Faculty Bibliography

The clinical behavior of giant cell tumors (GCTs) is unpredictable. To gain insight into this tumor's biological behavior, matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) were studied. These substances play essential roles in wound healing and neoplastic invasion and metastasis. Paraffin-embedded tissue was collected from 18 cases of histologically benign GCT, with 17 treated by curettage and 1 by resection. Eight cases showed no recurrence after a minimum of 2.5 years, and 10 had local recurrence. One showed metastasis. Antibodies to MMP-9, MMP-2, TIMP-1, and TIMP-2 were applied by immunohistochemical methods. In all cases, MMP-9 was strongly expressed in giant cells predominantly in a diffuse pattern and was strong but focal in stromal cells. MMP-2 decorated stromal cells and giant cells heterogeneously. TIMP-1 was variably expressed in giant cells of the nonrecurrent cases and was strongly present in a diffuse or patchy distribution in the stromal cells in 6 of 8 cases. However, in 9 of 10 recurrent cases, TIMP-1 was expressed weakly by both giant and stromal cells. TIMP-2 was variably expressed in the giant cells of the nonrecurrent cases, but 6 of 8 nonrecurrent cases showed strong stromal cell positivity for TIMP-2. Weak staining for TIMP-2 was observed in 7 of 10 recurrent cases in the stromal cells and 9 of 10 recurrent cases in the giant cells. These results indicate that expression of MMPs and TIMPs differs in giant cells and stromal cells in the same tumor. More significantly, in contrast to the nonrecurrent giant cell tumors, there is an imbalance in the MMPs and TIMPs in the recurrent tumors with a net excess of MMPs. This unopposed expression of MMPs in GCTs may play a role in breakdown of extracellular matrix and tissue invasion. Finally, these markers may prove useful in predicting behavior in these tumors

A prospective study was performed to determine the reliability of analysis of intraoperative frozen sections for the identification of infection during 175 consecutive revision total joint arthroplasties (142 hip and thirty-three knee). The mean interval between the primary and the revision arthroplasty was 7.3 years (range, three months to twenty-three years). To reduce selections bias, tissue was obtained for frozen sections during all revisions in patients who did not have active drainage from the wound or a sinus tract. Of the 175 patients, twenty-three had at least five polymorphonuclear leukocytes per high-power field on analysis of the frozen sections and were considered to have an infection. Of these twenty-three, five had five to nine polymorphonuclear leukocytes per high-power field and eighteen had at least ten polymorphonuclear leukocytes per high-power field. The frozen sections for the remaining 152 patients were considered negative. On the basis of cultures of specimens obtained at the time of the revision operation, nineteen of the 175 patients were considered to have an infection. Of the 152 patients who had negative frozen sections, three were considered to have an infection on the basis of the results of the final cultures. Of the twenty-three patients who had positive frozen sections, sixteen were considered to have an infection on the basis of the results of the final cultures; all sixteen had frozen sections that had demonstrated at least ten polymorphonuclear leukocytes per high-power field. The sensitivity and specificity of the frozen sections were similar regardless of whether an index of five or ten polymorphonuclear leukocytes per high-power field was used. Analysis of the frozen sections had a sensitivity of 84 per cent for both indices, whereas the specificity was 96 per cent when the index was five polymorphonuclear leukocytes and 99 per cent when it was ten polymorphonuclear leukocytes. However, the positive predictive value of the frozen sections increased significantly (p < 0.05), from 70 to 89 per cent, when the index increased from five to ten polymorphonuclear leukocytes per high-power field. The negative predictive value of the frozen sections was 98 per cent for both indices. The current study suggests that it is valuable to obtain tissue for intraoperative frozen sections during revision hip and knee arthroplasty. At least ten polymorphonuclear leukocytes per high-power field was predictive of infection, while five to nine polymorphonuclear leukocytes per high-power field was not necessarily consistent with infection. Less than five polymorphonuclear leukocytes per high-power field reliably indicated the absence of infection

BACKGROUND: The proliferation index (PI) and vascular density (VD) in giant cell tumors (GCT) of bone were studied to assess then value as prognostic markers. METHODS: Formalin fixed, paraffin embedded tissue from 7 nonrecurrent (NR-GCT) and 13 recurrent (R-GCT) tumors were stained with MIB-1, a monoclonal antibody against Ki-67 (nuclear proliferation antigen), and QBEND-10, a monoclonal antibody against CD34 (endothelial antigen). A minimum of ten fields/case were analyzed on the SAMBA 4000 Image Analyzer. Only mononuclear cell nuclei were analyzed for MIB-1 staining. RESULTS: Mean values +/- 1 Standard deviation (SD) for PI (stained nuclear area/total nuclear area) were: NR-GCT, 10.98 +/- 3.70; R-GCT (initial presentation), 8.94 +/- 3.57; and R-GCT (first recurrence), 9.25 +/- 3.52. In addition, the mean PI +/- 1 SD for mononuclear round-ovoid cells was 8.71 +/- 3.47 and was 9.16 +/- 10 for mononuclear spindle cells. The mean values +/- 1 SD for VD (stained area/total area of structures) were: NR-GCT, 10.61 +/- 6.37; R-GCT (initial curettage), 9.40 +/- 4.94; and R-GCT, (first recurrence), 12.56 +/- 5.88. Comparing the means for PI and VD for both groups of tumors using Student's t test showed no statistically significant differences (P = 0.34). In one case of histologically benign GCT that metastasized to the lungs, the PI of the metastatic tissue was not significantly different from the primary tumor. CONCLUSIONS: This study presents evidence that the degree of tumor cell proliferation and vascularity are not useful parameters to predict the recurrence of GCT of bone and that there are no significant differences between the PI of mononuclear round-ovoid cells and mononuclear spindle cells

Sarcoma associated with bone infarct is rare, and only 41 well-documented cases have been published. We describe five additional patients, three women and two men, aged 39 to 57 years. The tumors involved the femur (three patients), tibia (one patient), and humerus (one patient). In three patients, the infarcts were idiopathic. Radiologic evidence of malignancy was found in all patients, and bone infarcts were suspected in four. Four of the patients had malignant fibrous histiocytoma and one an osteosarcoma. Histologically, bone infarcts were seen in all patients, but in three they were mostly replaced by tumor. Portions of intact infarcts were seen adjacent to the tumor, indicating that they had preceded the development of the sarcoma. No hypercellular or atypical reparative tissue was found in the infarcted bones or in three additional uncomplicated infarcts studied from the same patients. The pathogenesis of sarcoma arising in bone infarct is unknown. The prognosis is poor; four of our five patients died within 2 years.

BACKGROUND: Surgical implantation of the intraocular sustained-release ganciclovir device is a safe and effective treatment for cytomegalovirus (CMV) retinitis. Previous histopathologic studies on eyes containing such implants have been limited by the necessity of removing the device before processing. Microtome sectioning of hard plastics within paraffin-embedded blocks is infeasible, and the anatomic relations of implant to eye are destroyed. METHODS: The authors studied four eyes from three patients who had undergone implant insertion. Globes with implants in place were fixed in neutral 10% formation, embedded in methylmethacrylate, sectioned on a special microtome, and stained with hematoxylin-eosin. RESULTS: After methacrylate embedding, the precise anatomic relations of the implant to the neighboring uveoscleral coats were preserved. In two eyes, the suture tab of the implant protruded through the sclera, exiting subconjunctivally. In two eyes, the implant was totally intravitreal. In all patients, the device was supported by fibrous tissue which emanated from a surgical coloboma of the pars plana ciliaris. Focal granulomatous inflammation adjoined suture and implant materials but no other inflammation or deleterious effects on the ocular structures were noted. CONCLUSION: This report is the first to document the intraocular histopathology of the ganciclovir implant. The subconjunctival location, enhancing the potential for endophthalmitis, may be avoided by trimming of the suture tab close to the anchoring suture and not tying it too tightly. Methylmethacrylate embedding is a useful technique for preserving the microanatomy of intraocular implants

This article describes 11 cases of myxoid chondrosarcoma (MCS), with 10 arising in soft tissues and one developing in bone. Most of the tumors (six) were located in the lower extremities. Two lesions developed in the fingers, a previously unreported location for MCS. Four cases showed secondary bone destruction, which is a rare feature of this tumor. S100 protein was expressed by tumor cells in all the specimens. Four out of eight tumors studied by electron microscopy contained intracisternal microtubular structures. Two tumors showed areas of spindle cell proliferation that merged with the areas of typical myxoid pattern. The cells in these areas had fibroblastic/myofibroblastic features by electron microscopy and were found to express cytokeratin by immunohistochemistry. The concomitant expression of cytokeratin and S100 protein in the spindle cells suggests that they represent a less differentiated cartilaginous component with unusual features. The clinical significance of the presence of such spindle cell areas presently remains unknown. Although myxoid chondrosarcoma is a slow-growing tumor, it has a high potential for metastases. Four of 11 patients in this series developed metastases.

Osteosarcoma is a malignant, mesenchymal, osteoid, and bone-forming tumor [1-3]. In most cases, typical radiographic features clearly illustrate the aggressive bone-forming nature of the lesion. These features include long-bone metaphyseal location, mixed areas of lysis and sclerosis, cortical destruction, periosteal new bone, and soft-tissue mass. However, numerous factors contribute to misleading radiographic patterns of osteosarcoma. They include histologic low-grade, lytic, or minimally sclerotic lesions, early detection, confinement to the intramedullary canal, benign-appearing periosteal reaction, rare intraosseous locations (subchondral, diaphyseal, intracortical), and rare skeletal sites (e.g., soft tissues, skull, ribs, tarsal bones). Secondary osteosarcomas, such as those arising from infarcts or fibrous dysplasia, may also produce a confusing radiologic picture. The purpose of this pictorial essay is to illustrate cases of osteosarcoma that proved to be difficult diagnostic dilemmas because of their subtle, rare, or misleading plain film features.