Systemic mast cell disease. Analysis of 58 cases and literature review.

Based on study of 58 histologically proved cases of SMCD, we believe that the prognosis of most SMCD patients can be anticipated at the time of initial diagnosis by using 5 independent significant predictors developed in a multivariate model. Our study confirms the significance of several previously reported poor prognostic factors: absence of skin involvement and the presence of hepatosplenomegaly, cytologic atypia, and a hypercellular bone marrow. However, in contrast to previous reports we did not find a uniform correlation between the presence or absence of skin involvement and prognosis. The observation that anemia was strongly related to so many prognostic variables may be due to the number of patients in our study with associated hematologic disorders. Alternatively, this evidence of ineffective erythropoiesis may support the concept that SMCD is a myeloid stem cell disorder and frequently affects other hematopoietic cell lines. The observation that death occurs within the first 3 years in most fatal cases of SMCD suggests that these patients should be followed carefully for this interval after initial diagnosis, especially if poor prognostic features are present. Currently there is no curative therapy for SMCD.

Three-year controlled, randomized trial of the effect of dose-specified loading and strengthening exercises on bone mineral density of spine and femur in nonathletic, physically active women.

The objectives of this study were to evaluate (1) the effect of spinal muscle strengthening by loading exercises on the bone mineral density (BMD) of the spine, and (2) the effect of upper extremity loading exercises on the BMD of the midradius and femur in healthy, premenopausal women. The study design was a randomized, controlled trial of 3 years' duration. Ninety-six healthy, premenopausal, white women aged 30-40 years participated; 67 completed the study. All subjects were in good health (normal menses) and were active, but not athletic (that is, not involved in a regular sport activity). Subjects were randomized to an exercise or control group. The exercise group performed a supervised, non-strenuous, weight-lifting exercise program. Exercise performance was supervised once a week at the medical facility. In addition, the subjects performed the exercises twice a week on their own. Dietary calcium intake was to be maintained at 1,500 mg/day in both groups. Bone density was measured at the lumbar spine and hip with dual-energy X-ray absorptiometry at 0, 1, and 3 years. BMD of the midradius was measured with single photon absorptiometry. Measurements of muscle strength were obtained at baseline and every 3 months for 3 years. Maximal oxygen uptake was measured, and the level of physical activity was recorded. Compliance with the exercise program was excellent during the first year of the study, but decreased thereafter. At the end of 3 years, subject withdrawal was about 34% from the exercise group and about 22% from the control group (total subject withdrawal was about 30%). Muscle strength in the exercise group increased significantly at all involved skeletal sites (p values all < 0.001). There was a modest positive correlation between the BMD of Ward's triangle with spinal flexor strength (r = 0.32, p = 0.008) and with grip strength (r = 0.38, p = 0.001). Comparing study groups, we found no significant effect of the loading and nonstrenuous strengthening exercises in the exercise group or free physical activity group (our control group) on BMD at the spine, hip, or midradius measurement sites. In active, but not athletic premenopausal women, additional moderate weight-lifting exercises showed no significant effect on BMD.

Bizarre parosteal osteochondromatous proliferation of bone (Nora's lesion).

Bizarre parosteal osteochondromatous proliferation was first described in 1983, when Nora et al. reported 35 examples of a proliferative lesion involving the small bones of the hands and, less often, the feet. No examples involving the large bones were reported. We present 65 cases of this condition, five from the Mayo Clinic files and 60 from our consultation files, including 34 females and 31 males; patients' ages ranged from 8 to 73 years (average, 33.9 years). Thirty-six lesions involved the hands, 10 the feet, 17 the long bones, one the skull, and one an unknown site. The long bones involved were the radius (three lesions), ulna (six), fibula (two), femur (three), tibia (two), and humerus (one lesion). Roentgenograms typically showed a heavily calcific mass attached to the underlying cortex and having a broad base. Histologically, a large amount of hypercellular cartilage showed maturation to trabecular bone, which frequently contained spindle cells in the intertrabecular spaces, an appearance that could lead to a mistaken diagnosis of parosteal osteosarcoma. A helpful feature was the distinct blue tinctorial characteristic of the bone in the lesion. Follow-up information was available for 40 patients; approximately 55% had a recurrence. No metastasis had been reported in any of the 65 cases. Bizarre parosteal osteochondromatous proliferations are a form of heterotopic ossification and should not be mistaken for chondrosarcoma or osteosarcoma.

Giant cell reaction (giant cell reparative granuloma) of the small bones of the hands and feet.

Giant cell reactions (giant cell reparative granulomas) are uncommon lesions that predominantly involve the small bones of the hands and feet. In 1980, only 13 cases of this entity had been described. Three patients with similar giant cell reactions were identified from the Mayo Clinic files, and an additional 27 patients were collected from the consultation files of one of the authors. Clinical information and follow-up data for these 30 patients suggest that the biologic behavior and, therefore, treatment of giant cell reactions differ from those of true giant cell tumors in the small bones of the hands and feet.

Osteochondromyxoma of bone: a congenital tumor associated with lentigines and other unusual disorders.

This article describes the clinical and pathologic features of four unusual bone tumors. Three were congenital or most likely so; the fourth, detected at age 1 year, was probably of considerable duration. The patients, three boys and one girl, each presented with a painless mass. Two had the Carney complex, a familial lentiginous and multiorgan tumorous syndrome; another probably had this disorder; the fourth did not show it, but his mother did. The tumors occurred in the nasal region (n = 2) and the diaphysis of the tibia and radius (n = 1 each). Roentgenographically, three had benign characteristics; the fourth, malignant features. Grossly, the tumors were gelatinous, cartilaginous. and bony. Microscopically, they featured benign-appearing polymorphic cells with few division figures arranged in sheets and lobules set in a myxomatous, cartilaginous, osseous, and hyaline fibrous matrix. Cellularity was low to moderate. The tumors eroded bone, one infiltrated between bony trabeculae, and three had soft tissue extension. Complete resection of one tumor was curative; incomplete excision of two tumors resulted in local recurrence (intracranial and fatal) in one and persistence in the other; the fourth tumor remains under observation after biopsy. No tumor metastasized.

Erosive spondyloarthropathy in long-term dialysis patients: relationship to severe hyperparathyroidism.

We describe the development of a destructive, erosive spondyloarthropathy in three long-term dialysis patients (mean duration of dialysis, 96 months). In all three patients, the lesions caused symptomatic vertebral pain and developed during a period of only a few months. All patients had extremely elevated levels of immunoreactive parathyroid hormone, and two patients had evidence of severe hyperparathyroidism on bone biopsy specimens. Two patients who underwent subtotal parathyroidectomy had rapid relief of symptoms and no further radiographic evidence of progression of the spondyloarthropathy. The third patient refused subtotal parathyroidectomy and had pronounced progression of the destructive spondyloarthropathy in the cervical spine. The limited experience of others, along with our currently reported findings, strongly suggests that hyperparathyroidism plays a major role in the development of this disorder. Erosive spondyloarthropathy is increasingly recognized in long-term dialysis patients and may be a unique clinical and radiographic manifestation of severe hyperparathyroidism in this population.

Chondrosarcoma in Maffucci's syndrome.

Nine patients with Maffucci's syndrome were seen at our institution; chondrosarcoma developed in five. On the basis of the cases of these patients and those reported in the English literature since 1973, we determined that the incidence of chondrosarcoma in patients with Maffucci's syndrome is 17.8 per cent.

Giant cell tumor of the small bones of the hands and feet.

Giant cell tumor of bone uncommonly occurs in the bones of the hands and feet. Previous reports suggested that the giant cell tumors in these locations occur in younger patients, are more commonly multifocal, and are associated with a higher risk for local recurrence and pulmonary metastasis than those at the ends of the long bones. A review of our experience with 43 patients having giant cell tumors in small bones is presented. Radiologic and histologic comparison is made with aneurysmal bone cyst and giant cell reparative granuloma (giant cell lesion) of the small bones. Followup information indicates that giant cell tumors of the small bones do occur in younger patients and appear to have a greater propensity for local recurrence than those of the long bones. As the lesions may be multifocal, a patient with documented giant cell tumor of the small bones should have a skeletal survey to search for other lesions.

The elimination of grids during intensified fluoroscopy and photofluoro spot imaging.

Grids can significantly increase the contrast of diagnostic radiologic images, but they increase the dose to the patient and staff by a factor of two or more. Image quality with and without grids for fluoroscopic and photofluoro spot imaging of lower gastrointestinal studies has been examined. The authors show that dose reductions between one-third and one-half can be obtained with little or no degradation in contrast and diagnostic image quality if grids are not used for gastrointestinal examinations involving image intensifiers.

Insufficiency fractures of the sacrum.

Insufficiency stress fractures may occur in the sacrum after radiation therapy or secondary to postmenopausal or steroid-induced osteoporosis. These fractures are often either overlooked or confused both clinically and radiographically with metastatic disease. Findings on plain films and conventional tomograms are often subtle. Radionuclide bone scans show a characteristic distribution of increased uptake. Computed tomography is the definitive technique for demonstrating the fractures.

Bone sarcomas associated with Ollier's disease.

Of 55 patients with Ollier's disease seen at the Mayo Clinic between 1907 and 1985, 16 had malignant bone neoplasms: 12 chondrosarcomas, two dedifferentiated chondrosarcomas, one chordoma, and one osteosarcoma. One patient had a chondrosarcoma in two different bones. These findings suggest that approximately 30% of patients with Ollier's disease will develop a malignant bone neoplasm, most probably chondrosarcoma. The prognosis for most patients is good. Five of the 16 patients survived more than 13 years after treatment.

Aluminum toxicity in patients undergoing dialysis: radiographic findings and prediction of bone biopsy results.

Aluminum toxicity in patients undergoing dialysis currently requires bone biopsy for definitive diagnosis. The authors retrospectively reviewed clinical, histologic, and radiographic findings in 63 patients undergoing dialysis. In 30 patients, biopsy specimens were negative for aluminum toxicity, and in 33 patients, specimens were positive. In 21 of the 30 patients who had a negative biopsy specimen, absence of aluminum toxicity could be predicted by a high immunoreactive parathyroid hormone level (greater than 2,000 microliter Eq/ml [2,210 pM]) and fewer than three fractures, by the presence of osteosclerosis on radiographs, or if serum aluminum levels were less than 30 ng/ml. None of the patients who had a positive biopsy specimen met these criteria. In 18 of 33 patients who had a positive biopsy specimen, aluminum toxicity could be predicted by a low immunoreactive parathyroid hormone level (less than 500 microliter Eq/ml [553 pM]) and more than three fractures, or if serum aluminum levels were greater than 300 ng/ml. None of the patients who had a negative biopsy specimen met these criteria. Thus, based on the criteria identified, the aluminum status of 62% of these patients would have been correctly diagnosed.

Mesenchymal chondrosarcoma of bone and soft tissue. A review of 111 cases.

A series of 111 mesenchymal chondrosarcomas was reviewed. The ages of the patients ranged from 5 to 74 years, and approximately 60% of them were in the second and third decades of life. There was no significant sex predilection. Seventy-two tumors, including 5 that involved multiple skeletal sites, arose in bone. Thirty-eight tumors were found in extraskeletal sites. At initial diagnosis, multifocal involvement, both in bone and in soft tissue, was observed in one case. Roentgenographically, the lesions in bone frequently resembled ordinary chondrosarcomas, showing osteolytic and destructive appearances with stippled calcification. Tumors in extraskeletal sites were almost always identified as calcified masses. Histologically, a combination of cellular zones composed of undifferentiated small cells and chondroid zones typically presented a bimorphic appearance that was virtually pathognomonic in most cases. Ablative surgical treatment seemed to be the procedure of choice. The value of irradiation or chemotherapy (or both) was difficult to assess in the current study. Prognosis for patients with mesenchymal chondrosarcoma is usually poor, and long-term follow-up is necessary. In a group of 23 patients from the Mayo Clinic, the 5-year survival rate was 54.6% and the 10-year survival rate was 27.3%.

High grade surface osteosarcoma: a clinicopathologic study of 46 cases.

BACKGROUND: High grade surface osteosarcoma is a rare subtype of osteosarcoma arising on the surface of bone, accounting for only 8.9% of surface osteosarcomas at the study institution. METHODS: This study reviews 46 cases of high grade surface osteosarcoma, comprised of 13 cases from the Mayo Clinic files and 33 from the authors' files. Histologic features were reviewed in all cases, and radiographs were reviewed in 29 cases. RESULTS: There was a definite male predominance, and 70% of the patients were in the second and third decades of life. Forty-four of the 46 patients had lesions involving the long bones, the most common site being the midportion of the femur. Radiographically, the majority of lesions showed dense to moderate mineralization with a fluffy, immature appearance. Radiating spicules of bone perpendicular to the long axis of the bone, characteristic of periosteal osteosarcoma, were sparse. Histologic findings were identical to those of conventional osteosarcoma. Overall, survival at 5 years was 46.1%. Statistical analysis revealed that marginal excision was associated with an increased risk of local recurrence and that the patients with Broders Grade 3 tumors had a better prognosis than those with Grade 4 tumors. A good response to chemotherapy was associated with better clinical outcome. CONCLUSIONS: High grade surface osteosarcoma is a rare subtype of surface osteoscarcoma that has a prognosis similar to that of conventional osteosarcoma, in contrast to the more common type of osteosarcoma arising on the surface of bone. Wide excision and effective systemic chemotherapy are associated with better clinical results.

Radiographic features of Ewing's sarcoma of the bones of the hands and feet.

The radiographic features of Ewing's sarcoma of the bones of the hands and feet are reviewed utilizing cases obtained from the Mayo Clinic patient files and the consultation files of Drs. D.C. Dahlin and K.K. Unni. This series consists of a total of 43 cases of pathologically proven Ewing's sarcoma involving the small bones of the hands and feet. The classic radiographic features of Ewing's sarcoma in the long bones, including lytic, permeative destruction, aggressive periosteal reaction, cortical violation, and a soft tissue mass, are also seen in the bones of the hands and feet, with similar frequency. These classic features are most commonly present in lesions affecting the short tubular bones. Lesions affecting the tarsal bones more often demonstrate atypical radiographic features. These atypical radiographic appearances may play a role in the reported delay in diagnosis of Ewing's sarcoma within the tarsal bones.

Comparison of mammography and transillumination light scanning in the detection of breast lesions.

A prospective study was done involving 822 women who had both film screen mammography and a breast transillumination light scan examination. The study population was not randomized; a modified phase-2 study was done. Mammography was superior for detecting malignancy: of the 67 pathologically proved breast cancers, 64 (95.5%) were detected by mammography and 45 (67.2%) were detected by transillumination. Biopsy revealed that 74 patients had benign lesions. In this group of patients, the false-positive rate was 12.2% for light scanning and 79.7% for mammography; however, 117 other patients had false-positive light scans.

Significance of systemic mast cell disease with associated hematologic disorders.

A clinical and hematopathologic review of 66 patients with systemic mast cell disease (SMCD) was undertaken to investigate the frequency and the clinical significance of associated hematologic disorders. Twenty-two patients were found to have a second hematologic disorder, 19 of which involved the myeloid cells (ten dysmyelopoietic syndromes, five myeloproliferative disorders, three acute nonlymphocytic leukemias, and one chronic neutropenia), and three of which involved the lymphoid cells (three malignant lymphomas). A chromosome analysis of the bone marrow revealed abnormalities characteristic of neoplastic myeloid disorders in four patients. Five-year survival for patients with hematologic disorders was 28% compared with 61% for other SMCD patients (P = 0.004). Patients with hematologic disorders differed significantly from other SMCD patients in that they were about 7 years older (P = 0.039), and they presented more commonly with anemia (P less than 0.001) and constitutional symptoms (P = 0.007). These patients also had less frequent skin symptoms (P = 0.003) and urticaria pigmentosa (P = 0.018). By definition, patients with hematologic disorders had a greater percent of hematopoiesis (P less than 0.001) and decreased fat cells (P = 0.011) on bone marrow biopsies. A multivariate model demonstrated that the following independent variables were associated with the presence of hematologic disorders: low hemoglobin (P = 0.001), the absence of hepatomegaly (P = 0.016), high leukocyte count (P = 0.021), and the presence of pathologic fractures (P = 0.051). The frequent coexistence of SMCD with dysplastic and neoplastic disorders of myeloid cells is consistent with the concept that SMCD itself is a disorder of myeloid cells and that the mast cell may be myeloid in origin.

Chondrosarcoma of small bones of the hands and feet.

BACKGROUND: Cartilaginous tumors of the hands and feet are not uncommon. Most are enchondromas, but they tend to show high cellularity, enlargement of nuclei, and many double-nucleated cells. Hence, differentiation between a benign lesion and chondrosarcoma may be difficult. METHODS: The files of patients treated at the Mayo Clinic and the consultation files were reviewed for examples of chondrosarcoma of small bones of the hands and feet. Histologic features and clinical charts were reviewed in all cases, and radiographs were reviewed in 111 cases. RESULTS: Seventy-five lesions involved the feet and 88 involved the hands. Bones of the fifth finger and the calcaneus were the most common sites of involvement. Nineteen tumors were secondary. Of the 104 intramedullary lesions studied radiologically, 96 showed cortical destruction, 83 a soft tissue mass, and 52 a permeative lytic pattern. Histologically, soft tissue extension and permeation of preexisting bone indicated malignant disease. One hundred sixteen tumors were Grade 1, 44 were Grade 2, and 3 were Grade 3. Of the 12 patients with distant metastasis from chondrosarcoma, 7 died of disease. Chondrosarcomas of the calcaneus and the talus were more likely to metastasize. CONCLUSIONS: Chondrosarcoma of small bones of the hands and feet has the potential to be fatal.