Differential Diagnosis of Bone Dysplasia C. A. Leftridge, Jr, MD Gainesville, Florida
History The patient was a 13-year-old white female who presented with a history of lassitude, hepatosplenomegaly, and occasional unexplained epistaxis. She also complained that her vision and, to a lesser degree, her hearing were decreasing. On clinical examination, this pale, lethargic patient showed obvious growth retardation and palpation of the abdomen suggested hepatosplenomegaly. The patient's mother related that the patient had had "frequent touches of pneumonia." As part of the work-up, a chest radiogra ph was obtained which prompted additional radiographs. Three are presented here for your evaluation (Figures 1-3). Considering the above information and radiographs, which is the most likely diagnosis in this patient?
Requests for reprints should be addressed to Dr. C. A. Leftridge, Jr., Department of Radiology, Shands Teaching Hospital, Gainesville, FL 32601
750
1. Cooley's anemia (thalassemia major) 2. Osteopetrosis (Albers-Schbnberg disease) 3. Osteopoikilosis 4. Pyknodysostosis 5. Progressive diaphyseal dysplasia (Engelmann's disease)
Discussion Cooley's Anemia While these patients are, by definition, anemic, the radiologic changes are quite distinctive and sufficiently characteristic to remove this entity from serious consideration. The bones reveal marked marrow expansion with thinned cortices. Owing to the mnarrow overgrowth, the trabeculae are resorbed and those which remain are coarsened1 giving the bones a cobweb-like appearance. Both hepatosplenomegaly and growth retardation are frequent features of Cooley's anemia. Often the skull will reveal the socalled hair-on-end appearance, particularly in the area of the frontal bone. Marrow hyperexpansion in all perinasal sinuses (except the ethmoid air cells) is also a frequent feature.'
Osteopoikilosis This bone entity is asymnptomatic
and usually uncovered serendipitously, though joint pain may be present in up to 20 percent of affected patients. This symptom, however, may be entirely unrelated to the disorder.2 As in thalassemia major, the bone lesions in osteopoikilosis are characteristic enough to remove this disorder from contention. Punctate, round lesions ranging from 0.2-2 cm are the characteristic findings. The sclerotic densities which represent compact bone in the spongiosa are most often seen at the ends of the tubular bones and, if the growth plate is open, in the epiphyseal ossification centers. The density of the uninvolved bone, as well as its contour, is normal.
Pyknodysostosis In this disorder, there is a tendency toward a generalized bony sclerosis with metaphyseal modeling deformities. Neither, as a rule, approach the degree of severity manifested by the patient presented here. In addition to frequent shortening of the acromial end of the clavicles, patients with pyknodysostosis show a propensity for shortening of the distal phalanges of both fingers and feet. Anemia and hepatosplenomegaly are not present,3 nor is evidence of cranial nerve compression.4
JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION, VOL. 69, NO. 10, 1977
Figure 1. Single PA radiograph of the chest revealing cardiomegaly, dense, "chalk-white" bones but no evidence of pulmonary inflammatory disease.
Progressive diaphyseal dysplasia Cortical thickening and sclerosis are two of the radiographic hallmarks of this disease but the changes are usually limited to the diaphysis. In the late stages of the disease, metaphyseal and epiphyseal involvement can be seen. There is both endosteal and periosteal bone proliferation with encroachment upon the medullary cavity which may lead to anemia with subsequent hepatosplenomegaly.5 Malnutrition, muscular weakness, and a peculiar waddling gait are frequent presenting complaints. Thickening of the skull base with cranial nerve embarrassment has been noted.5
Osteopetrosis This disease is characterized by extreme bone density ("marble bones") in which the fairly clear-cut boundaries between cortex, medullary cavity, growth plate, and trabecular pattern is lost.6 Polyostotic involvement is the rule. The metaphyseal ends of major long bones reflect abnormalities in tubulation, appearing "canoepaddle" in configuration. From time to time a "bone-withina-bone" pattern and/or transverse bands of alternating bone density is present which suggests that the process may be cyclic. Calvarial involvement is not as prominent as skull base involvement with the latter frequently reducing the caliber of the cranial nerve foramina which at times leads to progressive visual and auditory impairment.
Figure 3. Single PA of the right hand showing changes in bone almost identical to that in the right knee. There seems to be a "bone within a bone" appearance of the metacarpals. The medullary canal is almost nonexistent.
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Clinical and laboratory findings often reveal pallor, growth retardation, optic atrophy, hepatosplenomegaly, thrombocytopenia, and anemia. Interestingly enough, the blood chemistries are usually normal except for occasional hypercalcemia. Fractures, osteomyelitis, and dental caries are frequently noted.7 Mental status is usually normal. The diagnosis in the patient presented is osteopetrosis.
Literature Cited
Figure 2 Single AP view of the right femur and knee demonstrating modeling deformities of tibia and femur with dense sclerotic bone.
JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION, VOL. 69, NO. 10, 1977
1. Edeiken J, Hodes PJ: Roentgen Diagnosis of Diseases of Bone, vol 1, ed 2. Baltimore, Williams and Wilkins, 1973, p 375 2. Spranger JW, Langer LO, Wiedeman HR: Bone Dysplasias. Philadelphia, WB Saunders, 1974, p 305 3. Caffey J: Pediatric X-Ray Diagnosis, vol 2, ed 6. Chicago, Year Book Medical Publishers, 1973, p 1066 4. Warkany J: Congenital Malformations. Chicago, Year Book Medical PubIishers, 1971, p 869 5. Paul LW, Juhl JH: Essentials of Roentgen Interpretation, ed 3. New York, Harper and Row, 1972, p 50 6. Edeiken J, Hodes PJ: Roentgen Diagnosis of Diseases of Bone, vol 1, ed 2. Baltimore, Williams and Wilkins, 1973, p 197 7. Nelson WE: Textbook of Pediatrics. Philadelphia, WB Saunders, 1964, p 1362
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History The patient was a 13-year-old white female who presented with a history of lassitude, hepatosplenomegaly, and occasional unexplained epistaxis. She also complained that her vision and, to a lesser degree, her hearing were decreasing. On clinical examination, this pale, lethargic patient showed obvious growth retardation and palpation of the abdomen suggested hepatosplenomegaly. The patient's mother related that the patient had had "frequent touches of pneumonia." As part of the work-up, a chest radiogra ph was obtained which prompted additional radiographs. Three are presented here for your evaluation (Figures 1-3). Considering the above information and radiographs, which is the most likely diagnosis in this patient?
Requests for reprints should be addressed to Dr. C. A. Leftridge, Jr., Department of Radiology, Shands Teaching Hospital, Gainesville, FL 32601
750
1. Cooley's anemia (thalassemia major) 2. Osteopetrosis (Albers-Schbnberg disease) 3. Osteopoikilosis 4. Pyknodysostosis 5. Progressive diaphyseal dysplasia (Engelmann's disease)
Discussion Cooley's Anemia While these patients are, by definition, anemic, the radiologic changes are quite distinctive and sufficiently characteristic to remove this entity from serious consideration. The bones reveal marked marrow expansion with thinned cortices. Owing to the mnarrow overgrowth, the trabeculae are resorbed and those which remain are coarsened1 giving the bones a cobweb-like appearance. Both hepatosplenomegaly and growth retardation are frequent features of Cooley's anemia. Often the skull will reveal the socalled hair-on-end appearance, particularly in the area of the frontal bone. Marrow hyperexpansion in all perinasal sinuses (except the ethmoid air cells) is also a frequent feature.'
Osteopoikilosis This bone entity is asymnptomatic
and usually uncovered serendipitously, though joint pain may be present in up to 20 percent of affected patients. This symptom, however, may be entirely unrelated to the disorder.2 As in thalassemia major, the bone lesions in osteopoikilosis are characteristic enough to remove this disorder from contention. Punctate, round lesions ranging from 0.2-2 cm are the characteristic findings. The sclerotic densities which represent compact bone in the spongiosa are most often seen at the ends of the tubular bones and, if the growth plate is open, in the epiphyseal ossification centers. The density of the uninvolved bone, as well as its contour, is normal.
Pyknodysostosis In this disorder, there is a tendency toward a generalized bony sclerosis with metaphyseal modeling deformities. Neither, as a rule, approach the degree of severity manifested by the patient presented here. In addition to frequent shortening of the acromial end of the clavicles, patients with pyknodysostosis show a propensity for shortening of the distal phalanges of both fingers and feet. Anemia and hepatosplenomegaly are not present,3 nor is evidence of cranial nerve compression.4
JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION, VOL. 69, NO. 10, 1977
Figure 1. Single PA radiograph of the chest revealing cardiomegaly, dense, "chalk-white" bones but no evidence of pulmonary inflammatory disease.
Progressive diaphyseal dysplasia Cortical thickening and sclerosis are two of the radiographic hallmarks of this disease but the changes are usually limited to the diaphysis. In the late stages of the disease, metaphyseal and epiphyseal involvement can be seen. There is both endosteal and periosteal bone proliferation with encroachment upon the medullary cavity which may lead to anemia with subsequent hepatosplenomegaly.5 Malnutrition, muscular weakness, and a peculiar waddling gait are frequent presenting complaints. Thickening of the skull base with cranial nerve embarrassment has been noted.5
Osteopetrosis This disease is characterized by extreme bone density ("marble bones") in which the fairly clear-cut boundaries between cortex, medullary cavity, growth plate, and trabecular pattern is lost.6 Polyostotic involvement is the rule. The metaphyseal ends of major long bones reflect abnormalities in tubulation, appearing "canoepaddle" in configuration. From time to time a "bone-withina-bone" pattern and/or transverse bands of alternating bone density is present which suggests that the process may be cyclic. Calvarial involvement is not as prominent as skull base involvement with the latter frequently reducing the caliber of the cranial nerve foramina which at times leads to progressive visual and auditory impairment.
Figure 3. Single PA of the right hand showing changes in bone almost identical to that in the right knee. There seems to be a "bone within a bone" appearance of the metacarpals. The medullary canal is almost nonexistent.
-~~~~~~~~~~~~..
Clinical and laboratory findings often reveal pallor, growth retardation, optic atrophy, hepatosplenomegaly, thrombocytopenia, and anemia. Interestingly enough, the blood chemistries are usually normal except for occasional hypercalcemia. Fractures, osteomyelitis, and dental caries are frequently noted.7 Mental status is usually normal. The diagnosis in the patient presented is osteopetrosis.
Literature Cited
Figure 2 Single AP view of the right femur and knee demonstrating modeling deformities of tibia and femur with dense sclerotic bone.
JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION, VOL. 69, NO. 10, 1977
1. Edeiken J, Hodes PJ: Roentgen Diagnosis of Diseases of Bone, vol 1, ed 2. Baltimore, Williams and Wilkins, 1973, p 375 2. Spranger JW, Langer LO, Wiedeman HR: Bone Dysplasias. Philadelphia, WB Saunders, 1974, p 305 3. Caffey J: Pediatric X-Ray Diagnosis, vol 2, ed 6. Chicago, Year Book Medical Publishers, 1973, p 1066 4. Warkany J: Congenital Malformations. Chicago, Year Book Medical PubIishers, 1971, p 869 5. Paul LW, Juhl JH: Essentials of Roentgen Interpretation, ed 3. New York, Harper and Row, 1972, p 50 6. Edeiken J, Hodes PJ: Roentgen Diagnosis of Diseases of Bone, vol 1, ed 2. Baltimore, Williams and Wilkins, 1973, p 197 7. Nelson WE: Textbook of Pediatrics. Philadelphia, WB Saunders, 1964, p 1362
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