Overview of ovarian tumors — Medicine Library

Summary

The ovaries consist of different types of tissue (epithelial, germ cells, and sex cord tissue), which may give rise to benign or malignant tumors. Epithelial ovarian tumors are the most common tumor subtype.

For information about ovarian cancer, see “Ovarian cancer.”

Classification of ovarian tumors

Epithelial ovarian tumors
- Arise from ovarian surface epithelium
- Most commonly benign
Germ cell
ovarian tumors
- Arise from the primordial germ cells (e.g., oocytes)
- Can be benign or malignant
Sex cord and stromal
ovarian tumors
- Arise from sex cord cells (e.g., Sertoli or granulosa cells) or stromal cells (e.g., fibroblasts or primitive gonadal stroma)
- Can be benign or malignant

Cellular origins of ovarian tumors

Epithelial ovarian tumors

Frequency
[3]
- Most common benign and malignant ovarian tumor subtype
- Epithelial tumors account for ∼ 90% of all ovarian malignancies
Histological classification
- Benign: lack hyperproliferative and invasive behavior
- Borderline ovarian tumors: a histopathological term that describes an ovarian tumor of low malignant potential that expresses cytologic features of malignancy without frank invasion
- Malignant: evidence of invasion
Clinicopathological classification
[4]
- Type I ovarian tumors: low-grade, indolent tumors that typically manifest as large, unilateral, cystic neoplasms
  
  Histologic subtypes include low-grade serous, endometrioid, clear cell, mucinous carcinomas, and malignant Brenner tumors
  
  Account for ∼ 10% of ovarian cancer deaths
  
  Associated with low levels of chromosomal instability
  
  p53 mutations are uncommon.
- Type II ovarian tumors: high-grade, aggressive tumors that typically involve both ovaries and are diagnosed at an advanced stage
  
  Histologic subtypes include high-grade serous, carcinosarcoma, and undifferentiated carcinoma
  
  Account for ∼ 90% of ovarian cancer deaths
  
  Associated with high levels of chromosomal instability
  
  p53 mutations are common

Types of epithelial ovarian tumors
Type		Cystadenoma		Brenner tumor[5]	Cystadenocarcinoma		Endometrioid carcinoma [3][6]	Clear cell tumors [3][7]
Type		Ovarian serous cystadenoma	Ovarian mucinous cystadenoma	Brenner tumor[5]	Serous	Mucinous [8]	Endometrioid carcinoma [3][6]	Clear cell tumors [3][7]
Classification		Benign			Malignant
Epidemiology		Most (serous) and second most common (mucinous) benign ovarian tumor		Rare Peak age: 40–60 years	Most common malignant ovarian tumor	Rare Can also be metastatic from GI malignancies (e.g., of the appendix)	10% of epithelial tumors Concomitant endometrial carcinoma in 10–15% of cases	5–10% of epithelial tumors Most commonly occur in perimenopausal women
Epidemiology				Rare Peak age: 40–60 years	Most common malignant ovarian tumor		Associated with endometriosis [9]
Clinical features		Typically asymptomatic Symptoms of abdominal displacement may be present (e.g., pain, ↑ urinary frequency)				Acute abdominal pain Pseudomyxoma peritonei [10] Rupture of a mucinous cystadenoma or cystadenocarcinoma leading to the spread of tumor cells throughout the peritoneum. Mucinous cells cause gelatinous ascites and intraabdominal adhesions.	Pelvic pain Symptoms of abdominal displacement may be present (e.g., pain, ↑ urinary frequency) Abnormal vaginal bleeding
Ultrasound appearance		Unilocular cystic mass Absent flow on Doppler	Large, multilocular cystic tumor	Mostly small tumors with a solid component and calcifications Absent or only minimal flow on Doppler	Cystadenocarcinomas are often bilateral (serous >> mucinous)		Mostly large, unilateral, solid or multilocular-solid tumor with papillary projections	Large (up to 30 cm in diameter), cystic/solid unilateral masses
Ultrasound appearance		Unilocular cystic mass Absent flow on Doppler	Large, multilocular cystic tumor		Tumor with mixed cystic/solid components and heterogeneous texture May contain papillary projections and/or thick septations	Similar to mucinous cystadenoma Additional solid components and signs of malignancy (e.g., invasion of adjacent structures) may be present Mural thickening
Pathology	Gross examination	Cysts with watery fluid	Smooth or bosselated appearance Cyst is loculated; loculi contain gelatinous material	Encapsulated, pale yellow solid tumor	Similar to serous cystadenoma	Cysts filled with mucoid material, cellular debris, and/or blood	Possible appearances are: Smooth surface with cystic spaces filled with blood-stained fluid Completely solid with necrosis/hemorrhage	Endometriosis-associated tumors are filled with chocolate-colored fluid
Pathology	Histology	May contain small papillary projections Psammoma bodies Cyst is lined by serous epithelial cells (similar to the epithelium of fallopian tubes)	Cyst is lined by columnar epithelium that secretes thick mucus (similar to the epithelium of cervix)	Similar to transitional cells of the bladder (urothelium) Circular patches of cells with coffee bean nuclei	Tumor cells with papillary structures and small cytoplasm Psammoma bodies are a typical feature .	Cystic or colloid type, depending on intracellular or extracellular mucin deposition Cystic type: > 50% of intracellular mucin in ≥ 90% of tumor cells Colloid type: large quantities of extracellular mucin (≥ 50% of tumor volume)	Characteristic confluent glandular/expansile pattern Tightly packed, back-to-back glands lined with tumor cells Absent intervening stroma	Variable appearance: tubulocystic, papillary, and solid
Tumor marker		CA-125

CA-125 is used as a tumor marker for epithelial ovarian cancer but can also be elevated in endometriosis, cirrhosis, and malignancies (e.g., uterine leiomyoma).

Most ovarian tumors are benign, not malignant.

**Mucinous cystadenocarcinoma of the ovary**
Source: “Mucinous Cystadenocarcinoma of the Ovary” by Ed Uthman, Flickr, licensed under CC BY 2.0.

**Mucinous cystic tumor of the ovary**
Macroscopic specimen of a right ovary (longitudinal section)
The ovary is significantly enlarged and completely transformed into a multilocular cyst. The ovarian surface is smooth on all sides (examples indicated by arrows). The cysts have partly smooth (examples indicated by green overlay) and partly polypoid raised inner walls (examples indicated by black lines) and were found to contain mucinous contents. In some areas, the cyst walls are noticeably thickened (examples indicated by blue overlay).
Histological examination revealed a mucinous borderline tumor of the ovary.

Source: “Proliferating Mucinous Tumor of the Ovary (1)” by Ed Uthman, Flickr, licensed under CC BY 2.0. The supplementary image with overlays of relevant areas was adapted from the image mentioned above (© AMBOSS).

**Serous papillary cystadenoma of the ovary with Psammoma bodies**
Histopathology slide of the ovary (H&E stain)
In addition to papillary tumor cells, there are two Psammoma bodies located in the lower left corner of the image (red overlay). Psammoma bodies are concentric, lamellar calcifications, which are characteristic for serous tumors of the ovary.

Source: © IMPP

**Ovarian mucinous cystadenoma**
Photomicrograph of an ovarian tissue specimen (H&E stain; high magnification)
A cyst (green overlay) lined by a single layer of columnar mucinous epithelium (white dashed line) is visible. The nuclei can be seen at the basal aspect of the cells (black arrow) with mucinous vacuoles visible apically. No cytologic atypia is visible.
This appearance is typical of an ovarian mucinous cystadenoma.

Source: “Ovarian_mucinous_cystadenoma_-_a2_--_intermed_mag” by Nephron, Wikimedia Commons, licensed under CC BY-SA 3.0. The supplementary image with overlays of relevant areas was adapted from the image mentioned above and licensed under CC BY-SA 3.0.

**High-grade serous carcinoma of ovary**
Photomicrograph of specimen from an ovarian cystic mass (H&E stain, medium magnification):
The carcinoma has a complex papillary architecture, with stromal cores lined by atypical, intensely staining (serous) epithelial cells. At higher magnification, these cells show hyperchromatic (dark blue staining), pleomorphic nuclei that often contain mitotic or apoptotic figures.
Click on the Smartzoom button to view the entire specimen through a virtual microscope.

Source: © Smart Zoom, Smart In Media. Image and annotations in digital microscopy: PD Dr. Alberto Perez Bouza

**Brenner tumor**
Photomicrograph of ovary tissue (H&E stain; 300x magnification)
Circular aggregations of tumor cells forming nests (examples indicated by green overlays) are visible throughout the specimen. These nests appear to be embedded in fusiform stroma (white overlay).
These findings are characteristic of a benign type of epithelial tumor known as a Brenner tumor.
Click on the Smartzoom button to view the entire specimen through a virtual microscope.

Source: © Smart Zoom, Smart In Media. Image and annotations in digital microscopy: PD Dr. med. Alberto Perez Bouza, Facharzt für Pathologie

Ovarian germ cell tumors

Frequency: ∼ 5% of all ovarian tumors [3]
Subtypes are determined by structural differentiation
- Extraembryonic differentiation: yolk sac tumor
- Somatic differentiation: teratoma
- No differentiation: dysgerminoma

Types of ovarian germ cell tumors
Type	Teratoma			Yolk sac tumor of the ovary (endodermal sinus tumor) [11]	Dysgerminoma [12]	Nongestational choriocarcinoma [13]	Embryonal carcinoma of the ovary
Type	Dermoid cysts (mature cystic teratoma)	Struma ovarii (mature teratoma) [14]	Immature teratoma [15]	Yolk sac tumor of the ovary (endodermal sinus tumor) [11]	Dysgerminoma [12]	Nongestational choriocarcinoma [13]	Embryonal carcinoma of the ovary
Classification	Benign		Malignant, aggressive
Epidemiology	Most common of all germ cell tumors (90% of all cases) Most common ovarian tumor in women < 30 years [16]	∼ 5% of all ovarian teratomas [17]	Rare Peak age: women < 20 years of age [18]	Occurs mainly in children and adolescents [18]	Most common malignant ovarian germ cell tumor in adolescents and young women [18]	∼ 5% of all malignant germ cell tumors [18]	Occurs mainly in children and adolescents
Clinical features	Mostly asymptomatic		Unspecific symptoms, including: Painful abdominal mass Amenorrhea	Rapid growth; acute onset of symptoms (pelvic mass and pain)			Precocious puberty Menstrual irregularities
Clinical features	Larger tumors may cause: ↑ Abdominal girth Pressure symptoms (e.g., ↑ urinary frequency) Lower abdominal pain	Symptoms of hyperthyroidism Palpable lower abdominal mass and pain					Precocious puberty Menstrual irregularities
Ultrasound appearance	Heterogeneous mass Hyperechoic nodule Echogenic shadowing Absent internal vascularity and/or fluid-fluid levels	Multilocular solid appearance Struma pearl may be present.	Large tumor with a solid component Solid component arises from the wall of the cyst and makes up ≥ 15% of total cyst size; contains smaller, fluid-filled cysts (e.g., blood, mucus). Small areas of calcification	Well vascularized tumor Contains a slightly hyperechoic solid component with an irregular, but still fine-textured appearance No acoustic shadowing	Large, solid, well- vascularized, multilobulated tumor that is well-defined relative to its surroundings Heterogeneous internal echogenicity	Well-vascularized mass with inhomogeneous texture Irregular contour Ovarian crescent sign may be present	Large, solid, well-defined tumor
Histopathology	Contains somatic tissue (e.g., hair, teeth, sebaceous glands) from any of the three embryonic germ layers: Endoderm Mesoderm Ectoderm	Endodermal differentiation into thyroid tissue [17]	Composed of immature neuroectodermal tissue	Macroscopic appearance: yellow, friable mass (due to hemorrhage) Schiller-Duval bodies (resemble glomeruli on microscopy) [19]	Equivalent to seminoma (e.g., presence of fried egg cells; see “Seminoma” for more details)	Cytotrophoblasts/syncytiotrophoblasts without chorionic villi	Syncytiotrophoblast-like tumor cells Aggregates of primitive embryonal cells Glandular or papillary pattern
Tumor markers	None		LDH (rare) [20]		LDH [21] hCG (rare: ∼ 5%)	hCG	hCG AFP
Tumor markers	None		AFP (rare) [22] CA-125 (rare)	AFP [23]	LDH [21] hCG (rare: ∼ 5%)	hCG	hCG AFP
Risk of malignant transformation	∼ 1% (usually to squamous cell carcinoma) [24]	Very rarely into thyroid carcinoma	N/A

Dermoid cyst (mature teratoma) Mature teratoma of the ovary Struma ovarii Dysgerminoma Schiller-Duval body

**Struma ovarii**
Photomicrograph of ovarian tissue specimen (H&E stain; low magnification)
Teratoma with endodermal differentiation into thyroid tissue. Numerous thyroid follicles (examples indicated by green overlay) filled with colloid and lined by simple flat/cuboidal epithelium are visible. Normal ovarian stroma (OS) is visible on the left and in the center of the image.

Source: “Struma ovarii - intermed mag” by Michael Bonert ("Nephron"), Wikimedia Commons, licensed under CC BY-SA 3.0. The supplementary image with overlays of relevant areas was adapted from the image mentioned above and licensed under CC BY-SA 3.0.

**Schiller-Duval body**
Photomicrograph of a testicular tumor sample (H&E stain; very high magnification)
A central blood vessel (red overlay) is surrounded by tumor cells (blue overlay) with enlarged nuclei and coarse chromatin, resulting in a glomerulus-like appearance (Schiller-Duval body).
Schiller-Duval bodies are a classic finding in yolk sac tumors. The diagnosis was confirmed by immunohistochemical findings (positive for α-fetoprotein and glypican 3).

Source: “Yolk sac tumor schiller duval body” by Jensflorian, Wikimedia Commons, licensed under CC BY-SA 3.0. The supplementary image with overlays of relevant areas was adapted from the image mentioned above and licensed under CC BY-SA 3.0.

**Dysgerminoma**
Photomicrograph of an ovary tissue specimen (H&E stain; high magnification)
Sheets of uniform cells with a fried-egg appearance (large nucleus and clear cytoplasm) are visible throughout (examples indicated by green overlay). These sheets of cells are separated by fibrous septa with lymphocytic infiltration.
These findings are consistent with dysgerminoma.

Source: “Dysgerminoma, very high mag.2” by CoRus13, Wikimedia Commons, licensed under CC0 1.0. The supplementary image with overlays of relevant areas was adapted from the image mentioned above (© AMBOSS).

Sex cord-stromal tumors of the ovary

Frequency: < 5% of all ovarian tumors [25]

Types of sex cord-stromal tumors of the ovary
Type		Ovarian fibroma [26]	Theca cell tumor (thecoma) [27]	Sertoli-Leydig cell tumor [28][29][30][31]	Granulosa cell tumor [28][32][33]
Classification		Benign		Usually benign	Malignant
Epidemiology		Peak age: postmenopause [34]		Rare Peak age: 30–40 years	Most common type of sex cord-stromal malignancy (∼ 90%) Peak age: 50–55 years
Clinical features		No hormonal activity Lower abdominal discomfort and/or a pulling-sensation in the inguinal area May be associated with Meigs syndrome: ascites and pleural effusion in association with a benign ovarian tumor; surgical removal of the tumor leads to complete resolution of symptoms. [35]	Abnormal postmenstrual bleeding due to estrogen production	Symptoms of excessive androgens and/or estrogen production ↑ Testosterone Virilization, hirsutism, acne, temporal balding Amenorrhea, clitoral enlargement, ↓ fertility ↑ Estrogen Menstrual bleeding abnormalities Endometrial polyps and hyperplasia	Symptoms caused by estrogen and/or progesterone secretion Adult subtype: menstrual irregularities (e.g., postmenopausal bleeding, endometrial hyperplasia with metrorrhagia) Juvenile subtype: precocious puberty Breast tenderness Associated with increased risk of endometrial cancer
Ultrasound appearance		Round or oval solid tumor with minimal to moderate vascularization Regular to slightly irregular internal echogenicity Cystic spaces may be present.	Ultrasound appearances include: Well-defined hypoechoic, solid mass with clear margins Echogenic mass with distal acoustic attenuation Anechoic lesion with through-transmission Visible endometrial thickening (secondary to hyperestrogenism)	Most commonly between 5–15 cm in diameter Large papillary projections may be visible.	Typically, large tumor with multilocular solid appearance with > 10 small locules Typically mixed or low level echogenicity
Pathology	Gross examination	Smooth, lobulated Cut surface: chalky, firm, yellow-to-white color	Solid yellow-orange tumor	Small, yellow-brown tumor	Tan/yellow color Encapsulated; smooth lobulated surface, possibly with areas of necrosis/hemorrhage
Pathology	Histology	Clusters of spindle-shaped cells (fibroblasts)	Ovarian stromal cells filled with lipids on microscopy	Seminiferous-like tubules lined by Sertoli cells and Reinke crystals	Call-Exner bodies: granulosa cells arranged in clusters surrounding a central cavity with eosinophilic secretions, resembling primordial follicles
Tumor markers		None			Inhibin

Call-Exner bodies are characteristic of Granulosa cell tumors: “Call your Ex and Grandparents!”

Call-Exner bodies

References

"Ovarian Cancer Including Fallopian Tube Cancer and Primary Peritoneal Carcinoma Version 1.2020". https://www.nccn.org/professionals/physician_gls/pdf/ovarian.pdf. [2020-03-11]
Meinhold-Heerlein I, Fotopoulou C, Harter P, et al. "The new WHO classification of ovarian, fallopian tube, and primary peritoneal cancer and its clinical implications.". Arch Gynecol Obstet. 293(4). :695-700. (2016)
Torre LA, Trabert B, DeSantis CE, et al. "Ovarian cancer statistics, 2018". CA Cancer J Clin. 68(4). :284-296. (2018)
Kurman RJ, Shih IeM. "The Dualistic Model of Ovarian Carcinogenesis: Revisited, Revised, and Expanded.". Am J Pathol. 186(4). :733-47. (2016)
Dierickx I, Valentin L, Van Holsbeke C, et al. "Imaging in gynecological disease (7): clinical and ultrasound features of Brenner tumors of the ovary". Ultrasound in Obstetrics & Gynecology. 40(6). :706-713. (2012)
Moro F, Magoga G, Pasciuto T, et al. "Imaging in gynecological disease (13): clinical and ultrasound characteristics of endometrioid ovarian cancer". Ultrasound in Obstetrics & Gynecology. 52(4). :535-543. (2018)
Pozzati F, Moro F, Pasciuto T, et al. "Imaging in gynecological disease (14): clinical and ultrasound characteristics of ovarian clear cell carcinoma". Ultrasound in Obstetrics & Gynecology. 52(6). :792-800. (2018)
Babaier A, Ghatage P. "Mucinous Cancer of the Ovary: Overview and Current Status". Diagnostics. 10(1). :52. (2020)
Wentzensen N, Poole EM, Trabert B, et al. "Ovarian Cancer Risk Factors by Histologic Subtype: An Analysis From the Ovarian Cancer Cohort Consortium". J Clin Oncol. 34(24). :2888-2898. (2016)
Smith JW, Kemeny N, Caldwell C, et al. "Pseudomyxoma peritonei of appendiceal origin. The memorial sloan-kettering cancer center experience". Cancer. 70(2). :396-401. (1992)
Anfelter P, Testa A, Chiappa V, et al. "Imaging in gynecological disease (17): ultrasound features of malignant ovarian yolk sac tumors (endodermal sinus tumors)". Ultrasound in Obstetrics & Gynecology. 56(2). :276-284. (2020)
Guerriero S, Testa AC, Timmerman D, et al. "Imaging of gynecological disease (6): clinical and ultrasound characteristics of ovarian dysgerminoma". Ultrasound in Obstetrics & Gynecology. 37(5). :596-602. (2011)
Mascilini F, Moro F, Di Grazia FM, et al. "Clinical and ultrasound features of non‐gestational ovarian choriocarcinoma". Ultrasound in Obstetrics & Gynecology. 52(1). :121-123. (2017)
Weinberger V, Kadlecova J, Minář L, et al. "Struma ovarii – ultrasound features of a rare tumor mimicking ovarian cancer". Medical Ultrasonography. 20(3). :355. (2018)
Abdullahi Idle S, Hayes K, Ross J. "Ultrasound features of immature ovarian teratomas: Case series and review of literature". Ultrasound. 28(2). :82-90. (2020)
Comerci JT Jr, Licciardi F, Bergh PA, Gregori C, Breen JL. "Mature cystic teratoma: a clinicopathologic evaluation of 517 cases and review of the literature.". Obstet Gynecol. 84(1). :22-8. (1994)
M.Roth L, Talerman A. "The enigma of struma ovarii". Pathology. 39(1). :139-146. (2007)
Smith HO, Berwick M, Verschraegen CF, et al. "Incidence and Survival Rates for Female Malignant Germ Cell Tumors". Obstet Gynecol. 107(5). :1075-1085. (2006)
Kurman RJ, Norris HJ. "Endodermal sinus tumor of the ovary.A clinical and pathologic analysis of 71 cases". Cancer. 38(6). :2404-2419. (1976)
Kawai M, Kano T, Kikkawa F, et al. "Seven tumor markers in benign and malignant germ cell tumors of the ovary". Gynecol Oncol. 45(3). :248-253. (1992)
Levato F, Martinello R, Campobasso C, Porto S. "LDH and LDH isoenzymes in ovarian dysgerminoma.". Eur J Gynaecol Oncol. 16(3). :212-5. (1995)
Ihara T, Ohama K, Satoh H, et al. "Histologic grade and karyotype of immature teratoma of the ovary". Cancer. 54(12). :2988-2994. (1984)
Gershenson DM, Del Junco G, Herson J, Rutledge FN. "Endodermal sinus tumor of the ovary: the M. D. Anderson experience.". Obstet Gynecol. 61(2). :194-202. (1983)
Park J-Y, Kim D-Y, Kim J-H, et al. "Malignant transformation of mature cystic teratoma of the ovary: Experience at a single institution". Eur J Obstet Gynecol Reprod Biol. 141(2). :173-178. (2008)
Quirk JT, Natarajan N. "Ovarian cancer incidence in the United States, 1992–1999". Gynecol Oncol. 97(2). :519-523. (2005)
Paladini D, Testa A, Van Holsbeke C, et al. "Imaging in gynecological disease (5): clinical and ultrasound characteristics in fibroma and fibrothecoma of the ovary". Ultrasound in Obstetrics and Gynecology. 34(2). :188-195. (2009)
"Ovarian thecoma". https://radiopaedia.org/articles/ovarian-thecoma
Lim D, Oliva E. "Ovarian sex cord-stromal tumours: an update in recent molecular advances". Pathology. 50(2). :178-189. (2018)
Zanotti KM. "The clinical manifestations and diagnosis of Sertoli-Leydig cell tumors of the ovary.". CME Journal of Gynecologic Oncology. 7. :129-133. (2002)
Young RH, Scully RE. "Ovarian Sertoli - Leydig cell tumors". Am J Surg Pathol. 9(8). :543-569. (1985)
Demidov VN, Lipatenkova J, Vikhareva O, et al. "Imaging of gynecological disease (2): clinical and ultrasound characteristics of Sertoli cell tumors, Sertoli–Leydig cell tumors and Leydig cell tumors". Ultrasound in Obstetrics and Gynecology. 31(1). :85-91. (2007)
Young RH. "Sex cord-stromal tumors of the ovary and testis: their similarities and differences with consideration of selected problems". Mod Pathol. 18(S2). :S81-S98. (2005)
Van Holsbeke C, Domali E, Holland TK, et al. "Imaging of gynecological disease (3): clinical and ultrasound characteristics of granulosa cell tumors of the ovary". Ultrasound in Obstetrics and Gynecology. 31(4). :450-456. (2008)
Tanaka YO, Tsunoda H, Kitagawa Y, et al. "Functioning Ovarian Tumors: Direct and Indirect Findings at MR Imaging". RadioGraphics. 24(suppl_1). :S147-S166. (2004)
Brun J-L. "Demons syndrome revisited: A review of the literature". Gynecol Oncol. 105(3). :796-800. (2007)