Pathology and genetics of tumors of soft tissue and bone

Autograft is considered ideal for grafting procedures, providing osteoinductive growth factors, osteogenic cells, and an osteoconductive scaffold. Limitations, however, exist regarding donor site morbidity and graft availability. Allograft on the other hand, posses the risk of disease transmission. Synthetic graft substitutes lack osteoinductive or osteogenic properties. Composite grafts combine scaffolding properties with biological elements to stimulate cell proliferation and differentiation and eventually osteogenesis. We present here an overview of bone grafts and graft substitutes available for clinical applications.

Bone substitutes: an update.

People with diabetes are more likely to be hospitalized and to have longer durations of hospital stay than those without diabetes. A recent survey estimated that 22% of all hospital inpatient days were incurred by people with diabetes and that hospital inpatient care accounted for half of the 174 billion USD total U.S. medical expenditures for this disease (1). These findings are due, in part, to the continued expansion of the worldwide epidemic of type 2 diabetes. In the U.S. alone, there are ∼1.6 million new cases of diabetes each year, with an over all prevalence of 23.6 million people (7.8% of the population, with one-fourth of the cases remaining undiagnosed). An additional 57 million American adults are at high risk for type 2 diabetes (2). Although the costs of illness-related stress hyperglycemia are not known, they are likely to be considerable in light of the poor prognosis of such patients (3–6).

There is substantial observational evidence linking hyperglycemia in hospitalized patients (with or without diabetes) to poor outcomes. Cohort studies as well as a few early randomized controlled trials (RCTs) have suggested that intensive treatment of hyperglycemia improved hospital outcomes (5–8). In 2004, this evidence led the American College of Endocrinology (ACE) and the American Association of Clinical Endocrinologists (AACE), in collaboration with the American Diabetes Association (ADA) and other medical organizations, to develop recommendations for treatment of inpatient hyperglycemia (9). In 2005, the ADA added recommendations for treatment of hyperglycemia in the hospitalto itsannual Standards of Medical Care (10). Recommendations from the ACE and the ADA generally endorsed tight glycemic control in critical care units. For patients in general medical and surgical units, where RCT evidence regarding treatment targets was lacking, glycemic goals similar to those advised for outpatients were advocated (9, …

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American Association of Clinical Endocrinologists and American Diabetes Association Consensus Statement on Inpatient Glycemic Control

Tumors and tumorous conditions of the bones and joints

A panel of experts representing the Histiocyte Society has suggested that the original terminology for the various syndromes in the “histiocytosis X” category (eosinophilic granuloma, Letterer-Siwe disease, and Hand-Christian-Schuller syndrome) be discarded and replaced by the term Langerhans cell histiocytosis (LCH) (Chu et al. 1987). This is because the proliferative cell which causes these entities is known to be the Langerhans cell.

https://acsjournals.onlinelibrary.wiley.com/doi/pdf/10.1002/%28SICI%291097-0142%2819990515%2985%3A10%3C2278%3A%3AAID-CNCR25%3E3.0.CO%3B2-U

Langerhans cell histiocytosis: diagnosis, natural history, management, and outcome.

Aneurysmal bone cyst (ABC) is a nonneoplastic expansile bone lesion that mainly affects children and young adults. Primary ABC is relatively rare, with an incidence one half that of giant cell tumor of bone. In 238 patients with ABC studied in the Mayo Clinic files, more than 80% of the lesions were in long bones, flat bones, or the spinal column. Of the lesions initially treated at the Mayo Clinic, 95% were typical ABC; the rest were "solid" variants. Except for the absence of obvious cavernous channels and spaces, there was no significant histologic difference between solid variant and typical ABC. Radiographically, ABC is an eccentric expansile lesion commonly located at the metaphysis of long bones. Computed tomography and magnetic resonance imaging may show multiple internal septations or fluid levels. In the 153 patients treated, 19% had recurrence after curettage (intralesional excision). Recurrence was most common during the first 2 postoperative years.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/1097-0142%2819920615%2969%3A12%3C2921%3A%3AAID-CNCR2820691210%3E3.0.CO%3B2-E

Aneurysmal bone cyst. A clinicopathologic study of 238 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%. Cancer 57:2444–2453, 1986.

https://acsjournals.onlinelibrary.wiley.com/doi/pdf/10.1002/1097-0142%2819860615%2957%3A12%3C2444%3A%3AAID-CNCR2820571233%3E3.0.CO%3B2-K

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

A total of 422 patients with malignant lymphoma of bone who were seen at the Mayo Clinic from 1907 through 1982 were placed into four major groups based on stage of disease. There was one group with primary lymphoma of bone, one group with multifocal osseous lymphoma, and two groups with lymphoma of bone and nodal or soft tissue (or both) disease. The last-mentioned two groups were separated on the basis of time of onset of osseous lymphoma in relation to the nonosseous disease. The stage of disease was the single most important prognostic indicator of overall survival in malignant lymphoma of bone. The 5- and 10-year survival rates were, respectively, 58% and 53% for patients with primary bone lymphoma, 22% and 12.5% for patients with bone and nodal or soft tissue (or both) disease, and 42% and 35% for patients with multifocal osseous disease. Features having no significant prognostic value were sex of the patient, histologic grade of the lymphoma (according to the Working Formulation and the Kiel system), and presence of T-cell features or cleaved cells (or both). This study is not able to adequately address efficacy of treatment. In fact, treatment may be very important in outcome.

https://acsjournals.onlinelibrary.wiley.com/doi/pdf/10.1002/1097-0142%2819861215%2958%3A12%3C2646%3A%3AAID-CNCR2820581217%3E3.0.CO%3B2-U

Malignant lymphoma of bone

Background. Langerhans' cell histiocytosis (LCH) of bone is a disorder of histiocytic proliferation with variable and often unpredictable behavior.



Method. The authors evaluated the clinical and pathologic features of 263 patients (172 children, 91 adults) with biopsy-proven LCH examined during an 80-year period at the Mayo Clinic. Only patients with bone involvement pathologically and/or radiographically were included in the study. Clinical follow-up was available for 245 patients and ranged from 3 months to 50 years (mean, 12 years: median, 10 years). Chi-square tests were used to determine associations between age, gender, extent of osseous involvement, visceral disease, and pathologic features. Survival analyses were performed by univariate and multivariate Cox regression methods.



Results. Age at presentation ranged from 2 months to 71 years with a clear predominance in children. The most common presenting complaint was pain, often worse at night. The skull was the most frequent osseous site in children and adults. Diabetes insipidus was documented in 40 patients. Forty-four children developed skeletal recurrence and/or new bone lesions, 19 of whom had diabetes insipidus. Fourteen children and 3 adults died either directly or indirectly from LCH. One adult patient developed systemic amyloidosis. All but two of these pediatric patients were 3 years of age or younger at presentation. All children with hepatosplenomegaly (7 patients) and/or thrombocytopenia (9 patients) died. Nine of the 14 children who died presented initially with three or more bone lesions.



Conclusions. The clinical behavior of LCH of bone is often unpredictable; however, young age at diagnosis, hepatosplenomegaly, thrombocytopenia, and polyostotic (≥3 bones involved) disease are associated with a poor prognosis (P < 0.005). Recrudescence in children, but not in adults, strongly correlates with the presence of diabetes insipidus (P < 0.0005).

Langerhans' cell histiocytosis (histiocytosis X) of bone. A clinicopathologic analysis of 263 pediatric and adult cases.

The magnetic resonance (MR) imaging characteristics of bone tumors are described and the clinical utility of MR imaging in patient evaluation is reported. Fifty-two patients with skeletal lesions were examined with a Picker MR imager (0.15-T resistive magnet). Twenty-five patients had primary malignancies, seven had benign bone neoplasms, 15 had skeletal metastases, and five had neoplasm simulators. Forty-five patients had CT scans available for comparison. For demonstrating the extent of tumor in marrow, MR was superior to CT in 33% of cases, about equal to CT in 64%, and inferior to CT in 2%. For delineating the extent of tumor in soft tissue, MR was superior to CT in 38% of cases and about equal to CT in 62%. CT was superior in all cases for demonstrating calcific deposits and pathologic fractures. In four patients with metal prostheses or surgical clips, MR was superior to CT in documenting recurrent tumor because of artifactual degradation of the CT image. Direct sagittal and coronal images from MR permit accurate assessment of the relationship of tumor to adjacent normal structures, including the physis, joints, and neurovascular structures. MR is useful in the evaluation of bone tumors: it is of greatest value in evaluations of the peripheral skeleton, the medullary canal, soft tissues, and postoperative tumor recurrence. With a 0.15-T magnet, MR is less useful in the evaluation of the axial skeleton and cortical bone.

Thomas C. Shives

Papers

Aneurysmal bone cyst. A clinicopathologic study of 238 cases.

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

Malignant lymphoma of bone

Langerhans' cell histiocytosis (histiocytosis X) of bone. A clinicopathologic analysis of 263 pediatric and adult cases.

Bone tumors: magnetic resonance imaging versus computed tomography.