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Uterus

Stromal tumors

Smooth muscle tumors of unknown malignant potential


Reviewer: Nat Pernick, M.D. (see Reviewers page)
Revised: 6 November 2011, last major update August 2011
Copyright: (c) 2002-2011, PathologyOutlines.com, Inc.

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

Bell criteria for problematic smooth muscle uterine tumors
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● 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

   
Moderate and marked atypia

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


Coagulative tumor cell necrosis

● 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


Hyalinizing necrosis

● 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)

Clinical features
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● Suggested to consider as tumor of low malignant potential because may recur (Am J Surg Pathol 2009;33:992), rarely as leiomyosarcoma (Gynecol Oncol 2009;113:324)

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

End of Uterus > Stromal tumors > Smooth muscle tumors of unknown malignant potential


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