UTERINE CARCINOMA

Introduction

1. Malignant tumors of the uterine corpus are broadly divided into three main
types: carcinomas, sarcomas, and carcinosarcomas
2. Pure sarcomas differentiate toward smooth muscle (leiomyosarcoma) or
toward endometrial stroma (endometrial stromal tumors).
3. Carcinosarcomas are mixed tumors demonstrating both epithelial and stromal
components.
a. These have also been known as malignant mixed müllerian tumor
(MMMT)
4. In general, uterine sarcomas and carcinosarcomas grow quickly, lymphatic or
hematogenous spread occurs early, and the overall prognosis is poor.

Epidemiology and risk factor

1. Sarcomas account for approximately 3 to 8 percent of all malignancies of the

uterine corpus
2. In 2009, the International Federation of Gynecology and Obstetrics (FIGO)
reclassified carcinosarcomas as a metaplastic form of endometrial carcinoma.
3. Because of their infrequency, uterine sarcomas and carcinosarcomas have few
identified risk factors. These include chronic excess estrogen exposure,
tamoxifen use, African American race, and prior pelvic radiation. In contrast,
combination oral contraceptive pill use and smoking appear to lower risks for
some of these tumors

Pathogenesis

1. Leiomyosarcomas have a monoclonal origin, and although commonly believed

to arise from benign leiomyomas, for the most part they do not.
a. Endometrial stromal tumors (ESS) have heterogeneous chromosomal
aberrations However, the pattern of rearrangements is clearly
nonrandom, and chromosomal arms 6p and 7p are frequently involved
2. Uterine carcinosarcomas are monoclonal, biphasic neoplasms. Namely, they
are composed of separate but admixed malignant epithelial and malignant
stromal elements
a. Both the carcinoma and sarcoma components are thought to arise from
a common epithelial progenitor cell. Acquisition of any number of
genetic mutations, including defects in p53 and DNA mismatch repair
genes, may be sufficient to trigger tumorigenesis

Diagnosis

1. Sign and symptomps

a. As in endometrial cancer, abnormal vaginal bleeding is the most frequent
symptom for uterine sarcomas and carcinosarcomas
 b. Pelvic or abdominal pain is also common.
c. Up to one third of women will describe significant discomfort that may result
from passage of clots, rapid uterine enlargement, or prolapse of a
sarcomatous polyp through an effaced cervix
d. Profuse, foul-smelling discharge may be obvious, and gastrointestinal and
genitourinary complaints are also frequent.
e. With rapid growth, a uterus may extend out of the pelvis into the mid- or
upper abdomen
f. Although uterine leiomyosarcomas do tend to grow quickly, no criteria
define what constitutes significant growth. Despite these often-dramatic
presentations, many women with uterine sarcoma and carcinosarcoma will
have few symptoms other than abnormal vaginal bleeding and a seemingly
normal uterus on physical examination.
2. Diagnosis
a. Endometrial sampling
i. The sensitivity of an office endometrial biopsy or dilatation and
curettage (D & C) to detect sarcomatous elements is lower than
that for endometrial carcinomas.
ii. With carcinosarcoma, sampling will more often lead to a correct
diagnosis, although in many cases only the carcinomatous
features are evident.
b. Lab Testing
i. Elevated preoperative serum cancer antigen 125 (CA125) levels
may indicate extrauterine disease and deep myometrial invasion
in patients with carcinosarcoma. After surgery, CA125
measurement may be a somewhat useful marker to monitor
disease response
c. Imaging
i. Imaging studies are often helpful if sarcoma is diagnosed before
hysterectomy. In most cases, a computed tomography (CT) scan
of the abdomen and pelvis is routinely performed. This serves at
least two purposes. First, sarcomas often violate normal soft
tissue planes in the pelvis, and therefore, unresectable tumors
may be identified preoperatively. Second, extrauterine
metastases may be found. In either case, treatment may be
altered based on radiographic findings.

Pathology

1. Uterine mesenchymal tumors are classified broadly into pure and mixed
tumors
2. Also, the term homologous denotes tissues normally found in the uterus and
heterologous refers to tissue foreign to the uterus.
3. Pure sarcomas are virtually all homologous and differentiate into mesenchymal
tissue that is normally present within the uterus, such as smooth muscle
(leiomyosarcoma) or stromal tissue within the endometrium (endometrial
stromal tumors).

WHO Histological Classification of Mesenchymal Tumors of the Uterus

Mesenchymal tumors
 Leiomyoma
o Cellular leiomyoma
o Leiomyoma with bizarre nuclei
o Mitotically active leiomyoma
o Hydropic leiomyoma
o Apoplectic leiomyoma
o Lipomatous leiomyoma (lipoleiomyoma)
o Epithelioid leiomyoma
o Myxoid leiomyoma
o Dissecting (cotyledonoid) leiomyoma
o Diffuse leiomyomatosis
o Intravenous leiomyomatosis
o Metastasizing leiomyoma
 Smooth muscle tumor of uncertain malignant potential
 Leiomyosarcoma
o Epithelial leiomyosarcoma
o Myxoid leiomyosarcoma
 Endometrial stromal and related tumors
o Endometrial stromal nodule
o Low grade endometrial stromal sarcoma
o High grade endometrial stromal sarcoma
o Undifferentiated endometrial sarcoma
o Uterine tumor resembling ovarian sex cord tumor
 Miscellaneous mesenchymal tumors
o Rhabdomyosarcoma
o Perivascular epithelioid cell tumor
 Benign
 Malignant
 Others

Mixed epithelial and mesenchymal tumors

 Adenomyoma
 Atypical polypoid adenomyoma
 Adenofibroma
 Adenosarcoma
 Carcinosarcoma (malignant müllerian mixed tumor,
metaplastic carcinoma)

4. Mixed sarcomas contain a malignant mesenchymal component admixed with

an epithelial element. If the epithelial element is also malignant, the tumor is
 termed carcinosarcoma. If the epithelial element is benign, the term
adenosarcoma is used. Carcinosarcomas can be either homologous or
heterologous, reflecting the pluripotentiality of the uterine primordium.

5. Leiomiosarcoma
a. Leiomyosarcomas account for 1 to 2 percent of all uterine malignances.
b. The median age at presentation was 52 years.
c. Most tumors (68 percent) were stage I at the time of diagnosis, and stage
II (3 percent), stage III (7 percent), and stage IV cancer (22 percent)
formed the remainder
d. The histologic criteria for diagnosing leiomyosarcoma are somewhat
controversial but include the frequency of mitotic figures, extent of nuclear
atypia, and presence of coagulative tumor cell necrosis

Diagnostic Criteria for Uterine Leiomyosarcoma

Coagulative Mitotic Index a Degree of Atypia
Tumor Cell
Necrosis
Present ≥10 MF/10 HPF None
Present Any Diffuse, significant
Absent ≥10 MF/10 HPF Diffuse, significant
MF/10 HPF = the total number of mitotic figures (MF) counted when 10
high-powered fields (HPF) are examined.

e. Leiomyoma (A, B) and leiomyosarcoma (C, D). A. Leiomyomas tend to be

well-circumscribed masses. This leiomyoma shows a well-demarcated
interface (arrows) with the less cellular myometrium above it. B. Although
leiomyomas may have variable histologic features, most are composed of
bland spindled cells with blunt-ended nuclei and limited mitotic activity. C.
Leiomyosarcoma is a malignant smooth muscle neoplasm that may differ
markedly in its microscopic appearance from case to case. Generally,
leiomyosarcoma shows some combination of coagulative tumor necrosis,
increased mitotic activity, and/or nuclear atypia. This example has marked
nuclear atypia and pleomorphism and an infiltrative growth pattern at its
periphery. This differs from the usually smooth, pushing border of typical
leiomyomas. D. This particular example has moderate to marked nuclear
atypia.
Staging

FIGO Staging for Uterine Sarcomas (Leiomyosarcomas, Endometrial Stromal

Sarcomas, Adenosarcomas, and Carcinosarcomas)
Stage Characteristics
Leiomyosarcomas
I Tumor limited to uterus
IA <5 cm
IB >5 cm
II Tumor extends to the pelvis
IIA Adnexal involvement
IIB Tumor extends to extrauterine pelvic tissue
III Tumor invades abdominal tissues (not just protruding into the
IIIA abdomen)
IIIB One site
IIIC >One site
Metastasis to pelvic and/or paraaortic lymph nodes
IV
IVA Tumor invades bladder and/or rectum
IVB Distant metastasis
Adenosarcomas and endometrial stromal sarcomasa
I Tumor limited to uterus
IA Tumor limited to endometrium/endocervix with no myometrial invasion
IB Less than or equal to half myometrial invasion
 IC More than half myometrial invasion
II Tumor extends to the pelvis
IIA Adnexal involvement
IIB Tumor extends to extrauterine pelvic tissue
III Tumor invades abdominal tissues (not just protruding into the
IIIA abdomen)
IIIB One site
IIIC >One site
Metastasis to pelvic and/or paraaortic lymph nodes
IV
IVA Tumor invades bladder and/or rectum
IVB Distant metastasis
Carcinosarcomas
Carcinosarcomas should be staged as carcinomas of the endometrium (Table 33-9).
a

Note: Simultaneous tumors of the uterine corpus and ovary/pelvis in association with
ovarian/pelvic endometriosis should be classified as independent primary tumors.