Spinal cord compression due to extramedullary hematopoiesis in homozygous thalassemia Case report WILLEM LUYENDIJK, M.D., LODEWIJKWENT, D.Sc., AND HANS D.G. SCHAAD,M.D.
Department of Neurosurgery and Department of Human Genetics, Faculty of Medicine, University of Leiden, The Netherlands, and Department of Medicine, Faculty of Medicine, Paramaribo, Surinam ~," The authors report a case of homozygous thalassemia in which a mass of hematopoietic tissue in the vertebral canal caused spastic paraparesis. Surgical removal of the tissue plus radiotherapy were successful. The pathological findings indicated direct extension of hematopoietic tissue from the adjacent bone marrow into the epidural space of the vertebral canal. KEYWORDS thalassemia
9 spinal cord compression
H
EMATOPOIESIS in the spinal epidural space has been reported in only eight patients. Myelofibrosis was the primary diagnosis in three; the other five were said to have thalassemia, laa,12 The nature of the thalassemia was not well substantiated in these cases. We are reporting the findings in a patient whose case we were able to study in somewhat greater detail. Case Report
This 42-year-old male resident of Surinam was of predominantly Negro ancestry. He was admitted to the Hospital of The Medical School in Paramaribo in September, 1970, because of progressive spastic paraparesis 2]2
9 hematopoiesis
9
and urinary and fecal incontinence. At the age of 26 years he had been seen because of poor healing of leg wounds, requiring skin transplantations. He was markedly anemic and had an enlarged liver and spleen. Examination. An incomplete transverse lesion of the spinal cord was present at the level of the 8th to 9th dorsal segment. The lumbar cerebrospinal fluid had a somewhat yellowish appearance and an initial pressure of 5 to 6 cm H20; the Queckenstedt sign was barely discernible. The protein content was 40 mg/100 ml and only one cell was seen. The mucous membranes were pallid, and the axillary and cervical lymph glands were enlarged. The spleen was enlarged 14 cm below the costal margin and the liver 4 cm.
J. Neurosurg. / Volume 42 / February, 1975
Spinal cord compression due to thalassemia TABLE I
Hematological data of the patient and his family Family Member
Age (yrs.)
Hb (gm/lO0 ml)
Hct (~o)
MCHC (7o)
patient brother sister halfbrother son daughter daughter daughter
42 48 40 53 10 8 6 5
10.0 14.4 12.2 13.9 11.8 11.1 10.9 11.8
33 47 405 445 39 36 36~ 395
30 3@ 30 31 30 31 30 30
Ret Serum Fe (~o) (~g/lO0ml) 4.3 1.6 1.2 0.6 1.5 0.5 1.1 0.8
76 110 94 210 120 90 60 60
Bili (mg/lO0 ml) 3.0 0.6 0.7 0.6 0.6 0.8 0.6 0.6
Hb/F (~o) 48 1.4 4.2 1.4 1.1 1.0 2.7 1.9
Hb/A~ (~o) 6.7 5.7 5.4 6.4 6.4 6.1 6.4 5.4
Hb=hemoglobin; Hct=hematocrit; MCHC=mean corpuscular hemoglobin concentration; Ret.= reticulocytes; Bill.= bilirubin.
Table 1 summarizes the results of hematological investigations. In addition to the anemia, these revealed m a r k e d morphological abnormalities of the red cells, including poikilocytosis, anisocytosis, polychromasia, basophil stippling, and target cells. White cell count was 4300/ul, and differential count was normal. The sickle cell test was negative. Further studies detailed below led to the conclusion that the patient must be suffering from thalassemia major or Cooley's anemia. X-ray examination showed a trabecular configuration of the vertebral bodies and arches and marked thickening of the skull especially in the parietal region. Myelography revealed an incomplete block extending from the 5th to the 8th thoracic vertebrae with irregular impressions on the dorsal side. On the basis of the neurological and radiological findings, the patient was transferred to Leiden for surgery. Operation. Laminectomy of T5-7 was performed; the bone tissue of the spinous processes and the vertebral laminae was unusually soft and the marrow was dark brown. A mass surrounded by a thin membrane was found on the dorsal side of the dural sac. It was clearly connected to the vertebral arches and was easily and completely removed with its membrane. The tumor was composed of soft brown tissue and measured about 9 X 3 X 1 cm. Following removal of the tumor the dural sac regained its normal pulsations. Scattered small hard white particles were observed' in the tumor; these appeared to be bone fragments. Pathology. Pathological examination revealed hematopoietic tissue containing all
J. Neurosurg. / Volume 42 / February, 1975
elements of erythro- and myelopoiesis including megakaryocytes. However, erythropoiesis dominated; large foci consisted almost exclusively of young erythroid elements. The overall appearance (Fig. 1 left) closely resembled that of a sternal bone marrow biopsy from the same patient. The disseminated small white particles appeared to be fragments of osseous tissue (Fig. 1 right). Postoperative Course. Postoperative recovery was uneventful. No abnormalities of motion, coordination, or sensation were found on examination 2 months later. A repeat myelogram still suggested abnormal tissue on the dorsal side of the spinal canal in the region of the laminectomy. Radiotherapy was started during which a mild pancytopenia developed; the treatment was therefore stopped after application of 2800 rads. Hematological response was good and the patient was discharged and returned to Surinam. Three years later the patient was still in a satisfactory condition. He had a feeling of stiffness along the medial side of his legs after walking approximately 1000 meters. He had no urinary or fecal incontinence. Leg motion and tendon, abdominal, and cremaster reflexes were normal bilaterally; no pathological reflexes could be evoked. Coordination and sensation were intact except for a slight hypesthesia. Hematological Studies. Table 1 details the laboratory findings in the patient and in the members of his family available for study. The level of fetal hemoglobin (Hb F) of the patient was repeatedly around 50% and the Hb As 6% of total hemoglobin. The level of Hb F in the young red cells obtained by cen2"13
W. Luyendijk, L. Went and H. D. G. Schaad
FIG. 1. Photomicrographs of the surgical specimen. Left: Extramedullary hematopoietic tissue. H & E, • 400. Right: An area containing small patches of bone tissue. H & E, • 160. trifugation was 22% on two occasions and Hb A2 was 12%. The centrifugal red cells contained 20% reticulocytes. The glycine: alanine ratio at position 136 of the 3' chain of isolated Hb F was 0.66, a figure comparable to the normal value for 3' chains of Hb F in umbilical cord blood. The four children, two siblings, and one half-sibling of the patient all had markedly increased levels of Hb A2 (5.4% to 6.4%) and slight increases of Hb F (1.0% to 4.2%). The bilirubin was within normal limits, but serum Fe was moderately high in some. Discussion
Since the term thalassemia is used to describe a variety of genetic conditions, it should be briefly discussed. Originally four groups of ~3-thalassemia were distinguished clinically: 1) thalassemia major or Cooley's anemia; 2) thalassemia intermedia; 3) thalassemia minor; and 4) thalassemia minima. It is now recognized that the only correct subdivision of thalassemia should be on a genetic basis, namely, in heterozygotes and homozygotes. These two groups encompass the original clinical groups; more complex genetic situations may be responsible for mild to severe anemias superficially resembling thalassemia. Homozygotes for thalassemia genes for the Mediterranean area and 214
from Southeastern Asia produce a very severe anemia that is usually fatal unless frequent blood transfusions are administered; homozygotes of /3-thalassemia from other racial groups, notably those of Negro origin, may show a much milder anemia not requiring transfusions; I' these may even have a normal Hb level, n But whatever the racial origin and severity of the thalassemia, the levels of fetal hemoglobin in the blood of homozygous patients are practically always well over 50% of all hemoblogin, x3 Considering the fetal hemoglobin level of around 50%, the increase in the level of Hb A2, the typical morphology of the red cells, and the absence of abnormal hemoglobins in the electrophoretic study of a hemolysate, homozygosity for ~-thalassemia seems to be the only possible diagnosis in our patient. This is further supported by the observation that his four children and three of his siblings all had findings diagnostic of heterozygosity for a/3-thalassemia gene. Table 2 summarizes the findings in the six reported cases of thalassemia with hematopoietic tissue in the spinal epidural space. Definite proof for homozygosity of a thalassemia gene is available only for our patient. In four of these patients, including our own, the lesion was discovered as a consequence of J. Neurosurg. / Volume 42 / February, 1975
Spinal cord compression due to thalassemia TABLE 2 Extradural hematopoiesis in the vertebral canal in patients with thalassemia
Author, Year Gatto, et al., 1954
Sex, Age (yrs.)
Patient's Racial Group
Type of Neurological Location Thalassemia Findings
M 26 Italian
probably incomplete T5 - I0 heterozygote transverse spinal cord lesion F 4 Italian -T8 - 12 Marinozzi, probably (at autopsy) 1958 homozygote incomplete T5 - 8 Sorsdahl, et al., M 40 Negro probably 1964 homozygote transverse (3 discrete spinal cord lesions) lesion probably incomplete T4 - 8 Cauthen, etal., M 47 Negro (brother of homozygote transverse 1968 Sorsdahl's spinal cord patient) lesion mild T-8 - L-3 Heffner and M 21 Italian probably Koehl, 1970 homozygote (at autopsy) Luyendijk, et al., M 42 Negro homozygote incomplete T5 - 7 transverse 1975 spinal cord lesion
incomplete spinal cord lesion; in the other two the lesion was discovered at autopsy, a'7 The patient of Sorsdahl, et al., ~2 and the brother of that patient, reported by Cauthen, et al., 1 are the only ones of the five published cases that resemble ours; each probably was homozygous for a relatively mild form of 13thalassemia; both were of predominantly African ancestry, had comparable neurological complaints, and have survived into adult life without transfusions or splenectomy. The patient reported by Gatto, et al., 2 was clinically comparable to our patient, had a relatively mild anemia and was splenectomized, but was certainly not homozygous for thalassemia. These limited observations plus the knowledge that thalassemia is a common inherited disease in many areas of the world suggest that spread of hematopoietic tissue into the spinal epidural space is rare in patients with homozygous thalassemia. Two studies involving a systematic search for neurological defects in patients with thalassemia further support this idea. Quattrin 9 reviewed 200 Italian patients, and Logothetis, et al., 5 reviewed 138 Greek patients, all homozygous for a thalassemia gene. None of these patients had signs nor symptoms of spinal cord compression; J. Neurosurg. / Volume 42 / February, 1975
Therapy
Results
surgery
no marked improvement; radiotherapy incomplete recovery --surgery
good
surgery; Co-60 irradiation
good
--
--
surgery; good radiotherapy
however, all of the patients were young. The finding of this lesion in three adult patients of Negro origin with a mild form of homozygous thalassemia, a rare disorder in Negroes, suggests that the chance of a spinal cord lesion is far from negligible in a patient with congenital anemia, if the patient lives long enough. Different explanations have been given for the extramedullary hematopoietic tissue in the vertebral canal. Saleeby 1~ has suggested that it may originate from tissue of distant origin. Prader 8 believed that it may result from stimulation of embryonic rests; Knoblich4 also believed that multipotential cells in the epidural space can be transformed into marrow under proper circumstances. Lyall 6 suggests the possibility of a direct extension from the marrow cavity into the epidural space. This last possibility may be the correct explanation for the findings in our patient in view of the small bone particles found throughout the hematopoietic tissue removed at operation. Like Heffner and Koehl, 3 we conclude that spinal cord disease in a young to middle-aged patient with life-long hyperactivity of the bone m a r r o w as seen in homozygous thalassemia seriously suggests epidural hematopoiesis, usually in the thoracic region. 2]5
W. Luyendijk, L. Went and H. D. G. Schaad Acknowledgments We thank Dr. G. Th. A. M. Bots for the neuropathological examination, Dr. R. E. M. Hekster for the myelographic studies, and Miss A. Gelderblom for expert technical hematological assistance.
References 1. Cauthen JC, McLaurin LP, Foster MT, et al: Spinal cord compression secondary to extramedullary hematopoiesis in two brothers. Report of two cases. J Neurosurg 29:529-531, 1968 2. Gatto I, Terraria V, Biondi L: Compressione sul midollo spinale da proliferazione di midollo osseo spazio epidurale in sogetto affetto da malattia di Cooley splenectomizatto. Haematologiea 38:61-76, 1954 3. Heffner RR, Koehl RH: Hemopoiesis in the spinal epidural space. J Neurosnrg 32:485490, 1970 4. Knoblich R: Extramedullary hematopoiesis presenting as intrathoracic tumors. Cancer 13:462-468, 1960 5. Logothetis J, Constantoulakis M, Economidou J, et al: Thalassemia major (homozygous beta-thalassemia). A survey of 138 cases with emphasis on neurologic and muscular aspects. Neurology (Minneap) 22:294-304, 1972
216
6. Lyall A: Massive extramedullary bone marrow formation in a case of pernicious anaemia. J Pathoi Bact 41:469-472, 1935 7. Marinozzi V: Aspetti insoliti dell'iperplasia midollare helle anemie emolitiche. Haematologica 43:737-759, 1958 8. Prader A: Die friihembryonale Entwicklung der menschlichen Zwischenwirbelscheibe. Acta Anat 3:68-83, 1947 9. Quattrin N: Personal communication, 1971 10. Saleeby ER: Heterotopia of bone marrow without apparent cause. Am J Pathol 1:69-76, 1925 11. Schokker RC, Went LN, Bok J: A new genetic variant of ~3-thalassaemia. Nature 209:44-46, 1966 12. Sorsdahl OS, Taylor PE, Noyes WD: Extramedullary hematopoiesis, mediastinal mass and spinal cord compression. JAMA 189:343-347, 1964 13. WeatheraU D J: The Thalassaemia Syndromes. London, Blackwell Scientific Publishers, 1972 14. Went LN, MacIver JE: Thalassemia in the West Indies. Blood 17:166-181, 1961
Address reprint requests to: Willem Luyendijk, M.D., Department of Neurosurgery, University Hospital, Leiden, The Netherlands.
J. Neurosurg. / Volume 42 / February, 1975
Department of Neurosurgery and Department of Human Genetics, Faculty of Medicine, University of Leiden, The Netherlands, and Department of Medicine, Faculty of Medicine, Paramaribo, Surinam ~," The authors report a case of homozygous thalassemia in which a mass of hematopoietic tissue in the vertebral canal caused spastic paraparesis. Surgical removal of the tissue plus radiotherapy were successful. The pathological findings indicated direct extension of hematopoietic tissue from the adjacent bone marrow into the epidural space of the vertebral canal. KEYWORDS thalassemia
9 spinal cord compression
H
EMATOPOIESIS in the spinal epidural space has been reported in only eight patients. Myelofibrosis was the primary diagnosis in three; the other five were said to have thalassemia, laa,12 The nature of the thalassemia was not well substantiated in these cases. We are reporting the findings in a patient whose case we were able to study in somewhat greater detail. Case Report
This 42-year-old male resident of Surinam was of predominantly Negro ancestry. He was admitted to the Hospital of The Medical School in Paramaribo in September, 1970, because of progressive spastic paraparesis 2]2
9 hematopoiesis
9
and urinary and fecal incontinence. At the age of 26 years he had been seen because of poor healing of leg wounds, requiring skin transplantations. He was markedly anemic and had an enlarged liver and spleen. Examination. An incomplete transverse lesion of the spinal cord was present at the level of the 8th to 9th dorsal segment. The lumbar cerebrospinal fluid had a somewhat yellowish appearance and an initial pressure of 5 to 6 cm H20; the Queckenstedt sign was barely discernible. The protein content was 40 mg/100 ml and only one cell was seen. The mucous membranes were pallid, and the axillary and cervical lymph glands were enlarged. The spleen was enlarged 14 cm below the costal margin and the liver 4 cm.
J. Neurosurg. / Volume 42 / February, 1975
Spinal cord compression due to thalassemia TABLE I
Hematological data of the patient and his family Family Member
Age (yrs.)
Hb (gm/lO0 ml)
Hct (~o)
MCHC (7o)
patient brother sister halfbrother son daughter daughter daughter
42 48 40 53 10 8 6 5
10.0 14.4 12.2 13.9 11.8 11.1 10.9 11.8
33 47 405 445 39 36 36~ 395
30 3@ 30 31 30 31 30 30
Ret Serum Fe (~o) (~g/lO0ml) 4.3 1.6 1.2 0.6 1.5 0.5 1.1 0.8
76 110 94 210 120 90 60 60
Bili (mg/lO0 ml) 3.0 0.6 0.7 0.6 0.6 0.8 0.6 0.6
Hb/F (~o) 48 1.4 4.2 1.4 1.1 1.0 2.7 1.9
Hb/A~ (~o) 6.7 5.7 5.4 6.4 6.4 6.1 6.4 5.4
Hb=hemoglobin; Hct=hematocrit; MCHC=mean corpuscular hemoglobin concentration; Ret.= reticulocytes; Bill.= bilirubin.
Table 1 summarizes the results of hematological investigations. In addition to the anemia, these revealed m a r k e d morphological abnormalities of the red cells, including poikilocytosis, anisocytosis, polychromasia, basophil stippling, and target cells. White cell count was 4300/ul, and differential count was normal. The sickle cell test was negative. Further studies detailed below led to the conclusion that the patient must be suffering from thalassemia major or Cooley's anemia. X-ray examination showed a trabecular configuration of the vertebral bodies and arches and marked thickening of the skull especially in the parietal region. Myelography revealed an incomplete block extending from the 5th to the 8th thoracic vertebrae with irregular impressions on the dorsal side. On the basis of the neurological and radiological findings, the patient was transferred to Leiden for surgery. Operation. Laminectomy of T5-7 was performed; the bone tissue of the spinous processes and the vertebral laminae was unusually soft and the marrow was dark brown. A mass surrounded by a thin membrane was found on the dorsal side of the dural sac. It was clearly connected to the vertebral arches and was easily and completely removed with its membrane. The tumor was composed of soft brown tissue and measured about 9 X 3 X 1 cm. Following removal of the tumor the dural sac regained its normal pulsations. Scattered small hard white particles were observed' in the tumor; these appeared to be bone fragments. Pathology. Pathological examination revealed hematopoietic tissue containing all
J. Neurosurg. / Volume 42 / February, 1975
elements of erythro- and myelopoiesis including megakaryocytes. However, erythropoiesis dominated; large foci consisted almost exclusively of young erythroid elements. The overall appearance (Fig. 1 left) closely resembled that of a sternal bone marrow biopsy from the same patient. The disseminated small white particles appeared to be fragments of osseous tissue (Fig. 1 right). Postoperative Course. Postoperative recovery was uneventful. No abnormalities of motion, coordination, or sensation were found on examination 2 months later. A repeat myelogram still suggested abnormal tissue on the dorsal side of the spinal canal in the region of the laminectomy. Radiotherapy was started during which a mild pancytopenia developed; the treatment was therefore stopped after application of 2800 rads. Hematological response was good and the patient was discharged and returned to Surinam. Three years later the patient was still in a satisfactory condition. He had a feeling of stiffness along the medial side of his legs after walking approximately 1000 meters. He had no urinary or fecal incontinence. Leg motion and tendon, abdominal, and cremaster reflexes were normal bilaterally; no pathological reflexes could be evoked. Coordination and sensation were intact except for a slight hypesthesia. Hematological Studies. Table 1 details the laboratory findings in the patient and in the members of his family available for study. The level of fetal hemoglobin (Hb F) of the patient was repeatedly around 50% and the Hb As 6% of total hemoglobin. The level of Hb F in the young red cells obtained by cen2"13
W. Luyendijk, L. Went and H. D. G. Schaad
FIG. 1. Photomicrographs of the surgical specimen. Left: Extramedullary hematopoietic tissue. H & E, • 400. Right: An area containing small patches of bone tissue. H & E, • 160. trifugation was 22% on two occasions and Hb A2 was 12%. The centrifugal red cells contained 20% reticulocytes. The glycine: alanine ratio at position 136 of the 3' chain of isolated Hb F was 0.66, a figure comparable to the normal value for 3' chains of Hb F in umbilical cord blood. The four children, two siblings, and one half-sibling of the patient all had markedly increased levels of Hb A2 (5.4% to 6.4%) and slight increases of Hb F (1.0% to 4.2%). The bilirubin was within normal limits, but serum Fe was moderately high in some. Discussion
Since the term thalassemia is used to describe a variety of genetic conditions, it should be briefly discussed. Originally four groups of ~3-thalassemia were distinguished clinically: 1) thalassemia major or Cooley's anemia; 2) thalassemia intermedia; 3) thalassemia minor; and 4) thalassemia minima. It is now recognized that the only correct subdivision of thalassemia should be on a genetic basis, namely, in heterozygotes and homozygotes. These two groups encompass the original clinical groups; more complex genetic situations may be responsible for mild to severe anemias superficially resembling thalassemia. Homozygotes for thalassemia genes for the Mediterranean area and 214
from Southeastern Asia produce a very severe anemia that is usually fatal unless frequent blood transfusions are administered; homozygotes of /3-thalassemia from other racial groups, notably those of Negro origin, may show a much milder anemia not requiring transfusions; I' these may even have a normal Hb level, n But whatever the racial origin and severity of the thalassemia, the levels of fetal hemoglobin in the blood of homozygous patients are practically always well over 50% of all hemoblogin, x3 Considering the fetal hemoglobin level of around 50%, the increase in the level of Hb A2, the typical morphology of the red cells, and the absence of abnormal hemoglobins in the electrophoretic study of a hemolysate, homozygosity for ~-thalassemia seems to be the only possible diagnosis in our patient. This is further supported by the observation that his four children and three of his siblings all had findings diagnostic of heterozygosity for a/3-thalassemia gene. Table 2 summarizes the findings in the six reported cases of thalassemia with hematopoietic tissue in the spinal epidural space. Definite proof for homozygosity of a thalassemia gene is available only for our patient. In four of these patients, including our own, the lesion was discovered as a consequence of J. Neurosurg. / Volume 42 / February, 1975
Spinal cord compression due to thalassemia TABLE 2 Extradural hematopoiesis in the vertebral canal in patients with thalassemia
Author, Year Gatto, et al., 1954
Sex, Age (yrs.)
Patient's Racial Group
Type of Neurological Location Thalassemia Findings
M 26 Italian
probably incomplete T5 - I0 heterozygote transverse spinal cord lesion F 4 Italian -T8 - 12 Marinozzi, probably (at autopsy) 1958 homozygote incomplete T5 - 8 Sorsdahl, et al., M 40 Negro probably 1964 homozygote transverse (3 discrete spinal cord lesions) lesion probably incomplete T4 - 8 Cauthen, etal., M 47 Negro (brother of homozygote transverse 1968 Sorsdahl's spinal cord patient) lesion mild T-8 - L-3 Heffner and M 21 Italian probably Koehl, 1970 homozygote (at autopsy) Luyendijk, et al., M 42 Negro homozygote incomplete T5 - 7 transverse 1975 spinal cord lesion
incomplete spinal cord lesion; in the other two the lesion was discovered at autopsy, a'7 The patient of Sorsdahl, et al., ~2 and the brother of that patient, reported by Cauthen, et al., 1 are the only ones of the five published cases that resemble ours; each probably was homozygous for a relatively mild form of 13thalassemia; both were of predominantly African ancestry, had comparable neurological complaints, and have survived into adult life without transfusions or splenectomy. The patient reported by Gatto, et al., 2 was clinically comparable to our patient, had a relatively mild anemia and was splenectomized, but was certainly not homozygous for thalassemia. These limited observations plus the knowledge that thalassemia is a common inherited disease in many areas of the world suggest that spread of hematopoietic tissue into the spinal epidural space is rare in patients with homozygous thalassemia. Two studies involving a systematic search for neurological defects in patients with thalassemia further support this idea. Quattrin 9 reviewed 200 Italian patients, and Logothetis, et al., 5 reviewed 138 Greek patients, all homozygous for a thalassemia gene. None of these patients had signs nor symptoms of spinal cord compression; J. Neurosurg. / Volume 42 / February, 1975
Therapy
Results
surgery
no marked improvement; radiotherapy incomplete recovery --surgery
good
surgery; Co-60 irradiation
good
--
--
surgery; good radiotherapy
however, all of the patients were young. The finding of this lesion in three adult patients of Negro origin with a mild form of homozygous thalassemia, a rare disorder in Negroes, suggests that the chance of a spinal cord lesion is far from negligible in a patient with congenital anemia, if the patient lives long enough. Different explanations have been given for the extramedullary hematopoietic tissue in the vertebral canal. Saleeby 1~ has suggested that it may originate from tissue of distant origin. Prader 8 believed that it may result from stimulation of embryonic rests; Knoblich4 also believed that multipotential cells in the epidural space can be transformed into marrow under proper circumstances. Lyall 6 suggests the possibility of a direct extension from the marrow cavity into the epidural space. This last possibility may be the correct explanation for the findings in our patient in view of the small bone particles found throughout the hematopoietic tissue removed at operation. Like Heffner and Koehl, 3 we conclude that spinal cord disease in a young to middle-aged patient with life-long hyperactivity of the bone m a r r o w as seen in homozygous thalassemia seriously suggests epidural hematopoiesis, usually in the thoracic region. 2]5
W. Luyendijk, L. Went and H. D. G. Schaad Acknowledgments We thank Dr. G. Th. A. M. Bots for the neuropathological examination, Dr. R. E. M. Hekster for the myelographic studies, and Miss A. Gelderblom for expert technical hematological assistance.
References 1. Cauthen JC, McLaurin LP, Foster MT, et al: Spinal cord compression secondary to extramedullary hematopoiesis in two brothers. Report of two cases. J Neurosurg 29:529-531, 1968 2. Gatto I, Terraria V, Biondi L: Compressione sul midollo spinale da proliferazione di midollo osseo spazio epidurale in sogetto affetto da malattia di Cooley splenectomizatto. Haematologiea 38:61-76, 1954 3. Heffner RR, Koehl RH: Hemopoiesis in the spinal epidural space. J Neurosnrg 32:485490, 1970 4. Knoblich R: Extramedullary hematopoiesis presenting as intrathoracic tumors. Cancer 13:462-468, 1960 5. Logothetis J, Constantoulakis M, Economidou J, et al: Thalassemia major (homozygous beta-thalassemia). A survey of 138 cases with emphasis on neurologic and muscular aspects. Neurology (Minneap) 22:294-304, 1972
216
6. Lyall A: Massive extramedullary bone marrow formation in a case of pernicious anaemia. J Pathoi Bact 41:469-472, 1935 7. Marinozzi V: Aspetti insoliti dell'iperplasia midollare helle anemie emolitiche. Haematologica 43:737-759, 1958 8. Prader A: Die friihembryonale Entwicklung der menschlichen Zwischenwirbelscheibe. Acta Anat 3:68-83, 1947 9. Quattrin N: Personal communication, 1971 10. Saleeby ER: Heterotopia of bone marrow without apparent cause. Am J Pathol 1:69-76, 1925 11. Schokker RC, Went LN, Bok J: A new genetic variant of ~3-thalassaemia. Nature 209:44-46, 1966 12. Sorsdahl OS, Taylor PE, Noyes WD: Extramedullary hematopoiesis, mediastinal mass and spinal cord compression. JAMA 189:343-347, 1964 13. WeatheraU D J: The Thalassaemia Syndromes. London, Blackwell Scientific Publishers, 1972 14. Went LN, MacIver JE: Thalassemia in the West Indies. Blood 17:166-181, 1961
Address reprint requests to: Willem Luyendijk, M.D., Department of Neurosurgery, University Hospital, Leiden, The Netherlands.
J. Neurosurg. / Volume 42 / February, 1975
