Uterus
Smooth muscle tumors
Smooth muscle tumors of uncertain malignant potential
Author: Gulisa Turashvili, M.D., Ph.D.
Editorial Board Member: C. Blake Gilks, M.D.
Deputy Editor-in-Chief: Jennifer A. Bennett, M.D.
Topic Completed: 19 August 2021
Minor changes: 30 November 2021
Copyright: 2002-2021, PathologyOutlines.com, Inc.
PubMed search: Smooth muscle tumor of uncertain malignant potential [title]
Table of Contents
Definition / general | Essential features | Terminology | ICD coding | Epidemiology | Sites | Pathophysiology | Etiology | Clinical features | Diagnosis | Radiology description | Prognostic factors | Case reports | Treatment | Gross description | Gross images | Frozen section description | Microscopic (histologic) description | Microscopic (histologic) images | Virtual slides | Positive stains | Negative stains | Sample pathology report | Differential diagnosis | Additional references | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2Cite this page: Turashvili G. Smooth muscle tumors of uncertain malignant potential. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/uterusSTUMP.html. Accessed December 3rd, 2021.
Definition / general
- Smooth muscle tumor with morphologic features exceeding diagnostic criteria for leiomyoma (including subtypes) but insufficient for a diagnosis of leiomyosarcoma
Essential features
- STUMPs are morphologically heterogeneous and diagnostically challenging, requiring generous sampling for microscopic examination
- Variable diagnostic criteria proposed for spindle cell, myxoid and epithelioid STUMPs
- Usually occur in women of reproductive age or postmenopausal women
- Recurrence rates are 7 - 28%, with higher recurrence rates for epithelioid and myxoid STUMPs
- Recurrent tumors may look histologically similar to the initial STUMP or may be consistent with leiomyosarcoma
Terminology
- Spindle cell STUMP
- Myxoid STUMP
- Epithelioid STUMP
ICD coding
- ICD-O: 8897/1 - smooth muscle tumor of uncertain malignant potential
- ICD-11: 2F76 & XH1EN1 - neoplasms of uncertain behaviour of female genital organs & smooth muscle tumor of uncertain malignant potential
Epidemiology
- Rare
- Usually occurs in women of reproductive age or postmenopausal women
- Mean age ~43 years, 10 years less than mean age for women with leiomyosarcoma (Histopathology 2018;73:284)
- STUMPs that recur are diagnosed in women 10 years younger than women with STUMPs behaving in a benign fashion (Gynecol Oncol 2009;113:324, Am J Surg Pathol 2009;33:992, Best Pract Res Clin Obstet Gynaecol 2011;25:691)
Sites
- Myometrium
- Rarely, broad ligament, ovaries, cervix or vagina
Pathophysiology
- Genomic heterogeneity similar to leiomyosarcoma (ranging from few chromosomal alterations to high chromosomal instability)
- Less frequent chromosomal gains compared with leiomyosarcoma (Mod Pathol 2015;28:1001, Mod Pathol 2018;31:816, Mod Pathol 2019;32:1688)
- Copy number variation may be used diagnostically in spindle cell and myxoid STUMPs (Mod Pathol 2015;28:1001, Anticancer Res 2015;35:6445)
- MED12 mutations in 10% (PLoS One 2012;7:e40015, Eur J Cancer 2015;51:1603, Hum Pathol 2014;45:65)
Etiology
- Unknown
Clinical features
- Symptoms similar to uterine leiomyoma
Diagnosis
- Microscopic examination
Radiology description
- Ultrasonography:
- Usually circumscribed, showing isoechoic or mixed echogenicity with microcystic anechoic areas, poorly or moderately vascularized with both circumferential and intralesional flows and rarely shadowing (Eur J Obstet Gynecol Reprod Biol 2020;251:167)
- Magnetic resonance imaging based on limited data:
- Differentiating STUMP from leiomyosarcoma can be challenging, as both can appear hyperintense on T1 and T2 weighted images (due to necrosis if present) (Abdom Radiol (NY) 2021 May 31 [Epub ahead of print])
- On postcontrast images, both STUMP and leiomyosarcoma can show heterogeneous enhancement (Eur Radiol 2008;18:72)
- STUMPs can demonstrate homogeneous enhancement (Eur J Radiol 2010;74:241)
Prognostic factors
- Recurrence rates are 7 - 28% (Gynecol Oncol 2019;154:631)
- Epithelioid and myxoid STUMPs may be more likely to recur (Am J Surg Pathol 2008;32:98, Histopathology 2018;73:284)
- Mean time to recurrence is 47 months (longer than that for leiomyosarcoma)
- Recurrent tumors may show histologic similarity to the initial STUMP or may be consistent with leiomyosarcoma (Int J Gynecol Cancer 2018;28:233)
- Median survival of 5.5 years for recurrent tumors (Best Pract Res Clin Obstet Gynaecol 2011;25:691)
- Markers of poor prognosis:
- Loss of ATRX or DAXX expression (J Pathol Clin Res 2015;1:95, Cancer 2018;124:4650, PLoS Genet 2016;12:e1005850)
- Genomic index of > 35, 5p and 17p gain, chromosome 13 loss (Mod Pathol 2015;28:1001, Mod Pathol 2018;31:816)
- Immunohistochemical markers (p16, p53, Ki67, p21, BCL2, ER, PR) have no prognostic value (Int J Gynecol Pathol 2008;27:326, Am J Surg Pathol 2013;37:634, Histopathology 2017;71:743)
- Atypical mitoses have no prognostic value (APMIS 2021;129:165)
Case reports
- 37 year old woman with a morcellator port site implantation of STUMP 6 years after minimally invasive myomectomy (J Minim Invasive Gynecol 2016;23:647)
- 37 year old woman treated for infertility and presented with an asymptomatic cervical STUMP (SAGE Open Med Case Rep 2021;9:2050313X211012516)
- 41 year old woman with a giant (38.5 cm) STUMP (Gynecol Oncol Rep 2020;34:100663)
- 41 year old woman with a successful pregnancy following myomectomy of STUMP (Gynecol Oncol Rep 2015;15:1)
Treatment
- Surveillance is warranted every 6 months for 5 years and then yearly (Gynecol Oncol 2019;154:631)
Gross description
- Overlapping features with typical leiomyoma (see leiomyoma)
- Median size: 6.7 cm (range: 2.5 - 12.2 cm) (Histopathology 2018;73:284)
- Tumors associated with recurrence may have irregular borders (Histopathology 2018;73:284)
Gross images
Images hosted on other servers:
Intramural tumor with hemorrhage
Frozen section description
- Not usually diagnosed on frozen section
Microscopic (histologic) description
- Morphologically heterogeneous and diagnostically challenging
- Generous sampling advised for microscopic examination (Mod Pathol 2016;29:S104)
- General diagnostic criteria:
- 1 of the 3 criteria for leiomyosarcoma (coagulative tumor cell necrosis, cytologic atypia, elevated mitotic activity) should be present
- Other useful parameters include atypical mitoses, vascular involvement and infiltrative / irregular margins (Histopathology 2018;73:284, Am J Surg Pathol 2008;32:98)
- General guidelines for spindled smooth muscle tumors:
- Tumors with focal / multifocal or diffuse cytologic atypia and 2 - 4 mitoses / mm2 (6 - 9 mitoses / 10 high power fields [HPF] of 0.55 mm field of diameter [FD] and 0.24 mm2 in area) but lacking coagulative necrosis Am J Surg Pathol 2009;33:992, Am J Surg Pathol 2008;32:98, Histopathology 2018;73:284, Int J Clin Exp Pathol 2014;7:8136, Oncol Lett 2016;11:1425, Am J Surg Pathol 1994;18:535, Int J Gynecol Cancer 2008;18:1121, Int J Gynecol Pathol 2009;28:529, Am J Surg Pathol 2011;35:1626):
- 12 - 17% of STUMPs have these features
- Some STUMPs with fewer mitoses have recurred
- Tumors with unequivocal coagulative necrosis but lacking cytologic atypia or elevated mitotic activity:
- 28% (5/18) of reported cases have recurred (Am J Surg Pathol 2008;32:98, Am J Surg Pathol 1994;18:535, Histopathology 2018;73:284, Int J Gynecol Cancer 2005;15:1210, Eur J Obstet Gynecol Reprod Biol 2018;228:1)
- Distinguishing between coagulative necrosis and early infarct type necrosis can be difficult (Am J Surg Pathol 2007;31:1215, Am J Surg Pathol 2013;37:650)
- Tumors with elevated mitotic activity at > 6 mitoses / mm2 or > 15 mitoses / 10 HPF (FD = 0.55, 0.24 mm2 in area) but lacking coagulative necrosis or cytologic atypia:
- 0% (0/42) of reported cases have recurred (Am J Surg Pathol 1994;18:535, Am J Surg Pathol 2009;33:992, Histopathology 2018;73:284)
- Tumors with diffuse cytologic atypia and uncertain mitotic count, often due to prominent karyorrhexis but lacking coagulative necrosis:
- PHH3 immunohistochemistry may be helpful for accurate assessment of mitotic figures (Histopathology 2017;70:746, Int J Gynecol Pathol 2009;28:316, Int J Clin Exp Pathol 2015;8:4418)
- Tumors with focal / multifocal or diffuse cytologic atypia and 2 - 4 mitoses / mm2 (6 - 9 mitoses / 10 high power fields [HPF] of 0.55 mm field of diameter [FD] and 0.24 mm2 in area) but lacking coagulative necrosis Am J Surg Pathol 2009;33:992, Am J Surg Pathol 2008;32:98, Histopathology 2018;73:284, Int J Clin Exp Pathol 2014;7:8136, Oncol Lett 2016;11:1425, Am J Surg Pathol 1994;18:535, Int J Gynecol Cancer 2008;18:1121, Int J Gynecol Pathol 2009;28:529, Am J Surg Pathol 2011;35:1626):
- Epithelioid STUMP:
- Tumors exceeding the criteria for epithelioid leiomyoma (rounded or polygonal cells with eosinophilic granular or clear cytoplasm lacking cytologic atypia, < 0.8 mitoses / mm2 or < 2 mitoses / 10 HPF, FD = 0.55, 0.24 mm2 in area) but falling short of a diagnosis of epithelioid leiomyosarcoma (moderate to severe cytologic atypia or coagulative necrosis or ≥ 1.6 mitoses / mm2 or ≥ 4 mitoses / 10 HPF, FD = 0.55, 0.24 mm2 in area) (Am J Surg Pathol 1997;21:38, Cancer 1976;37:1853)
- Myxoid STUMP:
- Tumors exceeding the criteria for myxoid leiomyoma (circumscribed, hypocellular and myxoid tumor lacking cytologic atypia or mitotic activity) but falling short of a diagnosis of myxoid leiomyosarcoma (moderate to severe cytologic atypia or coagulative necrosis or > 0.4 mitoses / mm2 / > 1 mitosis / 10 HPF, FD = 0.55, 0.24 mm2 in area or infiltrative / irregular borders) (Am J Surg Pathol 2016;40:285, Adv Anat Pathol 2017;24:354)
Microscopic (histologic) images
Contributed by Gulisa Turashvili, M.D., Ph.D.
Coagulative necrosis
Elevated mitoses
Epithelioid morphology
Irregular borders
Virtual slides
Images hosted on other servers:
Epithelioid STUMP
Epithelioid STUMP
Epithelioid STUMP
Positive stains
- Desmin
- H-caldesmon
- Smooth muscle actin
- Estrogen receptor / ER and progesterone receptor / PR (Am J Surg Pathol 2009;33:992)
- WT1
- Note: expression of smooth muscle markers can be weak in epithelioid and myxoid STUMPs
Sample pathology report
- Uterus with cervix, total hysterectomy:
- Myometrium:
- Smooth muscle tumor of uncertain malignant potential (see comment)
- Leiomyomas and adenomyosis
- Endometrium: proliferative
- Cervix and uterine serosa: unremarkable
- Comment: The largest myometrial nodule is well circumscribed and measures 7.5 cm. Microscopically, it is a smooth muscle neoplasm composed of intersecting fascicles of spindle cells lacking cytologic atypia or elevated mitotic activity (3 mitoses seen per 10 HPF, FD = 0.55). However, multiple foci of unequivocal coagulative tumor cell necrosis are present in several blocks. Despite the lack of cytologic atypia or elevated mitoses, the presence of coagulative necrosis warrants classification as a smooth muscle tumor of uncertain malignant potential.
- Myometrium:
Differential diagnosis
- Conventional (spindle cell) leiomyoma:
- Intersecting fascicles of spindle cells, eosinophilic fibrillary cytoplasm and cigar shaped nuclei lacking coagulative necrosis, cytologic atypia or elevated mitotic activity
- Cellular leiomyoma:
- More cellular compared with the surrounding myometrium
- Thick walled vessels and cleft-like spaces
- Usually spindled cells with scant cytoplasm
- No coagulative necrosis, cytologic atypia or elevated mitoses
- Epithelioid leiomyoma:
- Rounded or polygonal cells with eosinophilic granular or clear cytoplasm with low mitotic count at < 0.8 mitoses / mm2 or < 2 mitoses / 10 HPF (FD = 0.55, 0.24 mm2 in area) and lacking cytologic atypia
- Myxoid leiomyoma:
- Circumscribed, hypocellular, myxoid tumor lacking cytologic atypia or mitotic activity
- Leiomyoma with bizarre nuclei:
- Cells with bizarre nuclei in a background of typical leiomyoma, lacking coagulative necrosis or elevated mitotic activity (usually < 2 mitoses / mm2 or < 5 mitoses / 10 HPF, FD = 0.55 mm, 0.24 mm2 in area)
- Fumarate hydratase deficient leiomyoma:
- Leiomyoma with staghorn vessels, alveolar type edema, scattered cells with bizarre nuclei, enlarged nuclei with prominent nucleoli and perinucleolar haloes, eosinophilic cytoplasmic inclusions
- Mitotically active leiomyoma:
- Leiomyoma with elevated mitotic count at 2.5 - 6 mitoses / mm2 or 6 - 14 mitoses / 10 HPF (FD = 0.55 mm, 0.24 mm2 in area) but lacking coagulative necrosis or cytologic atypia
- Conventional (spindle cell) leiomyosarcoma:
- 2 of 3 diagnostic features present, including coagulative necrosis, cytologic atypia, elevated mitotic count at ≥ 4 mitoses / mm2 or ≥ 10 mitoses / 10 HPF (FD = 0.55, 0.24 mm2 in area)
- Epithelioid leiomyosarcoma:
- Predominant epithelioid morphology (> 50% of overall tumor volume)
- Moderate to severe cytologic atypia or coagulative necrosis or ≥ 1.6 mitoses / mm2 / ≥ 4 mitoses / 10 HPF (FD = 0.55, 0.24 mm2 in area)
- Myxoid leiomyosarcoma:
- Moderate to severe cytologic atypia or coagulative necrosis or > 0.4 mitoses / mm2 / > 1 mitosis / 10 HPF (FD = 0.55, 0.24 mm2 in area) or infiltrative / irregular borders
Additional references
Board review style question #1
Which of the following smooth muscle tumors falls short for a diagnosis of STUMP?
- Smooth muscle tumor lacking coagulative necrosis and cytologic atypia, with 16 mitoses / 10 HPF
- Smooth muscle tumor with 3 mitoses / 10 HPF, lacking coagulative necrosis and cytologic atypia
- Smooth muscle tumor with coagulative necrosis and 2 mitoses / 10 HPF, lacking cytologic atypia
- Smooth muscle tumor with epithelioid morphology and 3 mitoses / 10 HPF, lacking coagulative necrosis and cytologic atypia
- Smooth muscle tumor with myxoid morphology, focally irregular borders and mild cytologic atypia, lacking coagulative necrosis or mitotic activity
Board review style answer #1
B. Smooth muscle tumor with 3 mitoses / 10 HPF, lacking coagulative necrosis and cytologic atypia
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Reference: Smooth muscle tumors of uncertain malignant potential
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Reference: Smooth muscle tumors of uncertain malignant potential
Board review style question #2
Which immunohistochemical markers are useful for differentiating leiomyoma from STUMP?
- CD10, hormone receptors, p53 and p16
- Desmin, h-caldesmon, p53 and p16
- Desmin, h-caldesmon, SMA, CD10 and fumarate hydratase
- Desmin, h-caldesmon, SMA, CD10 and hormone receptors
- Immunohistochemistry has no value in this differential diagnosis
Board review style answer #2
E. Immunohistochemistry has no value in this differential diagnosis
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Reference: Smooth muscle tumors of uncertain malignant potential
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Reference: Smooth muscle tumors of uncertain malignant potential
