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Primary Intramedullary Histiocytic Sarcoma Gentian Toshkezi1, Faramarz Edalat1, Carl O’Hara2, Ivana Delalle2, Lawrence S. Chin1
Intramedullary primary central nervous system lymphoma (PCNSL) is a rare central nervous system (CNS) malignancy affecting mostly the brain, but it may also involve the leptomeninges, eyes, and spinal cord. A 71-year-old woman presented with back pain and progressive unilateral lower extremity weakness owing to an intramedullary primary histiocytic sarcoma of the spine, a rare PCNSL subtype. To the authors’ knowledge, this is the first case of an intramedullary PCNSL caused by histiocytic sarcoma.
INTRODUCTION First reported in 1929 by Bailey (3), primary central nervous system lymphoma (PCNSL) is a rare variant of non-Hodgkin lymphoma (NHL) that affects the brain, spinal cord, leptomeninges, and eyes (6). PCNSL represents 0.5%–1.2% of intracranial masses (28), 1%–3% of malignant central nervous system (CNS) diseases (25), 2%–3% of NHL cases, and less than 1% of extranodal NHL cases (28). There has been considerable interest in this disease because of an increase in incidence over the last 3 decades, with a tripling of age-adjusted incidence from 1973–1984 comKey words 䡲 Chemotherapy 䡲 Intramedullary 䡲 Non-Hodgkin lymphoma 䡲 Primary central nervous system lymphoma 䡲 Radiation therapy 䡲 True histiocytic lymphoma Abbreviations and Acronyms CNS: Central nervous system CSF: Cerebrospinal fluid MRI: Magnetic resonance imaging NHL: Non-Hodgkin lymphoma PCNSL: Primary central nervous system lymphoma From the Departments of 1Neurosurgery and 2 Pathology, Boston University School of Medicine and Boston Medical Center, Boston, Massachusetts, USA To whom correspondence should be addressed: Lawrence S. Chin, M.D. [E-mail:
[email protected]] Citation: World Neurosurg. (2010) 74, 4/5:523-527. DOI: 10.1016/j.wneu.2010.07.002 Journal homepage: www.WORLDNEUROSURGERY.org Available online: www.sciencedirect.com 1878-8750/$ - see front matter © 2010 Elsevier Inc. All rights reserved.
pared with 1985–1997, according to the Surveillance, Epidemiology and End Results (SEER) registries (25). With the incidence of acquired immunodeficiency syndrome (AIDS) peaking in the early 1990s and its subsequent decline owing to use of highly active antiretroviral therapy, AIDS can no longer account for the increasing incidence of PCNSL, although it may have contributed to the initial increase (12). Of concern is the increasing incidence of PCNSL in immunocompetent patients (28), although some studies have shown stabilizing or decreasing incidence in this population. PCNSL has a predilection for the brain, followed by the leptomeninges, ocular globe, and spinal cord; less than 1% occur in the spinal cord (12). PCNSL of the spinal cord are most commonly due to dissemination directly from the caudal brainstem or via cerebrospinal fluid (CSF) (12). More infrequent are intramedullary PCNSL with only 19 reported cases (5, 7, 8, 10, 14, 16-18, 20-24, 26, 27, 29-31, 33). More than 90% of PCNSL consist of diffuse large B-cell lymphomas (28), with T-cell, low-grade, anaplastic, and Hodgkin lymphomas less frequently seen (6). Primary histiocytic sarcoma, previously described in the literature as “true histiocytic lymphoma” and “malignant histiocytosis,” is a rare disease of hematopoietic origin representing less than 1% of all NHL (34). To this date, only six cases of primary CNS histiocytic sarcomas have been reported (9, 11, 32). Our case is the seventh case of primary CNS histiocytic sarcoma and the first case of primary intramedullary histiocytic sarcoma of the spinal cord.
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Figure 1. Gadolinium-enhanced T1-weighted axial (A) and sagittal (B) MRI. A 2.5 ⫻ 1 ⫻ 1.1 cm intramedullary enhancing lesion with a central area of necrosis is present at the level of T11-12.
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Figure 2. Intraoperative view through operating microscope of the intraspinal tumor. Tumor is being debulked through the ventrolateral side of the spinal cord.
CASE REPORT A 71-year-old, right-handed woman with a past medical history of chronic obstructive pulmonary disease presented initially with a
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1-month history of low back pain and progressive right lower extremity weakness. At that time, her examination was notable for 4/5 muscle strength in her right lower extremity, a normal sensory examination, no bowel and bladder symptoms, and no reflex asymmetry. The remainder of her neurologic examination was normal. Magnetic resonance imaging (MRI) revealed an enhancing intramedullary lesion at the T11-12 level. Surgery was scheduled, but before her date of surgery, the patient presented to the emergency department with a 3-day history of worsening right lower extremity weakness resulting in frequent falls. Her motor examination showed 1/5 muscle strength in the right lower extremity, 3/5 strength in the left lower extremity, and decreased sensation to pain and light touch at approximately the T12 sensory level. Dexamethasone (Decadron) was started in the
emergency department, and MRI revealed enlargement of the enhancing intramedullary lesion measuring 2.5 ⫻ 1 ⫻ 1.1 cm associated with central necrosis and associated edema. There was also leptomeningeal enhancement from the T9 level to the cauda equina (Figure 1). Brain MRI did not reveal an intracranial mass, and selective spinal angiography did not identify an angiographic blush. The patient was taken urgently to the operating room, where a T10-12 laminectomy was performed. An intramedullary mass was seen growing out of the spinal cord and extending to the dura but not attached to it (Figure 2). The mass infiltrated several nerve roots and could not be dissected from the surrounding spinal cord. A subtotal resection of the tumor was performed using the ultrasonic aspirator. Permanent sections (Figure 3) revealed a tumor that was
Figure 3. (A-C) Histologic image of histiocytic cells with abundant cytoplasm, vesicular nuclei, and prominent nucleoli (hematoxylin-eosin, magnification ⫻20 [A] and ⫻40 [B]) Immunohistochemistry for CD68 is strongly positive (⫻40 [C]).
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Table 1. Review of Previous Reported Cases of Intramedullary Primary Central Nervous System Lymphoma Reference
Age, Sex
Location
Extramedullary Involvement —
Treatment
Survival
Reznik 1975 (27)
33, M
Cervical and thoracic cord
Mitsumoto 1980 (24)
60, F
L1-5
Bluemke 1990 (7)
61, M
C-4
Current case
71, F
T11-12
Slager 1982 (30)
45, F
C1-5
Bruni 1977 (8)
53, M
C1-T1
Pels 2003 (26)
75, M
T7-11
Bekar 2001 (5)
41, M
C2-4
Third and fourth ventricle
Fisher 1979 (14)
51, F
T1-2
Pons, midbrain, supraclavicular 3 yr before
Local XRT, chemotherapy
12 months
Landan 1987 (21)
37, F
Multiple levels
Cortex, brainstem, cerebellum, vertebral bodies, paravertebral lymph nodes
Supportive care
12 months
Herrlinger 2002 (18)
36, F
Cervical cord
Abdominal lymph nodes
Local XRT, chemotherapy
15 months
Itami 1986 (20)
24, F
C2-T6
—
Craniospinal XRT
⬎18 months
Slowik 1990 (31)
49, F
C3-6
—
Local XRT, chemotherapy
⬎24 months
Craniospinal XRT
30 months
Local XRT
⬎36 months
Parieto-occipital lobe
Surgery
Death 1 month postoperatively
Craniospinal XRT
4 months
—
Local XRT
5 months
—
Subtotal resection, XRT
5 months
Supportive care
7 months
—
Supportive care
8 months
—
Local XRT, chemotherapy
⬎8 months
Subtotal resection, local XRT, chemotherapy
⬎11 months
Midline cerebellum
McDonald 1995 (23)
46, M
C2-6
Schild 1995 (29)
59, F
T11
Periventricular, maxillary sinus
Herbst 1976 (17)
51, M
T12-L1
Cerebellum, brainstem
Local XRT; chemotherapy after recurrence
⬎48 months
Caruso 1998 (10)
77, M
C4-5, T5-6
Pterygoid mass
Chemotherapy after recurrence
⬎60 months
Machiya 2007 (22)
60, F
Cervical cord
Not mentioned
Not mentioned
—
—
XRT, radiation therapy.
composed of large cells with vesicular nuclei, prominent nucleoli, and vacuolated cytoplasm, growing in a diffuse growth pattern and associated focally with necrosis. Mitotic figures were identifiable in addition to prominent apoptosis. Immunoperoxidase studies showed variable positive staining of the tumor cells for leukocyte common antigen and strong positive staining for CD68 and lysozyme. Stains for cytokeratins (AE1/3), cytokeratin-7, cytokeratin-20, TTF-1, CD1a, HAM56, S100, CD3, and CD20 were negative. Immunoglobulin heavy chain or T-cell receptor gene rearrangements were not present. Additional staining showed that staining for CD163 and CD45RO was positive, supporting the diagnosis of histiocytic sarcoma, also known in literature as “true histiocytic lymphoma.” The staging work-up of bone marrow and lymphoma panel was unremarkable. Positron emission tomography/computed tomography revealed increased radiotracer uptake at T10-11 and T11-12 levels indicating
residual tumor but no evidence of local invasion or metastasis. Postoperatively, the patient’s neurologic deficit improved to 2/5 muscle strength in the right lower extremity. The patient was discharged 6 days after her operation to a rehabilitation facility while she underwent radiation therapy to a total dose of 4400 cGy at 200-cGy daily fractions. Over the next few months, the patient developed progressive lower extremity paraplegia and complete sensory loss below the T12 dermatome. She became incontinent for urine, and she ultimately declined chemotherapy. She died 5 months after diagnosis from complications of respiratory failure and presumed tumor progression.
DISCUSSION PCNSL of the spinal cord are most commonly due to dissemination directly from the caudal brainstem or via CSF (12). Our
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case is the 20th case of intramedullary PCNSL reported (Table 1). The clinical manifestations of intramedullary PCNSL, as with other intramedullary tumors, depends on location. In the 20 reported cases, the cervical and thoracic vertebral levels were commonly involved, each in 60% of the cases, followed by lumbar involvement in 25%. The presentation is usually subacute. Spine MRI shows the location, size, and appearance of intramedullary PCNSL (15, 18). Histopathologic examination is the “gold standard” for diagnosis of PCNSL. When the diagnosis is made, a comprehensive baseline evaluation and staging work-up should be performed, in accordance with the recommendation from the International Primary CNS Lymphoma Collaborative Group (1). The recommended clinical evaluation consists of a physical and neurologic examination, peripheral lymph node examination, and performance status baseline through the Eastern Cooperative On-
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cology Group (ECOG) performance scale. Laboratory evaluation includes serum lactate dehydrogenase and hepatic and renal function tests for patients who are to undergo high-dose methotrexate treatment. Further evaluation includes MRI with gadolinium of the brain and total spine; CSF analysis; ophthalmologic examination including a slit-lamp examination; and systemic staging that consists of computed tomography of chest, abdomen, and pelvis; bone marrow biopsy, and human immunodeficiency virus (HIV) testing (1). An elevated CSF protein level has been determined to be an important prognostic factor according to the Prognostic Scoring System for Primary CNS Lymphoma by the International Extranodal Lymphoma Study Group and the Memorial Sloan-Kettering Cancer Center Prognostic Model (2, 13). In older men, a testicular ultrasound scan should be considered to exclude the possibility of a primary testicular lymphoma (31). Surgical resection was attempted in our case because the working diagnosis was astrocytoma or ependymoma and acute neurologic deterioration. In a setting where lymphoma is suspected, surgery should be confined to biopsy alone. The degree of surgical resection confers no additional benefit, particularly in cases of intracerebral involvement (4, 12). The prognosis of PCNSL remains poor with a median survival of 3 months in untreated patients (19). PCNSL is a radiosensitive tumor, and the use of high-dose methotrexate combined with whole-brain radiation increases median survival to 36 – 60 months (19). In addition to radiation, PCNSL is sensitive to chemotherapy. High-dose methotrexate has shown the most activity, particularly in combination with radiation. In the other intramedullary PCNSL cases, the median survival was 10 months from the time of diagnosis. Histiocytic sarcoma of the CNS carries a poorer prognosis. Because of the rarity of intramedullary PCNSL, there is no standard treatment regimen. Reported treatments include supportive care, surgical resection, radiation therapy, and combination of radiation therapy and chemotherapy. Patients receiving supportive care alone had a median survival of 9 months (range of 7–12 months). Of the seven patients undergoing radiation therapy only, the overall median survival was 14.5 months,
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and three patients survived more than 24 months. Dividing this group into local spinal radiation versus craniospinal radiation did not reveal obvious differences. Of the three patients receiving local radiation therapy, survival was 5 months, more than 36 months, and more than 48 months. In the four patients receiving craniospinal radiation, survival was 4 months, more than 18 months, 24 months, and 30 months. Five patients received combination therapy, and the median survival was 13.5 months with one patient surviving more than 24 months (5, 7, 8, 10, 14, 16-18, 20-24, 26, 27, 29-31, 33).
6. Bhagavathi S, Wilson JD: Primary central nervous system lymphoma. Arch Pathol Lab Med 132: 1830-4, 2008. 7. Bluemke DA, Wang H: Primary spinal cord lymphoma: MR appearance. J Comput Assist Tomogr 14:812-4, 1990. 8. Bruni J, Bilbao JM, Gray T: Primary intramedullary malignant lymphoma of the spinal cord. Neurology 27:896-8, 1977. 9. Cao M, Eshoa C, Schultz C, Black J, Zu Y, Chang CC: Primary central nervous system histiocytic sarcoma with relapse to mediastinum: a case report and review of the literature. Arch Pathol Lab Med 131:301-5, 2007. 10. Caruso PA, Patel MR, Joseph J, Rachlin J: Primary intramedullary lymphoma of the spinal cord mimicking cervical spondylotic myelopathy. AJR Am J Roentgenol 171:526-7, 1998.
CONCLUSIONS Primary intramedullary lymphoma is uncommon, we report here the first case of intramedullary histiocytic sarcoma. The unexpected biopsy result underscores the need for histology in all cases of intramedullary tumors. Primary intramedullary histiocytic sarcoma is an aggressive tumor, and the outcome is poor. Radiation therapy alone or combined with chemotherapy prolongs survival compared with surgery alone.
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received 13 November 2009; accepted 30 June 2010 Citation: World Neurosurg. (2010) 74, 4/5:523-527. DOI: 10.1016/j.wneu.2010.07.002 Journal homepage: www.WORLDNEUROSURGERY.org Available online: www.sciencedirect.com 1878-8750/$ - see front matter © 2010 Elsevier Inc. All rights reserved.
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