Pathology Thread

VII. Malignant Neoplasms

Objectives:

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 outcome

1. Endometrial Adenocarcinoma

Epidemiology

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 syndrome.

Question: What is the role of cigarette smoking in the etiology of endometrial cancer.

 

Clinical presentation

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 cavity.

Histology

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

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?

 

2. Leiomyosarcoma

Leiomyosarcoma is a malignant tumor of smooth muscle origin. It is rare.

Clinical presentation

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.

Leiomyosarcoma

Histology

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 cells.

Clinical behavior

Younger patients have more favorable outcome.

3. 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.

Clinical presentation

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.

Histology

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 (skeletal muscle).

Malignant Mixed Müllerian Tumor. Note malignant glands and stroma.

Malignant Mixed Müllerian Tumor. Malignant stroma.

Malignant Mixed Müllerian Tumor. Malignant bone (heterologous osteosarcoma).

Clinical behavior

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 of diagnosis.