Pathology of the ovaries





Objectives


On completion of this chapter, you should be able to:




  • Describe the effects of hormones on the ovarian cycle



  • State the characteristics of the simple ovarian cyst and a functional ovarian cyst



  • Discuss the sonographic findings of the common cystic and complex ovarian masses, common solid ovarian masses, and ovarian neoplasms



  • List the characteristics of the ovarian syndromes discussed in this chapter



  • Discuss the benign pelvic masses found in neonates and adolescent girls



  • Differentiate between mucinous and serous types of tumors



  • Explain the Doppler parameters used in ovarian torsion





Sonography is clinically useful to characterize adnexal masses, evaluate abnormal bleeding, assess infertility, monitor follicular growth, perform endovaginal needle aspiration and biopsy, and screen for ovarian carcinoma. Both transabdominal and transvaginal sonography are important in these evaluations. Transabdominal imaging furnishes a global survey of anatomy, whereas transvaginal imaging provides better characterization of internal architecture of the ovary, vascular anatomy, and adnexal area. It is important to note that information from the clinical pelvic examination is required for optimal interpretation of the sonographic studies, thus necessitating good communication between the referring physician and the sonologist.


A woman will ovulate nearly 400 times in her reproductive life, and a quarter of a million follicles will be stimulated to varying degrees during this time. It is not surprising that an organ as dynamic as the ovary can form more than 100 different types of tumors, both benign and malignant. These masses are described on the sonographic examination as primarily cystic, complex, or predominantly solid. However, the final diagnosis is left to the pathologist on surgical excision. Precise diagnosis on the basis of sonography alone is highly predictive, although not conclusive until the surgery. The primary role of sonography is to indicate the need for surgical or medical intervention.




Anatomy of the ovaries


The ovaries are paired, almond-shaped structures situated one on each side of the uterus close to the lateral pelvic wall ( Figure 44-1 ). The ovaries can vary in position and are influenced by the uterine location and the ligament attachments. In the anteflexed midline uterus, the ovaries are usually identified laterally or posterolaterally. When 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. When the uterus is enlarged, the ovaries tend to be displaced more superiorly and laterally. Following hysterectomy, the ovaries tend to be located more medially and directly superior to the vaginal cuff. They can be located high in the pelvis or in the cul-de-sac. Superiorly or extremely laterally placed ovaries may not be visualized by the transvaginal approach because they are out of the field of view. Ovaries are ellipsoid in shape, with their craniocaudad axes paralleling the internal iliac vessels, which lie posterior and serve as a reference point.




FIGURE 44-1


​Normal anatomy of the female pelvis. Note the relationship of the ovaries to the lateral walls of the uterus and the position of the fallopian tubes to the ovaries.


Normal sonographic appearance


The normal ovary has a homogeneous echotexture, which may exhibit a central, more echogenic medulla. Small anechoic or cystic follicles may be seen peripherally in the cortex ( Figure 44-2 ). The appearance of the ovary varies with age and the menstrual cycle ( Figure 44-3 ). During the reproductive years, three phases are recognized sonographically during each menstrual cycle. During the early proliferative phase, many follicles develop and increase in size until about day 8 or 9 of the menstrual cycle. This is due to stimulation by both follicle-stimulating hormone (FSH) and luteinizing hormone (LH). At that time one follicle becomes dominant, reaching up to 2 to 2.5 cm at the time of ovulation. The cumulus oophorus may occasionally be detected as an eccentrically located, cystlike, 1-mm internal mural protrusion. Although visualization of the cumulus indicates a mature follicle and imminent ovulation, no reproducible sonographic sign is reliable. The other follicles become atretic. A follicular cyst develops if the fluid in the nondominant follicles is not reabsorbed. Usually the dominant follicle disappears immediately after rupture at ovulation. Occasionally the follicle decreases in size and develops a wall that appears crenulated (scalloped). Fluid in the cul-de-sac commonly occurs after ovulation and peaks in the early luteal phase. Following ovulation in the luteal phase, a mature corpus luteum develops and may be identified sonographically as a small hypoechoic or isoechoic structure peripherally within the ovary. It may appear irregular with echogenic crenulated walls and contain low-level echoes. Less frequent appearances include a typical “ring” color Doppler pattern around the wall of an isoechoic corpus luteum. In the absence of fertilization, the corpus luteum begins to undergo involutional changes on postovulatory day 8 or 9 and disappears shortly before or with the onset of menstruation.




FIGURE 44-2


​Normal transvaginal image of the ovaries with multiple follicles. A, Both ovaries are well seen with multiple follicles. B, Long left ovary. C, Transverse left ovary. D, Normal color Doppler of the ovary. E, Long right ovary. F, Transverse right ovary.



FIGURE 44-3


​Diagram of cyclic changes of the normal ovary.


Multiple small, punctate, echogenic foci are commonly seen in the normal ovary. These foci are reported to be a common finding with transvaginal examination. They are generally very small (1 to 2 mm) and located in the periphery. The foci are nonshadowing and can be multiple. A possible source of these foci of specular reflections is from the walls of tiny unresolved cysts below the spatial resolution of ultrasound. More central punctate echogenic foci are thought to represent stromal reaction to previous hemorrhage or infection. Because they do not indicate significant underlying disease, no follow-up is necessary.


Following menopause, the ovary atrophies and the follicles disappear with increasing age. For this reason, the postmenopausal ovary may be difficult to visualize sonographically because of the smaller size and lack of discrete follicles. A stationary loop of the bowel may mimic a small shrunken ovary, so scanning must be done slowly to look for peristalsis in the bowel. After a hysterectomy, the ovaries can be difficult to visualize with ultrasound. The use of both transabdominal and transvaginal approaches increases the chance of visualization.


Because of the variability in ovarian shape and size, the volume measurement is the best method for determining overall ovarian size. The volume measurement is based on the prolate ellipse formula (0.523 × length × width × height). In the adult menstruating female, a normal ovary may have a volume as large as 22 ml, with a mean ovarian volume of 9.8 ± 5.8 ml. An ovarian volume of more than 8 ml is definitely considered abnormal for the postmenopausal patient. An ovarian volume more than double that of the opposite side should also be considered abnormal, regardless of the actual size. Three-dimensional (3D) ultrasound may provide the most accurate method of ovarian volume measurement by allowing accurate determination of the ovarian long axis and objective calculation of stromal and cystic volume components. Further development in this technology will define future applications.




Sonographic evaluation of the ovaries


Simple cystic masses


An ovary’s function is to mature oocytes until ovulation under the influence of LH and FSH hormone from the pituitary. At the same time, the ovary synthesizes androgens (male hormones) and converts them to estrogens (female hormones). Finally, it produces progesterone after ovulation to sustain early pregnancy until the placenta can do so at 10 to 12 weeks of gestation.


Usually only one follicle enlarges from 3 mm to approximately 24 mm over about 10 days in the mid- and late-follicular phases of the cycle. This is followed by ovulation. The resulting corpus luteum or an abnormal unruptured follicle can persist as a simple or complex cystic structure from 1 to 10 cm in size. These so-called functional cysts may produce discomfort or delayed menses but can be observed to regress within 8 weeks with serial ultrasound studies. If a cyst greater than 6 cm persists more than 8 weeks, surgical intervention may be considered.


Ultrasound-guided needle aspiration has become another option for reducing recurrent simple ovarian cysts in carefully selected cases. The majority of ovarian masses are simple cysts, most of which are benign. Sonographic criteria for a simple cyst include a thin smooth wall, anechoic contents, and acoustic enhancement ( Figure 44-4 , A ). In premenopausal women, these cysts usually are functional. The differential considerations of simple adnexal cysts include functional cyst, paraovarian cyst, cystadenoma, cystic teratoma, endometrioma, and rarely tubo-ovarian abscess ( Box 44-1 ).




FIGURE 44-4


A, Simple ovarian cyst. The cyst is well defined and anechoic, with increased through-transmission. B, Complex ovarian cyst. Transvaginal sagittal image of a simple cyst that has hemorrhaged; this mass had resolved spontaneously when the patient was rescanned 2 weeks later. The borders of the mass are well defined; there are low-level internal echoes within the mass. On real-time imaging, swirling of these echoes could be seen. C, Solid mass. Transvaginal sagittal image of a large, solid ovarian mass in a 56-year-old woman. The mass has irregular borders with a heterogeneous texture and decreased through-transmission. This was a dermoid tumor.


BOX 44-1

Common Cystic or Homogeneous Ovarian Masses





  • Follicular cyst



  • Corpus luteum cyst of pregnancy



  • Cystic teratoma



  • Paraovarian cyst



  • Hydrosalpinx



  • Endometrioma (low-level echoes)



  • Hemorrhagic cyst




Small anechoic cysts may be seen in postmenopausal ovaries. They can disappear or change in size over time. Serial sonographic studies can monitor the size and document any changes. Surgery is generally recommended for postmenopausal cysts greater than 5 cm and for those containing internal septations or solid nodules.


Complex masses


Any simple cyst that hemorrhages as it involutes may appear as a complex mass ( Box 44-2 ). In patients of reproductive age, the classic differential considerations of a complex adnexal mass are ectopic pregnancy, endometriosis, and pelvic inflammatory disease (PID) ( Figure 44-4 , B ). Dermoids and other benign tumors can appear in a similar fashion.



BOX 44-2

Common Complex Masses





  • Cystadenoma



  • Dermoid cyst



  • Tubo-ovarian abscess



  • Ectopic pregnancy



  • Granulosa cell tumor




Solid tumors


Mixed solid to cystic ovarian masses are typical of all the epithelial ovarian tumors; the most common are the serous types: cystadenoma and cystadenocarcinoma ( Figure 44-4 , C ). During the peak fertile years, only 1 in 15 is malignant; this ratio becomes 1 in 3 after age 40.


The more sonographically complex the tumor, the more likely it is to be malignant, especially if associated with ascites. The epithelium of serous tumors is tubal in type, and there may be one or multiple cysts. One fourth of them are bilateral, and most occur in women over age 40. They are large and often fill the pelvic cavity.


The differential considerations of a solid-appearing adnexal mass include pedunculated fibroid, dermoid, fibroma, thecoma, granulosa cell tumor, Brenner tumor, and metastasis. Tubo-ovarian abscess, ovarian torsion, hemorrhagic cysts, and ectopic pregnancy also may appear solid. Solid adnexal masses are often difficult to diagnose because normal ovarian size varies widely. However, as previously noted, an ovary that has a volume double that of the opposite side is generally considered abnormal. When a solid mass is found, care should be taken to identify a connection with the uterus to differentiate an ovarian lesion from a pedunculated fibroid ( Box 44-3 ). The use of color Doppler can be helpful, as color can be used to identify a vascular pedicle between the uterus and the mass, as can often be identified with pedunculation.



BOX 44-3

Common Solid Masses





  • Solid teratoma



  • Adenocarcinoma



  • Arrhenoblastoma



  • Fibroma



  • Dysgerminoma



  • Torsion




Doppler of the ovary


When any abnormality of the ovary is detected, Doppler examination should be performed. In the case of a suspected cystic lesion, color Doppler is helpful in differentiating a potential cyst from adjacent vascular structures ( Figure 44-5 ). Color also can be used to localize flow to further determine flow velocity with pulsed Doppler, which can be obtained on all ovarian masses. Pulsed Doppler interrogation of the adnexal branch of the uterine artery, the ovarian artery, or intratumoral flow is performed to determine the resistive index or pulsatility index ( Figure 44-6 ). Patients with normal menstrual cycles are best scanned in the first 10 days of the cycle to avoid confusion with normal changes in intraovarian blood flow, because high diastolic flow occurs in the luteal phase ( Figure 44-7 ).




FIGURE 44-5


​Color or power Doppler is useful to distinguish cystic structures from vessels.



FIGURE 44-6


A, Cystic lesion with internal echoes in asymptomatic 52-year-old woman. B, Increased color doppler flow. C, Pulse wave Doppler demonstrating higher diastolic flow.



FIGURE 44-7


​Transvaginal color Doppler view of the right adnexa in a woman during the hyperstimulation phase. Note the prominent flow to the ovary during this phase of treatment for infertility.


A debate in the literature exists regarding the value of a resistive index (RI) in distinguishing between benign and malignant adnexal masses. The largest study in the literature uses a cutoff of greater than 0.4 as a normal RI in a nonfunctioning ovary. Other investigators employ a pulsatility index of greater than 1 as normal. , Intratumoral vessels, low-resistance flow, and absence of a normal diastolic notch in the Doppler waveform are signs that may be worrisome for malignancy. In addition, abnormal waveforms can be seen in inflammatory masses, metabolically active masses (including ectopic pregnancy), and corpus luteum cysts. The most significant problem in the use of an RI is that it is not a sensitive indicator of malignancy. One study found a low RI in only 25% of malignant lesions.


The color Doppler central distribution of the small arteries within an ovarian mass may be an important factor in malignancy. Two pulsed Doppler indices have been analyzed, comparing the relative amount of diastolic to systolic components of their arterial waveforms. The pulsatility index (PI) is calculated as peak-systolic velocity minus end-diastolic velocity divided by the mean velocity. The resistive index (RI ) is the peak-systolic velocity minus the end-diastolic velocity divided by the peak-systolic velocity. Although these indices have different cutoff values, increased diastolic flow suggests neovascularity and the likelihood of malignancy. The cutoff value for the PI is 1 and the value for the RI is 0.4, with malignancy considered more likely below and benign disease more likely above these values. Inflammatory masses, active endocrine tumors, and trophoblastic disease (ectopic pregnancies) may give low indices, thus mimicking cancer.


A mass showing a complete absence or minimal diastolic flow (very elevated RI and PI values) is usually benign. A diastolic notch in early diastole may also be a sign of benign disease. This finding is not often noted and its absence has no diagnostic value.


The PI and RI values may vary considerably in the fertile patient during the menstrual cycle, and this can complicate the pulsed Doppler analysis. In the first 7 days, the flow to the ovaries has the greatest resistance with the lowest diastolic flow and the indices are at their highest. Later in each cycle, the diastolic flow increases, particularly to the dominant ovary, and may lower the indices sufficiently to falsely suggest a malignant process. A Doppler study can be performed at any time during the cycle. If the indices are in the benign range, they do not need to be repeated. However, if a suspicious mass is present and the indices suggest possible malignancy and are expected to affect management, a repeat study should be performed to confirm the abnormal indices in the first week of another cycle.




Benign adnexal cysts


Functional ovarian cysts


Functional cysts result from the normal function of the ovary. They are the most common cause of ovarian enlargement in young women. Functional cysts include follicular, corpus luteum, hemorrhagic, and theca-lutein cysts. Hormonal therapy is sometimes administered to suppress a cyst. Most cysts measure less than 5 cm in diameter and regress during the subsequent menstrual cycle. A follow-up sonographic examination in 6 weeks usually documents change in size.


Follicular cysts.


​A follicular cyst forms when a mature follicle fails to ovulate or involute postovulation ( Box 44-4 ). These cysts are usually unilateral, asymptomatic, and less than 2 cm in size, but they can be as large as 20 cm in diameter. They regress spontaneously and are frequently detected incidentally on sonographic examinations.



BOX 44-4

Follicular Cysts





  • Occur when a dominant follicle does not succeed in ovulating and remains active though immature



  • Usually unilateral



  • Thin-walled, translucent, watery fluid; may project above or within surface of the ovary



  • May grow 1 to 8 cm



  • Usually disappear spontaneously by resorption or rupture



  • Clinical findings: Asymptomatic to dull, adnexal pressure and pain, abnormal ovarian function, torsion of the ovary resulting in severe pain



  • Sonographic findings: Simple cyst




Corpus luteum cysts.


Corpus luteum cysts result from failure of resorption or from excess bleeding into the corpus luteum. These cysts usually are less than 4 cm in diameter and are unilateral. They are prone to hemorrhage and rupture. The presenting feature is often pain. If the ovum is fertilized, the corpus luteum continues as the corpus luteal cyst of pregnancy during the first trimester of pregnancy, when maximum size is reached by 10 weeks, and resolution occurring by 12 to 16 weeks ( Box 44-5 ).



BOX 44-5

Corpus Luteum Cysts





  • Result from hemorrhage within a persistently mature corpus luteum



  • Filled with blood and cystic fluid



  • May grow 1 to 10 cm in size



  • May accompany intrauterine pregnancy



  • Clinical findings: Irregular menstrual cycle, pain, mimic ectopic pregnancy, rupture



  • Sonographic findings: “Cystic” type of lesion; may have internal echoes secondary to hemorrhage and increased color




Sonographic findings.


Because of the hemorrhagic nature of these cysts, they usually appear as complex masses with central blood clot and echogenic septations ( Figure 44-8 ). This appearance is difficult to distinguish from ectopic pregnancy and endometriosis. They may exhibit posterior acoustic enhancement, depending on the content.




FIGURE 44-8


​Hemorrhagic corpus luteum cyst. Transabdominal (A) and transvaginal (B) views of the right adnexa demonstrate a 3.5-cm cystic mass with internal echoes. The acoustic enhancement posterior to this mass confirms its cystic nature.


Duplex Doppler reveals prominent diastolic flow in corpus luteum cysts. This low-velocity waveform is present throughout the luteal phase of the cycle. They may also have a peripheral rim of color around the wall of color Doppler, sometimes termed the “ring of fire.”


Hemorrhagic cysts.


​Internal hemorrhage may occur in follicular cysts or more commonly in corpus luteal cysts. The patient may present with an acute onset of pelvic pain.


Sonographic findings.


The sonographic picture is variable depending on the amount of hemorrhage, clot formation, and time passed since hemorrhage ( Figure 44-9 ). The internal characteristics are better visualized by transvaginal scanning, but transabdominal scanning should also be performed for a global view. An acute hemorrhagic cyst is usually hyperechoic and may mimic a solid mass. It usually has a smooth posterior wall and shows posterior acoustic enhancement indicating its cystic component. Diffuse low-level echoes may be seen but are more commonly seen in endometriomas. As time goes on, the internal pattern becomes more complex. The clotted blood becomes more echogenic and may show a fluid level. Echogenic free intraperitoneal fluid in the cul-de-sac can help confirm the diagnosis of a ruptured or leaking hemorrhagic cyst. This may mimic a ruptured ectopic pregnancy, so it is critical to know if the patient has a positive pregnancy test.




FIGURE 44-9


​Hemorrhagic cysts on transvaginal scans—spectrum of appearances. A, Acute hyperechoic hemorrhagic cyst. B, Acute hemorrhagic cyst mimicking a solid lesion. C, Color Doppler shows peripheral ring of vascularity, but not vascularity within the cyst. D, Large cyst containing multiple internal low-level echoes. E, Reticular pattern of internal echoes and septations within cyst. F, Reticular pattern. G–I, Variations in clot retraction. The clot in I suggests a solid mass. Lack of color Doppler signal supports its benign nature.


Theca-lutein cysts.


Theca-lutein cysts are the largest of the functional cysts and appear as very large, bilateral, multiloculated cystic masses. They are associated with high levels of human chorionic gonadotropin (hCG). They are seen most frequently in association with gestational trophoblastic disease (30%). Similar cysts occur in normal pregnancies, especially multiple gestations, and in some patients being treated with infertility drugs, particularly Pergonal ( Box 44-6 ). These cysts may undergo hemorrhage, rupture, and torsion ( Figure 44-10 ).



BOX 44-6

Theca-Lutein Cysts





  • Large, bilateral, multiloculated cysts



  • Associated with high levels of human chorionic gonadotropin



  • Seen in 30% of patients with trophoblastic disease



  • Clinical findings: Nausea and vomiting



  • Sonographic findings: Multilocular cysts in both ovaries





FIGURE 44-10


​Transabdominal image of the left ovary demonstrates enlargement of the ovary, measuring 10.9 cm. Multiple thin-walled cysts represent a theca-lutein cyst of the ovary.


Ovarian syndromes


Ovarian hyperstimulation syndrome.


​Ovarian hyperstimulation syndrome is a frequent iatrogenic complication of ovulation induction. This hyperstimulation can result in mild, moderate, and severe forms. In the mild form, the patient presents with pelvic discomfort but no significant weight gain. The ovaries are enlarged but measure less than 5 cm in diameter ( Figure 44-11 ). With severe hyperstimulation, the patient has severe pelvic pain, abdominal distention, and notably enlarged ovaries, measuring greater than 10 cm in diameter. There can also be associated ascites, pleural effusions, and numerous large, thin-walled cysts throughout the periphery of the ovary. When treated, this condition usually resolves within 2 to 3 weeks.




FIGURE 44-11


​Ovarian hyperstimulation. A, Transvaginal image showing a notably enlarged and round ovary with multiple complicated cysts. B, Coronal image of the left ovary. C, Sagittal image of the prominent right ovary. D, Increased vascularity of the hyperstimulated ovary on the right.


Polycystic ovarian syndrome.


Polycystic ovarian syndrome (PCOS), which includes Stein-Leventhal syndrome (infertility, oligomenorrhea, hirsutism, and obesity), is an endocrine disorder associated with chronic anovulation ( Box 44-7 ). An imbalance of LH and FSH results in abnormal estrogen and androgen production. The serum LH level is high and the FSH level is low. An elevated LH/FSH ratio is characteristic. Pathologically, the ovaries are rounded, usually 2 to 5 times normal size, with an increased number of follicles. Clinically, PCOS encompasses a spectrum of findings from hyperandrogenism in lean, normally menstruating women to obese women with severe hirsutism and oligomenorrhea or amenorrhea, as originally described by Stein and Leventhal. Manifestations of unopposed estrogenic hyperplasia and endometrial carcinoma occur in a significant proportion of patients, so long-term follow-up is recommended. PCOS is a common cause of infertility and a higher-than-usual rate of early pregnancy loss.



BOX 44-7

Polycystic Ovarian Syndrome





  • Includes Stein-Leventhal syndrome



  • Bilaterally enlarged polycystic ovaries



  • Occurs in late teens through twenties



  • May have endocrine imbalance



  • Spectrum of ultrasound appearances



  • Clinical findings: Amenorrhea, obesity, infertility, hirsutism



  • Sonographic findings: Multiple tiny cysts around the periphery of the ovary; ovary may be normal size or enlarged




Sonographic findings.


On sonography, the ovaries appear normal or enlarged with echogenic stroma ( Figure 44-12 ). Multiple small follicles are seen, often bilaterally, in the size range of 5 to 8 mm. The reported number of immature follicles varies in the literature from 11 to less than 15. The ovaries have a more rounded shape, with the follicles usually located peripherally, commonly referred to as the “string of pearls.” Small cysts of variable size can also occupy both the subcapsular and stromal parts of the ovary. It is the multitude of these small cysts that contributes to the enlarged size of the ovary. Transvaginal sonography is more sensitive for detecting these small follicles than is transabdominal scanning. The diagnosis of PCOS is usually made biochemically, but sonography is useful. Serial studies show the follicles persist because ovulation does not occur.


May 29, 2019 | Posted by in ULTRASONOGRAPHY | Comments Off on Pathology of the ovaries
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