Adenomyomas of Vagina, Rectum, Sigmoid Colon, and Ovary

A History of Endometriosis

6. Adenomyomas of Vagina, Rectum, Sigmoid Colon, and Ovary

Ronald E. Batt¹

(1)

State University of New York at Buffalo, Buffalo, New York, USA

Abstract

Diagnosis and surgical treatment of adenomyomas of the rectovaginal pouch of Douglas, so-called adenomyomas of the rectovaginal septum, awaited emergence of surgical pathology in the late nineteenth century. The subspecialty of surgical pathology in North America developed in academic departments of surgery at Johns Hopkins (gynecology), Columbia-Presbyterian, and Washington University-Barnes Hospital and in non-university settings at Memorial Hospital, The Mayo Clinic, and the Armed Forces Institute of Pathology.¹

Extrauterine Adenomyomas

In 1896 Cullen described his first case of an extrauterine adenomyoma, an adenomyoma of the round ligament of the uterus.² Recently awakened by von Recklinghausen to the significance of uterine adenomyomas, Cullen adopted his descriptive term adenomyoma.³ However, Cullen modified the term. He inserted a hyphen separating adeno from myoma – creating adeno-myoma – to comport with his conviction that the adenomatous tissue flowed into chinks and thereby modified a preexisting myoma.

Even more interesting, Cullen found the pseudo-glomerular structures of von Recklinghausen. Examining thin histologic sections cut with a microtome, Cullen recognized, described and illustrated a microscopic section of a pseudo-glomerulus. “Traversing the nodule in all directions are glands … surrounded by stroma similar to that of the uterine mucosa. It would be impossible to distinguish some of these from uterine glands.” Cullen continued: “In many places the glands present a peculiar arrangement and correspond to v. Recklinghausen’s pseudo-glomeruli.”⁴ Cullen postulated the pathogenesis of adeno-myoma of the round ligament from müllerian rests, but not without homage to von Recklinghausen. “The glandular elements in our case correspond very closely to those found by v. Recklinghausen in adeno-myomata of the uterus. In those cases he was able to trace a marked resemblance between the tumor glands and remains of the Wolffian body, and came to the conclusion that the glands were derived from this source. While admitting the probability of the glands in our case being due to remains of the Wolffian body, we cannot, from their striking resemblance to those of the uterine mucosa, and from the fact that their stroma resembles that of the mucosa, refrain from suggesting the possibility that they may be due to an abnormal embryonic deposit of a portion of Müller’s duct.”⁵

This conclusion indicates that, while Cullen could not attribute an isolated adenomyoma of the round ligament to direct invasion from the uterine mucosa, he could remain consistent with a müllerian pathogenesis of both the uterine and extrauterine lesions by attributing the latter to embryonic müllerian rests. Cullen argued by analogy. The microscopic appearance of the adenomyoma of the round ligament resembled the microscopic appearance of uterine endometrium; hence he concluded both must be derived from müllerian tissue, not Wolffian tissue. In his extrauterine case, Cullen was not as confident of his argument as he was in asserting the demonstrable pathogenesis of diffuse uterine adenomyomas. In 1898, Cullen published further observations on adenomyomata of the round ligament.⁶Despite the commotion raised by the Flexner report, Cullen continued active research and described umbilical tumors containing uterine mucosa in 1911 and 1912 and abdominal wall tumors that he also attributed to misplaced remnants of Müller’s duct.⁷ He returned to adenomyomas of the round ligament in 1916.⁸ Disorders of the umbilicus so fascinated him that as his last definitive work he wrote a large monograph on the Embryology, Anatomy, and Diseases of the Umbilicus in 1916.⁹

Notwithstanding his publications on extrauterine adenomyomas of the upper pelvis and abdominal wall, Cullen and his fellow gynecologic surgeons at Johns Hopkins – including Howard Kelly – apparently remained oblivious to the presence of extrauterine adenomyomas deep in the female pelvis.¹⁰ Given the volume of gynecologic surgery at Johns Hopkins Hospital and the severity of the disease encountered, it seems unlikely that Cullen – with his interest in the disease – had not encountered an adenomyoma of the bowel or pelvic floor during manual exploration of the pelvis and abdomen in all those years. How can one explain Cullen’s apparent lack of peripheral vision? One must remember that Cullen first encountered a uterine adenomyoma in the laboratory while examining uterine fibroids for one of Howard Kelly’s studies. While fibroids may distort the uterus, they are usually confined to the uterus, or if they extend outward and become intraligamentary, they usually remain attached to the uterus. Completely isolated parasitic fibroids are uncommon. Cullen probably assumed that most adenomyomas – like fibroids – were confined to the uterus or the round ligaments and he did not explore elsewhere. Moreover, Cullen and his colleagues usually performed supracervical hysterectomy in noncancerous cases. Given this surgical approach to benign pelvic conditions, they operated above adenomyomas of the rectovaginal septum.

Cullen awakened to the existence of deep pelvic adenomyomas in January 1913 when DSD Jessup, pathologist at the New York Skin and Cancer Hospital, sent him two specimens removed by William S. Bainbridge.¹¹Bainbridge, the first North American surgeon to remove adenomyomas of the rectovaginal septum, gave Jessup and his research fellow Archer Brown permission to publish both of his cases.¹²Jessup sent the surgical specimens to Cullen for his expert opinion and expected Cullen to confirm his diagnosis of adenomyoma of the rectovaginal septum.¹³ Cullen, long familiar with the naked-eye and microscopic appearances of extrauterine adenomyomas of the round ligament, replied to Jessup: “There is not a shadow of a doubt but that we are dealing with adenomyoma of the uterus in both cases. From what I can gather the growth is undoubtedly of the uterine type and not of the rectal and the fact that the rectal mucosa is perfectly normal and in no way encroached on also favors the idea of the uterine origin. Furthermore, if we are dealing with an adenomyoma of the rectum then we should expect the glands scattered throughout the tumor to consist of rectal glands and not uterine. Both of these growths are essentially adenomyomas of the uterus and they have undoubtedly involved the rectum secondarily. As you know, a certain number of these adenomyomas are particularly prone to form adhesions. This would naturally be more frequent in the cervical portion because the uterus there lies in close contact with the rectum.”¹⁴

Cullen later reported that “Within forty-eight hours after I had sent my report to Dr. Jessup, the February number of the Proceedings of the Royal Society of Medicine reached me, and in it was a similar case reported in full by Cuthbert Lockyer of London.”¹⁵ Alerted by Jessup in January and Lockyer in February to the existence of adenomyoma of the rectovaginal septum, at the June 1913 meeting of the Canadian Medical Association, Cullen “incidentally referred to two cases of this character that had recently come under [his] care.”¹⁶ On December 16, 1913 Cullen read a paper entitled “Adenomyoma of the rectovaginal septum” before the Southern Surgical and Gynecological Society in Atlanta, Georgia.¹⁷ Before the end of 1913, Cullen published his two cases complete with illustrations along with a review of Lockyer’s two cases, in the Transactions of the Southern Surgical and Gynecological Association.¹⁸ He evidently adopted the “rectovaginal septum” terminology from Lockyer. Cullen published the same data in the March 14, 1914 issue of the Journal of the American Medical Association.¹⁹

Cullen reported Lockyer’s cases in some detail and included an excellent microscopic illustration and a superb illustration of the en-bloc specimen of uterus and rectum.²⁰ An illustration of Lockyer’s case 2, labeled adenomyoma of the rectovaginal septum, actually shows a retrocervical adenomyoma with complete obliteration of the rectovaginal pouch of Douglas forming a false or “pseudo-septum” above the true anatomical rectovaginal septum that Denonvilliers described in 1836.²¹ The extent of invasion may be gauged by the fact that Lockyer performed a Wertheim radical panhysterectomy and en-bloc segmental resection of the rectum and permanent colostomy on the assumption that he was dealing with malignancy. In his discussion of Lockyer’s case, Cullen recognized the need for an accurate preoperative diagnosis. “Cancer of the rectum starts in the mucous membrane, gradually infiltrates the bowel and then extends to the peritoneum and at a later stage may involve the cervix. Clinically there is a history of hemorrhage from the bowel. In adenomyoma of the rectovaginal septum, on the other hand, the only rectal symptom is painful defecation, or there are obstructive symptoms. On rectal examination the bowel mucosa may be found puckered but still intact. Thus it is seen that the differential diagnosis is relative easy.”²²

Cullen saw his first case of adenomyoma of the rectovaginal septum in consultation on March 17, 1913 and operated the patient on 22 March. A classically beautiful illustration by Broedel, labeled as adenomyoma of the rectovaginal septum, actually shows a large retrocervical adenomyoma occupying the rectovaginal pouch of Douglas from its floor to the level of the internal cervical os of the uterus.²³The adenomyomatous mass formed not a “septum” but a voluminous mass with “islands of typical uterine mucosa and at another point … a miniature uterine cavity,”²⁴ the whole directly above, but not involving, the true anatomical rectovaginal septum of Denonvilliers.²⁵ Cullen described the operation. “I did a complete hysterectomy, removing the uterus and appendages, and then shelled out a myoma, 1 cm in diameter, from the left side of the pelvic floor and another, about 4 cm in diameter, with a secondary nodule, 1 cm in diameter, lying on its surface. The combined nodule was situated between the rectum and vagina on the left.”²⁶ Cullen dissected the adenomyomatous lesion from the rectovaginal pouch of Douglas without injury to vagina, rectum, or left ureter. His second case proved more challenging.

Cullen’s treatment of patients with adenomyoma of the rectovaginal septum was deeply influenced by the fatal outcome of his second surgical case reported in 1913.²⁷ Two years previously, in San Francisco, the patient had undergone a high subtotal hysterectomy and removal of both large cystic ovaries along with a small portion of the rectum “on account of dense adhesions.” The cervix and lower uterus were not removed. During a stormy postoperative course the patient developed a bowel obstruction. “After leaving the hospital she had a great deal of pain in the lower abdomen and for months had had almost continuous bleeding from the cervix.” The patient was admitted to Johns Hopkins Hospital on June 4, 1913 “much weakened from the loss of blood.” On examination “the right broad ligament was indurated and board-like” with thickening of the left broad ligament. Cullen and his staff tried to stabilize the patient without improvement and “a few days later felt that it was imperative to explore the abdomen.” At surgery Cullen found a 6 centimeter cystic adenomyoma with a 2.5 centimeter irregular cavity filled with “chocolate colored fluid;” the whole attached to the rectum. “We removed a greater part of the growth, but left a portion still attached to the rectum and did not dare explore the right broad ligament.”²⁸ At the start of surgery, the pulse was 45, but by the time the mass was partially removed, “the patient’s pulse had become almost imperceptible, the rate being between 180 and 190, although she had lost practically no blood.” The patient died postoperatively on June 10, 1913.

This case is reported in some detail because it directly influenced Cullen’s surgical judgment and led to his aggressive treatment of adenomyoma of the rectum and rectovaginal septum. Also, given his status as an authority on adenomyotic disease, Cullen was in a position to influence the surgical judgment of others. Even though the patient had continued to menstruate profusely, Cullen assumed that both ovaries had been completely removed by the surgeons in San Francisco. Cullen came to believe that even without the ovaries – that is, even with no ovariantissue remaining – severe adenomyotic disease of the rectovaginal septum would continue to worsen. Unfortunately for the patient, all ovarian tissue was not removed at the first surgery in San Francisco due to the dense adhesions encountered at that surgery. Remnants of ovary must have stimulated the uterus and caused profuse and nearly continuous uterine bleeding. The ovarian remnant syndrome was unknown when Cullen was writing.²⁹Notwithstanding, even if the San Francisco surgeons had known of the existence of the ovarian remnant syndrome, it is unlikely that they could have successfully found and removed the ovarian remnants deeply buried in adhesions in the pelvic side wall tissues. In 1913, curare was not available for use by anesthetists as an adjunctive agent to relax abdominal muscles to facilitate such tedious exploratory surgery.

On the other hand, had the surgeons in San Francisco removed all uterine tissue above the cervix, the patient would not have menstruated. Without continuous blood loss, she would have recovered her strength. However, the patient would have continued to suffer deep pelvic pain because ovarian hormones from ovarian remnants would have continued to stimulate the deep pelvic adenomyomas. This was a complicated case. Unfortunately, the surgeons in San Francisco did not remove all functioning uterine tissue so the patient continued to bleed profusely. When admitted 2 years later to Johns Hopkins Hospital she was in desperate circumstances and beyond help.

Cullen never did explain the profuse vaginal bleeding, but he did state clearly his theory of origin of these adenomyomatous lesions. “In my group of adenomyomas of the uterus were several of cervical origin. If these grow posteriorly, owing to their inherent tendency to become attached, they will spread out into the rectovaginal septum, and become adherent to the rectum; or the peritoneal surface of the cervix may grow fast to the peritoneal surface of the rectum. In either case the rectum becomes fixed to the cervix…. The glands in these growths undoubtedly arise from the uterine mucosa or from remnants of Müller’s duct.”³⁰

Cullen would consider neither the Wolffian rest theory of von Recklinghausen, nor the serosal theory of Iwanoff.³¹ Until a historic day in 1925, when he heard Sampson speak, Cullen held that the pathogenesis of adenomyomas of the rectovaginal septum arose from the uterine mucosa or from remnants of the müllerian duct, müllerian rests.³² Cullen republished his first two cases of adenomyoma of the rectovaginal septum in identical form in 1914 in volume 62 of the Journal of the American Medical Association.³³ Duplicate publication in this instance should not be judged by twenty-first century standards. Before World War I, except for subscribers to the Transactions of the Southern Surgical and Gynecological Association, physicians in private practice would have had to browse the printed Index Medicus to find his original article. Likely Cullen believed this subject sufficiently important that he needed to bring it to the attention of a national audience that could be reached through duplicate publication in the Journal of the American Medical Association.

Jessup read his paper before the Section on Pathology and Physiology of the Sixty-fifth Annual Meeting of the American Medical Association in Atlantic City, New Jersey in June of 1914. His article appeared in 1914 in volume 63 of the Journal of the American Medical Association.³⁴ It was illustrated with two simple drawings and five microscopic sections. The drawings show the retrocervical location of the adenomyoma in each case and also show precisely where the low- and high-power microscopic sections were taken. Jessup’s first case was a 36 year old married woman, Mrs. D, without children who presented with a 2 year history of “excessive menstruation, vaginal discharge and pain in the lower part of the abdomen.” On admission to the New York Skin and Cancer Hospital, examination revealed a “mass between the uterus and rectum and attached to each.” The preoperative diagnosis was “precancerous” uterus and “probable malignant mass in culdesac.” The surgeon Bainbridge performed total abdominal hysterectomy and bilateral salpingo-oophorectomy and “partial excision of the rectal wall.” In his pathology laboratory, Jessup observed: “To the portion of the posterior wall of the uterus there is attached by a band of fibrous tissue a section of rectal mucous membrane.” Microscopic examination showed glands and stroma that “resemble the uterine mucosa.” The second patient, a Mrs. F, was a 40 year old mother of two children, the youngest 13 years of age. “A distinct hard mass was felt in the culdesac of Douglas, beginning to adhere to rectum.” Again suspecting malignancy, Bainbridge performed a total abdominal hysterectomy, bilateral salpingo-oophorectomy, and partial excision of the rectal wall. Microscopic examination revealed “as in case 1, the rectal mucosa is normal. Beneath it is a growth of smooth muscle which extends through and is continuous with that of the cervix. Glands appear within 2 mm of the rectal epithelium.” Jessup noted the importance of Bainbridge’s willingness to operate these cases stating: “in both of our cases other surgeons had previously examined the patients and pronounced their condition inoperable on account of the apparent involvement of the rectum by a malignant growth.” Jessup continued: “That they may occur should be recognized by the surgeon, as the diagnosis can be made microscopically by a preliminary [histological] section [of a biopsy taken at surgery]. A simple excision of the mass would then cure the patient and there would be avoided the more serious operation of hysterectomy which would have been indicated if clinical diagnosis alone were relied on.”³⁵

Jessup’s reference to “preliminary section” alluded to Cullen’s rapid method of making an immediate intraoperative histologic diagnosis in the laboratory from a biopsy specimen while the patient was still on the operating table. Cullen’s technique of frozen section diagnosis from intraoperative biopsy specimens allowed the operating surgeon to proceed by selecting with renewed confidence the appropriate operative procedure based on whether the lesion was malignant or benign.³⁶

In the first decades of the twentieth century some surgeons like Lockyer, thinking they were operating for cancer of the rectum, initially performed Wertheim radical abdominal hysterectomy, with or without permanent colostomy, for adenomyomas of the rectovaginal septum.³⁷ Before the availability of frozen section diagnosis, confirmation of the preoperative diagnosis awaited examination of permanent histological sections of the surgical specimen. As surgical pathologists soon realized, adenomyomas of the rectum originated on the outer serosal surface of the rectum and invaded inwardly toward the rectal mucosa, but did not involve the mucosa. Whereas rectal cancer originated on the inner mucosal lining of the rectum and invaded outwardly through the rectal wall to spread to regional lymph nodes and by metastases to distant organs. In rectal cancer, the involved rectal mucosa was fixed to the cancer and did not move on rectal examination; in adenomyoma of the rectal wall the uninvolved rectal mucosa moved easily over the tumor.³⁸ Consequently, a careful rectal examination was sufficient to make a presumptive diagnosis of adenomyoma before operation. However, a definitive diagnosis required biopsy before or during surgery.

In 1915, Cullen reported his third case and second surgical fatality in a patient with adenomyoma of the rectovaginal septum. A 30 year-old unmarried woman had consulted him with “almost unbearable” pain that incapacitated her for 2 days before and after her menstrual period. The patient insisted on treatment. The fatality followed a complete hysterectomy and trans-anal low anterior resection of the rectum for adenomyoma of the rectovaginal septum with almost complete obstruction of the rectum. Cullen described the situation at surgery. “The growth, situated between the cervix and the rectum, was intimately blended with both … After the rectum had been freed for about eight inches the pelvis was packed with gauze and the anal margin all the way around was incised … About eight inches of rectum were then drawn through the anus and removed together with the growth. The rectum was then attached to the skin.”³⁹ When he described the surgical specimen, Cullen pondered a less radical surgical approach.

“The growth is a typical adenomyoma of the rectovaginal septum, evidently starting in or near the cervix and gradually invading the rectum by continuity, but respecting the rectal mucosa at all points. The bowel was so nearly obstructed, however, that we were forced to remove at least 8 inches. The ideal method would have been to excise the area of the growth and then close up the defect.”⁴⁰

In 1915, Stickney, in a brief five paragraph note, reported what might be the first case in the American literature of a discrete circumscribed extrauterine adenomyoma adherent to the left ureter, an adenomyoma simulating a ureteral calculus. Following a supravaginal hysterectomy for diffuse uterine adenomyoma of the uterus, Stickney dissected the left ureter free and then dissected the adenomyoma from the anterior surface of the ureter.⁴¹

In 1916, Cullen reported his fourth and fifth cases of adenomyoma of the rectovaginal septum, with illustrations showing the anatomical localization of the disease. He observed that the “growths occur in women, are noted in the childbearing period, are usually situated directly behind the cervix and as a rule, are firmly adherent to the rectum.”⁴² He carefully surveyed the literature in Index Medicus on adenomyomas of the rectovaginal septum; proposed a tentative classification system; detailed typical symptoms that patients complained of; described five surgical options depending on the severity of the disease; and speculated on pathogenesis. By 1916, Cullen had become aware of reports of adenomyomas of the rectovaginal septum dating back as early as 1910: Stevens, 1910⁴³; Nadal, 1911⁴⁴; Lockyer, 1913⁴⁵; Jessup, 1914⁴⁶; and Stevens, 1915.⁴⁷ In the discussion that followed Cullen’s presentation at the annual meeting of the American Medical Association in Detroit, Dr. Culbertson of Chicago called attention to Stevens’ claim that he had reported a case in 1909.⁴⁸ Culbertson also remarked on cases of “posterior paravaginitis and parametritis with proliferation of epithelium” that Robert Meyer had described in 1908 and to the more recent case of Aman which that author referred to as “retrocervical fibro-adenomatous serositis.”⁴⁹ Contrary to Robert Meyer’s suggestion that his lesion resulted from an inflammatory process, Cullen stated in his concluding remarks to the discussion that “In our cases of adenomyoma of the rectovaginal septum there has been no indication whatever of inflammation.”⁵⁰

In Cullen’s fourth case, clearly and unequivocally the adenomyoma occupied the rectovaginal pouch of Douglas (RVPD) and not the rectovaginal septum which extends from the base of the RVPD to the perineal body.⁵¹ The adenomyoma invaded deeply “extending out to the right pelvic wall and constricting some of the pelvic nerves … The mass in question was about 3 cm long and densely adherent to the side of the rectum, to the posterior vaginal wall, and also to the lateral wall of the pelvis.”⁵² On histologic examination, the interface between adenomyoma and normal tissue was “particularly instructive”: adipose tissue was gradually replaced by “connective tissue and here and there … muscle and connective tissues are enveloping the nerves” and accounted for the pain in the right side of the pelvis extending down the right leg.⁵³ Cullen described clearly how the invasive adenomyotic disease replaced adipose tissue and encircled nerves. “This was well shown in my Case 4 … Here the young connective tissue cells and the muscle fibers gradually replace the adipose tissue of the broad ligament, and finally engulf it completely. They encircle nerves and gradually compress them.”⁵⁴ Cullen described this tumor as “an adenomyoma of the type usually found in the rectovaginal septum, and in parts cannot be differentiated from an adenomyoma of the uterine wall.”⁵⁵

In Cullen’s fifth case, the illustration clearly and unequivocally shows an adenomyoma occupying the retrocervical portion of the rectovaginal pouch of Douglas and not the anatomical rectovaginal septum: “Adenomyoma of the rectovaginal septum. The black area between the cervix and rectum indicates the location and approximate size of the supposed inflammatory thickening …”⁵⁶ The patient had previously had a subtotal hysterectomy, with removal of the left tube and ovary and part of the right ovary. On August 7, 1912 the operating surgeon, Cullen’s colleague Dr. Richardson, described the pelvic mass as the size of a small hen’s egg that “was situated 4 cm from the anus. It had infiltrated the anterior surface of the bowel and extended out laterally.”⁵⁷ Richardson removed the mass composed of cervical stump, adenomyoma, and rectum. He sutured the rectum to the anus. Unfortunately, the patient died of surgical shock 10 h later. This was the third operative mortality for extrauterine adenomyomas at Johns Hopkins Hospital and the second mortality related to low resection of the rectum; the first such had been reported by Cullen in 1915. Cullen proposed a “tentative classification” of adenomyoma of the rectovaginal septum based on the Johns Hopkins experience and from data gleaned from the literature. He assigned cases to the stage he thought appropriate based on the extent of disease. In effect, Cullen made the first attempt to plot the natural history of this invasive lesion.

Small adenomyomas lying relatively free in the rectovaginal septum

Adenomyomas adherent to the posterior surface of the cervix and at the same time to the anterior surface of the rectum

Adenomyomas gluing the cervix and rectum together and spreading out into one or both broad ligaments

Adenomyomas involving the posterior surface of the cervix, the rectum and broad ligaments, and forming a dense pelvic mass that cannot be liberated⁵⁸

Even at this relatively early date, Cullen recognized that the adenomyomata of the rectovaginal septum was a progressive disease and that “a case which today belongs to Group 1 may in a few years belong to Group 2 or to Group 3.”⁵⁹ As the lesions progressed, patients complained of profuse menstruation, rectal pain, and pain with defecation.⁶⁰

At a meeting in Münster, Germany in 1912, Füth had discussed his experience with adenomyomatous lesions of the rectum and rectovaginal pouch and concluded that “although an excision of the rectum might appear to be indicated, the patients get well without it [i.e. if a portion of infiltrated bowel is left behind.]”⁶¹ This was a sensible conservative approach to surgical treatment of bowel adenomyoma in an era before antibiotics, and combined mechanical and antibacterial cleansing preparations of the bowel to neutralize dangerous bacterial flora of the rectum and large bowel. In 1912, surgeons were treating patients for adenomyoma-associated health and pain problems, not infertility. Either Cullen did not know of Füth’s conservative approach or rejected conservatism based on his personal experience. Cullen’s treatment of patients with adenomyoma of the rectovaginal septum was deeply influenced by the fatal outcome of the second case he operated and reported in 1913.⁶²

Cullen never did explain the profuse vaginal bleeding in his surgical fatality of 1913. Instead, 3 years later he expressed his conviction: “Some might argue that simple removal of the appendages [both tubes and ovaries] would cause atrophy of the uterine mucosa contained in the adenomyomas of the rectovaginal septum. My Case 2 is a sufficient answer. Although a supracervical hysterectomy had been performed two years before for a myomatous uterus; the pelvic condition had grown steadily worse.”⁶³

So saying and without further analysis, Cullen outlined his aggressive surgical management of adenomyoma of the rectovaginal septum. His surgical management, like his tentative classification, plotted the natural history of invasive adenomyomas of the rectovaginal septum: “(1) Where small discrete nodules exist in the posterior vaginal vault, these may be readily removed through a vaginal incision, as was so successfully done by Stevens. (2) Where the growth occupies the posterior surface of the cervix and extends laterally, after the ureters have been dissected out carefully, a complete abdominal hysterectomy should be performed. (3) If the growth be firmly adherent to the rectum, a wedge of the rectum should be removed, together with the uterus. It has been found best, after freeing the uterus on all sides, to open up the vagina anteriorly and laterally. The uterus and the rectum can then be lifted farther out of the pelvis, thus facilitating the removal of the necessary wedge of the anterior rectal wall. The uterus really acts as a handle, and the necessary rectal tissue and the uterus rare removed as one piece. (4) Where the lumen of the bowel is greatly narrowed, a complete segment of the rectum should be removed with the uterus, and an anastomosis should be made. (5) In desperate cases, where everything in the pelvis is glued together, as in my Case 2, an ideal operation is out of the question. The patient will not stand a long operation, and, if she could, a satisfactory result could not be obtained. In such a case it would be better to cut across the sigmoid, invert the lower end, close it, and bring the upper end out through the abdominal wall of the left iliac fossa, making a permanent colostomy. When the patient has to some extent regained her strength, the uterus, the lower portion of the rectum and the broad ligament tissue can be shelled out as one piece.”⁶⁴ Cullen concluded his aggressive surgical management of adenomyomas of the rectovaginal septum with a statement that confirmed his conviction that adenomyomata of the rectum and rectovaginal septum should be completely excised. “These growths, while histologically not malignant, remind one of glue. Unless they are completely removed, further trouble is liable to occur.”⁶⁵

Based on his personal experience and his knowledge of the literature, Cullen forcibly opined: “The glands in the adenomyomas of the rectovaginal septum look like, and act exactly like, those of the mucosa of the body of the uterus, and they undoubtedly arise from uterine glands or from remnants of Müller’s duct.”⁶⁶ Cullen’s default position, that adenomyomas of the rectovaginal septum were derived from “remnants of Müller’s duct,” would resurface in the latter part of the twentieth century as a vigorously defended theory for the pathogenesis of adenomyomas of the rectovaginal septum.⁶⁷

In 1916, Stevens related the English experience. “The origin of these tumours is still far from settled.” He listed four possible “sources: (1) the endometrium, (2) Müllerian remnants in the recto-vaginal septum, (3) Wolffian remnants in this situation, and (4) the peritoneal endothelium” [Iwanoff-Meyer theory]. Though he thought the origin from Wolffian remnants was “untenable,” he believed the origin from “Müllerian ducts … cannot be disproved.”⁶⁸ Opining that the origin from peritoneal endothelium appeared “to be an unnecessary theory,” Stevens mentioned specifically that Archibald Leitch, among others, was “inclined to favour the endometrium as the source of all adenomyomata, including those which, apparently, are isolated in the recto-vaginal septum.” Stevens explained: “The suggestion is that endometrial tubules grow out through the muscular coats of the uterus, accompanied by their own stroma and by a new growth of fibro-muscular tissue. This is obviously the case in the more common instances of diffuse adenomyomata of the endometrium, and the continuity of the tubules with the endometrial glands is easily demonstrated. In the case of growths in the recto-vaginal septum, however, the distance from the endometrium is considerable, and although it has been done, it is difficult to trace the continuity of the growth tubules with the endometrial glands. It is quite possible, too, that the connexion between the two has been completely lost during the process of growth. Once started, however, the tumour continues to grow whether it preserves its connexion with the endometrium or not.” ⁶⁹

Many investigators reported cases, but few analyzed as thoroughly as Thomas G. Stevens. He referred to a case of adenomyoma of the rectovaginal septum that he had “demonstrated” to the Obstetrical and Gynaecological Section of the Royal Society of Medicine in 1909, “as far as I can ascertain, this was the first case of the kind described in this country.”⁷⁰ In Stevens’ Case I, (the same case he demonstrated in 1909) the adenomyoma was accompanied by a cyst of probable Wolffian origin in the anterior vaginal fornix. He then described five additional cases, all with adenomyomas located in the posterior vaginal fornix.⁷¹ Stevens illustrated each case by a sagittal section drawing and by a drawing of the histology. Illustrations of all six cases show retrocervical lesions. In Case IV, “the true pouch of Douglas was … obliterated.” In addition to the adenomyoma in Case IV, Stevens considered it “very significant that in this case there was a large vaginal cyst as well as the adenomyoma. The vaginal cyst, there can be no doubt, is of Gartnerian [Wolffian] origin, as it extended some distance up the lateral wall of the vagina.”⁷² Stevens deduced that in the presence of one abnormality from Wolffian remnants, that “it seems possible” the adenomyomas “may have arisen also from some remnant … possibly a Müllerian duct abnormality.”⁷³ In Case VI the illustration shows the adenomyoma directly continuous with extensive adenomyosis of the posterior uterine wall.

Following his methodical case reports, in the “remarks” section of the article, Stevens stated “the growths were limited to the posterior fornix, but at the same time were closely adherent to the back of the cervix …” He continued: “the site⁷⁴ in which these growths are found in all my cases was the recto-vaginal septum.” It was then that Stevens corrected himself and made the following insightful comment: “Perhaps it is not quite correct to say the septum, because it was really in the loose connective tissue above the posterior fornix, which is bounded by the back of the cervix in front, the rectum behind, and the peritoneum above.”⁷⁵ To my knowledge this is the first statement in the medical literature that correctly localizes adenomyomas to the retrocervical portion of the rectovaginal pouch of Douglas.⁷⁶Stevens recognized this retrocervical site was not the anatomical rectovaginal septum; rather it was the wall of tissue that separates the posterior vaginal fornix from the anterior rectovaginal pouch of Douglas. Unfortunately, the strength of his conviction was insufficient to advocate a change in terminology. Neither did Stevens change the title of his article. Perhaps he could not think of a better term.

Cullen was well aware of Stevens’ article for he referred to it and cited it in a footnote.⁷⁷ Needless to say, we can conclude that Cullen was unimpressed with Stevens’ insight.⁷⁸ For Cullen, Stevens was just another investigator among many who had reported several cases. Cullen’s ear was attuned to Lockyer, a friend and fellow gynecologist and pathologist.⁷⁹ It was a classic case of initial conditions setting the terminology. In 1913, when Cullen sent his consultation to Jessup and received Lockyer’s article in the mail the following day,⁸⁰ the precedent for the nomenclature – adenomyoma of the rectovaginal septum – was already set for him; he did not question it. Stevens’ insight was published 3 years later in 1916, and apparently was not convincing. Cullen persisted in using the anatomically incorrect term “rectovaginal septum,” and thus – adenomyoma of the rectovaginal septum – became entrenched in the medical literature. Stevens made a second insightful comment regarding the life history of adenomyomas of the rectovaginal septum when he wrote: “nothing is known as to their rate of growth or the age at which they commence.”⁸¹ Cullen did not comment on that insight either.

Foster S. Kellogg of Boston⁸² was directly informed of the existence of adenomyomas of the rectovaginal septum and their aggressive surgical management by reading Cullen’s article in the Journal of the American Medical Association.⁸³ Kellogg seems to have been impressed by Cullen’s statement: “These growths, while histologically not malignant, remind one of glue. Unless they are completely removed, further trouble is liable to occur.”⁸⁴Kellogg reported a pelvic tumor in his patient that eroded through the posterior vaginal wall “with rather free bleeding.”⁸⁵ He described the findings at surgery. The tumor “was found to be an integral part of the cervix, the vagina and the rectum. It was determined to dissect it from the rectum and remove it with the uterus and vaginal cuff.”⁸⁶ Kellogg’s description of the rectal involvement is both graphic and typical of the invasive pattern of rectal adenomyomas. “The tumor apparently penetrated all coats of the rectum except the mucous membrane, and it was soon apparent that it would be impossible to dissect it free without opening the rectum; in addition, the rectum was accordioned onto the tumor, so that perhaps four or five inches was in apposition with the one to one and a half inch tumor (Italics added). In this way a very small nick, as the rectum was freed up, became a long rent.”⁸⁷

Kellogg performed a total hysterectomy, removed the vaginal tumor, the fallopian tubes, but did not remove the ovaries. He dissected the adenomyomatous tissue from the rectal wall and in the process opened and repaired three rents in the rectum. “The patient came off the table in shock, which persisted in considerable degree for 48 hours; she gradually improved … On the 8th day a recto-vaginal fistula developed, but the patient continued to pass gas and feces through the anus … At the end of the 7th week … only gas came through the fistula … at the end of the 8th week the fistula closed.” Pathology confirmed an infiltrating “adeno-leiomyoma.”⁸⁸ The patient lived.

Cullen published four more cases of adenomyoma of the rectovaginal septum in 1917. He began his discussion with a description of the constituent elements of deep pelvic adenomyomas of the rectovaginal septum, the precise anatomical area of their origin and their growth pattern. He retained his tentative classification and his aggressive surgical management outlined the previous year: [Description] “Adenomyoma of the recto-vaginal septum is a diffuse growth consisting of non-striated muscle and fibrous tissue with large or small areas of mucosa identical with the mucosa of the body of the uterus scattered throughout it. This mucosa swells at the menstrual period and, as there is usually no escape for the blood, the gland spaces tend to become cystic and are filled with blood; or there is hemorrhage into the matrix of the tumor.”⁸⁹ [Origin and Growth Pattern] Vaginal involvement was the crucial localizing feature. “The tumor in the beginning is very small and starts in the vaginal vault just behind the cervix; or it may be recognized as a round or irregular thickening, not over 1 cm in diameter, behind and usually attached to the cervix. The growth gradually spreads in a diffuse and irregular manner, involves the adjacent anterior rectal wall and spreads into one or both broad ligaments, until finally, everything in the pelvis may be firmly glued into one mass.”⁹⁰

Cullen’s Case 6 was the earliest rectovaginal adenomyoma he had seen to date. He removed the entire uterus, but not the tubes and ovaries. “On vaginal examination a small hard nodule could be felt in the vaginal vault just behind the cervix. On opening the abdomen we found in the mid-line just below and behind the cervix a puckered scar, about 1 cm in diameter.”⁹¹ Histologic section of the nodule revealed non-striped muscle and fibrous tissue containing “uterine glands surrounded by the characteristic stroma of the uterine mucosa [and in one area] a miniature uterine cavity.”⁹²

Max Broedel’s illustration of Cullen’s Case 7 is the most dramatic and explicit depiction of bilateral ureteral encirclement and compression by retrocervical adenomyomatous tissue – resulting in bilateral ureteral obstruction and bilateral hydroureter – that the author has ever seen.⁹³ Both ureters were encircled and constricted by the adenomyomatous growth in the broad ligaments, so much so that above the point of involvement the ureters were greatly dilated, each being over 1 cm in diameter.⁹⁴ The adenomyomatous growth was so aggressive that it “welled into the posterior vaginal vault, forming polypi, and in some places the growth has literally burst into the vagina, uterine mucosa projecting into and lining the vaginal vault.”⁹⁵ The patient bled from the endometriotic lesion of the posterior vaginal fornix. A very large sagittal section through the uterus, cervix, and vaginal cuff reveals unequivocally and explicitly the retrocervical location of the adenomyoma labeled “adenomyoma of the recto-vaginal septum with formation of vaginal polypi.”⁹⁶ Very large histological sections reveal typical adenomyomatous tissue consisting of “non-striated muscle and fibrous tissue … tubular glands lined with one layer of cylindrical epithelium and embedded in a stroma identical with that normally found in the mucosa lining the uterine cavity.”⁹⁷At surgery in 1914 the left ovary contained an orange-size cyst filled with old blood. However, in 1916 both ovaries appeared normal judging from Broedel’s full pelvic illustration depicting bilateral hydroureters.⁹⁸ Cullen performed a total hysterectomy and removed the left tube and ovary and dissected both ureters free. He did not attempt to remove the rectal adenomyoma because the patient’s condition deteriorated during surgery. Cullen removed the right tube but did not remove the right ovary. One can only surmise that he preserved the right ovary because of the patient’s young age, not wanting to precipitate premature menopause. But given the devastatingly aggressive nature of the disease in this 26 -year-old woman, did Cullen fully appreciate the potential consequences of leaving an ovary in the presence of invasive rectal adenomyomatous disease in a patient who had complained of “severe pain in the rectum which radiated down the left thigh”? To judge from Cullen’s decision, the pathophysiology of invasive adenomyotic disease was not fully appreciated in the World War I era, even at Johns Hopkins Hospital. In support of that conclusion we have the statement by Lockyer: “My own feeling is one of profound respect for the part played by ovarian tissue in convalescence after hysterectomy in the case of younger women.”⁹⁹

Whereas Cullen’s seventh case was extraordinarily interesting from both medical and medical-historical perspectives, his Case 8 turned desperate when he became entrapped by more extensive disease than he had anticipated. The patient was a 37 -year-old woman who “for the past year at least … had menstruated more frequently through the rectum than from the vagina” despite having undergone a supravaginal hysterectomy, removal of both fallopian tubes, appendix and the left ovary 2 years previously.¹⁰⁰ Examination elsewhere had revealed “a good deal of thickening in the vaginal vault behind the cervix” consistent with adenomyoma.¹⁰¹ The patient was admitted to Johns Hopkins Hospital and at surgery on May 26, 1917 Cullen “found the cervix firmly glued to the rectum over a wide area.”¹⁰² He removed the cervix with a cuff of vagina and the adenomyoma of the rectum en blocplanning to repair the surgical defect in the rectal wall.¹⁰³ However, Cullen ran into the same problem experienced by Kellogg, the accordion effect whereby the extent of the rectal involvement was greater than he anticipated. He found himself confronted with “only a ribbon of the posterior rectal wall about 1.5 cm broad; consequently we had to do a complete resection, removing about 12 cm of the rectum … with a two layer “end-to-end anastomosis.”¹⁰⁴The patient nearly died on the operating table. To compound the problem, a good amount of liquid fecal matter had spilled during the bowel resection. Consequently the postoperative course was “stormy” for two and a half weeks. On the seventh postoperative day feces escaped into the vagina through a rectovaginal fistula; on the tenth postoperative day urine escaped into the vagina through a vesico-vaginal fistula: in essence a cloaca.”¹⁰⁵

Examination of the surgical specimen showed that the “growth [occupied] the posterior wall of the cervix and … had extended to and involved the outer coats of the anterior and lateral rectal walls, and … also extended to the vaginal mucosa posterior to the cervix.”¹⁰⁶ A very large sagittal section through the surgical specimen showed a huge adenomyoma emanating from the posterior aspect of the cervix and involving almost the entire 12 cm length of excised rectum, a remarkable illustration.¹⁰⁷ Another large sagittal section– labeled as adenomyoma of the rectovaginal septum – clearly depicts an adenomyoma invading the posterior cervix and “extending into the rectum.”¹⁰⁸ A final large histological section shows the adenomyoma invading the rectal wall and “encroaching on the rectal mucosa.”¹⁰⁹

Case 9 was a 28-year-old woman with tuberculosis of both fallopian tubes. On examination, Cullen palpated “marked induration in the vaginal vault behind the cervix.”¹¹⁰ At surgery Cullen observed that “behind the cervix at the level of the internal os was a hard indurated mass, 2.5 cm in diameter. This involved the posterior wall of the cervix and the anterior wall of the rectum. The bowel wall and the uterine wall at this point were intimately blended together, [in other words] an adenomyoma of the rectovaginal septum.”¹¹¹ After removing both tubes and ovaries, the patient’s pulse rose, varying between 160 and 170 beats/min. Cullen deferred definitive surgery.

Based on his experience with nine patients with adenomyomas of the rectovaginal septum, Cullen described his treatment plan for future cases. “If the growth be firmly adherent to the rectum, a wedge of the rectum should be removed, together with the uterus. It has been found best, after freeing the uterus on all side, to open up the vagina anteriorly and laterally. The uterus and the rectum can then be lifted farther out of the pelvis, thus facilitating the removal of the necessary wedge of the anterior rectal wall. The uterus can be used as a handle, and the necessary rectal tissue and the uterus removed as one piece.”¹¹² This was the same technique he attempted with Case 8 before becoming entrapped.

Cullen viewed adenomyomas of the rectovaginal septum as invasive disease, albeit benign, that had to be totally excised because any remnants would resume growing and cause more problems. It seems likely that he based his aggressive surgical approach upon radical operations for carcinoma of the cervix reported by Sampson in 1905,¹¹³ and the even more successful 5-year survival results reported by Wertheim in 1907.¹¹⁴ He defended the aggressive treatment he had recommended in 1916 by writing: “Some might argue that simple removal of the appendages (tubes and ovaries) would cause atrophy of the uterine mucosa contained in the adenomyomas of the rectovaginal septum.”¹¹⁵ Recalling his second case that ended in a fatality, Cullen responded: “My Case 2 is a sufficient answer.”¹¹⁶ In desperate cases, “where everything in the pelvis is glued together, as in my Case 2, an ideal operation is out of the question.”¹¹⁷

For such desperate cases Cullen recommended a two-stage operation, repeating his advice of 1916 in explicit detail. “In desperate cases … it would be better to cut across the sigmoid, invert the lower end, close it, and bring the upper end out through the abdominal wall of the left iliac fossa, making a permanent colostomy. When the patient has to some extent regained her strength, the uterus, the lower portion of the rectum and the broad ligament tissue can be shelled out as one piece.”¹¹⁸

This would not be the last time that Cullen would offer this advice. Incomplete knowledge of the pathogenesis and pathophysiology of adenomyomata of the deep pelvis often led to heroic surgery as Cullen and other pioneers attempted by trial and error to work out the safe and appropriate surgical management of extensive extrauterine adenomyotic disease. As noted above, the second stage amounted to a posterior exenteration with total removal of the uterus, tubes and ovaries, all adenomyotic disease and the rectum.¹¹⁹ In effect, Cullen consciously chose a permanent colo-cutaneous fistula (colostomy) in order to avoid a rectovaginal fistula or vesicovaginal fistula or disastrous double fistulas with feces and urine pooled in a vaginal cloaca. In 1908, Sampson had graphically illustrated and discussed a complication of uterine cancer: “a cloaca into which both the rectum and bladder empty.”¹²⁰Henceforth Cullen wanted to avoid this dreaded complication.

Lockyer published a monograph in 1918 summarizing the medical literature on uterine fibroids and uterine adenomyomas up to the early years of World War I (1914–1918).¹²¹ Citing Robert Meyer’s article in 1903, Lockyer noted that, lacking a true submucosa, the mucosa of the uterus and fallopian tube has the capacity to invade the surrounding muscle. Meyer had gone to great lengths to explain that mucosal invasion was not synonymous with malignancy.¹²² Nonetheless, Lockyer reported cases of carcinomatous change in uterine adenomyoma with metastases to the liver.¹²³ Cullen acknowledged that Cuthbert Lockyer had a remarkable command of the foreign literature.¹²⁴ Lockyer emphasized contributions to the literature on “extrauterine” adenomyomas for the benefit of his British audience.¹²⁵

He collected 47 cases of adenomyoma of the recto-genital space between 1897 and 1915. The first was that of the well-known German gynecologist, Johannes Pfannenstiel in 1897.¹²⁶ The second case was reported by von Herff the same year.¹²⁷ The third report, from Ludwig Pick in 1899 described a diffuse adenomyoma of the posterior vaginal fornix.¹²⁸ “The tumor lay above the posterior fornix; it was the size of a plum, and slightly movable, but the vaginal wall was firmly fixed to it; the mucous surface of the vagina was smooth and intact. Histologically the growth consisted of muscle and branching gland-tissue; it resembled the growths shown by Pfannenstiel and von Herff.”¹²⁹ Much can be learned by consideration of a few more of these early cases, for they give the reader an idea of the invasiveness of adenomyomas of the pelvic floor. Lockyer described the fourth case, that of Schickele.¹³⁰“Schickele described a small hard growth the size of a nut; it lay in the upper half of the posterior vaginal wall, at the level of the portio vaginalis,”¹³¹ and the vaginal mucosa was moveable over it, but the growth was very adherent to the rectum, so that a part of the bowel was removed with the tumour … the uterus was removed on the assumption that it was the seat of the hypothetical primary malignant focus. The case was one of an “adenofibroma, the greater part of which lay in the recto-vaginal septum, and the smaller part in the submucosa of the vagina.”¹³² The last of the early cases was that of Füth.¹³³ In 1903 he performed a Wertheim radical hysterectomy on a 31-year-old woman who had never borne a child. On examination the “posterior vaginal vault was depressed and there was an ulcerated surface the size of half-a-crown on the posterior vaginal wall, extending nearly to the external os. A fixed growth the size of a fist lay behind the cervix and uterus; it extended on the right to the pelvic wall, on the left it projected only slightly beyond the cervix. The rectal mucosa could be moved over the growth. [This indicated that the growth was not a rectal cancer.] The rectum was not resected.” The mass extending to the right pelvic wall was not resected either. In 1905, 2 years after surgery, the patient was in good health.¹³⁴ Lockyer’s 31st case of adenomyoma of the recto-genital space was his own case that he had reported in 1913.¹³⁵

Lockyer stressed that the differential diagnosis of adenomyoma of the rectovaginal space must include cancer of the rectum and vagina. He did acknowledge the value of the clinical sign of “freedom of movement” of the rectal mucosa over an adenomyomatous lesion,¹³⁶ and that rectal malignancy would fix the mucosa to the tumor. Unlike Cullen, who seemed to put more faith in the accuracy of clinical diagnosis, Lockyer did not recommend relying on clinical examination to differentiate carcinoma from benign invasive adenomyomas of the rectovaginal septum. He believed that biopsy was necessary to rule out malignancy. Also, the presence of uterine fibroids or adnexal masses tended to interfere with diagnosis of adenomyoma of the recto-genital space. In such circumstances Lockyer stated that laparotomy may be required for accurate diagnosis.¹³⁷

Lockyer noted that Cullen was dogmatic in stating that “the glands in these growths undoubtedly arise from the uterine mucosa, or from remnants of Müller’s duct.”¹³⁸ According to Lockyer, Cullen was equally dogmatic about treatment, stating, “When the growth has invaded the rectum to a limited extent, it is necessary to remove only a small portion of the anterior wall of the rectum … When the rectal involvement is extensive, as in Lockyer’s Case 2, resection of that portion of the bowel will, as a rule, be necessary.”¹³⁹ This aggressive surgical approach coincided with Cullen’s views on prognosis: “If portions be left these will continue to grow, and will lead to more pelvic adhesions, and finally produce complications that may result in death or permanent invalidism.”¹⁴⁰ Relying on their own clinical experience, authorities on this enigmatic disease sometimes found themselves not only physically separated by the Atlantic Ocean, but nearly as separated in their recommendations for treatment.¹⁴¹

Lockyer, like Füth, believed it was not necessary to remove all adenomyomatous disease from the rectum: “For extensive growths in the recto-genital space, it has been shown that total removal or excision of the invaded bowel is, as a rule, unnecessary.”¹⁴² However Lockyer believed that operation was indicated for invasive lesions of the bowel to relieve stenosis and chronic intestinal obstruction and for invasive lesions of the posterior vaginal fornix to prevent ulceration and bleeding.

Treatment of bowel endometriosis marked a frontier of medical science in the first two decades of the twentieth century. Two of the leading practitioners, Lockyer and Cullen, had completely different approaches to the problem. Lockyer’s approach proved better when both tubes and ovaries were removed. Operating in the 1920s, John Sampson set the standard in North America by successfully following the example of Füth and Lockyer. For extensive endometriosis in the absence of bowel obstruction, Sampson performed a hysterectomy, removed both tubes and ovaries as well as easily accessible endometriotic lesions, but he did not resect the bowel. In short, Sampson did not follow the advice of Cullen. How does one account for Cullen’s aggressive approach to bowel endometriosis? Likely based on his adverse experience, Cullen came to the belief that hormone-resistant endometriosis would continue to invade the bowel and cause problems even after hysterectomy and removal of both tubes and ovaries. However, such was not the case, except in rare instances. Such a rare case of hormone-resistant endometriosis following total abdominal hysterectomy and bilateral salpingo-oophorectomy with supporting correlative studies of steroid receptor content and histology was reported in the last decade of the twentieth century.¹⁴³

In 1918, less than two decades after the introduction of radiation therapy, Lockyer reported disappointing results with all types of radiation therapy applied to adenomyomas. “All forms of radio-therapy (Radium, X-Rays, Mesothorium) for adenomyoma are disappointing; only in one case, that of Griffith’s, have I ever heard of radium doing good. It is my belief that such treatment is liable to excite the inflammatory process, which is the pathological basis of the disease.”¹⁴⁴ The year before, Cullen had expressed similar disappointment with the results of radium treatment of his adenomyoma of the rectovaginal septum. “In Case 7 the patient was too weak to allow us to resect the bowel and a portion of the growth still remains n the anterior recto-vaginal wall. Radium had been used, but the growth in the rectal wall is becoming thicker and sooner or later, I believe, it will be necessary to remove the portion of the rectum that is involved.”¹⁴⁵

By 1918 Lockyer could state: “The literature on adenomyoma of the recto-genital space is already quite extensive, and the condition is now sufficiently well recognized to prevent the error of treating it as a malignant process – an error which more than one operator excusably made, before the true benign character of the infiltrating adenomyoma was properly understood.”¹⁴⁶ Lockyer defined adenomyoma. “The term ‘adenomyoma’ implies a new formation composed of gland-elements, hyperplastic cellular connective tissue, and smooth muscle.”¹⁴⁷ The symptoms or complaints of patients with recto-vaginal adenomyomas are “far more distinctive and definite” compared to adenomyomas confined to the uterus. The chief complaint was pain – painful intercourse, pain with bowel movement. Over time, some patients suffered from “blood-stained vaginal discharge” if the endometriosis invaded anteriorly through the retrocervical area into the posterior vaginal fornix, and obstinate constipation leading in some cases to actual bowel obstruction, if the endometriosis invaded posteriorly and deeply into the bowel wall and constricted the lumen of the rectum or sigmoid colon.¹⁴⁸ None of the cases reported by Lockyer experienced rectal bleeding because endometriosis rarely invades through the submucosa of the bowel.¹⁴⁹ Recall that the uterus and vagina have no submucosa to act as a barrier to invasion, but the rectum, large and small intestine do have a submucosa to limit invasion.

Contrary to Cullen’s earlier assertion that: “In our cases of adenomyoma of the rectovaginal septum there has been no indication whatever of inflammation,”¹⁵⁰ Lockyer and other investigators believed inflammation was involved in the pathogenesis of pelvic adenomyomas. Many investigators in this period noted the frequent association of adenomyoma with pelvic peritonitis. Lockyer called attention to tuberculosis, with demonstrable tubercle bacilli frequently contributing to the inflammation associated with tubal adenomyomas in the nineteenth and early twentieth centuries.¹⁵¹ He summarized: “The intimate relationship with pelvic peritonitis is of great importance for the point of view of prognosis. Therefore, if we summarize the outlook, we must regard an ‘adenomyoma’ as a hemorrhagic and painful structure which is found in bad company, its intimate associates being adnexal tumours, pelvic peritonitis, parametritis, and infiltrations into bowel, whilst it can claim caseating tubercle, carcinoma, and sarcoma as causal acquaintances.”¹⁵²

Lockyer described the clinical signs detected by vaginal and rectal examination, in patients with moderate to advanced disease. Reminiscent of Robert Meyer’s 1908 theory of an inflammatory pathogenesis, Lockyer stated in 1918 that: “Broadly speaking, the physical picture is that of a spreading inflammatory induration felt in the posterior fornix of the vagina. The posterior vaginal wall in all marked cases is most intimately adherent to, and is penetrated by, the growth. Puckerings, petechiae, actual haemorrhagic points, ulcerations, polypoid fringes, and teat-like projections are to be found on the free surface of the posterior vaginal fornix” when viewed through a vaginal speculum. He continued: “the posterior wall of the cervix beneath the peritoneal reflection is fixed by the invading adenomyomatous process. The mobility of the cervix as a whole is lost. The anterior wall of the rectum beneath the peritoneum is fixed to the indurated mass … between the bowel and the cervix uteri.”¹⁵³ (Lockyer’s italics).

Lockyer’s descriptions – Beneath the peritoneum and beneath the peritoneal reflection – refer not to the normal peritoneal floor of the anatomical rectovaginal pouch of Douglas, but to a false floor created above the invasive disease by fusion of the visceral peritoneum of the cervix and uterus to the visceral peritoneum of the rectum. Thus a vertical pseudo-rectovaginal septum is formed above the true anatomical rectovaginal septum of Denonvilliers by fusion of diseased cervix and uterus to the rectum. This obliterates the rectovaginal pouch of Douglas. The true anatomical rectovaginal septum of Denonvilliers located below remains intact and uninvolved with invasive adenomyotic disease.

Lockyer had described a completely frozen pelvis with obliteration of the rectovaginal pouch of Douglas by extensive, invasive endometriotic disease. Pioneer pelvic surgeons in the early decades of the twentieth century had to deal with such extensive disease. The more aggressive the surgical approach, the greater risk for complications. Examination of tissue under the microscope revealed the remarkable resistance of the submucosa of the rectum, a barrier that prevented extrauterine adenomyotic disease from burrowing into the lumen of the bowel. In Lockyer’s experience: “The invasion has never been proved histologically to go beyond the submucous [submucosa] into the mucous coat of the bowel.”¹⁵⁴ In sharp contrast adenomyotic disease invaded completely through the posterior vaginal wall into upper vagina behind the cervix. Furthermore, in the vagina wall – lacking a submucosa – “the gland-tubules have been shown to have burst through the mucous membrane.”¹⁵⁵

From his description of invasive adenomyomas of the rectovaginal pouch of Douglas one can readily appreciate why more research was needed to achieve early diagnosis, safe treatment, and to understand the pathogenesis and pathophysiology of extrauterine pelvic adenomyomas.

At the end of World War I, the debate over pathogenesis of adenomyoma of the intestinal tract centered on “foetal relics or whether it is a purely inflammatory process accompanied by the phenomenon of epithelial heterotopy” of Meyer.¹⁵⁶ Lockyer, referring to Archibald Leitch’s recent concept of ‘migratory adenomyoma,’ was concerned that it was “liable to convey a wrong impression if it is taken to mean that the uterine mucosa is the fons et origo[source and origin] of all adenomyomas.”¹⁵⁷ Lockyer added emphatically: “Adenomyoma is not confined to the uterus, nor is it always dependent upon changes in the adult mucosa. It is a pseudo-neoplasm, the result of an inflammatory lesion in the neighborhood of an epithelial tract.”¹⁵⁸ Outside of a single case of adenomyoma invading the floor of the urethra, Lockyer did not identify any adenomyomas of the urinary tract. He confirmed that during pregnancy, characteristic decidual changes occur within uterine and extrauterine adenomyomas and noted Cullen’s position that Whitridge Williams’ famous case of decidual reaction of pregnancy in diffuse uterine adenomyoma “proved” the origin of the tissue from uterine mucosal invasion.¹⁵⁹ Robert Meyer’s research indicated that rare cystic adenomyoma in the midline of the uterus might have a fetal origin from the epithelium of the müllerian ducts before the formation of the glands of the uterine mucosa, or cystic adenomyomas might develop from mature mucous membrane of the uterine corpus.¹⁶⁰ “The central sagittal plane of the uterine body is the situation where Meyer has found epithelial rests in foetal uteri and in uteri up to the age of puberty.”¹⁶¹ Frankl described a cystic adenomyoma in the sagittal plane of the uterine fundus and like Meyer attributed its development from embryonic müllerian tissue.¹⁶²

Writing during World War I (1914–1918), Lockyer stated: “I cannot bring myself to admit that the mature uterine mucosa has ever been proved to have provided the gland-tissue in any extrauterine growth, wherever situated. [Alluding to the metaplasia theory of Iwanoff-Meyer, Lockyer opined]: It is much more likely that the peritoneum or vagina is the source of the epithelium in the majority of cases. That Müllerian relics may play a part in the formation of some recto-vaginal ‘tumours’ is quite probable.”¹⁶³ Such were the convictions of Cuthbert Lockyer, who had conducted the most extensive review of the literature on uterine and extrauterine adenomyomas and had weighed the theories of pathogenesis of the leading academic investigators.

Lockyer gathered all the classifications of adenomyotic disease up to 1916 except Cullen’s 1916 classification of extrauterine adenomyomas:

Von Recklinghausen classified uterine adenomyomas by pathogenesis into two classes:¹⁶⁴

Those located at the periphery of the uterus and in the tube – derived from Wolffian tubules

Those arising centrally – originated from uterine mucous membrane

Von Recklinghausen classified uterine adenomyomas by morphology into four varieties:¹⁶⁵

Hard – “muscle-tissue in excess of gland-elements.”

Cystic – cavity visible to naked eye, “possessing gland-tissue and muscle in equal amounts.”

Soft – gland-tissue predominates and “appears microscopically as islands.”

Telangiectatic – “soft, very vascular growths, which are almost devoid of cysts.”

Cullen classified uterine adenomyomas by location.¹⁶⁶

Intramural within a uterus of normal contour that may be two or three times enlarged.

Subperitoneal or intraligamentary

Submucous

Lockyer classified extrauterine adenomyomas by organ.¹⁶⁷

Fallopian tube

Round ligament

Ovarian ligament

Broad ligament

Recto-genital space

Alimentary tract

Umbilicus (Cullen)

In 1916 Cullen had “tentatively” classified adenomyomas of the rectovaginal septum by extent of disease.¹⁶⁸

Small adenomyomas lying relatively free in the rectovaginal septum.

Adenomyomas adherent to the posterior surface of the cervix and at the same time to the anterior surface of the rectum.

Adenomyomas gluing the cervix and rectum together and spreading out into one or both broad ligaments.

Adenomyomas involving the posterior surface of the cervix, the rectum and broad ligaments, and forming a dense pelvic mass that cannot be liberated.

Cullen’s presentation of the “tentative” classification of adenomyomas of the rectovaginal septum before the Section of Obstetrics, Gynecology and Abdominal Surgery at the American Medical Association meeting in June 1916 amounted to a subtle call for early diagnosis and treatment.

By 1919, he was more forceful. In an address before the New York State Medical Society at Syracuse, Cullen expressed his belief that “in time,” untreated endometriosis of the rectovaginal septum would render the woman a “chronic invalid, and in some instances” was a potentially lethal disease. He continued: “The growth sometimes encircles one or both ureters … Occasionally, as the growth progresses, the polypoid condition in the vaginal wall directly behind the cervix becomes very prominent, and in those cases in which the growth breaks through the vaginal mucosa, there may be a menstrual flow from the vaginal vault … Finally, if nothing is done, the pelvis may become so choked with growth that the patient dies from the extreme loss of blood coupled with partial intestinal obstruction.”¹⁶⁹ This was not Cullen the pathologist, but Cullen the master physician and humanitarian – the ombudsmen for women – pleading for early diagnosis and treatment.

Perhaps stimulated by Lockyer’s classification of extrauterine adenomyomas, in 1919 Cullen also found time to write a short article entitled “The distribution of adenomyomata containing uterine mucosa.” He gave a “bird’s eye picture” of adenomyomas, their distribution and briefly described “the clinical picture noted in the various localities in which it occurs.”¹⁷⁰ The title, “The distribution of adenomyomata containing uterine mucosa,” is particularly revealing; Cullen did not quite know how to classify certain ovarian lesions: the solid and cystic lesion of WW Russell and the cystic lesions (later known as endometriomas) lined with uterine mucosa. They did not fall neatly in place with solid adenomyomas elsewhere, hence the modifier “containing uterine mucosa” in the title. Cullen classified and illustrated with a sagittal drawing the anatomical location of all uterine and extrauterine adenomyomata that he had observed. An obviously unsigned preliminary sketch by Max Broedel demonstrates “the various points at which I [Cullen] have found uterine mucosa.”¹⁷¹ Seven number labels indicated seven locations: “adenomyoma of the body of the uterus,” rectovaginal septum, round ligament, anterior surface of the ovary,¹⁷² utero-ovarian ligament, uterosacral ligament, and umbilicus.¹⁷³

Cullen followed closely Lockyer’s classification of extrauterine adenomyomas with the following notations: Cullen added lesions of the uterosacral ligament and ovary, used the term rectovaginal septum which Lockyer called recto-genital space, and omitted adenomyomas of the gastrointestinal tract. However, Cullen did discuss adenomyomas of the rectum under the heading of rectovaginal septum. Perhaps he was thinking of Kellogg’s experience as well as his own when he expressed his by then time-honored caveat: “Sometimes it will be necessary to remove a wedge of the adherent anterior rectal wall with the uterus. In cases in which the growth is widespread, a preliminary permanent colostomy is imperative. Later the pelvis structures can be removed en bloc.” ¹⁷⁴ Thus Cullen revealed that both his experience and terminology differed from that of his London colleague. Then he expressed a truism attested to by all pelvic surgeons: “The removal of an extensive adenomyoma of the rectovaginal septum is infinitely more difficult than a hysterectomy for carcinoma of the cervix.”¹⁷⁵

In a particularly revealing and characteristically honest comment in his “bird’s eye picture” address before the New York State Medical Society annual meeting in May 1919, Cullen acknowledged that he had no personal surgical experience with adenomyomas of the uterosacral ligament until “my colleague, Dr. W. W. Russell removed a pea-sized nodule from the uterosacral ligament.”¹⁷⁶ Here again is an example of a phenomenon we have seen before. Despite his expertise in uterine adenomyomas, time and again Cullen needed to be alerted to extrauterine phenotypes of this complex disease. Recall that in 1913 Jessup and Lockyer brought the existence of adenomyomata of the rectovaginal septum to his attention. As a young attending in 1899, Cullen seems to have ignored Russell’s report of uterine mucosa in the ovary and for the next 20 years was oblivious to ovarian involvement until awakened by Norris in 1918 and Casler in 1919.¹⁷⁷ Many manifestations of extrauterine adenomyomata as well as the ubiquitous chocolate cysts seem to have remained hidden in plain sight, unobserved by Cullen until he was alerted to their presence.

During 1919, Cullen had been preoccupied with the imminent departure of Kelly and the upcoming administrative duties as professor of clinical gynecology and head of the division of gynecology in the department of surgery under Halsted.¹⁷⁸ According to Cullen’s successor Richard Te Linde, Howard A. Kelly was not only Cullen’s chief but also his “idol.”¹⁷⁹ To celebrate that momentous occasion, Cullen wrote an informative biographical essay to celebrate the career of Kelly.¹⁸⁰ He also arranged for Minnie Blogg, librarian of Johns Hopkins Hospital, to publish an invaluable bibliography of Kelly’s works from 1882 through his retirement in 1919.¹⁸¹ The bibliography contains 485 titles that included books, pamphlets, and journal articles.¹⁸²

Adenomyomas of the Ovary

During the second decade of the twentieth century, the subject of menstruation and ovulation still remained a “mysterious mechanism.”¹⁸³ In 1917 Emil Novak – an instructor in clinical gynecology at Johns Hopkins Medical School who also worked in Cullen’s gynecologic pathology laboratory – published a study of hemorrhagic cysts of the ovary.¹⁸⁴ Among 85 surgical specimens of ovarian hematomas varying between 2 and 6 cm in diameter, Novak found none that contained uterine glands and stroma, though he was particularly interested in pathogenesis of the smaller cysts which usually had a more intact lining. Interestingly, Novak may have shed some light upon Cullen’s lack of interest in ovarian hematomas associated with adenomyomas of the rectovaginal septum when he commented: “There is no organ of the body which is so frequently the seat of hemorrhages as is the ovary. Indeed, so common are they that no clinical significance is attached to the small hematomata so frequently found in the ovaries removed at operation … By far the largest proportion of hematomata studied, as a matter of fact, were quite small, not exceeding 2 cm in diameter. These smaller lesions afford a much better opportunity than the more extensive ones of solving the important question of pathogenesis.”¹⁸⁵

This study, coming from Cullen’s own laboratory, explains why Cullen considered an ovary with a small – 3 cm hematoma – unimportant. Furthermore, Novak found the “surface appearance of an ovary of little importance as an index of its internal structure.”¹⁸⁶ Novak’s observations may explain not only Cullen’s apparent disinterest in ovarian hematomas accompanying extrauterine adenomyomas, but also the disinterest of most gynecologists at the time.

In 1918, Lockyer addressed the topic of adenomyomatous tissue in the ovary under the heading of adenomyoma of the ovarian ligament.¹⁸⁷ He began the discussion with an unexpected verbal thrust at Cullen. “Adenomatous elements within the substance of the ovary have been described by Cullen. I suppose he would refer these to the paroophoron.”¹⁸⁸ By this Lockyer undoubtedly meant that Cullen considered such adenomyomatous elements to be embryonic remnants, but ironically remnants of the Wolffian duct, not the müllerian duct.¹⁸⁹ Lockyer illustrated a case of Semmelink and de Joselin de Jong¹⁹⁰ in which the adenomyomatous tissue invaded a cystic ovary.¹⁹¹ A “blood-cyst lined by cytogenous tissue and gland-tissue (Adenomyoma) occupied a central portion of the ovary.” A large amount of adenomyomatous tissue in that specimen was situated in the hilum of the ovary.¹⁹² Lockyer concluded his short discussion with mention of a cherry-sized adenomyoma in the hilum of an ovary reported by Ludwig Pick in 1900.¹⁹³

Casler’s Menstruating Ovarian-Uterus

By invitation of the American Gynecological Society in 1919, De Witt Casler of Johns Hopkins Hospital presented one of the more remarkable case reports in the annals of gynecology.¹⁹⁴ In all probability the invitation was arranged by Cullen. The patient was a single 39 year old nurse who first consulted Casler in January 1913 with the complaint of painless excessive menstruation of 2 years duration. Examination revealed an irregular myomatous uterus that filled the pelvis and extended two finger’s breaths above the pubic bone. On January 13, 1913 Casler performed a panhysterectomy and removed the right tube and ovary, the left tube, and the appendix. Preoperatively the patient, a nurse, insisted the Casler not remove all ovarian tissue because she dreaded an artificial menopause.¹⁹⁵ Finding the left ovary normal, the surgeon complied with his patient’s request. Casler placed a small cigarette drain into the vagina, a surgical decision that would in time contribute to a unique experiment of nature.

Before closing the abdominal incision, Casler opened the uterus as was customary on the Johns Hopkins’ gynecologic service. “The uterine cavity was found to contain one large and several smaller liver-colored polypi … From the mucosa to the peritoneal surface the walls were everywhere converted into a coarse meshwork by tough bands of muscle or fibrous tissue running in all directions, and in the interstices of the meshwork and standing out prominently above the cut surface were small comedo-like areas of an appearance we had never seen before … They were elevated above the surface, while in a diffuse adenomyoma we would have numerous depressions, with characteristic chocolate-colored fluid.”¹⁹⁶ Microscopic examination was equally unusual. The mucosa was composed only of endometrial stroma without glands. The stromal masses consisted of: “an embryonic tissue made up of oval and spindle-shaped nuclei closely packed together … The pathological process beginning in the polyp is really an orderly overgrowth of the stroma, which has gradually exterminated the uterine glands by strangulation, and then in the same manner has attacked the uterine musculature.”¹⁹⁷

In his autobiography, Robert Meyer recalled “As early as 1909 I had observed that it was the stroma of the endometrium which had the ability to destroy other tissue, especially elastic tissues (Virchows Archiv). At that time it was not known that one tissue could dissolve another without being malignant … I found that the histolytic quality is not only responsible for the destruction of the interfascicular connective tissue but also for the musculature which undergoes necrosis to a greater or lesser degree.”¹⁹⁸ Emge called this lesion “endometrial stromatosis,” an aglandular form of internal endometriosis that, unlike adenomyosis, tends to dedifferentiate into sarcoma.¹⁹⁹

Casler examined his patient at 3–4 month intervals for 4 years and at each examination the left ovary was “normal in size and not enlarged or tender.”²⁰⁰ “During this period of 4 years, the patient consistently maintained that at regular monthly intervals she menstruated for a part of 1 day each month. Just as constantly I assured her she must be mistaken, for a panhysterectomy had been done and menstruation was out of the question.”²⁰¹

Then on January 1, 1917, exactly 4 years after the hysterectomy, the patient returned complaining of “obstinate constipation, with rather flattened stools” followed by diarrhea since November and of severe crampy pains of 2 weeks duration that the patient thought might be a partial bowel obstruction. Casler found “on vaginal examination the old drainage tract in the upper vaginal vault had opened slightly, and through this tract could be felt an irregular, nodular but cystic mass in the region of the left ovary. This was slightly moveable and was evidently the cause of the partial obstruction of the bowel.”²⁰²Recall that at the initial operation on January 13, 1913, before closing the abdomen Casler had inserted a “cigarette drain” through the vaginal cuff.²⁰³ In all probably the drain prevented healing by primary intention and by its presence created a fistulous channel between the vagina and the right ovary, a channel through which the patient menstruated.

At surgery on January 3, 1917 Casler found a grapefruit-sized semicystic ovarian tumor in the left lower pelvis densely adherent to the upper rectum and sigmoid colon with almost complete bowel obstruction.²⁰⁴ He removed “about 20 cm of the sigmoid and upper part of the rectum with the ovarian tumor,” and performed an end-to-end anastomosis. The ovarian tumor ruptured during removal and spilled “several ounces of dirty, chocolate-colored fluid and several reddish, liver-colored polypi escaped.”²⁰⁵ The postoperative course was essentially uneventful until the tenth day when the patient “was seized with a severe attack of abdominal pain, nausea and vomiting, and died from what was apparently a mesenteric thrombosis.”²⁰⁶ While no autopsy was permitted, Casler did have the opportunity to study the surgical specimens. “On opening the ovarian growth … we find a cystic tumor with walls of varying thickness. In the region near the attached sigmoid the walls are quite thick and cartilaginous, measuring 4 cm, while in other portions they are much thinned out and are 2–3 mm in thickness. The walls present an unusual appearance. In that portion adjacent to the sigmoid which forms the thickest portion of the tumor we find a tough and cartilaginous tissue.”²⁰⁷ “Microscopic examination reveals an ovarian cyst made up almost entirely of uterine tissue, the interior of the cyst corresponding to the uterine cavity and filled with blood while the walls contain may normal glands and others which show glandular dilatation. A pathological change has also occurred and we have an overgrowth of the interglandular stroma much resembling that seen 4 years previously in the uterus … The entire cyst, or uterine cavity, as it really is, is lined throughout by a single layer of tall columnar epithelium of the uterine type and in places cilia can be made out.”²⁰⁸

Casler gave three somewhat ambiguous descriptions of the sigmoid colon, one at operation and two of the pathological specimen, but no microscopic examination. “At operation a semicystic tumor, about the size of a grapefruit was found occupying the left lower portion of the pelvis. Over the top of this cystic mass, and firmly attached to it, and almost completely obstructed by it, coiled the sigmoid flexure and the upper portion of the rectum, displaced by the growth toward the right. The ovarian mass was densely adherent to the lateral wall of the pelvis, was extremely vascular, and there was a marked infiltration of the bowel wall.”²⁰⁹ [The gross specimen.] “The sigmoid is closely attached to the growth and the lumen of the bowel is almost shut off at its middle portion by the encircling tumor. The mucosa of the bowel is normal while the muscular walls above the obstruction are somewhat hypertrophied.”²¹⁰ [The gross specimen.] “The mucous membrane of the intestine is normal and the muscular coats of the bowel have not been invaded, but this infiltration of the tissue has gone around the sigmoid, so that for fully one-half of its circumference it is surrounded and compressed by this [ovarian] growth, thus causing the almost complete obstruction.”²¹¹

The operative and laboratory descriptions suggest that the ovarian tumor not only bled through the fistulous tract on a monthly basis, but also ruptured into the left pelvis and invaded the wall of the sigmoid colon producing a near “napkin-ringlike constriction” of the bowel wall.²¹² Casler opined this unique ovarian tumor originated from remnants of the müllerian duct.²¹³ From the advantage of historical perspective, the pathogenesis more likely is attributable to transmural spread of aggressive uterine stromal endometriosis through veins and lymphatics to the ovary. In 1920 Casler republished his presentation in Surgery, Gynecology and Obstetrics.²¹⁴

Footnotes

Juan Rosai, ed., Guiding the Surgeon’s Hand: The History of American Surgical Pathology [Washington, DC: Armed Forces Institute of Pathology, 1997], 3.

Cullen TS. Adenomyoma of the round-ligament. Johns Hopkins Hospital Bulletin. 1896; VII:112–14.

Von Recklinghausen F. Adenomyomas and cystadenomas of the wall of the uterus and tube: Their origin as remnants of the Wolffian body. Wien klin Wschr 1896;8:530.

Cullen TS. Adenomyoma of the round-ligament. Johns Hopkins Hospital Bulletin. 1896; VII:112–14:113.

Cullen TS. Adeno-myoma of the round-ligament. Johns Hopkins Hospital Bulletin. 1896; VII:112–14.

Cullen TS. Further remarks on adeno-myoma of the round ligament. Johns Hopkins Hospital Bulletin 1898; IX:142.

Cullen TS. Umbilical tumors containing uterine mucosa or remnants of Mueller’s duct. Transactions Southern Surgical and Gynecological Association, 1911. Cullen TS. Umbilical tumors containing uterine mucosa or remnants of Mueller’s duct. Surg Gynecol Obstet 1912;l4:479–491.

Cullen TS. Adenomyoma of the round ligament and incarcerated omentum in an inguinal hernia, together forming one tumor. Surg Gyn and Obstet. 1916;23:258–260.

Thomas S. Cullen. Embryology, Anatomy, and Diseases of the Umbilicus [Philadelphia: W. B. Saunders, 1916].

Cuthbert Lockyer, Fibroids and Allied Tumours (Myoma and Adenomyoma): Their Pathology, Clinical Features and Surgical Treatment [London: Macmillan and Company, 1918], 301. As Lockyer pointed out, Cullen’s experience between 1894 and 1908 when he wrote his “monumental” work Adenomyomata of the Uterus, published in 1908, was limited to uterine adenomyomata and adenomyomata of the utero-ovarian and round ligaments. Lockyer stated further: “up to that date this well-know author had met with no case of ‘adenomyoma’ in the recto-genital space.”

Cullen TS. The distribution of adenomyomata containing uterine mucosa. Am J Obstetrics Diseases Women and Children 1919;180:130–138:134. In 1913 Jessup’s and Lockyer’s “communications set me thinking and I at once felt sure that two of my cases undoubtedly belonged to this category, although the histological examination had given no inkling of such a condition. I had many more sections made and was finally rewarded by finding in each case the typical picture in other portions of the specimen. Since then I have been on the look out for this condition and have had in all 15 cases.”

Jessup, DSD. Adenomyoma of the rectovaginal septum. JAMA 1914;LXIII: 383–387.

Jessup, DSD. JAMA 1914;LXIII: 383–387:387.

Jessup, DSD. JAMA 1914;LXIII: 383–387. Jessup preserved Cullen’s first assessment of adenomyoma of the rectovaginal septum.

Cullen TS. Adenomyoma of the rectovaginal septum. Transactions of Southern Surgical & Gynecological Association. 1913;26:106–118. Lockyer, Cuthbert. Adenomyoma of the rectovaginal septum. Proceedings Royal Society Medicine. February 1913; vi, No. 4.

Cullen TS. Adenomyoma of the rectovaginal septum. Trans Southern Surgical and Gynecological Assoc 1913;26:106–118. Cullen made reference to his “Address in Gynecology” before the Canadian Medical Association in June 1913, published in the Canadian Medical Association Journal, August 1913.

Cullen TS. Adenomyoma of the rectovaginal septum. JAMA 1914;62:835–839. See footnote page 835.

Cullen TS. Adenomyoma of the rectovaginal septum. Trans Southern Surgical and Gynecological Assoc 1913;26:106–118.

Cullen TS. Adenomyoma of the rectovaginal septum. JAMA 1914;LXII: 835–839. The only difference, in the 1913 version large full-page illustrations were clustered in mid-article, in 1914 version the illustrations were smaller and integrated within the text.

Cullen TS. Adenomyoma of the rectovaginal septum. Trans Southern Surgical and Gynecological Assoc 1913;26:106–118.

Cullen TS. Adenomyoma of the rectovaginal septum. Trans Southern Surgical and Gynecological Assoc 1913;26:106–118, Figure 1. Lockyer, Cuthbert. Adenomyoma of the rectovaginal septum. Proceedings Royal Society Medicine. February 1913; vi, No. 4. Denonvilliers, CPD. Bull Soc Anatomy of Paris (Series 3) 1836:20:105.

Cullen TS. Adenomyoma of the rectovaginal septum. Trans Southern Surgical and Gynecological Assoc 1913;26:106–118:116–7.

Cullen TS. Adenomyoma of the rectovaginal septum. 1913;26:106–118:116–7, Figure 3.

Cullen TS. Adenomyoma of the rectovaginal septum. 1913;26:106–118. In 1918, Lockyer remarked, “The term ‘miniature uterine cavities’ for small cystic spaces in adenomyomas has often been employed by Thomas S. Cullen.” Cuthbert Lockyer, Fibroids and Allied Tumours (Myoma and Adenomyoma): Their Pathology, Clinical Features and Surgical Treatment [London: Macmillan and Company, 1918], 401.

Denonvilliers, CPD. Bull Soc Anatomy of Paris (Series 3) 1836:20:105. See also: Nichols DH, Milley PS. Surgical significance of the rectovaginal septum. Am J Obstet Gynecol 1970;108:215–220. See also: Nichols DH, Milley PS. “Clinical anatomy of the vulva, vagina, lower pelvis, and perineum. In Gynecology and Obstetrics, Vol. 1. [Hagerstown, MD: Harper & Row Publishers, Inc., 1977], 15. Figure 1–12. “The rectovaginal septum. Sections showing the partly dissected rectovaginal septum. It extends from the pouch of Douglas to the perineal body and forms the anterior surface of the rectovaginal space. Its adherence to the posterior vaginal wall is illustrated along with its posterolateral curve.” (From Nichols DH, Milley PS: Surgical significance of the rectovaginal septum. Am J Obstet Gynecol 108:215, 1970.)”

Cullen TS. Adenomyoma of the rectovaginal septum. Transactions of the Southern Surgical & Gynecological Association. 1913;26:106–118:111–112.

Cullen TS. Adenomyoma of the rectovaginal septum. 1913;26:106–118:112–114.

Shemwell RE, Weed JC. Ovarian remnant syndrome. Obstet Gynecol 1970;36:299. In the ovarian remnant syndrome fragments of ovarian tissue not removed at surgery survive and function by parasitically deriving their blood supply from other organs or tissues. In 1970, Shemwell and Weed demonstrated the existence of the ovarian remnant syndrome in an experimental model. They fixed fragments of ovarian cortex to the pelvic side wall of cats with sutures [creating artificial adhesions]; the isolated ovarian cortical fragments survived as functioning ovarian cortical tissue by acquiring a parasitic blood supply from vessels in the lateral pelvic wall.

Cullen TS. Adenomyoma of the rectovaginal septum. Transactions of the Southern Surgical & Gynecological Association. 1913;26:106–118.

Cuthbert Lockyer, Fibroids and Allied Tumours (Myoma and Adenomyoma): Their Pathology, Clinical Features and Surgical Treatment [London: Macmillan and Company, 1918], 320. Referring to page 252 of Cullen’s 1908 publication, Adenomyoma of the Uterus, Lockyer pointed out that “Cullen will have nothing to do with the serosal theory.” In 1898, N.S. Iwanoff published his theory that glandular cystic spaces in fibromyomas originated by an ingrowth of overlying serosa. Iwanoff NS. Drusiges cystenhaltiges Uterusfibromyom compliciert durch Sarcom und Carinom. Monatsschr fur Geb und Gynak 1898; Bd. vii: S. 295.

Sampson JA. Heterotopic or misplaced endometrial tissue. Am J Obstet Gynecol 1925;10:649–664. Cullen TS. Discussion: Symposium on misplaced endometrial tissue. Am J Obstet Gynecol 1925;10:732–33. “We are great debt to Sampson for the careful, painstaking and brilliant work that he has done toward establishing the modes of origin of peritoneal adenomyomata.”

Cullen TS. Adenomyoma of the rectovaginal septum. JAMA 1914;62:835–839.

Jessup, DSD. Adenomyoma of the rectovaginal septum. JAMA 1914;LXIII: 383–387.

Cullen, TS. A rapid method of making permanent specimens from frozen sections by the use of formalin

. Bull Johns Hopkins Hosp 1895;6:67.

Lockyer, Cuthbert. Adenomyoma of the rectovaginal septum. Proceedings Royal Society Medicine. February 1913;vi, No. 4. Not realizing the benign nature of the disease, Lockyer had performed a Wertheim radical hysterectomy, a permanent colostomy, and resection of the rectum.

Cullen TS. Adenomyoma of the rectovaginal septum. Trans Southern Surgical and Gynecological Assoc 1913;26:106–118:117.

Cullen TS. A further case of adenomyoma of the rectovaginal septum. Surg Gynecol Obstet 1915;20:263–265.

Cullen TS. A further case of adenomyoma of the rectovaginal septum. 1915;20:263–265.

Stickney GL. A case of diffuse adenomyoma of the uterus, with discrete adenomyoma over the left ureter. Johns Hopkins Hospital Bulletin 1915;xxvi:304.

Cullen TS. Adenomyoma of the rectovaginal septum. JAMA 1916;LXVII:401–406:405.

Stevens TG. Adenomyoma of the rectovaginal septum. Proc Roy. Soc Med., 1910;iii:57.

Nadal, Pierre. Bull. de l’Assn. franc. Pour l’etude du cancer. 1911;iv:338.

Lockyer, Cuthbert. Adenomyoma of the rectovaginal septum. Proceedings Royal Society Medicine. February 1913;vi, No. 4.

Jessup, DSD. Adenomyoma of the rectovaginal septum. JAMA 1914;LXIII: 383–387:385.

Stevens TG. Adenomyoma of the rectovaginal septum. Proc Roy. Soc Med., 1916;ix: Obst. and Gynec. Section, p. 1.

Cullen TS. Adenomyoma of the rectovaginal septum. JAMA 1916;LXVII:401–406:406:406.

Cullen TS. JAMA 1916;LXVII:401–406:406:406.

Cullen TS. JAMA 1916;LXVII:401–406:406. See Figure 1 (case 4).

Cullen TS. JAMA 1916;LXVII:401–406:401. Figure 2.

Cullen TS. Adenomyoma of the rectovaginal septum. JAMA 1916;LXVII:401–406:402.

Cullen TS. JAMA 1916;LXVII:401–406:404. See also Figure 3 (Case 4), page 403. “Muscular and fibrous tissue in an adenomyoma of the broad ligament encircling and compressing nerves. This section is from the right broad ligament. It shows the diffuse myomatous and fibrous tissue surrounding nerves. There were definite symptoms of nerve pressure.”

Cullen TS. JAMA 1916;LXVII:401–406:402.

Cullen TS. JAMA 1916;LXVII:401–406:402:404. Figure 4 (Case 5). “A reference to the description of the specimen shows that the mass was a typical adenomyoma.”

Cullen TS. JAMA 1916;LXVII: 401–406:402. The rectovaginal pouch of Douglas in women with and without children often extends caudally below the mid-level of the vagina. See also: Cullen, Thomas S. The distribution of adenomyomas containing uterine mucosa. Archives of Surgery. 1920;1:215–283. “Adenomyoma of the rectovaginal septum usually starts just behind the cervix, and on bimanual examination, one can feel in this region a small, somewhat moveable nodule scarcely more than a centimeter in diameter.”

Cullen TS. Adenomyoma of the rectovaginal septum. JAMA 1916;LXVII:401–406s:403.

Cullen TS. JAMA 1916;LXVII:401–406:403.

Cullen TS. JAMA 1916;LXVII:401–406:404.

Füth. Zentr f Gynak 1912;xxxvi:1356. Cited by Cuthbert Lockyer, Fibroids and Allied Tumours (Myoma and Adenomyoma): Their Pathology, Clinical Features and Surgical Treatment [London: Macmillan and Company, 1918], 333.

Cullen TS. Adenomyoma of the rectovaginal septum. Trans Southern Surgical and Gynecological Association 1913;26:106–118:112–114. Cullen was also influenced deeply by the operative mortality of Richardson.

Cullen TS. Adenomyoma of the rectovaginal septum. JAMA 1916;LXVII:401–406:405.

Cullen TS. Adenomyoma of the rectovaginal septum. JAMA 1916;LXVII:401–406:405–6.

Cullen TS. JAMA 1916;LXVII:401–406:406.

Cullen TS. JAMA 1916;LXVII:401–406:405.

Nisolle M, Donnez J. Peritoneal endometriosis, ovarian endometriosis, and adenomyotic nodules of the rectovaginal septum are three different diseases. Fertility Steril 1997;68:585–96. See also: Michelle Nisolle and Jacques Donnez, Peritoneal, Ovarian and Recto-vaginal Endometriosis: The identification of three separate diseases [New York: Parthenon Publishing Group, 1997], and J Donnez, O Donnez, J Squifflet, and M. Nisolle, “The concept of retroperitoneal adenomyotic disease is born.” An Atlas of Operative Laparoscopy and Hysteroscopy, 2nd ed. Ed. J. Donnez and M. Nisolle [New York: Parthenon Publishing Group, 2001], 113–117.

Stevens TG. Adenomyoma of the rectovaginal septum. Proc Roy. Soc Med., Obstet Gynaecol Section 1916;ix:1–17:16–17.

Stevens TG. Proc Roy. Soc Med., Obstet Gynaecol Section 1916;ix:1–17:16.

Stevens TG. Proc Roy. Soc Med., Obstet Gynaecol Section 1916;ix:1–17:1. In a footnote on page 6, Stevens identified Case I as the same case he had “demonstrated” in 1909 and published in a brief note: Stevens TG. Adenomyoma of the vaginal wall. “Proceedings, 1910, iii, p. 57.” The author has a copy of the 1910 publication.

The posterior fornix of the vagina is bounded anteriorly by that portion of the uterine cervix that protrudes into the vagina and posteriorly by the rectovaginal pouch of Douglas. See Illustrated Stedman’s Medical Dictionary. 24th ed. [Baltimore, MD: Williams & Wilkins, 1982], 555. The vaginal fornix or fornix uteri is “the recess at the vault of the vagina; it is divided into a pars anterior, pars posterior, and pars lateralis with respect to its relation the cervix of the uterus.”

Stevens TG. Adenomyoma of the rectovaginal septum. Proc Roy. Soc Med., Obstet Gynaecol Section 1916;ix:1–17:6.

Stevens TG. Proc Roy. Soc Med., Obstet Gynaecol Section 1916;ix:1–17:6.

Stevens italicized the word site for emphasis.

Stevens TG. Adenomyoma of the rectovaginal septum. Proc Roy. Soc Med., Obstet. and Gynecol. 1916;ix:1–17. When the rectovaginal pouch of Douglas [RVPD] becomes obliterated by disease, the adenomyomatous lesion is enclosed superiorly by adhesion of the serosal surface of the posterior cervix or posterior uterus to the serosal surface of the rectum. This creates the false impression that the floor of the RVPD is above the lesion. Actually the floor of the RVPD is below the lesion. The adenomyoma (deeply invasive endometriosis) is situated between the true floor of the RVPD below (caudad), and the false floor above created by cervix or uterus adherent to rectum above (cephalad).

Stevens’ insight was an important step in the evolution of the pathogenesis of deeply invasive endometriosis involving the vagina, cervix, and rectum. It would be left to Johns A. Sampson’s implantation theory to place the site of origin of endometriosis on the peritoneum of the rectovaginal pouch of Douglas.

Cullen TS. Adenomyoma of the rectovaginal septum. JAMA 1916;LXVII:401–406:401. Cullen’s footnote 5 on page 401 reads: Stevens, T. G.: Adenomyoma of the Rectovaginal Septum, Proc. Roy. Soc. Med., 1916, ix, Obstet. and Gynecol. Section. p. 1.

Cullen TS. JAMA 1916;LXVII:401–406:401.

Judith Robinson, Tom Cullen of Baltimore [London, Toronto, New York: Oxford University Press, 1949], 176. Whenever in London, Cullen visited Lockyer for casual evenings; the two corresponded for years.

Cullen TS. The distribution of adenomyomata containing uterine mucosa. American Journal of Obstetrics and Diseases of Women and Children 1919;180:130–138.

Stevens TG. Adenomyoma of the rectovaginal septum. Proc Roy. Soc Med., Obstet. and Gynecol. 1916;ix:1–17.

Kellogg, FS. Adenomyoma of the recto-vaginal septum. Boston Medical and Surgical Journal 1917;176–177:22–24.

Cullen TS. Adenomyoma of the rectovaginal septum. JAMA 1916;LXVII:401–406:401.

Cullen TS. JAMA 1916;LXVII:401–406:406.

Kellogg, FS. Boston Medical and Surgical Journal 1917;176–177:22–24:23.

Kellogg, FS. Adenomyoma of the recto-vaginal septum. Boston Medical and Surgical Journal 1917;176–177:22–24:24.

Kellogg, FS. Boston Medical and Surgical Journal 1917;176–177:22–24:24.

Cullen TS. Adenomyoma of the recto-vaginal septum. Johns Hopkins Hospital Bulletin 1917;28:343–349:343.

Cullen TS. Johns Hopkins Hospital Bulletin 1917;28:343–9. Plate LXV, Figure 1.

Cullen TS. Johns Hopkins Hospital Bulletin 1917;28:343–9. Plate LXVI, Figure 2.

Cullen TS. Johns Hopkins Hospital Bulletin 1917;28:343–9. Plate LXVII, Figure 3.

Cullen TS. Johns Hopkins Hospital Bulletin 1917;28:343–49. See Figure 3, Plate LXVII.

Cullen TS. Johns Hopkins Hospital Bulletin 1917;28:343–49:347.

Cullen TS. Adenomyoma of the recto-vaginal septum. Johns Hopkins Hospital Bulletin 1917;28:343–9. Plate LXVIII, Figure 5.

Cullen TS. Johns Hopkins Hospital Bulletin 1917;28:343–9. Plate LXX, Figure 7. See also other large histologic sections: Plate LXIX, Figure 6; Plate LXXL, Figure 8 showing a “miniature uterine cavity;” Plate LXXII, Figure 9; Plate LXXIII, Figure 10; Plate LXXIV, Figure 11, depicting an adenomyomatous polyps projecting into the posterior vaginal vault; and Plate LXXV, Figure 12.

Cullen TS. Johns Hopkins Hospital Bulletin 1917;28:343–9. Plate LXVII, Inset upper left corner, Figure 3. The orange sized cyst filled with blood that was observed in 1914 possibly represented a hemorrhagic corpus luteum cyst. It is unlikely that an endometrioma of that size would have completely resolved in two years leaving the ovary to appear normal.

Cuthbert Lockyer, Fibroids and Allied Tumours (Myoma and Adenomyoma): Their Pathology, Clinical Features and Surgical Treatment [London: Macmillan and Company, 1918], 262.

100

Cullen TS. Adenomyoma of the recto-vaginal septum. Johns Hopkins Hospital Bulletin 1917;28:343–9:347.

101

Cullen TS. Johns Hopkins Hospital Bulletin 1917;28:343–9:347.

102

Cullen TS. Johns Hopkins Hospital Bulletin 1917;28:343–9:348.

103

Cullen TS. Johns Hopkins Hospital Bulletin 1917;28:343–49:347, Case 8.

104

Cullen TS. Johns Hopkins Hospital Bulletin 1917;28:343–49:348.

105

Cullen TS. Johns Hopkins Hospital Bulletin 1917;28:343–349:348.

106

Cullen, Thomas S. Adenomyoma of the recto-vaginal septum. Johns Hopkins Hospital Bulletin 1917;28:343–49.

107

Cullen TS. Johns Hopkins Hospital Bulletin 1917;28:343–9. Plate LXXVI, Figure 13.

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Cullen TS. Johns Hopkins Hospital Bulletin 1917;28:343–9. Plate LXXVII, Figure 14.

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Cullen TS. Johns Hopkins Hospital Bulletin 1917;28:343–9. Plate LXXVIII, Figure 15.

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Cullen TS. Johns Hopkins Hospital Bulletin 1917;28:343–9:349.

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Cullen TS. Johns Hopkins Hospital Bulletin 1917;28:343–9. Plate LXXIX, Figures 16 and 17. At surgery Cullen removed both ovaries and both pus filled tubes caused by tuberculosis. The patient was to return to surgery later for removal of adenomyomatous disease.

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Cullen TS. Adenomyoma of the recto-vaginal septum. Johns Hopkins Hospital Bulletin 1917;28:343–49:344.

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Sampson JA. The importance of early diagnosis in cancer of the uterus. JAMA 1905;xliv:1586–1593.

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Wertheim E. The radical abdominal operation in carcinoma of the cervix uteri. Surg Gynecol Obstet 1907;4:1–10, discussion:101–13. Sampson referred to both of these papers in a review article on uterine cancer entitled: The clinical manifestations of uterine cancer. International Clinics 1908; (Series 18) (2):176–201:199.

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Cullen TS. Johns Hopkins Hospital Bulletin 1917;28:343–49:344.

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Cullen TS. Johns Hopkins Hospital Bulletin 1917;28:343–49:344.

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Cullen TS. Johns Hopkins Hospital Bulletin 1917;28:343–49:344.

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Cullen TS. Adenomyoma of the recto-vaginal septum. Johns Hopkins Hospital Bulletin 1917;28:343–9:344.

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Cullen TS. Johns Hopkins Hospital Bulletin 1917;28:343–49:344.

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Sampson JA. The clinical manifestations of uterine cancer. International Clinics 1908;(Series 18 (2)):176–201:196–197. Figure 22, page 196 is particularly graphic!

121

Cuthbert Lockyer, Fibroids and Allied Tumours (Myoma and Adenomyoma): Their Pathology, Clinical Features and Surgical Treatment [London: Macmillan and Company, 1918], vii.

122

Cuthbert Lockyer, Fibroids and Allied Tumours (Myoma and Adenomyoma): Their Pathology, Clinical Features and Surgical Treatment [London: Macmillan and Company, 1918], 419. Lockyer cited Robert Meyer. Uber adenomatose Schleimhautwucherungen in der Uterus- und Tubenwand und ihre pathologisch-anatomische Bedeutung. Virchow’s Arch 1903;l172:394–409.

123

Cuthbert Lockyer, Fibroids and Allied Tumours, 422, 427.

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Cullen TS. Adenomyoma of the recto-vaginal septum. Johns Hopkins Hospital Bulletin 1917;28:343–9:343. See footnote 4. “For an admirable review of the foreign literature on adenomyomas of the recto-vaginal septum consult Cuthbert Lockyer in Eden & Lockyer’s New System of Gynaecology, Vol. II, p. 350. It is brim-full of interest.” Cuthbert Lockyer, Fibroids and Allied Tumours (Myoma and Adenomyoma): Their Pathology, Clinical Features and Surgical Treatment [London: Macmillan and Company, 1918]. The author is deeply indebted to Cuthbert Lockyer’s scholarly scientific monograph of 1918, an indebtedness also acknowledged by Thomas Cullen and John Sampson. Lockyer presented chronologically and in some detail the pertinent German, French, English, and American literature on adenomyomas to the outbreak of World War I.

125

Cuthbert Lockyer, Fibroids and Allied Tumours, viii.

126

Pfannenstiel JH: Uber die Adenomyoma, etc. Verhdlg d. Deutschen Ges f Gynak, Leipzig 1897: S. 195. Cited by Cuthbert Lockyer, Fibroids and Allied Tumours (Myoma and Adenomyoma): Their Pathology, Clinical Features and Surgical Treatment [London: Macmillan and Company, 1918], 333.

127

Von Herff. Uber Cystomyome, etc. Verhdlg d. Deutschen Ges f. Gynak, Leipzig 1897: S. 189.

128

Pick L. Virchow Archiv 1899; Bd clvi: S. 507. Cited by Cuthbert Lockyer, Fibroids and Allied Tumours (Myoma and Adenomyoma): Their Pathology, Clinical Features and Surgical Treatment [London: Macmillan and Company, 1918], 333.

129

Cuthbert Lockyer, Fibroids and Allied Tumours, 334.

130

Schickele G. Weitere Beitrage zur Lehre von den mesonephritischen Tumoren. Beitr z. Geb. Bd. vi. S. 449.

131

Cuthbert Lockyer, Fibroids and Allied Tumours, 275. Lockyer cites: Schickele, Zentr. F. all. Path. und Anat., 1904;xv. S. 275.

132

Cuthbert Lockyer, Fibroids and Allied Tumours, 334.

133

Cuthbert Lockyer, Fibroids and Allied Tumours, 276. Lockyer cites: Firth, Zur Kasuistik der Adenomyome der Uterus. Zentr. F. Gynak 1903, Bd. xxvi: S. 626.

134

Cuthbert Lockyer, Fibroids and Allied Tumours (Myoma and Adenomyoma): Their Pathology, Clinical Features and Surgical Treatment [London: Macmillan and Company, 1918], 335.

135

Cuthbert Lockyer, Fibroids and Allied Tumours, 335. Lockyer C. Proc Roy Soc Med London (Obst and Gyn Sect.), 1913.

136

Cuthbert Lockyer, Fibroids and Allied Tumours, 371.

137

Cuthbert Lockyer, Fibroids and Allied Tumours, 371.

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Cuthbert Lockyer, Fibroids and Allied Tumours, 361.

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Cuthbert Lockyer, Fibroids and Allied Tumours, 361.

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Cuthbert Lockyer, Fibroids and Allied Tumours, 361.

141

Surgeons, then as now, often must rely on their clinical experience and clinical judgment. Controlled clinical trials with medication are much easier to justify and conduct than for surgery. In the twentieth century, prospective controlled surgical trials were first accepted in the study of cancer, only later for the study of benign disease. Even then, due to rampant medical legal litigation, studies were more readily conducted in countries with socialized medicine and limited liability.

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Cuthbert Lockyer, Fibroids and Allied Tumours, 444.

143

Metzger DA, Lessey BA, Soper JT, McCarty, Jr. KS, Haney AF. Hormone-resistant endometriosis following total abdominal hysterectomy and bilateral salpingo-oophorectomy: correlation with histology and steroid receptor content. Obstet Gynecol 1991;78:946–950.

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Cuthbert Lockyer, Fibroids and Allied Tumours, 444.

145

Cullen TS. Adenomyoma of the recto-vaginal septum. Johns Hopkins Hospital Bulletin 1917;28:343–349:344. See also: Cullen TS. 1917;28:343–9. Plate LXVII, Figure 3.

146

Cuthbert Lockyer, Fibroids and Allied Tumours, 332–3.

147

Cuthbert Lockyer, Fibroids and Allied Tumours, 265.

148

Cuthbert Lockyer, Fibroids and Allied Tumours, 366–7.

149

Cuthbert Lockyer, Fibroids and Allied Tumours, 366–7.

150

Cullen TS. Adenomyoma of the rectovaginal septum. JAMA 1916;LXVII:401–406:406.

151

Cuthbert Lockyer, Fibroids and Allied Tumours, 433.

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Cuthbert Lockyer, Fibroids and Allied Tumours, 443.

153

Cuthbert Lockyer, Fibroids and Allied Tumours, 367–8.

154

Cuthbert Lockyer, Fibroids and Allied Tumours, 369.

155

Cuthbert Lockyer, Fibroids and Allied Tumours, 369.

156

Cuthbert Lockyer, Fibroids and Allied Tumours, 371.

157

Cuthbert Lockyer, Fibroids and Allied Tumours, 372.

158

Cuthbert Lockyer, Fibroids and Allied Tumours, 372.

159

Cuthbert Lockyer, Fibroids and Allied Tumours, 380. Williams, JW. Decidual formation throughout the uterine muscularis: a contribution to the origin of adenomyoma of the uterus. Trans Southern Surgical Assoc 1904;17:119–132. “In this paper it is my object to describe a case of unusual decidual formation occurring in a uterus, the seat of a placenta praevia, which to my mind offers conclusive proof of the extension downward into the muscularis of processes from the endometrium, which could readily afford the basis from which a adenomyoma might be derived.” Williams reviewed the literature on uterine adenomyomas to 1904.

160

Cuthbert Lockyer, Fibroids and Allied Tumours, 395.

161

Meyer, Robert. Cited by Cuthbert Lockyer, Fibroids and Allied Tumours, 398.

162

Cuthbert Lockyer, Fibroids and Allied Tumours, 397. Cited Frankl, Oskar. Archiv fur Gynak Bd. xciii. Tafel xii.

163

Cuthbert Lockyer, Fibroids and Allied Tumours, 371.

164

Cuthbert Lockyer, Fibroids and Allied Tumours (Myoma and Adenomyoma): Their Pathology, Clinical Features and Surgical Treatment [London: Macmillan and Company, 1918], 270–11. Lockyer opined “The description he (v. Recklinghausen) gives of his second variety (actually his second “class”), i.e. the centrally situated growth hold good to this day.”

165

Cuthbert Lockyer, Fibroids and Allied Tumours, 270–11

166

Cuthbert Lockyer, Fibroids and Allied Tumours, 303.

167

Cuthbert Lockyer, Fibroids and Allied Tumours, 306.

168

Cullen TS. Adenomyoma of the rectovaginal septum. JAMA 1916;LXVII:401–406:403. Lockyer did not include Cullen’s 1916 classification; it was published too late for inclusion in his book.

169

Cullen TS. The distribution of adenomyomata containing uterine mucosa. American Journal of Obstetrics and Diseases of Women and Children. 1919;180:130–138. In 1917, Foster S. Kellogg recognized the importance of Cullen’s classification by republishing it verbatim in the Boston Medical and Surgical Journal. Kellogg FS. Adenomyoma of the recto-vaginal septum. Boston Medical and Surgical Journal 1917;CLXXVI:22–24.

170

Cullen TS. The distribution of adenomyomata containing uterine mucosa. American Journal of Obstetrics and Diseases of Women and Children. 1919;180:130–138:130.

171

Cullen TS. The distribution of adenomyomata containing uterine mucosa. 1919;180:130–138:136.

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Cullen TS. The distribution of adenomyomata containing uterine mucosa. 1919;180:130–138:137. Referring to uterine mucosa in the ovary, Cullen stated: “In due time a sufficient number of such cases will undoubtedly be reported and then we shall be able to give a composite picture of both the clinical course and of the histological changes that occur in this most unusual group of cases.”

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Cullen TS. The distribution of adenomyomata containing uterine mucosa. 1919;180:130–138:136.

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Cullen TS. The distribution of adenomyomata containing uterine mucosa. American Journal of Obstetrics and Diseases of Women and Children. 1919;180:130–138:135.

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Cullen TS. The distribution of adenomyomata containing uterine mucosa. 1919;180:130–138:135.

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Cullen TS. The distribution of adenomyomata containing uterine mucosa. 1919;180:130–138:133.

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178

Te Linde, RW. In Memoriam: Thomas Stephen Cullen, 1868–1953. Trans American Gynecological Society 1953;76:227–229:228.

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Te Linde, RW. In Memoriam: Trans American Gynecological Society 1953;76:227–229:228.

180

Cullen TS. Dr. Howard A. Kelly: Professor of Gynecology in the Johns Hopkins University and Gynecologist-in Chief to the Johns Hopkins Hospital. Bull Johns Hopkins Hospital 1919;xxx:287–293.

181

Blogg, MW. Bibliography of Howard A. Kelly, M. D., LL.D., Hon. F.R.C.S. Johns Hopkins Hospital Bulletin 1919;xxx:293–302.

182

Blogg, MW. Bibliography of Howard A. Kelly, 1919;xxx:293–302.

183

Novak E. Hematoma of the ovary, including corpus luteum cysts. Bulletin Johns Hopkins Hospital 1917;28:349–354:350. Novak actively investigated the interrelationship of the corpus luteum and menstruation. See: Novak E. The corpus luteum –Its life cycle and its role in menstrual disorders. JAMA 1916;lxvii:1285.

184

Novak E. Hematoma of the ovary, including corpus luteum cysts. Bulletin Johns Hopkins Hospital 1917;28:349–354.

185

Novak E. Hematoma of the ovary, including corpus luteum cysts. Bulletin Johns Hopkins Hospital 1917;28:349–354: 349–50.

186

Novak E. Hematoma of the ovary, including corpus luteum cysts. 1917;28:349–354:350.

187

Cuthbert Lockyer, Fibroids and Allied Tumours (Myoma and Adenomyoma): Their Pathology, Clinical Features and Surgical Treatment [London: Macmillan and Company, 1918], 321–329.

188

Cuthbert Lockyer, Fibroids and Allied Tumours, 327.

189

Illustrated Stedman’s Medical Dictionary. 24th ed. [Baltimore, MD: Williams & Wilkins, 1982], 1033. “Paroophoron: Corpus pampiniforme; parovarium; a few scattered rudimentary tubules in the broad ligament between the epoophoron and the uterus; remnants of the tubules and glomeruli of the lower part of the Wolffian body.”

190

Semmelink and de Joselin de Jong. Monatsschr für Beb u Gyun Bd. xxii:244, Figure 7.

191

Cuthbert Lockyer, Fibroids and Allied Tumours (Myoma and Adenomyoma): Their Pathology, Clinical Features and Surgical Treatment [London: Macmillan and Company, 1918], 328. Figure 198.

192

Semmelink and de Joselin de Jong. Monatsschr für Beb u Gyn Bd. xxii:244, Figure 7. Cuthbert Lockyer, Fibroids and Allied Tumours (Myoma and Adenomyoma): Their Pathology, Clinical Features and Surgical Treatment [London: Macmillan and Company, 1918], 328. Figure 198.

193

Pick L. Ist das Vorhandensein der Adenomyome des Epoophoron erwiesen? Centr f. Gynak 1900, No. 15, S. 389.

194

195

Casler DB. A unique, diffuse uterine tumor, really an adenomyoma, with stroma, but no glands. Menstruation after complete hysterectomy due to uterine mucosa in remaining ovary. Transactions of the American Gynecological Society. 1919;44:69–84:70–71. A panhysterectomy means removal of the entire uterus including the cervix. A supracervical or partial hysterectomy means removal of the body of the uterus but not the cervix.

196

Casler DB. Transactions of the American Gynecological Society. 1919;44:69–84:72.

197

Casler DB. Transactions of the American Gynecological Society. 1919;44:69–84:74.

198

Robert Meyer, Autobiography of Dr. Robert Meyer (1864–1947): A Short Abstract of a Long Life [New York: Henry Schuman, 1949], 70–71.

199

Emge LA. The elusive adenomyosis of the uterus. Am J Obstet Gynecol 1962;83:1541–1563:1554. Emge added that stromatosis was first described in 1864 by Virchow. Robert Meyer, Autobiography of Dr. Robert Meyer (1864–1947): A Short Abstract of a Long Life [New York: Henry Schuman, 1949], 63. “In 1919 I published a case of adenomyosis sarcomatosa, unknown before that. In definite adenomyosis of the uterus, its stroma grows deeper and through the whole uterine wall inside the lymphatics (Zentralbl. F. Gyn. 1919, 43). The same sarcoma of the stroma endometrii is described under a different name in the United States.”

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201

Casler DB. Transactions of the American Gynecological Society. 1919;44:69–84:76.

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Casler DB. Transactions of the American Gynecological Society. 1919;44:69–84:76.

203

A cigarette drain is a made from a long tubular piece of thin rubber filled with gauze sponges.

204

Casler DB. Transactions of the American Gynecological Society. 1919;44:69–84:76–77. See Fig. 6. “Drawing of ovarian tumor and adherent sigmoid, showing almost complete obstruction of the sigmoid, due to growth.”

205

Casler DB. Transactions of the American Gynecological Society. 1919;44:69–84:77. See Figure 6,

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Casler DB. Transactions of the American Gynecological Society. 1919;44:69–84:77.

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Casler DB. Transactions of the American Gynecological Society. 1919;44:69–84:77–78.

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Casler DB. Transactions of the American Gynecological Society. 1919;44:69–84:78–79. Figure 10.

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210

Casler DB. Transactions of the American Gynecological Society. 1919;44:69–84:77.

211

Casler DB. Transactions of the American Gynecological Society. 1919;44:69–84:77, 80.

212

Ancel Blaustein, “Pelvic endometriosis,” in Pathology of the Female Genital Tract, ed. Ancel Blaustein [New York: Springer-Verlag, 1977], 404–419. See figure 22.29, page 416. “Napkin-ringlike constriction of the [bowel] wall, intramural endometriosis present.”

213

Casler DB. Transactions of the American Gynecological Society. 1919;44:69–84:82.

214

Casler DB. A unique diffuse uterine tumor, really an adenomyoma with stroma but no glands; menstruation after complete hysterectomy due to uterine mucosa in remaining ovary. Surg Gynecol Obstet 1920;31:150.

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