Ewing's sarcoma in bones of the hands and feet: a clinicopathologic study and review of the literature.

Review of current data from the Intergroup Ewing's Sarcoma Study (IESS) shows that Ewing's sarcoma (ES) is rare in bones of the hands and feet. Only 12 of 377 evaluable patients in the first two IESS studies had a primary tumor in these small, distal bones. The age distribution was typical for that seen in patients with ES at other sites. Males were affected twice as often as females, and tumors in the bones of the feet were much more common than those in the hands. All signs and symptoms were local in distribution. As in other sites, the dominant histologic pattern was categorized as diffuse. With the exception of those patients with lesions in the calcaneus, the prognosis for disease-free survival was excellent. A literature review of cases of ES reported in bones of the hands and feet showed generally comparable results.

"Café-au-lait spots" caused by vitiligo in McCune-Albright syndrome.

Café-au-lait spots, fibrous dysplasia of bone, and endocrine gland hyperactivity are the principal features of McCune-Albright syndrome (MAS). Café-au-lait spots appear at, or soon after, birth. We illustrate "café-au-lait spots" acquired during middle age in a patient with MAS that are an illusion caused by vitiligo. This 64-year-old woman is the oldest patient reported with this disorder.

Doubling skeletal mass during adult life: the syndrome of diffuse osteosclerosis after intravenous drug abuse.

A former intravenous substance abuser, seropositive for hepatitis C virus infection, was referred for diffuse osteosclerosis. There was no history of fracture or skeletal deformity. Cortical and trabecular bone density was approximately twice the mean value for controls. Skeletal histology revealed dense lamellar bone. Recognized causes of acquired generalized osteosclerosis or hyperostosis were excluded. This patient verifies the syndrome of painful diffuse osteosclerosis after intravenous drug abuse and shows that skeletal mass can be markedly increased with histologically normal, structurally sound bone during adult life. Elucidation of the etiology and pathogenesis could offer an effective treatment for osteoporosis.

Expansile skeletal hyperphosphatasia: a new familial metabolic bone disease.

We describe a new familial metabolic bone disease characterized by expanding hyperostotic long bones, early onset deafness, premature tooth loss, and episodic hypercalcemia. The condition affects a mother and daughter studied at the age of 36 years and 11 years, respectively. Both individuals lost all hearing in early childhood and suffered premature shedding of teeth. Skeletal pains began just before puberty. Swelling and aching of most middle phalanges in the hands is an especially troublesome manifestation. The mother also had episodes of symptomatic hypercalcemia first documented in late childhood and subsequently during intercurrent illness and postpartum lactation. Radiographs show hyperostosis and/or osteosclerosis predominantly in the skull and appendicular skeleton. Long bones also are expanded considerably, especially the middle phalanges in the fingers. The mother's skeletal abnormalities are more severe. Biochemical parameters of bone turnover, including serum alkaline phosphatase (ALP) activity, are elevated substantially. In the proposita, dynamic histomorphometry of nondecalcified sections of iliac crest revealed rapid skeletal remodeling. In the mother, who had been treated with bisphosphonates, electron microscopy (EM) showed disorganized collagen bundles as well as necrotic and apoptotic bone cells but no osteocytic osteolysis. Measles virus gene transcripts were not detected in peripheral blood monocytes. Karyotyping was normal, 46,XX. Hyperphosphatasia with bone disease previously has been reported as either a sporadic or autosomal recessive condition. Expansile skeletal hyperphosphatasia (ESH) is probably inherited as an autosomal dominant trait with a high degree of penetrance.

Juvenile Paget disease: life-long features of a mildly affected young woman.

Unusually mild Juvenile Paget Disease (JPD) was extensively investigated in a mentally retarded 21-year-old white woman. Progressive bowing deformitity of her lower limbs began at age 1 1/2 years. Nontraumatic fractures of both femora and both tibias occurred between ages 9 and 14 years. During adulthood, cortical thickening, osteosclerosis, and bowing affected these bones. Serum alkaline phosphatase (ALP) activity was persistently elevated. We found her serum osteocalcin and urinary hydroxyproline and pyridinoline/deoxypyridinoline to also be increased. The iliac crest histology, at ages 14 and 21 years, showed wide cortices and enhanced skeletal remodeling yet the bone was exclusively lamellar. Features of classic Paget Bone Disease (PBD)--such as hypermultinucleated osteoclasts, peritrabecular fibrosis, and mosaic or woven bone--were absent. Electron microscopy revealed no cytoplasmic or nuclear inclusions. Her dermal fibroblasts in culture synthesized unremarkable levels of ALP with proper membrane topography and lipid anchoring; ALP released into the medium also appeared normal. Six months of synthetic human calcitonin therapy daily appeared to reduce here lower limb pain and warmth, but the radiographs, biochemical parameters of skeletal turnover, and bone scintigraphy were unaltered. Lamellar bone has been reported in JPD but accompanied by excessive amounts of woven bone. Our patient reveals that lamellar bone without features of PBD can characterize the skeletal histopathology of the especially rare case of mild JPD.

Hepatitis C-associated osteosclerosis: late onset after blood transfusion in an elderly woman.

A 69-yr-old woman with hepatitis C virus (HCV) infection from blood transfusion 14 yr earlier was evaluated in 1997 for increasing appendicular skeletal pain. Diffusely elevated radioisotope uptake on bone scanning had appeared during the past 15 months. Radiographs spanning 1978-1997 showed remarkable restoration of bone mass and a skeleton like that of a young woman. Bone mineral densities of the femoral neck and lumbar spine were above the mean peak bone mass of young women (T scores, +1.8 and +1.3, respectively) and 160% and 147% of mean values for age-matched female controls (Z-score, +3.7 and +3.6, respectively). Biochemical markers of skeletal remodeling were substantially increased. Bone marrow biopsy showed normal lamellar bone. Serum alkaline phosphatase activity assays suggested that accelerated skeletal turnover began 6-12 months before symptoms. HC-associated osteosclerosis has been reported in nine individuals 27-73 yr of age, most with a history of i.v. drug abuse. Our patient demonstrates that parenteral exposure to blood rather than illicit drugs is the feature common to all affected subjects. Furthermore, we document that there can be a long latency between HCV infection and the development of skeletal abnormalities. We also find that bone mass can be restored by this disorder in a postmenopausal woman. Routine radiographs, however, may not show overt osteosclerosis in the elderly. The precise pathogenesis of this disorder is unknown. Understanding and control of the mechanism of HC-associated osteosclerosis could potentially lead to correction of low bone mass from osteoporosis with good quality skeletal tissue.

Paget bone disease involving young adults in 3 generations of a Korean family.

Although the etiology of Paget bone disease (PBD) is unknown, increasing evidence implicates a "slow virus" infection of the skeleton, perhaps in genetically predisposed individuals. PBD is rare in Asia. We describe a Korean family with PBD. The propositus noticed bowed limbs at approximately 25 years of age. Radiologic studies made when he was 55 years old revealed essentially panostotic PBD. Serum alkaline phosphatase (ALP) activity and osteocalcin (OC) levels were markedly elevated. An iliac crest specimen showed classic histopathologic changes of PBD. Additionally, palpable swellings were first observed at age 45 years at his occiput, pubic ramus, ileum, and facial bones. They contained numerous multinucleated cells and were originally diagnosed as giant cell tumors. However, we found that, like osteoclasts, these cells expressed considerable tartrate-resistant acid phosphatase activity. These "extraskeletal osteoclastomas" resolved rapidly with dexamethasone treatment. Two daughters, 20- and 24-years-of-age, were discovered by study of his 5 children to have elevated serum ALP activity and OC levels and widespread PBD. Both women, however, are without palpable masses and are asymptomatic. The propositus' father, who died at age 55 years, had similar skeletal deformities beginning at age 20 years, but was not examined. Leukocytopenia was found in the 3 living family members with PBD. There was no evidence for linkage of the PBD to HLA loci. The condition appears to be transmitted as an autosomal dominant trait and is manifest in young adult life. Multicentric extraskeletal osteoclastomas with remarkable sensitivity to dexamethasone treatment appear to be another unusual feature of this family's disorder. In this family, the stimulus for PBD is so great that the PBD is apparent at an early age, affects essentially the entire skeleton, and leads to the formation or extension of osteoclast-like cells into nonosseous tissues (extraskeletal osteoclastomas). This 3-generation kindred in Korea, where PBD is rare, shows a strong clustering of PBD compatible with autosomal dominant inheritance. Leukocytopenia appears to distinguish affected family members, but any role for this abnormality in the pathogenesis of PBD is unclear. Our findings support a heritable diathesis for PBD, perhaps mediated by an immune deficiency.

Duplication of the inferior vena cava in thromboembolic disease.

Recurrent pulmonary embolism from the lower extremities or pelvis, despite anticoagulation, often requires interruption of the inferior vena cava (IVC). We report two patients in whom interruption of the IVC failed to ameliorate symptoms. Both patients demonstrated a previously unrecognized duplication of the IVC. We stress the importance of excluding abdominal venous anomalies prior to interrupting the IVC using surgical or percutaneous methods.

In vivo analysis of single, pre- and postprocessing quantitative CT techniques.

Measurements of bone mineral using single and dual-energy quantitative computed tomography (CT) are examined in vivo in 108 vertebral bodies scanned on a Siemens DRH scanner. Pre and postprocessing dual-energy techniques are compared. In the range of clinically useful kilovoltage, the choice of beam energy does not make a significant difference to the single-energy bone mineral measurement. Postprocessing dual-energy measurement in vivo shows a statistically significant decrease in the amount of mineral measured compared to single-energy measurements, whereas the preprocessing measurement shows a significant increase.

Improved accuracy of single-energy computed tomography bone mineral determination using threshold analysis.

Single-energy CT for bone-mineral determination underestimates the degree of mineralization because of error caused by fat in the marrow space. A correction using set theory and threshold analysis was developed to reduce this error. Corrections between 4.7% and 130.9% of fat-induced error are observed. The amount of correction is related directly to the amount of osteopenia present, and is patient specific. This technique may be appropriate for clinical evaluation because the major application of quantitative CT (QCT) is for bone mineral analysis in a population with increasing marrow space fat over time. This technique may allow reduction of the uncertainty of normal data developed using single energy QCT, thereby making the technique more sensitive to early detection of osteopenia.

Quantitative analysis of solitary lesions of bone.

RATIONALE AND OBJECTIVES: To quantitate the radiographic features of common solitary lesions of bone using vector analysis to optimize their radiographic description. METHODS: Plain radiographs of 709 solitary bone lesions were reviewed. Relevant demographic, anatomic, and structural data were cataloged. These data were used to approximate the vector space defined by all possible solitary lesions of bone. Vector space analysis on the entire set of lesions was performed to determine similarities among and between lesion types. RESULTS: The 709 lesions generated 614 separate vectors within the appearance vector space. Only 10 vectors were represented more than 3 times, indicating great variability among and between most lesion types. Osteochondromas (with two vectors repeated 10 and 15 times, respectively) and peripheral chondrosarcomas (with one vector repeated 5 times) were relatively uniform in appearance. Gender bias was present for multiple types of lesions. Larger lesions that involved more than one anatomic center were more likely to be malignant. Lesions occurring in the femoral diaphysis and pelvic flat bones were statistically more likely to be malignant. CONCLUSIONS: Analysis shows that most lesions have highly varied vectors in the appearances within the vector space. More in-depth analysis of each lesion type using this quantitative technique is required to better define individual lesion subspaces and hence their radiographic appearances with respect to other bone lesions.

Quantitative analysis of the plain radiographic appearance of Ewing's sarcoma of bone.

RATIONALE AND OBJECTIVES: The authors quantitate the radiographic features that distinguish the plain radiographic appearance of Ewing's sarcoma (ES) from other solitary lesions of bone. METHODS: A total of 709 cases of focal bone lesions, including 44 ES, were analyzed according to demographic, anatomic, and plain radiographic features. Vector analysis of groups of features was performed to determine those that are most sensitive and specific for the appearance of ES in contrast with other lesions in the database. RESULTS: In our sample, Ewing's sarcoma is most consistently a medullary-based (91%) lytic (89%) lesion with at least a partially permeative appearance (82%), poorly defined edges (82%), no margination (91%), and a soft-tissue mass (61%). When these lesions occur in long bones, they most commonly are found in the diaphysis (75%) and are proximal more often than distal. Vector analysis suggests that any primary bone lesion without radiographically visible matrix and with either a soft-tissue mass, an appearance of permeative destruction alone or in combination with other patterns of bone destruction is suspect for the diagnosis. This small subset of common features appears to have a high sensitivity (89%) and prevalence (47%) of ES among the lesions meeting these criteria. Limiting the age of the patients to progressively younger age groups increases the specificity but lowers sensitivity. The vector analysis-generated differential diagnoses includes osteosarcoma, giant-cell tumor, lymphoma, and chondrosarcoma. CONCLUSIONS: A relatively specific set of radiographic features can be defined, which will assist in the radiographic diagnosis of ES and improve upon current textbook descriptions.

Two postprocessing CT techniques for determining the composition of trabecular bone.

Two dual-energy CT techniques have been developed to analyze the mineral and fat content of trabecular bone. Both are postprocessing techniques that employ calibration standards. Experiments were performed to test these techniques against conventional single-energy techniques and two other dual-energy techniques. As expected, all of the dual-energy methods estimate the mineral content more accurately when fat is present. In contrast to the other dual-energy methods, the new methods described in this article are unique because they make a separate estimate of the fat content of the bone. The results of preliminary tests of these techniques in estimating fat content have been encouraging. Although not exact, the estimates show the correct trend in increasing proportionately as the fat content increases. Possible applications of the techniques in the study of osteoporosis and other bone diseases are described.

Quantitative analysis of the plain radiographic appearance of Brodie's abscess.

RATIONALE AND OBJECTIVES: The authors quantitate the radiographic features that distinguish the plain radiographic appearance of Brodie's abscess (BA) from other solitary lesions of bone. METHODS: Plain radiographs of 709 solitary bone lesions were reviewed, including 21 BAs. These were analyzed according to demographic, gross anatomic, and structural features. Vector analysis of groups of features was performed to determine those that are most sensitive and specific for the radiographic appearance of BA relative to other lesions of bone. RESULTS: Brodie's abscesses, in our series, are most commonly medullary-based (86%) lytic lesions (100%), with a geographic pattern of destruction (100%), well-defined edges (90%), marginal sclerosis (86%), and no bone enlargement (95%). In general, they have no periosteal reaction (71%), cortical break (95%), or visible matrix (90%). They typically are localized to the diaphysis or metaphysis (86%) of tubular bones, particularly in the lower extremity (63%). By vector analysis, the radiographic and demographic description of BA that provided the greatest sensitivity (67%-76%) while maintaining high prevalence (20%-21%) included a well-defined lytic lesion with a geographic pattern of destruction, and no bone enlargement or matrix or cortical break arising in patients younger than 40 years old. Although BAs commonly are small lesions with maximum diameters < 50 mm, size criteria did not greatly affect the sensitivity or specificity for detection of BA in our database. The differential diagnosis generated by vector analysis includes osteoid osteoma, nonossifying fibroma, giant cell tumor, eosinophilic granuloma chondroblastoma, and fibrous dysplasia, as the major lesions. CONCLUSIONS: Although BA can present with a variety of radiographic features, a relatively specific set of radiographic characteristics can be defined to assist in plain-film diagnosis and to help refine the differential diagnosis of similar-appearing lesions.

Diagnosis of focal bone lesions using neural networks.

RATIONALE AND OBJECTIVES: Use of a neural network to diagnose focal lesions of bone was evaluated. METHODS: Imaging features of 709 lesions were encoded into a predetermined database. Data were divided into four groups and were analyzed using cross-validation by a two-layer feed-forward neural network. RESULTS: The lesions comprised 43 different pathologic diagnoses. Overall, the network was 85% accurate in distinguishing benign from malignant lesions. With a differential list of five diagnoses, the list was internally consistent regarding benign and malignant lesions 81.9% of the time. The network correctly diagnosed 56% of the lesions by pathologic diagnosis as its first choice. It included the correct diagnosis 71.8% of the time in a differential list of three diagnoses and 87.3% of the time in a differential list of nine diagnoses. CONCLUSION: Although not yet adequate for clinical use, neural network diagnosis of bone lesions is in its infancy and has important implications for the future analysis of focal bone lesions.

Quantitative analysis of the plain radiographic appearance of central chondrosarcoma of bone.

RATIONALE AND OBJECTIVE: To quantitate radiographic features that distinguish the plain radiographic appearance of central chondrosarcoma from other solitary bone lesions. MATERIALS AND METHODS: Seven hundred nine cases of focal bone lesions, including 37 central chondrosarcomas, were analyzed according to demographic, anatomic, and plain radiographic features. Vector analysis of groups of features was performed to determine those that are most sensitive and specific for the appearance of central chondrosarcoma in contrast with other lesions in the data base. RESULTS: The most specific appearance of long bone central chondrosarcomas was a lesion within the medullary cavity with geographic destruction, containing calcified matrix and a diameter greater than 5.9 cm, or arising within the proximal metaphysis or diaphysis. These features all are present in 9 (39%) of the 23 long bone central chondrosarcomas and in less than 1% of other lesions. In flat bone lesions, calcified matrix and either geographic bone destruction, medullary location, or enlargement of the host bone were 100% specific but of low sensitivity, identifying 7 (50%), 7 (50%), and 6 (41%) of the 14 flat bone chondrosarcomas, respectively. Inclusion of calcified matrix in the description is essential to make the criteria specific but excludes several of the most aggressive long bone chondrosarcomas. The vector analysis-generated differential diagnosis include osteosarcoma, fibrous dysplasia, unicameral bone cysts, aneurysmal bone cysts, malignant fibrous histiocytoma, and Ewing sarcoma. CONCLUSIONS: A relatively specific set of radiographic features can be defined to assist in plain film diagnosis of central chondrosarcoma, but there are many chondrosarcomas that fall outside these parameters. Thus, while not sufficiently sensitive to allow accurate plain film diagnosis in all cases, these criteria serve as an improved foundation for differential diagnosis.

Quantitative analysis of the plain radiographic appearance of aneurysmal bone cysts.

RATIONAL AND OBJECTIVES: To quantitate radiographic features that distinguish the plain radiographic appearance of aneurysmal bone cyst (ABC) from other solitary lesions of bone. MATERIALS AND METHODS: Seven hundred nine cases of focal bone lesions, including 32 ABCs were analyzed according to demographic, anatomic, and plain radiographic features. Vector analysis of groups of features was performed to determine those that are most sensitive and specific for the appearance of ABC in contrast with other lesions in the data base. RESULTS: Aneurysmal bone cysts most consistently are medullary-based, either eccentric or centric (94%), show lysis (100%), cortical thinning (97%), enlargement of the host bone (100%), and geographic bone destruction (94%). They have well-defined edges (84%), no fallen fragment (100%), no evidence of periosteal reaction (75%), and no visible matrix (91%). Although they typically occur in the metadiaphysis of long bones, the anatomic location and demographic data did not significantly affect the sensitivity or specificity for detection of ABCs. The vector analysis-generated differential diagnoses include giant cell tumor, unicameral bone cyst, nonossifying fibroma, enchondroma, and fibrous dysplasia as the major lesions.

Prospective optimization of patient selection for emergency cranial computed tomography: univariate and multivariate analyses.

RATIONALE AND OBJECTIVES: To determine if the clinical variables that are important for selecting patients for emergency cranial computed tomography (CT) are population dependent. METHODS: Prior to obtaining scans, physicians working in an emergency department in a level II trauma center completed a form describing the indication for the CT examination. These data were matched to the CT scan results and analyzed statistically using univariate and multivariate methods. These results were compared with a prior study at a level I trauma center. RESULTS: Of 551 patients having cranial CT, neurologic examination was positive in 340 and CT scan was positive in 122. The neurologic examination correlated strongly with the results of the CT scan (P < 0.00001). In this patient population, the most important clinical predictors of 17 abnormal CT scans from the 211 patients without positive neurologic examinations were seizure and a history of neoplasm. These high-yield variables differ from our prior retrospective study in which intoxication and amnesia were the important predictors in patients with negative examinations. The difference in predictors between the populations most likely results from different prevalences of trauma and ischemic disease. CONCLUSIONS: Abnormal neurologic examination is the most important criterion available to select patients for emergency cranial CT. Other variables (eg, seizure, amnesia, intoxication, and history of neoplasm) that help select patients without neurologic findings appear to be population dependent.

Quantitative analysis of the plain radiographic appearance of unicameral bone cysts.

RATIONALE AND OBJECTIVES: The authors determine the features that distinguish the radiographic appearance of unicameral bone cysts (UBC) from other solitary lesions of bone and to develop an ordered differential of similar-appearing lesions. MATERIALS AND METHODS: Seven hundred nine cases of solitary bone lesions, including 40 UBCs, were analyzed according to demographic, anatomic, and plain radiographic features. Vector analysis of both classic and new groups of features was performed to determine the sensitivity and specificity of radiographs for UBC and an ordered differential based on radiographic features. RESULTS: The features of the UBCs in this study compared favorably with those in the literature. The male:female ratio was 3.3:1, with an average age of 15 +/- 13 years. Age ranges and lesion diameters were similar for both sexes. Thirty-three of the 40 (83%) UBCs were in long bones, and seven were in the pelvis or calcaneus. All 40 UBCs were geographic, medullary, and lytic. None had an associated soft-tissue mass. Fifty-five percent had pathologic fractures, and 10% had fallen fragment signs. Ninety-eight percent had no cortical break, and 88% had well-defined margins. CONCLUSION: Classic descriptions of UBCs can be refined to improve sensitivity without sacrificing specificity. The best vector in this study had a sensitivity of 80% and a specificity of 93% and included these radiographic features: metaphyseal, diaphyseal, or flat bone location, geographic, lytic, medullary-based, no matrix, no satellite lesions, no subarticular extension, no soft-tissue mass, no cortical break, and central location in long bones. An ordered differential diagnosis, starting with the most likely lesion, includes enchondroma, aneurysmal bone cyst, fibrous dysplasia, nonossifying fibroma, Brodie abscess, and chondrosarcoma.

Quantitative analysis of the plain radiographic appearance of eosinophilic granuloma.

RATIONALE AND OBJECTIVES: To quantitate features that distinguish the plain radiographic appearance of eosinophilic granuloma (EG) from other solitary lesions of bone. MATERIALS AND METHODS: Seven hundred nine focal bone lesions, including 26 EGs, were analyzed according to demographic, anatomic, and plain radiographic features. Vector analysis of groups of features was performed to determine those that are most sensitive and specific for the appearance of EG in contrast to other lesions in the data base. RESULTS: The radiographic appearance of EGs was most consistently that of a medullary based lytic lesion (100%) with geographic destruction (76.9%), lobular contour (73.1%), and well-defined edges (73.1%). Long bone lesions showed these features more frequently than EGs in other locations. Periosteal reaction was visible in all long bone lesions but in only one nonlong bone lesion (5.9%). Characterization of EG in long bones as a lytic, medullary-based metaphyseal or diaphyseal lesion with geographic destruction, lobular contours, periosteal reaction, no matrix, and no subarticular extension showed a sensitivity of 55.6% of EG and prevalence of 22.7%. The vector analysis-generated differential diagnoses include unicameral bone cyst, aneurysmal bone cyst, giant cell tumor, Brodie's abscess, enchondroma, chondrosarcoma, and malignant fibrous histiocytoma. CONCLUSIONS: The radiographic appearance of EG is relatively nonspecific but, using vector analysis, can be better elucidated than in current textbook descriptions.