VII. Malignant Neoplasms
After completing this section you will be able to:
- classify the malignant tumors of the uterine corpus
- describe epidemiological features including risk factors
- describe clinical appearance
- describe/recognize histologic features and grade lesions
- predict clinical behavior and discuss factors influencing
- Endometrial Adenocarcinoma
This is a common neoplasm in women. The incidence varies widely throughout
the world. It is the most common invasive tumor of the female genital tract
in the U.S. and is decreasing in frequency in women in their 50s in whom it
is related to unopposed estrogen stimulation. However, there is a slight but
continuous increased rates for women older than 60 years, which is probably
not related to unopposed estrogen exposure. In developing countries, the incidence
is four to five times less than in Europe and N. America. Worldwide, it is
the fifth commonest cancer in women.
Risk factors include obesity (women with upper body fat have 3X the risk
of women with lower body fat), estrogen therapy, nulliparity (as a result
of infertility due to chronic anovulation), chronic anovulation, late menopause,
hypertension, diabetes, tamoxifen therapy, and high socioeconomic status.
The disease may follow atypical hyperplasia but may occur independently of
it especially in older patients.
Multiple or synchronous malignancies: Simultaneous or subsequent primary
cancers involving the breast, ovary and large intestines occur more frequently
in patients with endometrial adenocarcinoma than might be expected. The converse
also appears to be true in that women with breast and ovarian cancers have
a higher than expected risk of developing subsequent primary endometrial carcinoma.
This is believed to be due to a genetic predisposition a cancer family
Question: What is the role of cigarette smoking in the etiology of
Most patients are between 50 and 59 years. Approximately 5% of affected women
are under 40 years of age. Nearly 50% of these women who are under 40 years
are nulliparous and more than 75% of them are obese.
Endometrial adenocarcinoma manifests as abnormal vaginal bleeding. The tumor
may grow in a diffuse or polypoid pattern. It often involves multiple areas
of the endometrium.
Endometrioid adenocarcinoma presenting as a polypoid mass filling the endometrial
The tumors are composed of glandular cells. The commonest type is Endometrioid
adenocarcinoma. Other types include clear cell, adenosquamous, and papillary
serous carcinoma. Endometrioid carcinoma may show areas of squamous differentiation
in which the squamous epithelium is well differentiated with very little atypia.
A tumor with such features is referred to as adenoacanthoma. In adenosquamous
carcinoma both glandular and squamous components appear malignant.
Well-differentiated endometrioid adenocarcinoma
Poorly differentiated endometrioid carcinoma. Sheets of cells with little
evidence of gland formation.
Poorly differentiated endometrioid carcinoma. Note large pleomorphic cells
with large nuclei, prominent nucleoli and forming sheets with no gland formation.
Clinical behavior of endometrial adenocarcinoma depends on the histologic
type, the grade (degree of differentiation) and the stage (extent of spread).
Endometrioid carcinoma has a better prognosis than the other histologic types,
which tend to occur at a higher stage. Staging is based on degree of myometrial
invasion, cervical, adnexal and adjacent pelvic organ invasion, result of
peritoneal fluid cytology and distant organ metastasis. Lymph node status
is an important prognostic factor. 75% of patients present with stage I disease
and these have 95% 5-year survival. Those tumors associated with unopposed
estrogen tend to have low histologic grade and clinical stage, hence tend
to have better prognosis. These usually occur in young women.
Question: How is endometrial adenocarcinoma staged?
Leiomyosarcoma is a malignant tumor of smooth muscle origin. It is rare.
The tumors are similar in appearance to leiomyoma (fibroid) but have irregular
borders (due to invasion into adjacent myometrium) and have soft foci with
of hemorrhage and necrosis. Approximately 5 to 10% are reported to originate
in a leiomyoma. Like its benign counterpart, it is more common in black women.
The histologic appearances are interlacing bundles of smooth muscle cells
with variable uniformity. In some tumors, the cells are well differentiated
and resemble leiomyoma. Mitotic rate (count of 10 or more mitoses per 10 high
power fields) is important in distinguishing these from leiomyoma. In others,
the tumor cells are more anaplastic, with atypical nuclei and multinucleated
cells, and numerous mitoses.
Leiomyosarcoma. Note mitotic figures and large nuclear size.
Another example. This shows more cellular pleomorphism with some multinucleated
Younger patients have more favorable outcome.
- Malignant Mixed Müllerian Tumor (MMMT) (Carcinosarcoma)
This is a malignant tumor in which the epithelial and stromal components
are both highly malignant. These tumors are derived from multipotential stromal
cells. If they contain mesynchymal components such as skeletal muscle, bone,
cartilage or fat, which are foreign to the uterus, they are classified as
heterologous. If endometrial stromal components are present without other
elements, the tumor is termed homologous.
The tumors present as large, polypoid mass that usually fills the endometrial
cavity and may protrude through the external os, in an elderly woman. The
patient may complain of postmenopausal bleeding, lower abdominal pain, palpable
abdominal mass or abdominal distension.
Malignant mixed mullerian tumor presenting as a large polypoid mass filling
the endometrium and extending into the endocervical canal.
Tumors contain adenocarcinoma admixed with one or more malignant stromal
elements, which may be endometrial stroma, smooth muscle, skeletal muscle,
bone, cartilage or fat. The commonest heterologous element is rhabdomyosarcoma
Malignant Mixed Müllerian Tumor. Note malignant glands and stroma.
Malignant Mixed Müllerian Tumor. Malignant stroma.
Malignant Mixed Müllerian Tumor. Malignant bone (heterologous osteosarcoma).
The prognosis is poor. The tumors often present at an advanced stage. Occult
metastases may be present even in those with stage I or II disease. Strongest
factor correlating with a poor outcome is deep myometrial invasion. Invasion
to the middle or outer third of myometrium is invariably associated with microscopic
lymphatic and vascular channel invasion, therefore lymph node and hematogenous
spread to lung and liver are common. The presence of heterologous elements
appears to have no effect on prognosis but the type of adenocarcinoma present
influences the prognosis. Metastases usually consist of the adenocarcinomatous
element. The 5-year survival rate is about 30%. There are virtually no long-term
survivors among those whose tumors have extended beyond the uterus at time