• WHO: uterine smooth muscle tumor that cannot be histologically diagnosed as unequivocally benign or malignant
• Also known as STUMP

• Note: criteria do not apply to extrauterine tumors
• Note: must rigidly apply following criteria for atypia, mitotic figures and coagulative tumor cell necrosis (Mod Pathol 2000;13:328)

Atypia:

• Classify as none / mild or moderate / severe, based on nuclear pleomorphism, nuclear size, nuclear membrane irregularities, chromatin density and nucleoli size/prominence
• No / mild atypia: uniform nuclei that may be enlarged, but with smooth nuclear contours, evenly distributed chromatin; minimal variation in nuclear size and shape, small nucleoli
• Moderate / severe should be detectable at low power
• Moderate atypia: large, plump and irregular nuclei with coarse chromatin; if 1 - 2 enlarged abnormal mitotic figures, call moderate atypia
• Severe atypia: obvious pleomorphism, numerous cells with enlarged bizarre nuclei with dense chromatin; frequent giant cells, often multinucleated, enlarged and sometimes atypical nucleoli

Mitotic figures criteria:

1. Hairy extensions of chromatin must be present, extending from a central clot-like dense mass of chromosomes; hairy extensions from an empty center favor a non mitosis
   • Count 4 sets of 10 fields in area of highest mitotic activity, and use the highest count
2. No nuclear membrane
3. Must rule out lymphocytes, mast cells, stripped nuclei, degenerated cells and precipitated hematoxylin
4. Count only definite mitotic figures

Necrosis:

• Presence or absence is powerful predictor of outcome for patients with uterine smooth muscle tumors
• Must distinguish coagulative tumor cell necrosis and hyalinizing necrosis
• Coagulative tumor cell necrosis: abrupt transition between necrotic cells and preserved cells; ghost outlines of nuclei of necrotic cells are often seen in necrotic area, but inflammatory cells are uncommon; common in clinically malignant smooth muscle tumors - DON'T IGNORE

• Hyalinizing necrosis: zone of hyalinized collagen between dead cells and preserved cells, reminiscent of infarcted region organized by granulation tissue; eosinophilic collagen matrix common; if dead nuclei present, nuclei are uniform and chromatin is often faint, compared to nuclear hyperchromasia and pleomorphism in tumor cell necrosis; common in leiomyomas

• Necrosis secondary to ulceration in submucous leiomyomas features acute inflammatory cells and a peripheral reparative process, whereas ghost outlines of nuclei are usually inconspicuous or absent

Leiomyomas: no coagulative tumor cell necrosis, no significant atypia, but any degree of mitotic activity; can call "with significant mitotic activity" if 5+ mitotic figures/10 HPF, but have benign behavior

Atypical leiomyoma: moderate / severe atypia, < 10 mitotic figures/10 HPF, no coagulative tumor cell necrosis

Leiomyosarcoma: usually hemorrhagic and soft, marked pleomorphism, 15 - 30 mitotic figures/10 HPF with abundant abnormal mitotic figures; coagulative tumor cell necrosis

STUMP: minimally atypical smooth muscle neoplasms with a low mitotic index but with uncertainty about the histologic type (standard vs. myxoid or standard vs. epithelioid); combination of standard smooth muscle differentiation, marked diffuse severe atypia, low mitotic index and uncertainty about whether coagulative tumor cell necrosis is present; moderate to severe atypia plus uncertain mitotic index because possible mitotic figures may be degenerating nuclei mimicking mitotic figures

Algorithm:

• No / mild atypia, no tumor cell necrosis → leiomyoma
• Moderate / severe atypia, no tumor cell necrosis → atypical leiomyoma if < 10 mitotic figures/HPF or leiomyosarcoma if 10+ MF/10 HPF
• Moderate / severe atypia and tumor cell necrosis → leiomyosarcoma (mitotic figures don’t matter)

• Conservative because low likelihood of leiomyosarcomatous transformation (Ann Acad Med Singapore 2010;39:625)