J Neurosurg 72:663-667,1990
Intradural granulocytic sarcoma presenting as a lumbar radiculopathy Case report FRED S. C. KIM, M . D . , JAMES T. RUTKA, M . D . , PH.D., MARK BERNSTEIN, M.D., F.R.C.S.(C), LOTHAR RESCH, M.D., F.R.C.P.(C), ELLEN WARNER, M.D., F.R.C.P.(C), AND DOMINIC PANTALONY, M.D., F.R.C.P.(C)
Department of Pathology, Toronto Western Hospital Toronto, Ontario, Canada u- Granulocytic sarcoma usually occurs in the setting of leukemia and myeloproliferative disorders. Rarely, it can occur in isolation at various anatomical sites without hematological evidence of leukemia. The unique case of an elderly man presenting with right L2-3 radiculopathy is described. Intradural granulocytic sarcoma of the L-2 and L-3 nerve roots with extradural extension was found at surgery and he was treated with incomplete resection and antileukemic chemotherapy. Local recurrence at 3 months was treated with irradiation. Granulocytic sarcoma is frequently misdiagnosed and invariably progresses to acute leukemia. The chloroacetic acid esterase, granulocytic immunohistochemical markers, and electron microscopy appearance can aid in diagnosis. The prognosis is improved with initial aggressive antileukemic chemotherapy and local irradiation. KEY WORDS
"
granulocytic sarcoma
G
RANULOCYTIC sarcoma has been defined as an invasive and destructive tumor mass of ira, mature leukemic cells. 21 The term "chloroma has been applied to describe the green color seen in these tumors; however, since only some of these tumors display the typical green color, "granulocytic sarcoma" is the preferred term. 25 Granulocytic sarcoma most commonly arises in the setting of existing leukemia or a myeloproliferative disorder, but there have been reports of solid tumors occurring in isolation and preceding the disseminated disease. Granulocytic sarcoma is most frequently found in periosteum, but can involve other soft tissues as well as the central nervous system (CNS). 13,j~ With improvement in the treatment of leukemia, the observed incidence of CNS involvement has been increasing. 5'24'28 Aleukemic granulocytic sarcoma affecting the spinal cord is a rare occurrence and is usually extradural. 4,22 We report a unique case of granulocytic sarcoma involving the L-2 and L-3 dorsal root ganglia and extending distally to affect the retroperitoneum and proximally along the nerve roots into the subarachnoid space without cerebrospinal fluid (CSF) abnormality or sys-
J. Neurosurg. / Volume 7 2 / A p r i l 1990
9 chloroma
9 dorsal nerve root
temic evidence of leukemia. The diagnosis and treatment of granulocytic sarcoma in the absence of systemic leukemia are discussed. C a s e Report
This 70-year-old m a n presented with a progressive 6month history of right-leg pain, numbness, and weakness. The pain radiated down the lateral aspect of the right thigh and was worsened by movement. On admission, the patient could walk only 50 feet before the pain forced him to stop. In addition, he noted an area of decreased sensation over the anterolateral aspect of his right thigh. His left leg felt completely normal, and he had normal bowel and bladder control. His medical history included an aortocoronary bypass procedure for ischemic heart disease, gout, and a cholecystectomy. There was no history of trauma. He was systemically well without fever, chills, weight loss, or malaise.
E x a m i n a t i o n . The general physical examination was unremarkable. Cranial nerve testing was normal. The upper extremities were found to be normal on motor and sensory testing. Examination of the lower 663
F. S. C. Kim, et al.
FIG. 1. Left: Lumbar myelogram showing incomplete intradural obstruction at L2-3 with a nodular filling defect medial to the right pedicle of L-3. Right: Postmyelogram computerized tomography scan at rostral L-3 showing a nodular intradural mass.
FIG. 3. Electron micrograph of neoplastic cells showing Auer rod (black arrow) and lysosomal granule (white arrow). Bar = 1 #.
FIG. 2. Photomicrograph of the neoplasm. Bar = 25 u. A: Section composed of monomorphic cells with granular pink cytoplasm infiltrating the dorsal root ganglion. Asterisk denotes a ganglion cell and curved arrow a typical neoplastic cell. Hematoxylin-phloxine-saffron stain. B: Positive staining of granules in neoplastic cell (curved arrow). Leder stain. C: Immunohistochemical staining for Leu M 1 showing intense staining of cytoplasm of neoplastic cells (curved arrows). 664
J. Neurosurg. / Volume 72/April, 1990
I n t r a d u r a l g r a n u l o c y t i c s a r c o m a o f the l u m b a r n e r v e roots extremities revealed an atrophic fight quadriceps muscle. The right hip flexor and knee extensor muscles were weak (grade 4/5). The fight-knee jerk was depressed. The fight femoral stretch test was positive. There was decreased sensation to pinprick over the L2-3 dermatomes of the right side. A chest x-ray film was normal. A computerized tomography (CT)-myelogram showed an intradural dumbbell-shaped lesion partially eroding the pedicle of L-2 (Fig. 1). This lesion passed under the L-2 pedicle and was contiguous with a large paraspinal mass with overlying atrophied right psoas muscle. Another smaller, entirely intradural lesion was identified at L-3. The differential diagnosis included neurofibromas or schwannomas of the L 2 - 3 nerve roots.
Operation. An L 1 - 3 laminectomy was performed and the dura was opened. Two spherical bluish intradural lesions, each measuring 1 cm in diameter and inextricably related to the L-2 and L-3 dorsal roots, were identified. The m o r e rostral lesion was adherent to the anterolateral aspect of the dura and extended under the L-2 pedicle through the intervertebral foramen to a large paraspinal soft-tissue mass. A quick section biopsy o f the rostral lesion was interpreted as a "small cell t u m o r . " There was no good plane of cleavage between the nerve roots and the lesion, therefore the lesions were excised with sacrifice of the two nerve roots. The paraspinal t u m o r was subtotally excised. Pathological Examination. The formalin-fixed specimen was grayish-tan and brown on cut section. Microscopically, the tissue consisted of dorsal root ganglion cells and nerve fibers infiltrated by a m o n o m o r phic t u m o r (Fig. 2A). The cells were 15 to 20 u in diameter and regular in appearance. Nuclei were round to oval in shape but 5 % were cleaved or were irregularly lobed. The chromatin was finely stippled and evenly dispersed. Most cells contained a single centrally placed pale nucleolus. The majority of the cells had a broad band of cytoplasm and, in some regions, m a n y contained eosinophilic granules. Scattered degenerating cells were present along with two to four mitoses per high-power field. The Giemsa stain showed the presence of both eosinophilic and neutrophilic blast cells. In addition, the granulated cells were periodic acid-Schiffand chloroacetic acid esterase (Leder stain)-positive, verifying their myeloid origin (Fig. 2B). Immunohistochemical staining for Leu M I (CD 15) was positive in about 30% of the neoplastic cells, again confirming the granulocytic nature of the lesion (Fig. 2C). These cells were negative with panels of B-cell and T-cell markers (that is, lambda, kappa, immunoglobulin (Ig)A, IgG, IgM, UCHL-1, and L26), as well as keratin, melanin (HMB-45), myosin, desmin, vimentin, and alpha-1antichymotrypsin. Electron microscopy showed t u m o r cells with the typical granulocytic granules in abundance and infrequent Auer rods (Fig. 3). Postoperative Course. The pain in the patient's right leg improved; however, numbness in the right J. Neurosurg. / Volume 72/April, 1990
thigh persisted. Staging investigations were performed: CT scans of the thorax and a b d o m e n were normal, a bone marrow aspirate showed hypercellular but nonneoplastic marrow, and a lumbar puncture revealed normal CSF glucose and protein without malignant cells. The peripheral blood count and smear were entirely normal. The patient was discharged on the 9th postoperative day but was readmitted after 2 weeks for intravenous and intrathecal chemotherapy. Through an O m m a y a reservoir and a H i c k m a n line, he received arabinosylcystosine (Ara-C) 40 mg/sq m intrathecally twice weekly for 3 weeks, Ara-C 200 mg/sq m intravenously for 7 days, and daunorubicin 60 mg/sq m intravenously on Days 5, 6, and 7. H e became severely pancytopenic 10 days after the start o f chemotherapy and became septic and hypotensive. All cultures, including CSF analysis, were negative for organisms. He was treated with Ancef (cefazolin), piperacillin, and tobramycin. He gradually improved and his blood indices returned to normal within 2 weeks. At 3 months, the patient returned with increasing leg weakness. A C T - m y e l o g r a m showed a recurrent mass at the fight L 3 - 4 foramen. The bone marrow and CSF examinations were again normal. He was then started on local radiation therapy of 35 Gy in 10 fractions. Discussion Burns 3 has been credited with reporting the first case of granulocytic sarcoma in 1823 in a patient presenting with proptosis and a green retro-orbital tumor. In 1853, King lj described a similar case and coined the term "chloroma" because of the green hue of the tumor. D o c k 6 first made the association between chloroma and leukemia in 1893. The terms "chloromyeloma," "chloromyelosarcoma," "granulocytic leukosarcoma," "myeloblastoma," " m y e l o s a r c o m a , " and "myelocytom a " have been used to describe these tumors. 21 It was Rappaport 2~ who popularized the term "granulocytic sarcoma" since some of these tumors did not d e m o n strate the green color. The color is attributed to the verdoperoxidase, a myeloperoxidase which loses its color 1 to 3 hours after exposure to air. Most cases of granulocytic sarcoma have been reported in the setting of existing leukemia or myeloproliferative disorders.5,13A 7,19,21,24
This lesion is m o r e c o m m o n l y reported in children with acute or chronic myelocytic leukemia in blastic transformation. ~3'21'24'29 The incidence of granulocytic sarcoma in acute leukemia has been estimated as 2.9%; 12 however, this rate is somewhat higher in autopsy series (3% to 8%), with the majority of the asymptomatic masses located in the abdominal viscera. '~,~8'21 With recent chemotherapeutic improvements resulting in enhanced remission rate, there has been an increase in the incidence o f granulocytic sarc o m a ? In the setting of leukemia, granulocytic sarcoma occurs most c o m m o n l y in periosteum followed by
665
F. S. C. Kim, et al. lymph nodes, epidural, and perineural spaces. 19 Occasionally, granulocytic sarcoma has been reported to occur in the absence of systemic leukemia, as in our case. Krause, 12 in his analysis of 950 leukemic patients, found the incidence of this disease preceding the diagnosis of leukemia to be 0.6%. No satisfactory explanation has been postulated for development of granulocytic sarcoma before blood and bone marrow abnormalities. Since the majority of cases diagnosed in isolation progress to leukemia, it is possible that the localized mass could represent an early metastasis from primarily a bone marrow lesion or from an extramedullary source with high propensity for systemic spread. The diagnosis o f granulocytic sarcoma in the absence of systemic leukemia poses a diagnostic challenge. The primitive granulocytes may lack visible granules on light microscopy and can easily be confused with lymphoma. 7'16 Other diagnoses that can be confused with granulocytic sarcoma are anaplastic carcinoma, Ewing's sarcoma, eosinophilic granuloma, and reticulum-cell sarcoma? 6 The characteristic cells in granulocytic sarcoma contain numerous eosinophilic granules of variable sizes and round to oval nuclei on hematoxylin and eosin staining. The granulocytic nature can be confirmed with the Leder stain and special immunohistochemical stains directed against granulocytic antigens. 25 Nieman, et al.,19 report 25 % false-negative findings with cellulose acetate electrophoresis, but all of those specimens were Zenker-fixed or acid-decalcified. They could not find any correlation between the histological appearances and positivity with the Leder stain. The electron microscopy appearance is diagnostic: variablesized granules representing lysozymes and Auer rods indicative of their myelogenous origin.15 The clinical presentation of granulocytic sarcoma is variable depending upon its site of occurrence. Given its rarity, aleukemic granulocytic sarcoma involving the spinal cord is relatively more common, 22'23 and is also frequently the presenting feature of acute leukemia. 2~ Most of the spinal lesions present as extradural m a s s e s . 2~ Nerve root infiltration by granulocytic sarcoma is extremely rare. Mirvis, et al., 17 reported a case of nerve root infiltration by leukemic cells identified in a leukemic patient based on radiographic findings. Our case is unique in that aleukemic granulocytic sarcoma involved the dorsal root ganglia as well as the retroperitoneum. It is difficult to postulate the site of origin of this tumor. As we have stressed before, the CSF, peripheral blood, and bone marrow examinations were entirely normal. Other more commonly reported sites of involvement in aleukemic granulocytic sarcoma are skin and lymph nodes. 7-16 In a review of the English literature, we identified 69 cases o f aleukemic granulocytic sarcoma. ~'2,4'7,9a~ 14.16.~9.~2.26 Because o f its rarity, no controlled studies concerning its management have been reported to date. Regardless of the site, almost all patients with aleukemic granulocytic sarcoma reported in the literature do develop leukemia with local treatment alone, evi666
dent in both bone marrow and blood examinations. The larger series report mean intervals to development of systemic disease o f 6 to 10 89months. 1z'19 Furthermore, those who develop leukemia uniformly perform poorly, with death following within 2 yearsJ 2 Aside from an isolated case of an extradural granulocytic sarcoma treated with surgical decompression and local radiotherapy, 4 the only reports of prolonged survival in the literature are of patients who received aggressive adjuvant chemotherapy of the type used for acute myelogenous leukemia (that is, pyrimidine analog and an anthracycline with or without other agents) 8 at the time of the initial diagnosis. 7'19Meis, et al., 16reported that six of 16 patients who presented with granulocytic sarcoma had no evidence o f leukemia at 9 months to 16 years after diagnosis, although one of the four patients who did not receive radiation therapy had local recurrence at 15 months. All had received at least a remission-induction combination of antileukemic chemotherapy. 16Eshghabadi, et aL,7 reviewed the literature up to 1986 and found that, o f 35 well-documented cases of aleukemic granulocytic sarcoma, only four patients had received up-front antileukemic chemotherapy. Three of these patients also received irradiation. Two remain disease-free at 9+ and 64+ months and the other two had multiple aleukemic relapses at 17 and 49 months. However, excluding the two patients who died within a m o n t h o f diagnosis, all 29 patients who were treated initially with local therapy alone or with inappropriate chemotherapy relapsed, generally with acute leukemia. 7 Although granulocytic sarcoma presents as a localized mass, autopsy series report numerous clinically silent lesions. 13 Therefore, chemotherapy is essential in preventing leukemia in aleukemic granulocytic sarcoma. The radiosensitivity of granulocytic sarcoma has been well documented in the literature. 26 The local recurrence in our case and that of Meis, et aL, 16 emphasizes the need for local radiation therapy especially after an incomplete resection. Mirvis, et al., 17 reported a leukemic patient whose radiographic evidence of nerve root infiltration by leukemia persisted with chemotherapy alone and disappeared completely only when local radiation was delivered. The blood-brain barrier may explain the failure o f chemotherapy in the above cases. The use of local radiation treatment is prudent, especially if a large t u m o r is left behind and it involves the CNS. In summary, granulocytic sarcoma usually occurs in the setting of leukemia and myeloproliferative disorders. Rarely, this lesion can occur in isolation with varied clinical presentations, but it invariably progresses to acute leukemia with a poor overall prognosis. Diagnosis with light microscopy can be difficult in these cases, but Leder stain, immunohistochemical markers, and electron microscopy can establish the diagnosis. Improved prognosis is reported with aggressive antileukemic chemotherapy and local radiation treatment, especially when resection is incomplete. J. Neurosurg. / Volume 7 2 / A p r i l , 1990
Intradural g r a n u l o c y t i c s a r c o m a of the l u m b a r n e r v e roots References
1. Beck TM, Day JC, Smith CE, et al: Granulocytic sarcoma treated as an acute leukemia. Report of a case. Cancer 53:1764-1766, 1984 2. Brugo EA, Larkin E, Molina-Escobar J, et al: Primary granulocytic sarcoma of the small bowel. Cancer 35: 1333-1340, 1975 3. Burns A: Observations on the Surgical Anatomy of the Head and Neck. Baltimore: F. Lucas, 1823, p 380 4. Chan JKC, Lau WH, Saw D: Extradural granulocytic sarcoma of the spine. A unique case of long survival after local therapy. Am J Hematol 22:439-441, 1986 5. Dawson DM, Rosenthal DS, Maloney WC: Neurological complications of acute leukemia in adults: changing rate. Ann Intern Med 79:541-544, 1973 6. Dock G: Chloroma and its relation to leukaemia. Am J Med Sci 106:152-185, 1893 7. Eshghabadi M, Shojania AM, Cart I: Isolated granulocytic sarcoma: report of a case and review of the literature. J Clin Oncol 4:912-917, 1986 8. Foon KA, Gale RP: Acute myelogenous leukemia. Current status of therapy in adults. Recent Results Cancer Res 93:216-239, 1984 9. Hicklin GA, Drevyanko TF: Primary granulocytic sarcoma presenting with pleural pulmonary involvement. Chest 94:655-656, 1988 10. Ifrah N, Saint-Andr6 JP, Rousselet MC, et al: Aleukemic granulocytic sarcoma. Br J Clin Pract 41:891-893, 1987 11. King A: A case of chloroma. Monthly J Med Sci 7:97, 1853 12. Krause JR: Granulocytic sarcoma preceding acute leukemia. A report of six cases. Cancer 44:1017-1021, 1979 13. Liu PI, Ishimaru T, McGregor DH, et al: Autopsy study of granulocytic sarcoma (chloroma) in patients with myelogenous leukemia, Hiroshima-Nagasaki, 1949-1969. Cancer 31:948-955, 1973 14. Mason TE, Demaree RS Jr, Margolis CI: Granulocytic sarcoma (chloroma), two years preceding myelogenous leukemia. Cancer 31:423-432, 1973 15. McCarthy KS, Wortman J, Daly J, et al: Chloroma (granulocytic sarcoma) without evidence of leukemia: fascilitated light microscopic diagnosis. Blood 56:104-108, 1980 16. Meis JM, Butler JJ, Osborne BM, et al: Granulocytic
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17. 18. 19. 20.
21.
22. 23. 24. 25.
26. 27. 28. 29.
sarcoma in nonleukemic patients. Cancer 58:2697-2709, 1986 Mirvis S, Stewart M, Rao KCVG: Myelographic demonstration of "nodular radiculopathy" in acute myelogenous leukemia. AJNR 5:641-643, 1984 Muss HB, Moloney WC: Chloroma and other myeloblastic tumors. Blood 42:721-728, 1973 Nieman RS, Barcos M, Berard C, et al: Granulocytic sarcoma: a clinopathologic study of 61 biopsied cases. Cancer 48:1426-1437, 1981 Petursson SR, Boggs DR: Spinal cord involvement in leukemia. A review of the literature and a case of Ph + acute myeloid leukemia present with a conus medullaris syndrome. Cancer 47:346-350, 1981 Rappaport H: Tumors of the hematopoietic system, in Atlas of Tumonr Pathology. Section III, Fascicle 8. Washington, DC: Armed Forces Institute Pathology, 1966, pp 241-243 Ripp DJ, Davis JW, Rengachary SS, et al: Granulocytic sarcoma presenting as an epidural mass with cord compression. Nenrosurgery 24:125-128, 1989 Spiegelmann R, Ram Z, Findler G, et al: Spinal cord involvement as the presenting symptom of acute monocytic leukemia. Surg Nenrol 29:145-148, 1988 Wei G: Leukemia of the nervous system. A clinical analysis of 22 cases. Chin Med J 99:105-110, 1986 Welch P, Grossi C, Carroll A, et al: Granulocytic sarcoma with an indolent course and destructive skeletal disease. Tumor characterization with immunologic markers, electron microscopy, cytochemistry and cytogenic studies. Cancer 57:1005-1010, 1986 Wiernik PH, Serpick AA: Granulocytic sarcoma (chloroma). Blood 35:361-369, 1970 Wilhyde DE, Jane JA, Mullan S: Spinal epidural leukemia. Am J Med 34:281-287, 1963 Wolk RW, Masse SR, Conklin R, et al: The incidence of central nervous system leukemia in adults with acute leukemia. Cancer 35:863-869, 1974 Woo E, Yue CP, M a n n KS, et al: Intradural chloromas. Clin Neurol Nenrosurg 88:135-139, 1986
Manuscript received August 8, 1989. Address reprint requests to: Lothar Resch, M.D., Department of Pathology, Toronto Western Hospital, 399 Bathurst Street, Toronto, Ontario M5T 2S8, Canada.
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Intradural granulocytic sarcoma presenting as a lumbar radiculopathy Case report FRED S. C. KIM, M . D . , JAMES T. RUTKA, M . D . , PH.D., MARK BERNSTEIN, M.D., F.R.C.S.(C), LOTHAR RESCH, M.D., F.R.C.P.(C), ELLEN WARNER, M.D., F.R.C.P.(C), AND DOMINIC PANTALONY, M.D., F.R.C.P.(C)
Department of Pathology, Toronto Western Hospital Toronto, Ontario, Canada u- Granulocytic sarcoma usually occurs in the setting of leukemia and myeloproliferative disorders. Rarely, it can occur in isolation at various anatomical sites without hematological evidence of leukemia. The unique case of an elderly man presenting with right L2-3 radiculopathy is described. Intradural granulocytic sarcoma of the L-2 and L-3 nerve roots with extradural extension was found at surgery and he was treated with incomplete resection and antileukemic chemotherapy. Local recurrence at 3 months was treated with irradiation. Granulocytic sarcoma is frequently misdiagnosed and invariably progresses to acute leukemia. The chloroacetic acid esterase, granulocytic immunohistochemical markers, and electron microscopy appearance can aid in diagnosis. The prognosis is improved with initial aggressive antileukemic chemotherapy and local irradiation. KEY WORDS
"
granulocytic sarcoma
G
RANULOCYTIC sarcoma has been defined as an invasive and destructive tumor mass of ira, mature leukemic cells. 21 The term "chloroma has been applied to describe the green color seen in these tumors; however, since only some of these tumors display the typical green color, "granulocytic sarcoma" is the preferred term. 25 Granulocytic sarcoma most commonly arises in the setting of existing leukemia or a myeloproliferative disorder, but there have been reports of solid tumors occurring in isolation and preceding the disseminated disease. Granulocytic sarcoma is most frequently found in periosteum, but can involve other soft tissues as well as the central nervous system (CNS). 13,j~ With improvement in the treatment of leukemia, the observed incidence of CNS involvement has been increasing. 5'24'28 Aleukemic granulocytic sarcoma affecting the spinal cord is a rare occurrence and is usually extradural. 4,22 We report a unique case of granulocytic sarcoma involving the L-2 and L-3 dorsal root ganglia and extending distally to affect the retroperitoneum and proximally along the nerve roots into the subarachnoid space without cerebrospinal fluid (CSF) abnormality or sys-
J. Neurosurg. / Volume 7 2 / A p r i l 1990
9 chloroma
9 dorsal nerve root
temic evidence of leukemia. The diagnosis and treatment of granulocytic sarcoma in the absence of systemic leukemia are discussed. C a s e Report
This 70-year-old m a n presented with a progressive 6month history of right-leg pain, numbness, and weakness. The pain radiated down the lateral aspect of the right thigh and was worsened by movement. On admission, the patient could walk only 50 feet before the pain forced him to stop. In addition, he noted an area of decreased sensation over the anterolateral aspect of his right thigh. His left leg felt completely normal, and he had normal bowel and bladder control. His medical history included an aortocoronary bypass procedure for ischemic heart disease, gout, and a cholecystectomy. There was no history of trauma. He was systemically well without fever, chills, weight loss, or malaise.
E x a m i n a t i o n . The general physical examination was unremarkable. Cranial nerve testing was normal. The upper extremities were found to be normal on motor and sensory testing. Examination of the lower 663
F. S. C. Kim, et al.
FIG. 1. Left: Lumbar myelogram showing incomplete intradural obstruction at L2-3 with a nodular filling defect medial to the right pedicle of L-3. Right: Postmyelogram computerized tomography scan at rostral L-3 showing a nodular intradural mass.
FIG. 3. Electron micrograph of neoplastic cells showing Auer rod (black arrow) and lysosomal granule (white arrow). Bar = 1 #.
FIG. 2. Photomicrograph of the neoplasm. Bar = 25 u. A: Section composed of monomorphic cells with granular pink cytoplasm infiltrating the dorsal root ganglion. Asterisk denotes a ganglion cell and curved arrow a typical neoplastic cell. Hematoxylin-phloxine-saffron stain. B: Positive staining of granules in neoplastic cell (curved arrow). Leder stain. C: Immunohistochemical staining for Leu M 1 showing intense staining of cytoplasm of neoplastic cells (curved arrows). 664
J. Neurosurg. / Volume 72/April, 1990
I n t r a d u r a l g r a n u l o c y t i c s a r c o m a o f the l u m b a r n e r v e roots extremities revealed an atrophic fight quadriceps muscle. The right hip flexor and knee extensor muscles were weak (grade 4/5). The fight-knee jerk was depressed. The fight femoral stretch test was positive. There was decreased sensation to pinprick over the L2-3 dermatomes of the right side. A chest x-ray film was normal. A computerized tomography (CT)-myelogram showed an intradural dumbbell-shaped lesion partially eroding the pedicle of L-2 (Fig. 1). This lesion passed under the L-2 pedicle and was contiguous with a large paraspinal mass with overlying atrophied right psoas muscle. Another smaller, entirely intradural lesion was identified at L-3. The differential diagnosis included neurofibromas or schwannomas of the L 2 - 3 nerve roots.
Operation. An L 1 - 3 laminectomy was performed and the dura was opened. Two spherical bluish intradural lesions, each measuring 1 cm in diameter and inextricably related to the L-2 and L-3 dorsal roots, were identified. The m o r e rostral lesion was adherent to the anterolateral aspect of the dura and extended under the L-2 pedicle through the intervertebral foramen to a large paraspinal soft-tissue mass. A quick section biopsy o f the rostral lesion was interpreted as a "small cell t u m o r . " There was no good plane of cleavage between the nerve roots and the lesion, therefore the lesions were excised with sacrifice of the two nerve roots. The paraspinal t u m o r was subtotally excised. Pathological Examination. The formalin-fixed specimen was grayish-tan and brown on cut section. Microscopically, the tissue consisted of dorsal root ganglion cells and nerve fibers infiltrated by a m o n o m o r phic t u m o r (Fig. 2A). The cells were 15 to 20 u in diameter and regular in appearance. Nuclei were round to oval in shape but 5 % were cleaved or were irregularly lobed. The chromatin was finely stippled and evenly dispersed. Most cells contained a single centrally placed pale nucleolus. The majority of the cells had a broad band of cytoplasm and, in some regions, m a n y contained eosinophilic granules. Scattered degenerating cells were present along with two to four mitoses per high-power field. The Giemsa stain showed the presence of both eosinophilic and neutrophilic blast cells. In addition, the granulated cells were periodic acid-Schiffand chloroacetic acid esterase (Leder stain)-positive, verifying their myeloid origin (Fig. 2B). Immunohistochemical staining for Leu M I (CD 15) was positive in about 30% of the neoplastic cells, again confirming the granulocytic nature of the lesion (Fig. 2C). These cells were negative with panels of B-cell and T-cell markers (that is, lambda, kappa, immunoglobulin (Ig)A, IgG, IgM, UCHL-1, and L26), as well as keratin, melanin (HMB-45), myosin, desmin, vimentin, and alpha-1antichymotrypsin. Electron microscopy showed t u m o r cells with the typical granulocytic granules in abundance and infrequent Auer rods (Fig. 3). Postoperative Course. The pain in the patient's right leg improved; however, numbness in the right J. Neurosurg. / Volume 72/April, 1990
thigh persisted. Staging investigations were performed: CT scans of the thorax and a b d o m e n were normal, a bone marrow aspirate showed hypercellular but nonneoplastic marrow, and a lumbar puncture revealed normal CSF glucose and protein without malignant cells. The peripheral blood count and smear were entirely normal. The patient was discharged on the 9th postoperative day but was readmitted after 2 weeks for intravenous and intrathecal chemotherapy. Through an O m m a y a reservoir and a H i c k m a n line, he received arabinosylcystosine (Ara-C) 40 mg/sq m intrathecally twice weekly for 3 weeks, Ara-C 200 mg/sq m intravenously for 7 days, and daunorubicin 60 mg/sq m intravenously on Days 5, 6, and 7. H e became severely pancytopenic 10 days after the start o f chemotherapy and became septic and hypotensive. All cultures, including CSF analysis, were negative for organisms. He was treated with Ancef (cefazolin), piperacillin, and tobramycin. He gradually improved and his blood indices returned to normal within 2 weeks. At 3 months, the patient returned with increasing leg weakness. A C T - m y e l o g r a m showed a recurrent mass at the fight L 3 - 4 foramen. The bone marrow and CSF examinations were again normal. He was then started on local radiation therapy of 35 Gy in 10 fractions. Discussion Burns 3 has been credited with reporting the first case of granulocytic sarcoma in 1823 in a patient presenting with proptosis and a green retro-orbital tumor. In 1853, King lj described a similar case and coined the term "chloroma" because of the green hue of the tumor. D o c k 6 first made the association between chloroma and leukemia in 1893. The terms "chloromyeloma," "chloromyelosarcoma," "granulocytic leukosarcoma," "myeloblastoma," " m y e l o s a r c o m a , " and "myelocytom a " have been used to describe these tumors. 21 It was Rappaport 2~ who popularized the term "granulocytic sarcoma" since some of these tumors did not d e m o n strate the green color. The color is attributed to the verdoperoxidase, a myeloperoxidase which loses its color 1 to 3 hours after exposure to air. Most cases of granulocytic sarcoma have been reported in the setting of existing leukemia or myeloproliferative disorders.5,13A 7,19,21,24
This lesion is m o r e c o m m o n l y reported in children with acute or chronic myelocytic leukemia in blastic transformation. ~3'21'24'29 The incidence of granulocytic sarcoma in acute leukemia has been estimated as 2.9%; 12 however, this rate is somewhat higher in autopsy series (3% to 8%), with the majority of the asymptomatic masses located in the abdominal viscera. '~,~8'21 With recent chemotherapeutic improvements resulting in enhanced remission rate, there has been an increase in the incidence o f granulocytic sarc o m a ? In the setting of leukemia, granulocytic sarcoma occurs most c o m m o n l y in periosteum followed by
665
F. S. C. Kim, et al. lymph nodes, epidural, and perineural spaces. 19 Occasionally, granulocytic sarcoma has been reported to occur in the absence of systemic leukemia, as in our case. Krause, 12 in his analysis of 950 leukemic patients, found the incidence of this disease preceding the diagnosis of leukemia to be 0.6%. No satisfactory explanation has been postulated for development of granulocytic sarcoma before blood and bone marrow abnormalities. Since the majority of cases diagnosed in isolation progress to leukemia, it is possible that the localized mass could represent an early metastasis from primarily a bone marrow lesion or from an extramedullary source with high propensity for systemic spread. The diagnosis o f granulocytic sarcoma in the absence of systemic leukemia poses a diagnostic challenge. The primitive granulocytes may lack visible granules on light microscopy and can easily be confused with lymphoma. 7'16 Other diagnoses that can be confused with granulocytic sarcoma are anaplastic carcinoma, Ewing's sarcoma, eosinophilic granuloma, and reticulum-cell sarcoma? 6 The characteristic cells in granulocytic sarcoma contain numerous eosinophilic granules of variable sizes and round to oval nuclei on hematoxylin and eosin staining. The granulocytic nature can be confirmed with the Leder stain and special immunohistochemical stains directed against granulocytic antigens. 25 Nieman, et al.,19 report 25 % false-negative findings with cellulose acetate electrophoresis, but all of those specimens were Zenker-fixed or acid-decalcified. They could not find any correlation between the histological appearances and positivity with the Leder stain. The electron microscopy appearance is diagnostic: variablesized granules representing lysozymes and Auer rods indicative of their myelogenous origin.15 The clinical presentation of granulocytic sarcoma is variable depending upon its site of occurrence. Given its rarity, aleukemic granulocytic sarcoma involving the spinal cord is relatively more common, 22'23 and is also frequently the presenting feature of acute leukemia. 2~ Most of the spinal lesions present as extradural m a s s e s . 2~ Nerve root infiltration by granulocytic sarcoma is extremely rare. Mirvis, et al., 17 reported a case of nerve root infiltration by leukemic cells identified in a leukemic patient based on radiographic findings. Our case is unique in that aleukemic granulocytic sarcoma involved the dorsal root ganglia as well as the retroperitoneum. It is difficult to postulate the site of origin of this tumor. As we have stressed before, the CSF, peripheral blood, and bone marrow examinations were entirely normal. Other more commonly reported sites of involvement in aleukemic granulocytic sarcoma are skin and lymph nodes. 7-16 In a review of the English literature, we identified 69 cases o f aleukemic granulocytic sarcoma. ~'2,4'7,9a~ 14.16.~9.~2.26 Because o f its rarity, no controlled studies concerning its management have been reported to date. Regardless of the site, almost all patients with aleukemic granulocytic sarcoma reported in the literature do develop leukemia with local treatment alone, evi666
dent in both bone marrow and blood examinations. The larger series report mean intervals to development of systemic disease o f 6 to 10 89months. 1z'19 Furthermore, those who develop leukemia uniformly perform poorly, with death following within 2 yearsJ 2 Aside from an isolated case of an extradural granulocytic sarcoma treated with surgical decompression and local radiotherapy, 4 the only reports of prolonged survival in the literature are of patients who received aggressive adjuvant chemotherapy of the type used for acute myelogenous leukemia (that is, pyrimidine analog and an anthracycline with or without other agents) 8 at the time of the initial diagnosis. 7'19Meis, et al., 16reported that six of 16 patients who presented with granulocytic sarcoma had no evidence o f leukemia at 9 months to 16 years after diagnosis, although one of the four patients who did not receive radiation therapy had local recurrence at 15 months. All had received at least a remission-induction combination of antileukemic chemotherapy. 16Eshghabadi, et aL,7 reviewed the literature up to 1986 and found that, o f 35 well-documented cases of aleukemic granulocytic sarcoma, only four patients had received up-front antileukemic chemotherapy. Three of these patients also received irradiation. Two remain disease-free at 9+ and 64+ months and the other two had multiple aleukemic relapses at 17 and 49 months. However, excluding the two patients who died within a m o n t h o f diagnosis, all 29 patients who were treated initially with local therapy alone or with inappropriate chemotherapy relapsed, generally with acute leukemia. 7 Although granulocytic sarcoma presents as a localized mass, autopsy series report numerous clinically silent lesions. 13 Therefore, chemotherapy is essential in preventing leukemia in aleukemic granulocytic sarcoma. The radiosensitivity of granulocytic sarcoma has been well documented in the literature. 26 The local recurrence in our case and that of Meis, et aL, 16 emphasizes the need for local radiation therapy especially after an incomplete resection. Mirvis, et al., 17 reported a leukemic patient whose radiographic evidence of nerve root infiltration by leukemia persisted with chemotherapy alone and disappeared completely only when local radiation was delivered. The blood-brain barrier may explain the failure o f chemotherapy in the above cases. The use of local radiation treatment is prudent, especially if a large t u m o r is left behind and it involves the CNS. In summary, granulocytic sarcoma usually occurs in the setting of leukemia and myeloproliferative disorders. Rarely, this lesion can occur in isolation with varied clinical presentations, but it invariably progresses to acute leukemia with a poor overall prognosis. Diagnosis with light microscopy can be difficult in these cases, but Leder stain, immunohistochemical markers, and electron microscopy can establish the diagnosis. Improved prognosis is reported with aggressive antileukemic chemotherapy and local radiation treatment, especially when resection is incomplete. J. Neurosurg. / Volume 7 2 / A p r i l , 1990
Intradural g r a n u l o c y t i c s a r c o m a of the l u m b a r n e r v e roots References
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Manuscript received August 8, 1989. Address reprint requests to: Lothar Resch, M.D., Department of Pathology, Toronto Western Hospital, 399 Bathurst Street, Toronto, Ontario M5T 2S8, Canada.
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