Cervical cancer differential diagnosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Nima Nasiri, M.D.[2]

Overview

Cervical cancer must be differentiated from other diseases that cause abnormal vaginal bleeding, such as cervical polyp, cervical leiomyoma, invasion of the cervix from primary uterine malignancy, vaginal cancer, cervical lymphoma, metastases to cervix, and cervical ectopic pregnancy.

Cervical cancer differential diagnosis

• Cervical cancer must be differentiated from a mass involving the cervix, and causing abnormal vaginal bleeding:

• Cervical polyp
• Cervical leiomyoma
• Cervical lymphoma
• Cervical sarcoma
• Metastases to the cervix
• Cervical ectopic pregnancy
• Cervicitis
• Cervical erosion ( Ectropion )
• IUD use
• Pelvic inflammatory disease
• Endometriosis
• Adenomyosis
• Nabothian cyst

Abnormal Uterine bleeidng differential diagnosis
Ob-Gyn neoplasm and diseases	Clinical manifestations							Para-clinical findings					Gold standard
	Symptoms					Physical exam		Lab Findings		Imaging		Histopathology
	Abnormal vaginal bleeding	Other Genitourinary/ Gastrointestinal symptoms	Abdominal pain	Pelvic pain	B symptoms	Gynecological examinations	Abdominal mass	HPV Pap smear STI panel	Other labs	Ultrasound	Other imagings
Cervical cancer	Postmenopausal Intermenstrual Postcoital Bleeding after pelvic exam	Dysuria Urinary hesitancy Dyspareunia Vaginal discharge Itching or burning of the vulva	+	+	+	Cervical mass on exam	+	± HPV Atypical cells on Pap smear STI: ± Chlamydia	↑ CA-125 Leukomoid reaction	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	Cervical intraepithelial neoplasia: CIN1: mild dysplasia CIN2: moderate dysplasia CIN3: high degree of dysplasia/metastases	Colposcopy/biopsy
Cervical polyp	Postcoital Intermenstrual Postmenopausal Bleeding after exam	Vaginal discharge Dyspareunia	−	−	−	Mass on exam	−	−	↓ RBC count ↓ Hemoglobin, ↓ Hct ↓ Serum Iron	Hyper/hypoechogenic masses with or without cysts Filling the endocervical or vaginal canal		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 Vaginal discharge	+	+	−	Large,irregular pelvic mass	±	−	Erythrocytosis	Well circumscribed hyperechoic mass	T2-weighted MRI: Hypointense masses Homogeneous enhancement Red degeneration	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	+	+	+	Larrge uterine/cervix mass Irregularity	+	Pap smear: Small round blue cells High nuclear/cytoplasm ratio, Scant cytoplasm	Immunohistochemistry markers: CD19, CD20, CD79a, PAX5	Well-defined, solid, concentric, hypoechoic mass	MRI: Intramyometrial infiltrative nodules	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 pelvic Vaginal discharge	+	+	±	Cervical mass Lump protruding from vagina/vulva	+	−	Leiomyosarcoma markers: Positive for for S-100 and vimentin and are negative for desmin, myoglobin and actin.	Endometrial mass with heterogeneous echogenicity	MRI: Endometrial polypoid mass Hypointense hypervascular solid components	Poorly circumscribed bulky mass protruding from cervical canal Different subtypes: Leiomyosarcoma Endocervical sarcoma Embryonal rhabdomyosarcoma( Sarcoma botryoides)	Biopsy
Cervical erosion(Ectropion)	Light bleeding after pelvic exam Spotting	Post-coital pain Painful cramps Dyspareunia Vaginal discharge Itching of vulvovaginal area	+	+	−	Red, glandular area around os of cervix	−	−	N/A	N/A	N/A	Squamous metaplasia Vascular ectasia Lymphocytic infiltration	Colposcopy and biopsy
Cervicitis	Intermenstrual bleeding Postcoital Bleeding after pelvic exam	Pain during urination Pain during sex Painful menstruation Purulent vaginal discharge Itching of vulva	+	+	May have fever only	Red,inflammed swollen cervix Inflammation/irritation of vulva/vagina	−	STI panel: Chlamydia Gonorrhea Herpes simplex Trichomonas vaginalis	↑ WBC + NAAT for chlamydia, gonorrhea		MRI: May be detected as retention cysts in cervix.	Non-specific, lymphocytic infiltration may be seen in microscopic histology. Koilocytic changes in case of HPV as cause of chronic cervicitis.	Nucleic acid amplification tests (NAATs)
Endometriosis	Heavy mentrual bleeding	Painful menstruation Burning/painful urination Painful bowel movement Pain during or after sex Infertility Watery vaginal discharge	+	Pelvic pain Back pain	−	Tender uterosacral nodularity Immobile uterus Cervical motion tenderness Retroverted uterus	+	−	↑ IL-6 ↑ TNF-α ↑ CA-125 (limited value)	Ground glass echogenicity of the cyst fluid (Endometrioma) Cysts are unilocular	MRI findings is variable, depending upon the sites of endometriosis such as peritoneal implants, ovarian endometrioma, pelvic endometriosis.	Endometrial type glands and stroma presence is charracteristic histology findings, suggestive for endometriosis.	Visual inspection by laparoscopy
Pelvic inflammatory diseases	Bleeding after sex Intermenstrual bleeding	Fever Pelvic pain Dyspareunia Dysmenorrhea Dysuria Dyschezia Smelly grey/white/yellow vaginal discharge Itching and burning of vulvovaginal area	+	Pelvic pain Cervical motion tenderness	Oral temperature >101F	Vaginal/vulvar tender lesion depending on microbial causes	−	STI panel: Chlamydia Gonorrhea	↑ CRP ↑ ESR ↑ WBC Oral temperature >101F	Ultrasound: Thickened, fluid-filled tubes with or without free pelvic or tubo-ovarian complex	MRI findings: Inflammation in pelvic soft tissue Hydrosalpinx Tubo-ovarian abscess in chronic PID.	Inflamed, purulent fallopian tubes	Clinical diagnosis is gold standard for diagnosing PID Laparoscopy is confirmatory in acute salpingitis
Adenemyosis	Abnormal uterine bleeding	Painful menstruation	+	+	−	Polypoid mass protruding into the endocervical canal.	Enlarged uterus may present as abdominal mass	−	↑ CA-125	Subendometrial striations Myometrial cysts Asymetrical thickness in myometrium walls Heterogenous echotexture of myometrium	MRI: Thickened junctional zone	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.	±	−	↑ β-HCG	Empty uterine Thickened endometrium	T2-weighted MRI: Hypointense large mass T1-weighted MRI: Partially hyperintense mass	Necrotic hemorrhagic mass with chorionic villus	Hysterectomy and biopsy
Vaginal cancer	Postcoital bleeding	Tenesmus Dysuria Urinary frequency Constipation Pelvic pain Vaginal discharge	+	+	±	Ill-defined vaginal ulcer Vaginal lump Inguinal lymphadenopathy Edema and ulceration of vaginal wall Foul-odor blood tinged vaginal discharge Vaginal prolapse Cystocele	In case of metastases to internal organs	Pap smear can be normal ± HPV	↓ RBC count	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	Biopsy findings: Squamous cell carcinoma of vagina	Biopsy
Paget's disease of vulva to cervix	Bleeding from lesion	± Vaginal discharge Pain in vulva Itching or burning sensation in vulva	−	−	−	Scaly eczematoid lesion in vulva. Erythematous plaques with white scaling. Inguinal lymphadenopathy in case of metastases.	−	−	Positive for cytokeratin(CK7) Negative for S-100 and Melan-A	N/A	MRI: Hyperintense on diffusion weighted imaging	Thick vulvar skin "Cake-icing effect", pathognomic for vulvar paget's disease Intraepidermal adenocarcinoma which involves epidermis	Biopsy of lesion
Nabothian cyst	Postcoital bleeding	Pain during sex Vaginal discharge	In very rare cases depending upon the size of cyst it can cause abdominal pain and amenorrhea	−	−	Majority of them are asymptomatic due to their small size( few milimeters) Cystic mass on exam	−	−	N/A	Anechoic well defined cystic lesions	T1-weighted Intermediate or slightly high signal intensity T2-weighted High signal intensity on T2-weighted images Benign cystic lesion	Multiple benign cystic masses, usually few milimieters in diameter.	Histopathological exam if large cystic masses
IUD use	Heavy bleeidng	Painful menstruation ± Vaginal discharge	+ In cases of uterine rupture and far migration of IUD, it can cause adhesion, bowel obstruction, perforation.	+	−	Normal	−	−	May have decreased RBC count	Linear echogenic intrauterine structures	N/A	N/A	Transvaginal ultrasound