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A 62-year-old woman presented to her gynecologist with a one-month history of pelvic pressure. Workup included a CT scan, which revealed a 10 cm pelvic mass. She underwent an exploratory laparotomy that revealed a mass involving the posterior uterine fundus. A total abdominal hysterectomy and bilateral salpingo-oophorectomy were performed. The specimen consisted of a 731 gram uterus measuring 14.0 x 11.0 x 10.0 cm that contained a well-circumscribed 9.0 x 9.0 x 7.0 cm submucosal mass involving the posterior uterine wall. This mass had a biphasic gross appearance with some areas that were white and whorled intermixed with other areas that were fleshy and light brown/cream colored. There were multifocal areas of hemorrhage but no gross evidence of necrosis. Bilateral ovaries and fallopian tubes were unremarkable.
Archive Case and Diagnosis:
This case first appeared as Performance Improvement Program (PIP) in Surgical Pathology 2007, Case 17, and the correct diagnosis is an epithelioid leiomyosarcoma.
Criteria for Diagnosis and Comments:
This epithelioid-appearing tumor, forming a large intrauterine mass, represents an epithelioid leiomyosarcoma. The slides show a circumscribed tumor with an admixture of spindled but predominantly epithelioid tumor cells. There is multifocal significant cytologic atypia (ie, atypia discernible at low power) and a mitotic rate of > 3 mitoses per 10 high power fields. Despite its lack of myometrial infiltration, necrosis or vascular invasion, this tumor is best classified as malignant based upon a combination of epithelioid cytomorphology, the presence of cytologic atypia, and mitotic activity.
Leiomyosarcoma is typically a solitary or dominant mass within the uterus with a mean diameter of 9 cm. Although some may grossly resemble a leiomyoma, most have a distinctly different appearance, usually being less well circumscribed (although some as in this case are well circumscribed), with a softer consistency, grey to cream color, and variable amounts of randomly distributed geographic necrosis and/or hemorrhage. Although any of these unusual gross features may raise the possibility of malignancy (and should prompt extensive sampling), the diagnosis of leiomyosarcoma is based solely on the tumor’s histologic appearance. The vast majority of leiomyosarcomas are of the spindle cell type; however, epithelioid and myxoid variants occur, and these morphologies may be intermixed. Tumors with a predominance of rounded tumor cells with abundant eosinophilic or clear cytoplasm are classified as epithelioid leiomyosarcomas.
The validation of diagnostic criteria used to reliably predict the behavior of smooth muscle tumors with epithelioid differentiation is limited by the rarity of this tumor subtype. Only a limited number of series have been published and even with these studies, classification and prognostication continues to be problematic. Based on the published literature, and reflecting a conservative approach to these tumors, a diagnosis of a benign epithelioid leiomyoma should only be considered in those tumors in which necrosis is absent, there is no to minimal nuclear atypia, and the mitotic count measures less than 3 mitoses per 10 high power fields. Other features that have correlated with a benign behavior include a well-circumscribed margin and tumor size less than 6 cm. Malignant behavior, on the other hand, was associated with the presence of tumor cell necrosis, vascular invasion, moderate to severe nuclear atypia and a mitotic count greater than 3 per 10 high power fields. Infiltrative margins have also correlated with malignant behavior.
Atypical leiomyoma, which is also known as ‘symplastic’, ‘bizarre’ or ‘pleomorphic’ leiomyoma (but defined as ‘atypical’ leiomyoma in the most recent WHO classification), is characterized by the presence of cells with enlarged, pleomorphic, often multiple nuclei, which may be unifocal, multifocal, or diffuse in their distribution. These pleomorphic cells, which are always discernible upon low power examination, may also have nuclear pseudo-inclusions and coarse chromatin. An epithelioid appearance, however, is not a feature of this subtype of leiomyoma. Most atypical leiomyomas have a similar gross appearance to leiomyomas of the usual type, but a subset may have a more yellow appearance and a softer consistency. Most measure less than 5.5 cm and typically occur in reproductive-aged women with a mean age of 40 years. In addition to the presence of significant nuclear atypia, a defining histologic feature is a mitotic count that numbers less than 7 mitoses per 10 high power fields, particularly in tumors with diffuse nuclear atypia.
Endometrial stromal tumors are neoplasms composed of cells that morphologically resemble non-neoplastic proliferative phase endometrial stroma that proliferate around numerous small blood vessels in a characteristic growth pattern. Endometrial stromal tumors are separated into benign and malignant categories, termed endometrial stromal nodule and endometrial stromal sarcoma respectively, based upon the presence or absence of an infiltrative border. On rare occasions, in patients treated with progestins, the neoplastic cells of an endometrial stromal tumor may appear epithelioid due to the increased amount of eosinophilic cytoplasm that forms (pseudo-decidualized appearance). In these instances, the characteristic growth pattern, which is maintained, helps exclude an epithelioid smooth muscle tumor. In difficult cases, application of a panel of biomarkers including desmin and h-caldesmon, which are diffusely positive in smooth muscle tumors, may be helpful.
Undifferentiated uterine sarcomas are composed of neoplastic cells that show marked cellular atypia and numerous mitoses including atypical forms without evidence of differentiation towards a recognizable uterine component (endometrial stromal or smooth muscle). In contrast to an epithelioid leiomyosarcoma, these tumors don’t have a uniform appearance of tumor cells with abundant eosinophilic or clear cytoplasm. In addition, they would lack evidence of smooth muscle differentiation by immunohistochemistry.