Introduction

As the fallopian tube is the intermediary between the ovary and the uterus, it is the seat of various interactions that culminate in a normally implanted pregnancy. Its multiple functions include conditioning of both gametes before fertilization, guiding their journeys before encounter, providing an appropriate chemical environment for fertilization, supplying nutriment to the fertilized ovum for its first few hours of life, and delivering it to the uterine cavity at the proper time for nidation. The exact processes by which these various mechanisms are accomplished are still rather poorly understood, partly because many of them vary significantly from species to species, so that the study of experimental animals does not always help to understand the situation in women. Recently, the fallopian tube has been implicated for its potential role in a more sinister pathologic process. A growing body of evidence strongly suggests that the distal fallopian tube is the site of origin for some proportion of high-grade pelvic serous cancers previously classified as primary ovarian or peritoneal malignancies. For a detailed discussion of this concept, see Chapter 25 .

Anatomy, Histology, and Function of the Fallopian Tube

Histology

The fallopian tube is composed of a mucosal lining, a muscular layer, and an outer serosa. The mucosa consists of nonstratified epithelium and a sparse underlying fibrovascular lamina propria. The epithelium ( Figure 21.1 ) comprises three cell types: ciliated cells, secretory cells, and intercalated (or peg) cells. The ciliated cells have a centrally placed nucleus with a perinuclear halo, a prominent terminal bar, and definable surface cilia. The nuclei of the secretory cells vary in position, depending on the stage in the menstrual cycle. The intercalated cells are secretory cells that have discharged their secretions with the result that the cell walls are collapsed around the nucleus. The ciliated component is the most prominent near the fimbrial end of the tube and the secretory cells are more numerous in the isthmus than they are in the ampulla.

Normal tubal epithelium An admixture of secretory and ciliated cells constitute the majority of the cells.

The tubal epithelium shows well-defined histologic alterations in response to cyclic hormonal variations, which affect the height of the epithelial cells, rather than the number of cilia, as happens in other primates. In the proliferative phase of the cycle the estrogen predominance results in epithelial cells with increasing height whereas in the progesterone-dominated secretory phase, the cell height may be as little as half that seen in the first half of the cycle. Similarly, the height of both epithelial cell types is low in pregnancy. Oral contraceptives produce a similar appearance to those of pregnancy; the epithelial cells are relatively flat and show a lack of secretory activity, features that doubtless play some part in the effectiveness of the medication. In the late postmenopausal state, the epithelium becomes thin and atrophic ( Figure 21.2 ).

Atrophic tubal mucosa. The epithelium is thin and atrophic and the plical lamina propria is fibrotic.

In cross section, at low-power magnification, the mucosa of the tubal ampulla ( Figure 21.3 ) forms a complicated maze-like pattern of folds (the plicae) that branch but do not join. The epithelial surfaces of the plicae are apposed to one another so that even in the widest part of the tube the traversing ovum is not floating in a spacious lumen but is at all times nurtured by the ciliated and secretory epithelium with which it is in contact on all sides. These folds become less complex as the medial end of the tube is approached, becoming stellate in the isthmus ( Figure 21.4 ) and forming an irregular, almost rounded, outline to the lumen in the interstitial part. In postmenopausal women, the plical stroma becomes fibrous and the plicae themselves club shaped, an appearance that may be mistaken for one sequela of infection, and the epithelium flattened.

Normal ampulla. The mucosa forms a complex maze-like pattern of folds that branch but do not join.

Normal isthmus. The lumen is narrow and stellate and the wall is thick.

The tubal musculature is arranged in a basket-weave fashion. This layer is thinnest at the tube’s distal end and becomes progressively thicker as the cornu is approached. A subepithelial layer of mainly longitudinal muscle appears at the isthmus and continues along the interstitial portion. At this point, the spiral muscle becomes continuous with the myometrium.

Mucosal Epithelial Alterations

Secretory Cell Outgrowths and p53 Signatures

Expansions of morphologically unremarkable secretory cells, uninterrupted by ciliated cells, can occasionally be identified as discrete, linear foci in a background of the usual mixed ciliated and secretory cells populating the fallopian tube epithelium. Such expansions have been designated as secretory cell outgrowths (SCOUTs) when they comprise at least 30 or more secretory cells. The majority are associated with loss of expression of PAX2 , a member of the pair box gene family, which is normally expressed in structures derived from the müllerian duct. The related p53 signature is also composed of secretory cells, but with the incremental changes of acquired p53 mutation, evidence of DNA damage, and relative predominance in the distal portion of the fallopian tube ( Figure 21.5A and B ). Neither SCOUTs nor p53 signatures exhibit significant proliferative activity ( Figure 21.5C ). Both are currently interpreted as early clonal expansions short of neoplastic proliferation.

(A–C) The p53 signature is a histologically unremarkable stretch of tubal epithelium (A) that is associated with p53 mutations, exhibiting strong nuclear staining for p53 (B) and has a low MIB1 index (C) .

Both SCOUTs and p53 signatures are candidate early steps toward high grade serous tubal carcinoma, as discussed in Chapter 25 . The reader is cautioned, however, that the prospective cancer risk of women with isolated SCOUTs and/or p53 signature is unknown, so neither is a diagnostic entity that should be invoked in clinical practice. Fallopian tubes from women with high-grade pelvic serous carcinoma harbor a significantly higher frequency of SCOUTs than those from women whose tubes were removed for a non-malignant condition. Tubes in which serous tubal intraepithelial carcinoma is present are more likely to contain p53 signatures than those without; in some cases, a p53 signature may be found in direct continuity with intraepithelial carcinoma. In a given case of pelvic serous carcinoma, shared p53 mutations may be identified among p53 signatures, serous tubal intraepithelial carcinoma, and invasive tumor elsewhere in the pelvis.

Other Mucosal Epithelial Proliferations

Another notable pattern of epithelial growth in the fallopian tube, which does not appear to be associated with malignancy, either in the tube or elsewhere, is characterized by an apparent ‘hyperplasia’ of the normal mucosal epithelial cells. Such areas are populated by a mix of ciliated and secretory cells, which appear stratified or are arranged as small tufts. These areas may be focal or more diffuse. The cells themselves may exhibit some nuclear atypia, but not to the degree found in intraepithelial carcinoma. Mitotic activity is generally minimal ( Figure 21.6 ). This mucosal alteration may be seen in the setting of pregnancy, but can be found in the tubes of non-pregnant women as well.

Mucosal epithelial proliferation. A prominent tufted appearance is present.

Anatomy

The fallopian tubes are derived from the müllerian ducts, which begin as invaginations of the celomic lining epithelium lateral to the cranial end of the mesonephric ducts at 5 weeks of intrauterine development. The lower ends fuse to the mesonephric ducts in the 7 week embryo, after which the mesonephric ducts undergo regression. The tube is 9–12 cm long in vivo but, being a muscular organ, its length can vary considerably. After fixation, it appears shorter, shrinking to a serpentine form. At the medial end, the tube is attached to the uterine cornu above and in front of the ovarian ligament, and above and behind the round ligament of the uterus. A sheet of pelvic peritoneum is folded over the tube, joining beneath it to form the mesosalpinx and then, beneath the mesovarium and ovarian ligament, to become the broad ligament. On the lateral wall of the pelvis, the tube arches backward over the ovary, its ostium facing the medial aspect of the latter.

The fallopian tube is divided into four zones, which, extending distally to proximally, are the infundibulum, the ampulla, the isthmus, and the interstitial (or intramural) portions. The infundibulum is the distal end of the tube and forms the funnel-like expansion opening onto the peritoneal cavity, about 1 cm in length and diameter that ends in a variable number of irregular, fringe-like extensions, the fimbriae. Proximal to the infundibulum and making up about half of the length of the tube is the ampullary portion. The ampulla is narrower than the infundibulum and runs a tortuous course. The isthmus, which is 2–3 cm in length, has a narrower lumen and more muscular wall than the ampulla. The interstitial portion of the tube has a lumen with a simple, stellate, or almost circular cross section. In this segment of the tube, the muscle of the tubal wall merges with that of the myometrium.

Histology

The fallopian tube is composed of a mucosal lining, a muscular layer, and an outer serosa. The mucosa consists of nonstratified epithelium and a sparse underlying fibrovascular lamina propria. The epithelium ( Figure 21.1 ) comprises three cell types: ciliated cells, secretory cells, and intercalated (or peg) cells. The ciliated cells have a centrally placed nucleus with a perinuclear halo, a prominent terminal bar, and definable surface cilia. The nuclei of the secretory cells vary in position, depending on the stage in the menstrual cycle. The intercalated cells are secretory cells that have discharged their secretions with the result that the cell walls are collapsed around the nucleus. The ciliated component is the most prominent near the fimbrial end of the tube and the secretory cells are more numerous in the isthmus than they are in the ampulla.

Normal tubal epithelium An admixture of secretory and ciliated cells constitute the majority of the cells.

The tubal epithelium shows well-defined histologic alterations in response to cyclic hormonal variations, which affect the height of the epithelial cells, rather than the number of cilia, as happens in other primates. In the proliferative phase of the cycle the estrogen predominance results in epithelial cells with increasing height whereas in the progesterone-dominated secretory phase, the cell height may be as little as half that seen in the first half of the cycle. Similarly, the height of both epithelial cell types is low in pregnancy. Oral contraceptives produce a similar appearance to those of pregnancy; the epithelial cells are relatively flat and show a lack of secretory activity, features that doubtless play some part in the effectiveness of the medication. In the late postmenopausal state, the epithelium becomes thin and atrophic ( Figure 21.2 ).

Atrophic tubal mucosa. The epithelium is thin and atrophic and the plical lamina propria is fibrotic.

In cross section, at low-power magnification, the mucosa of the tubal ampulla ( Figure 21.3 ) forms a complicated maze-like pattern of folds (the plicae) that branch but do not join. The epithelial surfaces of the plicae are apposed to one another so that even in the widest part of the tube the traversing ovum is not floating in a spacious lumen but is at all times nurtured by the ciliated and secretory epithelium with which it is in contact on all sides. These folds become less complex as the medial end of the tube is approached, becoming stellate in the isthmus ( Figure 21.4 ) and forming an irregular, almost rounded, outline to the lumen in the interstitial part. In postmenopausal women, the plical stroma becomes fibrous and the plicae themselves club shaped, an appearance that may be mistaken for one sequela of infection, and the epithelium flattened.

Normal ampulla. The mucosa forms a complex maze-like pattern of folds that branch but do not join.

Normal isthmus. The lumen is narrow and stellate and the wall is thick.

The tubal musculature is arranged in a basket-weave fashion. This layer is thinnest at the tube’s distal end and becomes progressively thicker as the cornu is approached. A subepithelial layer of mainly longitudinal muscle appears at the isthmus and continues along the interstitial portion. At this point, the spiral muscle becomes continuous with the myometrium.

Mucosal Epithelial Alterations

Secretory Cell Outgrowths and p53 Signatures

Expansions of morphologically unremarkable secretory cells, uninterrupted by ciliated cells, can occasionally be identified as discrete, linear foci in a background of the usual mixed ciliated and secretory cells populating the fallopian tube epithelium. Such expansions have been designated as secretory cell outgrowths (SCOUTs) when they comprise at least 30 or more secretory cells. The majority are associated with loss of expression of PAX2 , a member of the pair box gene family, which is normally expressed in structures derived from the müllerian duct. The related p53 signature is also composed of secretory cells, but with the incremental changes of acquired p53 mutation, evidence of DNA damage, and relative predominance in the distal portion of the fallopian tube ( Figure 21.5A and B ). Neither SCOUTs nor p53 signatures exhibit significant proliferative activity ( Figure 21.5C ). Both are currently interpreted as early clonal expansions short of neoplastic proliferation.

(A–C) The p53 signature is a histologically unremarkable stretch of tubal epithelium (A) that is associated with p53 mutations, exhibiting strong nuclear staining for p53 (B) and has a low MIB1 index (C) .

Both SCOUTs and p53 signatures are candidate early steps toward high grade serous tubal carcinoma, as discussed in Chapter 25 . The reader is cautioned, however, that the prospective cancer risk of women with isolated SCOUTs and/or p53 signature is unknown, so neither is a diagnostic entity that should be invoked in clinical practice. Fallopian tubes from women with high-grade pelvic serous carcinoma harbor a significantly higher frequency of SCOUTs than those from women whose tubes were removed for a non-malignant condition. Tubes in which serous tubal intraepithelial carcinoma is present are more likely to contain p53 signatures than those without; in some cases, a p53 signature may be found in direct continuity with intraepithelial carcinoma. In a given case of pelvic serous carcinoma, shared p53 mutations may be identified among p53 signatures, serous tubal intraepithelial carcinoma, and invasive tumor elsewhere in the pelvis.

Other Mucosal Epithelial Proliferations

Another notable pattern of epithelial growth in the fallopian tube, which does not appear to be associated with malignancy, either in the tube or elsewhere, is characterized by an apparent ‘hyperplasia’ of the normal mucosal epithelial cells. Such areas are populated by a mix of ciliated and secretory cells, which appear stratified or are arranged as small tufts. These areas may be focal or more diffuse. The cells themselves may exhibit some nuclear atypia, but not to the degree found in intraepithelial carcinoma. Mitotic activity is generally minimal ( Figure 21.6 ). This mucosal alteration may be seen in the setting of pregnancy, but can be found in the tubes of non-pregnant women as well.

Mucosal epithelial proliferation. A prominent tufted appearance is present.

Secretory Cell Outgrowths and p53 Signatures

Expansions of morphologically unremarkable secretory cells, uninterrupted by ciliated cells, can occasionally be identified as discrete, linear foci in a background of the usual mixed ciliated and secretory cells populating the fallopian tube epithelium. Such expansions have been designated as secretory cell outgrowths (SCOUTs) when they comprise at least 30 or more secretory cells. The majority are associated with loss of expression of PAX2 , a member of the pair box gene family, which is normally expressed in structures derived from the müllerian duct. The related p53 signature is also composed of secretory cells, but with the incremental changes of acquired p53 mutation, evidence of DNA damage, and relative predominance in the distal portion of the fallopian tube ( Figure 21.5A and B ). Neither SCOUTs nor p53 signatures exhibit significant proliferative activity ( Figure 21.5C ). Both are currently interpreted as early clonal expansions short of neoplastic proliferation.

(A–C) The p53 signature is a histologically unremarkable stretch of tubal epithelium (A) that is associated with p53 mutations, exhibiting strong nuclear staining for p53 (B) and has a low MIB1 index (C) .

Both SCOUTs and p53 signatures are candidate early steps toward high grade serous tubal carcinoma, as discussed in Chapter 25 . The reader is cautioned, however, that the prospective cancer risk of women with isolated SCOUTs and/or p53 signature is unknown, so neither is a diagnostic entity that should be invoked in clinical practice. Fallopian tubes from women with high-grade pelvic serous carcinoma harbor a significantly higher frequency of SCOUTs than those from women whose tubes were removed for a non-malignant condition. Tubes in which serous tubal intraepithelial carcinoma is present are more likely to contain p53 signatures than those without; in some cases, a p53 signature may be found in direct continuity with intraepithelial carcinoma. In a given case of pelvic serous carcinoma, shared p53 mutations may be identified among p53 signatures, serous tubal intraepithelial carcinoma, and invasive tumor elsewhere in the pelvis.

Other Mucosal Epithelial Proliferations

Another notable pattern of epithelial growth in the fallopian tube, which does not appear to be associated with malignancy, either in the tube or elsewhere, is characterized by an apparent ‘hyperplasia’ of the normal mucosal epithelial cells. Such areas are populated by a mix of ciliated and secretory cells, which appear stratified or are arranged as small tufts. These areas may be focal or more diffuse. The cells themselves may exhibit some nuclear atypia, but not to the degree found in intraepithelial carcinoma. Mitotic activity is generally minimal ( Figure 21.6 ). This mucosal alteration may be seen in the setting of pregnancy, but can be found in the tubes of non-pregnant women as well.

Mucosal epithelial proliferation. A prominent tufted appearance is present.

Function

The fallopian tube has three main functions in the reproductive process. First, it is responsible for transferring the ovum into its lumen when discharged from the ovary’s rupturing follicle. Second, it provides an environment in which the sperm can fertilize the ovum. Third, it transfers the fertilized, cleaving embryo into the uterus after an interval of 3–4 days.

Sperm Transport

The mechanisms of sperm transport in the tube are not known. It is apparent that there is a rapid postcoital sperm movement along the whole genital tract and that, in different segments of the tract, including the tube, a number of ‘storage compartments’ are established from which sperm release occurs slowly. Although reduced sperm motility is a factor in male infertility, it is accepted that sperm do not have to be motile to be transported along the female genital tract. No information is known about the active part, if any, that the tube plays in sperm transport.

Ovum Transport

Ovum transport has been studied in detail, and the two essential elements are muscular activity and ciliary action. It would seem that these two mechanisms play a complementary role in ovum transport. Even so, each does not always appear necessary. Reproduction can take place when the muscular activity is paralyzed and ciliary action alone will carry the ovum across the ampullary part of the tube. The muscular contractions of the tubal wall are both phasic and tonic; it can undergo transient contractions as well as alter its basal tone. Contractile activity of the muscle takes place in coordinated waves. These result in peristaltic pulses along segments of the tube, although these are propagated only along random short lengths, with junctional pauses. Some claim that muscular activity is not essential for transport of the oocyte along its course.

The ciliary action in the tube is toward the uterus and is under the influence of many mediators. Physiologic levels of prostaglandins F _2α , E ₁ , and E ₂ stimulate the ciliary activity as do β-adrenergic agonists; the latter effect is potentiated by estrogen and progesterone. Recent data have shown that progesterone affects the tubal ciliary beat frequency. Incubation with progesterone suppresses the beat frequency by 40–50% but estradiol has no effect. Cilia from the tubal ampulla beat significantly faster than those from fimbrial segments.

Approach to Examining Tubal Specimens

Bilateral Tubal Ligation for Sterilization

Many methods are used, and the most popular is the Pomeroy operation and methods incorporating the use of clips or rings. The Pomeroy operation is an open procedure in which a loop of the tubal isthmus is pulled up and ligated with an absorbable suture followed by excision of the isolated loop. Histologic examination provides evidence that the operation has been carried out properly. Clips are also widely used. The clips are placed over the isthmus, where the tube is thinnest, so that the tubal lumen is completely occluded. Falope rings, made of Silastic, are placed over a loop of tube that is pulled up. The application of clips and rings is usually done as a laparoscopic procedure.

The most important aspect in the sectioning and preparation of the excised specimen for microscopic examination is that sufficient sections are made to show the complete cross section of the tube ( Figure 21.7 ). An efficient method is to cut the fallopian tube into sections no more than 1–2 mm thick so that a single slide contains up to six sections. In this manner, even if some sections are embedded improperly or cut on a bias, at least a few should show the complete cross section, if in fact it is present. Any case where none of the pieces shows a complete cross section should be reported as incomplete ( Figure 21.8 ). This can occur when the surgeon has removed arteries and fascia or only the tubal fimbriae. In these cases, it commonly happens that the clinician had difficulty definitively identifying the fallopian tube, even though this information was not transmitted to the pathologist. It is most important that an incomplete ligation be clearly reported in part for medicolegal consideration. The pathologist must be careful not to interpret a paratubal cyst as fallopian tube lumen; the latter has a much thicker wall with ample smooth muscle.

Sterilization procedure, complete transection. This section of the tube shows the complete circumference of muscular wall surrounding the mucosa, confirming complete transection of the tube.

Sterilization procedure, incomplete transection. This is one of many sections from this sterilization procedure. Although tubal mucosa and muscular wall are present, the muscle does not surround the mucosa completely so that the transection cannot be confirmed as complete.

Salpingectomy (with or Without Oophorectomy And/or Hysterectomy)

The SEE-FIM Protocol

The majority of early serous carcinomas in the fallopian tube are detected microscopically rather than by gross examination, in the distal portion of the fallopian tube, in the fimbriae. Salpingectomy performed in high-risk patients, such as those undertaken prophylactically in BRCA mutant women, are a common setting for clinically and grossly occult disease. In an effort to facilitate a thorough examination of the distal fallopian tube a protocol for sectioning and extensively examining the fimbriated end (SEE-FIM) was developed (see also Chapter 35 ). According to this protocol, the entire fallopian tube is first well fixed to prevent exfoliation of the mucosal epithelial cells. The fimbriae are then amputated from the proximal tube and sectioned longitudinally into multiple sections to permit maximum exposure of the fimbrial mucosa. The remainder of the tube is cross sectioned at 2−3 mm intervals and the entire tube is submitted for histopathologic review ( Figure 21.9 ).

(A-C) The protocol for sectioning and extensively examining the fimbriated end (SEE-FIM protocol). Tubes are first fixed. The fimbriae are then amputated from the rest of the tube (A) , sectioned longitudinally into multiple sections (B) , and then submitted with the remainder of the tube, which has been cross sectioned at 2–3 mm intervals. Longitudinal sectioning permits maximum evaluation of the fimbrial mucosal epithelium ( C , low-power magnification).

Indications for extensive tubal sampling are not yet clearly defined by clinical necessity, but should be considered in cases where it is desirable to maximize the likelihood of detecting early tubal cancer. Appropriate specimen types might include risk-reducing (prophylactic) salpingectomies; salpingectomies from women with a history of breast cancer; and salpingectomies in the setting of uterine, ovarian, or peritoneal disease. Some consensus is emerging from within the pathology community, with, for example, the Association of Directors of Anatomic and Surgical Pathology recommending an approach similar to SEE-FIM in prophylactically removed specimens, with an emphasis on longitudinal sectioning of the fimbriae. This group also recommends sampling fimbriae as part of processing of routine tubal specimens.

Given that the distal fallopian tube is the site most likely to harbor occult tubal malignancy, the suggestion has been made by some authors to submit the entire fimbriae for histopathologic review even in cases in which tubes are removed for benign disease. Currently, the incidence of occult carcinoma in the fallopian tube in the general population is unknown. However, with increasing attention focused on the distal tube, incidental tubal cancers are being discovered in cases otherwise unsuspected of harboring a malignancy. A standard clinical response to incidentally discovered occult in situ tubal cancer has not yet been formulated, but there is a possibility for identification of individuals who may benefit from increased surveillance, or even early disease intervention.

Bilateral Tubal Ligation for Sterilization

Many methods are used, and the most popular is the Pomeroy operation and methods incorporating the use of clips or rings. The Pomeroy operation is an open procedure in which a loop of the tubal isthmus is pulled up and ligated with an absorbable suture followed by excision of the isolated loop. Histologic examination provides evidence that the operation has been carried out properly. Clips are also widely used. The clips are placed over the isthmus, where the tube is thinnest, so that the tubal lumen is completely occluded. Falope rings, made of Silastic, are placed over a loop of tube that is pulled up. The application of clips and rings is usually done as a laparoscopic procedure.

The most important aspect in the sectioning and preparation of the excised specimen for microscopic examination is that sufficient sections are made to show the complete cross section of the tube ( Figure 21.7 ). An efficient method is to cut the fallopian tube into sections no more than 1–2 mm thick so that a single slide contains up to six sections. In this manner, even if some sections are embedded improperly or cut on a bias, at least a few should show the complete cross section, if in fact it is present. Any case where none of the pieces shows a complete cross section should be reported as incomplete ( Figure 21.8 ). This can occur when the surgeon has removed arteries and fascia or only the tubal fimbriae. In these cases, it commonly happens that the clinician had difficulty definitively identifying the fallopian tube, even though this information was not transmitted to the pathologist. It is most important that an incomplete ligation be clearly reported in part for medicolegal consideration. The pathologist must be careful not to interpret a paratubal cyst as fallopian tube lumen; the latter has a much thicker wall with ample smooth muscle.

Sterilization procedure, complete transection. This section of the tube shows the complete circumference of muscular wall surrounding the mucosa, confirming complete transection of the tube.

Sterilization procedure, incomplete transection. This is one of many sections from this sterilization procedure. Although tubal mucosa and muscular wall are present, the muscle does not surround the mucosa completely so that the transection cannot be confirmed as complete.

Salpingectomy for Tubal Ectopic Gestation

Record the site and location of the gestation, if apparent. A rupture site, if present, should be described and sampled. If the ectopic pregnancy is not obvious, a focal enlargement or swelling should be sought. Blood distending the lumen should be documented. Blood clot should be examined carefully for gross evidence of chorionic villi. Multiple cross sections of the fallopian tube at the site of swelling and/or blood clot should be submitted for histopathologic review. Sections of fallopian tube adjacent to the site of swelling should also be sampled to look for evidence of prior salpingitis. Ectopic pregnancy removal by salpingostomy with preservation of the tube itself should be clearly conveyed in the report, as the patient is at risk for recurrence.

Salpingectomy (with or Without Oophorectomy And/or Hysterectomy)

The SEE-FIM Protocol

The majority of early serous carcinomas in the fallopian tube are detected microscopically rather than by gross examination, in the distal portion of the fallopian tube, in the fimbriae. Salpingectomy performed in high-risk patients, such as those undertaken prophylactically in BRCA mutant women, are a common setting for clinically and grossly occult disease. In an effort to facilitate a thorough examination of the distal fallopian tube a protocol for sectioning and extensively examining the fimbriated end (SEE-FIM) was developed (see also Chapter 35 ). According to this protocol, the entire fallopian tube is first well fixed to prevent exfoliation of the mucosal epithelial cells. The fimbriae are then amputated from the proximal tube and sectioned longitudinally into multiple sections to permit maximum exposure of the fimbrial mucosa. The remainder of the tube is cross sectioned at 2−3 mm intervals and the entire tube is submitted for histopathologic review ( Figure 21.9 ).

(A-C) The protocol for sectioning and extensively examining the fimbriated end (SEE-FIM protocol). Tubes are first fixed. The fimbriae are then amputated from the rest of the tube (A) , sectioned longitudinally into multiple sections (B) , and then submitted with the remainder of the tube, which has been cross sectioned at 2–3 mm intervals. Longitudinal sectioning permits maximum evaluation of the fimbrial mucosal epithelium ( C , low-power magnification).

Indications for extensive tubal sampling are not yet clearly defined by clinical necessity, but should be considered in cases where it is desirable to maximize the likelihood of detecting early tubal cancer. Appropriate specimen types might include risk-reducing (prophylactic) salpingectomies; salpingectomies from women with a history of breast cancer; and salpingectomies in the setting of uterine, ovarian, or peritoneal disease. Some consensus is emerging from within the pathology community, with, for example, the Association of Directors of Anatomic and Surgical Pathology recommending an approach similar to SEE-FIM in prophylactically removed specimens, with an emphasis on longitudinal sectioning of the fimbriae. This group also recommends sampling fimbriae as part of processing of routine tubal specimens.

Given that the distal fallopian tube is the site most likely to harbor occult tubal malignancy, the suggestion has been made by some authors to submit the entire fimbriae for histopathologic review even in cases in which tubes are removed for benign disease. Currently, the incidence of occult carcinoma in the fallopian tube in the general population is unknown. However, with increasing attention focused on the distal tube, incidental tubal cancers are being discovered in cases otherwise unsuspected of harboring a malignancy. A standard clinical response to incidentally discovered occult in situ tubal cancer has not yet been formulated, but there is a possibility for identification of individuals who may benefit from increased surveillance, or even early disease intervention.

The SEE-FIM Protocol

The majority of early serous carcinomas in the fallopian tube are detected microscopically rather than by gross examination, in the distal portion of the fallopian tube, in the fimbriae. Salpingectomy performed in high-risk patients, such as those undertaken prophylactically in BRCA mutant women, are a common setting for clinically and grossly occult disease. In an effort to facilitate a thorough examination of the distal fallopian tube a protocol for sectioning and extensively examining the fimbriated end (SEE-FIM) was developed (see also Chapter 35 ). According to this protocol, the entire fallopian tube is first well fixed to prevent exfoliation of the mucosal epithelial cells. The fimbriae are then amputated from the proximal tube and sectioned longitudinally into multiple sections to permit maximum exposure of the fimbrial mucosa. The remainder of the tube is cross sectioned at 2−3 mm intervals and the entire tube is submitted for histopathologic review ( Figure 21.9 ).

(A-C) The protocol for sectioning and extensively examining the fimbriated end (SEE-FIM protocol). Tubes are first fixed. The fimbriae are then amputated from the rest of the tube (A) , sectioned longitudinally into multiple sections (B) , and then submitted with the remainder of the tube, which has been cross sectioned at 2–3 mm intervals. Longitudinal sectioning permits maximum evaluation of the fimbrial mucosal epithelium ( C , low-power magnification).

Indications for extensive tubal sampling are not yet clearly defined by clinical necessity, but should be considered in cases where it is desirable to maximize the likelihood of detecting early tubal cancer. Appropriate specimen types might include risk-reducing (prophylactic) salpingectomies; salpingectomies from women with a history of breast cancer; and salpingectomies in the setting of uterine, ovarian, or peritoneal disease. Some consensus is emerging from within the pathology community, with, for example, the Association of Directors of Anatomic and Surgical Pathology recommending an approach similar to SEE-FIM in prophylactically removed specimens, with an emphasis on longitudinal sectioning of the fimbriae. This group also recommends sampling fimbriae as part of processing of routine tubal specimens.

Given that the distal fallopian tube is the site most likely to harbor occult tubal malignancy, the suggestion has been made by some authors to submit the entire fimbriae for histopathologic review even in cases in which tubes are removed for benign disease. Currently, the incidence of occult carcinoma in the fallopian tube in the general population is unknown. However, with increasing attention focused on the distal tube, incidental tubal cancers are being discovered in cases otherwise unsuspected of harboring a malignancy. A standard clinical response to incidentally discovered occult in situ tubal cancer has not yet been formulated, but there is a possibility for identification of individuals who may benefit from increased surveillance, or even early disease intervention.

Non-Neoplastic Lesions

Non-Granulomatous Salpingitis

Non-granulomatous salpingitis is predominantly a disease of young, sexually active women, and 70% of those with the disease are under the age of 25. Other factors that have an influence on the development of salpingitis include the method of contraception, induced abortion, and instrumentation of the cervix. Among the infectious organisms responsible for salpingitis, Chlamydia trachomatis and Neisseria gonorrhoeae remain of paramount importance and are responsible for ascending salpingitis. Other causative microbial agents are the anaerobic bacteria (bacteroides, clostridia, and streptococci), Mycoplasma hominis , and Ureaplasma urealyticum , and miscellaneous organisms such as Haemophilus influenzae and group A streptococci. Bacterial vaginosis is a common concurrent disorder of women with acute salpingitis, and bacterial vaginosis microorganisms are commonly isolated from the upper genital tracts of patients with pelvic inflammatory disease. Salpingitis caused by Actinomyces israelii is associated with the presence of an intrauterine contraceptive device, and may result in the development of a tubo-ovarian abscess ( Figure 21.10 ). Actinomyces -like organisms can be identified in the pus ( Figure 21.11 ). In practice, however, microbiologic investigations often show that the cultured material is already sterile by the time of the investigation, or else there is a combination of organisms.

Actinomyces infection causing a tubo-ovarian abscess.

Actinomyces -like organisms in pus.

The spread of etiologic organisms from the lower to the upper genital tract is canalicular, through the cervical canal and endometrial cavity and then into the fallopian tubes. Blockage of this route, either by cornual resection of the fallopian tubes or by sterilization, reduces the risk of salpingitis. Salpingitis begins as a mucosal rather than a serosal infection.

Gross Features

In the acute phase of the disease, the tube is swollen, edematous, and congested. The acutely inflamed tube is rarely seen histologically, as treatment of the acute phase is medical rather than surgical.

In chronic salpingitis, the tube is thickened and congested, with adhesions on the surface, often binding the tube and ovary closely together. A pyosalpinx is a grossly enlarged tube, increased in both diameter and length, and containing pus. A hydrosalpinx characteristically shows a fusiform shape and is greatly enlarged with paper-thin walls. In both conditions, the fimbrial ends fuse, sealing the tube. Not uncommonly, the fimbriae cannot be identified.

Microscopic Features

The plicae are greatly swollen and densely infiltrated by neutrophils ( Figure 21.12 ). The epithelial cells soon lose their cilia and the epithelium is shed in severe disease. The lumen contains pus ( Figure 21.13 ). As the disease progresses to chronic salpingitis ( Figures 21.14 and 21.15 ), the inflammatory infiltrate consists predominantly of plasma cells and then lymphocytes. The progression from acute to chronic non-granulomatous salpingitis may take several courses. If the fimbrial end of the tube remains patent, a chronic interstitial salpingitis may ensue, in which case the tube is thickened and the plicae fuse to form epithelial-lined cysts, which are the hallmark of chronic salpingitis. ‘Follicular salpingitis’ ( Figure 21.16 ) rather confusingly refers to the epithelium-lined spaces rather than lymphoid collections. The inflammatory process may eventually become quiescent, leaving only the architectural sequelae of chronic salpingitis ( Figure 21.17 ). Severe inflammation in the tube may spread to the adjacent ovary, resulting in a tubo-ovarian abscess ( Figure 21.18 ). Occlusion of the fimbrial end of the tube prevents release of the tubal contents, so that a pyosalpinx may result ( Figure 21.19 ). In pyosalpinx, the lumen is filled with pus ( Figure 21.20 ) and the wall is thinned, although the attenuation is commonly less marked than in hydro­salpinx. Acute and chronic inflammatory cells infiltrate the plicae and wall. As the exudate is reabsorbed into the tubal wall concurrently with the quiescence of the inflammatory process, clear fluid replaces this pus and a hydrosalpinx results ( Figures 21.21 and 21.22 ). In hydrosalpinx, the epithelium is generally thin and non-ciliated, although a few areas of morphologically normal cells may be seen. The wall of a hydrosalpinx is markedly thinned, with attenuation of smooth muscle and plicae. Usually, by this advanced stage in the disease process, there is little, if any, residual inflammatory infiltrate in the tissues of the wall. From a practical point of view, hydrosalpinx with tubo-ovarian adhesions is commonly misdiagnosed as ovarian ‘serous cystadenoma’ since it commonly presents as an adnexal mass. A careful microscopic examination identifying the muscular layer is diagnostic for hydrosalpinx. A small hydrosalpinx in which there is plical conglutination will have a ‘honeycomb’ cut surface and is termed a ‘hydrosalpinx follicularis’ ( Figure 21.23 ). The relations among these inflammatory changes are shown in Figure 21.24 .

Acute salpingitis. The plicae are edematous and infiltrated by neutrophils.

Acute salpingitis. The lumen is filled with pus and the plicae are engorged and inflamed.

Chronic salpingitis. In this early stage of the disease, the plicae are infiltrated by plasma cells and lymphocytes and there is pus in the lumen. The epithelium is intact, although containing inflammatory cells.

Chronic salpingitis. The infiltrate is now predominantly lymphocytic, with germinal centers.

Chronic salpingitis. The plicae are partly fused, forming separate epithelium-lined spaces or ‘follicles’ separate from the central lumen (‘follicular salpingitis’). Inflammation is still active.

Chronic salpingitis, healed. The inflammation has subsided and is near absent, but the plicae remain fused by fibrosis.

Tubo-ovarian abscess. The central mass is the ovary, which contains an abscess. Its cavity communicates with pus in the lumen of the tube (arrow).

Pyosalpinx.

Pyosalpinx. The lumen contains pus.

Hydrosalpinx.

Hydrosalpinx. The convoluted shape (often called ‘retort shaped’) of the tube is seen on section.

Hydrosalpinx follicularis.

Relations among the appearances and stages of inflammation of the fallopian tube.

The term ‘pelvic inflammatory disease’ (PID) implies chronic salpingitis with involvement of the surrounding structures, including ovary and parametrium. Adhesions are present on the surface of the tube, often spreading to involve the uterine serosa. PID typically has remissions and exacerbations and is difficult to eradicate. As a result of this cycle of events, in which acute salpingitis leads to chronic salpingitis, quiescence and then an exacerbation of the acute episode again, the histologic finding of acute and chronic salpingitis is commonplace. In these circumstances, the background architectural features of chronic salpingitis are seen, but the cellular infiltrate is predominantly of neutrophils, with pus in the lumen.

Granulomatous Salpingitis

Granulomatous salpingitis is nearly always tuberculous in origin. All age groups may be affected but the pattern of the disease has changed over the last few decades. Until the 1970s, tuberculosis of the female genital tract in the developed world affected mainly women of childbearing age but more recently the majority of cases are in postmenopausal women. Whereas previously the main complaint of these women was infertility, tuberculosis accounting for about 40% of all cases of infertility, the common symptoms are now pain and bleeding. When tuberculosis affects the female genital tract, the tube is affected in nearly all cases and involvement of the endometrium is always secondary to it. The pelvic disease is, in turn, secondary to primary disease in the lungs or bowel, spreading to the tubes by hematogenous and lymphatic routes, respectively.

Gross Features

Tuberculous salpingitis is nearly always bilateral. The tube is thickened and congested and there are serosal adhesions. The fimbrial end of the tube is usually patent and the lumen may contain caseous debris ( Figure 21.25 ). The wall is thickened and foci of caseation may be recognized within the tissue of the wall.

Tuberculous salpingitis. The wall is greatly distended and thinned and the lumen contains caseous material.

Microscopic Features

The hallmark of tuberculous salpingitis histologically is the epithelioid cell granuloma that is situated in the lamina propria of the plicae ( Figures 21.26 and 21.27 ) and, rarely, within the muscular wall. Caseation may or may not be present, but is more often seen in older women. A surrounding, dense lymphocytic infiltrate is found, both in the plical lamina propria and in the muscle, the latter is usually more conspicuous. A frequent finding is the presence of striking epithelial proliferation of the endosalpinx, a feature that may cause confusion with carcinoma (see later). Schaumann bodies are occasionally seen in tuberculous salpingitis ( Figure 21.26 ). Although typically associated with sarcoidosis, these rounded, concentrically laminated calcified bodies may be seen in most forms of epithelioid cell granuloma. The histologic suggestion of tubal tuberculosis is confirmed if acid-fast bacilli are found in the sections, but this is achieved in only 1% of cases in which the culture proves positive. On a practical basis, staining is not useful. With the development of molecular pathology, polymerase chain reaction-based tuberculosis-specific bacilli DNA can be detected in 48 hours. The differential diagnosis of tuberculous salpingitis in Europe is sarcoidosis, Crohn disease, and foreign-body granuloma. Worldwide, other conditions include schistosomiasis, blastomycosis, coccidioidomycosis, histoplasmosis, and enterobiasis. A positive tissue diagnosis of tuberculosis is often not possible and the decision to treat the patient must rest on the degree of clinical suspicion.

Tuberculous salpingitis. Epithelioid cell granulomas are present with giant cells. Schaumann bodies are also seen (arrows).

Tuberculous salpingitis.

Salpingitis Isthmica Nodosa

Definition

An abnormality of the fallopian tube, salpingitis isthmica nodosa (SIN), occurs in 1% of Caucasian women and 10% of black women with a mean of 26 years. SIN consists of nodular swelling of the isthmic segment of the fallopian tube and is associated with diverticula of the lumen and smooth muscle proliferation. It has characteristic radiologic features and is significantly more common in women with ectopic pregnancy and infertility.

Pathology

SIN may be recognized grossly as a rounded, firm swelling, up to 2 cm in diameter, at the isthmic end of the tube ( Figure 21.28 ), often merging with the cornual extremity of the uterus. The nodules are often bilateral and, occasionally, there may be more than one swelling on each tube. Most cases, however, cannot be detected macroscopically. The histologic appearances are striking and consist of a thickened wall due to hypertrophied musculature with epithelial-lined channels running between the muscle bundles and reaching close to the serosa ( Figures 21.29 and 21.30 ). The epithelium lining these spaces is of normal, tubal type. The central lumen is always recognizable and the additional channels communicate with it and with each other, but not with the peritoneal cavity.

Salpingitis isthmica nodosa. The firm, round, isthmic nodule is bisected to demonstrate the central lumen.

Salpingitis isthmica nodosa. The original lumen is still discernible near the center (arrow). The wall of the tube is greatly thickened by muscular hypertrophy and separate channels are present throughout the wall.

Salpingitis isthmica nodosa.

Histogenesis

The histogenesis of SIN remains unknown. Three potential mechanisms include:

• 1.
  

  The condition is postinflammatory.

  
  
• 2.
  

  The outcome results from ‘mechanical’ pressure, analogous to diverticular disease of the large bowel.

  
  
• 3.
  

  It is a developmental anomaly.

That SIN is the result of inflammatory changes is unlikely because of its low incidence compared with salpingitis, its position in the isthmus (inflammatory changes are more often in the ampulla), and the absence of fibrosis and of a cellular infiltrate. In favor of the mechanical theory is the finding of continuity between the original lumen and the peripheral channels, as well as the demonstration of small, direct outpouchings of epithelium into the muscle, which appear to initiate the process. The proposal that the condition reflects abnormal embryonic development could explain the findings.

Differential Diagnosis

SIN should be distinguished from endometriosis, chronic (infectious) salpingitis, and neoplasia. A diagnosis of endometriosis requires the presence of endometrial-type stroma surrounding the epithelial component, the latter consisting predominantly of non-ciliated, columnar cells, although areas of ciliation may be seen. Stroma is absent in SIN, the epithelium abutting directly onto the muscle. The distinction from chronic salpingitis is made by identifying smooth muscle bundles, which usually are prominent between the multiplicity of epithelial channels in SIN. In the inflammatory condition the channels are formed by fusion of the plicae with the result that fibrous tissue only, not muscle, intervenes between the diverticula. SIN is distinguished from carcinoma by the regular distribution of widely spread glands, lack of nuclear atypia, and the absence of a reactive stromal response.

Tubal Pregnancy

Etiology and Pathogenesis

Any factor that impairs the tube’s ability to transport the fertilized ovum will predispose to tubal implantation of the ovum. Hence, congenital tubal abnormalities, failed tubal ligation, reconstructive tubal surgery, SIN, and, most importantly, postinflammatory tubal damage are all associated with an increased incidence of tubal pregnancies.

The fertilized ovum may on occasion also implant in a normal tube. It has been argued that in these cases conception occurred during a cycle in which the non-implanted ovum was flushed back into the tube by a reflux of menstrual blood. Findings that support this hypothesis are that tubal gestation occurs only in humans and in primates that menstruate, and by the not uncommon finding that the tube with the pregnancy is on the side opposite to the corpus luteum of pregnancy. This latter phenomenon can also be due to transperitoneal or transuterine migration of the fertilized ovum into the contralateral tube where, due to its relatively advanced stage of development, it implants.

Natural History

Implantation occurs most commonly in the ampulla and may be plical, plicomural, or mural. It may also occur in the isthmus and interstitial portion. The earliest stages of pregnancy usually proceed in a manner that does not differ in any significant respect from the same process in an intra­uterine site. The complications of tubal abortion, hemorrhage, or rupture soon supersede in all cases.

Tubal Abortion.

A high proportion of tubal pregnancies abort at an early stage and may be expelled from the fimbrial end of the tube. This is invariably the case if implantation has been fimbrial or plical, simply because these sites offer insufficient tissue for adequate placentation, but it is also seen with mural implantation. There is often intra­mural and intraluminal hemorrhage and subsequent fetal death. Following abortion, degenerating chorionic villi may be retained in the tube as so-called ‘chronic ectopic pregnancy’ or they may be expelled via the uterus or be gradually absorbed. Hyalinized ghost villi may be identified in the tube as an incidental finding many months later.

Tubal Hemorrhage.

Although decidual change may be seen in the lamina propria of the fallopian tube during uterine or ectopic gestation, the change is focal and poorly developed. In normal pregnancy in the uterine body, decidualized endometrium acts as a buffer that constrains trophoblastic invasion. In the absence of this buffering zone in a tubal pregnancy, trophoblast infiltrates destructively into the vessels and muscle of the tube wall, resulting in hemorrhage and rupture. Even if there is no rupture, hemorrhage is invariably present at the time of presentation of a tubal ectopic pregnancy. Massive hemorrhage into the uterine wall may result if the implantation is interstitial.

Tubal Rupture.

Tubal rupture complicates about 50% of cases of tubal pregnancy and appears to be due partly to the limited distensibility of the tube and partly to transmural trophoblastic invasion with penetration of the serosa. It is particularly likely to occur when the implantation is isthmic, because of this area’s limited distensibility. Rupture is usually acute and is accompanied by intraperitoneal hemorrhage and the clinical features of an acute abdomen. Less commonly, there is a slow leakage of tubal contents and blood from the tube, which results in a gradually enlarging peri­tubal hematoma with dense adhesions between the tube and surrounding structures such as omentum and intestines. Occasionally, the ureters obstruct as a result of involvement in this peritubal mass. Although tubal rupture usually results in fetal death, the fetus occasionally retains sufficient attachment to its blood supply to maintain its viability. The trophoblast grows out through the rupture site and forms a secondary placental site in the abdomen or broad ligament. A secondary abdominal pregnancy of this type can occasionally proceed to term.

Pathology

Tubal Changes.

The fallopian tube, as received by the pathologist after salpingectomy, can show a range of appearances that vary with the site of nidation, viability of the fetus, duration of pregnancy, and presence or absence of rupture. In typical cases the tube is focally or generally distended while the peritoneal surface is congested and sometimes inflamed ( Figure 21.31 ). The fimbrial ostium can be occluded by blood clot or blood may be oozing from the ostium. If rupture has occurred, blood clot and placental tissue are sometimes seen protruding through the rupture site ( Figure 21.32 ), and blood clot may envelop the tube. On opening the tube a complete amniotic sac and fetus is occasionally seen ( Figures 21.33 and 21.34 ). More commonly, the lumen contains only fresh and old blood clot ( Figure 21.35 ).

Tubal ectopic pregnancy.

Ruptured tubal ectopic pregnancy (arrow).

Tubal ectopic pregnancy. A fetus is present.

Tubal ectopic pregnancy. Twin fetuses are present.

Tubal ectopic pregnancy. Sectioning shows only blood clot.

Histologic examination is usually required to confirm the diagnosis of tubal gestation ( Figure 21.36 ). A critical aspect is determination of the tissue to be submitted for microscopic examination. In nearly all cases, tissue within the blood clot will contain chorionic villi. Occasionally, they will be attached to the tubal wall. The villi may appear fully normal, but more often show degenerative change such as fibrosis or hydropic swelling. Dysmorphic changes, associated with chromosomal anomalies or molar change (e.g., triploidy), are only rarely seen as these do not constitute the cause for the pregnancy loss. In some cases many sections of the blood clot have to be examined before placental villi are seen. In the rare case no residual villous tissue will be found, the only detectable abnormalities are the presence of inflammatory debris and nonspecific granulation tissue. Even in such circumstances, however, an implantation site can often be identified by the presence of extravillous trophoblastic cells that have infiltrated the tubal wall and invaded the vascular spaces. Curiously, tubal tissue more than a short distance from the region of the ectopic pregnancy may show no abnormality other than a minor degree of nonspecific inflammation. It is important to take a block from the fallopian tube medial to the implantation site to assess the presence or absence of pre-existing salpingitis, usually manifest as plical adhesions, as this offers not only some pointer as to a likely cause of the present ectopic, but is useful in the further management of the patient. Salpingitis is usually bilateral and a second ectopic in the contra­lateral tube is more likely in such patients (who frequently end up having some form of assisted conception).

Tubal ectopic pregnancy, showing a virtually intact gestation sac. Chorionic villi are easily identifiable. A tiny fragment of embryo is present in the gestational sac itself. The fallopian tube parenchyma (right) shows evidence of old healed salpingitis with confluent plicae.

Laparoscopic Salpingostomy.

Although salpingectomy offers almost a 100% cure, laparoscopic methods are widely used that not only prevent maternal hemorrhage but also allow rapid recovery, preserve fertility, and reduce costs. Linear salpingostomy is now the standard laparoscopic operation when an ectopic pregnancy is unruptured but measures more than 4 cm by ultrasound. The products of conception are removed after an incision is made along the bulging antimesenteric border of the tube. The specimen the pathologist receives consists mainly of blood clot but frequently contains chorionic villi and trophoblastic fragments, enabling the diagnosis to be confirmed.

Uterine Changes.

In tubal pregnancies the uterine endometrium undergoes decidual change to a degree similar to that found in an intrauterine pregnancy in about 45% of cases. The endometrial glands are hypersecretory and an Arias-Stella change is seen focally in 60–70% of cases showing gestational changes. These appearances can, however, occur in any type of pregnancy and are not a specific feature of an ectopic gestation. In contrast to intrauterine pregnancies, curetted material shows little necrosis or inflammation. Indeed, this often is an important clue to the presence of an ectopic pregnancy. Depending on the time interval between fetal demise and curettage, the endometrium may show relatively poorly formed secretory changes and be inactive or even proliferative. In evaluating a curettage or biopsy specimen as part of a clinically suspected ectopic pregnancy, we have never personally encountered the situation where there was a documented pregnancy in the fallopian tube and chorionic villi were simultaneously found in the endometrial cavity. However, the pathologist must always be aware that villi are easily dislodged during tissue processing and may be artifactually introduced as contaminants from another case. Clues as to this possibility include position of the villi relative to other tissue fragments, lack of implantation site in the maternal tissues, and discordance between villous maturity and clinically suspected ectopic gestational age.

Cysts

Cysts lying alongside the fallopian tube are referred to as paratubal cysts ( Figure 21.37 ). They can be classified based on their origin as müllerian (paramesonephric), wolffian (mesonephric), or mesothelial. These subtypes are not always diagnostic at the time of presentation, because of either uncertain anatomic relationships or distortion of the wall and lining by dilation.

This paratubal cyst is thin walled and contains clear watery fluid.

Paramesonephric Cysts

Paramesonephric cysts, when small, tend to be more laterally situated than those of mesonephric origin. The hydatid of Morgagni, usually seen as a cyst on a pedicle arising from the fimbria, is the most common example of a paramesonephric cyst. Others are found in close proximity to the tube or on its subserosal aspect. Paramesonephric cysts, often also termed ‘broad ligament cysts,’ are lined by a single layer of columnar cells that may be ciliated or non-ciliated ( Figures 21.38 and 21.39 ). Smooth muscle is often present in their wall but is less prominent than in the mesonephric variety. Distinction between the two types of cyst is not always possible. Larger paramesonephric cysts may have papillary excrescences arising from the internal surface ( Figure 21.40 ).

Broad ligament ‘paratubal’ cyst.

Paramesonephric (müllerian) cyst. Coarse, polypoid projections into the lumen may be seen.

Paramesonephric (müllerian) cyst. A large cyst has papillary excrescences that arise from the internal surface.

Mesonephric Cysts

The mesonephric remnants are the epoophoron and paroophoron, which continue as vestigial tubular structures between the tube and ovary (rete ovarii), passing medially toward the body of the uterus, to enter it at about the level of the internal cervical os and pass anterolaterally in the cervix as Gartner’s duct. Non-neoplastic, noncystic mesonephric remnants are universally present between the tube and the ovary and are seen as a collection of thick-walled tubular structures lined by cuboidal epithelium with smooth muscle in their walls ( Figure 21.41 ). These remnants may become cystic at any point along their course, so that meso­nephric cysts may be found within the mesosalpinx and broad ligament or they may be pedunculated and situated just lateral to the ovary (Kobelt’s cyst). Typically, the mesonephric cyst is lined by a single layer of epithelium that is of low columnar or cuboidal, non-ciliated type. Smooth muscle may be prominent in the wall of these cysts, often together with dense connective tissue and elastic fibers.

Mesonephric remnants.

Mesothelial Inclusion Cysts

Paratubal cysts lined by mesothelial cells can demonstrate a variety of morphologic appearances and exhibit a range of sizes. The cysts may be multilocular or unilocular, the latter of which are sometimes referred to as simple cysts. Their thin walls are composed of fibrous tissue. The lining cells are generally flattened or cuboidal and ciliated cells are absent. Transitional, or müllerian, metaplasia can also be observed within surface inclusion cysts.

Metaplasias and Rests

As in the cervix and endometrium, it is questionable whether the finding of a type of müllerian epithelium that is inappropriate to the site should strictly be referred to as ‘metaplasia.’ Nevertheless, the presence of mucinous epithelium and endometrial epithelium in the fallopian tube mucosa must be considered abnormal.

Mucinous Metaplasia

This is an uncommon finding in which mucinous epithelium, exhibiting either an endocervical or gastrointestinal phenotype, replaces areas of tubal epithelium ( Figure 21.42 ). Tubal mucinous metaplasia may occur in women with Peutz–Jeghers syndrome and has been reported in women with both ovarian and cervical mucinous tumors; this phenomenon may be associated with a mutation in the tumor suppressor gene STK11 . Tubal metaplasia in the setting of multifocal mucinous metaplasia and neoplasia of the female genital tract has also been described in women without Peutz–Jeghers syndrome. The histogenesis of these multifocal mucinous lesions is unclear.

Mucinous metaplasia.

Endometriosis and Endosalpingiosis

Uterine endometrium is found in the interstitial and isthmic segments of the fallopian tube ( Figure 21.43 ) in up to 25% and 10% of women, respectively. This change is identified both as an incidental finding in hysterectomy specimens and, more significantly, in cornual resections for infertility. The lesion represents a shift of the junction between endometrium and fallopian tube mucosa into the fallopian tube. It may be considered a normal morphologic variation even though it is often called ‘endometriosis’ or ‘endometrial colonization.’ This phenomenon, which may be related to the microenvironment adaptation, is often encountered in histologic examination of the tubal proximal stump, usually 1–4 years after tubal ligation. Endometrial colonization can also be caused by complete occlusion of the fallopian tube. It accounts for 15–20% of cases of infertility and may be associated with tubal pregnancy.

Endometrial replacement (‘endometrialization or endometrial colonization’). Endometrial glands and stroma replace the tubal mucosa in the isthmus.

Typical or serosal tubal endometriosis is most commonly associated with endometriosis elsewhere in the pelvis. In this condition, the myosalpinx and mucosa are not usually involved. In some cases of pelvic endometriosis, with or without tubal involvement, the plicae are expanded by masses of pseudoxanthoma cells, a lesion called pseudoxanthomatous salpingitis or pseudoxanthomatous salpingiosis.

Endosalpingiosis involving the tube and paratubal tissue is morphologically identical to that found elsewhere in the peritoneum. The glandular deposits of benign tubal epithelium can be found on the serosal surface of the tube and in the mesosalpinx. Not infrequently, psammoma bodies are present in association with the epithelium. Occasionally it is identified in women who also have endometriosis, suggesting a common etiology in some cases. A thorough discussion of both endometriosis and endosalpingiosis can be found in Chapter 22 .

Transitional Metaplasia

Walthard rests are extremely common, small collections of transitional cells, rarely more than 1 mm in diameter, situated immediately beneath the tubal serosa ( Figures 21.44 and 21.45 ). Grossly, Walthard rests are clear to tan-white soft nodules, usually less than 1 mm in diameter ( Figure 21.46 ). The cells are of a rather nondescript type but some show longitudinal grooves in the nuclear membrane, resembling the appearance seen in Brenner tumor of the ovary. There is speculation that the cells of the Walthard rest and Brenner tumor arise in the same way, by transitional cell metaplasia of the serosal mesothelium. They may be solid or cystic. Walthard rests are of no significance whatsoever, apart from the importance of being recognized grossly for what they are and not mistaken clinically for pelvic tuberculosis, endometriosis, or disseminated tumor.

Walthard (urothelial differentiation) rest.

Walthard rest.

Walthard rests. Cystic Walthard rests (arrows) are present on the surface of the tube.

Compared with the very common transitional cell metaplasia of the serosa that Walthard rests represent, transitional cell metaplasia of the mucosa is extremely rare. It is likely that this is the same change that is described as ‘reserve cell metaplasia’ and may serve as a possible source of tubal transitional cell carcinomas.

Adrenal Rest

An encapsulated collection of adrenal cortical cells is encountered as 1–3 mm yellow nodules in the broad ligament or mesosalpinx in as many as one-fourth of women ( Figure 21.47 ). Also termed ‘Marchand rest,’ the heterotopic adrenal cells are identical to those of the adrenal cortex and are arranged in cords mimicking the zona fascicularis of the latter ( Figure 21.48 ). Benign and malignant tumors may arise from them.

Adrenal rests. Although no longer related to the fallopian tubes, the adrenal rests (arrows) are clearly seen in these dissected organs from an infant.

Adrenal rest.

Pseudodecidual Change (Ectopic Decidua)

The stromal cells of the fallopian tube lamina propria and subserosa readily undergo pseudodecidual change ( Figure 21.49 ). It is seen in about one-third of salpingectomy specimens containing ectopic pregnancies, and in 5–8% of tubal segments excised for sterilization performed during cesarean section or in the immediate postpartum period.

Pseudodecidual change.

Torsion of the Fallopian Tube

The fallopian tube usually undergoes torsion with the ovary. Both become twisted together, often because the ovary is enlarged. However, torsion may affect either organ independently and the tube is particularly at risk if it is diseased, as with a hydrosalpinx. The torsed tube is swollen and dark red-blue ( Figure 21.50 ). Microscopy shows marked congestion initially ( Figure 21.51 ), followed by infarction.

Torsion of the tube. A hydrosalpinx is present, an abnormality that precipitated twisting.

Torsion of the tube. At this early stage there is marked congestion. Infarction may follow.

Epithelial Proliferation Associated with Salpingitis

Definition

Reactive hyperplasia of tubal epithelium is associated with salpingitis. It may be mistaken for carcinoma since the salpingitis may present as pseudocarcinomatous hyperplasia.

Microscopic Features

This change results in the formation of multiple small glandular structures, often arranged in a highly complex pattern, amid inflamed, often edematous, tubal plicae ( Figures 21.52–21.54 ). The complexity of the architectural pattern is compounded by the fusion of adjacent plicae, resulting in a striking back-to-back pseudoglandular pattern or a sieve-like pattern. Epithelial stratification is often present and there may be loss of nuclear polarity. Nuclear atypia is of a mild to moderate degree only. Nucleoli are prominent in only half of the cases. Mitotic figures are rarely observed and these are normal. Moderate to marked chronic inflammatory changes are, of course, always present.

Epithelial proliferation associated with salpingitis. The diameter of the tube is greatly increased by what appears to be solid tissue.

Epithelial proliferation associated with salpingitis.

Epithelial proliferation associated with salpingitis. At higher power, the combination of inflammatory infiltrate and epithelial proliferation is apparent.

Reactive atypical hyperplasia may be distinguished from adenocarcinoma by the lack of solid epithelial areas, a feature nearly always seen in tubal carcinoma, the presence of only mild to moderate nuclear atypia and sparse, normal mitotic figures. Adenocarcinoma commonly shows moderate to severe atypia with prominent nucleoli and frequent mitotic figures.

Inflammation of the Fallopian Tubes

Inflammatory disease resulting from infection of the fallopian tubes and adjacent ovary is an increasing problem. The investigation and treatment of women with the disease is demanding more and more in the way of time and other resources. Identification of the disease early in its natural history is important to enable treatment to be effected before the damage becomes extensive and the consequent surgery destructive.

Infectious Salpingitis

Infectious salpingitis may be divided into the two major categories of non-granulomatous and granulomatous (or tuberculous) salpingitis.

Non-Granulomatous Salpingitis

Non-granulomatous salpingitis is predominantly a disease of young, sexually active women, and 70% of those with the disease are under the age of 25. Other factors that have an influence on the development of salpingitis include the method of contraception, induced abortion, and instrumentation of the cervix. Among the infectious organisms responsible for salpingitis, Chlamydia trachomatis and Neisseria gonorrhoeae remain of paramount importance and are responsible for ascending salpingitis. Other causative microbial agents are the anaerobic bacteria (bacteroides, clostridia, and streptococci), Mycoplasma hominis , and Ureaplasma urealyticum , and miscellaneous organisms such as Haemophilus influenzae and group A streptococci. Bacterial vaginosis is a common concurrent disorder of women with acute salpingitis, and bacterial vaginosis microorganisms are commonly isolated from the upper genital tracts of patients with pelvic inflammatory disease. Salpingitis caused by Actinomyces israelii is associated with the presence of an intrauterine contraceptive device, and may result in the development of a tubo-ovarian abscess ( Figure 21.10 ). Actinomyces -like organisms can be identified in the pus ( Figure 21.11 ). In practice, however, microbiologic investigations often show that the cultured material is already sterile by the time of the investigation, or else there is a combination of organisms.

Actinomyces infection causing a tubo-ovarian abscess.

Actinomyces -like organisms in pus.

The spread of etiologic organisms from the lower to the upper genital tract is canalicular, through the cervical canal and endometrial cavity and then into the fallopian tubes. Blockage of this route, either by cornual resection of the fallopian tubes or by sterilization, reduces the risk of salpingitis. Salpingitis begins as a mucosal rather than a serosal infection.

Gross Features

In the acute phase of the disease, the tube is swollen, edematous, and congested. The acutely inflamed tube is rarely seen histologically, as treatment of the acute phase is medical rather than surgical.

In chronic salpingitis, the tube is thickened and congested, with adhesions on the surface, often binding the tube and ovary closely together. A pyosalpinx is a grossly enlarged tube, increased in both diameter and length, and containing pus. A hydrosalpinx characteristically shows a fusiform shape and is greatly enlarged with paper-thin walls. In both conditions, the fimbrial ends fuse, sealing the tube. Not uncommonly, the fimbriae cannot be identified.

Microscopic Features

The plicae are greatly swollen and densely infiltrated by neutrophils ( Figure 21.12 ). The epithelial cells soon lose their cilia and the epithelium is shed in severe disease. The lumen contains pus ( Figure 21.13 ). As the disease progresses to chronic salpingitis ( Figures 21.14 and 21.15 ), the inflammatory infiltrate consists predominantly of plasma cells and then lymphocytes. The progression from acute to chronic non-granulomatous salpingitis may take several courses. If the fimbrial end of the tube remains patent, a chronic interstitial salpingitis may ensue, in which case the tube is thickened and the plicae fuse to form epithelial-lined cysts, which are the hallmark of chronic salpingitis. ‘Follicular salpingitis’ ( Figure 21.16 ) rather confusingly refers to the epithelium-lined spaces rather than lymphoid collections. The inflammatory process may eventually become quiescent, leaving only the architectural sequelae of chronic salpingitis ( Figure 21.17 ). Severe inflammation in the tube may spread to the adjacent ovary, resulting in a tubo-ovarian abscess ( Figure 21.18 ). Occlusion of the fimbrial end of the tube prevents release of the tubal contents, so that a pyosalpinx may result ( Figure 21.19 ). In pyosalpinx, the lumen is filled with pus ( Figure 21.20 ) and the wall is thinned, although the attenuation is commonly less marked than in hydro­salpinx. Acute and chronic inflammatory cells infiltrate the plicae and wall. As the exudate is reabsorbed into the tubal wall concurrently with the quiescence of the inflammatory process, clear fluid replaces this pus and a hydrosalpinx results ( Figures 21.21 and 21.22 ). In hydrosalpinx, the epithelium is generally thin and non-ciliated, although a few areas of morphologically normal cells may be seen. The wall of a hydrosalpinx is markedly thinned, with attenuation of smooth muscle and plicae. Usually, by this advanced stage in the disease process, there is little, if any, residual inflammatory infiltrate in the tissues of the wall. From a practical point of view, hydrosalpinx with tubo-ovarian adhesions is commonly misdiagnosed as ovarian ‘serous cystadenoma’ since it commonly presents as an adnexal mass. A careful microscopic examination identifying the muscular layer is diagnostic for hydrosalpinx. A small hydrosalpinx in which there is plical conglutination will have a ‘honeycomb’ cut surface and is termed a ‘hydrosalpinx follicularis’ ( Figure 21.23 ). The relations among these inflammatory changes are shown in Figure 21.24 .

Acute salpingitis. The plicae are edematous and infiltrated by neutrophils.

Acute salpingitis. The lumen is filled with pus and the plicae are engorged and inflamed.

Chronic salpingitis. In this early stage of the disease, the plicae are infiltrated by plasma cells and lymphocytes and there is pus in the lumen. The epithelium is intact, although containing inflammatory cells.

Chronic salpingitis. The infiltrate is now predominantly lymphocytic, with germinal centers.

Chronic salpingitis. The plicae are partly fused, forming separate epithelium-lined spaces or ‘follicles’ separate from the central lumen (‘follicular salpingitis’). Inflammation is still active.

Chronic salpingitis, healed. The inflammation has subsided and is near absent, but the plicae remain fused by fibrosis.

Tubo-ovarian abscess. The central mass is the ovary, which contains an abscess. Its cavity communicates with pus in the lumen of the tube (arrow).

Pyosalpinx.

Pyosalpinx. The lumen contains pus.

Hydrosalpinx.

Hydrosalpinx. The convoluted shape (often called ‘retort shaped’) of the tube is seen on section.

Hydrosalpinx follicularis.

Relations among the appearances and stages of inflammation of the fallopian tube.

The term ‘pelvic inflammatory disease’ (PID) implies chronic salpingitis with involvement of the surrounding structures, including ovary and parametrium. Adhesions are present on the surface of the tube, often spreading to involve the uterine serosa. PID typically has remissions and exacerbations and is difficult to eradicate. As a result of this cycle of events, in which acute salpingitis leads to chronic salpingitis, quiescence and then an exacerbation of the acute episode again, the histologic finding of acute and chronic salpingitis is commonplace. In these circumstances, the background architectural features of chronic salpingitis are seen, but the cellular infiltrate is predominantly of neutrophils, with pus in the lumen.

Gross Features

In the acute phase of the disease, the tube is swollen, edematous, and congested. The acutely inflamed tube is rarely seen histologically, as treatment of the acute phase is medical rather than surgical.

In chronic salpingitis, the tube is thickened and congested, with adhesions on the surface, often binding the tube and ovary closely together. A pyosalpinx is a grossly enlarged tube, increased in both diameter and length, and containing pus. A hydrosalpinx characteristically shows a fusiform shape and is greatly enlarged with paper-thin walls. In both conditions, the fimbrial ends fuse, sealing the tube. Not uncommonly, the fimbriae cannot be identified.

Microscopic Features

The plicae are greatly swollen and densely infiltrated by neutrophils ( Figure 21.12 ). The epithelial cells soon lose their cilia and the epithelium is shed in severe disease. The lumen contains pus ( Figure 21.13 ). As the disease progresses to chronic salpingitis ( Figures 21.14 and 21.15 ), the inflammatory infiltrate consists predominantly of plasma cells and then lymphocytes. The progression from acute to chronic non-granulomatous salpingitis may take several courses. If the fimbrial end of the tube remains patent, a chronic interstitial salpingitis may ensue, in which case the tube is thickened and the plicae fuse to form epithelial-lined cysts, which are the hallmark of chronic salpingitis. ‘Follicular salpingitis’ ( Figure 21.16 ) rather confusingly refers to the epithelium-lined spaces rather than lymphoid collections. The inflammatory process may eventually become quiescent, leaving only the architectural sequelae of chronic salpingitis ( Figure 21.17 ). Severe inflammation in the tube may spread to the adjacent ovary, resulting in a tubo-ovarian abscess ( Figure 21.18 ). Occlusion of the fimbrial end of the tube prevents release of the tubal contents, so that a pyosalpinx may result ( Figure 21.19 ). In pyosalpinx, the lumen is filled with pus ( Figure 21.20 ) and the wall is thinned, although the attenuation is commonly less marked than in hydro­salpinx. Acute and chronic inflammatory cells infiltrate the plicae and wall. As the exudate is reabsorbed into the tubal wall concurrently with the quiescence of the inflammatory process, clear fluid replaces this pus and a hydrosalpinx results ( Figures 21.21 and 21.22 ). In hydrosalpinx, the epithelium is generally thin and non-ciliated, although a few areas of morphologically normal cells may be seen. The wall of a hydrosalpinx is markedly thinned, with attenuation of smooth muscle and plicae. Usually, by this advanced stage in the disease process, there is little, if any, residual inflammatory infiltrate in the tissues of the wall. From a practical point of view, hydrosalpinx with tubo-ovarian adhesions is commonly misdiagnosed as ovarian ‘serous cystadenoma’ since it commonly presents as an adnexal mass. A careful microscopic examination identifying the muscular layer is diagnostic for hydrosalpinx. A small hydrosalpinx in which there is plical conglutination will have a ‘honeycomb’ cut surface and is termed a ‘hydrosalpinx follicularis’ ( Figure 21.23 ). The relations among these inflammatory changes are shown in Figure 21.24 .

Acute salpingitis. The plicae are edematous and infiltrated by neutrophils.

Acute salpingitis. The lumen is filled with pus and the plicae are engorged and inflamed.

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