ARTICO, Marco

CIAPPETTA, Pasqualino

DELFINI, Roberto

L. Cervoni

RACO, Antonino

SALVATI, Maurizio

English

Archivio della ricerca- Università di Roma La Sapienza

PRIMARY SPINAL EPIDURAL NON-HODGKIN'S LYMPHOMAS: A CLINICAL STUDY Maurizio Salvati, M.D., Luigi Cervoni, M.D., * Marco Artico, M.D., Pharm.D., Antonino Raco, M.D., Pasquale Ciappetta, M.D., and Roberto Delfini, M.D. Department of Neurological Sciences, Neurosurgery, and *Chair of Human Anatomy, Faculty of Pharmacy, "La Sapienza" University of Rome, Rome, Italy Salvati M, Cervoni L, Artico M, Raco A, Ciappetta P, Delfini R. Primary spinal epidural non-Hodgkin's lymphomas: a clinical study. Surg Neurol 1996;46:339-44. BACKGROUND The spinal epidural space is an uncommon presenting site in primary non-Hodgkin's lymphoma. The occurrence of spinal epidural disease ranges from 0.1%-6.5% among patients with non-Hodgkin's lymphoma. METHODS We report a retrospective study regarding 19 patients with primary epidural non-Hodgkin's lymphomas analyz-ing the factors influencing prognosis of this tumor, with emphasis on treatment. RESULT Ten patients were females and nine males. The neuro-logic conditions of patients were assessed preoperatively and postoperatively according to Shaw's classification for neurologic disability. All cases underwent surgery accompanied by radiotherapy in 16 cases as well as che-motherapy in 13 cases. Histologically, the tumor proved to be a low-grade non-Hodgkin's lymphoma in three cases, intermediate-grade in four cases and, high-grade in 12 cases. At average follow-up of 7.2 years (range 5-15 years), 15 patients had died after an average interval of 31 months from treatment (range 3-130 months) and four patients are alive after an average interval of 61 months (range 32-86 months). CONCLUSION It appears that the outcome in these patients depends on the gravity of preoperative deficits, whereas the survival is influenced by the type of treatment. KEYWORDS Primary lymphoma, spinal cord compression, extradural spaces. This work was partly presented in the poster section of the Annual Meeting of the American Association of Neurological Surgeons, Boston, April 24-29, 1993. Address reprint requests to: Maurizio Salvati, M.D., University of Rome "La Sapienza", Department of Neurological Sciences, Neurosurgery, viale dell' Universita 30/4 00185, Rome, Italy. Received July 22, 1993; accepted February 2, 1995. © 1996 by Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010 E pidural lymphomas account for 9% of epidural spinal tumors and 0.1 %-3.3% of all lymphomas [7,11]. Non-Hodgkin's lymphomas have a spinal 10-calization in 0.1-6.5% of cases [1,16,18-19]. We report 19 cases of primary epidural non-Hodgkin's lymphomas (PENHLS) and analyze the factors influencing prognosis of this tumor, with emphasis on treatment. PATIENTS AND METHODS Nineteen patients with PENHLS were operated on in the Department of Neurological Sciences of Rome University "La Sapienza" between 1975 and 1987. Histologic classification of the tumor followed the NCI Working Formulation [17]. The neurologic conditions of patients were as-sessed preoperatively and postoperatively accord-ing to Shaw's classification for neurologic disability [21]: grade 1: able to walk normally; grade 2: weak legs but able to walk unaided; grade 3: walking but with aid; grade 4: unable to walk but able to move the legs; and grade 5: paraplegic. Before or after surgery all patients were thor-oughly evaluated to identify any other systemic lesions (e.g., total body CT, bone scintigraphy, bone marrow examination). All patients had their disease staged according to the Ann Arbor classification. Epidural lymphoma was detected by myelogra-phy, myelo-CT, and MRI with gadolinium. Surgical treatment consisted either of laminectomy or a combined transthoracic or transabdominal ap-proach. The prognostic factors considered were the histologic aspect of the tumor, patient age, clin-ical condition, and the type of treatment. 0090-3019/96/$15.00 Pll S0090-30 19(96)00042-0 340 Surg Neurol 1996;46:339 -44 II Characteristics of 19 Patients with Epidural Lymphoma PT PREOP No SEX/AGE SITE GRADE STAGE 1 m/42 Do IE 2 f/51 Do 2 IE 3 m/52 Ce 3 IE 4 f/51 LS 5 IE 5 m/48 LS 3 IE 6 m/46 LS 4 IE 7 f/53 Do IE 8 f/47 Do 2 IE 9 m/48 LS 5 IE 10 f/48 Do 4 IE 11 m/47 Do 4 IE 12 f/56 LS 2 IE 13 m/55 Do 3 IE 14 4/51 Do 4 IE 15 m/52 Do 4 IE 16 f/51 Ce 3 IE 17 m/53 Do 4 IE 18 f/53 Do 4 IE 19 m/55 Do 4 IE TREATMENT DOSE OFRxT SIC R = 40 Gy S SIR = 40 Gy SIC R = 40 Gy S SIC R = 40 Gy SIR = 40 Gy SIC R = 40 Gy S SIC R = 40 Gy SIC R = 40 Gy SIC R = 40Gy SIR = 40 Gy SIC R = 40 Gy SIC R = 40Gy SIC R = 40 Gy SIC R = 40 Gy SIC R = 40Gy SIC R = 40 Gy POSTOP GRADE 5 2 3 5 4 4 3 3 3 2 3 Salvati et al STATUS, SURVIVAL HISTOLOGY CAUSE OF DEATH H A 32 months L 03 months Rei within CNS 051 months Syst/Tr H 032 months Syst 07 months SystjTr H A 86 months 051 months Syst H 013 months Rei within CNS LOS months Syst H 019 months Syst 039 months SystjTr H A 54 months L 038 months Syst H 019 months H 022 months Syst H A 72 months H 012 months Syst H 032 months Syst H 012 months Rei within CNS Abbreviations: A = alive; C = chemotherapy; Ce = cervical; D = died; Do = dorsal; f = female; H = high-grade; L = low-grade; LS = lumbosacral; I = intermediate-grade; m = male; no = number; Preop = preoperative; Postop = postoperative; Pt = patient; R = radiotherapy; Rei = relapse; S = surgery; Syst = systemic progression; Tr = histologic transformation. RESULT Ten patients were females and nine males (M/F ratio: 1.1:1) (fable 1). Average age was 51 years (median 53 years; range 42-63 years). In nine cases the duration of symptoms was shorter than 3 days; in five cases from 3 days-1 month; in four cases from 1-2 months; and in one case more than 2 months. Pain was a common feature in all 19 cases. There was a motor deficit of the lower limbs in 17 cases, sphincter disturbances in 13 cases (urine retention in 10 and urine incontinence in three) and 19 patients had a level of hypoesthesia. The pa-tients' neurologic status on admission was grade I in two cases; grade II in three cases; grade III in four cases; grade IV in eight cases; and grade V in two cases. Neuroradiologic investigation showed an os-teolitic lesion of the vertebral bodies in two cases (10.5%). Myelography, performed in nine cases, documented a total block in seven and a partial block in two cases. Myelo-CT with sagittal and coro-nal reconstruction always showed an isodense le-sion displacing the spinal cord with moderate en-hancement and in two cases displayed erosion of the vertebral body. MRI with gadolinium, per-formed in four cases, showed a hyperintense lesion in T cweighted images with moderate enhancement Spinal Lymphomas II Preoperative MRI showed an extradural cervical hy-perintense lesion and vertebral body destruction. (Figure 1). The site of the tumor was thoracic in 12 cases, lumbosacral in five and cervical in two. Sur-gical removal of the lesion was subtotal in all 19 patients. In eight cases the approach was anterior or anterolateral with surgical stabilization. Sixteen patients underwent local radiotherapy (40 Gy in 4 weeks), 13 patients were also given polychemo-therapy (MACOP-B in seven; BACOP in six). In two of the 13 patients given chemotherapy hemopoietic factors were also administered (GSF-GM) to treat leukopenia (granulocytopenia). Histologically, the tumor proved to be a low-grade non-Hodgkin's lymphoma in three cases, intermediate-grade in four, and high-grade in 12 cases. At average follow-up of 7.2 years (range 5-15 years), 15 patients had died after an average inter-val of 31 months from treatment (range 3-130 months) and four are alive after an average interval of 61 months (range 32-86 months). Death was due to systemic progression of the disease in 13 pa-tients and relapse within the CNS in two patients. In three of the 15 patients who died the lymphoma had undergone transformation from low-grade to high-grade. Neurologic conditions evaluated in the 15 patients who died, before the disease reappeared, and in the four survivors improved in 10 cases and were unchanged in nine. In the latter, the duration of preoperative symptoms was at least 1 month. Favorable prognosis depended on good preopera-tive neurologic status grade II-III. Combined treat-ment with surgery, radiotherapy, and chemother-apy increased survival times but did not Significantly influence prognosis. Average survival was 5 months in the three patients treated by sur-gery alone, 21 months in those treated by surgery and radiotherapy, and 43 months in those treated by chemotherapy. Moreover, surgical treatment im-Surg Neurol 34 1 1996;46:339-44 ~ Postoperative MRI showed subtotal removal of cer-r:=I vical lymphoma. proved the preoperative deficits in 13 cases (68%) while radiotherapy and chemotherapy did not have any effect on postoperative deficits. DISCUSSION The origin of PENHLS is still unknown. Rubinstein [20] believes that it derives from the lymphatic tissue present in the epidural space. However, other authors [13] support the hypothesis that PENHLS originates from the paravertebral lymph nodes or from the vertebral body, later extending to the epidural space. Recent immunocytochemical and electron microscope studies have shown that the tumor most frequently originates from the B lymphocytes [19]. In our series, PENHLS was diag-nosed on the basis of absence of other systemic localizations; brief clinical history (average 20 days); and no, or only secondary, erosion of the vertebral body. PENHLS usually presents in the 4th-5th decade of life and occurs most often in the male sex (66%-76% of cases) [6,10]. In our series, PENHLS affected the fifth decade of life and had an almost equal incidence in both males and females. Both the mass effect of the tumor and the compres-sion it exerts on the medullary vessels contribute to the symptomatology of PENHLS [2,6,9,21]. The most affected site was the thoracic spine [2,4,5]. Some authors [2,4,19] consider this to be a result of both the greater length of the thoracic portion in relation to others and to the particular lymphatic drainage of the vertebral column. The cervical lo-calization of PENHLS observed in two of our cases was an exceptional finding [4,5,22]. The neurologic symptoms present in our patients were typical of spinal epidural neoplasm: back pain in all patients 342 Surg Neurol 1996;46:339-44 ~ Photomicrography reveals a a diffused, mixed, small cleaved and large NHL ex 200). and motor impairment in 89%, ranging from slight spasticity to serious flaccid paraplegia. A sensory level was always present and bladder control im-pairment occurred in 68% of our patients. Treatment of PENHLS is based not only on sur-gery but also on radiotherapy and recently on che-motherapy [3,12] . Previously, some authors [5,6] have suggested that radiotherapy and chemother-apy be used in all cases to eradicate clinically oc-cult disease; other authors [19,22] retain useful subtotal removal of PENHLS because of a dis-proportionate number of relapses and deaths in patients treated with either therapy alone. We think that a simple decompression of the cord is useful for neurologic improvement and histologic diagno-sis, though we must avoid complete removal or multilevel decompression, once the diagnosis of PENHLS has been established. Local radiotherapy and polychemotherapy are considered the treat-ment of choice, because the tumor is particularly sensitive to these modalities. Surgery ameliorated the preoperative motor deficits in 13 of our cases (68%), especially in patients operated within 72 hours from onset of symptoms (100%). Radiother-apy and polychemotherapy helped to consolidate the patients ' clinical improvement. Average sur-vival in patients with PENHLS is about 3 years. Cappellani [2], in his series of 17 patients treated by surgery and radiotherapy, reports an average sur-vival of 31 months and 40% survival rate at 4 years from treatment. Eeles [5], in a study of 20 patients who underwent surgery, radiotherapy and chemo-Salvati et al therapy (the latter not in all cases), gives average survival as 42 months (20% at 5 years). In his series of five patients, Epelbaum [6] noted that average survival in patients treated by surgery and radio-therapy was 26 months while in those who also received chemotherapy it was 33 months. In our series average survival was 36 months (24% at 5 years). In three of our cases, the tumor, firstly a low-grade, became high-grade, a rare occurrence in the literature [5]. Prognosis in our series was sig-nificantly influenced by preoperative neurologic condition. In fact, in the 9 grade I-III patients, aver-age survival was 46 months compared to 25 months in the 10 grade IV-V patients. It is worth noting that in patients with similar neurologic status, average survival differed according to whether they were treated by surgery and radiotherapy alone or whether chemotherapy was used. CONCLUSION This study shows that the outcome in patients with PENHLS is essentially related to preoperative defi-cits, while for the survival, combined treatment (surgery, radiotherapy, and chemotherapy) en-sures the best results. REFERENCES 1. Bucy PC, Jerva MJ. Primary epidural spinal lympho-sarcomas. J Neurosurg 1962; 19: 142-52. Spinal Lymphomas 2. Cappellani G, Giuffre F, Tropea R, Guarnera F, Augello G, Chiaramonte I, Mancuso P. Primary spinal epidural lymphomas. J Neurosurg Sci 1986;30:147-51. 3. Connors JM, Klimo P, Mushoff K, Smithers OW, Tubi-ana M. Brief chemotherapy and involved field radia-tion therapy for limited stage, histologically aggres-sive lymphoma. Ann Intern Med 1987;107:25. 4. DeVita VT, Jaffe ES, Helman S. Hodgkin's disease and the non-Hodgkin's lymphomas. In: DeVita VT, Hell-man S, Rosenberg SA, eds., Cancer. Principles and practice of oncology. Philadelphia, Lippincott, 1985. 5. Eeles RA, O'Brien P, Horowich A, Brada M. Non-Hodgkin's lymphoma presenting with extradural spi-nal cord compression: functional outcome and sur-vival. Br J Cancer 1991;63:126-9. 6. Epelbaum R, Nissim H, Ben-Shahar M, Ben-Arie Y, Feinsod M, Cohen Y. Non-Hodgkin's lymphoma pre-senting with spinal epidural involvement. Cancer 1986;58:2120-4. 7. Freeman C, Beng JW, Cutler SJ. Occurence and prog-nosis of extranodallymphomas. Cancer 1972;29:252-60. 8. Friedman M, Kim TH, Panahon AM. Spinal cord com-pression in malignant lymphoma. Cancer 1980; 45:545-52. 9. Grant JW, Kaech 0, Jones DB. Spinal cord compres-sion as the first presentation of lymphoma: a review of 15 cases. Histopathology 1986;10:1191-202. 10. Haddad P, Thaell JF, Kiely JM, Harrison EG, Miller RH. Lymphomas of the spinal epidural space. Cancer 1976;38:1862-6. 11. Herman TS, Hammond N, Jones SE, Butler JJ, Byrne GE, McKelvey EM. Involvement of the central nervous system by non-Hodgkin's lymphoma. Cancer 1979;43: 390-7. 12. Hochberg FH, Loeffler JS, Prados M. The therapy of primary brain lymphoma. J Neurooncol 1991;10:191-201. 13. Iwanow G, Romodanowsky K. Uber den anatomischen Zusammanhang der zerebralen und spinalen submen-ingealen Raume mit dem Iymphsystem: I. Methodik uns wichtigste Beobachtungen. Z Ges Exp Med 1927; 56:596. 14. Love JC, Miller RH, Kernohan JW. Lymphomas of the spinal epidural space. Arch Surg 1954;69:66-76. 15. MacVicar 0, Williams MP. CT scanning in epidural lymphoma. Clin Radiol 1991;43:95-102. 16. Maiuri F, Gangemi M, Giamundo A, laconetta G, De Chiara AR. Primary spinal epidural lymphomas. Acta Neurol (Napoli) 1988;10:213-9. 17. Non-Hodgkin's lymphoma pathologic classification project. National Cancer Institute sponsored study of classifications of non-Hodgkin's lymphomas. Cancer 1982;49:2112-35. 18. Oviatt DL, Kirshner HS, Stein RS. Successful chemo-therapeutic treatment of epidural compression in non-Hodgkin's lymphoma. Cancer 1982;49:2446-8. 19. Perry JR, Deodhare SS, Bilbao JM, Murray 0, Muller P. The significance of spinal cord compression as the initial manifestation of lymphoma. Neurosurg 1993; 32:157-62. 20. Rubinstein LJ. Tumors of the nervous system. Atlas of tumour pathology. Fascicle 6. Tumours of the Iym-phoreticular system. Washington, AFIP, 1972. Surg Neurol 343 1996;46:339-44 21. Shaw MD, Rose JE, Paterson A. Metastatic extradural malignancy of the spine. Acta Neurochir 1980;52: 113-20. 22. Vasuved Rao T, Narayanaswamy KS, Shankar SK, Deshpande DH. "Primary" spinal epidural lympho-mas. A clinico-pathological study. Acta Neurochir 1982;62:307-17. COMMENTARY Dr. Salvati and his colleagues provide a very nice review of this relatively rare pathology. It is impor-tant to note that, in their series, approximately 50% of the patients (9/16) had symptoms of three days' duration or less. Surgery resulted in an improve-ment in preoperative symptoms in all patients who underwent surgery within 72 hours of clinical pre-sentation, but in only 69% of the patients who were surgically treated after that period. Therefore, it should be recognized that surgery is more effica-cious in providing immediate symptomatic relief in patients in whom some neurological function re-mains, if performed within a fairly limited temporal window. In addition, all three patients who had surgery alone died of systemic disease during the follow-up period, whereas the long-term survivors (4/19) were those who had a combination of surgery, che-motherapy, and radiation therapy, confirming the value of these adjunctive measures for achieving a long-term success in controlling the systemic illness. Ziya Gokaslan, M.D. Raymond Sawaya, M.D. Department of Neurosurgery MD. Anderson Cancer Center Houston, Texas The treatment of epidural spinal cord compression presented in the paper by Salvati et al differs from what is currently practiced in most medical centers in this country. When the nature of the pathology is known and the cancer is radiosensitive as is non-Hodgkin's lymphoma, radiotherapy will be the first rung of treatment. Exceptions will be rapid onset ( <24 hours) of neurological deficit or progression during or after treatment with radiation. This course of treatment is unfortunately not based on prospective randomized studies which are lacking in this important area. Many clinicians believe that the most expeditious way to reverse neurological deficit and achieve best results in 

Primary spinal epidural non-Hodgkin's lymphomas: a clinical study

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Primary spinal epidural non-Hodgkin's lymphomas: a clinical study

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