Uterus
Smooth muscle tumors
Leiomyosarcoma
Author: Paulette Mhawech-Fauceglia, M.D.
Editorial Board Member: Jennifer A. Bennett, M.D.
Editor-in-Chief: Debra L. Zynger, M.D.
Topic Completed: 5 December 2019
Minor changes: 20 September 2021
Copyright: 2002-2021, PathologyOutlines.com, Inc.
PubMed search: Leiomyosarcoma[TI] uterus[TI] pathology full text[sb]
Table of Contents
Definition / general | Essential features | Terminology | ICD coding | Epidemiology | Sites | Etiology | Clinical features | Radiology description | Radiology images | Prognostic factors | Case reports | Treatment | Clinical images | Gross description | Gross images | Frozen section description | Microscopic (histologic) description | Microscopic (histologic) images | Positive stains | Negative stains | Molecular / cytogenetics description | Sample pathology report | Differential diagnosis | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2Cite this page: Mhawech-Fauceglia P. Leiomyosarcoma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/uteruslms.html. Accessed December 6th, 2021.
Definition / general
- Rare tumor derived from smooth muscle
- Most common uterine sarcoma
Essential features
- Rare, de novo tumor
- 3 types: spindle / conventional, epithelioid and myxoid
- Triad of histologic features: severe atypia, increased mitoses and tumor cell necrosis
- Poor prognosis and limited therapeutic options (Oncol Res Treat 2018;41:680, Curr Probl Cancer 2019;43:283)
Terminology
- Uterine leiomyosarcoma
ICD coding
- ICD-10: C55 - malignant neoplasm of uterus, part unspecified
Epidemiology
- Peaks at ages 40 - 69; average age is 51 (Curr Probl Cancer 2019;43:283, Int J Gynaecol Obstet 2018;143:51)
Sites
- Uterus
Etiology
- De novo
- Very rare cases from a pre-existing leiomyoma (J Minim Invasive Gynecol 2019 Jun 29 [Epub ahead of print])
Clinical features
- Usually discovered incidentally during hysterectomy for fibroids (Am J Obstet Gynecol 2019;220:179.e1)
- Symptoms include abnormal vaginal bleeding and those related to a pelvic mass
- 70 - 75% of patients present with stage I and II disease
Radiology description
- CT: might show irregular central zones of low attenuation, suggesting extensive necrosis and hemorrhage
- MRI: has been speculated that an irregular margin of leiomyoma could be suggestive of sarcomatous transformation but it is not specific (J Magn Reson Imaging 2019;49:e282)
Radiology images
Images hosted on other servers:
Very large mass
Lung metastasis
Prognostic factors
- Even with tumor confined to uterus, it is considered aggressive
- There is no consensus on how to grade; therefore, it is not advised to grade as low or high grade
- Most powerful prognostic factor is tumor stage; however, other factors such as tumor size, mitotic count and percentage of necrosis have been suggested to predict patient's outcome (Curr Probl Cancer 2019;43:283)
Case reports
- 16 year old girl with leiomyosarcoma in a prior benign myomectomy site (Gynecol Oncol Rep 2019;29:126)
- 30 year old woman with leiomyosarcoma (Oncol Res Treat 2018;41:680)
- 50 year old woman with synchronous well differentiated endometrioid adenocarcinoma and leiomyosarcoma (Int J Gynecol Pathol 2019 May 30 [Epub ahead of print])
- 51 year old woman with pulmonary metastasis (J Gen Fam Med 2017;18:418)
- 52 year old woman with pelvic mass (Case Rep Obstet Gynecol 2019;2019:9381230)
- 54 year old woman with leiomyosarcoma metastasized to the scalp (Diagn Pathol 2012;7:85)
Treatment
- Total abdominal hysterectomy, bilateral salpingo-oophorectomy for postmenopausal females and those with metastatic disease
- Total abdominal hysterectomy without bilateral salpingo-oophorectomy for premenopausal females
- Lymph node sampling is unnecessary, as < 3% of patients will have lymph node involvement
- Adjuvant chemotherapy / radiotherapy has not been proven beneficial (Sarcoma 2019;2019:3561501)
- Hormonal therapy may be an option in hormone receptor positive tumors
Clinical images
Images hosted on other servers:
Very large mass
Gross description
- Bulky, fleshy tumor invading into myometrial wall or polypoid tumor projecting into lumen
- Often hemorrhagic or necrotic
- Grossly appears invasive / infiltrative
- Very large with a mean diameter of 10 cm
- Myxoid leiomyosarcoma:
- Gelatinous cut surface
- May appear well circumscribed
Gross images
Images hosted on other servers:
Large mass
Frozen section description
- Frozen section is not recommended for diagnosis
Microscopic (histologic) description
- Conventional / spindle cell type:
- Diagnosis requires 2 of 3 histologic features (marked cellular atypia, > 10 mitoses/10 high power fields and tumor cell necrosis)
- Cellular tumor comprised of spindled / fascicular cells with moderate to severe pleomorphism
- Mitotic index is typically high and atypical mitoses are often seen
- Often has an infiltrative border
- Multinucleated cells may be seen
- Myxoid leiomyosarcoma:
- Diagnosed based on presence of any cytologic atypia, tumor cell necrosis or > 1 mitosis/10 high power fields (Am J Surg Pathol 2016;40:285)
- Hypocellular tumor with abundant myxoid stroma
- Epithelioid leiomyosarcoma:
- Diagnosed based on the presence of moderate to severe cytologic atypia or tumor cell necrosis or ≥ 4 mitoses/10 high power fields
- Round or polygonal cells with eosinophilic or clear cytoplasm
- Tumor cells arranged in sheets, nests or cords
Microscopic (histologic) images
Contributed by Paulette Mhawech-Fauceglia, M.D.
Hypercellular tumor
Nuclear atypia
Numerous mitoses
Necrosis
Positive stains
- Smooth muscle markers including caldesmon, desmin and SMA (unless poorly differentiated or myxoid, Am J Surg Pathol 2001;25:253)
- ER / PR, as well as keratins, EMA and CD10 are common (Am J Surg Pathol 2002;26:403)
- p53 and p16 are often overexpressed (Histopathology 2017;70:1138)
Negative stains
- HMB45 is typically negative to focal
- Rare myxoid leiomyosarcomas are ALK positive (Am J Surg Pathol 2016;40:285)
- MelanA, MITF
Molecular / cytogenetics description
- Complex numerical and structural chromosomal aberrations suggesting that chromosomal instability is the hallmark of uterine smooth muscle tumors
- TP53 (33%), ATRX (26%), MED12 (21%) mutations (PLoS Genet 2016;12:e1005850)
- NR4A3-PGR fusion or PGR rearrangements have been documented in 35% of epithelioid leiomyosarcomas (Am J Surg Pathol 2019;43:810)
- PLAG1 rearrangements have been identified in ~25% of myxoid leiomyosarcomas (Am J Surg Pathol 2019;43:382)
Sample pathology report
- Uterus, total abdominal hysterectomy:
- Uterine leiomyosarcoma (see synoptic report)
Differential diagnosis
- Endometrial stromal sarcoma:
- Low grade endometrial stromal sarcoma:
- High grade endometrial stromal sarcoma:
- Leiomyoma variants:
- Mitotically active leiomyoma
- Cellular leiomyoma
- Leiomyoma with bizarre nuclei
- Myxoid leiomyoma
- Epithelioid leiomyoma
- Smooth muscle tumors of uncertain malignant potential (STUMP)
- Inflammatory myofibroblastic tumor:
- Myxoid stroma distributed among spindled and inflammatory cells resulting in a nodular fasciitis-like morphology
- Atypia can range from mild to severe
- ALK staining is seen in most tumors and ALK rearrangement is seen in 80% (Mod Pathol 2017;30:1489)
- Perivascular epithelioid cell tumor:
- Composed of epithelioid cells with variable atypia and mitoses
- Typically strongly HMB45 positive and often show melanA or MIFT expression
- A subset harbor TSC1 and TSC2 mutations or TFE3 fusion (Am J Surg Pathol 2018;42:1370)
Board review style question #1
Which of the following molecular alterations has been reported in uterine leiomyosarcomas?
- ALK fusions
- BCOR fusions
- JAZF1 fusions
- TP53 mutations
- TSC2 mutations
Board review style answer #1
Board review style question #2
A uterine mass in a 50 year old woman has a tumor shown in the photomicrograph which expresses SMA, ER, PR and caldesmon and is negative for CD10 and CD117 / KIT. What is your diagnosis?
- Endometrial stromal sarcoma
- Gastrointestinal stromal tumor
- High grade endometrial adenocarcinoma
- Leiomyosarcoma
Board review style answer #2
