Fibromatoses of the extremities: clinicopathologic study of 36 cases.

BACKGROUND AND OBJECTIVES: Fibromatoses of the extremities are rare and often recalcitrant to treatment. We evaluated the clinical and pathologic features of a group of extremity fibromatoses treated by surgical excision with or without adjuvant therapy to determine if any clinical or pathologic parameters were predictive of clinical outcome. METHODS: Thirty-six extremity fibromatoses were evaluated. A number of clinical and histologic features were correlated with risk of local recurrence. RESULTS: The cohort included 19 females and 17 males with ages ranging from 11-72 years (mean: 35 years), with 12 tumors of the upper and 24 tumors of the lower extremity. Tumors ranged in size from 1.5-15.5 cm (mean: 7.5 cm).Histologically, 26 were infiltrative, 3 had pushing borders and 7 had both. Mitotic counts ranged from 0-5/50 high-power fields (mean: 0.74). Surgical margins were positive in 22 cases. Seventeen patients were treated with postoperative adjuvant therapy including radiation therapy and tamoxifen. Follow-up information was available in 34 cases (from 1-202 months; mean: 83 months). Nineteen patients (56%) had recurrences, including 11 with multiple recurrences (range to first recurrence: 5-61 months; mean 23 months). Seventy-one percent of patients with a positive surgical margin and clinical follow-up had a local recurrence, compared to 31%with a negative surgical margin (P < 0.05). None of the other clinical or histologic parameters correlated with the risk for local recurrence. CONCLUSIONS: Local control in fibromatoses of the extremities remains problematic. Aside from positive surgical margins, none of the other clinical or histologic parameters evaluated in this study were useful in predicting the risk of local recurrence.

LCC15-MB: a vimentin-positive human breast cancer cell line from a femoral bone metastasis.

The LCC15-MB cell line was established from a femoral bone metastasis that arose in a 29-year-old woman initially diagnosed with an infiltrating ductal mammary adenocarcinoma. The tumor had a relatively high (8%) S-phase fraction and 1/23 positive lymph nodes (LN). Both the primary tumor and LN metastasis were positive for estrogen receptor (ER) and progesterone receptor (PgR), but lacked erbB2 expression. Approximately one year later, the patient presented with a 0.8 cm comedo-type intraductal mammary adenocarcinoma in the left breast that was negative for ER and PgR, but positive for erbB2. Thirty-five months after the initial diagnosis she was treated for acute skeletal metastasis, and stabilized with a hip replacement. At this time, tumor cells were removed from surplus involved bone, inoculated into cell culture, and developed into the LCC 15-MB cell line. The bone metastasis was a poorly differentiated adenocarcinoma lacking ER, PgR, and erbB2, characteristics shared by the LCC15-MB cells, although ER can be re-expressed by treatment of the LCC15-MB cells for 5 days with 75 microM 5-aza-2'-deoxycytidine. The LCC15-MB cell line is tumorigenic when implanted subcutaneously in NCr nu/nu mice and produces long-bone metastases after intracardiac injection. Although the bone metastasis from which the LCC15-MB cell line was derived lacked vimentin (VIM) expression, the original primary tumor and lymph node metastasis were strongly VIM positive, as are LCC15-MB cells in vitro and in nude mice. The karyotype and isozyme profiles of LCC15-MB cells are consistent with its origin from a human female, with most chromosome counts in the hypertriploid range. Thirty-two marker chromosomes are present. These cells provide an in vitro/in vivo model in which to study the inter-relationships between ER, VIM, and bone metastasis in human breast cancer.

Bone sialoprotein supports breast cancer cell adhesion proliferation and migration through differential usage of the alpha(v)beta3 and alpha(v)beta5 integrins.

Bone sialoprotein (BSP), a secreted glycoprotein found in bone matrix, has been implicated in the formation of mammary microcalcifications and osteotropic metastasis of human breast cancer (HBC). BSP possesses an integrin-binding RGD (Arg-Gly-Asp) domain, which may promote interactions between HBC cells and bone extracellular matrix. Purified BSP, recombinant human BSP fragments and BSP-derived RGD peptides are shown to elicit migratory, adhesive, and proliferative responses in the MDA-MB-231 HBC cell line. Recombinant BSP fragment analysis localized a significant component of these activities to the RGD domain of the protein, and synthetic RGD peptides with BSP flanking sequences (BSP-RGD) also conferred these responses. The fibronectin-derived RGD counterpart, GRGDSP (Gly-Arg-Gly-Asp-Ser-Pro), could not support these cellular responses, emphasizing specificity of the BSP configuration. Although most of the proliferative and adhesive responses could be attributed to RGD interactions, these interactions were only partly responsible for the migrational responses. Experiments with integrin-blocking antibodies demonstrated that BSP-RGD-induced migration utilizes the alpha(v)beta3 vitronectin receptor, whereas adhesion and proliferation responses were alpha(v)beta5-mediated. Using fluorescence activated cell sorting, we selected two separate subpopulations of MDA-MB-231 cells enriched for alpha(v)beta3 or alpha(v)beta5 respectively. Although some expression of the alternate alpha(v) integrin was still retained, the alpha(v)beta5-enriched MDA-MB-231 cells showed enhanced proliferative and adhesive responses, whereas the alpha(v)beta3-enriched subpopulation was suppressed for proliferation and adhesion, but showed enhanced migratory responses to BSP-RGD. In addition, similar analysis of two other HBC cell lines showed less marked, but similar RGD-dependent trends in adhesion and proliferation to the BSP fragments. Collectively, these data demonstrate BSP effects on proliferative, migratory, and adhesive functions in HBC cells and that the RGD-mediated component differentially employs alpha(v)beta3 and alpha(v)beta5 integrin receptors.

The LCC15-MB human breast cancer cell line expresses osteopontin and exhibits an invasive and metastatic phenotype.

We have characterized the LCC15-MB cell line which was recently derived from a breast carcinoma metastasis resected from the femur of a 29-year-old woman. LCC15-MB cells are vimentin (VIM) positive, exhibit a stellate morphology in routine cell culture, and form penetrating colonies when embedded in three-dimensional gels of Matrigel or fibrillar collagen. They show high levels of activity in the Boyden chamber chemomigration and chemoinvasion assays, and like other invasive human breast cancer (HBC) cell lines, LCC15-MB cells activate matrix-metalloproteinase-2 in response to treatment with concanavalin A. In addition, these cells are tumorigenic when implanted subcutaneously in nude mice and recolonize bone after arterial injection. Interestingly, both the primary lesion and the bone metastasis from which LCC15-MB were derived, as well as the resultant cell line, abundantly express the bone matrix protein osteopontin (OPN). OPN is also expressed by the highly metastatic MDA-MB-435 cells, but not other invasive or noninvasive HBC cell lines. Expression of OPN is retained in the subcutaneous xenograft and intraosseous metastases of LCC15-MB as detected by immunohistochemistry. Both VIM and OPN expression have been associated with breast cancer invasion and metastasis, and their expression by the LCC15-MB cell line is consistent with its derivation from a highly aggressive breast cancer. These cells provide a useful model for studying molecular mechanisms important for breast cancer metastasis to bone and, in particular, the implication(s) of OPN and VIM expression in this process.

Human breast cancer cell metastasis to long bone and soft organs of nude mice: a quantitative assay.

Bone is a common metastatic site in human breast cancer (HBC). Since bone metastasis occurs very rarely from current spontaneous or experimental metastasis models of HBC cells in nude mice, an arterial seeding model involving the direct injection of the cells into the left ventricle has been developed to better understand the mechanisms involved in this process. We present here a sensitive polymerase chain reaction (PCR) method to detect and quantitate bone and soft organ metastasis in nude mice which have been intracardially inoculated with Lac Z transduced HBC cells. Amplification of genomically incorporated Lac Z sequences in MDA-MB-231-BAG HBC cells enables us to specifically detect these cells in mouse organs and bones. We have also created a competitive template to use as an internal standard in the PCR reactions, allowing us to better quantitate levels of HBC metastasis. The results of this PCR detection method correlate well with cell culture detection from alternate long bones from the same mice, and are more sensitive than gross Lac Z staining with X-gal or routine histology. Comparable qualitative results were obtained with PCR and culture in a titration experiment in which mice were inoculated with increasing numbers of cells, but PCR is more quantifiable, less time consuming, and less expensive. This assay can be employed to study the molecular and cellular aspects of bone metastasis, and could easily be used in conjunction with RT-PCR-based analyses of gene products which may be involved with HBC metastasis.

Extensive photopenic osteomyelitis.

We present a case of a previously healthy child whose osteomyelitis and septic arthritis resulted in unusually extensive photopenia on bone scintigraphy. Uptake was absent in the humeral shaft and proximal epiphysis and decreased in the proximal physis. The subsequent complicated clinical course, including surgical interventions, and bone scans is described.

Chest wall fibromatosis associated with silicone breast implants.

Aggressive fibromatosis is a well described locally destructive benign lesion, comprising 0.3% of all solid tumors. Although the chest wall is a common location, this tumour has rarely been associated with breast tissue or breast implants. Herein is only the fourth case described in conjunction with a breast implant and the only case linked to a ruptured silicone implant. This tumour was locally aggressive and required wide surgical resection, including removal of the chest wall, to gain control. Wide surgical resection is recommended with the application of adjuvant radiation therapy being more controversial.

Results of the Wagner and Ilizarov methods of limb-lengthening.

We compared the results of the Wagner method of limb-lengthening in twenty extremities (nineteen patients) with those of the Ilizarov method in twenty-one extremities (eighteen patients). The Wagner external fixator was used in all twenty procedures in which the Wagner lengthening method was performed and in fourteen procedures in which the Ilizarov lengthening method was performed. The Ilizarov external fixator was used in the remaining seven procedures in which the Ilizarov method was performed. The average increase in length was 5.4 centimeters (range, 2.8 to 8.0 centimeters) with the Wagner technique and 5.9 centimeters (range, 1.0 to 16.8 centimeters) with the Ilizarov technique. The rate for the lengthening phase was nine days for one centimeter of length with the Wagner technique and twelve days for one centimeter with the Ilizarov technique. The rate for the consolidation phase was forty-four days for one centimeter with the Wagner technique and twenty-six days for one centimeter with the Ilizarov technique. The group of patients who were managed with the Wagner technique had thirty major complications, and the group of patients who were managed with the Ilizarov technique had only thirteen major complications. Forth complications were associated with the use of the uniaxial Wagner external apparatus and sixteen, with the use of the multiaxial Ilizarov external fixator.

Case report 810: Giant cell tumor of the first metatarsal.

And unusual case of giant cell tumor in a 3-year-old girl has been presented. The topic of giant cell tumors has been discussed at length. The pathology and the differential diagnosis have been considered. The incidence of giant cell tumors in children and adolescents has also been reviewed and proved to be extremely rare.

Ankle fusion: a retrospective review.

The results of ankle fusion were reviewed in 26 patients who underwent 32 arthrodesis procedures. Posttraumatic degenerative arthritis was the most common indication for fusion (54%). Crossed cancellous screws were the primary method employed (43%), with an external fixator being used in 22% of cases. The overall union rate was 81%, with both crossed cancellous screws and external fixation attaining the best results (86%). Nonunion and infection were the most frequent complications. Progression of subtalar arthritis was demonstrated in 29% of patients postoperatively. Seventy-eight percent of patients graded extremity appearance as excellent or good, with the majority being able to return to work.