Tumors with less than 5 MF/10 HPF behave in a benign fashion, and tumors with more than 10 MF/10 HPF are frankly malignant with a poor prognosis. Tumors with 5 to 10 MF/10 HPF, termed cellular leiomyomas or smooth muscle tumors of uncertain malignant potential, are less predictable. In addition to mitotic index greater than 10, other histologic indicators used to classify uterine smooth muscle tumors as malignant are severe cytologic atypia and coagulative tumor cell necrosis (430). Uterine smooth muscle tumors with any two of these three features are associated with a poor prognosis. Gross presentation of the tumor at the time of surgery is an important prognostic indicator. Tumors with infiltrating tumor margins or extension beyond the uterus are associated with poor prognosis, whereas tumors less than 5 cm, originating within myomas, or with pushing margins are associated with prolonged survival.
Five other clinical pathologic variants of uterine smooth muscle tumors deserve special comment: (i) myxoid leiomyosarcoma, (ii) leiomyoblastoma, (iii) intravenous leiomyomatosis, (iv) benign metastasizing uterine leiomyoma, and (v) disseminated peritoneal leiomyomatosis.
Myxoid leiomyosarcoma is characterized grossly by a gelatinous appearance and apparent circumscribed border. Microscopically, the tumors have a myxomatous stroma and extensively invade adjacent tissue and blood vessels (431). The mitotic rate is low (0 to 2 MF/10 HPF), which belies their aggressive behavior and poor prognosis. Surgical excision by hysterectomy is the mainstay of treatment. The low mitotic rate and abundance of intracellular myxomatous tissue suggest that these tumors would not be responsive to radiation therapy or chemotherapy.
Leiomyoblastoma includes smooth muscle tumors designated as epithelioid leiomyomas, clear cell leiomyomas, and plexiform tumorlets (432,433). This group of atypical smooth muscle tumors is distinguished by the predominance of rounded rather than spindle-shaped cells and by a clustered or cordlike pattern. These lesions should be regarded as specialized low-grade leiomyosarcomas with fewer than 5 MF/10 HPF. Leiomyoblastoma is treated with hysterectomy, and the prognosis is excellent.
Intravenous leiomyomatosis is characterized by the growth of histologically benign smooth muscle into venous channels within the broad ligament and then into uterine and iliac veins (434-437). The intravascular growth takes the form of visible, wormlike projections that extend
Figure 35.8 Leiomyosarcoma of the uterus. Interlacing bundles of spindle cells have fibrillar cytoplasm, irregular and hyperchromatic nuclei, and multiple mitotic figures. (Provided by
Gordana Stevanovic, MD, and Jianyu Rao, MD, Department of Pathology, UCLA.) out from a myomatous uterus into the parametria toward the pelvic sidewalls. It may be confused with low-grade stromal sarcoma. Symptoms are related to the associated uterine myomas. Most patients are in the late fifth and early sixth decades of life. The prognosis is excellent, even when tumor is left in pelvic vessels. Late local recurrences can occur, and deaths from extension into the inferior vena cava or metastases to the heart were reported. Estrogen may stimulate the proliferation of these intravascular tumors. Treatment should be total abdominal hysterectomy and bilateral salpingo-oophorectomy with removal of as much of the tumor as possible.