Diseases of the Fallopian Tube and Broad Ligament

Clinical Features

Torsion of the fallopian tube usually occurs at the level of the vascular pedicle and therefore involves the ipsilateral ovary. Isolated fallopian tube torsion is, in turn, infrequent. It is more common in premenopausal women, who typically present with severe acute abdominal and/ or pelvic pain. Temporary (self-limited) torsion is usually subclinical and manifests with intermittent pelvic pain. Torsion is more likely to occur after tubal enlargement secondary to hydrosalpinx, pyosalpinx, abscess, or occlusion (e.g., ligation).

Pathologic Features

Gross Findings

Macroscopic changes vary depending on the duration and the severity of blood flow obstruction. The tube usually appears enlarged and edematous in initial phases and frankly congested or hemorrhagic with severe and prolonged torsion ( Fig. 12.5A ). In massively infarcted tubo-ovarian specimens, it may be difficult to identify the fallopian tube and separate it from the engorged and hemorrhagic tubo-ovarian soft tissue. Generous sampling may be required.

Differential Diagnosis

Although the diagnosis is straightforward on clinical and pathologic examination in most patients, it is important to exclude a neoplasm causing tubal enlargement and secondary torsion. Even if the tissue is massively infarcted, a neoplastic proliferation will be identified microscopically in most cases. Extensive hemorrhage can also be due to trauma , endometriosis , or ectopic gestation . Unlike torsion, in these scenarios the adnexal vessels are not congested or occluded, and the tubal wall is viable.

Prognosis and Therapy

Intermittent torsion, which is diagnosed clinically, can be treated with surgical fixation of the adnexa to the pelvic wall to prevent further episodes. Complete tubal torsion with secondary infarction requires urgent surgical excision of the tube with or without the ovary. Complications include auto-amputation of the adnexa, rupture with hemoperitoneum, and superimposed infection.

Clinical Features

Salpingitis isthmica nodosa (SIN) is a disorder characterized by nodular swelling of the isthmic portion of the fallopian tube caused by diverticula of tubal epithelium into the muscular wall. The pathogenesis and etiology of this disease remain unclear; some authors have postulated a congenital origin, whereas others favor an acquired process, possibly postinflammatory. SIN most commonly occurs in women between 25 and 60 years of age (average age at diagnosis is 30 years) and is more frequent in black women. The incidence of SIN in the general population ranges from 0.6% to 11%; however, in tubes with ectopic gestation, its prevalence has been reported as high as 49%. The association of SIN with ectopic pregnancy and infertility is well documented; in the former, SIN is believed to trap the fertilized ovum within the fallopian tube, whereas in the latter, it interferes with upward sperm migration. The lesion is otherwise asymptomatic and discovered incidentally during work-up for infertility or ectopic gestation.

Radiologic Features

Hysterosalpingography, a common technique in the work-up of infertility, is reliable in the diagnosis of SIN, which is seen as small globular collections within the tubal wall, either discontinuous or in continuity with the tubal lumen. Tubal obstruction and hydrosalpinx are commonly seen as well. Other techniques include laparoscopic chromopertubation, salpingoscopy, and transvaginal hydrolaparoscopy (the latter allows visualization of the tubal mucosa).

Pathologic Features

Microscopic Findings

Diagnosis of SIN can be confirmed only on histopathologic examination, which requires a well-oriented complete cross-section of the isthmic region of the tube. On scanning magnification, SIN is characterized by glandular “outpouchings” of varying sizes within the tubal muscularis propria, with a distribution resembling adenomyosis of the uterus or even an infiltrative glandular proliferation ( Fig. 12.6 ). On high-power examination, the glandular structures are lined by benign tubal epithelium, and connection of the intramural epithelial diverticuli to the mucosa can be sometimes appreciated. The surrounding smooth muscle can be hypertrophic. The tubal serosal surface is uninvolved.

Differential Diagnosis

The differential diagnosis of SIN, given mostly its architectural low-power characteristics, includes chronic follicular salpingitis, endometriosis, and adenocarcinoma. Follicular salpingitis produces small glandular spaces in the submucosa, separated by lymphoplasmacytic inflammatory infiltrates and reactive fibroconnective tissue; however, there is no smooth muscle in between glands. Tubal intramural endometriosis can mimic SIN since it can be extensive and haphazardly distributed throughout the wall; however, the diagnosis of endometriosis requires the presence of endometrial-type stroma, which is absent in SIN. Adenocarcinoma involving the tube, primarily or secondarily, can mimic SIN; adenocarcinoma will show a frankly infiltrative and irregular proliferation, desmoplastic stromal reaction, and overt malignant cytologic features.

Prognosis and Therapy

Once suspected clinically and radiologically, patients with infertility and SIN can be managed with segmental resection with tubo-cornual anastomosis, and recanalization if tubal obstruction is detected. Success with gonadotrophin-releasing hormone analogues (GnRH-a) has been documented in terms of remission of nodularity and tubal patency. If fertility preservation is not desired, salpingectomy is recommended.

Clinical Features

Early gestations implanting outside the uterus can involve the ovary and other pelvic or abdominal organs. However, the fallopian tube is the site of the vast majority (∼95%) of ectopic pregnancies. Most cases involve the ampulla (∼80%), followed by the isthmus (∼10%) and infundibulum (∼5%). Abnormalities impairing the passage of the fertilized ovum to the uterine cavity, and therefore predisposing to ectopic pregnancy, include salpingitis and pelvic inflammatory disease (PID), endometriosis, prior tubal surgery, as well as structural tubal abnormalities such as SIN or congenital defects. Another mechanism is retrograde transit of the fertilized egg from the uterus into the tube, supported by the observation that in some cases the ectopic gestation occurs contralateral to the ovary with the corpus luteum of pregnancy. A significant number of ectopic pregnancies resolve spontaneously and are usually silent clinically. If the implanted gestation secures enough blood supply from the tube, it will grow causing hemorrhage, progressive distention, and eventual wall rupture. Thus, symptomatic ectopic gestation manifests with amenorrhea, shortly followed by abnormal vaginal bleeding and acute pelvic or lower abdominal pain. In ectopic pregnancy, β-hCG serum levels are lower and rise at a slower rate compared to uterine gestations.

Radiologic Features

Transvaginal ultrasound is used to evaluate the uterine cavity in search for a gestational sac, or in turn for the presence of an adnexal mass. Well-developed ectopic gestations will appear as a sac, sometimes with a visible embryo, associated with a thick or irregular tubal wall. If rupture has occurred, fluid in the cul-de-sac can be apparent.

Pathologic Features

Gross Findings

The fallopian tube will show an area of dilation associated with attenuation of the wall, congestion, and hemorrhage. In some cases, blood clot is present either on the external surface of the tube or detached. Sometimes, a disruption of the wall with irregular hemorrhagic edges is seen, which needs to be documented as it may represent the point of rupture. Blood oozing from the distal (fimbriated) end can be apparent. On cut surface, the distended area corresponds to hematosalpinx, in which placental and/or fetal tissues may be observed ( Fig. 12.7A ). Sampling needs to incorporate all abnormal areas of the tube, including possible sites of rupture, as well as detached blood clot, as it may signify an ectopic gestation extruded from the tube after rupture or intraoperatively. Submitting the entire specimen may be required, particularly if grossly normal.

Differential Diagnosis

In patients with clinically suspected ectopic pregnancy, abundant placental and/or embryonic tissue should be identified in the tube. If these are absent or only scant and there is no trophoblast infiltrating the wall, the possibility of intrauterine gestation or ectopic pregnancy outside of the tube must be considered and clinically excluded. A largely distended and hemorrhagic fallopian tube may also be seen in tubal torsion and endometriosis ; in these scenarios, gestational tissue is absent and the clinical features of ectopic pregnancy, such as abnormally rising β-hCG, are absent.

Prognosis and Therapy

Complications (rupture, bleeding, or placental invasion of pelvic organs) can be life-threatening; however, early diagnosis can be currently achieved clinically and radiologically in most cases, resulting in very low mortality rates (<0.1% in the last 30 years in the United States). Treatment of patients with small, noncomplicated tubal gestations is medical with methotrexate and close observation. Those who progress despite pharmacologic treatment or present with imminent or established rupture and hemoperitoneum require salpingectomy. Since predisposing factors are mostly unilateral, most women can achieve a normal pregnancy after having an ectopic tubal gestation.

Clinical Features

Endometriosis frequently involves the fallopian tube: it is seen in up to 10% of tubal resection specimens. It predominantly affects women of reproductive age. In this population, it is a prevalent cause of dysmenorrhea, chronic pelvic pain and infertility, which are related to chronic bleeding with subsequent inflammation, scarring, adhesion formation, and progressive tubal obstruction. It is postulated that endometriosis is caused by retrograde flow of endometrial cellular components and blood during menstruation. The pathogenesis of this disease is, however, still uncertain.

Pathologic Features

Microscopic Findings

Tubal endometriosis is seen in the form of endometrial elements (glands and stroma ± signs of hemorrhage) present in the fallopian tube serosa or muscularis ( Fig. 12.8A ). Involvement of the tubal mucosa by endometrium can also be seen as a form of endometriosis, although it may also represent colonization of the tubal epithelium, which is more common in the proximal aspect of the tube and has been associated with tubal ligation and complete occlusion of lumen ( Fig. 12.8B ). Endometriosis can undergo decidualization or Arias-Stella reaction depending on the hormonal background.

Differential Diagnosis

Macroscopically, diffuse involvement of the tube by endometriosis or a large endometriotic cyst can be confused with tubal torsion, abscess, or ectopic gestation, if the clinical context is unknown. Correlation with the clinical and histopathologic findings will clarify the diagnosis. It is important to note that endometriosis can be complicated with superimposed infection and abscess formation. The distinction between endometriosis and SIN was discussed earlier. Other important entities in the differential include endometrioid adenocarcinoma involving the tube and Müllerian adenosarcoma. Well-differentiated endometrioid carcinoma of either endometrial or primary tubal origin may resemble endometriosis; most cases, however, will display significant expansile or infiltrative growth and architectural complexity indicative of a malignant process (glandular confluence, cribriform, microacinar, or papillary architecture). Müllerian adenosarcoma should be considered if the lesion is predominantly solid and polypoid; attention to the classic architecture (leaf-like appearance, periglandular stromal condensation) and the presence of stromal cytologic atypia will aid in the diagnosis.

Prognosis and Therapy

Endometriosis is a morbid disease; infertility, chronic pelvic pain, and endometriosis-associated malignancy are its most important complications. Hormonal treatment is the mainstay of therapy, which has variable long-term responses. Surgical approach may be indicated in order to determine the extent of the disease and in the setting of large or refractory lesions. In the management of infertility, resection of endometriosis with lysis of tubal adhesions and intraluminal probing to assess for patency also has a role.

Clinical Features

Tubal epithelial hyperplasia has been reported in a significant proportion (∼18%) of fallopian tubes, although in the vast majority, the hyperplasia is mild (and likely largely unnoticed in routine practice). When florid, hyperplasia can mimic fallopian tube carcinoma, hence the term “pseudocarcinomatous hyperplasia” used by some authors. Florid hyperplasia is associated with exogenous or endogenous estrogenic stimulation, concurrent ovarian neoplasms and salpingitis. The latter has been documented in ∼50% of tubal hyperplasias and is a consistent feature of cases at the higher end of the spectrum (pseudocarcinomatous hyperplasia), in which the inflammation tends to be severe and related to PID. Patients are typically young and premenopausal (mean 28.6 years, range 27 to 40 years).

Pathologic Features

Microscopic Findings

Florid epithelial hyperplasia has a striking low-power appearance with numerous plicae occupying the tubal lumen and fusing together, which results in complex (cribriform, pseudoglandular, or sieve-like) patterns. Moreover, the epithelial proliferation may distend the lumen and compress the surrounding muscularis. Cytologically, the hyperplastic epithelium is bland or shows at most moderate nuclear atypia and pseudostratification as well as only occasional mitotic figures ( Fig. 12.9A ). A dense and diffuse chronic inflammatory infiltrate admixed with the epithelium is consistently present ( Fig. 12.9B ). Associated features of PID (acute salpingitis, tubo-ovarian abscess) can be observed.

Differential Diagnosis

The most important differential diagnosis of pseudocarcinomatous hyperplasia is carcinoma , particularly endometrioid or serous. Patients with tubal carcinoma tend to be older and present with a mass. Histologically, overt and destructive invasion into the wall will also be in keeping with a malignant process. High-grade serous carcinoma (HGSC) will show significant stratification and micropapillary tufting, loss of polarity, severe nuclear atypia, and conspicuous mitotic activity. Although the immunohistochemical profile of florid hyperplasia has not been thoroughly documented in the literature, an abnormal p53 expression pattern is more consistent with a malignant process. Endometrioid carcinoma may display villoglandular and cribriform architecture similar to tubal hyperplasia; however, it will also display endometrioid features (squamous, mucinous or secretory differentiation) and some degree of solid growth, which are all absent in florid hyperplasia.

Prognosis and Therapy

By itself, florid tubal epithelial hyperplasia is a benign process. It is important to identify and report any associated pathology that may require treatment (salpingitis, abscess).

Infectious Nongranulomatous Salpingitis

Pathologic Features

Gross Findings

In uncomplicated cases of PID, the tubes are removed only exceptionally. The process is typically bilateral and is characterized by hyperemia of the tubal serosal surface, edema of the wall, and purulent exudate from the surface or the fimbriated ends. Upon sectioning, the wall is thickened and congested, and the lumen is distended by fluid accumulation. In patients with chronic or recurring infective episodes, areas of adhesion and scarring can be noted throughout the tube, often with secondary hydrosalpinx or pyosalpinx ( Fig. 12.10A,B ). Tubo-ovarian abscesses vary in size but can be larger than 10 cm; on cut section, they are comprised of a cavitary lesion with purulent material, thickening fibrosis, and edema encasing the adnexa.

Microscopic Findings

Depending on the severity, acute salpingitis is characterized histologically by neutrophilic inflammation of varying amounts and extent. It tends to be more prominent in the mucosa, associated with edema and enlargement of the tubal plicae ( Fig. 12.11A ). Florid hyperplasia of the epithelium occurs often, sometimes mimicking a malignant proliferation (“pseudocarcinomatous”) ( Fig. 12.11B ). The lumen of the tube is filled with necrotic debris and neutrophilic exudate. Tubo-ovarian abscess is characterized by confluent neutrophilic exudate and necrotic debris occupying a central cavity, in turn surrounded by reactive fibrotic tissue and prominent mixed inflammation. In chronic salpingitis, the inflammatory infiltrate is mixed with plasma cells, lymphocytes, and histiocytes in a background of fibrosis and effacement of the mucosal folds. The plicae are shortened and blunted with secondary fusion.

Endometrial biopsy is sometimes performed as part of the work-up of PID, and chronic (plasma cell) endometritis has been regarded as a supporting finding of PID (and a surrogate for acute salpingitis). As discussed in Chapter 9 , the finding of plasma cells by itself is not specific and may be encountered in endometrial polyps and anovulation; therefore, the diagnosis of endometritis requires correlation with the clinical presentation and the background endometrium; plasma cells must be found in fragments of endometrium functionalis, which often shows metaplastic epithelial changes and other inflammatory cellular components.

Clinical Features

Tuberculous salpingitis tends to affect young women living in areas with endemic tuberculosis, typically in the setting of pulmonary or systemic tuberculosis with hematogenous spread. Over 90% of cases have bilateral tubal involvement, as well as compromise of other gynecologic organs. Common manifestations include subacute or chronic pain, abnormal vaginal bleeding, and infertility (seen in up to 66% of affected women); some patients manifest no genital symptoms.

Pathologic Features

Gross Findings

The tubes may appear normal or mildly edematous and enlarged. About 20% display soft tubercles on the serosal surface. The lumen may contain caseous debris ( Fig. 12.12A ) or serosanguineous fluid. Upon sectioning, the nodular tubercles contain central caseating necrosis with surrounding edema and/or fibrotic thickening.

Ancillary Studies

Identification of the microorganism on tissue sections may be achieved using the acid fast bacilli (AFB) stain. Moreover, isolation of the organism in culture can be attempted in fresh tissue if the diagnosis is suspected at the time of surgery and gross examination. These tests are highly specific and confirmatory of the diagnosis. However, AFB stain lacks sensitivity and culture results may take several days to weeks. Detection of the organism using nucleic acid amplification techniques has shown superior detection rates (68%) compared with AFB stain (32%). Immunohistochemistry with a monoclonal antibody against M. tuberculosis has been reported to have even higher sensitivity (96%) in routinely fixed material and aspirates.

Differential Diagnosis

In the setting of necrotizing granulomas, infectious agents other than M. tuberculosis need to be considered, particularly in a patient with no known history of tuberculosis. Clinical and epidemiologic history is critical to identify rare agents such as atypical mycobacteria or parasites. The latter are accompanied by a prominent eosinophilic response. In the case of Enterobium vermicularis , worms or their ova (25 × 30 μm in size and covered by a thick shell) can be seen in histologic sections. Schistosoma haematobium and Schistosoma mansoni have been reported in the tube, in some women associated with ectopic pregnancy; their eggs can be identified in the remaining tubal tissue after sodium hydroxide digestion; they are ovoid, approximately 150 μm in size, and have a lateral ( S. mansoni ) or terminal ( S. haematobium ) spine. Lipoidal salpingitis is a granulomatous reaction secondary to lipoidal contrast agents, which are seen in routine preparations as empty spaces of varying sizes within the lamina propria surrounded by histiocytes and foreign-body giant cell reaction. Xanthogranulomatous reaction in the tube is rare but can be seen in endometriosis; it contains large amounts of foamy hystiocytes but typically lacks other inflammatory cellular elements, and unaffected endometriosis is usually seen in the vicinity. Other non-infectious causes of granulomatous salpingitis include systemic conditions such as sarcoidosis, Crohn’s disease and traumatic or iatrogenic implantation of foreign material into the tube. The clinical history and identification of foreign bodies within the tube will aid in the correct diagnosis.

Prognosis and Therapy

Tuberculous salpingitis is associated with infertility in ∼66% of cases. As a sign of systemic infection, its management requires multidrug antibiotic treatment (6–9 months and may include isoniazid, rifampin, ethambutol, and pyrazinamide). Response is excellent in most patients.

Clinical Features

This type of infectious inflammatory process is presented separately given its distinct clinical risk factors and presentation. Actinomyces israelii is a filamentous, Gram-positive, anaerobic bacterial microorganism. Spread to the abdomen and pelvis can be caused by surgery, bowel perforation, or trauma. In addition, it can be secondary to colonization of an intrauterine device, which has been reported in 1%–12% of women using this contraceptive method. Not surprisingly, the majority of women affected are of reproductive age. Tubo-ovarian spread manifests clinically with subacute to chronic pelvic pain, bloating, fever, constitutional symptoms, vaginal bleeding, or purulent discharge. Not infrequently, it presents as an adnexal mass associated with pelvic adhesions and fluid collection, sometimes suspicious for a neoplasm clinically and radiologically. Some patients are first diagnosed after identification of the microorganism in cervicovaginal Papanicolaou smear.

Pathologic Features

Microscopic Findings

Microscopically, actinomycosis is seen as a symmetrical and round collection of filamentous bacteria arranged in a radiating fashion, which is the histologic correlate of the sulfur granule ( Fig. 12.13A,B ). The inflammatory component is mixed, with neutrophilic and lymphoplasmacytic populations admixed with granulomatous inflammation. Abscess formation appears as cavitary necrosis and confluent acute inflammation surrounded by reactive fibrosis and prominent inflammation ( Fig. 12.13A ).

Ancillary Studies

Gram, periodic acid Schiff (PAS), and methenamine-silver stains may be used to highlight the filamentous bacterial colonies.

Differential Diagnosis

The diagnosis of carcinoma may be clinically suspected, as most women with actinomycosis present with a complex tubo-ovarian abscess suspicious for malignancy on imaging. In these cases, generous sampling may be advisable; the histomorphology is otherwise typical and suffices to exclude a neoplastic process. Other types of tubo-ovarian abscess (gonorrhea, Chlamydia ) can be considered, particularly if the round radiating bacterial colonies are not apparent; in this scenario, a Gram stain may be of value. If fistulization has ensued, other causes such as inflammatory bowel disease , trauma , or diverticulitis need to be considered; correlation with clinical history and attention to the presence of bacterial granules is important. Pseudoactinomycotic radiate granules bear superficial resemblance to actinomyocytic sulfur granules but, unlike the latter, are nonreactive for the aforementioned special stains.

Prognosis and Therapy

Most women presenting with persisting or recurrent tubo-ovarian abscess and those with fistula formation require surgical excision and/or drainage followed by antibiotic treatment. Primary antibiotic therapy can be considered if the diagnosis is suspected clinically and there is no adnexal mass formation, and in patients diagnosed with actinomyces in Papanicolaou smear. Prophylactic treatment is considered in patients with intrauterine device, requiring change of the device every 4 years, along with penicillin or doxycycline treatment. Prognosis in treated patients is good; however, complications of PID such as chronic pain and infertility can be seen in these patients.