Moderator: Dr. Marisa Nucci
Myxoid Leiomyosarcoma of Uterus
Marisa R. Nucci, M.D.
Brigham and Women's Hospital
Boston, MA, USA
A 33-year-old woman presented with pelvic pain and abnormal uterine
bleeding. Clinical examination revealed a large uterine mass and the patient underwent total abdominal
hysterectomy and bilateral salpingo-oophorectomy. On gross examination, the uterus was asymmetrically
distorted by a 6.5 cm intramural mass, which on section was multinodular, white-grey and had a soft,
gelatinous consistency with areas of hemorrhage.
Myxoid Leiomyosarcoma of Uterus
Despite representing the most common uterine sarcoma (accounting for
approximately 25% of malignant mesenchymal tumors of the uterus), leiomyosarcoma is uncommon,
representing less than 2% of all uterine malignancies with an annual incidence estimated to be 0.64 cases
per 100,000 women.
Risk factors include oral contraceptive use and tamoxifen; in
addition, black women are at greater risk for the development of disease.
age of patients diagnosed with leiomyosarcoma is usually in the fifth to sixth decade and the most common
presenting symptoms are dysfunctional uterine bleeding and/or pelvic pain.
clinical examination typically reveals an enlarged uterus, many leiomyosarcomas are unsuspected and
presumed to be enlarged leiomyomata prior to surgery. In a postmenopausal patient, the clinical
impression of a large or rapidly enlarging fibroid should raise the suspicion for malignancy.
Uterine leiomyosarcoma is an aggressive tumor that has a propensity for local recurrence and/or
metastasis, most commonly to liver and lung. Lymph node dissection is typically only performed in
patients with clinically suspicious/enlarged nodes as regional lymph node involvement is unusual and is
only present in patients with advanced stage disease.
Estimates of overall 5-year
survival rates varies (with an estimated an overall 5 year survival rate between 45-65%) which is likely
the result of small numbers in some series, differences in the number of patients with early stage
disease, and shifting criteria for the diagnosis of leiomyosarcoma.
Overall, stage is a significant prognostic factor related to outcome.
Molecular Genetics :
Leiomyosarcoma, in contrast to leiomyomata, is characterized
cytogenetically by complex numerical and structural abnormalities, which may vary from one neoplastic
cell to the next within the same tumor mass, suggesting that there is a high degree of genomic
This genetic unrest is supported by comparative genomic hybridization,
which most commonly has shown loss of heterozygosity for the long arms of chromosomes 10 and 13.
Leiomyomata also have a different transcriptional profile than leiomyosarcoma (the latter
typically having downregulation of gene expression), supporting different pathogenetic pathways for the
development of these tumors. 
Pathologic Features :
Leiomyosarcomas are typically a solitary or dominant uterine mass, are
most commonly located within the wall but may be submucosal or subserosal, and have a mean diameter of 9
Most have a distinctly different appearance than leiomyomata, being less well
circumscribed with a softer consistency, grey to cream color and a variable amount of geographic
hemorrhage and necrosis, which may appear yellow or green on gross inspection. Although the presence of
any of these unusual gross features is worrisome for malignancy (and should prompt extensive sampling),
the diagnosis of leiomyosarcoma is entirely based on the tumor's histologic appearance. The vast
majority of leiomyosarcomas are of the spindle cell type, however, a myxoid variant does occur, which has
different criteria for the diagnosis of malignancy.
Spindle Cell Leiomyosarcoma
This histologic variant of leiomyosarcoma
is composed of intersecting fascicles of spindled cells with varying amounts of eosinophilic cytoplasm.
Criteria for malignancy is based on a landmark study by Bell et al.,  in which a
combination of histologic features is evaluated, which include: 1) the presence and extent of
significant nuclear atypia (practically defined as atypia discernible on low power examination, i.e. with
the10 X objective), 2) the mitotic rate and, 3) the presence or absence of coagulative tumor cell
necrosis. A diagnosis of leiomyosarcoma is made when:
This latter scenario is very uncommon and raises the significant diagnostic problem of what comprises
true tumor cell necrosis vs. benign, usually ischemic, degenerative changes. Coagulative tumor cell
necrosis is characterized by 1) an irregular, angulated border ('geographic' appearance), 2) a sharp
interface between the viable and necrotic cells (in contrast to a rim of granulation or hyalinized tissue
characteristic of ischemia), 3) the presence of apoptotic/nuclear debris at the interface and 4) atypical
ghost cells (for those tumors with nuclear atypia) within the necrotic areas.
- There is diffuse moderate to severe nuclear atypia AND the mitotic count
measures >10 per 10 high power fields (HPF)
- There is diffuse or multifocal moderate to severe nuclear atypia AND tumor
cell necrosis AND any degree of mitotic activity > 1 per 10 HPF
- There is no to minimal nuclear atypia AND there is tumor cell necrosis AND the mitotic count measures >10 mitoses per 10 HPF.
This variant of leiomyosarcoma
also typically affects women in their sixth decade who may present with abnormal vaginal bleeding, pelvic
pain and/or a pelvic mass. However, in contrast, myxoid leiomyosarcoma usually will have a more
gelatinous gross appearance with a glistening cut surface, although this may vary in extent depending on
the amount of extracellular myxoid matrix deposition. The tumor cells may be spindled or stellate and
the degree of (Alcian blue positive) extracellular matrix deposition may obscure the tumors fascicular
architecture. Although the majority of the tumor may have a bland cytomorphologic appearance, tumor
cells typically exhibit at least focal moderate atypia. Diagnostic criteria separating myxoid
leiomyosarcoma from myxoid leiomyoma is not well established since this type of tumor is rare. Atkins
et al. have suggested that a mitotic rate in excess of 2 per 10 high power
fields, regardless of the presence or absence of either atypia or necrosis, will separate benign and
malignant myxoid tumors. For practical purposes, the diagnosis of myxoid leiomyosarcoma should be
considered if any of the following is present:
- There is moderate to marked cytologic atypia.
- There is coagulative tumor cell necrosis.
- Mitotic activity exceeds 2 per 10 high power fields.
- There is destructive infiltration of the surrounding myometrium.
In addition to myxoid leiomyoma, the
differential diagnosis of myxoid leiomyosarcoma includes the myxoid variant of endometrial stromal
sarcoma and the relatively recently described inflammatory myofibroblastic tumor of the uterus. The
myxoid variant of endometrial stromal sarcoma 
1) more frequently presents as a polypoid endometrial mass, 2) has a characteristic
multinodular or tongue-like pattern of myometrial infiltration, 3) at least focally exhibits the presence
of typical endometrial stromal neoplasia with characteristic growth pattern and presence of arterioles,
and 4) is negative for the smooth muscle marker h-caldesmon. Inflammatory myofibroblastic
tumor  can be distinguished from
myxoid leiomyosarcoma by its 1) typically pushing border without vascular invasion, 2) its prominent
lymphoplasmacytic infiltrate and 3) its immunohistochemical expression of ALK.
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