Leiomyosarcoma Michael T. Deavers, M.D. The University of Texas M.D. Anderson Cancer Center Houston, Texas

Case History The patient is a 70-year old woman who presented to her primary care physician with shortness of breath and a cough. The patient's past medical history was significant for a TAH-BSO 15 years prior for uterine "fibroids". A chest X-ray and a subsequent CT of the chest demonstrated multiple pulmonary and pleural nodules. Later she was noted to have left hip and leg pain. An MRI revealed a lytic lesion that had destroyed part of the femur. She underwent resection of the distal femur (slide provided) and reconstruction with an endoprosthesis. The tumor involving the femur was positive for ER and WT-1; PR was negative. Figure 1 Click to view with ImageScope Click to view with a Web-Based Viewer The tumor involved the distal diaphysis and metaphysis, and extended through the cortex into adjacent soft tissue. The intramedullary component measured 21 x 4 x 4 cm, while the soft tissue component was 12 x 7 x 5 cm. Histologically, it was composed of intersecting fascicles of spindle cells with eosinophilic cytoplasm. The nuclei were elongated and oval with mild to moderate atypia; there were 3 mitoses per 10 high power fields. Focal coagulative tumor cell necrosis was present. The tumor infiltrated medullary boney trabeculae, but did not produce matrix itself. In addition to ER and WT-1, it was diffusely positive for SMA and desmin. A diagnosis of leiomyosarcoma was made. Leiomyosarcoma involving bone, whether primary or secondary, is unusual. Approximately 120 cases of primary leiomyosarcoma of the bone have been reported. The patients are generally middle-aged or older, men and women are equally affected, and the long bones of the extremities are most frequently involved. However, before a leiomyosarcoma can be accepted as arising from the bone, metastatic disease must be ruled out. In these cases, the uterus is one of the most common primary sites, with metastases occurring up to 19 years after hysterectomy, and it is recommended that all previous pathology be carefully re-reviewed. Unfortunately, the slides and blocks from the hysterectomy specimen in this case had been discarded, which illustrates the problems sometimes encountered with extrauterine smooth muscle tumors. The histologic features of uterine and extrauterine smooth muscle tumors are the same, and often the patient's gynecologic history is vague or unknown. Immunohistochemistry may offer some guidance in these cases. The majority of uterine smooth muscle tumors express hormone receptors. While virtually all leiomyomas are positive for ER and PR, 36-87% of leiomyosarcomas are positive for ER and 43-80% are positive for PR. This is in distinction to extrauterine smooth muscle tumors. Although some extrauterine leiomyomas are ER and PR positive, only 0-25% and 0-13% of extrauterine leiomyosarcomas express ER and PR, respectively. Additionally, while uterine leiomyosarcomas often have a diffuse distribution of receptors, ER and PR are usually only focal in the extrauterine tumors. In addition to their potential utility in helping to distinguish uterine from extrauterine leiomyosarcomas, ER and PR have also been investigated in regard to the diagnosis and prognosis of uterine smooth muscle tumors. Three studies have suggested that leiomyosarcomas, as a group, have decreased expression of hormone receptors as compared to benign smooth muscle tumors and STUMP. However, given the relatively limited experience and the overlap in staining between the groups, great caution should be exercised in individual cases. No significant correlation has been found between ER and PR expression and recurrence or survival. WT-1, the Wilms tumor gene involved in the development of the genitourinary system, has been noted recently to be present in uterine cellular leiomyomas. At M.D. Anderson, we undertook a study examining WT-1 expression in a wide range of mullerian and non-mullerian smooth muscle tumors. All of the gynecologic leiomyomas and STUMPs, and 60% of the leiomyosarcomas (including 5 of 7 metastases) were positive for WT-1. However, none of the non-gynecologic smooth muscle tumors (including 22 leiomyosarcomas) were positive. When faced with an extrauterine smooth muscle tumor of uncertain primary, the patient's history and a review of prior specimens are helpful for resolving questions of the tumor's origin. However, when this is not available, immunohistochemical staining for ER, PR, and WT-1 may be of assistance. References Agoff SN, Grieco VS, Garcia, Gown AM. Immunohistochemical distinction of endometrial stromal sarcoma and cellular leiomyoma. 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