2012 EDUCATIONAL BOOK - American Society of Clinical Oncology

Uterine Sarcomas: Histology and Its
Implications on Therapy
Overview: Uterine sarcomas are rare cancers, they comprise
only 5% of all uterine malignancies. There are about 2,000
cases of uterine sarcoma diagnosed annually in the United
States. Uterine sarcomas may be categorized as either
favorable-risk, low-grade malignancies with a relatively good
prognosis or as poor-risk, high-grade cancers that carry a
high risk for tumor recurrence and disease progression.
Expert histologic review is critical for appropriate diagnosis
and management. Uterine sarcoma histologies considered to
carry a more favorable prognosis include low-grade endometrial
stromal sarcomas and adenosarcomas. The high-grade
sarcomas include high-grade leiomyosarcomas, high-grade
undifferentiated endometrial sarcomas, and adenosarcomas
with sarcomatous overgrowth.
Low-Grade Endometrial Stromal Sarcomas
ENDOMETRIAL STROMAL sarcomas (ESS) are, by
definition, low-grade malignancies. Histologically they
have bland appearance, with few mitotic figures. Immunohistochemistry
(IHC) stains for desmin, CD10, estrogen
receptor (ER), and progesterone receptor (PR) are typically
positive. Smooth muscle markers (h-caldesmon, smooth
muscle actin) are generally negative in ESS. 1,2 A chromosomal
translocation, (t(7;17)(p15;q21), which fuses two zinc
finger genes, JAZF1/JJAZ, has been described in the majority
of ESS and may be useful for distinguishing ESS from
high-grade, undifferentiated endometrial sarcoma (HGUS)
and from leiomyosarcoma (LMS). 3,4
Fifteen percent to 30% of patients with ESS may have
evidence of metastatic disease at the time of diagnosis, with
lung being the most common site for metastatic disease.
However, reflecting the low-grade, favorable behavior of this
tumor, five-year survival rates are 60% to 90% across all
stages of disease. 5,6 There are no randomized trials assessing
the influence of bilateral salpingo-oophorectomy (BSO)
on recurrence and survival in ESS. Some retrospective
studies have shown higher recurrence rates among patients
with retained ovaries. 7 Surveillance, Epidemiology and End
Results (SEER) retrospective data did not show worse overall
survival for women who did not undergo BSO, but this
study did not address recurrence rates, and the number of
patients with retained ovaries was very small. 8 Lymph node
involvement has been reported to be found in zero to onethird
of patients, and whether routine lymph node dissection
of normal-appearing nodes in ESS is necessary remains
controversial. 8,9
For patients with uterus-limited, completely resected
ESS, there are no data to support routine adjuvant therapy.
Retrospective SEER data showed poorer overall survival
among patients who received adjuvant pelvic radiation
(80.1%) than among those who had surgery alone (90.7%). 10
There is no role for adjuvant cytotoxic therapy in ESS, and
adjuvant hormonal treatment has not been prospectively
studied. It is reasonable to avoid estrogen replacement
therapy in patients with as diagnosis of ESS, although there
are no prospective randomized trials addressing this issue.
356
By Martee L. Hensley, MD
The favorable histology, low-grade uterine sarcomas may be
cured with surgical resection of uterus-limited disease. These
tumors are often hormone-sensitive, and treatment with
hormonal therapies may be efficacious for patients with advanced,
unresectable disease. High-grade uterine leiomyosarcomas
and undifferentiated endometrial sarcomas carry a
high risk for recurrence, even after complete resection of
uterus-limited disease. No adjuvant intervention has been
shown to improve survival outcomes. Advanced, metastatic
disease is generally treated with systemic cytotoxic therapies,
which may result in objective response but is not curative.
Selected patients with isolated metastatic disease and a long
disease-free interval may benefit from metastatectomy.
Responses to cytotoxic chemotherapy for advanced disease
would be expected to be low in ESS, due to its indolent
growth rate. Since endometrial stromal sarcomas frequently
express ER and PR, objective responses of advanced disease
to hormonal interventions, such as treatment with aromatase
inhibitors, have been documented. 11,12
Adenosarcomas
Uterine adenosarcomas are low-grade malignancies that
arise most commonly in the uterine fundus. Histologically
they are characterized by a mixed histologic appearance that
contains benign-appearing glandular epithelial components
and low-grade endometrial stromal sarcoma. 13 Experienced
histologic review is required to exclude the presence of
“sarcomatous overgrowth” (see below), the presence of which
portends a poor prognosis.
In the absence of sarcomatous overgrowth, adenosarcomas
have a favorable prognosis, with 5-year survival rates
exceeding 90%. 14 Adenosarcomas are rarer than endometrial
stromal sarcomas, thus data regarding treatment are
very limited. Since the malignant portion of adenosarcomas
resembles endometrial stromal sarcoma, management recommendations
are sometimes extrapolated from ESS data.
Like ESS, adenosarcomas commonly express ER, PR, and
CD10 15 ; and, as with ESS, it is reasonable to perform
bilateral oophorectomy, and to avoid hormone replacement
therapy. Table 1 provides a summary of histologic features,
prognosis, and management issues for the favorable risk,
low-grade uterine sarcomas.
From the Memorial Sloan-Kettering Cancer Center, Weill Cornell Medical College, New
York, NY.
Author’s disclosures of potential conflicts of interest are found at the end of this article.
Address reprint requests to Author and Session Chair contact information: Martee L.
Hensley, MD, Associate Attending, Gynecologic Medical Oncology, Memorial Sloan-
Kettering Cancer Center, Associate Professor of Medicine, Weill Cornell Medical College,
300 E. 66 th Street, Suite 1355, New York, NY 10065; email: hensleym@mskcc.org.
© 2012 by American Society of Clinical Oncology.
1092-9118/10/1-10