Tests
1st tests to order
pelvic (transvaginal) ultrasound
Test
Pelvic (transvaginal) ultrasound can evaluate the endometrial thickness and uterine size and exclude a structural abnormality such as a polyp.[102]
Measurement of endometrial thickness by transvaginal ultrasound has a high sensitivity for detecting endometrial cancer (96% using an endometrial thickness of >5 mm), which makes it a good noninvasive initial test to determine if a biopsy is warranted.[126] Endometrial thickness ≤5 mm was associated with a 1% probability of endometrial cancer.[126]
An endometrial thickness <5 mm excludes most endometrial pathology.[127] A threshold of ≤4 mm has a >99% negative predictive value in women with postmenopausal bleeding.[101]
Result
endometrial thickening (stripe) >4 mm merits further investigation
office-based endometrial biopsy (with or without office-based hysteroscopy) and histopathology
Test
Confirms diagnosis histologically, identifies tumor subtype and grade. For women with endometrial cancer, guidelines recommend immunohistochemistry analysis for MMR status and/or testing for MSI status for all tumors. Further genetic evaluation should be carried out if the tumor is MMR deficient or MSI-high.[76][77]
Office-based biopsy using an endometrial suction catheter (pipelle endometrial suction curette) is often the initial diagnostic step given its high sensitivity, low cost, and ready availability.[68][104][105] The diagnostic accuracy of office-based biopsy can be improved by office hysteroscopy, if available.
Result
histopathology shows adenocarcinoma; may be positive for genetic variant
hysteroscopy, dilation and curettage (D&C), and histopathology
Test
Hysteroscopy and D&C under anesthesia is mandatory if an office-based biopsy is not technically feasible or cannot be tolerated by the patient.
Result
histopathology shows adenocarcinoma
Cervical cytology (Pap smear or liquid-based cytology)
Test
Primarily used to screen for cervical dysplasia. It is not a screening test for endometrial cancer.
However, in approximately 50% of cases it can identify abnormalities higher up in the genital tract.[110] This is particularly significant for women ages >40 years.
Identification of atypical glandular cells on cervical cytology should prompt immediate evaluation with endometrial sampling.[24][25][110]
Genetic analysis combined with liquid-based cytology may improve the diagnostic sensitivity of endometrial neoplasms.[128][129]
Result
atypical glandular cells on cervical cytology
CBC
Test
Hemoglobin <12 g/dL is suspicious for significant bleeding.
Result
anemia
Tests to consider
Molecular and genetic analysis
Test
For women with endometrial cancer, guidelines recommend immunohistochemistry analysis for MMR status and/or testing for MSI status for all tumours. Further genetic evaluation should be carried out if the tumour is MMR deficient or MSI-high.[76][77]
Immunohistochemistry can be carried out at initial biopsy or D&C, or on the final hysterectomy specimen. Further molecular profiling includes immunohistochemistry for p53 mutations and sequencing for POLE mutations.[19][76][106][107][108] Molecular analysis may be prognostic and guide treatment.[109]
Tumor mutational burden (TMB) testing with a validated assay may be considered, especially for advanced or recurrent disease. Estrogen receptor testing should be carried out for stage III and IV, and recurrent tumors. HER2 immunohistochemistry testing is recommended for serous carcinoma or carcinosarcoma, and may be considered for p53-abnormal tumors. NTRK gene fusion testing may be considered for metastatic or recurrent disease.[76]
Genetic risk assessment is recommended for patients with a strong family history of endometrial or colorectal cancer.[74][75]
Result
may be positive or negative for MMR deficiency/MSI-high, POLE mutation, p53 abnormality, HER2 expression, estrogen receptors and NTRK gene fusion; TMB-low or TMB-high
serum CA-125 level
Test
May be ordered when there is suspected extrauterine/metastatic disease, or when the histology is serous or clear cell.
Serum CA-125 is not routinely recommended because it may lead to unnecessary investigations and over-treatment (even though it may be useful for surveillance of endometrial cancer).
Result
typically <35 units/mL (depending on laboratory)
saline infusion sonohysterogram
Test
Can provide detailed imaging of the endometrium if routine pelvic (transvaginal) ultrasound is inconclusive; however, it is not routinely used.[101]
Involves the transcervical injection of sterile fluid (e.g., normal saline) into the uterine cavity during real-time ultrasound scanning of the endometrium.[103]
Result
mass lesions, uterine enlargement, and polyps are demonstrated
BUN and creatinine (renal function testing)
Test
Elevated creatinine may suggest renal system involvement or obstruction.
Result
serum creatinine elevated if renal involvement secondary to metastatic disease
LFTs
Test
May suggest liver or bone involvement.
Result
elevated alkaline phosphatase if metastatic spread to bones or liver
chest x-ray
Test
Only performed if clinically indicated to assess for lung metastases.
May inform staging. Also routinely performed as part of the work-up for surgery as appropriate patients will subsequently undergo major surgery, including hysterectomy.
Chest x-ray has a low sensitivity for early lung metastases and may be substituted by unenhanced chest CT.[123][124]
Result
lung mass, round lesions, or pleural effusions suggestive of metastases
CT scan of chest, abdomen, and pelvis
Test
CT of chest, abdomen, and pelvis is only used for initial imaging if the patient presentation suggests extrauterine disease (e.g., advanced and/or aggressive disease including deeply-invasive grade 3 tumor, serous or clear cell tumors, malignant Müllerian mixed tumor).[111][112]
This allows detection of lymphadenopathy, early metastasis, or peritoneal disease, which may affect treatment planning.[94][112]
Result
tissue invasion demonstrated in advanced disease
MRI of uterus, pelvis, and abdomen
Test
Shows depth of myometrial invasion and local extent of disease spread.
MRI is useful for assessment of local extent of disease and invasion of adjacent organs, to assess myometrial invasion in women who wish to conserve fertility and avoid surgery, for determination of resectability in cases of recurrent disease, and to plan radiation therapy.[94][112][130][131]
Result
tissue invasion demonstrated in advanced disease
PET/CT scan
Test
PET/CT may be of value in the assessment of women with endometrial cancer who are not surgical candidates. Can be used in the initial evaluation of disease; to monitor disease response to pharmacotherapy; and for surveillance, especially if recurrence is suspected.
PET/CT is the most sensitive imaging modality for identifying additional sites of disease when curative pelvic exenteration is planned.
Result
increased metabolic activity in areas of tumor involvement
Use of this content is subject to our disclaimer