Endometrial cancer overview

# Overview
In the United States, endometrial cancer is the fourth most common type of cancer among women. Development of endometrial cancer is the result of multiple genetic mutations. Genes involved in the pathogenesis of endometrial cancer include TP53, KRAS, and PTEN. Approximately 830% of patients with atypical endometrial hyperplasia may progress to develop endometrial cancer. The pathophysiology of  endometrial cancer depends on the 7 histological subtypes: endometrioid, uterine papillary serous, mucinous,  clear cell, squamous cell, mixed and undifferentiated. Common risk factors in the development of endometrial cancer are estrogen exposure, tamoxifen, obesity, diabetes, high blood pressure and genetic disorders. The hallmark of endometrial cancer is abnormal vaginal bleeding. A positive history of bleeding between normal periods in premenopausal women and vaginal bleeding and/or spotting in postmenopausal women is suggestive of endometrial cancer. Pelvic MRI and endometrial biopsy may be diagnostic of endometrial cancer. Depending on the extent of the tumor at the time of diagnosis, the prognosis may vary. However, the prognosis is generally regarded as good. The optimal therapy for endometrial cancer depends on the stage at diagnosis and comprises total hysterectomy and bilateral salpingo-oophorectomy to most patients if they are surgical candidates.

# Historical Perspective
The earliest descriptions of endometrial cancer were reported in the early 1900s. The association between estrogen and development of endometrial cancer was first reported in the 1970s when the incidence of endometrial cancer significantly increased between 1970 and 1975 following the introduction of estrogen replacement therapy.

# Classification
Endometrial cancer may be classified according to histology into either type I comprising 80% of endometrial cancers or type II accounting for around 20%.

# Pathophysiology
Development of endometrial cancer is the result of multiple genetic mutations. Genes involved in the pathogenesis of endometrial cancer include TP53, KRAS, and PTEN. The pathophysiology of endometrial cancer depends on the histological subtype.

# Causes
Causes of endometrial cancer include genetic mutations of the KRAS gene, TP53 gene, TP16 gene, and/or PTEN gene. Other genetic mutations have also been described.

# Differential Diagnosis
Endometrial cancer in early stage must be differentiated from diseases that cause abnormal uterine bleeding and endometrial thickening on ultrasound, such as endometrial hyperplasia, endometrial polyp, and submucosal uterine leiomyoma. In advanced stages endometrial cancer must be differentiated from uterine sarcoma and uterine lymphoma.

# Epidemiology and Demographics
In the United States, endometrial cancer is the fourth most common type of cancer among women. In 2011, the age-adjusted prevalence was approximately 232 per 100,000 and the age-adjusted incidence was approximately 27 per 100,000 in the USA.

# Risk Factors
Common risk factors in the development of endometrial cancer are estrogen exposure, tamoxifen use, obesity, diabetes, high blood pressure and genetic disorders.

# Screening
There is insufficient evidence to recommend routine screening for endometrial cancer.

# Natural History, Complications and Prognosis
If left untreated, approximately 830% of patients with atypical endometrial hyperplasia may progress to develop endometrial cancer. Common complications of endometrial cancer include menorrhagia and metastasis. Depending on the extent of the tumor at the time of diagnosis, the prognosis may vary.  However, the prognosis is generally regarded as good.

# Diagnosis

## Staging
According to the FIGO Staging System, there are 4 stages of endometrial cancer.

## History and Symptoms
The hallmark of endometrial cancer is abnormal vaginal bleeding. A positive history of bleeding between normal periods in premenopausal women and vaginal bleeding and/or spotting in postmenopausal women is suggestive of endometrial cancer.

## MRI
The MRI is not needed for the diagnosis of endometrial cancer. However, an MRI may be helpful in staging of the disease.

## Ultrasound
On transvaginal ultrasound, endometrial cancer is characterized by thickening of the endometrium and disruption of a subendometrial halo.

## Other Diagnostic Studies
Other diagnostic studies for endometrial cancer include endometrial biopsy

# Treatment

## Medical therapy
The optimal therapy for endometrial cancer depends on the stage at diagnosis. A combination of chemotherapy and radiation therapy is indicated in stages IIIB- IV.

## Surgery
Surgery is the mainstay of treatment for endometrial cancer stage I-III.

## Primary Prevention
Effective measures for the primary prevention of endometrial cancer include administration of combination oral contraceptives.