Leiomyosarcoma of Somatic Soft Tissues

Abstract

Leiomyosarcomas of the somatic soft tissues (SST) are rare compared with their retroperitoneal and cutaneous counterparts and, therefore, have not been extensively studied. We have analyzed the clinicopathologic features of 42 SST leiomyosarcomas referred in consultation to determine what factors affect outcome. Cutaneous, visceral, retroperitoneal, uterine, gastrointestinal, and major vessel leiomyosarcomas were excluded. By definition all lesions possessed at least focal cytologic atypia and mitotic activity, although the latter varied from <1/10 high power fields to 66/10 high power fields. The patients (21 females and 21 males) ranged in age from 26 to 86 years (mean 60 years); tumors developed in the lower (n = 28) or upper extremity (n = 11) and trunk (n = 3). Most arose in deep (n = 27) as opposed to superficial (n = 15) soft tissue; 39 arose from a small vein. During the follow-up period (mean 47 months, range 9-162 months), 3 of 38 (8%) patients developed local recurrence and 17 of 38 metastasized (45%) mostly to the lungs. In a univariate analysis age >62 years, size >4 cm, extensive necrosis, modified updated French Federation of Cancer Centers (FFCC) grade, and whether the tumor had been "disrupted" by a previous incisional biopsy or incomplete excision were significantly correlated with metastasis. AJCC stage also approached significance (p = 0.096) but could not be reliably tested because of the sparseness of the data. In multivariate analyses the logistic regression model that best predicted metastasis at 36 months incorporated the effects of age, FFCC grade, and disruption and had a sensitivity of 94.1% and a specificity of 95.2%. Disruption was the only significant risk factor for metastasis in a multivariate analysis (relative risk 2.70; p = 0.0001) but was strongly correlated with large size and deep location. Other parameters did not improve the predictive power of the model significantly. We concluded that the majority of SST leiomyosarcomas are actually of vascular origin, an observation that has clinical and possibly biologic ramifications. Our histologic definition of leiomyosarcoma to include atypia and any level of mitotic activity appears warranted by the biologic outcome in our cases. The risk of metastasis can be calculated from a model incorporating age, FFCC grade, and disruption. Because disruption correlates with size and depth, it could represent a surrogate as opposed to causal marker for metastasis. Nevertheless, in view of their vascular origin, the possibility that tumor disruption may facilitate or promote access to the bloodstream merits further study.

Cutaneous Leiomyosarcoma: Treatment and Outcomes with a Standardized Margin of Resection

“…Subcutaneous LMS, thought to arise from smooth muscle of small vessels, and have been reported to have a tendency to metastasize earlier with a worse prognosis. [5, 8] In contrast, findings from a review of 225 patients with nonvisceral soft tissue LMS form the Scandinavian Sarcoma group, revealed no patients with strictly cutaneous LMS whom metastasized or died of tumor-related causes. [9]…”

MicroRNAs in Soft Tissue Sarcomas: Overview of the Accumulating Evidence and Importance as Novel Biomarkers

“…Although the effectiveness of chemo- and radiotherapy is uncertain, a clear survival benefit of chemo- or radiotherapy is evident if surgical margins are not clear of tumor cells. For patients with LMS in the extremities, the reported local recurrence rate is 10%–25%, whereas the 5-year survival rate is 64% [41]. …”

Classification, Molecular Characterization, and the Significance ofPtenAlteration in Leiomyosarcoma

“…It appears for now, though, that genital and inguinal LMSs share some commonalities with other somatic LMSs. For example, somatic LMS often presents at a smaller size than those of the retroperitoneum but remains an aggressive group with a reported 5- year survival rate of 64% [8, 17]. Increasing tumor size, grade, and depth correlates with decreased survival [8, 11, 17–20].…”

“…For example, somatic LMS often presents at a smaller size than those of the retroperitoneum but remains an aggressive group with a reported 5- year survival rate of 64% [8, 17]. Increasing tumor size, grade, and depth correlates with decreased survival [8, 11, 17–20]. Increasing mitotic index has also been shown to adversely affect prognosis [20, 21], but this correlation has not been true in other studies [8, 11, 17, 18].…”

“…Increasing tumor size, grade, and depth correlates with decreased survival [8, 11, 17–20]. Increasing mitotic index has also been shown to adversely affect prognosis [20, 21], but this correlation has not been true in other studies [8, 11, 17, 18]. Interestingly, at least one-quarter [11] to one-third [17] of somatic LMSs originate from a vessel wall but these lesions are distinguished from the major vessel LMS group, which arises in large vessels, most commonly the inferior vena cava (IVC) [22], have a worse prognosis, and pose uniquely challenging clinical management issues.…”