Dysmenorrhea, dyspareunia, and pelvic, back, and rectal pain—the more common symptoms of endometriosis—have been assumed to be caused by endometrial implants. However, the development of such symptoms is not diagnostic of the disease state. In one random survey of women in the general population, more than 60% reported dyspareunia at some point in their lives, and 33% had persistent discomfort. The prevalence of laparoscopically diagnosed endometriosis in patients with chronic pelvic pain has ranged from 4% to 52% in published series. Leibson et al. reported the age of peak diagnosis of endometriosis based on presenting symptom is pelvic pain, age 15 to 24 years; infertility, age 25 to 34 years; and dysfunctional uterine bleeding, age 35 to 44 years.

Some authorities have suggested that the symptoms may be dependent on the location of the implants, the presence of adhesions, distortion of ovarian anatomy by endometriosis, and involvement of other organs, such as the ureter or rectum. However, Fedele and colleagues found no significant association between the American Fertility Society (AFS; now known as the American Society for Reproductive Medicine) classification of stage and the presence and severity of dysmenorrhea, pelvic pain, and dyspareunia in a prospective study of 160 women. The pain profiles of the patients with ovarian lesions were similar to those of the patients with peritoneal or ovarian and peritoneal disease. Conversely, in a later study by the same group, ovarian endometriomas were the only lesions significantly associated with severe dysmenorrhea and pelvic pain in infertile women. In a more recent prospective study of symptoms experienced by women diagnosed with histologically proven endometriomas, Chapron et al. showed no correlation of the intensity of the pain with the size of the endometrioma. In this study, severe pelvic pain was significantly associated with the secondary finding of deeply infiltrating endometriotic lesions.

Koninckx and coworkers demonstrated that the presence of pelvic pain did not correlate with the total area of endometriosis, type of lesion, or volume of disease. The only significant discriminator proved to be the depth of infiltration; endometriotic lesions greater than 1 cm in depth were associated with
severe discomfort (Fig. 22.2). This supports earlier data that strongly linked pain with deep infiltration of the fibromuscular tissue of the pelvis. Hsu and colleagues found dysuria and midline anterior pain were the only symptoms associated with the location of superficial endometriosis lesions.

Pain symptoms generally correlate with fluctuations in steroid hormone concentrations. In response to cyclic stimulation by ovarian estradiol and progesterone, endometriotic lesions undergo epithelial and stromal proliferation, variable secretory changes, stromal pseudodecidual reaction, and periodic regression in a manner more disorganized than, yet similar to, that of normal endometrium. Surgical castration and ovarian hormonal suppressive therapy result in diminution of pain in most patients.

Bimanual pelvic examination may reveal tender uterosacral ligaments, cul-de-sac nodularity, induration of the rectovaginal septum, fixed retroversion of the uterus, adnexal masses, and generalized or localized pelvic tenderness. The adherent tube and ovary may constitute a tender, irregular mass that is similar in characteristics to the mass palpated in cases of chronic salpingo-oophoritis. Uterosacral nodules occasionally reach 1 cm or more in size. Lesions implanted in the retrocervical area or rectovaginal wall are frequently more easily felt than seen and can be missed if the physical examination is omitted. A perceptible, painful swelling of the implant before and at menstruation remains a classic and reliable clinical sign of active rectovaginal or retrocervical endometriosis.

Cancer antigen 125 (CA-125), a high molecular weight glycoprotein expressed on the cell surface of some derivatives of embryonic coelomic epithelium, is often elevated toward the end of the luteal phase and during menstruation in patients with AFS stages II to IV endometriosis. Barbieri and colleagues reported that a value higher than 35 U/mL had a positive predictive value of 0.58 and a negative predictive value of 0.96 in establishing the presence of endometriosis. Many other conditions have been associated with an elevated CA-125 concentration, including acute pelvic inflammatory disease, adenomyosis, uterine leiomyoma, menstruation, pregnancy, epithelial ovarian cancer, pancreatitis, and chronic liver disease. Pittaway and colleagues reported that 80% of women with pelvic pain and endometriosis had a CA-125 titer greater than 16 U/mL, whereas only 6% of patients with pelvic pain and without endometriosis had an increased serum concentration of this cell surface antigen.

Increased concentrations of CA-125 and placental protein 14 (PP14) have been related specifically to the presence of endometriotic cysts and deep endometriosis. The results of most studies, however, suggest that CA-125 is not sufficiently sensitive to identify lesser stages of endometriosis and is therefore not reliable as a screening test.

Somigliana and colleagues report transvaginal ultrasonography has high sensitivity (84% to 100%) and specificity (90% to 100%) in identifying ovarian endometriomas as based upon characteristics of low-level, homogeneous internal echoes. Doppler sonographic evaluation of resistance indices in the vessels of adnexal masses increases the sensitivity and negative predictive values of two-dimensional sonography and CA-125, but this yields many false-positive results because of the neovascularity of benign tumors. Magnetic resonance imaging (MRI) may be helpful in assessing deep pelvic and extrapelvic endometriosis, including lesions that involve the bladder, vagina, or sigmoid (Table 22.5). Small studies have indicated that transrectal sonography or rectal endoscopic sonography is useful for detecting rectal wall involvement if performed by a skilled radiologist or gastroenterologist.

The patient with unexplained lower abdominal pain or a presentation suggesting endometriosis requires laparoscopy for definitive diagnosis. Ultrasonography and other noninvasive procedures cannot provide the specific information needed to diagnose or classify the extent or severity of disease. For proper laparoscopic evaluation, a double puncture technique is essential. The ancillary probe or forceps placed through the lower abdominal sheath permits mobilization of the tubes and ovaries. A methodical regimented approach should be used to thoroughly inspect the lateral sidewalls, all ovarian surfaces, both sides of the broad ligaments, the
bladder and bowel serosa, and the inferior aspects of the cul-de-sac. Uterine manipulation with a cannula fixed to the cervix facilitates evaluation of the uterosacral ligaments and rectal serosa. Photography and video recording are useful for documentation of findings.

Awareness of the wide range of visual appearances of endometriosis is necessary for accurate diagnosis and appropriate surgical therapy of the disease. Although darkly pigmented lesions are readily recognizable and are considered a classic presentation of endometriosis, less discernible yet common forms of implants were described as early as the 1920s, when Sampson noted “red raspberries, purple raspberries, blueberries, blebs, and peritoneal pockets.” The black or blue puckered “powder-burn” implant is a late consequence of cyclic growth and regression of the lesion, to the point that bleeding and hemosiderin staining of the tissue have occurred. Biopsy of such areas reveals inactive endometrial glands and fibrous stroma.

Distinctive morphologic variations include vesicles, flat plaques, raised lesions, polypoid structures, areas of fibrosis and adhesion formation, and peritoneal defects (Table 22.6). Yellow, brown, blue, or black coloration is proportional to the amount of hemosiderin deposition. Red polypoid lesions share the closest histologic characteristics with native endometrium and are thought to have the greatest metabolic activity, as is suggested by their high concentrations of prostaglandin metabolites. Biopsy of nonpigmented implants (i.e., implants that are the same color as adjacent peritoneum) may reveal active endometriotic glands and stroma. White lesions are predominantly fibromuscular scarring with scattered glandular and stromal elements, and brown lesions are mainly hemosiderin deposits. Peritoneal defects and subovarian adhesions contain endometriosis in 40% to 70% of cases. Because other peritoneal lesions share morphologic features similar to those of endometriosis, the differential diagnosis is broad and includes old suture locations, epithelial malignancies, endosalpingiosis, hemangioma, inflammatory reaction to infection or oil-based hysterosalpingogram dye, and carbon deposition from laser surgery. Rectovaginal endometriotic lesions consist of smooth muscle with active glandular epithelium and scanty stroma. They share similar characteristics to adenomyomas.

Small endometriotic lesions become more visible during the premenstrual and menstrual phases of the cycle, because during this time, microfoci of peritoneal disease become congested with blood and debris. In addition, vascular dilatation, superficial hemorrhage, and ecchymosis formation cause accentuation of the more typical features of endometriosis. Performance of laparoscopy at a time when ovarian steroidogenesis is suppressed by medications such as GnRH analogues or progestogens can lead to inaccuracies in the assessment of extent of disease.

Jansen and Russell reported the presence of nonpigmented lesions in 38% of their 202 patients with biopsy-proven endometriosis; 15% had only nonpigmented implants. Most areas of pigmented endometriosis are surrounded by nonpigmented endometriosis. These subtle lesions may represent the first stage of development of peritoneal disease. Recognition of nonpigmented endometriosis may be enhanced by “painting” the peritoneum with the patient’s blood or by filling the pelvis with irrigation fluid and submerging the laparoscope to appreciate the three-dimensional configuration of clear lesions. Subtle lesions are likely to originate from microscopic glands; they appear and disappear like blebs on the peritoneal surface. With progressive fibrosis, these implants become the classic pigmented, scarred lesions, and finally, when fibrosis replaces the stroma, they appear as white, inactive disease.

The ability to detect subtle lesions of endometriosis increases with the experience of the surgeon and is reinforced by histologic confirmation. Although depth perception is impaired when the monocular lens of the laparoscope is used to view the pelvic cavity, the magnification ability of this lens when closely approximated to the peritoneum may allow identification of subtle surface irregularities present in occult disease. Magnification up to 10× power can be obtained with the laparoscope, depending on the working distance. Microscopic implants of endometriosis not visible even with 10× magnification have been documented by scanning electron microscopy in peritoneal biopsies of patients with unexplained infertility who had no evidence of disease at the time of laparoscopy. A scanning electron microscopy study of samples of supposedly normal tissue from endometriosis patients has documented the presence of endometriotic foci in 25% of cases. Lesions as
small as 200 µm have been identified through this technique. Hence, surgical treatment of all visible disease is more accurately described as cytoreductive rather than ablative.

An ovarian endometrial cyst is usually formed by an inversion of the ovarian cortex. The frontal surface of the ovary in proximity to the hilus is the most common site for the invagination process to occur. Repetitive bleeding from the endometrial implants on the surface of the ovary may promote the growth of such lesions. Alternatively, invaginated epithelial inclusions may form endometriomas through coelomic metaplasia. Adhesions are common from the ovary to the fossa ovarica or to the posterior leaf of the parametrium.

Preoperative sonographic evaluation is a useful screening test for the presence of small endometrial cysts; their identification may affect the disease categorization to which the patient is assigned. Sonographic patterns may indicate purely cystic features, cystic features with few septations or minimal debris, complex combinations of cystic and solid elements, and largely solid features. More recently, fat-saturated MRI has been shown to be an acceptable tool for detecting endometriomas larger than 4 mm in diameter.

An adnexal mass in a patient with known pelvic endometriosis cannot be assumed to be an endometrial cyst of the ovary. Ovarian malignancy must remain in the differential diagnosis; the size of the mass has been correlated with malignancy. In a study of 180 women, 1% of masses smaller than 5 cm, 11% of masses between 5 and 10 cm, and 72% of masses larger than 10 cm were malignant. Most of these malignant tumors were adenocarcinoma.

The rules that apply to the management of all women in whom an adnexal mass develops also apply to patients with endometriosis with an adnexal mass. Among women of reproductive age, unilateral adnexal masses that are cystic and unilocular with regular borders on ultrasound examination are likely to be benign, whereas masses with solid areas, septa, papillations, or irregular borders have a greater likelihood of being malignant. Endometriomas vary in their appearance but usually have regular borders and slightly thickened and diffuse internal echoes unless fresh hemorrhage is present. Sensitivity and specificity of transvaginal ultrasound have been reported by Eskenazi and colleagues to be 84% to 100% and 90% to 100%, respectively.

Recognition of deep ovarian endometriosis is necessary for correct surgical staging. Small endometriomas were diagnosed in 48% of infertile women with mildly enlarged ovaries (3.5 to 5 cm in diameter) when the ovaries were punctured with a 16-gauge needle. The ovarian surfaces were without gross disease in this series of patients. Deep ovarian endometriosis is frequently associated with the presence of intestinal or more extensive pelvic disease.

Vercellini and colleagues studied the visual diagnostic parameters of ovarian endometriomas at laparotomy in 245 women with ovarian cysts. The gross characteristics that established the diagnosis included a size smaller than 12 cm in diameter; adhesions to the pelvic sidewall, to the posterior broad ligament, or to both; the presence of powder-burn lesions; superficial endometriosis with adjacent puckering on the surface of the ovary; and tarry, thick, chocolate-colored fluid content. These criteria yielded a sensitivity of 97%, a specificity of 95%, and an accuracy of 96%.

The depth of peritoneal infiltration by endometriosis cannot be evaluated by inspection alone. Deep endometriosis, which is almost exclusively localized to the posterior cul-desac and the uterosacral ligaments, is better detected by palpation and becomes even more apparent during excision. Deep endometriosis has been recognized to become smaller with increasing depth, although in some women, the largest volume is hidden under an adhesion involving the bowel or is buried in the rectovaginal septum. Diagnosis is enhanced if clinical examinations are performed during menstruation in women with chronic pelvic pain, severe dysmenorrhea, or deep dyspareunia. In most cases, a nodule is more palpable at this time. Koninckx and Martin have described three types of infiltrating endometriosis. Type I is characterized by a large pelvic area of typical or subtle lesions surrounded by white sclerotic tissue. During excision, deep disease becomes obvious and grows progressively smaller with deeper sectioning of tissue (like a cone). Type II is formed by retraction of the bowel and is recognized clinically as a small classic lesion associated with retraction. In some women, no implant is visible, but induration is associated with the retraction. Excision usually reveals the presence of a nodule. Type III is nodular endometriosis of the rectovaginal septum. This category is clinically suspected at the time of rectovaginal examination when painful nodularities are noted. Occasionally, nodular endometriosis presents as small, typical lesions at laparoscopy or as dark blue cysts at the vaginal fornix during speculum examination. Type III disease is the most severe and often spreads laterally to involve the ureter.