Child's Nerv Syst (1991) 7:223-225
i
NS
9 Springer-Verlag 1991
Spinal extradural hematopoiesis in adolescents with thalassemia Report of two cases and a review of the literature A. Amirjamshidi 1, K. Abbassioun 2, and S.E. Ketabchi 1 1 Department of Neurosurgery, Sina Hospital, Tehran University, Imam Avenue, Tehran, Iran 2 Department of Neurosurgery, Arad Hospital, Somaye Avenue, Tehran, Iran Received November 25, 1990
Abstract. Extramedullary hematopoietic tissue occurring within the extramedullary space and causing cord compression is an unusual occurrence in childhood and adolescence, and only four cases have been reported during the first two decades of life. We had the opportunity to treat a 16-year-old girl and a 14-year-old boy with paraparesis secondary to extradural extramedullary hematopoiesis. Findings in these cases are discussed, and an attempt is made to stress once more the possibility of congenital hematopoietic rests as the origin of such hyperplastic tissue. The various modes o f therapy are discussed and related literature is reviewed.
Key words: Adolescence - Extramedullary hematopoiesis - Radiotherapy - Spinal cord compression - Beta thalassemia
gists and neurosurgeons to this curable condition in chronically anemic patients with paraparesis.
Case reports Case 1
A 16-year-old girl was admitted to the hospital suffering from a progressive weakness in both legs of about 2 weeks' duration. The patient was known to have Cootey's anemia with Hb F= 82%. She was paraparetic with increased reflexes in both legs, unsustained bilateral clonus, and upturned toes. In plain X-rays sagittal cleft vertebra was evident at the T9 level (Fig. 1). A myelogram performed on the same day of admission showed a complete block at the level of T9- I 0. Because of the worsening of paraparesis following myelography, an emergency laminectomy was performed. TS-10 laminae were removed, and lobulated reddish gray and moderately bleeding tissue located in the epidural space from T9 down to T10 was easily removed from the dura. There was no extension of this tissue into the surrounding bones. The postoperative course was
Expansion of the red m a r r o w is the primary compensatory mechanism for anemia in patients with leukemia, polycythemic myelofibrosis [4] or any kind of chronic anemia producing hemoglobinopathies [1, 3]. The second compensatory mechanism is extramedullary hematopoiesis (EMH), which occurs notably in the spleen, liver, and lymph nodes [1, 13, 23], but also rarely in the paravertebral region of the thorax, prostate, adrenals, pleura, breast, epidydimis, thymus, kidney, sweat glands, broad ligament, retroperitoneal space [9, 11, 14, 15, 17, 23], choroid plexus [6, 14], cranial dural folds [6], within the peripheral nerves [I], and even within brain tumors [14]. Spinal extradural space is another occasional site of proliferation of this hematopoietic tissue, which can produce signs and symptoms of cord compression. However, as this compensatory proliferative mechanism might need time to produce neurological deficits, this clinical presentation is not limited to the pediatric and adolescent age periods. Two cases are described to draw the attention of pediatricians and pediatric neuroloOffprint requests to: A. Amirjamshidi
Fig. 1. Sagittal cleft vertebra of T9 in AP view
224
Fig. 2. Hyperplastic hematopoietic tissue with numerous darker staining red-cell precursors, normoblasts, and megakaryocytes. This erythroblastic hyperplasia is diagnostic for extramedullary hematopoiesis in thalassemia patients. (H&E, x 132)
Table 1. Reported cases of extradural extramedullary hematopoiesis which occurred in the first two decades of life Reference Marinozzi 1958 [22]
Age (years)/sex 4/F
Histology
Level
Thalassemia
T5-8
Bree et al. 1974 [5]
17/M
?
T8-10
Abbassioun et al. 1982 [1]
19/M 19/M
Thalassemia Thalassemia
T8-11 T6-7
Amirjamshidi et al., this report
16/F 14/M
Thalassemia Thalassemia
T9-10 T5-11
uneventful and complete recovery of function occurred within a few days. The tumor was hematopoietic granulomatous tissue with remarkable erythroid proliferation (Fig. 2). Two blood transfusions were performed in the hospital; at present, the patient is under the care of a pediatric hematologist.
Case 2 A 14-year-old boy was admitted complaining of weakness of the legs of about 4 weeks' duration. He was spastic, paraparetic, and a vague sensory level was detectable at the T 8 - 9 level. Lumbar myelography showed the rostral end of the blockage at the T5-6 level. He was anemic with an Hb level of 8.8 g%, and normal white count and differentiation. HbF was 35% and HbA=4.1%, compatible with beta thalassemia intermedia. With the impression of extradural EMH (ED-EMH) as the cause of paraparesis, laminectomy was performed from T5 down to the T l l level. The laminae were moderately friable and vascular. A purplish lobulated tumor was observed surrounding the dura without any extension towards the vertebral bone and pedicles. It was bleeding profusely and teased off the dura with great difficulty. Subtotal excision of the lesion was made. The histological examination in this case was als0 compatible with hematopoietic tissue (Fig. 3 a, b). The postoperative course was uneventful and paraparesis improved rapidly. Several transfusions were performed in the hospital and he was given fractionated localized 1500 tad radiation a month after healing of the wound.
Fig. 3. a The well-demarcated, capsulated margin of epidural t mor is clearly visible in this slide. Numerous sheets of macron0 moblasts surround the fat-laden sinusoids. (H &E, x 79). b TI features of erythroblastic hyperplasia are demarcated with predor inance of nucleated red blood cells, occasional hemosiderin d posits, and disappearance of fat cells. (H&E, x 416)
Discussion E x t r a m e d u l l a r y h e m a t o p o i e s i s is u n c o m m o n in the cm tral n e r v o u s system. O n l y f o u r k n o w n cases h a v e bee r e p o r t e d to o c c u r d u r i n g the first t w o d e c a d e s o f liJ (Table 1) a n d we n o w a d d two new cases. T h a l a s s e m i a is an i n h e r i t a b l e d i s o r d e r o f autosom~ recessive type. It involves defective synthesis o f b e t a glot ulin a n d c o m p e n s a t o r y synthesis o f g a m m a c h a i n g l o b l lin, l e a d i n g to synthesis o f h e m o g l o b i n F. I n the h( m o z y g o u s p a t i e n t the c o n c e n t r a t i o n o f H b F u s u a l l y e" ceeds 15%. T h e c o m p e n s a t o r y m e c h a n i s m includes ma: r o w e x p a n s i o n a n d E D - E M H . E D - E M H l e a d s to spin~ c o r d c o m p r e s s i o n a n d s e c o n d a r y n e u r o l o g i c a l deficits. A s in o u r two cases, t h e r e is a n o t a b l e p r e d i l e c t i o n f( such e x t r a m e d u l l a r y h e m a t o p o i e t i c tissue to o c c u r in tl~ t h o r a c i c r e g i o n [1, 3, 4, 7, 10, 16, 1 9 - 2 1 , 23, 24, 26 Several h y p o t h e s e s h a v e b e e n p r o p o s e d to e x p l a i n th: s t r a n g e l o c a l i z a t i o n . M a s s e s o f h e m a t o p o i e t i c tissue als o c c u r in the t h o r a x , especially in the p a r a s p i n a l , p l e u r a a n d r e t r o p l e u r a l a r e a s [11, 15]. This significant develo]~
225 ment of the extramedullary hematopoietic tissue has been attributed to extension from bone marrow cavities of the vertebrae [1, 23] or thinned trabeculated proximal end of the ribs and costovertebral junctions [1, 18, 23]. Alternatively, these activated blood-forming masses possibly originate from embryonic rests, including retropleural corpuscles [11,20, 23] or lymph nodes [9]. The association of a congenital vertebral anomaly at the level of E M H tissue may reinforce this second hypothesis (case 1). The lobulated shape of these hematopoietic tissues in the extradural space may also suggest that they have originated from the primitive rests lying in a segmental pattern at the thoracic level. Different modes of therapy have been suggested for E D - E M H , including decompressive laminectomy, followed by transfusion and local irradiation [1, 8, 10, 17, 20] and overtransfusion with or without localized radiation [2]. The latter may be more appropriate in children to prevent unpredictable complications o f wide laminectomies.
References 1. Abbassioun K, Amirjamshidi A (1982) Curable paraplegia due to extradural hematopoiesis in thalassemia. Neurosurgery 11:804-807 2. Abbassioun K, Amirjamshidi A, Zamanianpour M (1985) Curable paraplegia (Letter). Neurosurgery 17:528 3. Ammouni AA, Sher JH, Schmelka D (1975) Spinal cord compression by extramedullary hematopoietic tissue in sickle cell anemia. J Neurosurg 43:483-485 4. Appleby A, Batson GA, Lassman LP, Simpson CA (1964) Spinal cord compression by extramedullary hematopoiesis in myelosclerosis. J Neurol Neurosurg Psychiatry 27:313- 316 5. Bree RL, Neiman HL, Hodak JA (1974) Extramedullary hematopoiesis in the spinal epidural space. J Can Assoc Radiol 25:297-299 6. Brown AJ, Gomez-leon G (1984) Subdural hemorrhage secondary to extramedullary hematopoiesis in polycythemic myeloid metaplasia. Neurosurgery 14:588-591 7. Bucy PC, Ladpli R (1963) Recoverable paraplegia. JAMA 185:685 691 8. Cauthen LC, McLaurin LP, Foster MT, Roberta L (1968) Spinal cord compression secondary to extramedullary hematopoiesis in two brothers. Report of two cases. J Neurosurg 29:529 531
9. Close AS, Taira Y, Cleveland DA (1958) Spinal cord compression due to extramedullary hematopoiesis. Am J Med 48:421427 10. Cross JN, Morgan OS, Gibbs WN, Cheruvanky I (1977) Spinal cord compression in thalassemia. J Neurol Neurosurg Psychiatry 40:1120-1122 11. Da Costa JL, Loh YS, Hanam E (1974) Extramedullary hematopoiesis with multiple tumor simulating masses in hemoglobin E-thalassemia disease. Chest 65:210-212 12. Davis DV, Coupland RE (1969) Gray's anatomy, descriptive and applied, 34th edn. Longmans Green, London, pp 186-188 13. Fessas P, Loukopoulos D (1974) The beta-thalassemias. In: Weatheral DJ (ed) Clinics in hematology, vol 3. Saunders, London, pp 411-435 14. Gregorios JG, Bay JW, Dudley AW Jr (1983) Extramedullary hematopoiesis in malignant meningioma. Neurosurgery 13:447-451 15. Hanford RB, Schneider GF, MacCarthy JD (1960) Massive thoracic extramedullary hemopoiesis. N Engl J Med 263:120123 16. Heffez DS, Sawaya R, Udverhely GB, Mann R (1982) Spinal epidural extramedutlary hematopoiesis with cord compression in a patient with refractory sideroblastic anemia. J Neurosurg 57:399-406 17. Heffner RR, Koehl RH (1970) Hemopoiesis in the spinal epidural space. Case report. J Neurosurg 32:485-490 18. Logothesis J, Constantouiakis M, Economidou J, Steranis C, Hakas P, Augoutaki O, Sofroniadou K, Loewenson R, Bilek M (1972) Thalassemia major (homozygous beta-thalassemia). A survey of 138 cases with emphasis on neurologic and muscular aspects. Neurology 22:294-304 19. Luitjes WF, Braakman R, Abels J (1982) Spinal cord compression in a new homozygous variant of beta-thalassemia. Case report. J Neurosurg 57:846-848 20. Luyendijk W, Went L, Schaad HDG (1975) Spinal cord compression due to extramedullary hematopoiesis in homozygous thalassemia. Case report. J Neurosurg 42:212-216 21. Mann KS, Chung PY, Chan KH, Ma LT, Ngan H (1987) Paraplegia due to extramedullary hematopoiesis in thalassemia. J Neurosurg 66:938-940 22. Marinozzi V (1958) Aspetti insoliti dell'iperplegia midollare nelle anemie emolitiche. Haematologica 43:737-759 23. Mihindukulasuriya JCL, Chanmugam D, Machado V, Samarasinghe CA (1977) A case ofparaparesis due to extramedullary hematopoiesis in HbE-thalassemia. Postgrad Med J 53:393397 24. Prabhakar S, Chopra JS, Khosla VK, Dash S, Banerjee AK (1980) Spinal cord compression in homozygous beta-thalassemia. Surg Neurol 13:351-354 25. Ross P, Logan W (1969) Roentgen findings in extramedullary hematopoiesis. AJR 106:604-613 26. Sorsgahl OS, Taylor PE, Noyes WD (1964) Extramedullary hematopoiesis, mediastinal masses and spinal compression. JAMA 189:343-347
i
NS
9 Springer-Verlag 1991
Spinal extradural hematopoiesis in adolescents with thalassemia Report of two cases and a review of the literature A. Amirjamshidi 1, K. Abbassioun 2, and S.E. Ketabchi 1 1 Department of Neurosurgery, Sina Hospital, Tehran University, Imam Avenue, Tehran, Iran 2 Department of Neurosurgery, Arad Hospital, Somaye Avenue, Tehran, Iran Received November 25, 1990
Abstract. Extramedullary hematopoietic tissue occurring within the extramedullary space and causing cord compression is an unusual occurrence in childhood and adolescence, and only four cases have been reported during the first two decades of life. We had the opportunity to treat a 16-year-old girl and a 14-year-old boy with paraparesis secondary to extradural extramedullary hematopoiesis. Findings in these cases are discussed, and an attempt is made to stress once more the possibility of congenital hematopoietic rests as the origin of such hyperplastic tissue. The various modes o f therapy are discussed and related literature is reviewed.
Key words: Adolescence - Extramedullary hematopoiesis - Radiotherapy - Spinal cord compression - Beta thalassemia
gists and neurosurgeons to this curable condition in chronically anemic patients with paraparesis.
Case reports Case 1
A 16-year-old girl was admitted to the hospital suffering from a progressive weakness in both legs of about 2 weeks' duration. The patient was known to have Cootey's anemia with Hb F= 82%. She was paraparetic with increased reflexes in both legs, unsustained bilateral clonus, and upturned toes. In plain X-rays sagittal cleft vertebra was evident at the T9 level (Fig. 1). A myelogram performed on the same day of admission showed a complete block at the level of T9- I 0. Because of the worsening of paraparesis following myelography, an emergency laminectomy was performed. TS-10 laminae were removed, and lobulated reddish gray and moderately bleeding tissue located in the epidural space from T9 down to T10 was easily removed from the dura. There was no extension of this tissue into the surrounding bones. The postoperative course was
Expansion of the red m a r r o w is the primary compensatory mechanism for anemia in patients with leukemia, polycythemic myelofibrosis [4] or any kind of chronic anemia producing hemoglobinopathies [1, 3]. The second compensatory mechanism is extramedullary hematopoiesis (EMH), which occurs notably in the spleen, liver, and lymph nodes [1, 13, 23], but also rarely in the paravertebral region of the thorax, prostate, adrenals, pleura, breast, epidydimis, thymus, kidney, sweat glands, broad ligament, retroperitoneal space [9, 11, 14, 15, 17, 23], choroid plexus [6, 14], cranial dural folds [6], within the peripheral nerves [I], and even within brain tumors [14]. Spinal extradural space is another occasional site of proliferation of this hematopoietic tissue, which can produce signs and symptoms of cord compression. However, as this compensatory proliferative mechanism might need time to produce neurological deficits, this clinical presentation is not limited to the pediatric and adolescent age periods. Two cases are described to draw the attention of pediatricians and pediatric neuroloOffprint requests to: A. Amirjamshidi
Fig. 1. Sagittal cleft vertebra of T9 in AP view
224
Fig. 2. Hyperplastic hematopoietic tissue with numerous darker staining red-cell precursors, normoblasts, and megakaryocytes. This erythroblastic hyperplasia is diagnostic for extramedullary hematopoiesis in thalassemia patients. (H&E, x 132)
Table 1. Reported cases of extradural extramedullary hematopoiesis which occurred in the first two decades of life Reference Marinozzi 1958 [22]
Age (years)/sex 4/F
Histology
Level
Thalassemia
T5-8
Bree et al. 1974 [5]
17/M
?
T8-10
Abbassioun et al. 1982 [1]
19/M 19/M
Thalassemia Thalassemia
T8-11 T6-7
Amirjamshidi et al., this report
16/F 14/M
Thalassemia Thalassemia
T9-10 T5-11
uneventful and complete recovery of function occurred within a few days. The tumor was hematopoietic granulomatous tissue with remarkable erythroid proliferation (Fig. 2). Two blood transfusions were performed in the hospital; at present, the patient is under the care of a pediatric hematologist.
Case 2 A 14-year-old boy was admitted complaining of weakness of the legs of about 4 weeks' duration. He was spastic, paraparetic, and a vague sensory level was detectable at the T 8 - 9 level. Lumbar myelography showed the rostral end of the blockage at the T5-6 level. He was anemic with an Hb level of 8.8 g%, and normal white count and differentiation. HbF was 35% and HbA=4.1%, compatible with beta thalassemia intermedia. With the impression of extradural EMH (ED-EMH) as the cause of paraparesis, laminectomy was performed from T5 down to the T l l level. The laminae were moderately friable and vascular. A purplish lobulated tumor was observed surrounding the dura without any extension towards the vertebral bone and pedicles. It was bleeding profusely and teased off the dura with great difficulty. Subtotal excision of the lesion was made. The histological examination in this case was als0 compatible with hematopoietic tissue (Fig. 3 a, b). The postoperative course was uneventful and paraparesis improved rapidly. Several transfusions were performed in the hospital and he was given fractionated localized 1500 tad radiation a month after healing of the wound.
Fig. 3. a The well-demarcated, capsulated margin of epidural t mor is clearly visible in this slide. Numerous sheets of macron0 moblasts surround the fat-laden sinusoids. (H &E, x 79). b TI features of erythroblastic hyperplasia are demarcated with predor inance of nucleated red blood cells, occasional hemosiderin d posits, and disappearance of fat cells. (H&E, x 416)
Discussion E x t r a m e d u l l a r y h e m a t o p o i e s i s is u n c o m m o n in the cm tral n e r v o u s system. O n l y f o u r k n o w n cases h a v e bee r e p o r t e d to o c c u r d u r i n g the first t w o d e c a d e s o f liJ (Table 1) a n d we n o w a d d two new cases. T h a l a s s e m i a is an i n h e r i t a b l e d i s o r d e r o f autosom~ recessive type. It involves defective synthesis o f b e t a glot ulin a n d c o m p e n s a t o r y synthesis o f g a m m a c h a i n g l o b l lin, l e a d i n g to synthesis o f h e m o g l o b i n F. I n the h( m o z y g o u s p a t i e n t the c o n c e n t r a t i o n o f H b F u s u a l l y e" ceeds 15%. T h e c o m p e n s a t o r y m e c h a n i s m includes ma: r o w e x p a n s i o n a n d E D - E M H . E D - E M H l e a d s to spin~ c o r d c o m p r e s s i o n a n d s e c o n d a r y n e u r o l o g i c a l deficits. A s in o u r two cases, t h e r e is a n o t a b l e p r e d i l e c t i o n f( such e x t r a m e d u l l a r y h e m a t o p o i e t i c tissue to o c c u r in tl~ t h o r a c i c r e g i o n [1, 3, 4, 7, 10, 16, 1 9 - 2 1 , 23, 24, 26 Several h y p o t h e s e s h a v e b e e n p r o p o s e d to e x p l a i n th: s t r a n g e l o c a l i z a t i o n . M a s s e s o f h e m a t o p o i e t i c tissue als o c c u r in the t h o r a x , especially in the p a r a s p i n a l , p l e u r a a n d r e t r o p l e u r a l a r e a s [11, 15]. This significant develo]~
225 ment of the extramedullary hematopoietic tissue has been attributed to extension from bone marrow cavities of the vertebrae [1, 23] or thinned trabeculated proximal end of the ribs and costovertebral junctions [1, 18, 23]. Alternatively, these activated blood-forming masses possibly originate from embryonic rests, including retropleural corpuscles [11,20, 23] or lymph nodes [9]. The association of a congenital vertebral anomaly at the level of E M H tissue may reinforce this second hypothesis (case 1). The lobulated shape of these hematopoietic tissues in the extradural space may also suggest that they have originated from the primitive rests lying in a segmental pattern at the thoracic level. Different modes of therapy have been suggested for E D - E M H , including decompressive laminectomy, followed by transfusion and local irradiation [1, 8, 10, 17, 20] and overtransfusion with or without localized radiation [2]. The latter may be more appropriate in children to prevent unpredictable complications o f wide laminectomies.
References 1. Abbassioun K, Amirjamshidi A (1982) Curable paraplegia due to extradural hematopoiesis in thalassemia. Neurosurgery 11:804-807 2. Abbassioun K, Amirjamshidi A, Zamanianpour M (1985) Curable paraplegia (Letter). Neurosurgery 17:528 3. Ammouni AA, Sher JH, Schmelka D (1975) Spinal cord compression by extramedullary hematopoietic tissue in sickle cell anemia. J Neurosurg 43:483-485 4. Appleby A, Batson GA, Lassman LP, Simpson CA (1964) Spinal cord compression by extramedullary hematopoiesis in myelosclerosis. J Neurol Neurosurg Psychiatry 27:313- 316 5. Bree RL, Neiman HL, Hodak JA (1974) Extramedullary hematopoiesis in the spinal epidural space. J Can Assoc Radiol 25:297-299 6. Brown AJ, Gomez-leon G (1984) Subdural hemorrhage secondary to extramedullary hematopoiesis in polycythemic myeloid metaplasia. Neurosurgery 14:588-591 7. Bucy PC, Ladpli R (1963) Recoverable paraplegia. JAMA 185:685 691 8. Cauthen LC, McLaurin LP, Foster MT, Roberta L (1968) Spinal cord compression secondary to extramedullary hematopoiesis in two brothers. Report of two cases. J Neurosurg 29:529 531
9. Close AS, Taira Y, Cleveland DA (1958) Spinal cord compression due to extramedullary hematopoiesis. Am J Med 48:421427 10. Cross JN, Morgan OS, Gibbs WN, Cheruvanky I (1977) Spinal cord compression in thalassemia. J Neurol Neurosurg Psychiatry 40:1120-1122 11. Da Costa JL, Loh YS, Hanam E (1974) Extramedullary hematopoiesis with multiple tumor simulating masses in hemoglobin E-thalassemia disease. Chest 65:210-212 12. Davis DV, Coupland RE (1969) Gray's anatomy, descriptive and applied, 34th edn. Longmans Green, London, pp 186-188 13. Fessas P, Loukopoulos D (1974) The beta-thalassemias. In: Weatheral DJ (ed) Clinics in hematology, vol 3. Saunders, London, pp 411-435 14. Gregorios JG, Bay JW, Dudley AW Jr (1983) Extramedullary hematopoiesis in malignant meningioma. Neurosurgery 13:447-451 15. Hanford RB, Schneider GF, MacCarthy JD (1960) Massive thoracic extramedullary hemopoiesis. N Engl J Med 263:120123 16. Heffez DS, Sawaya R, Udverhely GB, Mann R (1982) Spinal epidural extramedutlary hematopoiesis with cord compression in a patient with refractory sideroblastic anemia. J Neurosurg 57:399-406 17. Heffner RR, Koehl RH (1970) Hemopoiesis in the spinal epidural space. Case report. J Neurosurg 32:485-490 18. Logothesis J, Constantouiakis M, Economidou J, Steranis C, Hakas P, Augoutaki O, Sofroniadou K, Loewenson R, Bilek M (1972) Thalassemia major (homozygous beta-thalassemia). A survey of 138 cases with emphasis on neurologic and muscular aspects. Neurology 22:294-304 19. Luitjes WF, Braakman R, Abels J (1982) Spinal cord compression in a new homozygous variant of beta-thalassemia. Case report. J Neurosurg 57:846-848 20. Luyendijk W, Went L, Schaad HDG (1975) Spinal cord compression due to extramedullary hematopoiesis in homozygous thalassemia. Case report. J Neurosurg 42:212-216 21. Mann KS, Chung PY, Chan KH, Ma LT, Ngan H (1987) Paraplegia due to extramedullary hematopoiesis in thalassemia. J Neurosurg 66:938-940 22. Marinozzi V (1958) Aspetti insoliti dell'iperplegia midollare nelle anemie emolitiche. Haematologica 43:737-759 23. Mihindukulasuriya JCL, Chanmugam D, Machado V, Samarasinghe CA (1977) A case ofparaparesis due to extramedullary hematopoiesis in HbE-thalassemia. Postgrad Med J 53:393397 24. Prabhakar S, Chopra JS, Khosla VK, Dash S, Banerjee AK (1980) Spinal cord compression in homozygous beta-thalassemia. Surg Neurol 13:351-354 25. Ross P, Logan W (1969) Roentgen findings in extramedullary hematopoiesis. AJR 106:604-613 26. Sorsgahl OS, Taylor PE, Noyes WD (1964) Extramedullary hematopoiesis, mediastinal masses and spinal compression. JAMA 189:343-347
