Ovary pathology
Chapter 44: Pathology of the Ovaries
Anatomy of the Ovaries
Structure: Paired, almond-shaped structures situated one on each side of the uterus, close to the lateral pelvic wall. They typically measure approximately in reproductive-aged women.
Position Variability: Their position is variable and influenced by the uterine location and ligament attachments, specifically the suspensory ligament (infundibulopelvic ligament) laterally and the ovarian ligament medially. Blood supply is primarily from the ovarian arteries originating from the aorta, and venous drainage is via the ovarian veins.
In an anteflexed midline uterus, the ovaries are usually identified laterally or posterolaterally, within the ovarian fossa (Fossa of Waldeyer).
Positioning Based on Uterus Orientation:
If the uterus lies to one side of the midline, the ipsilateral ovary often lies superior to the uterine fundus.
In a retroverted uterus, the ovaries tend to be lateral and superior, near the uterine fundus, often draped over the posterior uterine body.
When the uterus is enlarged (e.g., due to fibroids or pregnancy), the ovaries tend to be displaced more superiorly and laterally, sometimes making them more difficult to visualize.
Post-Hysterectomy Position:
Following hysterectomy, ovaries tend to be located more medially, directly superior to the vaginal cuff, due to the loss of uterine support and ligamentous changes.
Ovaries can be located high in the pelvis or in the cul-de-sac (Pouch of Douglas), a common site for fluid accumulation and metastatic disease.
Superiorly or extremely laterally placed ovaries may not be visualized by transvaginal ultrasound (TVS) due to being out of the field of view, necessitating transabdominal scanning or other imaging modalities.
Shape and Orientation: Ovaries are ellipsoid in shape, with craniocaudad axes paralleling the internal iliac vessels, serving as a reliable reference point for orientation and identification during ultrasound exams.
Normal Sonographic Appearance
Echotexture: Normal ovaries exhibit homogeneous echotexture, indicating uniform tissue composition. This helps to distinguish them from masses with heterogeneous or complex patterns.
May show a central, more echogenic medulla, which contains blood vessels and connective tissue.
Small anechoic or cystic follicles (typically 2-9 mm in diameter) may be visualized peripherally in the cortex, especially during the reproductive years. These represent developing primordial and primary follicles.
The appearance varies significantly with age and menstrual cycle due to hormonal influences.
Menstrual Cycle Phases:
During reproductive years, three phases are recognized sonographically:
Early Proliferative Phase (Day 1-10): Many follicles (often 5-10 in each ovary) develop and increase in size, typically ranging from 5-11 mm, until around day 8 or 9. This growth is primarily stimulated by Follicle-Stimulating Hormone (FSH), with a later surge of Luteinizing Hormone (LH).
A dominant follicle emerges, identified as the largest follicle, and typically reaches 2.0 to 2.5 cm (range ) just prior to ovulation. This follicle then ruptures to release the oocyte.
Cumulus Oophorus: Occasionally visible as an eccentrically located, cyst-like 1-mm internal mural protrusion within the dominant follicle, indicating the presence of the oocyte and signaling a mature follicle and imminent ovulation (within 24-36 hours).
Other non-dominant follicles become atretic (degenerate and reabsorb) after the selection of the dominant follicle due to hormonal changes.
Follicular Cysts: Can develop if fluid in non-dominant follicles is not reabsorbed or if the dominant follicle fails to ovulate, persisting as a simple cyst. The dominant follicle usually disappears immediately after ovulation but can occasionally decrease in size and develop crenulated walls as it transforms into a corpus luteum.
Post-Ovulation Features (Luteal Phase): Following ovulation, nodules commonly seen within the ovary may include:
Corpus Luteum: Identifiable as a small hypoechoic or isoechoic structure with thick, often echogenic, crenulated walls. It may contain low-level internal echoes due to hemorrhage, giving it a somewhat complex appearance. Color Doppler typically shows a characteristic circumferential “ring of fire” pattern due to increased peripheral vascularity, indicating active progesterone production.
Fluid Accumulation: Physiological fluid in the cul-de-sac (posterior to the uterus) is commonly observed after ovulation, peaking in the early luteal phase as a result of follicular fluid release.
Menopausal Considerations: Postmenopausal ovaries atrophy significantly, leading to the disappearance of follicles and a reduction in overall size (mean volume ). This smaller size, often accompanied by increased stromal echogenicity, can make them visually challenging to identify by ultrasound.
Ovarian Volume
Normal Volumes:
Ovarian volume is considered a critical parameter in evaluating ovarian health. Adult menstruating females may have ovarian volumes as large as 22 cc, with a mean volume of . Volume calculation is typically performed using the prolate ellipsoid formula: .
Abnormal Measurements: Ovarian volume exceeding 8.0 cc is considered abnormal in postmenopausal patients and warrants further investigation for potential pathology. Furthermore, a volume more than twice that of the opposite side in any age group should also be flagged as abnormal, even if the absolute volume is within the normal range, as it suggests unilateral enlargement.
Simple Cystic Masses
Functionality: The ovary's primary function includes maturing oocytes until ovulation, under the pulsatile influence of FSH and LH. Concurrently, the stromal cells synthesize androgens and convert them to estrogens, and eventually, the corpus luteum produces progesterone post-ovulation to sustain early pregnancy until the placenta assumes this function (around 7-9 weeks gestation).
Ovarian Cycle:
During a typical cycle, usually only one follicle enlarges from about 3 mm to approximately 24 mm over a span of 10 days within the mid- to late-follicular phases, followed by ovulation.
The resulting corpus luteum or an unruptured follicle can persist beyond its normal lifespan, forming simple or complex cysts ranging from 1 to 10 cm in size. These are often functional cysts and typically resolve spontaneously.
Persistence and Intervention:
Cysts larger than 6 cm persisting beyond 8 weeks may necessitate surgical intervention due to an increased risk of torsion, rupture, or a low but present malignant potential. Ultrasound-guided aspiration is a potential treatment for reducing recurrent symptomatic cysts under careful selection, particularly for benign-appearing simple cysts.
Benign Characteristics: The vast majority of ovarian masses are simple cysts, which are typically benign and often functional. Sonographic criteria defining a classic simple cyst include:
Thin, smooth walls, usually less than 3 mm thick.
Anechoic (fluid-filled) contents, indicating no internal echoes or solid components.
Posterior acoustic enhancement, a phenomenon where sound waves pass easily through the fluid, causing structures behind the cyst to appear brighter.
Complex Masses
Definition: Any simple cyst that hemorrhages during involution (e.g., a hemorrhagic corpus luteum or follicular cyst) can appear as a complex mass, presenting with internal echoes or septations. The appearance can vary over time as the blood clots and lyses.
Differential Diagnosis for complex adnexal masses in reproductive-age females is broad and includes:
Ectopic pregnancy: Often presents as an adnexal mass with a positive pregnancy test, frequently involving a complex appearance and may show a live embryo or yolk sac outside the uterus. The “ring of fire” sign on Doppler can also be seen, but it's typically peripheral to a gestational sac.
Endometriosis (Endometrioma): Characterized by blood-filled cysts (chocolate cysts) that appear as well-defined, unilocular or multilocular cysts with diffuse, low-level internal echoes (ground glass appearance) and sometimes small echogenic foci in the walls.
Pelvic Inflammatory Disease (PID): Can manifest as tubo-ovarian abscesses (TOAs), which are complex, multiloculated masses with thick, irregular walls and internal echoes, often accompanied by hyperemia and tenderness.
Dermoids (Mature Cystic Teratomas): Benign germ cell tumors that contain components from all three germ layers, appearing as complex masses with highly echogenic components (fat, hair, teeth), fluid-fluid levels, and often causing posterior shadowing (the "tip of the iceberg" sign).
Other benign tumors: Such as serous or mucinous cystadenomas that have undergone hemorrhage or infection.
Solid Tumors
Characteristics: Mixed solid to cystic masses are typical of all epithelial ovarian tumors, with the most common types being serous tumors, including cystadenoma (benign) and cystadenocarcinoma (malignant). The solid components represent proliferating epithelial tissue.
Incidence: During peak fertile years (20-40 years), the malignancy ratio for ovarian masses is approximately 1 in 15; this escalates significantly to 1 in 3 after the age of 40, highlighting the importance of thorough evaluation in older patients.
Malignancy Indicators: Generally, the more complex the tumor appearance (e.g., multiple septations, solid components, papillary projections), the more likely it is to be malignant, particularly if associated with ascites (fluid in the peritoneal cavity) or metastatic implants on peritoneal surfaces.
Serous tumors are typically tubal epithelium in type, often presenting as bilateral cysts and frequently filling the pelvic cavity, sometimes with exophytic papillary projections.
Volume Changes: An ovary with a volume twice that of the opposite side, especially in postmenopausal women, is generally considered abnormal. Identification of connection with the uterus (e.g., a vascular pedicle) is critical to differentiate ovarian lesions from pedunculated fibroids, which originate from the uterus.
Use of color Doppler can be essential in identifying vascular pedicles between the uterus and mass, confirming its uterine origin, or demonstrating feeding vessels within an ovarian mass.
Sonographic Evaluation of Ovarian Neoplasms
Malignancy Rates: Only 3% of ovarian cysts <5 cm are malignant, especially if they are simple cysts. However, cysts >5 cm, particularly those with complex features, are typically recommended for surgical removal or close follow-up due to an increased risk of malignancy or complications like torsion.
Benign versus Malignant Characteristics:
Well-defined anechoic lesions with thin walls are more likely to be benign.
Lesions with irregular walls, thick irregular septations (>3 \text{ mm}), mural nodules, solid echogenic elements, or abnormal color Doppler flow patterns strongly favor malignancy.
Doppler Findings: Malignant tumors often exhibit increased neovascularization (new blood vessel formation) with low-resistive flow patterns, characterized by a low Resistive Index (RI) (typically <0.4 for malignancy) and a low Pulsatility Index (PI). This contrasts with benign lesions which usually show higher resistance flow. Peritoneal carcinomatosis with ascites (diffuse peritoneal tumor implants) should be evaluated in advanced stages, often appearing as omental caking or nodular peritoneal thickening.
Changes in ovarian echogenicity or volume exceeding 20 ml (in reproductive age) or any significant unilateral enlargement should raise suspicion, especially in postmenopausal women.
Ovarian Carcinoma
Epidemiology: Ovarian carcinoma is the fourth leading cause of cancer death in women in developed countries, killing more women than cancers of the uterine cervix and body combined.
Approximately 1 in 70 women develop the disease, predominantly in those aged 40 to 60 years, with incidence increasing significantly after menopause.
Symptoms: Often asymptomatic in the early stages, making early detection challenging. When symptoms do occur, they are typically vague and non-specific, such as abdominal bloating, pelvic or abdominal pain, urinary frequency/urgency, early satiety, or changes in bowel habits. These non-specific symptoms frequently lead to a delayed diagnosis until advanced stages, hence its poor prognosis. Frequently, variable adnexal findings are noted on examination.
Diagnostic Indicators:
Blood chemistry test (CA 125) can be useful in monitoring treatment response and recurrence, but it is not strong for screening due to its lack of specificity (false positives can occur in benign conditions like endometriosis, uterine fibroids, PID, and even pregnancy) and its insensitivity (only half of patients with early-stage cancer and some advanced-stage cancers do not show elevated levels).
Sonographic Appearances: Generally observed as complex cystic or solid masses, often with irregular borders, papillary projections, and thick septations. Approximately 20% of cases are bilateral. Differential diagnoses may include endometriosis, hemorrhagic cysts, ovarian torsion, PID, and benign tumors.
Risk Factors: Family history of ovarian or breast cancer (especially BRCA1/BRCA2 mutations) is the strongest risk factor, alongside age, nulliparity (never having given birth), infertility, late menopause, and uninterrupted ovulation (e.g., early menarche, never using oral contraceptives). Conversely, factors that suppress ovulation (e.g., oral contraceptive use, multiple pregnancies, lactation) are protective.
Staging of Cancer: Based on the International Federation of Gynecology and Obstetrics (FIGO) staging system:
Stage I: Limited to ovaries. IA: one ovary, capsule intact; IB: both ovaries, capsules intact; IC: tumor on surface, capsule ruptured, or positive peritoneal washings.
Stage II: Limited to the pelvis, involving uterus/fallopian tubes or other pelvic tissues. IIA: extension to uterus/fallopian tubes; IIB: extension to other pelvic tissues (e.g., bladder, rectum).
Stage III: Involves abdominal extension, including retroperitoneal lymph nodes or small peritoneal metastases. IIIA: microscopic peritoneal or retroperitoneal lymph node involvement; IIIB: macroscopic peritoneal involvement <2 \text{ cm}; IIIC: macroscopic peritoneal involvement >2 \text{ cm} or parenchymal liver/spleen metastases.
Stage IV: Hematogenous spread beyond the abdomen (e.g., pleural effusion with positive cytology, distant metastases to lung, bone, brain).
Types of Tumors
Epithelial Tumors
Description: Arise from the surface epithelium covering the ovary and underlying stroma. These are the most common type, accounting for approximately 65% to 75% of all ovarian neoplasms. They are classified based on the type of epithelial cells they resemble.
Serous and Mucinous Tumors: Serous tumors (30% of all ovarian tumors) are the most common, followed by mucinous tumors (20-25%). Other types include endometrioid, clear cell, and Brenner tumors.
Characteristics: Benign forms are termed adenomas (e.g., serous cystadenoma), malignant forms as adenocarcinomas (e.g., serous cystadenocarcinoma). Prefixes like cyst- and fibroma are used based on tumor characteristics (e.g., cystic versus solid components).
Metastatic Spread: Primarily occurs intraperitoneally, with direct extension to surrounding structures (e.g., omentum, peritoneum, bowel) very common due to the intraperitoneal location of the ovaries.
Mucinous Cystadenoma
Profile: Constitutes 20-25% of benign ovarian neoplasms, usually affecting women aged 13-45. Predominantly benign (80-85%). These can grow to enormous sizes, potentially filling the entire abdomen.
Sonographic Features: Typically shows large, multilocular cysts with numerous internal septations, creating a honeycomb or spoke-wheel appearance. The compartments vary in echogenicity due to the presence of mucoid material, which can appear as fine, low-level echoes within the anechoic fluid. Unlike serous tumors, they are rarely bilateral.
Mucinous Cystadenocarcinoma
Profile: Less common than benign mucinous tumors, occurring in women aged 40-70; accounts for 5-10% of malignant ovarian neoplasms. Bilateral occurrence is relatively common (15-20%). Large, ruptured tumors can cause pseudomyxoma peritoneum, a severe condition where mucin-producing cells spread throughout the peritoneal cavity, leading to ascites and abdominal distention.
Sonographic Characteristics: Typically has thick, irregular walls, numerous coarse or irregular septations, and papillary projections or solid nodules along the internal surfaces. These features are similar in appearance to serous counterparts but often involve larger masses and denser mucin content.
Germ Cell Tumors
Category: Account for 15-20% of ovarian neoplasms, with the vast majority (95%) being benign. Among them, the cystic teratomas (dermoids) are prominent. Other more aggressive variants include dysgerminoma, embryonal carcinoma, choriocarcinoma, and endodermal sinus (yolk sac) tumor, which are typically malignant and found in younger women.
Clinical Presentation: Symptoms may include pelvic or abdominal pain due to mass effect or torsion, with palpable masses (average diameter up to 15 cm) often unilateral. Sonographically, cystic teratomas are characterized by diverse tissue elements, often containing calcification (teeth or bone), fat (appears highly echogenic), and hair, leading to variable complex appearances, shadowing, and fluid-fat levels.
Fibroma and Thecoma
Description: Solid tumors arising from ovarian stroma. Thecomas are more common, often benign, and frequently produce estrogen, leading to symptoms like abnormal uterine bleeding in postmenopausal women. Fibromas are typically larger, hypoechoic, solid masses presenting with pressure symptoms or ascites, sometimes associated with Meigs syndrome (ascites and pleural effusion with an ovarian fibroma), which resolves after tumor removal.
Granulosa Cell Tumor
Profile: The most common hormone-active estrogenic tumor, prevalent primarily post-menopause. These tumors produce estrogen, potentially causing postmenopausal bleeding, endometrial hyperplasia, or even endometrial carcinoma. Clinical symptoms may involve estrogenic effects (e.g., precocious puberty in children, endometrial changes in adults) and can lead to complications like torsion or rupture due. Sonographically, they often appear as solid, homogeneous, sometimes cystic masses.
Evaluation of Metastatic Disease
Occurrence: The ovaries are more prone to metastatic disease from other primary cancers than any other pelvic organ, often resembling advanced stages II to III ovarian cancer. This can occur via direct extension, lymphatic spread, or transcoelomic (peritoneal) seeding.
Common Sources: Primary cancers of the breast, upper GI tract (stomach, colon, pancreas), and other pelvic organs (endometrium, contralateral ovary).
Krukenberg Tumors: Characteristic metastases from GI tract tumors (especially the stomach, but also colon and breast). Sonographically, they appear as solid, often bilateral ovarian masses, typically with a heterogeneous,