Sarcomas in general account for less than 6% of malignant effusions, and if diagnosed in an effusion, are usually only done so in cases in which a known primary tumor is present1. One reason for this may be the tendency of most sarcomas to not exfoliate cells. Leiomyosarcomas, specifically, generally do not exfoliate, unless ulcerated, necrotic or if undergoing fine needle aspiration2. This case is unusual in that the effusion presented before a known primary tumor was discovered. When present in a body fluid, sarcomas often display features, such as the rounding up of spindled cells, that differ from those of the original tumor, which may make them difficult to diagnose in these sites1,3. Cytologic features which many sarcomas, including leiomyosarcomas, have been found to display when in an effusion include scant cellularity, single cell distribution, indistinct cell borders, high nuclear to cytoplasmic ratios, bi- and multi-nucleation, and nuclear pleomorphism1. A background of proteinaceous material with lysed blood and mononuclear inflammatory cells has also been found to be helpful in diagnosing sarcomatous effusions1. One study done exclusively on metastatic uterine sarcomas found them to have variability in chromatin pattern, bipolar cytoplasmic processes and indistinct cell borders4,6. Rounded cells with dense cytoplasm, present in a proteinaceous background with inflammatory cells, were displayed by leiomyosarcomas from another study1.
Even though the cells of a leiomyosarcoma, as with most other sarcoma, should be readily recognized as malignant, establishing a specific diagnosis usually is not possible unless other information, such as history or immunohistochemical results 5, is available. The presence of spindled cells, although rare, may be helpful in classifying a malignancy as a sarcoma as opposed to an epithelial tumor. Other diagnoses to consider when encountering spindled cells in an effusion include fibrosarcoma, malignant peripheral nerve sheath tumor, mesothelioma, and rheumatoid effusions. A rheumatoid effusion is characterized cytologically by a necrotic background, multinucleated giant cells, and epithelioid histiocytes, which may resemble fibroblasts due to their elongate, spindled shape. In contrast to the cells seen in this case and in most sarcomas, however, the nuclei of epithelioid histiocytes are often pyknotic. Also, their cytoplasm tends to have a granular quality. The cells of a squamous cell carcinoma, although rarely found in body fluids, should have a glassy quality. Mesotheliomas generally lack the presence of a discrete foreign population of cells3. Anytime cells with unusual cytologic features are found in body fluid cytology, though, the possibility of a sarcoma should be kept in mind, and appropriate immunohistochemical workup should be done 5, if possible. Even patients with grossly apparent disease can have negative findings on cytologic examination but on occasion a positive fluid wash can be helpful. Patients with negative cytologic findings generally have a better prognosis than patients with positive cytologic findings, who generally have a poor prognosis. However, patients with positive cytologic findings are more likely also to also have other poor prognostic factors (such as lymph node metastases or extrauterine spread), and do poorly regardless of cytologic status. On the other hand, favorable prognostic indicators are neutralized by positive cytology. Therefore, cytologic findings are particularly important in patients with good prognostic factors6,7.
The surgical specimen showed invasive high-grade leiomyosarcoma. Leiomyosarcoma is a malignant tumor showing smooth muscle differentiation. In addition to the usual morphological criteria of smooth muscle cells, typically it is a highly cellular tumor composed predominantly of intersecting fascicles of large spindled cells with markedly atypical nuclei, numerous mitotic figures, which are frequently atypical (Figs. 12-23). The nuclei tend to have blunt or rounded ends, coarsely clumped chromatin, and solitary or multiple prominent nucleoli; multinucleate giant cells are often seen. Small amounts of collagenous stroma are usually seen between tumor cells, and foci of hemorrhage and necrosis may be prominent10. The margins of the tumor usually show at least focal infiltration of the surrounding myometrium, and massive invasion of both myometrium and blood vessels may be present 9,10.
Rarely, microscopic examination provides a suggestion of the origin of the leiomyosarcoma in a benign leiomyoma (Figs. 9-15).
Most leiomyosarcomas show the combination of hypercellularity, atypia, and numerous mitotic figures (usually over 20 per 10 HPF), but occasional diagnostic problems arise in the case of tumors that are less cellular, less atypical, or less mitotically active. Most authors believe that mitotic activity is the single most reliable indicator of malignancy in these tumors. Thus, if mitoses are to be counted, it is strongly recommend that this be done uniformly and point to the caveats quoted by Kempson and Hendrickson8,10:
A mitotic count of greater than 10 mitotic figures per 10 HPF for cellular neoplasms, and over 5 mitotic figures per 10 HPF for tumors demonstrating anaplasia, pleomorphism, giant cells, or epithelioid patterns be considered diagnostic of leiomyosarcoma.
It is distinctly uncommon for leiomyosarcomas to arise from a leiomyoma9. Due to ubiquitousness of uterine leiomyomas, many researchers have attempted to establish the link that leiomyosarcomas results from sarcomatous changes in preexisting leiomyomas. A thorough review of the literature reveals the frequency of this sarcomatous change varies from 0.13% to 10% of all uterine leiomyomas, averaging at 1.46%8-10.
Contributed by Deepak Mohan, MD, Elise Hoff, MD, Mirka Jones, MD, David J Dabbs, MD