Among mesenchymal
tumors of the uterus, smooth muscle
neoplasms are most common. The wide morphologic spectrum, especially within the category of
leiomyomas, is responsible for diagnostic problems more frequently with
leiomyosarcoma (including mitotically active, apoplectic, and
leiomyoma with bizarre nuclei) but also with
endometrial stromal tumors. In the former scenario, clinical information, gross appearance as well as strict utilization of morphologic criteria including cytologic atypia, mitotic activity, and
tumor cell
necrosis are clues in establishing the correct diagnosis. It is important to keep in mind that mitotic rate thresholds vary for the different subtypes of
leiomyosarcoma. Of note, p16 should be used with caution in supporting a diagnosis of
leiomyosarcoma as it is often positive in
leiomyomas with bizarre nuclei and
leiomyomas with apoplectic change (in the latter most frequently and more intense near areas of
necrosis). MED12 mutations have also a very limited role in this differential diagnosis.
Endometrial stromal tumors are by far, less common than
smooth muscle tumors, but can be confused with
leiomyosarcomas if they are associated with an undifferentiated uterine
sarcoma and the low-grade component is overlooked or they have a myxoid/fibroblastic morphology. The differential diagnosis may be confounded if the latter is associated with a high-grade
endometrial stromal sarcoma. It is important to highlight that CD10 is not a reliable marker in these differentials and should be used as a part of a panel of
antibodies that also includes
desmin and h-
caldesmon. Two other recently categorized
tumors in the uterus that merit special mention are
PEComa and inflammatory myofibroblastic
tumor as they enter in the differential diagnosis of
smooth muscle tumors.
PEComa may be part of the
tuberous sclerosis syndrome and may show either a predominantly epithelioid or spindle morphology or combination thereof. Rarely, it may contain
melanin pigment. There is variable positivity for HMB-45,
MelanA, MiTF, and CathepsinK, and some
tumors have been shown to express TFE-3 especially when associated with "clear cell" morphology. Patients with adverse outcome have
tumors with ≥2 of the following features: ≥5 cm, infiltration, high-grade cytologic features, mitotic rate ≥1/50 high-power fields,
necrosis, or lymphovascular invasion. Inflammatory myofibroblastic
tumor is important to recognize as it often mimics myxoid
smooth muscle tumors, either benign or malignant. The presence of an associated lymphoplasmacytic infiltrate should alert to that possibility and ALK studies (immunostain or FISH) are helpful in establishing this diagnosis. These
tumors can behave in a malignant manner if large, associated with abundant myxoid change, brisk mitotic rate or show
tumor cell
necrosis.