Endometrial cancer differential diagnosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Qurrat-ul-ain Abid, M.D.[2]; Monalisa Dmello, M.B,B.S., M.D. [3]Roukoz A. Karam, M.D.[4]

Overview

In early stages endometrial cancer 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.

Differentiating Endometrial Cancer From Other Diseases

• In early stages endometrial cancer 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.

Diseases	Clinical manifestations				Para-clinical findings							Gold standard
	Symptoms			Physical examination
					Lab Findings			Imaging		Pap Smear	Histopathology
	Bleeding	Pelvic Pain/pressure/ discomfort	Other	Abdomino-pelvic examination	Hb	B-HCG	CA-125	Ultrasound	MRI
Endometrial cancer	Menorrhagia Metrorrhagia in premenopausal women Postcoital bleeding Intermenstrual bleeding	±	Polyuria and dysuria (due to compression) Fatigue Weight loss	Enlarged fixed uterus Vaginal bleeding Vaginal discharge Lymphadenopathy Mesenteric nodules (metastasis)	↓	–	+	A thickened endometrial lining >4mm	Endometrial thickening Lymph node involvement Pelvic metastasis	Atypical glandular cells	Endometrial malignant cells Low grade Type I High grade Type II	Biopsy
Uterine leiomyosarcoma	May have menorrhagia Intermenstrual bleeding	±	Abdominal pain Urinary symptoms Abdominal distension Asymptomatic	Abdominal distension Enlarged or normal sized uterus Lymphadenopathy	↓	–	+	Uterine mass Lymph node metastases	Shows details of uterine mass boundaries, extent and spread	Negative	Epithiloid shaped smooth muscle cells showing: High mitotic index Cellular atypia Coagulative necrosis Two variants of leiomyosarcoma: Epithelioid leiomyosarcoma Myxoid leiomyosarcoma (bland features)	Biopsy
Diseases	Bleeding	Pelvic Pain/pressure/ discomfort	Other	Pelvic examination	Hb	B-HCG	CA-125	Ultrasound	MRI	Pap Smear	Histopathology	Gold standard
Uterine leiomyoma	May have menorrhagia May have intermenstrual bleeding	+	Asymptomatic Dysmenorrhea (most common symptoms) Infertility Obstetric complications Obstructive symptoms (due to compression) Dyspareunia Torsion or degeneration	Enlarged mobile uterus Irregular contour Large fibroid uteri may cause abdominal distention	↓ or Nl	–	–	Transvaginal ultrasound shows: Hypoechoic, well-circumscribed round masses Location of fibroid: Submucosal, intramural, subserosal, and cervical fibroids	"Popcorn" calcification in the fibroid (degeneration) Differentiaites between leiomyomas, adenomyosis and adenomyomas	Normal	Normal appearing bundle of epithiloid shape smooth muscle cells with normal mitotic index	Imaging and histologic analysis
Uterine carcinosarcomas (Malignant mixed mullerian tumour (MMMT) of the uterus)	May have menorrhagia May have intermenstrual bleeding	±	Classical triad: Pain Bleeding Rapidly enlarging uterus	Enlarged uterus Pelvic mass Mass protruding through the cervical os Involvement of the cervix	↓	–	+	Enlarged uterine cavity Hyperechoic mass in uterus and cervix	Heterogenous bulky polypoid mass with intense enhancement		Biphasic: High grade carcinomatous (epithelial) contents Stromal sarcomatous (connective tissue)	Biopsy
Cervical cancer	Menorrhagia Intermenstrual bleeding Postcoital bleeding Vaginal passage of bleeding	± Pressure-related bowel and bladder symptoms	Copious malodorous vaginal discharge Hematuria	Enlarged uterus Concomitant cervical lesions Abdominal distention	↓	–	±	To evaluate tumor size, extent and parametrial invasion Usually not needed for diagnosis	To evaluate tumor size, local extent and staging	Squamous cell carcinoma Low-grade squamous intraepithelial lesions (LSILs) High-grade squamous intraepithelial lesions (HSILs) Adenocarcinoma Atypical glandular cells (AGC) Endocervical adenocarcinoma in situ (AIS)	Squamous cell carcinoma Adenocarcinoma Adenosquamous cervical tumors	Colposcopy and biopsy
Diseases	Bleeding	Pelvic Pain/pressure/ discomfort	Other	Pelvic examination	Hb	B-HCG	CA-125	Ultrasound	MRI	Pap Smear	Histopathology	Gold standard
Metastasis	Menorrhagia Intermenstrual bleeding	±	Asymptomatic Obstetric complications Dysmenorrhea (most common symptoms) Obstructive symptoms (due to urinary bladder and bowel compression) Dyspareunia	Enlarged uterus Abdominal distention	↓	–	–	Enlarged uterine cavity Hyperechoic mass in uterus and cervix	Shows involvement of uterus, lymph nodes, parmetrial area, and surrounding area	Normal May show malignant metastatic cells	Not recommended It may show the malignant cells of the primary site	Biopsy and histopathology analysis of the primary site of the tumor
Endometrial polyp	Menorrhagia Intermenstrual bleeding Postmenopausal bleeding	–	Asymptomatic Endometrial polyp prolapses (visible on speculum examination protruding through cervical os)	Normal sized uterus with smooth surface	↓	–	+ or Nl	Incidentally found on pelvic ultrasound (most common)	MRI will show polyp size and dimension in detail Not required for diagnosis	Normal	Localized hyperplastic growth of endometrial glands and stroma around a vessel	Imaging Histologic evaluation
Endometrial hyperplasia	Menorrhagia Intermenstrual bleeding Postmenopausal bleeding	–	Asymptomatic	Normal sized uterus with smooth surface	↓	–	+	Determines endometrial thickness Rules out other abnormalities	Thick endometrial lining	Abnormal glandular or endometrial cells on pap smear	Non-neoplastic changes: Disordered endometrial growth Benign hyperplasia Simple hyperplasia Complex hyperplasia without atypia Precancerous changes: Endometrial intraepithelial neoplasms Atypical complex hyperplasia	Endometrial sampling
Uterine adenomyosis	–	±	Dysmenorrhea Subfertility	Diffusely enlarged tender boggy uterus with smooth surface Uterus may develop masses	↓	–	+	Snow storm appearance in diffuse adenomyosis Shows a uterine mass in case of adenoma	Identifies diffuse or focal adenomyosis from leiomyoma	Mostly normal may show glandular cells in cervical cytology	Endometrial glands in myometrium of uterus	Imaging Histologic diagnosis
Diseases	Bleeding	Pelvic Pain/pressure/ discomfort	Other	Pelvic examination	Hb	B-HCG	CA-125	Ultrasound	MRI	Pap Smear	Histopathology	Gold standard
Hematometra (blood within the uterine cavity)	–	+ Cramping cyclic pain	Dysmenorrhea Amenorrhea Hypotension Vasovagal syncope	Firm and enlarged uterus Adenaxal tenderness Pelvic examination may be restricted due to pain	↓	–	–	Echogenic fluid in the uterine cavity occluding cervical os	Not required	Normal	Biopsy is not required for diagnosis	Ultrasound
Gestational trophoblastic disease	May have menorrhagia May have intermenstrual bleeding	+	Pulmonary metastasis: Dyspnea Chest pain Cough Hemoptysis Vaginal metastasis: Vaginal bleeding Purulent vaginal discharge Central nervous system metastasis: Asymptomatic Neurologic signs	Irregularly sized boggy enlarged uterus Adnexal fullness Abdominal distention	↓	±	+	Dilated grape like structures Diffuse hydropic swelling Multiples echoes Cystic spaces invading edometrium and myometrium (in case of invasive disease)	MRI defines the extent of primary lesion, invasion and distant metastasis	Trophoblastic cells	Dilated grape like villous structures Invasive malignant lesions	Imaging Histologic diagnosis
Incomplete abortion	Intermenstrual bleeding Vaginal bleeding	+	Abdominal pain/cramps	Enlarges uterus Abdominal distention	N/↓	±	+↓	Uterus shows fetus with absent cardiac activity in lower part of uterus	Not required for the diagnosis	Not required for the diagnosis	Suction biopsy and histology shows fetal and placental tissues	Imaging Histologic diagnosis
Pregnancy	Absent menstrual cycle May have intermenstrual bleeding	+	Nausea Fatigue	Enlarged gravid uterus Abdominal distention	–	+	–	Fetus inside uterine cavity	Not needed once ultrasound determines pregnancy	Normal or may show cervical cells	Not needed once ultrasound determines pregnancy	Transvaginal ultrasound
Uterine lymphoma	Menorrhagia Abnormal uterine bleeding Post-coital bleeding Intermenstrual bleeding Postmenopausal bleeding	+	Bladder obstruction Abdominal pain	Abdominal distension Abdominal mass protruding into abdomen	↓	-	-	Show pelvic mass	Shows pelvic mass , its extent in the uterus, and involvement of surrounding lymph nodes	May show malignant cells mostly non-specific	Histology may show primary malignant lymphomas Non-Hodgkin lymphomas, diffuse large B-cell lymphomas (most common)	Laparoscopy and biopsy
Diseases	Bleeding	Pelvic Pain/pressure/ discomfort	Other	Pelvic examination	Hb	B-HCG	CA-125	Ultrasound	MRI	Pap Smear	Histopathology	Gold standard