Oncogenic osteomalacia (OO) is a rare paraneoplastic syndrome of osteomalacia due to phosphate wasting. The phosphaturic mesenchymal tumor (mixed connective tissue variant) (PMTMCT) is an extremely rare, distinctive tumor that is frequently associated with OO. Despite its association with OO, many PMTMCTs go unrecognized because they are erroneously diagnosed as other mesenchymal tumors. Expression of fibroblast growth factor-23 (FGF-23), a recently described protein putatively implicated in renal tubular phosphate loss, has been shown in a small number of mesenchymal tumors with known OO. The clinicopathological features of 32 mesenchymal tumors either with known OO (29) or with features suggestive of PMTMCT (3) were studied. Immunohistochemistry for cytokeratin, S-100, actin, desmin, CD34, and FGF-23 was performed. The patients (13 male, 19 female) ranged from 9 to 80 years in age (median 53 years). A long history of OO was common. The cases had been originally diagnosed as PMTMCT (15), hemangiopericytoma (HPC) (3), osteosarcoma (3), giant cell tumor (2), and other (9). The tumors occurred in a variety of soft tissue (21) and bone sites (11) and ranged from 1.7 to 14 cm. Twenty-four cases were classic PMTMCT with low cellularity, myxoid change, bland spindled cells, distinctive "grungy" calcified matrix, fat, HPC-like vessels, microcysts, hemorrhage, osteoclasts, and an incomplete rim of membranous ossification. Four of these benign-appearing PMTMCTs contained osteoid-like matrix. Three other PMTMCTs were hypercellular and cytologically atypical and were considered malignant. The 3 cases without known OO were histologically identical to the typical PMTMCT. Four cases did not resemble PMTMCT: 2 sinonasal HPC, 1 conventional HPC, and 1 sclerosing osteosarcoma. Three cases expressed actin; all other markers were negative. Expression of FGF-23 was seen in 17 of 21 cases by immunohistochemistry and in 2 of 2 cases by RT-PCR. Follow-up (25 cases, 6-348 months) indicated the following: 21 alive with no evidence of disease and with normal serum chemistry, 4 alive with disease (1 malignant PMTMCT with lung metastases). We conclude that most cases of mesenchymal tumor-associated OO, both in the present series and in the reported literature, are due to PMTMCT. Improved recognition of their histologic spectrum, including the presence of bone or osteoid-like matrix in otherwise typical cases and the existence of malignant forms, should allow distinction from other mesenchymal tumors. Recognition of PMTMCT is critical, as complete resection cures intractable OO. Immunohistochemistry and RT-PCR for FGF-23 confirm the role of this protein in PMTMCT-associated OO.

The clinicopathologic features of 48 tumors that were histologically similar to gastrointestinal stromal tumors but occurred in the soft tissues of the abdomen were analyzed to determine their overall similarity to their gastrointestinal counterpart, their biologic behavior, and the parameters that predict risk for adverse outcome. Classic leiomyomas and leiomyosarcomas were specifically excluded. The tumors occurred in 32 women and 16 men, who ranged in age from 31 to 82 years (mean, 58 years). Forty tumors arose from the soft tissue of the abdominal cavity, and the remainder arose from the retroperitoneum. They ranged in size from 2.1 to 32.0 cm and varied from tumors composed purely of rounded epithelioid cells to those composed of short fusiform cells set in a fine fibrillary collagenous background with some cases showing a mixed pattern. Tumors displayed variable amounts of stromal hyalinization, myxoid change, and cyst formation. The tumors expressed CD117 (c-kit receptor) (100%), CD34 (50%), neuron-specific enolase (44%), smooth muscle actin (26%), desmin (4%), and S-100 protein (4%). Tumors were evaluated with respect to several parameters: size (<10 cm or >10 cm), cellularity (low or high), mitoses (0 to 2 per 50 high-power fields, >2 per 50 high-power fields), nuclear atypia (1 to 3؉), cell type (epithelioid, spindled, or mixed), and necrosis (absent or present). These parameters were then evaluated in univariate and multivariate analysis with respect to adverse or nonadverse outcome, the former defined as metastasis or death from tumor. Follow-up information was obtained for 31 patients (range, 4 to 84 months; median, 24 months). One patient presented with an adverse event and, therefore, was excluded from subsequent analysis. Twelve patients (39%) developed metastases or died of tumor. In univariate analyses, cellularity, mitotic activity (>2 per 50 high-power fields), and necrosis were associated with statistically significant increases in the risk for adverse outcome. Despite the relatively small sample size, in a multivariable analysis mitotic activity (relative risk, 7.46; P ‫؍‬ .09) and necrosis (relative risk, 3.75; P ‫؍‬ .07) displayed trends toward independent predictive value. Mesenchymal tumors that arise from the wall of the gastrointestinal tract have attracted a great deal of attention over the years. It is generally accepted that those that arise from the esophagus and rectum recapitulate the appearance of mature smooth muscle (1-3), whereas the vast majority of tumors that arise from the remainder of the gastrointestinal

Bone sarcomas are a clinically and molecularly heterogeneous group of malignancies characterized by varying degrees of mesenchymal differentiation. Despite advances in medical and surgical management, survival rates for high-grade tumors have remained static at 50% to 70%. Tumor stem cells have been recently implicated in the pathogenesis of other heterogeneous, highly malignant tumors. We demonstrate here the existence of a small subpopulation of self-renewing bone sarcoma cells that are capable of forming suspended spherical, clonal colonies, also called "sarcospheres," in anchorage-independent, serum-starved conditions. These bone sarcoma cells as well as tissue specimens express activated STAT3 and the marker genes of pluripotent embryonic stem (ES) cells, Oct 3/4 and Nanog. Expression levels of Oct 3/4 and Nanog are greater in sarcospheres than in adherent cultures. A subset of bone sarcoma cells displays several surface markers of mesenchymal stem cells (Stro-1, CD105, and CD44) as well as attributes of mesodermal, ectodermal, and endodermal differentiation. Although previously documented in brain and breast tumors, our results support the extension of the cancer stem cell hypothesis to include tumors of mesenchymal lineage. Furthermore, they suggest the participation of ES cell homeobox proteins in non-germ cell tumorigenesis.

Malignant Peripheral Nerve Sheath Tumors (MPNSTs) are rare tumors that often occur in patients with neurofibromatosis 1. Surgical resection represents the mainstay of treatment. Radiation and chemotherapy have a role in selected patients with MPNST. Accurate pathologic diagnosis remains a challenge in many cases of MPNST. There are many recent advances in the understanding of the molecular pathogenesis of MPNST which represent the best opportunities to develop new strategies for management of patients with MPNST.

Cutaneous angiosarcoma is a rare, aggressive malignancy that is optimally treated with resection and wide-field postoperative RT. The likelihood of local-regional failure is high, as is the risk of distant relapse. Chemotherapy may be useful for short-term palliation.

The mainstay of treatment is surgery and most patients are cured with one or more operations. A small subset of patients with incompletely resectable, aggressive, and/or recurrent ABCs may be cured with low-dose RT.

There is an increased risk of pulmonary metastasis of GCT of bone in patients who are younger, present with Enneking stage-3 disease, develop local recurrence, and/or present with axial disease. The mode of treatment was not found to be associated with the development of pulmonary metastasis.

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