still no consensus on the standard chemotherapy regimen, lacking prospective data. Complete elimination of the residual lesion could be achieved with early diagnosis and timely chemotherapy. Without sufficient clinical evidence, the role of postoperative adjuvant radiotherapy is difficult to ascertain, and needs further research. Though most of the published cases did not progress to leukemia in the follow-up period, the survival of patients were quite different. Due to limited treatment experience and followup data, we hold that, close follow-up with MRI semi-annually is necessary. This rare case, with its associated diagnostic and therapeutic challenges, emphasises the importance of combined neurosurgical and hematological assessment and management of myeloid sarcoma. Additionally, the diagnostic value of cerebrospinal fluid cytology, chromosome analysis and molecular methods should be placed a premium.
4. Conclusion CNS myeloid sarcoma, preceding peripheral blood or bone marrow involvement, is extremely rare. It often occurs as dural tumor, and the diagnostic and therapeutic challenges illustrate the importance of comprehensive evaluation, immediate diagnosis and adequate systematic treatment of myeloid sarcoma. The radiological appearance of myeloid sarcoma is non-specific, and a confident diagnosis depends on the pathology. Local surgical decompression combined with chemotherapy may be the mainstay treatment, while the operative schemes and resection range should be deliberately designed avoiding unnecessary neurological sequelae. Complete remission and a favorable outcome can be achieved, while further follow-up is still necessary. References [1] Gunaldi M, Kara IO, Duman BB, Ercolak V. Primary intracerebral myeloid sarcoma. Onkologie 2012;35:694–7. [2] Sandhu GS, Ghufoor K, Gonzalez-Garcia J, Elexpuru-Camiruaga JA. Granulocytic sarcoma presenting as cauda equina syndrome. Clin Neurol Neurosurg 1998;100:205–8. [3] Eshghabadi M, Shojania AM, Carr I. Isolated granulocytic sarcoma: report of a case and review of the literature. J Clin Oncol 1986;4:912–7. [4] Pileri SA, Ascani S, Cox MC, Campidelli C, Bacci F, Piccioli M, et al. Myeloid sarcoma: clinico-pathologic, phenotypic and cytogenetic analysis of 92 adult patients. Leukemia 2007;21:340–50. [5] Alexiev BA, Wang W, Ning Y, Chumsri S, Gojo I, Rodgers WH, et al. Myeloid sarcomas: a histologic, immunohistochemical, and cytogenetic study. Diagn Pathol 2007;2:42. [6] Yamauchi K, Yasuda M. Comparison in treatments of nonleukemic granulocytic sarcoma: report of two cases and a review of 72 cases in the literature. Cancer 2002;94:1739–46. [7] Widhalm G, Dietrich W, Mullauer L, Streubel B, Rabitsch W, Kotter MR, et al. Myeloid sarcoma with multiple lesions of the central nervous system in a patient without leukemia. Case report. J Neurosurg 2006;105:916–9. [8] Struhal W, Oberndorfer S, Lahrmann H, Lindeck-Pozza E, Hess B, Nussgruber V, et al. Myeloid sarcoma in the central nervous system: case report and review of the literature. Acta Clin Croat 2008;47:19–24.
Contents lists available at ScienceDirect
Clinical Neurology and Neurosurgery journal homepage: www.elsevier.com/locate/clineuro
Case report
Multifocal myeloid sarcoma in the central nervous system without leukemia Chenlong Yang a , Yuanbo Liu b , Guang Li c , Jiwei Bai a , Jun Qian b , Yulun Xu a,∗ a b c
Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, No. 6, Tiantan Xili, Chongwen District, Beijing 100050, China Department of Hematology, Beijing Tiantan Hospital, Capital Medical University, No. 6, Tiantan Xili, Chongwen District, Beijing 100050, China Department of Pathology, Beijing Tiantan Hospital, Capital Medical University, No. 6, Tiantan Xili, Chongwen District, Beijing 100050, China
a r t i c l e
i n f o
Article history: Received 16 October 2013 Received in revised form 18 February 2014 Accepted 23 February 2014 Available online 3 March 2014 Keywords: Myeloid sarcoma Chloroma Leukemia Chemotherapy CNS
1. Introduction Myeloid sarcoma is a localized tumor composed of primitive myeloid cells at an extramedullary site, which has often been described in association with leukemia or myeloid proliferative disorders. It is previously known as granulocytic sarcoma, chloroma, or extra-medullary myeloid tumor, and the 2008 World Health Organization classification adopted the term “myeloid sarcomas” as a subgroup of “acute myeloid leukemias, not otherwise categorized” [1]. Myeloid sarcoma most commonly occurs in the soft tissues of the head and neck, bone, and skin, while rarely in the central nervous system (CNS), especially spinal cord [2]. Herein, we describe a patient with multifocal myeloid sarcoma in the CNS. In particular, no leukemic manifestations were detected in bone marrow and peripheral blood examinations. 2. Case report In April 2012, a previously healthy 27-year-old man presented to us with a 6-month history of intermittent headache and a 3-month history of bilateral visual field defects. He was a radiology technician who had operated X-ray equipment for the previous 5 years. Physical examination revealed a homonymous
∗ Corresponding author. E-mail addresses: [email protected] (C. Yang), [email protected] (Y. Xu). http://dx.doi.org/10.1016/j.clineuro.2014.02.020 0303-8467/© 2014 Elsevier B.V. All rights reserved.
right lower quadrant visual field defect. Brain MRI showed a parasagittal mass involving the occipital lobes bilaterally. The lesion was isointense on T1-weighted images with homogeneous contrast enhancement, and mildly hyperintense on T2-weighted images (Fig. 1). Baseline laboratory data were normal: leukocyte count 8910/L with a normal differential, hemoglobin 132 g/L, and platelet count 204,000/L. A presumptive diagnosis of parasagittal meningioma was made, and subsequently a corresponding en-bloc tumorectomy was designed, not including a frozensection examination. Microscopically, gross total resection was performed of the intradural grayish mass with a well-defined cleavage plane. Immunohistological examination showed myeloid sarcoma (Fig. 2A) with positive staining for myeloperoxidase (MPO, Fig. 2B), CD34, CD45, CD68, CD99, and lysozyme. Postoperatively, his headaches resolved but the visual field defects remained. The postoperative MRI confirmed gross total resection. Subsequently, further cytogenetic examinations, bone marrow aspirates and adjuvant chemotherapy was recommended, nevertheless in vain due to the patient refusal. Five months after discharge, without any related intervention in the interim, the patient was readmitted with a 2-month history of pain and numbness in his right thigh, sphincter dysfunction, and occasional pain in the right flank. Neurological examination revealed a loss of sensation below the L2 dermatome on the right, and grade 4/5 right lower extremity weakness. Spinal MRI showed a giant mass in the spinal canal at L2–L3 that extended through the right L2–L3 intervertebral foramen, and a smaller mass at
100
C. Yang et al. / Clinical Neurology and Neurosurgery 120 (2014) 99–102
Fig. 1. The cranial MR images show a parasagittal mass involving bilateral occipital lobes (arrowheads). The lesion is isointense on axial T1-weighted images (A), and mildly hyperintense on axial T2-weighted images (B). After Gd-DTPA administration, the axial (C) and sagittal (D) images show homogeneous contrast enhancement. The corresponding MR images in the last follow-up (E–H) show tumor-free patterns.
S2–S3 (Fig. 3). The masses were suspected as myeloid sarcoma because of multiple occurrence or CSF dissemination. Cerebrospinal fluid smear examination was performed, identifying several typical immature cells with distinctive Auer rods (Fig. 2C). Resection of
the intra-spinal portion of the larger mass for local decompression and biopsy combined with six-cycle chemotherapy was scheduled. Intraoperatively, the larger mass was found epidural, and diffusely infiltrating into the right psoas muscle. Pathological examination
Fig. 2. H&E stain of the center of the resected brain tissue reveals myeloid sarcoma (A, ×200). Immunohistochemical stain shows positivity for myeloperoxidase (B, ×400). High-power views of cerebrospinal fluid smears show sporadic immature cells with Auer rods (C, ×1000). H&E stain of spinal tumor also reveals myeloid sarcoma (D, ×400).
C. Yang et al. / Clinical Neurology and Neurosurgery 120 (2014) 99–102
101
Fig. 3. The spinal MR images. (A) sagittal T1-weighted, (B) sagittal T2-weighted, (C) coronal T1-weighted with contrast, and (D) axial T1-weighted images with contrast show a giant mass in the spinal canal at L2–L3 that extended through the right L2–L3 intervertebral foramen (asterisks), and a smaller mass at S2–S3 (arrowhead). The corresponding MR images in the last follow-up confirm the elimination of the masses (E–H).
of the resected specimen revealed myeloid sarcoma (Fig. 2D). The extra-spinal portion and the sacral mass were not surgically intervened. The repeated complete blood counts, peripheral blood smears and bone marrow aspirates with flow cytometry analysis showed no abnormalities. The patient was referred to the hematology department for further chemotherapy. Repeat bone marrow aspirates were normal. Cytogenetic analysis revealed the AML1/ETO fusion gene. The patient initially underwent two courses of an AMLtype induction chemotherapy regimen using idarubicin 10 mg/day for 3 days and medium-dose cytarabine (1.5 g/day) for 3 days. Because of severe myelosuppression, the subsequent courses were changed to daunorubicin 60 mg/day for 3 days, cytosine arabinoside 150 mg/day for 7 days, and etoposide 100 mg/day for 4 days. Intrathecal cytarabine 50 mg or methotrexate 10 mg was administered twice a week during the treatment period. At discharge after 3 cycles of chemotherapy, no immature cells were detected in the cerebrospinal fluid, and his symptoms had improved, spinal MRI showing significant regression of the tumor. A total of 6 cycles of chemotherapy was performed, and then MRI showed total elimination of the masses (Fig. 3). At the last follow-up, 13 months postoperatively, no new onset neurological dysfunction or leukemia manifestation was noted. 3. Discussion Myeloid sarcoma is a rare neoplasm of primitive myeloid cell origin, most commonly found in association with an acute or chronic leukemia or myeloproliferative disorder, while it may
rarely occur de novo with no apparent sign or symptom of concomitant hematological disease [3]. Central nervous system involvement is extremely rare, with a reported incidence of 3.25% in patients with myeloid sarcoma [4]. The causes and natural history of this rare entity are unclear, and it is not known whether this patient’s radiation exposure increased his risk of tumorigenesis or even the future risk of progression to leukemia. The neurological symptoms and MRI manifestations of myeloid sarcoma in CNS may be nonspecific, and the differential diagnosis should include meningioma, lymphoma, and neurofibromatosis. Preoperative diagnosis is challenging, and elaborative cerebrospinal fluid cytological examinations, chromosome analysis and molecular methods may be helpful. The accurate diagnosis of myeloid sarcoma depends on pathological criteria and immunohistochemical staining, especially monoclonal antibodies against MPO [5]. Treatment of this condition may include surgical decompression, together with comprehensive assessment and treatment for underlying systemic disorder [6]. The optimal surgical scheme of myeloid sarcoma may differ from that with respect to other intrinsic tumor in CNS, in which case intraoperative frozen biopsy or stereotactic biopsy is of great value. From the surgical point of view, aggressive total resection may not be necessary, as myeloid sarcomas respond well to chemotherapy with which complete elimination of the residual lesion could be achieved. In this case, the visual functional sequelae may be associated with the surgical approach for the occipital mass. Auer rods in the cerebrospinal fluid smear and identification of
102
C. Yang et al. / Clinical Neurology and Neurosurgery 120 (2014) 99–102
the AML1/ETO fusion gene provided important diagnostic clues, suggesting potential or delayed AML, and induction chemotherapy was administered in the hope of achieving complete remission. Low-dose chemotherapy may be ineffective because of the blood-brain barrier, and medium- or high-dose chemotherapy may lead to myelosuppression and an increased risk of infection. Eventually, bone marrow or stem cell transplantation can be considered. According to the published literatures, very few cases of myeloid sarcoma in CNS without leukemia were reported [1,7]. The age at onset and tumor location varied considerably, without obvious sex predominance. While most of them are inclined to adhere to the dura mater resembling meningioma or hematoma, and the mass could be found intradural or epidural. To releasing the neurological symptoms, local surgical decompression could be attempted as to the brain or spinal myeloid sarcoma [8]. Additionally, myeloid sarcomas could respond well to chemotherapy, but there is still no consensus on the standard chemotherapy regimen, lacking prospective data. Complete elimination of the residual lesion could be achieved with early diagnosis and timely chemotherapy. Without sufficient clinical evidence, the role of postoperative adjuvant radiotherapy is difficult to ascertain, and needs further research. Though most of the published cases did not progress to leukemia in the follow-up period, the survival of patients were quite different. Due to limited treatment experience and followup data, we hold that, close follow-up with MRI semi-annually is necessary. This rare case, with its associated diagnostic and therapeutic challenges, emphasises the importance of combined neurosurgical and hematological assessment and management of myeloid sarcoma. Additionally, the diagnostic value of cerebrospinal fluid cytology, chromosome analysis and molecular methods should be placed a premium.
4. Conclusion CNS myeloid sarcoma, preceding peripheral blood or bone marrow involvement, is extremely rare. It often occurs as dural tumor, and the diagnostic and therapeutic challenges illustrate the importance of comprehensive evaluation, immediate diagnosis and adequate systematic treatment of myeloid sarcoma. The radiological appearance of myeloid sarcoma is non-specific, and a confident diagnosis depends on the pathology. Local surgical decompression combined with chemotherapy may be the mainstay treatment, while the operative schemes and resection range should be deliberately designed avoiding unnecessary neurological sequelae. Complete remission and a favorable outcome can be achieved, while further follow-up is still necessary. References [1] Gunaldi M, Kara IO, Duman BB, Ercolak V. Primary intracerebral myeloid sarcoma. Onkologie 2012;35:694–7. [2] Sandhu GS, Ghufoor K, Gonzalez-Garcia J, Elexpuru-Camiruaga JA. Granulocytic sarcoma presenting as cauda equina syndrome. Clin Neurol Neurosurg 1998;100:205–8. [3] Eshghabadi M, Shojania AM, Carr I. Isolated granulocytic sarcoma: report of a case and review of the literature. J Clin Oncol 1986;4:912–7. [4] Pileri SA, Ascani S, Cox MC, Campidelli C, Bacci F, Piccioli M, et al. Myeloid sarcoma: clinico-pathologic, phenotypic and cytogenetic analysis of 92 adult patients. Leukemia 2007;21:340–50. [5] Alexiev BA, Wang W, Ning Y, Chumsri S, Gojo I, Rodgers WH, et al. Myeloid sarcomas: a histologic, immunohistochemical, and cytogenetic study. Diagn Pathol 2007;2:42. [6] Yamauchi K, Yasuda M. Comparison in treatments of nonleukemic granulocytic sarcoma: report of two cases and a review of 72 cases in the literature. Cancer 2002;94:1739–46. [7] Widhalm G, Dietrich W, Mullauer L, Streubel B, Rabitsch W, Kotter MR, et al. Myeloid sarcoma with multiple lesions of the central nervous system in a patient without leukemia. Case report. J Neurosurg 2006;105:916–9. [8] Struhal W, Oberndorfer S, Lahrmann H, Lindeck-Pozza E, Hess B, Nussgruber V, et al. Myeloid sarcoma in the central nervous system: case report and review of the literature. Acta Clin Croat 2008;47:19–24.
