Uterine Malignancy-Sarcomas

AUTHORS: Christina Nestlerode, DO and Robert Neff, MD

Definition

Cancers of the uterus include tumors that originate from epithelial or mesenchymal tissue. Tumors that arise from the epithelium are referred to as adenocarcinomas, whereas tumors that arise from mesenchymal tissue (i.e., connective, muscular, vascular) are referred to as sarcomas. These tumors may be found in various locations of the uterus including the endometrium or myometrium.

Historically, endometrial adenocarcinomas were divided into two categories: Type 1 and Type 2. Type 1 endometrial carcinomas refer to endometrioid subtypes, whereas Type 2 endometrial carcinomas refer to serous, clear cell, and mixed Mullerian subtypes (see “Endometrial Cancer”). Recent molecular studies have shown carcinosarcomas (MMMT) to be closely related to epithelial tumors compared to sarcomas.

This chapter will focus on sarcomas of the uterus arising from the endometrial stroma or myometrium.

Sarcomas of the Uterus

Leiomyosarcomas

Endometrial stromal sarcoma

Adenosarcomas

Undifferentiated sarcoma

ICD-10CM CODES
C54.1		Malignant neoplasm of endometrium
C54.2		Malignant neoplasm of the myometrium
C54.0		Malignant neoplasm of isthmus uteri
C54.8		Malignant neoplasm of overlapping sites of corpus uteri

Epidemiology& Demographics

Incidence & Prevalence

Incidence of all uterine cancer is 28.1 per 100,000 women per yr with 4.9 deaths per 100,000 women as of 2018. In the most recent update from SEER Annual Report to the Nation, uterine cancer showed the highest increase frequency in death of all cancers among U.S. women. Endometrial cancer remains the most common uterine malignancy in the U.S; however, sarcomas of the uterus are rare. Sarcomas account for approximately 3% to 8% of all cancers of the uterine corpus. Sarcomas are associated with a poor prognosis compared to endometrial cancer.

Risk Factors

Box 1 describes risk factors for uterine sarcoma.

BOX 1 Risk Factors for Uterine Sarcoma

Nulliparity
Obesity
History of pelvic radiation
Exposure to tamoxifen

From Fielding JR et al: Gynecologic imaging, Philadelphia, 2011, Saunders.

Mean Age at Diagnosis

50 yr old.

Physical Findings & Clinical Presentation

Abnormal vaginal bleeding is the most common symptom (90% of women with diagnosis)
Vaginal discharge also may be a presenting symptom (10% of these patients have non-bloody discharge)
May also present as pelvic pain or pressure and pelvic mass on examination (10% of women with uterine sarcoma)
Urinary symptoms
Abdominal pain or distention
Weight loss

Etiology

Endometrial cancers are thought to derive from an excess of unopposed estrogen causing a proliferation of disorganized dysplastic endometrium.
A minority of patients may have a genetic predisposition for endometrial cancer (Lynch syndrome).
The exact etiology for sarcomas is largely unknown.

Diagnosis ⬆ ⬇

Endometrial biopsy or dilation and curettage with histologic evidence of malignancy

Postsurgical histologic examination of uterine tissue

Differential Diagnosis

Endometrial hyperplasia
Endometrial polyp
Leiomyoma

Workup

Diagnosis can be made histologically by biopsy for abnormal bleeding. Workup includes biopsy (in the office or operating room, in conjunction with hysteroscopy) and imaging (see “Imaging Studies” below). Surgical removal of the uterus is the most common way to diagnose a uterine sarcoma. Histologic criteria include mitotic index, cellular atypia, loss of polarity, and necrosis.

Laboratory Tests

CBC
Comprehensive metabolic panel (CMP)
CA-125 (high levels can be a sign of metastasis, not diagnostic, not always elevated)

Imaging Studies

Pelvic ultrasound is a lower-cost method of detecting uterine corpus mass or thickened endometrial lining. Features concerning for uterine sarcoma: Heterogeneous texture, central necrosis, irregular vessel distribution, and rapid growth of the uterus.
Chest x-ray examination should be considered for preoperative testing with suspicion of uterine sarcoma.
Computed tomography (CT) scans (Fig. 1), MRI, and PET may be useful for assessing tumor spread once diagnosis is made or characterizing a uterine mass.

Figure 1 A 50-yr-old patient with uterine sarcoma.

A, Axial contrast-enhanced computed tomographic (CT) image. Low-attenuation lobulated and infiltrating soft tissue fills the endometrial canal (arrows), extending into the myometrium. B, Axial contrast-enhanced CT image showing same as A. Low-attenuation, lobulated, and infiltrating soft tissue fills the endometrial canal, extending into the myometrium. C, Axial contrast-enhanced CT image. Low-attenuation lobulated and infiltrating soft tissue fills the endometrial canal. Subtle myometrial invasion is seen anterior and posterior (arrows). D, Axial contrast-enhanced CT image. Low-attenuation lobulated and infiltrating soft tissue fills the endometrial canal (arrow), showing same. Subtle myometrial invasion is seen fundally.

From Fielding JR et al: Gynecologic imaging, Philadelphia, 2011, Saunders.

Staging

Staging of endometrial carcinoma and uterine adenosarcoma is summarized in Tables 1 and 2.

TABLE 2 International Federation of Gynecology and Obstetrics 2009 Staging for Uterine Sarcoma (Including Leiomyosarcoma and Endometrial Stromal Sarcoma)

Stage
I		Tumor limited to the uterus
I_A		Tumor 5 cm or less in greatest dimension
I_B		Tumor more than 5 cm
II		Tumor extends beyond the uterus, within the pelvis
II_A		Adnexal involvement
II_B		Extrauterine pelvic tissue involvement
III		Involvement of abdominal tissues
III_A		1 site
III_B		>1 site
III_C		Regional lymph node metastasis
IV
IV_A		Tumor invades bladder or rectum
IV_B		Distant metastases

From Niederhuber JE: Abeloff’s clinical oncology, ed 6, Philadelphia, 2020, Elsevier.

TABLE 1 International Federation of Gynecology and Obstetrics 2009 Staging for Endometrial Carcinoma (Including Carcinosarcoma)

Stage
I		Tumor confined to uterine corpus including endocervical glands
I_A		Tumor confined to endometrium or invades <50% of the myometrium
I_B		Tumor invades 50% or more the myometrium
II		Tumor invades cervical stroma but confined to uterus
III		Tumor involving the serosa, adnexa, vagina, or parametria
III_A		Tumor invades uterine serosa or adnexa
III_B		Involvement of vagina or parametrium
III_C1		Metastasis to pelvic lymph nodes
III_C2		Metastasis to paraaortic lymph nodes
IV		Tumor involves bladder and/or bowel mucosa or distant metastasis
IV_A		Invasion of bladder or bowel mucosa
IV_B		Distant metastases including intraabdominal metastasis, inguinal lymph nodes, or both

From Niederhuber JE: Abeloff’s clinical oncology, ed 6, Philadelphia, 2020, Elsevier.

Treatment ⬆ ⬇

Treatment for sarcomas is based on the method in which diagnosis was made. If diagnosed after a hysterectomy, surgical resection for residual tumor or tube/ovary may be performed. If diagnosis made by biopsy, surgical resection is based on the symptoms and extent of the disease.
Further treatment depends on the type of cancer, histologic grade, and stage.
1. Low-grade endometrial stromal sarcoma: Stage 1 disease is usually followed up by surveillance after surgery. A higher staged disease may be offered external beam radiation therapy and/or antiestrogen hormone therapy.
2. High-grade endometrial stromal sarcoma, undifferentiated uterine sarcoma, and uterine leiomyosarcoma: Stage 1 disease can be followed with surveillance. Chemotherapeutic agents and external beam radiation therapy can be considered for stage 2 or higher.

Disposition

Survival varies with each type of sarcoma but is generally very poor. Box 2 describes uterine prognostic factors.
5-yr survival for grade I endometrial stromal sarcoma is 91% and drops to 42% for grade III.
5-yr survival for leiomyosarcoma ranges from 76% for stage 1 to 29% for stage 4.
5-yr survival for undifferentiated sarcoma ranges from 70% for stage 1 to 23% for stage 4.

BOX 2 Uterine Sarcoma Prognostic Factors

Tumor stage
Tumor grade
Tumor size
Patient age
Vascular space involvement
Mitotic count
Residual disease at surgery or uterine morcellation
Adjuvant chemotherapy

From Fielding JR et al: Gynecologic imaging, Philadelphia, 2011, Saunders.

Referral

A gynecologic oncologist should manage uterine sarcoma.

Key points in the management of uterine sarcoma are described in Box 3.

BOX 3 Uterine Sarcoma: Key Points

The disease mainly affects women aged 40-60 yr old depending on the type of sarcoma.
Patients may present with abnormal uterine bleeding, abdominal distention, enlarging pelvic mass, pelvic pain/pressure, or may be asymptomatic.
The primary treatment is hysterectomy and bilateral salpingo-oophorectomy.
Adjuvant radiotherapy to the pelvis and/or systemic chemotherapy may be considered if >stage 1 sarcoma.

From Greer IA et al: Mosby’s color atlas and text of obstetrics and gynecology, London, 2001, Harcourt.

Related Content

Uterine Cancer (Patient Information)

Endometrial Cancer (Related Key Topic)

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Diagnosis ⬆ ⬇

Treatment ⬆ ⬇

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