Endometrial Lesions, Unusual Tumors, and Extrauterine cancer
Table 10.1 Tumors of the uterine corpus
Endometrial carcinoma
Endometrioid adenocarcinoma (and variants)
Mucinous adenocarcinoma
Serous adenocarcinoma
Clear cell adenocarcinoma
Mixed carcinomas
Rare types—squamous, transitional, small cell, undifferentiated
endometrial stromal nodule (benign)
endometrial stromal sarcoma (low-grade and undifferentiated)
Leiomyoma (benign), with growth and histologic variants.
rare types—perivascular epithelioid cell tumor, adenomatoid
Mixed epithelial and mesenchymal
Adenofibroma and adenomyoma (benign)
Carcinosarcoma (or malignant mixed mullerian tumor)
Gestational trophoblastic disease
Hydatidiform mole, choriocarcinoma, and trophoblastic tumors
Metastatic tum ors and lymphoma and miscellaneous
adapted from the Who histological classification.
deep myometrial involvement, invade lymphovascular spaces,
and exhibit both nodal and peritoneal metastases. In compari-
son to their type I counterpart, type II carcinomas are responsi-
ble for a disproportionately large number of endometrial cancer
deaths.4 Intraepithelial carcinoma of serous and clear types are
considered to be the precursor lesion.5-8 Estrogenic states do not
predispose to the development of type II carcinoma.
The separation of endometrial carcinoma into two distinct
diseases can lead to diagnostic challenges in some cases. For
example, some endometrial carcinomas showed a mixed type
I and II morphology. In addition, poorly differentiated endo-
metrioid adenocarcinomas (type I) show significant overlap
in both cytologic features and behavior with type II adeno-
Molecular Pathology of Endometrial
Molecular genetic studies of endometrial adenocarcinoma are
incomplete but have served to confirm the division of endome-
trial carcinoma into types I and II. Type I carcinomas are char-
acterized by derangements in PTEN, the DNA mismatch repair
system, and in the K-ras proto-oncogene. The tumor suppressor
gene p53 may have a role in the progression of type I carci-
nomas, but not in their initiation. The most frequently altered
gene, PTEN, is a tumor suppressor gene involved in signal trans-
duction of cell growth and apoptosis, and is altered not only in
up to one-half of type I carcinomas, but also in a proportion
of both atypical and non-atypical endometrial hyperplasias.
Alterations in PTEN may be central to initiation of type I
In contrast, the p53 tumor suppressor gene is altered in the
vast majority of type II carcinomas, as well as their precursor
lesion, endometrial intraepithelial carcinoma. The marked, dif-
fuse immunohistochemical staining for p53 protein can be used
to confirm the histopathologic diagnosis of type II carcinomas.
clinical epidemiology of endometrial
Endometrial carcinoma is one of the most common cancers in
women living in developed countries. For example, endometrial
cancer is the fourth most common cancer of Canadian women
(after breast, lung, and colorectal), and composes more than
5% of all new cancer cases. Since most women with endome-
trial carcinoma present with early stage disease, however, the
case fatality rate is lower than that in many other cancer sites.
Consequently, the mortality rate from endometrial carcinoma
ranks ninth in comparison to other tumoral sites in Canadian
Presentation and Spread of endometrial
The clinical presentation of types I and II carcinomas are often
different. About 80-90% of all endometrial carcinomas are type I.
Women with type I carcinoma are usually premenopausal, peri-
menopausal, or early postmenopausal. Chronic anovulation
in the reproductive aged women, a state resulting in sustained
estrogen stimulation, is associated with an increased risk of type
I carcinoma in this age group. Other risk factors for the develop-
ment of type I carcinomas are obesity, diabetes mellitus, and
hypertension. Estrogen administration unopposed by the use
of progestins in the postmenopausal woman is associated with
the development of type I carcinomas. In contrast, the woman
with type II endometrial carcinoma is usually elderly and late
menopausal. Frequently, these women are not obese, diabetic,
or hypertensive.
Endometrial carcinomas may present as either a focal,
polypoid tumoral mass or as an irregular thickening of the
the usual presenting symptoms, are results of tumoral necro-
sis and breakdown. As the tumor advances the endometrium
is replaced by a diffuse carpet of friable tumor. The carcinoma
will penetrate into the myometrium and cervix. With access to
lymphatic spaces spread to regional (pelvic) lymph nodes will
occur. Spread through the fallopian tube to the peritoneum is
another source of metastatic disease and is common in type II
carcinomas. Advanced cases of endometrial carcinoma are char-
acterized by hematogeneous spread to more distant sites. The
"stage" of a tumor is the extent of spread of the carcinoma at
presentation, and is a key determinant of both prognosis and
management (Table 10.2).
The Histopathology of endometrial
Both types I and II endometrial carcinomas exhibit columnar cell
or glandular differentiation, and are thus designated as adeno-
carcinomas. Rarely, squamous and undifferentiated carcinomas
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