Endometrial carcinoma

Endometrial carcinomas begin in the lining of the uterus (endometrium). They are
the most common type of uterine cancer, accounting for more than 95% of all
uterine cancers.
 Endometrioid carcinoma is the most common type of endometrial cancer,
accounting for 75%–80% of all endometrial carcinomas. Endometrioid
carcinomas form in the glands in the endometrium. Variants of endometrioid
carcinoma include:
o with squamous differentiation
 adenocanthoma – made up of malignant glandular cells and
benign squamous cells
 adenosquamous – made up of malignant glandular cells and
malignant squamous cells
o villoglandular
o secretory
o ciliated cell
 mucinous adenocarcinoma
 serous adenocarcinoma (also called papillary serous carcinoma)
 clear cell adenocarcinoma
 mixed carcinoma
 squamous cell carcinoma
 transitional cell carcinoma
 small cell carcinoma
 undifferentiated carcinoma

Uterine sarcoma

Uterine sarcomas begin in the muscle or connective tissue of the uterus. thus many patients present with advanced disease.org/leiomyosarcoma. we shall focus on one subset . this adds to the dilemma of addressing survival rates given the variable time periods of these studies. In this review. although it is noteworthy to mention that leiomyosarcoma can arise from other gynecological primary sites. ULMS occur primarily in women 40 to 60 years of age.html An Introduction to Uterine Leiomyosarcomas Uterine sarcomas are a rare and aggressive form of uterine cancer. http://sarcomahelp. Less common symptoms include weight loss. weakness. and fever. The most frequent presenting symptoms are abnormal vaginal bleeding and pelvic or abdominal pain.uterine leiomyosarcomas (ULMS). The amount of bleeding ranges from spotting to menorrhagia and is often associated with foul-smelling vaginal discharge. lethargy. They account for approximately 2%–5% of all uterine cancers. and in some cases part of the tumor may prolapse through the cervical os and into the vaginal canal. the uterus is often enlarged.2 ULMS are considered neoplasms of high metastatic potential with 5-year overall survival rates varying between 0 and 73%. Leiomyosarcoma Leiomyosarcoma is the most common type of uterine sarcoma. . Diagnosis is usually not made before surgery. uterine sarcomas behave more aggressively and are associated with a poorer prognosis.5-7 On pelvic examination. ULMS are rare smooth muscle tumors accounting for approximately 1% of patients with uterine cancer1 with an estimated annual incidence of 0. It develops in the myometrium or muscle wall of the uterus.000 women.64 per 100. Compared to the more common endometrial carcinomas. Additionally.3-5 These discrepancies may be attributable to inconsistent definitions and variable sample sizes for diagnostic criteria. They arise from the endometrial lining or the myometrium in the uterus.

. Table 1: Gross pathological comparison of Leiomyoma and Leiomyosarcoma Leiomya Leiomyosarcoma Usually multiple Often solitary Variable size. See Figure 1 and Table 1. fleshy cut surface White Yellow or tan Hemorrhage and necrosis infrequent Hemorrhage and necrosis frequent The belief that the risk of ULMS is elevated among women with a "rapidly growing" uterus or leiomyoma was proven false in a study of 1322 women admitted to two community hospitals for hysterectomy or myomectomy. or age at menopause as risk factors are inconclusive.. Fibroids rarely.8. often >10cm Firm. usually 3-5cm Large. Data regarding parity.9 A history of pelvic irradiation is noted in 5-10% of patients. ULMS are much less common and not hormonally driven.10 Benign leiomyomas (fibroids) and ULMS often coexist in the same uterus. whorled surface Soft. if ever.12 Classification Tissues and Cells These sites will help readers to better understand this article: The Tissues of the Human Body and Inside the Cell. The rarity of these tumors has prevented the performance of large epidemiological studies to identify risk factors. there is approximately a two..2.to three-fold higher incidence of ULMS among African-American women compared to Caucasian women. onset of menarche.Figure 1: A uterus has been cut showing a large. Based on available United States data. but are genetically distinct entities. degenerate into ULMS. soft leiomyosarcoma.

poorly circumscribed mass with a soft. while heterologous indicates similarity to other cell types... including fat. liposarcoma). .e. fleshy consistency and a variegated cut surface that is grey-yellow to pink. with foci of hemorrhage and necrosis. now called carcinosarcomas. etc. but resemble sarcoma on histology. Homologous refers to similarity to endometrial stroma or myometrium. stromal sarcoma (analogous to endometrial stroma). The typical gross appearance is a large (>10cm). muscle. Malignant mixed mullerian tumors. osteosarcoma. 13 The histologic classification of uterine sarcomas is based upon homology to normal cell types and include ULMS (analogous to myometrium).. arise from endometrial adenocarcinoma..The Gynecologic Oncology Group (GOG) uses a classification scheme for uterine sarcomas that divides them into five categories:  Mixed homologous mullerian sarcoma  Mixed heterologous mullerian sarcoma  Leiomyosarcoma  Endometrial stromal sarcoma  Other Figure 2: Cut surface of this leiomyosarcoma showing.. and other heterologous cell types (i. Figure 3: Cut surface of this leiomyoma with infarction. See Figures 2 and 3.

Limited data has allowed some tumors. these stains are uncommonly used.14 See Definitions Sidebar. and infiltrative borders. 5. however. In practice. into the leiomyoma category and should be distinguished from their sarcomatous counterparts. formerly classified as STUMP. necrosis and cytologic atypia in determining the malignant potential of STUMP lesions. most ULMS are overtly malignant.. data is limited. The diagnosis of ULMS may be made in the presence of tumor necrosis and any mitoses. One study looked at the expression of particular markers that are of interest in gynecological cancers (p53. and Platelet Derived Growth Factor) in tissue samples from patients who had ULMS or benign leiomyomas. Mitotic rate is the most important determinant of malignancy. atypical mitoses. coagulative tumor cell necrosis. The study also suggested a prognostic interrelationship between expression of p53 and stage in ULMS.. with hypercellularity.17 Figure 5: Mitosis (center of slide). and Table 2. a high mitotic index is compatible with a benign clinical course. 16. Without tumor necrosis and significant atypia. however. Figure 4: Tumor necrosis consists of ghosts (no nuclei) of tumor. In the absence of tumor necrosis.15 A subset of smooth muscle tumors will not be easily classified based on the criteria and are designated as smooth muscle tumors of uncertain malignant potential (STUMP). Their data demonstrated significant and molecular differences between benign and malignant smooth muscle tumors of the uterus. cytologic atypia..Microscopically.. See Figures 4. The literature is unresolved on whether special studies such as proliferation index or stains for p53 add to the discriminating power of the basic criteria of mitoses.Epidermal Growth Factor. the diagnosis can be made with moderate to severe cytologic atypia and a mitotic index greater than 10mf/10hpf.abundant mitoses (>10 to 20 mitotic figures (mf) per 10 high power fields (hpf)). and definitive diagnosis of sarcoma is never reported based on these stains alone. .. but is modified by the presence of necrosis and cytologic atypia.

In the absence of coagulative tumor cell necrosis and significant atypia. *mf/hpf = mitotic figures/high power fields Any coagulative tumor cell necrosis In the absence of tumor cell necrosis. bizarre. cellular. Table 2: Diagnostic Criteria for LMS. . a high mitotic index is compatible with a benign clinical course. the chance of recurrence is low (less than 2-3%). the diagnosis requires diffuse. Figure 6: Atypia is seen. the diagnosis requires diffuse. Myxoid leiomyomas have myxoid material separating the tumor cells. Any coagulative tumor cell necrosis In the absence of tumor cell necrosis. Epithelioid leiomyomas are yellow or grey and may contain visible areas of hemorrhage and necrosis.14 See Figure 6. cytologic atypia and mitotic figures. Adapted from 2003 WHO Guidelines14 Standard smooth muscle Differentiation Epithelioid differentiation Myxoid differentiation Histolog y Cigar-shaped spindled cells with scanty to abundant eosinophilic cytoplasm Rounded cells with central nuclei. Atypical leiomyomas lack all the other components with the exception of atypia and have little recurrence potential. moderate to severe cytological atypia and a mitotic index of >5mf/10hpf. myxoid. If the mitotic index is < 10mg/10hpf. epithelioid. They are soft and translucent with circumscribed margins with neither cytologic atypia nor mitotic figures. or symplastic) tumors. the diagnosis required diffuse. and clear to eosinophilic cytoplasm Spindle shaped cells set within an abundant myxoid matrix Criteria for LMS Any coagulative tumor cell necrosisIn the absence of tumor cell necrosis. moderate to severe cytological atypia and a mitotic index of >5mf/10hpf. Mitotically active leiomyomas can occur in pre-menopausal women and have the typical macroscopic and histologic appearance of a leiomyoma with the exception that they have > 5mf/hpf. Cellular leiomyomas tend to have hypercellularity and can suggest the diagnosis of ULMS..Tumors now in the leiomyoma category include: mitotically active. moderate to severe cytological atypia and a mitotic index of > 10mf/10hpf*.. atypical (pleiomorphic. and tend to be solitary and softer than the usual leiomyoma. but they lack tumor cell necrosis.

and biopsy or any suspicious areas. Metastasis frequently involves the lung. the authors concluded that more than 50% of high signal on T2-weighted images and the presence of any small high-signal areas on T1-weighted images with un-enhanced pockets were considered MRI suggestive for STUMPS and LMS. extrafascial total abdominal hysterectomy. lymphoma. removal of enlarged lymph nodes. Contrast resolution in soft tissues (better than ultrasonography) and lack of ionizing radiation show great promise as an imaging tool to evaluated LMS. or STUMP. intravenous leiomyomatosis. uterine smooth muscle tumors are generally not graded. endometrial cancer. not clinical findings. bilateral salpingooophorectomy. clinical behavior is defined by the designation to categories of ULMS. or adenomyosis. chest imaging is necessary to evaluate for metastatic disease. Figure 7: The International Federation of Gynecology . Imaging studies and/or clinical findings are not specific for ULMS versus other uterine tumors. leiomyoma. See Figure 7.19-21 One study looked at patients (including nine patients with pathologically proven LMS and three with STUMP) in order to study the magnetic resonance characteristics of non-benign uterine smooth muscle tumors. Surgical staging for ULMS is the same as for endometrial carcinoma (see Figure 7). The surgery includes peritoneal washings for cytology. and hematogenous routes (see Figure 2). Size. The distinction is important since grading ULMS based on criteria at other body sites is misleading. Additionally.Unlike smooth muscle tumors at other sites.22 Staging Staging is based on surgical. they analyzed twelve cases of benign leiomyomas in which the gynecologists had suspected LMS. Diagnostic Evaluation Patients with abnormal uterine bleeding or a suspicious uterine lesion should undergo endometrial sampling. magnetic resonance imaging (MRI). Extensive local growth is a hallmark of ULMS and spread of these tumors occur by local. lymphatic. With some exceptions. or computed tomography (CT) do not reliably distinguish between sarcoma. leiomyoma. Ultrasound examination. location. The findings of atypical degeneration with irregular contours should bring LMS into the differential when evaluating leiomyomas (or other pelvic masses). signal intensity. Some oncologists recommend omentectomy and pelvic and paraaortic lymph node sampling.18 MRIs and Diagnosis The utility of MRI for diagnosis is being addressed in case reports. Rather. and contrast enhancement of the tumors were studied on an individual basis. If the diagnosis of ULMS is known preoperatively.

or adnexa.23 Based on these results. reexploration for surgical staging is probably unnecessary since this risk of metastasis to lymph nodes and beyond is minimal. pelvic serosa. 23 Though the involvement of lymph nodes is of prognostic significance.and Obstetrics (FIGO) Staging of ULMS Stage I Tumor confined to corpus uteri IA Tumor limited to the endometrium IB Tumor invades up to or less than 50% of the myometrium IC Tumor invades more than 50% of the myometrium Stage II Tumor invades cervix but does not extend beyond uterus IIA Endocervical glandular involvement only IIB Cervical stroma invasion Stage III Local and/or regional spread IIIA Tumor involves uterine serosa and/or adnexa (direct extension or metastasis) IIIB Vaginal involvement (direct extension or metastasis) IIIC Metastasis to the pelvic and/or para-aortic lymph nodes Stage IV IVA Tumor invades the bladder mucosa and/or bowel mucosa IVB Distant metastasis(excluding metastasis to vagina. Ovarian conservation may be an option for premenopausal women who wish to retain ovarian function. and/or inguinal lymph nodes) LMS should be grouped with regard to the degree of differentiation as follows: G1 5 percent or less of a nonsquamous or nonmorular solid growth G2 6 percent to 50 percent of a nonsquamous or nonmorular solid growth G3 More than 50% of a nonsquamous or nonmorular solid growth The importance of lymph node dissection is controversial. Two studies have suggested that retention of the ovaries may not adversely affect prognosis in women with Stage I ULMS.4%). most perform lymph node dissection only in patients with clinically suspicious nodes. Including metastasis to intra-abdominal lymph nodes other than para-aortic. Outcomes have been comparable among similarly staged patients who did or did not undergo lymphadenectomy.23 Informed consent as to the uncertainty of outcome with conservative surgery and close follow-up is clearly needed. lymphadenectomy has not been shown to be therapeutic. .24 When ULMS is diagnosed postoperatively. Patients with ULMS confined to the uterus have a low risk of occult nodal disease (2.