Uterine mesenchymal tumors are classified broadly into pure and mixed tumors (Table 34-1). Also, the term homologous denotes tissues normally found in the uterus and heterologous refers to tissue foreign to the uterus. Pure sarcomas are virtually all homologous and differentiate into mesenchymal tissue that is normally present within the uterus, such as smooth muscle (leiomyosarcoma) or stromal tissue within the endometrium (endometrial stromal tumors). Pure heterologous sarcomas, such as chondrosarcoma, are rare.
TABLE 34-1World Health Organization Histological Classification of Mesenchymal Tumors of the Uterus ||Download (.pdf) TABLE 34-1 World Health Organization Histological Classification of Mesenchymal Tumors of the Uterus
| Mesenchymal tumors |
Leiomyoma with bizarre nuclei
Mitotically active leiomyoma
Lipomatous leiomyoma (lipoleiomyoma)
Dissecting (cotyledonoid) leiomyoma
Smooth muscle tumor of uncertain malignant potential
Endometrial stromal and related tumors
Endometrial stromal nodule
Low grade endometrial stromal sarcoma
High grade endometrial stromal sarcoma
Undifferentiated endometrial sarcoma
Uterine tumor resembling ovarian sex cord tumor
Miscellaneous mesenchymal tumors
|Mixed epithelial and mesenchymal tumors |
Mixed sarcomas contain a malignant mesenchymal component admixed with an epithelial element. If the epithelial element is also malignant, the tumor is termed carcinosarcoma. If the epithelial element is benign, the term adenosarcoma is used. Carcinosarcomas can be either homologous or heterologous, reflecting the pluripotentiality of the uterine primordium.
Leiomyosarcomas account for 1 to 2 percent of all uterine malignances. In a Surveillance, Epidemiology, and End Results (SEER) database study of 1396 patients, the median age at presentation was 52 years. Most tumors (68 percent) were stage I at the time of diagnosis, and stage II (3 percent), stage III (7 percent), and stage IV cancer (22 percent) formed the remainder (Kapp, 2008).
The histologic criteria for diagnosing leiomyosarcoma are somewhat controversial but include the frequency of mitotic figures, extent of nuclear atypia, and presence of coagulative tumor cell necrosis (Fig. 34-2). In reading Table 34-2, each row illustrates combinations of histologic findings that may be found in leiomyosarcomas. In most cases, the mitotic index exceeds 15 mitotic figures total when 10 high-power fields are examined, moderate to severe cytologic atypia is seen, and tumor cell necrosis is prominent (Hendrickson, 2003; Zaloudek, 2011). Occasionally, a leiomyosarcoma will be reported as low-, intermediate-, or high-grade, but the overall utility of grading is controversial, and no universally accepted grading system exists.
TABLE 34-2Diagnostic Criteria for Uterine Leiomyosarcoma ||Download (.pdf) TABLE 34-2 Diagnostic Criteria for Uterine Leiomyosarcoma
|Coagulative Tumor Cell Necrosis ||Mitotic Index a ||Degree of Atypia |
|≥10 MF/10 HPF |
≥10 MF/10 HPF
Leiomyoma (A, B) and leiomyosarcoma (C, D). A. Leiomyomas tend to be well-circumscribed masses. This leiomyoma shows a well-demarcated interface (arrows) with the less cellular myometrium above it. B. Although leiomyomas may have variable histologic features, most are composed of bland spindled cells with blunt-ended nuclei and limited mitotic activity. C. Leiomyosarcoma is a malignant smooth muscle neoplasm that may differ markedly in its microscopic appearance from case to case. Generally, leiomyosarcoma shows some combination of coagulative tumor necrosis, increased mitotic activity, and/or nuclear atypia. This example has marked nuclear atypia and pleomorphism and an infiltrative growth pattern at its periphery. This differs from the usually smooth, pushing border of typical leiomyomas. D. This particular example has moderate to marked nuclear atypia. (Used with permission from Drs. Kelley Carrick and Raheela Ashfaq.)
Smooth Muscle Tumor of Uncertain Malignant Potential (STUMP)
Tumors that show some worrisome histologic features, such as necrosis or nuclear atypia, but that cannot be diagnosed reliably as benign or malignant based on generally applied criteria fall into this category. The diagnosis should be used sparingly and is reserved for smooth muscle neoplasms whose appearance is ambiguous (Hendrickson, 2003).
Endometrial Stromal Tumors
Significantly less common than leiomyosarcomas, the group of endometrial stromal tumors comprise fewer than 10 percent of all uterine sarcomas. In a SEER database study of 831 patients, the median age at diagnosis was 52 years (Chan, 2008). Although constituting a wide morphologic spectrum, endometrial stromal tumors are composed exclusively of cells that resemble the endometrial stroma, and this category includes both benign stromal nodules and malignant stromal tumors (see Table 34-1).
Historically, there has been controversy in subdividing these tumors. The division of endometrial stromal sarcomas into low-grade and high-grade categories has fallen out of favor. In its place, the designation endometrial stromal sarcoma is now best restricted to neoplasms that were formerly referred to as low-grade. Alternatively, the term high-grade undifferentiated sarcoma is believed to more accurately reflect those tumors without recognizable evidence of a definite endometrial stromal phenotype. These lesions are almost invariably high grade and often resemble the mesenchymal component of a uterine carcinosarcoma (Oliva, 2000). In this revised classification, the distinctions are not determined by mitotic count but by features such as nuclear pleomorphism and necrosis (Evans, 1982; Hendrickson, 2003).
Endometrial Stromal Nodule
Representing less than a quarter of tumors in the endometrial stromal tumor group, these rare nodules are benign, characterized by a well-delineated margin, and composed of neoplastic cells that resemble proliferative-phase endometrial stromal cells. Grossly, the tumor is a solitary, round or oval, fleshy nodule measuring a few centimeters. Histologically, they are distinguished from endometrial stromal sarcomas by their lack of myometrial infiltration (Dionigi, 2002). Because these nodules are benign, myomectomy is an appropriate option. However, because differentiation between endometrial stromal sarcoma and this benign lesion cannot be determined clinically, it is important to remove the entire nodule. Thus, for large lesions, hysterectomy may be required (Hendrickson, 2003).
Endometrial Stromal Sarcoma
The precise frequency of these tumors is difficult to estimate because they are excluded from some reports and included in others, and the terminology used has been inconsistent. In general, endometrial stromal sarcomas (formerly called low grade) are thought to be the most frequently encountered stromal tumor variant and are twice as common as high-grade undifferentiated sarcomas.
Typically, they extensively invade the myometrium and extend to the serosa in approximately half of cases (Fig. 34-3). Less often, they present as a solitary well-delineated, predominantly intramural mass that is difficult to grossly distinguish from an endometrial stromal nodule. Microscopically, endometrial stromal sarcomas resemble the stromal cells of proliferative-phase endometrium (Fig. 34-4).
Endometrial stromal sarcoma. The surgical specimen has been bisected and remains joined at the fundus.
Endometrial stromal sarcoma (ESS), same patient as in Figure 34-3. A. ESS is composed of cells morphologically similar to proliferative phase endometrial stromal cells. In this low-power view that involved the corpus and cervix, irregular tongues of tumor (asterisks) are seen dissecting into the cervical stroma. B. The tumor cells are spindled and relatively bland, similar to normal endometrial proliferative phase stroma. Two mitoses are identified in this single medium-power field (white arrows). C. Endometrial stroma marks positively with CD10, as does ESS. A battery of immunostains, including CD10, may be used to help distinguish ESS from other spindle cell neoplasms. (Used with permission from Dr. Kelley Carrick.)
Metastases are rarely detected prior to the diagnosis of the primary lesion. However, permeation of the lymphatic and vascular channels is characteristic. In up to one third of cases, extrauterine extension is present, often appearing as “worm-like” plugs of tumor within the vessels of the broad ligament and adnexa. At operation, this may resemble intravenous leiomyomatosis or a broad ligament leiomyoma, both described in Chapter 9. Frozen section analysis can usually make the distinction.
High-grade Undifferentiated Sarcoma
Compared with endometrial stromal sarcomas, these tumors tend to be larger and more polypoid, often filling the uterine cavity. Instead of an infiltrating pattern, high-grade undifferentiated sarcomas displace the myometrium more destructively, leading to prominent hemorrhage and necrosis.
Microscopically, the cells are larger and more pleomorphic. The presence of marked cellular atypia is characteristic. Typically, there are more than 10 mitoses per 10 high-power fields, but frequently there are more than 20 in the most active areas. These tumors lack specific differentiation and bear no histologic resemblance to endometrial stroma (Hendrickson, 2003; Zaloudek, 2011).
Accumulating clinical and pathologic evidence suggests that carcinosarcomas actually represent endometrial carcinomas that have undergone clonal evolution, resulting in the acquisition of sarcomatous features. In principle, these tumors are metaplastic carcinomas. Clinically, their pattern of spread more closely mirrors that of aggressive endometrial carcinomas than that of sarcomas. In addition, metastases usually show carcinomatous elements, with or without sarcomatous differentiation.
However, by convention, carcinosarcomas are usually grouped with uterine sarcomas, accounting for 2 to 3 percent of all uterine malignancies. Patients are often older, having an average age of 65 years. Fewer than 5 percent are diagnosed in women younger than 50. At the time of diagnosis, most cancers (40 percent) are stage I. Stage II (10 percent), stage III (25 percent), and stage IV disease (25 percent) make up the remainder (Sartori, 1997; Vaidya, 2006).
Grossly, the tumor is sessile or polypoid, bulky, necrotic, and often hemorrhagic (Fig. 34-5). It often fills the endometrial cavity and deeply invades the myometrium. On occasion, a large tumor protrudes through the external cervical os and fills the vaginal vault.
Carcinosarcoma. Photograph of the surgical specimen after it has been bisected and remains joined at the fundus.
Microscopically, carcinosarcomas have an admixture of epithelial and mesenchymal differentiation. The malignant epithelial element is typically an adenocarcinoma of endometrioid type, but serous, clear cell, mucinous, squamous cell, and undifferentiated carcinoma are also common (Fig. 34-6). Mesenchymal components can be homologous, usually resembling endometrial stromal sarcomas or fibrosarcomas. Alternatively, heterologous mesenchymal differentiation can be found in association with areas of endometrial stromal or undifferentiated sarcomas. Most commonly, rhabdomyosarcoma or chondrosarcoma compose these cases of heterologous mesenchymal differentiation (Fig. 34-7). Although interesting, there is no clinical importance to designating a uterine carcinosarcoma as homologous or heterologous (McCluggage, 2003).
A. Carcinosarcoma is a biphasic malignant neoplasm composed of both carcinomatous and sarcomatous elements. In this example, malignant endometrioid-type glands are present within an atypical spindled stroma. B. Immunohistochemical stain for cytokeratin marks the epithelial component but not the stromal component. C. Conversely, an immunohistochemical stain for vimentin (a mesenchymal marker) stains the sarcomatous component. (Used with permission from Dr. Raheela Ashfaq.)
Carcinosarcoma with heterologous elements. In this carcinosarcoma with cartilaginous differentiation, malignant glands are present at the periphery (arrows). Centrally is a focus of malignant cartilage (asterisk), with its characteristic lacunae embedded within a bluish chondroid matrix. (Used with permission from Dr. Kelley Carrick.)
This rare, biphasic neoplasm is characterized by a benign epithelial component and a sarcomatous mesenchymal component. Tumors may develop in women of all ages. Grossly, adenosarcomas grow as exophytic polypoid masses that extend into the uterine cavity (Fig. 34-8). Rarely, they may arise in the myometrium, presumably from adenomyosis. Microscopically, isolated glands are dispersed throughout the mesenchymal component and are often dilated or compressed into thin slits (Fig. 34-9). Typically, the mesenchymal component resembles an endometrial stromal sarcoma or fibrosarcoma and contains varying amounts of fibrous tissue and smooth muscle. In general, these are considered low-grade tumors with mild atypia and relatively few mitotic figures. However, 10 percent have a more malignant behavior due to one-sided proliferation of the sarcomatous, often high-grade, component. These adenosarcomas are designated as having “sarcomatous overgrowth,” and patients have a poor prognosis, similar to that of carcinosarcomas (Krivak, 2001; McCluggage, 2003).
Gross uterine specimen with adenosarcoma.
Adenosarcoma. A. A broad-based villous architecture is seen typically. B. Normal endometrial glands are surrounded by a cellular stroma consisting of a low-grade sarcoma. In this case, an endometrial stromal sarcoma is the sarcoma component. (Used with permission from Dr. Raheela Ashfaq.)