Leiomyosarcomas are the most common sarcomas of the female genital tract. Nearly all tumors originate in the smooth muscle of the uterine corpus, although they may be primary in the muscle of the uterine cervix and, exceedingly rarely, in other genital organs such as the fallopian tube or the wall of the vagina. The tumors are composed of crisscrossing bundles of abnormal smooth muscle cells, characterized by large, hyperchromatic nuclei. Several rare variants of these tumors are known to occur, chief among them the epithelioid leiomyosarcoma, a tumor composed of large, polygonal cells mimicking an epithelial tumor. The prognosis of uterine leiomyosarcomas depends on the size of the tumor, its relationship to adjacent organs, and its histologic differentiation or grade. Small tumors incidentally found within the myometrium or arising within benign leiomyomas generally offer an excellent prognosis. However, tumors attached to adjacent viscera are often fatal, regardless of grade. Well-differentiated tumors, closely resembling benign leiomyomas, except for nuclear abnormalities and sometimes high mitotic count (grade I), usually have a much better prognosis than tumors composed of bundles of clearly malignant cells (grade II). Highly disorganized tumors made up of bizarre large or small cancer cells (grades III and IV) have a nearly uniformly fatal prognosis (Spiro and Koss, 1965; Bodner et al, 2003). Voluminous literature pertaining to the classification and recognition of leiomyosarcomas, particularly the differentiation between atypical leiomyomas and low-grade leiomyosarcomas (Bell et al, 1994), has very limited bearing on cytologic observations.

Massoni and Hajdu (1984) stressed the very low rate of primary leiomyosarcomas recognized in cervicovaginal material. Cells from the well-differentiated forms of leiomyosarcoma (grade I) have never been seen by us or identified in routine smears. However, more anaplastic forms of this tumor (grades II through IV), once ulcerated or metastatic, may shed highly abnormal, often grotesque cancer cells. If such cells are elongated, as is sometimes the case, a more specific diagnosis of tumor type may be attempted (Fig. 17-1). Single or multiple abnormal nuclei of variable sizes may be noted. Nuclear hyperchromasia is variable, and irregular, large nucleoli may be present. The difference between cells of a high grade leiomyosarcoma and normal smooth muscle cells is obvious. Quite often, however, cancer cells shed from a leiomyosarcoma are polygonal rather than elongated and may be mistaken for cells of a carcinoma.

Elongated, spindly, or bizarre malignant cells are not unique to leiomyosarcomas and may occur in other sarcomas and in mesodermal mixed tumors. Similar cells may also occur in invasive epidermoid carcinomas, particularly of the spindle- and giant-cell variety (see below).

Klijanienko et al (2003) reported a large series of leiomyosarcomas of various types and primary extrauterine locations, diagnosed by direct thin needle aspiration. To my knowledge, no attempts have been made to apply this technique to uterine tumors.

The diagnosis of primary botryoid sarcomas is usually made by clinical inspection and biopsy. Cytologic diagnosis is superfluous in such instances. Even if vaginal smears are obtained, the tumor cells may be absent because of the protective epithelial layer. However, in recurrent and in metastatic tumors, small, elongated, spindly tumor cells may be observed in vaginal smears or in urinary sediment (see Chap. 26). In rare instances, cytoplasmic cross-striations may occur that allow a precise classification of the tumor.

Differentiated rhabdomyosarcomas are very rare in the female genital tract (Brand et al, 1989). One can then anticipate the finding of bizarre tumor cells with cytoplasmic cross-striations, characteristic of rhabdomyoblasts (see Fig. 17-6). The cytologic findings in two cases of alveolar rhabdomyosarcoma of the vulva were reported by Imachi et al (1991), who did not observe cytoplasmic striations in the tumor cells.

The low-grade, well-differentiated form of the tumor (previously named the endolymphatic stromal myosis) is composed
of orderly bundles of small cells similar to endometrial stroma, sometimes forming ribbon-like organoid structures (so called “plexiform tumorlets”) and occasionally small glands, mimicking primitive endometrial glands. Clement and Scully (1989) misinterpreted the “tumorlets” for sex cord-like elements, seen in rare ovarian tumors, but the origin of these structures from endometrial stroma has been clearly documented by Larbig et al (1965). The tumor cells may occasionally differentiate into smooth muscle cells, particularly in metastatic foci. Oliva et al (2001) pointed out that cells with markedly eosinophilic cytoplasm may occur in such tumors. The tumor has several other interesting features: it has the tendency to invade vessels of the uterus and adjacent pelvis, sometimes forming solid, spaghetti-like cylinders that can be pulled from the affected vessels by a forceps. For this reason, the tumor may be confused with intravenous leiomyomatosis, as in a paper by Clement et al (1988). The tumor may have an erratic, protracted clinical course, stretching over a period of many years (Koss et al, 1965). It may form local, retroperitoneal, or distant metastases, for example, to the bladder or lung, often many years after surgical removal of the primary tumor (28 years in a personally observed case), and still be consistent with long-term survival following aggressive treatment of metastases. Late pulmonary metastases were also described by Abrams et al (1989). The tumor may also respond to hormonal manipulation with progesterone, not unlike an endometrial carcinoma. Because of the unusual, often favorable behavior of this tumor, its diagnosis in metastatic foci may be life-saving.

The high grade endometrial stromal sarcomas are infrequent. In a small series by Koss et al (1965), only 1 of 10 stromal sarcomas could be so classified. The tumor has a similar distribution to the low-grade variant but is composed of obviously malignant larger cells and has aggressive behavior.

Several examples of this tumor were described in cervicovaginal smears (Hsiu and Stawicki, 1979; Becker and Wong, 1981) and in other cytologic samples such as effusions (Massoni and Hajdu, 1984; Hajdu and Hajdu, 1976). So far as one can tell, the reported cases represented the high-grade variant of the disease. In general, the authors stressed the small size and the relatively monotonous appearance of the round or oval malignant cells, accompanied by occasional elongated cells with tapering cytoplasm, named comet cells by Hsiu and Stawicki (1979). Except for hyperchromasia and variability in size, the nuclei had no distinguishing features. Mitotic figures were observed in two of three cases reported by Becker and Wong (1981). In all cases described, the tumor was far advanced and symptomatic; all patients, save one, died of disease shortly after diagnosis.

There are no reported cases of primary diagnosis of the low-grade stromal sarcoma. However, metastases of this tumor may be amenable to diagnosis by needle aspiration biopsy that may lead to aggressive treatment and long-term survival. As an example, the aspirate of one of many large, cannon-ball pulmonary metastases in a 38-year-old woman contained small, spindly, rather benign-looking cells and scattered glands, resembling benign endometrial glands (Fig. 17-2). The cytologic finding led to the review of hysterectomy material obtained 8 years previously, which was initially diagnosed as a benign abnormality (stromal nodule). The review disclosed a low-grade endometrial stromal sarcoma. After surgical removal of all but one of the pulmonary metastases, followed by progesterone therapy, the patient remained well for several years without any evidence of active disease. In another more recent case with only short follow-up, the aspirate of lung metastases yielded small cells resembling normal endometrial stroma (Fig. 17-3).