Vaginal cancer differential diagnosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Syed Musadiq Ali M.B.B.S.[2]

Overview

Vaginal cancer must be differentiated from cervical carcinoma, rectal carcinoma, uterine carcinoma, vaginal lymphoma, vaginal cyst, vaginal node of endometriosis, and uterine fibroids.

Differential diagnosis

For large lesions consider invasion of the vagina by:

• Cervical carcinoma
• Rectal carcinoma
• Uterine carcinoma

Malignant involvement of the vagina from metastatic spread is much more common, and except for isolated reports of metastases from extragenital cancers, the most common cause of metastatic disease is direct local invasion from the female urogenital tract. Therefore some authors state the diagnosis of primary vaginal carcinoma should be diagnosed only if other gynecologic malignancies have been excluded.

Other differential considerations include:

Diseases	Clinical manifestations									Para-clinical findings							Gold standard
	Symptoms							Physical exam		Lab Findings			Imaging			Histopathology
	Abnormal vaginal bleeding	Abnormal vaginal dyscharge	Pelvic pain	Itching or burning of the vulva	Other Genitourinary/ Gastrointestinal symptoms	B symptoms	Abdominal pain	Gynecological examinations	Abdominal mass	HPV	Pap smear	STI Panel	Ultrasound	MRI	CT Scan
Vaginal cancer	Postcoital bleeding	+	+	+/-	Tenesmus Dysuria Urinary frequency Constipation Pelvic pain	+/-	+	Vaginal lump Inguinal lymphadenopathy	In case of metastases to internal organs	−	−	−	Ultrasound: Hydronephrosis in case of pelvic metastases Multiple liver metastases	MRI: Isointense on T1-weighted images Soft-tissue mass with intermediate-to-high signal intensity on T2-weighted images	Provide information about size shape and location of tumor Detects metastases Detects lymph node involvement	Biopsy findings: Squamous cell carcinoma of vagina	Biopsy
Cervical cancer	Postmenopausal Intermenstrual Postcoital Bleeding after pelvic exam	+	+	+	Burning during urination Difficulty urinating Pain during sex	+	+	Cervical mass on exam	+	±	Negative Atypical cells	±Chlamydia	Large cervical cancer Angiogenesis on Doppler sonography Bladder involvement Lymph node involvement	T2-weighted MRI : Ovoid, heterogeneous tumor distending the cervical canal with stromal involvement.	PET/CT scan: Detect tumor size Lymph node involvement, Metastases to bladder or rectum	CIN1: mild dysplasia CIN2: moderate dysplasia CIN3: high degree of dysplasia/metastases	Colposcopy/biopsy
Cervical polyp	Postcoital Intermenstrual Postmenopausal Bleeding after exam	+	−	−	−	−	−	Mass on exam	−	−	−	−	Hyper/hypoechogenic masses with or without cysts Filling the endocervical or vaginal canal	May reveal presence of tumor	CT contrast may show presence of a well defined mass	Epithelial cells with no nuclear atypia/mitoses	Hysteroscopy /Biopsy
Cervical leiomyoma	Heavy/prolonged menstrual bleeding Intermenstrual bleeding	+	+	−	Urinary retention Constipation Infertility Bowel obstruction Increase in pregnancy/labor complications	−	+	Large,irregular pelvic mass	±	−	−	−	Well circumscribed hyperechoic mass	T2-weighted MRI: Hypointense masses Homogeneous enhancement Red degeneration	N/A	Spindle shaped smooth muscle cells Mature adipocytes Extracellular matrix consist of collagen,fibronectin.	Clinical diagnosis/ and Ultrasound
Cervical lymphoma	Postmenopausal bleeding	−	+	−	Difficulty urinating Post-coital pain	+	+	Large uterine/cervix mass Irregularity	+	−	−	−	Well-defined, solid, concentric, hypoechoic mass	MRI: Intramyometrial infiltrative nodules	Diffuse heterogeneous uterine/cervical mass & hypoechoic enlarged iliac lymph nodes	Small tumor cells with large nuclei High mitoses and proliferation	Biopsy diffuse large B-Cell lymphoma (DLBCL) most frequent type.
Cervical sarcoma	Intermentrual Postmenopausal	±	+	−	Post-coital pain Fullness in pelvis	±	+	Cervical mass Lump protruding from vagina/vulva	+	−	−	−	Endometrial mass with heterogeneous echogenicity	MRI: Endometrial polypoid mass Hypointense hypervascular solid components	N/A	Mitotic index Cellular atypia Coagulative necrosis	Biopsy
Cervical erosion(Ectropion)	Light bleeding after pelvic exam Spotting	+	+	±	Post-coital pain Painful cramps Pain after sex	−	+	−	−	−	−	-	N/A	N/A	N/A	Squamous metaplasia Vascular ectasia Lymphocytic infiltration	Colposcopy and biopsy
Cervicitis	Intermenstrual bleeding Postcoital Bleeding after pelvic exam	+	+	Itching	Pain during urination Pain during sex Painful menstruation	May have fever only	+/-	Red,inflammed swollen cervix Inflammation/irritation of vulva/vagina	−	−	−	Chlamydia Gonorrhea Herpes simplex Trichomonas vaginalis	To detect complications like PID	N/A	N/A	N/A	Nucleic acid amplification tests (NAATs)
IUD use	Heavy bleeding	±	+	Itching	Painful menstruation	−	+/-	Strings of IUD device Signs of inflammation Discharge Bleeding	−	−	−	±	To detect IUD location and pregnancy	N/A	N/A	N/A	Physical exam and ultrasound
Pelvic inflammatory diseases	Postcoital bleeding Intermenstrual bleeding	+	+	Itching/burning	Pain during sex Painful menstruation Burning sensation during urination Pain during bowel movement	Fever	±Abdominal pain Pelvic pain	Vaginal/vulvar tender lesion depending on microbial cause	−	−	−	Chlamydia Gonorrhea	Enlarged fallopian tubes Abscess Hyperemia Ectopic pregnancy/ovarian cyst/abscess	Thickened fluid filled fallopian tubes	N/A	May show endometritis	CDC diagnostic criteria of PID
Endometriosis	Heavy mentrual bleeding	±	Pelvic pain Back pain	−	Painful menstruation Burning/painful urination Painful bowel movement Pain during or after sex Infertility	−	+	Tender uterosacral nodularity Immobile uterus Cervical motion tenderness Retroverted uterus	+	−	−	−	Unilocular/multilocular cysts contating thin/thick septations Increased vascularity showing increased doppler flow	Hyperintensity on T1 weighted images Hypointensity on T2 weighted images	Catamenial pneumothorax, hemothorax & lung nodules	Presence of endometrial tissue outside the uterus	Visual inspection by laparoscopy
Adenomyosis	Abnormal uterine bleeding	−	+	−	Painful menstruation	−	+/-	Polypoid mass protruding into the endocervical canal.	+/-	−	−	−	Transvaginal US shows poorly marginated hypoechoic & heterogenous areas within myometrium Myometrial cysts Globular/enlarged uterus with asymmetry	MRI: Thickened junctional zone	Uterine enlargement Thickened inner myometrium Myometrial cysts	Presence of ectopic endometrial glands into the myometrium.	Histology findings post hysterectomy
Cervical ectopic pregnancy	Amenorrhea Bleeding after pelvic exam	−	−	−	Pelvic pain	−	+	Soft and disporportionally enlarged uterus.		−		−	Empty uterus Thickened endometrium	T2-weighted MRI: Hypointense large mass T1-weighted MRI: Partially hyperintense mass	N/A	Necrotic hemorrhagic mass with chorionic villus	Hysterectomy and biopsy
DES exposure (Clear cell adenocarcinoma)	Postcoital bleeding Postmenopausal bleeding	+	+/-	+/-	Abdominal pain Blood in feces	+/-	+	Normal looking cervix Cervical exophytic lesions Barrel shaped cervix	-	−	−	−	To determine uterine extent	To detect metastases	Irregular dense mass occupying inferior lip of cervix and posterior fornix	Tumor cells with abundant clear cytoplasm and round nuclei Nucleus show hyperchromasia, moderate pleomorphism & prominent nucleoli	Biopsy
Paget's disease of vulva to cervix	Bleeding from lesion Oozing	±	−	Itching/burning Pain in vulva	−	−	−	Scaly eczematoid lesion in vulva. Erythematous plaques with white scaling. Inguinal lymphadenopathy in case of metastases.	−	−	−	−	N/A	MRI: Hyperintense on diffusion weighted images	May show bilateral enlarged inguinal lymph nodes	Thickened vulvar skin "Cake-icing effect", pathognomonic for vulvavulvar paget's disease Intraepidermal adenocarcinoma which involves epidermis	Biopsy of lesion
Nabothian cyst	Postcoital bleeding	+	−	−	Pain during sex	−	-	Cystic mass on exam	−	−	−	−	An echoic well defined cystic masses	Intermediate or slightly high signal intensity on T1-weighted High signal intensity on T2-weighted images	Small cysts not visible on CT Large cysts seen as focal low attenuation region	Multiple benign cystic masses, usually few millimeters in diameter	Histological exam if large cystic masses
Rectal cancer	-	-	+	-	Constipation/diarrhea Absent bowel sounds Rectal mass/bleeding Abdominal tenderness	Weight loss +	LLQ +	NL	+	-	-	+/-	Endoscopic/transrectal US detects tumor extent	Determine tumor stage	Determine tumor stage	Sheets or cords of malignant cells Cellular atypia & pleomorphism High mitotic rate Necrotic debris in glandular lumina	Colonoscopy with biopsy
Submucous uterine leiomyoma	Menorrhagia	-	+	-	Constipation Urinary frequency/incontinence Hydronephrosis	-	+	Enlarged, irregular, firm, nontender uterus	+	-	-	-	Trans vaginal US: well defined hypoechoic Saline US: for submucous fibroids/polypoi	Provides information on no: of fibroids, size, vascularization, relationship with endometrial cavity & serosal surface	Not required	Not required	Physical examination with Ultrasound
Uterine cancer	Menometorrhagia Intermenstrual bleeding Postcoital bleeding	+	+	-	Polyuria Dysuria	Fatigue Weight loss	+	Enlarged uterus Lymphadenopathy Mesenteric nodules (metastases)	+	-	-	-	Thickened endometrial lining >4cm	Endometrial thickening Lymph node involvement Pelvic metastases	Not required	Endometrial malignant cells Low grade type 1 High grade type 2	Histologic diagnosis
Vaginal lymphoma	+	+	+	+	Abdominal/pelvic pain	-	+	Palpable mass between rectum & vagina	+/-	-	-	-	Diffuse mass in external cervical orifice & invading the vagina	Diffuse mass in external cervical orifice & invading the vagina	Not required	CD20 & CD79a positive	Immunohistochemistry & biopsy
Vaginal polyp	Postmenopausal bleeding	+	+	+	Dyspareunia Postcoidal bleeding Dysuria Constipation	-	+	Mass protruding from vagina	+/-	-	-	-	To exclude uterine hyperplasia/carcinoma	To determine the extent	N/A	Benign tissue/premalignant cells	Excisional biopsy
Vaginal adenosis	Intermenstrual bleeding Postmenopausal bleeding	+/-	+/-	+/-	-	-	-	Palpable cysts,nodularity or ulcers	-	-	-	-	N/A	N/A	N/A	Columnar cells in the ectocervix	Biopsy with histopathological examination