Ovarian cancer differential diagnosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Fahimeh Shojaei, M.D.

Differentiating [Disease name] from other Diseases

Diseases		Clinical manifestations							Para-clinical findings				Gold standard	Additional findings
		Age of onset	Symptoms			Physical examination
									Lab Findings	Imaging		Immunohistopathology
			pelvic/abdominal pain or pressure	vaginal bleeding/discharge	GI dysturbance	Pleural effusion	Fever	Tenderness		CT scan/US	MRI
Gynecologic
Ovarian	Follicular cysts						–							It is associated with hyperestrogenism and endometrial hyperplasia
	Theca lutein cysts						–				Bilateral Multiple			It is associated with hydatidiform moles and choriocarcinoma
	Serous cystadenoma/carcinoma	>55 y/o					–				Bilateral			Most common ovarian neoplasm
	Mucinous cystadenoma/carcinoma	>55 y/o					–							It may cause pseudomyxoma peritonei
	Endometrioma	Women in reproductive age (15 -45 y/o)	+	+	+/–	–	–	+	Iron deficiency anemia Elevated levels of serum cancer antigen-125 Increased levels of interleukin 1, chemoattractant protein-1, and interferon gamma	Complex mass on US Increased Doppler flow because of increased vascularture It may present with catamenial pneumothorax, hemothorax, and lung nodules in CT scan.	hyperintensity on T1-weighted images and a hypointensity on T2-weighted images Powder burn hemorrhages	Chocolate cyst	Laprascopy	It may cause infertility
	Teratoma	10-30 y/o					–		High level of HCG and LDH					It may cause ovarian torsion May content thyroid tissue and cause hyperthyroidism
	Dysgerminoma			+			–		High level of HCG and LDH Hypercalcemia			Sheets fried egg appearance cells	Biopsy	Same as male seminomas
	Choriocarcinoma	During or after pregnancy					–		High level of B-hCG			Trophoblastic tissue origin columns and sheets of trophoblastic tissue invading uterine muscle and blood vessels		It is associated with bilateral Theca lutein cysts Cannonball metastases to the lungs May cause hemoptysis
	Yolk sac tumor	Young children Male infants					–		High levels of AFP			Yellow appearance Hemorrhagic Schiller-Duval bodies (glomeruli like structures)	Biopsy	The other name is ovarian endodermal sinus tumor
	Fibroma	>50 y/o	Pulling sensation in the groin	–	–	+/–	–	+/–				Spindle-shaped fibroblast	Biopsy	It may cause Meigs syndrome (ovarian fibroma, ascites, and hydrothorax) It may cause ovarian torsion
	Thecoma			Postmenopausal bleeding			–		High level of estrogen
	Granulosa cell tumor	50-60 y/o	+	Postmenopausal bleeding	+/–	–	–	_	High level of estrogen and progestron We may see inhibin, calretinin, and Ki-67 on the surface of granulosa cell tumor cells	In US we may see solid, cystic, or multiloculated solid and cystic mass	We may see solid, cystic, or multiloculated solid and cystic mass	Call-Exner bodies	Biopsy	In postmenopausal women may cause breast tenderness
	Sertoli-leydig cell tumor	15 to 35 y/o	+/–	–	–	–	–	–	Elevated serum testosterone level Elevated alpha-fetoprotein	In US we may see unilateral Well-defined hypoechoic lesion	Low T2 signal intensity areas of high signal intensity	Lydig cells (Polygonal pink cells with eosinophilic cytoplasm Sertoli cells (clear vacuolated cytoplasm)	Biopsy	It may cause virilization symptoms and amenorrhea
	Brenner tumor	>55 y/o	+/–	–	–	–	_	_	_	In US we may see hypoechoic solid mass and calcification	Hypointense on T2 because of fibrous content	Yellow/pale appearance Transitional cell tumor (resembles bladder) Coffee bean nuclei on H&E	Biopsy	Most of the times it's an accidental finding
	Krukenberg tumor	>55 y/o	+/–	–	+/– Based on underlying malignancy	+/– Based on underlying malignancy	–	–	In case of metastatic GI cancers we may see iron deficiency anemia	Mostly bilateral, complex ovarian lesion In CT scan we may see evidence of concurrent malignancy in other organs	Mostly bilateral, complex ovarian lesion with solid components Internal hyperintensity on T1 and T2 weighted MR images because of mucin Evidence of concurrent malignancy in other organs	Mucin-secreting signet cell	Imaging/biopsy	The most common primary tumor is in colon, stomach, breast, lung, and contralateral ovary.
Tubal	tubo-ovarian abscess	Young women (15-30 y/o	+	+	–	–	+	+	High levels of inflammatory markers Leukocytosis	In US we may see multilocular complex lesion mostly bilateral with debry inside	We may see a pelvic mass filled with fluid with thick walls hypointense in T1 and heterogeneous in T2	In abscess aspiration we may see anaerobic organisms	History/imaging	The most common risk factors are previous PID, diabetes mellitus, intrauterine device and history of uterine surgery
	Ectopic pregnancy	Women in reproductive age (15 -45 y/o)	+	+	+/–	–	–	+	High level of BhCG Progesterone level ≤5 ng/ml	In US we may see empty uterine cavity, tubal ring sign, ring of fire sign (Doppler), extra-uterine fetal heart rate	NA	NA	History/imaging	Any women in reproductive age presenting with abdominal pain or amenorrhea should be screened for ectopic pregnancy
	Hydrosalpinx	NA	+	–	–	–	–	+/–	–	In US we may see tubal longitudinal folds thickening (cogwheel appearance) In CT scan we may see tubular adnexal lesion with fluid attenuation	Dilated Fallopian tube with fluid signal intensity	NA	Imaging	It is associated with endometriosis (haematosalpinx), ovulation induction, pelvic inflammatory disease, post-hysterectomy, tubal ligation, and tubal malignancy It may cause infertility
	Salpingitis	Women of reproductive age	+	+	–	–	+	+	Leukocytosis	In US we may see , edematous and thickened endosalpingeal folds	NA	NA	History/physical exam	It may cause infertility
	Fallopian tube epithelial carcinoma	>55 y/o	+	+/–	+	+	–	+/–					Biopsy	It is associated with para-neoplastic syndromes such as polyneuritis, dermatomyositis, cerebellar degeneration, disseminated intravascular coagulation, hemolytic anemia, acanthosis, or nephrotic syndrome
Uterine	Leiomyoma	Women of reproductive age	+	+	–	–	–	+/–	In chronic cases, we may see mild anemia	In US we may see hypoechoic mass with calcification and cystic areas of necrosis or degeneration may	Low to intermediate signal intensity on T1 and T2 In case of necrosis inside the mass, there might be some high signal lesions on T2	Smooth muscle	Imaging	It may cause infertility
	Leiomyosarcoma	>55 y/o	+	+	–	–	–	+/–	In some cases we may see elevated levels of CA 125 lactate dehydrogenase	Heterogeneous mass with central low attenuation (necrosis) and calcification.	Increased uterine size Irregular central zones of low signal intensity (tumor necrosis)	We may see atypical cells, high mitotic rate, geographic areas of coagulative necrosis separated from viable neoplasm	Biopsy	In case of rapid uterine growth in post menopausal women we may suspect uterine sarcoma
	Pregnancy	Women in reproductive age (15 -45 y/o)	+/−	+/−	+/−	–	–	–	High level of BhCG	In US we may see ​gestational sac, yolk sac, double bleb sign and fetal pore In CT scan we may see cystic structure filled with fluid, curvilinear enhancing structure (placenta) and fetal pore	Cystic structure filled with fluid Curvilinear enhancing structure (placenta) Fetal pore	NA	History/laboratory findings	We do not perform CT scan and MRI in pregnancy but We may unintentionally image the pregnancy with CT scan and MRI.
Non-gynecologic
GIT	Appendiceal abscess	NA	+	–	+	+	+/–	+	Leukocytosis	Fluid collection in the appendicular region appendicolith may be visualized.	Fluid collection in the appendicular region appendicolith may be visualized.	NA	Imaging/history	The most common complication of acute appendicitis
	Appendiceal neoplasm	60-70 y/o for adenocarcinoma, 30-50 y/o for carcinoid tumors	+	–	+	+	–	+/–	In adenocarcinoma type we may have high levels of CEA and CA 19-9 In carcinoid type we may see high levels of chromogranin A, 5-HIAA and Ki67	In CT scan we may see: Soft tissue thickening and Cystic lesion with Internal septation Wall irregularity Calcification Periappendiceal fat stranding	Soft tissue mass in the appendix We may see invasion to other structures	Gray/yellowi color Cystic structures with angiolymphatic invasion	Biopsy	It is associated with: MEN1 Syndome Ulcerative colitis Neurofibromatosis type 1 HNPCC Smoking
	Diverticular abscess	>50 y/o	+	–	+	+	+/–	+	Leukocytosis	Ill-defined lesion with air and fluid inside Adjacent bowel loop wall thickening Smudged mesenteric fat	We may see a lesion with air and fluid inside	NA	Imaging/history	Diverticular abscess happens in almost 30-40% of patients with diverticulitis
	Colorectal cancer	>50 y/o	+	–	+	–	–	+/–	Anemia Positive Fecal occult blood test High levels of CEA and CA 19-9	In CT scan we may see luminal narrowing, intestinal wall thickening,intussusception, bowel obstruction, hepatic metastases, intestinal perforation,enlarged lymph nodes	We may see tumor mass and the extension of tumor to other structures We may see metastasis to the liver, lung and brain	Based on the sub-type we may have different histopathological feature (for more information click here)	Biopsy	It is associated with smoking, positive family history, processed meat, low fiber diet, lynch Syndrome and familial adenomatous polyposis They have apple core lesion on barium enema xray
Renal Bladder	Pelvic kidney	NA	−/+ In case of sever hydronephrosis or renal stone we may have pelvic pain	–	−	−	−	−	−	In sonography we may see normal appearing kidney in pelvic position We may see renal calculi	We may see normal kidney structure Renal calculi	NA	Imaging	It may cause hypertension It may cause tract infection (UTI), obstruction, and renal calculi. It may be associated with (RCC)
	Bladder cancer	≥65 y/o	+	–	–	–	–	–	Low red blood cell count Elevated alkaline phosphatase Positive tumor markers such as BTA, NMP, and CEA	In CT scan we may see masses protruding into the bladder lumen or asymmetric thickening of the bladder calcifications Nodal metastases	isointense compared to muscle in T! slightly hyperintense compared to muscle in T2	Based on the sub-type we may have different histopathological feature (for more information click here)	Biopsy	It may presents with hematuria
Others	Retroperitoneal sarcoma	40-50 y/o	+	–	+	−	−	−	Mild leukocytosis. It may cause hypoglycemia because of production of insulinlike substances	We may see irregular solid, semisolid, liquefactive areas and patchy necrosis on CT scan	We may see retroperitoneal involement and degree of tumor extenstion We may see liver and lung metastasis	There are two types: liposarcoma and leiomyosarcoma In liposarcomas we may see background of adipocytes with scattered lipoblasts, and inflammatory cell infiltrate In leiomyosarcoma we may see smooth muscle cells	Biopsy	May cause lower extremity edema, Serous ascites we should perform chest CT scan to rule out pulmonary metastases

check sites of cancer that may metastasize to the ovaries (eg, stomach, colorectal, breast)

check rectum, liver, spleen, lungs, inguinal or supraclavicular lymph nodes for ovary metastase

• Bladder tumour–associated antigen (BTA)
• Nuclear matrix proteins (NMP)
• Mucin and carcinoembryonic antigen (CEA)