Practical issues in uterine pathology from banal to bewildering: the remarkable spectrum of smooth muscle neoplasia

Abstract

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.

Leiomiosarcoma asociado a embarazo

“…Los criterios histológicos recomendados para diagnosticar los leiomiosarcomas son la necrosis, atipia celular y la alta tasa mitótica. El tumor descrito cumplió con estos criterios (14) .…”

Uterine Smooth Muscle Tumors of Uncertain Malignant Potential (STUMP): Review of Pathophysiology, Classification, Diagnosis, Treatment, and Surveillance

“…In contrast, hyalinizing necrosis features a zone of hyalinized collagen interposed between the dead cells and the preserved cells, a pattern reminiscent of an infarcted region being organized by granulation tissue. Hyalinizing necrosis is common in leiomyomas, however is not helpful in predicting the malignant potential of a smooth muscle tumor [11,19,21,26,27].…”

“…Tumors with moderate atypia have cells with nuclei that are large, plump, and irregular with coarse chromatin and the presence of at least two enlarged abnormal mitotic figures. Tumors with severe atypia have obvious nuclear pleomorphism and cells with enlarged bizarre nuclei with dense chromatin [19,21,26,27].…”

“…3) Differential diagnosis: Lymphocytes, mast cells, stripped nuclei, degenerated cells, precipitated hematoxylin [19,21,26,27].…”

“…The classification of uterine smooth muscle tumors is based on the assessment of three histopathologic characteristics: Mitotic count activity or mitotic index (number of mitotic figures per 10 high power fields [hpf]), presence of coagulative tumor cell necrosis, and degree of cytological atypia [19][20][21][22]. Accurately diagnosing uterine smooth muscle neoplasms is clinically significant for correct patient management.…”