Microscopy and the Discovery of Endometriosis and Adenomyosis

A History of Endometriosis

3. Microscopy and the Discovery of Endometriosis and Adenomyosis

Ronald E. Batt¹

(1)

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

Abstract

Study of histologic sections of uterine tissue was essential to discover the new disease uterine endometriosis (adenomyosis) and to differentiate it from a degenerating uterine leiomyoma (fibroid) and from uterine cancer. Unfortunately, the Imperial reform of 1786 had demoted the mission and status of pathological anatomy by transferring microscopy to the department of physiology and thus deprived all subsequent pathological anatomic prosectors – including Rokitansky – use of the microscope.² Then two publications appeared in the 1830s that demonstrated the importance of microscopy in pathological anatomy. Between 1835 and 1840 Johannes Müller of Berlin published his highly acclaimed Handbook of Human Physiology. Between 1837 and 1844, Joseph Berres of Vienna published the first atlas of the histology of the human body entitled Anatomy of the Microscopic Formations of the Human Body.³ Both works appeared at a crucial point in Rokitansky’s career and they undoubtedly aroused his interest in microscopy.

Reconstructing the history of the discovery of the condition we today call adenomyosis is neither simple nor easy because for almost 90 years adenomyosis and endometriosis were considered – with the exception of ovarian endometriosis – as one disease: ‘adenomyoma.’ As such, the early history of adenomyosis is interwoven with the early history of endometriosis, and it was not until the mid-1920 that the two conditions were finally separated.

Benagiano and Brosens¹

Emergence of Microscopy in Rokitansky’s Department

In 1834, Rokitansky had been appointed associate professor of pathological anatomy by Baron von Türkheim, an appointment that put Rokitansky in a position to formally establish his research program. In rapid succession, von Türkheim founded the Second Vienna Medical School, inaugurated the Medical Yearbooks of the Imperial Royal Austrian State in 1836, and in 1837 organized the Vienna Society of Physicians to stimulate scientific research, discussion, and publication.⁴ The fact that von Türkheim built the Second Vienna Medical School around Rokitansky’s autopsy table gave Rokitansky space for innovation; incrementally he reintroduced microscopy into pathological anatomy at the University of Vienna.

As Rokitansky began gathering material for his Handbook of Pathological Anatomy, the need for histologic illustrations became pressing, given the illustrated treatises of Müller and Berres. While on an academic pilgrimage to Paris in 1842, arranged by Baron von Türkheim, Rokitansky not only bought a Brunner microscope, he availed himself of an opportunity to visit England.⁵ There he was entertained in the home of Joseph Jackson Lister, famous for improving the achromatic microscopic lens system.⁶ Between the years 1826 and 1830, Joseph Jackson Lister, the father of Joseph Lord Lister, had discovered the “law of aplanatic foci”⁷ which enabled him to construct an achromatic microscope lens system that was virtually freed from spherical and chromatic aberrations.⁸ Lister joined two achromatic lenses together with Canadian balsam by which process effective light was increased by nearly 100%.⁹

It is reasonable to infer from references in the 1846 edition of his Handbook of Pathological Anatomy that upon his return to Vienna Rokitansky made principal use of his microscope when he suspected cancer.¹⁰ The microscope did not live up to his expectations. “Microscopic analysis, therefore, from which important disclosures in relation to the diagnosis of benignant and of malignant growths, and tenable grounds for the establishment of a system were expected, has in reality thrown but an uncertain light upon the subject.”¹¹ However, when studying the development of cancer, he found the microscope more satisfying. “Cancer-cyst varies in respect to size from the microscopic, to the circumference of the colossal cysts, in the compound cystoid…Within the encysted parenchyma, again, is sometimes lodged a smaller, filial cyst…Upon this point and upon the development of the cancer-cyst microscopic inspection throws much light.”¹² He discussed microscopic examination of “excrescences occurring upon the inner surface of the cyst.”¹³ In 1846 Rokitansky was aware of cell-nuclei and had a rudimentary idea of the role of the cell in development, most likely from reading the microscopic research of Schwann on the notochord and of Müller and Virchow on cancer. He mentioned Virchow by name. “This history of cyst-development is essentially corroborated by the expansion of the cell-nuclei, of so frequent, although by no means exclusive, occurrence in cancer-cells; an expansion first pointed out with precision by Virchow, but which, owing to the identity of development of the normal gland vesicle, and of the cyst, cannot be regarded as heteroplastic. It consists in the development of the cell-nucleus into a comprehensive cyst, identical with that evolved out of the naked nucleus.”¹⁴

Rokitansky had long recognized malignancies by their macroscopic characteristics. “They reveal their cancerous nature by their external medullary characters, as well as by their vigorous growth. In the capillaries the coagulation assumes the form of the cancerous depot-so called metastasis (capillary phlebitis).”¹⁵ In the next passage, Rokitansky seems to be comparing his 19-year total immersion in macropathology with his emergent 4-year experience with histopathology. “We have the following forms, some more or less recognizable with the naked eye. (a) A medullary carcinoma etc.”¹⁶Nonetheless, even in 1846, there can be little doubt that Rokitansky appreciated the benefit of microscopy for diagnosis and study of cancer. “The differences, however, discoverable with the naked eye in carcinoma, are slight compared with those revealed in the elementary texture of medullary carcinoma, with the aid of a magnifying power.”¹⁷ Furthermore, even at this early stage of his experimentation with microscopy, Rokitansky can be seen studying not only development of mononuclear and multinucleated cells but also cellular “dissilience” or cell fragmentation. “Under a magnifying power of 90 diameters, the substance of fungus haematodes exhibits a stroma, consisting of two distinct webs, which appear to interlace each other in all directions…Further examination shows this wreath-like tissue, which at first seemed opaque and granular, to be studded with crowds of minute nucleated cells, which, under a magnifying power of 400, are distinctly set forth as round or oval cells, many, although not all, containing one or several nuclei, others engaged in the act of elongation, others again in process of dissilience.”¹⁸

Though Rokitansky never mastered the microscope personally, he used his considerable administrative and scientific influence to ensure that microscopy flourished in his department and the other departments of the University of Vienna. His assistant Joseph Engel was the first person in Vienna to give lectures on pathological histology.¹⁹ The question may be raised why Rokitansky did not send more of his tissues for histological examination by his assistants or colleagues. The answer may lie in a clash of personalities. Joseph Engel, an accomplished microscopist in the early 1840s, and “undoubtedly the most gifted and versatile” of Rokitansky’s assistants, quarreled with Rokitansky as he did later with colleagues in pathology in Prague and the St. Joseph’s Academy in Vienna. Unfortunately “this highly gifted man died in resigned isolation.”²⁰ Had their relationship been more cordial, Rokitansky might have been persuaded to send more of his interesting autopsy specimens for histologic examination and by so doing have discovered endometriosis earlier in his career. On the other hand, “staining and hardening techniques were still undeveloped” in the 1850s; this may be another reason why Rokitansky was not fully appreciative of the potential benefits from applying histology more widely in his personal research.²¹

Rokitansky and certain able assistants had some noteworthy accomplishments at the University of Vienna in the middle years of the century. Rokitansky appointed Carl Wedl (1815–1891) in 1846 and Carl Stellwag von Carion (1823–1904) in 1847 to perform histological work in his department. Then in 1853 he was responsible for the appointment of Carl Wedl as associate professor to an endowed Chair of Histology at the University of Vienna, the first in “German-speaking territories.”²² By 1854, Wedl had his own two-room Institute of Histology on the second floor of the Old Rifle Factory, another first of its kind in German-speaking lands. Wedl soon became “a very popular and prominent histopathologist of the Second Vienna Medical School.”²³ In 1855, Wedl published a comprehensive 825 page work entitled Rudiments of Pathological Histology.²⁴

Leo Graf v. Hohenstein Thun, successor to von Türkheim, carried on the latter’s reforms. He appointed the physiologist Ernst von Brücke, an assistant of Johannes Müller of Berlin, to the University of Vienna faculty to develop experimental methods “in order to bring the predominantly morphologically oriented Vienna Medial School completely up-to-date.”²⁵ Even with these innovations, the University of Vienna was far behind developments in pathological anatomy in German universities.²⁶ In 1855, Virchow first enunciated his cell theory in the famous formula “omnis cellula a cellula”²⁷; 1855 was also the year that Rokitansky published the revised second and final edition of his Handbook of Pathological Anatomy. With the second edition of his Handbook, Rokitansky completed his primary research objective – the classification of human pathological anatomy begun decades before by the French. At this stage in his career, Rokitansky was also occupied by many high-level administrative duties in the University of Vienna.

Several unrelated events in these years combined to make Rokitansky see the inevitability of microscopic histopathology. Joseph Lister married April 23, 1856 and after spending a month in England, started a tour of Europe during which the couple visited many celebrated medical schools including Vienna. Since the Listers and Rokitansky’s were family friends,²⁸ Rokitansky invited young Lister and his new wife to supper that evening in his home.²⁹In so doing, Rokitansky returned the courtesy of Joseph Jackson Lister in 1842 when Joseph Lister was yet an unknown.³⁰ Considering that happy memory and the fact that young Lister had just published two papers on microscopy in 1853,³¹ it is not improbable that they discussed the topic of microscopy. Also in 1853 came unexpected praise from Rudolph Virchow for Rokitansky’s own work and that of the Second Vienna Medical School.³² In 1858, Rudolph Virchow again influenced Rokitansky when he expanded his cell theory of 1855 – omnis cellula a cellula [all cells from other cells] – into a theory “that all disease was a disease of cells.”³³ Virchow “transformed pathology” in 1858 with the publication of Cellularpathologie.³⁴

Each of these events may well have contributed to Rokitansky’s decision in 1859 to permit Virchow’s lectures on cellular pathology to be taught in the Department of Pathology at the University of Vienna. “In the winter semester of 1859–60…Klob, Rokitansky’s assistant in Vienna, posted on his blackboard the following notice: ‘From Thursday on, lectures on pathological anatomy will be delivered according to the cell doctrine of Virchow.’”³⁵Furthermore, by the late 1850s there was mounting pressure at the University of Vienna, to go much further than importing just one German physiologist to integrate the German “experimental-physiological” approach of Johannes Müller and his school into pathological anatomy and other departments to make the classification of disease more precise.³⁶

The rise of surgery constituted another factor that contributed to the obsolescence of macroscopic morbid pathological anatomy. Influenced by Rokitansky and Skoda, Franz Schuh (1804–1865) elevated surgery to a science at the University of Vienna.³⁷ Schuh implemented the methods of microscopic and chemical research established by Johannes Müller for research into benign and malignant growths.³⁸On January 27, 1847, he introduced ether anesthesia in Vienna.³⁹ The availability of surgical anesthesia, chemical testing, and microscopic histopathology for research combined to increase the importance and prestige of the department of surgery.⁴⁰ In 1867, on the initiative of Rokitansky and several other professors, Theodor Billroth (1829–1894) was appointed professor of surgery, 1 year after the disastrous Austro-Prussian War of 1866.⁴¹ Having trained under Rudolf Wagner, Johannes Müller, Schonlein, Romberg, Traube, and von Langenbeck; Billroth “embodied all those tendencies which had made German medicine great since the middle of the nineteenth century.”⁴²

Once Rokitansky had completed his Handbook and, sensing the inevitability of microscopic histopathology, an aging master macroscopic pathologist made the decision to use microscopy to study the histopathology of select benign lesions. This step was a necessary precursor to the discovery of endometriosis. In sum, taking Rokitansky at his word – that he relied on his own experience – we can accept that the references to microscopy in the 1846 publication were based on his own, albeit, limited personal experience. Armed with his Brunner microscope, he had begun experimenting with the histopathology of malignancy only 4 years before Virchow devastated his hematohumoral theory of disease. Gradually Rokitansky accepted Virchow’s theory of cellular pathology and found it compatible with his own localistic pathology. Finally, he changed a lifelong habit and began to use the microscope to study the histopathology of interesting benign lesions. In the final analysis, Virchow’s influence was decisive.

Sigerist opined that “Upon the shoulders of Virchow rests the whole structure of modern pathology. Much preparatory work had been done macroscopically, especially by the Viennese, Rokitansky, but Virchow placed the microscope into the hands of pathologists. This only made it possible to see the minuter changes and to undertake a more exact classification of disease.”⁴³ With those words the German physician-medical historian Henry Sigerist recognized Virchow’s influence on Rokitansky. For the microscope was crucial not only for Rokitansky’s entrée to the histopathology of malignant disease; the microscope was also the instrument and histopathology the technique necessary for Rokitansky’s identification of benign uterine and extrauterine endometriosis.

1860: Discovery of Two New Diseases – Endometriosis and Adenomyosis

Sarcoma and carcinoma…Kindred new growths, important from their frequency no less than from the question arising, in every concrete case, as to their innocency or malignancy. We have selected the term sarcoma to designate the benign growths, not because of any especial analogy with muscle-flesh, but in order to fix and define a name familiarized by long usage, and also by no little abuse. [Italics added] The malignant we shall leave in possession of their ancient characteristic appellation cancer,-carcinoma.

Carl Rokitansky⁴⁴

After observing thousands of benign uterine fibroids, benign hemorrhagic ovarian cysts and benign uterine polyps macroscopically, what specimen so riveted Rokitansky’s attention in 1860 that he examined it microscopically?⁴⁵ It was a fresh surgical specimen! A fresh “fist sized uterine polyp” from a live patient!⁴⁶ That specimen, once examined microscopically, led to further investigation of autopsy specimens and specimens preserved in “wine-spirits.”⁴⁷ What is the evidence for this assumption? We must contrast the brilliant internist Adolph Kussmaul’s recollection of Rokitansky’s taciturn nature⁴⁸ with Rokitansky’s exclamation that he examined a fresh specimen. The invitation to examine a rare fresh specimen microscopically must have proved irresistible. Careful microscopic examination then led to the identification and description of endometriosis in several other specimens. The discovery of endometriosis was merely one of many pathologic lesions detected by his discerning gaze, but an incident of transcendent importance to the history of endometriosis.⁴⁹

In 1860 Rokitansky described three phenotypes of endometriosis containing endometrial stroma and glands: one invaded the uterine muscular wall (Sarcoma adenoids uterinum and the cystic variety: Cystosarcoma adenoids uterinum) accompanied by myometrial hypertrophy, the second invaded the endometrial cavity forming a polyp (Cystosarcoma adenoids uterinum polyposum), and the third invaded the ovary (Ein Ovarial-Cystosarcom).⁵⁰Rokitansky gave the three phenotypes descriptive Latin names following common practice at mid-nineteenth century. He selected the term sarcoma to designate a benign growth. At mid-nineteenth century, Rokitansky defined sarcoma and carcinoma:

Sarcoma and carcinoma…Kindred new growths, important from their frequency no less than from the question arising, in every concrete case, as to their innocency or malignancy. We have selected the term sarcoma to designate the benign growths, not because of any especial analogy with muscle-flesh, but in order to fix and define a name familiarized by long usage, and also by no little abuse. The malignant we shall leave in possession of their ancient characteristic appellation cancer,-carcinoma.⁵¹

Rokitansky was well aware that both cellular atypia and invasion were required to diagnose carcinoma (cancer).⁵²

From the beginning of their history, endometriosis and adenomyosis have been characterized as benign invasive diseases. Regarding adenomyosis (internal endometriosis), Rokitansky described the “wedge” of benign basal endometrium composed of endometrial glands and stroma that invaded the underlying muscle of the uterine wall.⁵³

On rare occasions the elongation of the uterine glands extend in both directions, towards the uterine cavity as well as into the parenchyma. In this case the incumbent bulge acts as a plug of parallel fibers driven into the uterus. Such a picture was encountered in the thick walled uterus of an older woman. Below the left tubal opening was a club-shaped, smooth polyp, about 1” 2’” long, with a 1 ½”’ diameter in the neck, and enlarging to 4–5”’ at the free end. A cut through the entire mass showed that the neck penetrated in a wedge-shaped fashion into the uterus to a depth of 4”’. The cut surface appears as thready-fibers in its entire length and can be unraveled in that direction. This arrangement is provided by extremely long glandular tubules kept together by a nuclei rich connective tissue.⁵⁴

Rokitansky also distinguished between benign solid tumors of the uterus – fibroids and adenomyomas. Adenomyomas composed of endometrial glands and stroma without an outer fibrous capsule invaded deeply within the uterine muscle making their removal difficult. To this benign lesion he gave the descriptive name “Sarcoma adenoids uterinum,” or in modern terminology, adenomyosis.⁵⁵ If this benign lesion degenerated and became cystic, Rokitansky called it “Cystosarcoma adenoids uterinum.” It cannot be emphasized often enough that Rokitansky defined sarcoma as a benign lesion. For other benign glandular tumors that projected into the cavity of the uterus, Rokitansky retained the old name: “Polyp, Uteruspolyp would be distinguished from the round fibroids prolapsed into the uterine cavity.”⁵⁶Rokitansky credited prior authorities as having described uterine polyps: H. Müller⁵⁷ of Würzburg (1854) ⁵⁸ and Paget’s “continuous growth,” the latter descriptive of adenomatous uterine polyps.⁵⁹

Rokitansky also described external endometriosis, a benign ovarian endometrioma as an “ovarian cystosarcoma.”⁶⁰

d) An Ovarian – Cystosarcoma. The autopsy performed on 2, March 1859 on a 68 years old, malnourished female yielded the following: the body is small and thin; both lungs for the most part are adherent, in the right upper lobe there is a walnut sized cavity with extensive, indurated desiccation of the tissue and an incorporated yellow, cheesy nodules. In the lung there are numerous thickened, airless areas infiltrated by tenacious, yellow – brownish pus. The ventricles of the heart contain loose fibrin clots. The liver is enlarged and fatty, the spleen s small, the stomach, bowels and kidneys are pale; in the capsule of the left kidney there is a white fibroid node and the bladder is empty. A small, retroflexed uterus is situated in the left recto-vaginal space whereas its fundus is wedged between the cervix and the left ovarian tumor. The latter is degenerated to a fist sized tumor, the right half presents as a dense, fibrous mass, whereas the left half consists of an aggregate of serous cysts. The largest of the cysts partially protruded into a cavity of the fibrous mass. The remaining small cysts were adherent to the rest of the surface. The entire tumor was twisted by its sheltered position so that the cystic portion pointed to the right. The tube was somewhat stretched over the tumor and fixed to it up to its fimbriated end. The right ovary was dense, atrophied and contained a bean sized cyst which protruded through the surface. Closer examination of the fibrous part of the tumor disclosed on cross-section, especially around the cysts, a glandular appearance with scattered, delicate vesicles and grainy nodules. In addition, it contained individual mucous containing cysts of millet – hemp corn size. The microscopic examination revealed numerous tubular, epithelial lined structures within a thick, connective tissue layer. On cross section of these tubular structures, individual slit-like, lacunar clefts were evident into which papillary excrescences of connective tissue intruded.

Rokitansky drew conclusions from his observations: Conclusions 1–4 related to sarcoma adenoides uterinum and cystosarcoma adenoides uterinum. Conclusion 5 relates to the degenerated left ovary and Conclusion 6 relates to the right ovary as well as the left ovary.

5. Sarcoma tissue in the form of papillary excrescences grow into the space of the cyst-like, degenerated tubules. The slit-like, lacunar clefts scattered within the sarcoma produce on cross section a granular appearance. The circumscribed nodes, which can be shelled out, and appear incorporated in the sarcoma mass doubtless originate from the filling of the greater cyst spaces by intruding tumor tissue – A common appearance, which is especially pronounced in cystosarcoma adenoides mammarium.

6. A sarcoma, containing uterine glandular tubules is also found in the ovaries and some cystic structures of the ovaries, therefore become a Cystosarcoma adenoides uterinum.

Recall once more that Rokitansky defined the term sarcoma as a benign lesion. “We have selected the term sarcoma to designate the benign growths, not because of any especial analogy with muscle-flesh, but in order to fix and define a name familiarized by long usage, and also by no little abuse.”⁶¹

With a few strokes of his pen, Rokitansky described several phenotypes of benign endometriosis. He established the objective diagnostic criteria for adenomyosis and endometriosis, the presence of endometrial glands and stroma by which endometriotic diseases have been defined ever since. The very definition of endometriosis – the microscopic identification of excess endometrial glands and stroma located in ectopic locations – is based on Rokitansky’s research. By the same strokes of his pen, Rokitansky established pathology as the premier basic science for gynecology and for endometriosis research for the next 100 years.

In 1861, Rokitansky discussed adenomyomas in the third volume of his Textbook of Pathological Anatomy.⁶² He observed several types of “omas” (benign tumors), which he classified as distinct phenotypes of endometriosis: benign solid and cystic intramural uterine adenomyomas, benign solid intracavitary uterine adenomas, and a benign cystic ovarian endometrioma. All were composed of excess müllerian tissue acquired after birth. Rokitansky set a precedent when he used the descriptive suffix “oma,” meaning a tumor or neoplasm, to denote the appearance of endometriotic lesions, both uterine and extrauterine. All investigators, from Rokitansky until Sampson’s pathbreaking research in the 1920s, saw only solid and cystic endometriotic “oma” tumors. Until Sampson, pathologists and surgeons saw only the “oma search image” that Rokitansky had prepared them to see.⁶³

The story leading up to Rokitansky’s discovery has chronicled his extensive experience, his educated medical gaze and exacting observation and his prepared mind. Commencing with his criticism of 1846, Rudolph Virchow influenced Rokitansky over the next decade and a half. Virchow reinforced the importance of microscopic cellular pathology as the key to the discovery and histological definition of endometriosis. From the start, technology influenced the emergence of knowledge regarding endometriosis and all benign müllerian diseases.

Rokitansky identified and described uterine and extrauterine endometriosis two decades before refrigeration systems were installed in European morgues to retard decomposition.⁶⁴ Even then the state of decay must have varied in direct proportion to the length of time between death and autopsy. Such were the conditions that in all probability long delayed the differentiation of uterine endometriosis from degenerated uterine fibroids and cancer, ⁶⁵and ovarian endometriomas from non-endometriotic chocolate cysts.⁶⁶ Regarding simple ovarian cysts, Rokitansky observed in 1846 that they may contain “an opaque chocolate-colored or inky fluid.”⁶⁷ Undoubtedly, some of them were ovarian endometriomas, ovarian cysts lined by ectopic endometrial glands and stroma containing old menstrual blood.

Rokitansky’s magnificent Handbook of Pathological Anatomy and his report of the new diseases endometriosis and adenomyosis in 1860 was based on dissections performed in “miserable quarters” of the old Leichenhaus, the University of Vienna autopsy house.⁶⁸ Considering the protocol for rapid evisceration of corpses under such circumstances, combined with limited light making it difficult to see into the depths of the pelvis, it is not surprising that Rokitansky first identified endometriosis in visceral organs – uterus and ovary – after removal from the pelvis. Extrauterine endometriosis in the deep pelvis awaited detection until the end of the nineteenth century when asepsis permitted safer surgery and surgical pathology afforded clinical pathological correlation. In sum, Rokitansky not only described adenomyosis and endometriosis microscopically – detailing the presence of endometrial glands and stroma; he differentiated uterine endometriosis (adenomyomas) from uterine fibroids, described ovarian endometriosis, gave the disease descriptive Latin names, and suggested chronic inflammation as possibly the pathogenesis of Sarcoma adenoids uterinum, Cystosarcoma adenoids uterinum, Cystosarcoma adenoids uterinum polyposum, and Ein Ovarial-Cystosarcom.⁶⁹

Two New Diseases with Descriptive Names

What is the importance of a name? Based on ontological theory of specific diseases, a descriptive name for an entity such as “Sarcoma adenoids uterinum,”⁷⁰ establishes a new disease, separate and distinct from other diseases, thereby focusing the attention of other physicians and investigators to identify similar cases.⁷¹ Equally important to discovering and naming a new disease is the professional stature of the author. Rokitansky possessed an international reputation when he described adenomyomas in 1860, which was an important reason for general acceptance of his findings. Endometriosis was a nameless disease before Rokitansky.⁷²

What did physicians perceive before Rokitansky diagnosed endometriosis? We have information in only one instance. One physician perceived and removed a uterine polyp, the fresh specimen that caught Rokitansky’s attention. What were the patient’s complaints before Rokitansky examined specimens that had been removed from their bodies at autopsy and diagnosed endometriosis? There is no record. However, from clinical experience, the author can be reasonably certain that one patient experienced “labor pains” as she delivered a fist-sized uterine polyp. Once named in 1860, the study of endometriosis took on a life of its own. But it was not until 1896 that Freund of Strassburg – and some years later Cullen of Baltimore – described patient’s complaints and the physical signs of uterine endometriosis detectable by physicians.

In support of Rokitansky as discover of endometriosis and adenomyosis, the author’s interpretation of the criteria of the eminent surgeon Owen H. Wangensteen may be applied: “(1) who showed the way; (2) continuance of the practice; (3) influence of the discovery on contemporary and current practice.”⁷³ In other words: (1) who discovered endometriosis, gave a detailed description, published the findings, and was cited and acknowledged as the discoverer by subsequent investigators;⁷⁴ (2) did other pathologists continued to diagnose uterine endometriosis by the same techniques as Rokitansky: macroscopic description and histopathology?⁷⁵ (3) Taking influence on practice to mean treatment of patients, did Rokitansky’s discovery influence clinical practice?⁷⁶

Rokitansky met the criteria of Wangensteen. First, Rokitansky discovered and described uterine endometriosis (adenomyoma, adenomyosis) and extrauterine endometriosis (ovarian endometriosis) and his priority has been acknowledged into the twenty-first century.⁷⁷ Second, innumerable pathologists have identified internal endometriosis – adenomyosis – using the diagnostic criteria established by Rokitansky. His former assistant Hans Chiari described tubal endometriosis (salpingitis isthmica nodosa). Third, through Chiari, Rokitansky influenced the eminent German pathologist von Recklinghausen and the German gynecologist Wilhelm A. Freund; the latter wrote the first clinical description of the disease uterine adenomyoma in 1896, a description that empowered physicians to make a presumptive diagnosis of uterine adenomyoma in the office. In evidence, von Recklinghausen cited: “Rokitansky’s Cystosarcoma adenoides uterinum” in 1893⁷⁸; Rokitansky’s “Lehrbuch der pathology. Anatomie. 1861. III. 475 u. 490” and “H. Chiari, Zur pathology. Anatomie d. Eileiterkatarrhs. Prager Zeitschr. F. Heilkunde. 1887. VIII. 457” in 1896.⁷⁹

Then the personal criteria of Robert Scully, the doyen of gynecologic pathology, may be considered. Scully held identification of two cases of a disease to be both necessary and sufficient proof to establish a new disease entity.⁸⁰ By Scully’s criteria, Rokitansky did not establish new disease entities in 1860. Rokitansky described one case of uterine endometriosis (adenomyosis) and one case of extrauterine endometriosis (bilateral ovarian endometriomas) as well as several cases of uterine polyps.

Henry Sigerist noted that pathology, like anatomy and physiology, is a natural science that “describes natural phenomena, arranges them in systems and inquires into their origin.” Viewed from the perspective of the social historian, Sigerist, there are four levels of pathological investigation embracing three analytic questions and one synthetic question. With respect to the disease endometriosis, Rokitansky might have asked three analytic questions: (1) what is its etiology, (2) its pathological anatomy, and (3) its pathologic physiology; and one synthetic question: what is its pathogenesis?⁸¹Rokitansky did not enquire into etiology or pathologic physiology, but he did describe macroscopic and microscopic pathological anatomy and he speculated on an inflammatory pathogenesis for adenomyosis. See Appendix II for the full translation of Carl Rokitansky’s New Growth of Uterine Glands in Sarcomas of the Uterus and Ovaries.⁸²

In 2011, Benagiano and Brosens offered what they believed would be two “uncontroversial criteria” upon which to attribute the discovery of endometriosis and adenomyosis. “We believe that the identification of the pathology we today distinguish in peritoneal, deep, and ovarian endometriosis and in adenomyosis must be based on two objective criteria: the observation of the presence of endometrial glands and stroma outside the uterine cavity and the specification that this invasion was ‘benign’ (non-neoplastic) in nature.”⁸³

Benagiano and Brosens’ objective criterion one – “the observation of the presence of endometrial glands and stroma outside the uterine cavity”⁸⁴ – was fulfilled for adenomyosis in 1860 by Rokitansky, which disease he named sarcoma adenoides uterinum and cystosarcoma adenoides uterinum.

On rare occasions the elongation of the uterine glands extend in both directions, towards the uterine cavity as well as into the parenchyma. In this case the incumbent bulge acts as a plug of parallel fibers driven into the uterus. Such a picture was encountered in the thick walled uterus of an older woman. Below the left tubal opening was a club-shaped, smooth polyp, about 1ii 2iii long, with a 1 ½”’ diameter in the neck, and enlarging to 4–5”’ at the free end. A cut through the entire mass showed that the neck penetrated in a wedge-shaped fashion into the uterus to a depth of 4”’. The cut surface appears as thready-fibers in its entire length and can be unraveled in that direction. This arrangement is provided by extremely long glandular tubules kept together by a nuclei rich connective tissue.⁸⁵

In 2006, Benagiano and Brosens accepted Rokitansky’s discovery and histologic description of adenomyosis (adenomyoma) and his name for the disease: cystosarcoma adenoides uterinum: “…the first description of the condition initially named ‘adenomyoma’ was that provided in 1860 by the German pathologist Carl von Rokitansky, who found endometrial glands in the myometrium and designated this finding as ‘cystosarcoma adenoids uterinum.’”⁸⁶

Benagiano and Brosens’ objective criterion one also was fulfilled for (ovarian) endometriosis in 1860 by Rokitansky, which disease he named Ovarial-Sarcomen and Ovarial-Cystosarcom.⁸⁷ Recall that Rokitansky described external endometriosis and ovarian endometrioma as an “ovarian cystosarcoma.”

Rokitansky drew conclusions from his observations: Conclusion 6 relates to the right ovary as well as the left ovary.

6. A sarcoma, containing uterine glandular tubules is also found in the ovaries and some cystic structures of the ovaries, therefore become a Cystosarcoma adenoides uterinum.⁸⁹

Note that Rokitansky equated the histology of the “uterine glandular tubules” found in the ovaries to the uterine glandular tubules of adenomyosis in the uterus: Cystosarcoma adenoides uterinum. In other words, both adenomyosis and ovarian endometriosis exhibited the same histologic structure.

Benagiano and Brosens’ objective criterion two – “the specification that this invasion was ‘benign’ (non-neoplastic) in nature”⁹⁰ – was fulfilled for adenomyosis in 1860 by Rokitansky; he named this disease sarcoma adenoides uterinum and cystosarcoma adenoides uterinum. Benagiano and Brosens’ objective criterion two also was fulfilled for endometriosis, which disease Rokitansky named ovarian cystosarcoma. Rokitansky was well aware that both cellular atypia and invasion were required to diagnose carcinoma (cancer).⁹¹ Rokitansky was repeatedly influenced by Virchow, so much so, that in 1859 he permitted Virchow’s lectures on cellular pathology to be taught in his Department of Pathology at the University of Vienna. “In the winter semester of 1859–60…Klob, Rokitansky’s assistant in Vienna, posted on his blackboard the following notice: ‘From Thursday on, lectures on pathological anatomy will be delivered according to the cell doctrine of Virchow.’”⁹² Furthermore, Rokitansky, the first full-time professor of pathology defined sarcoma as “benign growths” and carcinoma as “malignant” at mid-nineteenth century:

Sarcoma and carcinoma…Kindred new growths, important from their frequency no less than from the question arising, in every concrete case, as to their innocency or malignancy. We have selected the term sarcoma to designate the benign growths, not because of any especial analogy with muscle-flesh, but in order to fix and define a name familiarized by long usage, and also by no little abuse. The malignant we shall leave in possession of their ancient characteristic appellation cancer,-carcinoma.⁹³

This English translation from Rokitansky’s A Manual of Pathological Anatomy, Volume I was published by the prestigious Sydenham Society in 1855, just 5 years before Rokitansky discovered and described adenomyosis and ovarian endometriosis.

Rokitansky deserves full credit for the discovery of endometriosis and adenomyosis as well as for establishing them as new disease entities. His prodigious reputation was responsible for their recognition as new diseases and his publications of 1860 and 1861 were the printed medium for its dissemination.⁹⁴ Considering the long interval of observation required of the gifted Rokitansky to discover adenomyosis and endometriosis, a persuasive argument may be mounted that it is unlikely that anyone in the generation immediately preceding him or in more remote generations discovered either disease and fulfilled the criteria of discovery of Wangensteen, Sigerist, or Benagiano and Brosens. Several authorities credit Rokitansky for the discovery of adenomyosis (sarcoma adenoides uterinum and cystosarcoma adenoides uterinum): von Recklinghausen,⁹⁵ Cullen,⁹⁶ Emge,⁹⁷ Benagiano and Brosens,⁹⁸ and Hudelist, Keckstein, and Wright.⁹⁹ Other authorities credit Rokitansky for the discovery of ovarian endometriosis: Pick, ¹⁰⁰ Sampson,¹⁰¹ and Hudelist, Keckstein, and Wright.¹⁰²

In fact, Sampson noted in 1925: “When these endometrial hematomas or cysts were described by me in 1921, I was not aware that they had been previously recognized and described. Three years later I found that Pick had described them in 1905 and had designated them adenoma or cystoma endometroides ovarii. Pick suggest that these cysts may be the same as Rokitansky’s cystosarcoma adenoides ovarii uterinum, described by the latter in his textbook of pathologic anatomy published in 1861. Should anyone’s name be attached to these ovarian cysts, it should be Pick’s or Rokitansky’s, not mine.”¹⁰³

However, some authors such as Ridley¹⁰⁴ and Knapp¹⁰⁵ disagree. Ridley was the gynecologist who demonstrated experimentally that shed human endometrium could be transplanted into the patient’s abdominal wall to cause external endometriosis.¹⁰⁶ In his 1968 review of the histogenesis of endometriosis, Ridley stated that he reviewed the writings and references in a “pamphlet” of Breus¹⁰⁷ and found “several references” that antedated Rokitansky’s 1860 description of an adenomyoma.¹⁰⁸ Breus was concerned with the developmental pathology and embryology of the female reproductive organs and with cystic uterine fibroids and adenomyomas, some of huge proportions.¹⁰⁹He described two of great size,¹¹⁰ one the size of a child’s head, the other containing 7 L of fluid.¹¹¹ Some communicating cystic uterine adenomyomas grew laterally between the leaves of the broad ligament; other submucosal cystic uterine myomas or “polypoid cystic myomas” grew into the uterine cavity.¹¹² Breus speaks of cystic myomas and fibromas lined with “Flimmerepithelium,” glimmering or sparkling columnar epithelium.¹¹³ In the case described by Pfannenstiel, the “Flimmerepithelium” was associated with metastases from another organ, possibly the left ovary.¹¹⁴ Breus also cited Rokitansky (1861) as having described similar lesions in conjunction with cystic carcinoma of the ovaries and vegetations of the peritoneum.¹¹⁵ Referring to the copy of Breus that the author read, Ridley stated: “Breus¹¹⁶ (1894) described a typical ‘chocolate cyst’ using that term, of the uterus and cul-de-sac of Douglas. On page 15 of the pamphlet there is reference to a ‘chokoladebraunes’ secretion that filled a cyst. Since Breus not only had worked with Kolisko, a student of Kundrat,¹¹⁷ but also dedicated his pamphlet to Kundrat,¹¹⁸one of Rokitansky’s last assistants, surely Breus should have known of Rokitansky’s contributions on endometriosis. One might expect that Breus would have referred to adenomyomas by the Latin descriptive name assigned by Rokitansky, as von Recklinghausen did in his article of 1893.

In short, Ridley believed that documents Breus cited contained evidence that Rokitansky was not the first to describe endometriosis. However, none before Rokitansky fulfilled the aforementioned criteria of discover.¹¹⁹Applying the cardinal principle of genealogy to the history of disease, the researcher must be able to trace backward from the known to the unknown – generation by generation. To skip a generation is tantamount to pure speculation, yielding to wistful yearnings to extend the legacy, as if so doing increases legitimacy and stature of the disease. For some the temptation is irresistible. Everything from furniture to family pedigree gains a patina that comes only with age; the same might be said for diseases. Endometriosis may have existed for a very long time; millennia may be too short a time frame, considering that endometriosis is intimately related to a woman’s biology and sexuality, to her reproductive organs and more directly to the biologic phenomenon of menstruation. Despite the speculations of Ridley, there appears to be no documentation of endometriotic disease before mid-nineteenth century.¹²⁰

So said, Vincent J. Knapp, professor of History at Potsdam College, State University of New York launched a serious study of 12 manuscripts, 1 from 1690 and 11 dating from 1739 to 1797 that he found in the National Library of Medicine in Bethesda, Maryland.¹²¹ Knapp emphasized the 1690 manuscript of the German physician, Daniel Shroen. Key descriptive words that Knapp abstracted from the 12 manuscripts and translated into English included “ulcers, sores, inflammations, pus-filled, abscesses, loss of consciousness, convulsions, adhesions, one ovarian cyst, suppuration, developing abscess, ulceration, danger of gangrene, life threatening gangrene, pain”; and phrases: “these ulcers of the bladder could penetrate the rectum, where they could produce rectal-intestinal inflammations; the ovaries seemed to be the least damaged organ.” Knapp’s summation is not convincing: “To ask that European physicians, struggling to identify endometriosis in the late 17th and 18th centuries, [to] come up with tissue samples to distinguish the disease would be to write the present back into the past. Such histologic knowledge simply did not exist for them. However, given the plethora of organic damage that they recognized and recorded, along with identification of numerous constitutional symptoms, most of which today can be found repeated over and over again in medical and biologic journals and even in self-help books, one can come to a conclusion about their investigative efforts. They not only recognized the impact of endometriosis, albeit not in its entirety, but then perceptively and analytically linked together the disease case’s greater and lesser symptoms and quickly understood that there was a pathologic syndrome at work.”¹²²

Two letters were sent to the editor of Fertility and Sterility in response to Knapp’s provocative article. In the first letter, Brosens and Steno of Leuven, Belgium located one of five manuscripts that Knapp thought originated from the University of Leuven in Belgium, that of Jacobus Josephus Henry of August 10, 1796. On examination, Brosens and Steno concluded: “The article under discussion appeared to be about infection and without symptoms suggesting endometriosis or adenomyosis…From our reading of the documents in hand we must conclude that there is no evidence that endometriosis was an endemic or even a recognized disease in the eighteenth century in Belgium.”¹²³ Subsequently, Brosens and Benagiano reported they had read the original manuscripts of 3 of the 12 theses examined by Knapp. They concluded: “We could not find any description that would make us believe the lesions reported were in any way similar to endometriosis, adenomyoma or adenomyosis.”¹²⁴

The second letter to the editor of Fertility and Sterility, written by the author, noted that the manuscripts were written during the medical enlightenment of the eighteenth century. The author asked Knapp to clarify some clinical issues.¹²⁵ The observations of Brosens and Steeno and questions raised by the author went unanswered because unfortunately Professor Knapp died in the interim. Considering that the master macropathologist Rokitansky had not identified endometriosis in over 30 years of prodigious work, combined with the observations put forth by Brosens and his colleagues that none of the “lesions reported [by Knapp] were in any way similar to endometriosis, adenomyoma or adenomyosis,” the author has reached the conclusion that the isolated and scattered observations found by Knapp in the seventeenth- and eighteenth-century literature do not constitute a viable claim for the discovery of endometriosis.¹²⁶ In 2011, Benagiano and Brosens argued persuasively that the lesions reported by Knapp were not endometriosis.¹²⁷

In sum, this discussion has been as much about demonstrating the difficulty of recognizing and defining a new benign chronic disease in the interior of the human body in the middle third of the nineteenth century as it has been about granting Rokitansky “the honor of having rendered the first detailed description of adenomyosis, or internal endometriosis”¹²⁸ and ovarian endometriosis.

Footnotes

Benagiano G, Brosens I. History of adenomyosis. Best Pract Res Clin Obstet Gynecol 2006;20:449–63:450.

Erna Lesky, The Vienna Medical School of the 19th Century [Baltimore, MD: Johns Hopkins University Press, 1976], 68. Arleen Marcia Tuchman, Science, Medicine, and the State of Germany: The Case of Baden, 1815–1871 [New York: Oxford University Press, 1993], 86–7. Physiology amounted to “little more than microscopical anatomy accompanied by occasional chemical tests and investigations” until mid-nineteenth century when slowly the development of sophisticated instrumental techniques led to “a methodical approach to the study of function.”

Erna Lesky, 73–4. Berres (1796–1844), a Moravian surgeon-macroscopic-anatomist, stimulated by the work of a Viennese optician, had learned microscopy after he was appointed to Vienna.

Erna Lesky, The Vienna Medical School of the 19th Century [Baltimore, MD: Johns Hopkins University Press, 1976], 99, 106.

Prim. Univ.-Prof. Dr. Roland Sedivy, e-mail message to author, September 2, 2007. “In his autobiography Rokitansky mentioned that he bought 1842 Brunner microscope (fig. attached!). More details are currently not known. But I found in one archive the free-hand graphics of some histological figures he used in his second edition of his textbook. The size of cells in these figures allow [one] to get some idea of what magnification he might have used. I presume that he referred to a magnification in total (ocular × objective) between 50–100x.” See Erna Lesky, The Vienna Medical School of the 19th Century [Baltimore, MD: Johns Hopkins University Press, 1976], 99.

Rickman John Godlee, Lord Lister [Oxford: Clarendon Press, 1924], 55: “the Rokitanskys…had dined at Upton [with Joseph Jackson Lister and his family] fourteen years earlier (1842).”

Sherwin B. Nuland, Doctors: The Biography of Medicine. New York: Alfred A. Knopf, 1989:351.

Michael J. O’Dowd and Elliott E. Philipp, The History of Obstetrics and Gynaecology [New York: Parthenon Publishing Group, 1994], 220. Nuland, Sherwin B. Doctors: The Biography of Medicine. New York: Alfred A. Knopf, 1989:352. Nuland quoted from Joseph Lister’s 1900 Huxley Lecture. In 1900, when surgical pathology was a reality, Lister recalled that his father’s investigations “had raised the compound microscope from little better than a scientific toy to the powerful engine for investigation.” See also: Rickman John Godlee, Lord Lister [Oxford: Clarendon Press, 1924], 11–12. “Between 1824 and 1843, whilst actively engaged in business, he found time to make his mathematical calculations, actually to grind the glasses himself, and to supply the necessary data to Tulley, Ross, and Smith, who were the manufactures. This work gained for him the Fellowship of the Royal Society in 1832, and brought him into contact with a large scientific circle.” He wrote a paper in 1842–3 entitled “On the Limit to Defining Power, in Vision with the Unassisted Eye, the Telescope and the Microscope” that remained unpublished until it appeared in Journal of the Royal Microscopical Society, 1913, Part I: 34–55.

RM Allen, The Microscope [New York: D. Van Nostrand Company, 1940], 8. Arleen Marcia Tuchman, Science, Medicine, and the State of Germany: The Case of Baden, 1815–1871 [New York: Oxford University Press, 1993], 57. The Frenchman, Charles Chevalier is credited with having improved resolution at high magnifications by “inserting a biconcave lens between several achromatic lenses.” E. M. Tansey, “From the Germ Theory to 1945,” in Western Medicine, ed. Irvine Loudon [Oxford: Oxford University Press, 1997], 108. Subsequent improvements in microscopes “were matched by advances in the techniques of preserving, cutting, and selectively staining sections for histological examination….Improvements in microscopes for static observations and measurements were also made, especially after the invention of the achromatic lens by Joseph Lister (1786–1869), father of the surgeon Joseph (Lord) Lister. These were matched by advances in the techniques of preserving, cutting, and selectively staining sections for histological examination.” Erna Lesky, The Vienna Medical School of the 19th Century [Baltimore, MD: Johns Hopkins University Press, 1976], 171–2. However, “staining and hardening techniques were still undeveloped in the late 1850s.” Alexander Hellemans and Bryan Bunch, The Timetables of Science: A Chronology of the Most Important People and Events in the History of Science, Touchtone Edition [New York: Simon & Schuster, 1988], 362–4. However, some advances such as the microtome to slice thin tissue sections were not invented until 1885. The microtome was invented by Charles Darwin, son of Charles Darwin, author of The Origin of Species.

The 1855 translation of the 1846 edition by the Sydenham Society

Carl Rokitansky, A Manual of Pathological Anatomy, Volume I. General Pathological Anatomy. trans. William Edward Swaine [Philadelphia, PA: Blanchard & Lea, 1855], 76.

Carl Rokitansky, 174.

Carl Rokitansky, 176.

Carl Rokitansky, 184.

Carl Rokitansky, 197.

Carl Rokitansky, A Manual of Pathological Anatomy, Volume I. General Pathological Anatomy. trans. William Edward Swaine [Philadelphia, PA: Blanchard & Lea, 1855], 209.

Carl Rokitansky, 208.

Carl Rokitansky, 220.

Erna Lesky, The Vienna Medical School of the 19th Century [Baltimore, MD: Johns Hopkins University Press, 1976], 112.

Erna Lesky, The Vienna Medical School of the 19th Century [Baltimore, MD: Johns Hopkins University Press, 1976], 115–6.

Erna Lesky, 171–2.

Erna Lesky, 112, 219. Lesky, p. 465. “However, the true home and source of microscopists in Vienna, despite the existence of an official Chair of Histology was the Institute of Physiology, of which all the newer institutes were off shoots.”

Erna Lesky, The Vienna Medical School of the 19th Century [Baltimore, MD: Johns Hopkins University Press, 1976], 219.

Erna Lesky, 220. In German: Grundzüge der pathologischen Histologie, 1855.

Erna Lesky, 102.

Arleen Marcia Tuchman, Science, Medicine, and the State of Germany: The Case of Baden, 1815–1871 [New York: Oxford University Press, 1993], 76. German universities took the lead in introducing microscopy in the medical curriculum. “Between 1845 and 1855 fifteen medical faculties also began including microscopical demonstrations in their courses on pathology, histology, semiotics, and diagnostics.” Arleen Marcia Tuchman, Science, Medicine, and the State of Germany: The Case of Baden, 1815–1871 [New York: Oxford University Press, 1993], 82–83. By mid-century, the microscope had become for the symbol of excellence in teaching and research. In 1845, students in the University of Heidelberg held a torchlight parade in honor of Jacob Henle, a former assistant of Johann Müller, as a champion of microscopy in teaching and research, and “as a thinker and scientist who campaigns unremittingly and without stop at the head of those who are struggling and fighting against a desolate empiricism in our science.”

Erna Lesky, 221.

Owen H. Wangensteen and Sarah D. Wangensteen, The Rise of Surgery: From Empiric Craft to Scientific Discipline [Minneapolis, MN: University of Minnesota Press, 1978], 440.

Rickman John Godlee, Lord Lister [Oxford: Clarendon Press, 1924], 54–55. Earlier in the day Rokitansky spent over 3 h showing the Lister and other visitors specimens in the Vienna Pathological Museum.

Rickman John Godlee, 55: “The medical school at Vienna was the largest and most important he had yet seen. It provided much of general interest; (quoting Joseph Lister) ‘and best of all as yet, Professor Rokitansky, the most eminent pathologist in the world spend three hours and a quarter the other day, in going over his wonderfully rich museum of preparations of diseases, to me and some other visitors.’ Rokitansky was extremely hospitable; he had dined at Upton fourteen years before, and had been much impressed with Lister’s two sisters, though he had no recollection of the young surgeon, who, he said was ‘nothing in those days.’”

Rickman John Godlee, 22–23. Joseph Lister wrote two papers on microscopy, both published in the Quarterly Journal of Microscopical Science in 1853. The first dealt with muscular tissue of the iris of the eye. Joseph Lister, Quarterly Journal of Microscopical Science1853;1:8. The second involved observations on the involuntary muscular fibers of the skin. Joseph Lister, Quarterly Journal of Microscopical Science 1853;1:262.

Not only did Rokitansky engage in scholarly debates with Rudolph Virchow in the medical literature, at least on one occasion – November 10, 1853 – he wrote a formal letter to Virchow commenting on the latter’s “discovery of subependymal corpora amylacea of the brain ventricle,” adding his own observations on the subject. This letter was written in immediate response to Rokitansky receiving the “first issue of volume 6 of your Archives.” See Christian Andree and Roland Sedivy, “Discovery of a letter from Rokitansky to Virchow about subependymal corpora amylacea,” Virchow’s Archive2005;446:177–180. “Subependymal means beneath the ependyma (the cellular membrane lining the central canal of the spinal cord and the brain ventricles) and corpora amylacea means (one of a number of small ovoid or rounded, sometimes laminated, bodies resembling a grain of starch and found in nervous tissue, in the prostate, and in pulmonary alveoli; of little pathological significance, and apparently derived from degenerated cells or proteinaceous secretions.” Illustrated Stedman’s Medical Dictionary, 24th ed. [Baltimore, MD: Williams & Wilkins, 1982], 323, 473. Rokitansky’s letter to Virchow was found by Christian Andree at the Berlin-Brandenburg Academy of Sciences. Professor Sedivy sent the author an autographed reprint.

In the first pages of volume 6 of his journal, Virchow “unexpectedly praised Rokitansky’s work and the Vienna School of Medicine.” Rudolph Virchow, Uber eine im Gehirn und Ruckenmark des Menchen aufgefundene Substanz mit der chemischen Reaction der Cellulose. Arch Path Anat u Physiol u Klin Med 1854;6:135–138. Shortly thereafter in the very pages of Virchow’s Journal, Rokitansky found an article on subependymal corpora amylacea (CA) written by Virchow that prompted a letter to Virchow from Rokitansky, the only known correspondence between the two men. This episode reveals that not only did Rokitansky faithfully read Virchow’s journal, but also that he must have been pleased to read the unexpected praise for his own work and that of the Second Vienna School of Medicine; words of praise from his old critic. Andree and Sedivy noted that “Virchow mentioned in the addendum to his article that Rokitansky and Kolliker had seen CA in the N. opticus and retina, respectively. When mentioning Rokitansky, Virchow used the passive voice, indicating that he was not sure whether Rokitansky really had observed them.” From this observation, Andree and Sedivy speculated “that this fact was the background behind his letter to Virchow.” See Christian Andree and Roland Sedivy, “Discovery of a letter from Rokitansky to Virchow abut subependymal corpora amylacea,” Virchow’s Archive 2005;446:177–180.

To this may be added the further speculation that Rokitansky’s friendly, though formal letter to Virchow may have been possible in the first place because Virchow’s unexpected praise helped heal an old wound that Rokitansky had sustained in 1846. See Rudolph Virchow, Rokitansky, Handbuch der allgemeinen pathologischen Anatomie, Literarische Beilage, Preussische Medicinal-Zeitung 1846;XV:237–238, 243–244. Perhaps this rapprochement between the doyen of German pathology and the doyen of Austrian Pathology in 1854 may have contributed to Rokitansky’s greater interest in microscopy and histology that, further stimulated by the publication of Virchow’s Cellular Pathology in 1858, led Rokitansky to inaugurate Virchow’s lectures on pathology in his department in 1859.

7. E. M. Tansey, “From the Germ Theory to 1945,” in Western Medicine, ed. Irvine Loudon [Oxford: Oxford University Press, 1997], 102.

Paul Strathern, A Brief History of Medicine from Hippocrates to Gene Therapy [New York: Carroll & Graf, 2005], 211–212. Henry E. Sigerist, Man and Medicine: An Introduction to Medical Knowledge [New York: WW Norton & Company, 1932], 124. Referring to Virchow’s Cellular Pathology of 1858, the medical historian Henry Sigerist opined that “Virchow placed the microscope into the hands of pathologists. This only made it possible to see the minuter changes and to undertake a more exact classification of disease. The microscope alone gave us the opportunity of observing other processes of disease, inflammation for instance.” The dominance of naked-eye macromorphology gave way to micropathology as the first major step in the long process of reductionism that led to ultramicroscopic pathologic investigation and molecular biology in the twentieth century.

Fielding H. Garrison, Contributions to The History of Medicine. [New York: Hafner Publishing Company, 1966], 190. “In the winter semester of 1859–60…Klob, Rokitansky’s assistant in Vienna, posted on his blackboard the following notice: ‘From Thursday on, lectures on pathological anatomy will be delivered according to the cell doctrine of Virchow.’” Erna Lesky, The Vienna Medical School of the 19th Century [Baltimore, MD: Johns Hopkins University Press, 1976], 172. By the late 1850s, cellular pathology was taught in Vienna and “even in Rokitansky’s own institute.” Lesky, p. 112. “Rokitansky was not a professional microscopist. The task that his time posed before him was of a macromorphological nature and as a macromorphopathologist he fulfilled it. From the very beginning, however, he considered it to be the task of pathological anatomy to raise pathology to physiological pathology. This comprehensive concept as held by Rokitansky makes it possible to understand why he, being a genuine macromorphologist, not only encouraged the development of medical chemistry, and pathological histology, but also that of experimental pathology, and why he acquainted his school with these methods of research when he had exhausted his own method. This took place in the middle of the fifties. The year 1858 marked the beginning of the epoch of cellular pathology.”

Erna Lesky, The Vienna Medical School of the 19th Century [Baltimore, MD: Johns Hopkins University Press, 1976], 145.

Erna Lesky, 168.

Erna Lesky, 171.

Erna Lesky, 173.

Erna Lesky, 197. After Rokitansky’s retirement in 1874, the advent of Lister’s antisepsis would elevate surgery under Billroth to leadership in the University of Vienna. Billroth adopted antisepsis.

Erna Lesky, 293. Very high Austrian battle casualties were caused by the Prussian breech loading rifle in the Austro-Prussian War of 1866. The Prussian soldiers were able to fire and reload in the prone position which reduced their silhouette and vulnerability considerably. In contrast the Austrian soldiers had to stand upright when they reloaded their muzzle loading muskets which made them prime targets. “When the Medical Faculty submitted a proposal for a successor to Schuh in 1867, it demanded, on the initiative of Arlt, Brücke, Hebra, and Rokitansky, that the ministry appoint ‘a man to be professor of surgery of whom the greatest promotion of science may be expected, a man who is not only famous in the field of practical surgery, but also in areas of physiological and pathological research who has demonstrated a special genius as teacher, surgeon and writer, who is still in the prime of life, from whom it may be expected that he will represent the most modern trends in surgery in its relation to physiology and pathological anatomy, and who is able to establish a surgical school in Vienna which will bring fame to the university and the greatest benefit to the country.’” Erna Lesky, The Vienna Medical School of the 19th Century [Baltimore, MD: Johns Hopkins University Press, 1976], 261. To get some idea of the importance of this appointment, consider the words of Billroth: “…it almost seems a fairy tale that I am appointed Imperial Royal professor of the First Department of Surgery and the first Director of the Postgraduate Institute of surgery; appointed by His Apostolic Majesty, the Emperor of Austria…”

Erna Lesky, 274. With ready acceptance in Europe of Lister’s principles and practice of antisepsis combined with painless surgery afforded by general anesthesia, general surgery and gynecologic surgery assumed academic prominence over pathologic anatomy. Erna Lesky, The Vienna Medical School of the 19th Century [Baltimore, MD: Johns Hopkins University Press, 1976], 394. Europeans respected the impressive surgical results that the Englishman Spencer Wells (1818–1897) achieved in his operations for removal of ovarian tumors; surgical results supported by “objective statistical analysis.” There occurred a gradual shift from operating dead patients in the morgue to operating live patients in surgery, patients who now survived surgery in increasing numbers. This, in turn, generated need for examination of surgical specimens which led the transition from morbid to microscopic surgical pathology near the end of the century.

Henry E. Sigerist, Man and Medicine: An Introduction to Medical Knowledge [New York: WW Norton & Company, 1932], 124.

Carl Rokitansky, A Manual of Pathological Anatomy, Volume I. General Pathological Anatomy trans. William Edward Swaine [Philadelphia, PA: Blanchard & Lea, 1855], 189, 190.

Klemperer P. Notes on Carl von Rokitansky’s autobiography and inaugural address. Bulletin History Medicine 1961:374–380:378. In his professorial inaugural address of 1844, Rokitansky revealed the philosophical basis of his actions. “It is the painstaking study with all methods available to anatomic investigations of morphologic alterations according to tangible physical criteria; because soundest knowledge of morbid phenomena is gained by sensual perception of material appearances.”

Carl Rokitansky, Ueber Uterusdrüsen-Neubildung in Uterus- und Ovarial-Sarcomen. Zeitschift Gesellschaft der Aerzte in Wien. 1860;16:577–581. “Of the existing connective tissue tumors of the uterus, the round fibroids are to be differentiated from the so called fibrous polyps of the uterus in which glandular tubules are found. These are connective tissue tumors rooted in the basal stroma of the uterus and cannot be shelled out (Paget’s continuous growth) in contrast to the well circumscribe fibrous tumors.” Carl Rokitansky, Ueber Uterusdrüsen-Neubildung in Uterus- und Ovarial-Sarcomen. Zeitschift Gesellschaft der Aerzte in Wien. 1860;16:577–581. Carl Rokitansky, A Manual of Pathological Anatomy, Volume II. The Abdominal Viscera. trans. Edward Sieveking [Philadelphia, PA: Blanchard & Lea, 1855], ix. Editor’s Preface. Of the difficulties connected with the translation, I will only say that they are much increased by the figurative style of the author. He constantly uses terms in a sense peculiar to himself, and his total disregard for the ordinary rules of composition is an additional and frequent course of obscurity.” Translation of Rokitansky’s 1860 article was equally difficult.

Given that Rokitansky emphasized the fresh specimen, it is a reasonable to assume that the fresh surgical specimen caught Rokitansky’s attention and not one of the surgical specimens preserved in wine alcohol, nor any of the autopsy specimens.

Owen H. Wangensteen and Sarah D. Wangensteen, The Rise of Surgery: From Empiric Craft to Scientific Discipline [Minneapolis, MN: University of Minnesota Press, 1978], 440. Kussmaul spent 4 months assisting Rokitansky in his morgue. “During all that time the only words Rokitansky spoke to him occurred during an interruption of work while the two stood together for a few minutes in the doorway on a fine autumn morning. Rokitansky said: ‘Today we have beautiful weather.’ The astounded Kussmaul pulled himself together and replied, ‘Yes, it is truly a beautiful day.’” Robert Meyer, Autobiography of Dr. Robert Meyer (1864–1947): A Short Abstract of a Long Life [New York: Henry Schuman, 1949], 16–17. Meyer recalled his teacher, Adolph Kussmaul. “The most brilliant teacher was the internist, Adolf Kussmaul, known among the gynecologists for his book The Malformations of the Uterus. His diagnoses were not far from infallible, so that when he retired in 1887, von Recklinghausen at a banquet could say of him that he had not once been able to reverse a diagnosis after dissecting one of his patients. It was always astonishing how carefully he examined his patients in order to arrive at a diagnosis.”

Roland Sedivy, 200 Jahre Rokitansky – sein Vermachtnis fur die heutige Pathologie Wiener Klinische Wochenschrift 2004;116/23:779–787: Table 1, page 780. Histopathology for benign disease never became a routine in Rokitansky’s autopsy house.

Carl Rokitansky, Ueber Uterusdrüsen-Neubildung in Uterus- und Ovarial-Sarcomen. Zeitschift Gesellschaft der Aerzte in Wien. 1860;16:577–581.

Carl Rokitansky, A Manual of Pathological Anatomy, Volume I. 189, 190.

Carl Rokitansky, A Manual of Pathological Anatomy, Volume I. General Pathological Anatomy. trans. William Edward Swaine [Philadelphia, PA: Blanchard & Lea, 1855], 189, 190. See also Robert Meyer, Autobiography of Dr. Robert Meyer (1864–1947): A Short Abstract of a Long Life [New York: Henry Schuman, 1949], 34. Meyer “stressed the fact that the infiltrative proliferation alone does not necessarily mean malignancy (1903).”

Carl Rokitansky, 1860;16:577–581. See also Emge LA. The elusive adenomyosis of the uterus: its historical past and its present state of recognition. Am J Obstet Gynecol 1962;83:1541–1563:1542. “It is just one hundred years ago that there appeared in the Transactions of the Vienna Medical Society a report describing unusual proliferative qualities of the endometrial stroma and glands. Its author, the eminent pathologist Carl Rokitansky.” Though published in 1962, Ludwig A. Emge delivered the Eleventh Joseph L. Baer Lecture of the Chicago Gynecological Society on 21 October 1960, the 100th anniversary year of the discovery of endometriosis.

Carl Rokitansky, 1860;16:577–581.

Sarcoma adenoids uterinum of Rokitansky is equivalent to adenomyoma of von Recklinghausen which is equivalent to diffuse adenomyoma of Cullen and equivalent to the term internal endometriosis.

Carl Rokitansky, Ueber Uterusdrüsen-Neubildung in Uterus- und Ovarial-Sarcomen. Zeitschift Gesellschaft der Aerzte in Wien. 1860;16:577–581.

This was not Johannes Peter Müller (1801–1858).

Carl Rokitansky, 1860;16:577–581. His reference to Müller reads: “The mucosa hypertrophies in one or more circumscribed places accompanied by elongation of glands producing the bulge.” (H. Müller: Verhandl. D. Phys. Med. Gesellschaft in Würzburg, 4.1854.)

Carl Rokitansky, Ueber Uterusdrüsen-Neubildung in Uterus- und Ovarial-Sarcomen. Zeitschift Gesellschaft der Aerzte in Wien. 1860;16:577–581. Rokitansky’s reference to Paget reads: “Of the existing connective tissue tumors of the uterus, the round fibroids are to be differentiated from the so called fibrous polyps of the uterus in which glandular tubules are found. These are connective tissue tumors rooted in the basal stroma of the uterus and cannot be shelled out (Paget’s continuous growth) in contrast to the well circumscribed fibrous tumors. They commonly develop within or form the submucosal stratum and grow into the uterine cavity as so called polyps of various shapes (cylindric-, pear – or club shaped) and are covered by an adherent uterine mucosa. The various changes in its texture may appear identical to the changes seen as a result of chronic inflammation. In contrast to the easily removable fibrous tumors, we commonly consider these connective tissue tumors as sarcoma, here specifically as uterus sarcoma. These tumors growing into a mucosal cavity generally retain their old name of polyp and uterus polyp and, according to the discussion above, would be distinguished from the round fibroids prolapse into the uterine cavity.”

Carl Rokitansky, Ueber Uterusdrüsen-Neubildung in Uterus- und Ovarial-Sarcomen. Zeitschift Gesellschaft der Aerzte in Wien. 1860;16:577–581. “A sarcoma containing uterine glandular tubules is also found in the ovaries and some cystic structures of the ovaries, therefore become Cystosarcoma adenoids uterinum.”

Carl Rokitansky, A Manual of Pathological Anatomy, Volume I. General Pathological Anatomy trans. William Edward Swaine [Philadelphia, PA: Blanchard & Lea, 1855], 189, 190.

Carl Rokitansky, Lehrbuch der pathologischen Anatomie [Wien: Braumüller, 1861], III: 475–490.

Colin Tudge with Josh Young, The Link: Uncovering Our Earliest Ancestor [New York: Little, Brown and Company, 2009], 192, 193.

Vanessa R. Schwarz, Spectacular Realities: Early Mass Culture in Fin-de-Siecle Paris [Berkeley, CA: University of California Press, 1999], 49, 58. The first morgue in Paris was built in 1718. In 1864, 3 years after Rokitansky identified and described uterine endometriosis, a new Paris Morgue was built behind Notre-Dame on the quai de l’Archeveche. This morgue “can be seen in the context of growing state interest in and responsibility for the dead and as part of an ever-increasing reliance on the ‘expert knowledge’ of a professionalized corps of doctors of forensic medicine.” But it was not until 1882 that “the administration installed a system for the refrigeration of the corpses-a system that slowed their decay and thus extended display time…The new refrigeration system, modeled on one developed for the transport of meat to markets, ‘has served as a model for all the large European cities.’”

Carl Rokitansky, A Manual of Pathological Anatomy, Volume I. General Pathological Anatomy trans. William Edward Swaine [Philadelphia, PA: Blanchard & Lea, 1855]. “In an extended sense, the collective term fibroid texture may be made to comprise all fibrous tissues, the development of which has been already delineated, and the occurrence of which as a more or less essential component of various new growths, it becomes our business to discuss.” “Nowhere is the insufficiency of a mere anatomical principle more felt than here - a principle which would need occasion us to class side by side, the most heterogeneous new growths, for example, fibro-carcinoma and the perfectly benign fibroid tumor.”

Carl Rokitansky, A Manual of Pathological Anatomy, Volume I. General Pathological Anatomy trans. William Edward Swaine [Philadelphia, PA: Blanchard & Lea, 1855], 168. “Let us begin with the results of an examination with the naked eye of perfect cysts, and in particular of the exquisite specimens so frequently met with in the ovaries…We have the simple (unicancellated) and the compound cyst (Müller’s compound cystoid).” Carl Rokitansky, A Manual of Pathological Anatomy, Volume I. General Pathological Anatomy. trans. William Edward Swaine [Philadelphia, PA: Blanchard & Lea, 1855], 34. [Author’s] Introduction. “The female sex greatly favors the occurrence, in the sexual system, of cystoids, of cystosarcoma, of the majority of cancerous growths.”

Carl Rokitansky, A Manual of Pathological Anatomy, Volume II. The Abdominal Viscera. trans. Edward Sieveking [Philadelphia, PA: Blanchard & Lea, 1855], 248, 249. Chapter III. Abnormalities of the Female Sexual Organs.

Roswell Park, An Epitome of the History of Medicine, 2nd ed. [Philadelphia: FA Davis Company, 1908], 250–1. One year later a magnificent new Institute of Pathological Anatomy was erected specially for him, a building Rokitansky had demanded for years. Erna Lesky published illustrations of Rokitansky’s postmortem rooms from his student days until 1862 and of his new institute. Author’s note: Thus we are reassured by Erna Lesky that Rokitansky identified uterine and extrauterine endometriosis in his old “primitive” Leichenhaus described by Roswell Park. Erna Lesky, The Vienna Medical School of the 19th Century [Baltimore, MD: Johns Hopkins University Press, 1976], 262. “Rokitansky received an institute of pathological anatomy in 1862, something he had demanded persistently for thirty-years; in 1868 laboratory space for experimental pathology also was made available in this building. In 1874 a separate institute was founded for medical chemistry, and in 1873 one for embryology.” Erna Lesky, The Vienna Medical School of the 19th Century [Baltimore, MD: Johns Hopkins University Press, 1976], Illustration 20. “Rokitansky’s post-mortem rooms.” Illustration 21. Rokitansky’s new Institute of Pathological Anatomy. Both illustrations are at the back of the book.

Carl Rokitansky, Ueber Uterusdrüsen-Neubildung in Uterus- und Ovarial-Sarcomen. Zeitschift Gesellschaft der Aerzte in Wien. 1860;16:577–581. “The various changes in its texture may appear identical to the changes seen as a result of chronic inflammation…In view of the above discussion, it is important to recognize the changes occurring in the mucosa and the submucosal stratum of the uterus as consequences of chronic inflammation…7. The ones in question and the mucosa lined uterine polyps as a whole undergo changes in their texture which similarly occur in the uterine mucosa in the course or as the end result of chronic inflammation.” For many years the eminent gynecologic pathologist, Robert Meyer, would also believe chronic inflammation the pathogenesis for uterine endometriosis; eventually he changed his opinion.

Carl Rokitansky, 1860;16:577–581.

Knud Faber, Nosography in Modern Internal Medicine [New York: Paul B. Hoeber, Inc., 1923], 8–15, 37–39, 45, 53–54.

Ziporyn, Terra. Nameless Diseases. New Brunswick, NJ: Rutgers University Press, 1992:36–39. A disease remains nameless until recognized, described, and named by a medical scientist or medical practitioner. Similarly, in clinical practice a disease in the patient remains nameless until correctly diagnosed by her medical practitioner.

Owen H. Wangensteen and Sarah D. Wangensteen, The Rise of Surgery: From Empiric Craft to Scientific Discipline [Minneapolis, MN: University of Minnesota Press, 1978], 438. “In 1969 the senior author outlined three criteria to decide the role of discover: (1) who first showed the way; (2) continuance of the practice; (3) influence of the discovery upon contemporary and current practice.”

Emge LA. The elusive adenomyosis of the uterus: its historical past and its present state of recognition. Am J Obstet Gynecol 1962;83:1541–1563. Although Rokitansky only gave internal endometriosis a descriptive name, “cystosarcoma adenoids uterinum,” and not a proper name such as adenomyosis, Emge – a life-time student of adenomyosis – contended: “the honor of having rendered the first detailed description of adenomyosis, or internal endometriosis, rightly goes to him.”

Emge LA. The elusive adenomyosis of the uterus: its historical past and its present state of recognition. Am J Obstet Gynecol 1962;83:1541–1563:1542. According to Emge, Virchow did identify stromal endometriosis in 1864, 3 years after Rokitansky identified adenomyosis. Emge did not give a reference to Virchow’s contribution.

Owen H. Wangensteen and Sarah D. Wangensteen, The Rise of Surgery: From Empiric Craft to Scientific Discipline [Minneapolis, MN: University of Minnesota Press, 1978], 438.

Hudelist G, Keckstein J, Wright JT. The migrating adenomyoma: past views on the etiology of adenomyosis ad endometriosis. Fertil Steril 2009;92:1536–43.

Recklinghausen F. Uber die Adenocysten der Uterustumoren und Ueberreste des Wolff’schen Organs. Deutsche Medicinische Wochenschrift 1893;xix:825–826.

Friedrich v. Recklinghausen, Die Adenomyome und Cystadenome der Uterus- und Tubenwandung ihre Abkunft von Resten des Wolff’schen Korpers. Im Anhang: Von W. A. Freund, Klinische Notizen zu den voluminosen Adenomyomen des Uterus [Berlin: Verlag von August Hirschwald, 1896.]

Juan Rosai, A tribute to Robert E. Scully on his 80th Birthday. Seminars in Diagnostic Pathology. 2001;18:151–154. “Sometimes the question arises as to how many cases of an undescribed entity somebody needs to see before concluding that one is dealing with something ‘new.’” Dr. Scully, known to the world at large as “Mr. Gynecologic Pathology…gave me once the answer as it applies to himself when joking about the fact that he keeps a box of slides (he did not say whether in his office or in his head), each of them from a case that he thinks represents an undescribed entity, and he is simply waiting for the second case to come along and prove it.”

Henry E. Sigerist, Man and Medicine: An Introduction to Medical Knowledge [New York: WW Norton & Company, 1932], 127.

Carl Rokitansky, Ueber Uterusdrüsen-Neubildung in Uterus- und Ovarial-Sarcomen. Zeitschift Gesellschaft der Aerzte in Wien. 1860;16:577–581.

Benagiano G, Brosens I. Who identified endometriosis? Fertil Steril 2011;95:13–16.

Carl Rokitansky, Ueber Uterusdrüsen-Neubildung in Uterus- und Ovarial-Sarcomen. Zeitschift Gesellschaft der Aerzte in Wien. 1860;16:577–581.

Benagiano G, Brosens I. History of adenomyosis. Best Pract Res Clin Obstet Gynecol 2006;20:449–63.

Carl Rokitansky, Ueber Uterusdrüsen-Neubildung in Uterus- und Ovarial-Sarcomen. Zeitschift Gesellschaft der Aerzte in Wien. 1860;16:577–581.

Benagiano G, Brosens I. Who identified endometriosis? Fertil Steril 2011;95:13–16.

Carl Rokitansky, A Manual of Pathological Anatomy, Volume I. General Pathological Anatomy trans. William Edward Swaine [Philadelphia, PA: Blanchard & Lea, 1855], 189, 190. See also Robert Meyer, Autobiography of Dr. Robert Meyer (1864–1947): A Short Abstract of a Long Life [New York: Henry Schuman, 1949], 34. Meyer “stressed the fact that the infiltrative proliferation alone does not necessarily mean malignancy (1903).”

Carl Rokitansky, A Manual of Pathological Anatomy, Volume I. General Pathological Anatomy. trans.

William Edward Swaine [Philadelphia, PA: Blanchard & Lea, 1855], 189, 190.

Carl Rokitansky, Ueber Uterusdrüsen-Neubildung in Uterus- und Ovarial-Sarcomen. Zeitschift Gesellschaft der Aerzte in Wien. 1860;16:577–581. Carl Rokitansky, Lehrbuch der Pathologischen Anatomie III. Auflage 1855–1861. III. Band p. 488–491.

Recklinghausen F. Uber die Adenocysten der Uterustumoren und Ueberreste des Wolff’schen Organs. Deutsche Medicinische Wochenschrift 1893;xix:825–826. See also: Friedrich v. Recklinghausen, Die Adenomyome und Cystadenome der Uterus- und Tubenwandung ihre Abkunft von Resten des Wolff’schen Korpers. Im Anhang: Von W. A. Freund, Klinische Notizen zu den voluminosen Adenomyomen des Uterus [Berlin: Verlag von August Hirschwald, 1896.]

Cullen, Thomas S. Adeno-myoma uteri diffusum benignum. Johns Hopkins Hospital Reports, 1897, vol. vi, p. 133. Cullen, Thomas Stephen. Cancer of the Uterus: Its Pathology, Symptomatology, Diagnosis, and Treatment. Also the Pathology of Diseases of the Endometrium.New York: D. Appleton and Company, 1900: 535–536. Rokitansky is mentioned in the text, but not in the index. Cullen, Thomas Stephen. Adenomyoma of the Uterus. Philadelphia: WB Saunders Company, 1908. Cullen, Thomas Stephen. Cancer of the Uterus: Its Pathology, Symptomatology, Diagnosis, and Treatment. Also the Pathology of Diseases of the Endometrium. Philadelphia: WB Saunders Company, 1909: 535–536. The 1909 edition seems to be a reprint of the 1900 edition, with minor changes, but with a different publisher. A minor change: Rokitansky is mentioned in the text and in the index.

Emge LA. The elusive adenomyosis of the uterus: its historical past and its present state of recognition. Am J Obstet Gynecol 1962;83:1541–1563. Although Rokitansky only gave internal endometriosis a descriptive name, “cystosarcoma adenoids uterinum,” and not a proper name such as adenomyosis, Emge – a lifetime student of adenomyosis – contended: “the honor of having rendered the first detailed description of adenomyosis, or internal endometriosis, rightly goes to him.”

Benagiano G, Brosens I. History of adenomyosis. Best Pract Res Clin Obstet Gynecol 2006;20:449–63. Interestingly, the same authors in 1991 do not mention Rokitansky. See: Benagiano G, Brosens I. The history of endometriosis: Identifying the disease. Hum Reprod1991;6:963–8.

Hudelist G, Keckstein J, Wright JT. The migrating adenomyoma: past views on the etiology of adenomyosis and endometriosis. Fertil Steril 2009;92:1536–43.

100

Pick L. Ueber Neubildungen am Genitale bei Zwittern nebst Beitragen zur Lehre von den Adenomen des Hodens und Eierstockes. Arch f Gynaek 1905;lxxvi:251–275. On page 262, Pick cites Rokitansky: “1) Vielleicht ist diese Geschwulstform identisch mid dem alten Rokitansky-schen Cystosarcoma adeoides ovarii uterinum. (Lehrb. D. pathology. Anatom. III. Aufl. Bd.III. 1861. Wien. S. 423, 431).

101

Sampson JA. Heterotopic or misplaced endometrial tissue. Am J Obstet Gynecol 1925;10:649–664:655.

102

Hudelist G, Keckstein J, Wright JT. The migrating adenomyoma: past views on the etiology of adenomyosis and endometriosis. Fertil Steril 2009;92:1536–43.

103

Sampson JA. Heterotopic or misplaced endometrial tissue. Am J Obstet Gynecol 1925;10:649–664:655.

104

John H. Ridley, The histogenesis of endometriosis: A review of facts and fancies. Obstetrical and Gynecological Survey 1968;23:1–35.

105

Knapp VJ. How old is endometriosis? Late 17th- and 18-century European descriptions of the disease. Fertility Sterility 1999;72:10–14.

106

John H. Ridley, The validity of Sampson’s theory of endometriosis. American Journal Obstetrics Gynecology 1961;82:777–82.

107

C. Breus, Pamphlets-Liepzig und Wien-Pamphlet Vol. 4054 - Army Med. Library, Washington, DC While in Washington, DC, I attempted to get this pamphlet [Ridley’s reference number 10] but was unsuccessful. However I was successful in obtaining a pamphlet by C. Breus [Ridley’s reference number 9] that fits the description and which I believe is the same publication that Ridley refers to in his reference number 10. In short, I believe that Pamphlet Vol. 4054 by Breus and the 1894 pamphlet by Breus are one and the same publication. Carl Breus, Uber Wahre Epithel Führende Cystenbildung in Uterusmyomen [Leipzig und Wien: Franz Deuticke, 1894], 1–36. Appended are 25 pages of advertisements, a good source for contemporary books and data. In 1894, Breus was Privatdocent in Obstetrics and Gynecology at the University of Vienna. Appropriately, this small pamphlet on developmental pathology was dedicated to the memory of Hans Kundrat, former assistant to Rokitansky who was the second pathologist to succeed to Rokitansky’s chair as professor of pathological anatomy in Vienna. This volume was borrowed from The John Crerar Library in Chicago. Breus mentioned Kiwisch, Klinische Vortrage. II. Auflage. 1852. 1. Abtheilung, p. 389. The author was unable to obtain this document.

108

John H. Ridley, The histogenesis of endometriosis: A review of facts and fancies. Obstetrical and Gynecological Survey 1968;23:1–35.

109

Carl Breus, Uber Wahre Epithel Führende Cystenbildung in Uterusmyomen [Leipzig und Wien: Franz Deuticke,1894]. On pages 20, 21, Breus discussed congenital anomalies, embryonic rests; on pages 19, 23, 24 vestiges of the Gartner, Wolffian, and Müllerian ducts with an illustration on page 25.

110

Carl Breus, 26, figure 7. Cuthbert Lockyer, Fibroids and Allied Tumours (Myoma and Adenomyoma): Their Pathology, Clinical Features and Surgical Treatment [London: Macmillan and Company, 1918], 266. Lockyer, like Breus before him, illustrated some cystic and cavernous adenomyomas that stretch the imagination of the modern viewer accustomed to imaging techniques that would have detected them before they could reach such bizarre configurations and size.

111

Carl Breus, 27.

112

Carl Breus, 27, 29. See also Cuthbert Lockyer, Fibroids and Allied Tumours (Myoma and Adenomyoma): Their Pathology, Clinical Features and Surgical Treatment [London: Macmillan and Company, 1918], 266. “Breus records a case of a voluminous tumour which contained 7 liters of fluid, and on section presented many cysts lined by ciliated epithelium. The general structure was that of a myoma which had spread out into the broad ligament. There was a second growth, the size of a child’s head, in the posterior wall of the uterus, and this communicated with the cavity of the uterus by a canal.”

113

Carl Breus, 29, 33.

114

Carl Breus, 33, 34.

115

Rokitansky, Lehrbuch III. Auflage 1861. III. Band p. 488.

116

Carl Breus, Uber Wahre Epithel Führende Cystenbildung in Uterusmyomen [Leipzig und Wien, 1894], 1–36. [Ridley’s reference number 9]

117

Erna Lesky, The Vienna Medical School of the 19th Century [Baltimore, MD: Johns Hopkins University Press, 1976], 424, 516. Karl Breus, an associate professor of gynecology and Alexander Kolisko (1857–1918), a student of Kundrat and a professor of forensic medicine wrote “the standard work Die Pathologischen Beckenformen (Pathological Forms of the Pelvis) (Vienna and Leipzig. 1900–1912.”

118

Carl Breus, 1–36 plus 25 pages of advertisement. In 1894, Breus was Privatdocent in Obstetrics and Gynecology at the University of Vienna. Appropriately, this small monograph on developmental pathology was dedicated to the memory of Hans Kundrat, former assistant to Rokitansky who was the second of Rokitansky’s assistants to succeed to Rokitansky’s chair as professor of pathological anatomy in Vienna. This volume was borrowed from The John Crerar Library in Chicago.

119

John H. Ridley, The histogenesis of endometriosis: A review of facts and fancies. Obstetrical and Gynecological Survey 1968;23:1–35:2. For example, Ridley specified that Breus cited Kiwisch (1852) (The author has not been able to identify Kiwisch or find his work) and “Cruveilhier who in 1835 referred in his textbook of human anatomy to the existence of cysts of the adnexa, uterus, and vagina, forming along the course of the Wolffian (mesonephric) and Mullerian (paramesonephric) remnants.” (Jean Cruveilhier, Anatomie Pathologique du Corps Humain. Livraison XIII, Planche IV, Paris, 1835.) Then Ridley issued a disclaimer: “Although, here lacking are accurate descriptions, both gross and microscopic, it is plausible to think that such “cysts” were probably of an endometrial nature.” Parenthetically, it should be noted that Rokitansky had noted similar cystic formations about female internal reproductive organs in the 1846 edition of his Manual of Pathological Anatomy, translated by the Sydenham Society in 1855. (Carl Rokitansky, A Manual of Pathological Anatomy, Volume II. The Abdominal Viscera trans. Edward Sieveking [Philadelphia, PA: Blanchard & Lea, 1855], 248, 249. Chapter III. Abnormalities of the Female Sexual Organs. “In no part of the body are cysts so frequent, or so various as in the ovary, in the peritoneum, in the neighborhood of the internal sexual organs, or in the subperitoneal cellular tissue; as, for instance, between the laminae of the broad ligaments, and at the fimbriated extremities of the tubes. Moreover, the size attained by the ovarian cysts is extraordinary.”

120

King, Helen. The Disease of Virgins: Green Sickness, Chlorosis, and the Problems of Puberty. New York: Routledge, 2004, Helen King, The Disease of Virgins: Green sickness, chlorosis, and the problems of puberty [New York: Routledge, 2004], 30. Originally, amenorrhea or the absence of menstruation had been the defining characteristic of the disease of virgins. Helen King, The Disease of Virgins: Green sickness, chlorosis, and the problems of puberty [New York: Routledge, 2004], 24. Parenthetically, by the eighteenth century, diversion of menstruation or vicarious menstruation from various body orifices and tissues was considered by some physicians as disease; however there was nothing to suggest the clinical signs and symptoms of endometriosis. Helen King, The Disease of Virgins: Green sickness, chlorosis, and the problems of puberty [New York: Routledge, 2004], 30. By mid-nineteenth century, the focus on the disease of virgins changed from amenorrhea to the green color of the skin – green sickness or chlorosis. Helen King, The Disease of Virgins: 33. In reality, the skin color was not green, but pale or white, perhaps with a greenish hue. Helen King, The Disease of Virgins: Green sickness, chlorosis, and the problems of puberty [New York: Routledge, 2004], 116. Finally, “By the end of the nineteenth century, chlorosis had been reinvented yet again, this time as a blood disorder: hypochromic [iron deficiency] anaemia. In its earlier incarnation as the disease of virgins, blood was responsible for the symptoms because it was too thick and sticky to pass through a virgin’s narrow channels into the womb; its thickness could be due to a faulty diet.” King’s entire treatise resolves around iron deficiency anemia with none of the signs or symptoms of endometriosis. Several years ago, before publication of her book, the author spoke to Helen King at a meeting of the American Association of the History of Medicine when she spoke on this subject. At first hearing I thought the disease of virgins might be endometriosis, but when I read the book, it was obviously not. Jacalyn Duffin, History of Medicine: A Scandalously Short Introduction [Toronto: University of Toronto Press, 2000], 181–2. “Andral was the first to suggest that anemia could occur if red cells were destroyed (hemolysis), and he described anemia as a decrease in the number of red cells. He associated anemia with pregnancy and with chlorosis. Once called the ‘green sickness of virgins’ for the peculiar cast it gave to the complexion, chlorosis had been described in the sixteenth century by Johannes Lange, who recommended marriage as therapy. It has come to be synonymous with what we would now call iron-deficiency anemia, although it also resembles anorexia nervosa. Andral was the first to observe the small size of red cells in chlorosis.”

121

Knapp VJ. How old is endometriosis? Late 17th- and 18-century European descriptions of the disease. Fertil Steril 1999;72:10–14. Knapp thanked Jerome F. Strauss, III, MD and Celso-Ramon Garcia, MD, the latter an authority on endometriosis from the University of Pennsylvania, “for encouraging this study throughout.” Knapp also thanked Marc Laufer, MD of Harvard University, an authority on adolescent endometriosis, “for suggesting refinements in the text.” Knapp had published a book on disease in 1989: Vincent J. Knapp, Disease and Its Impact on Modern European History [Lewiston, NY: Mellon E. Press, 1989]. This treatise dealt with infectious diseases: plague, syphilis, smallpox, typhus and cholera, tuberculosis, and influenza and their demographic and sociological consequences. In addressing the possible early recognition of endometriosis, Knapp dealt with a chronic disease. Nevertheless, this was not his first venture into history of disease.

122

Knapp VJ. How old is endometriosis? Late 17th- and 18-century European descriptions of the disease. Fertil Steril 1999;72:10–14:13–14.

123

Brosens I, Steeno O. A compass for understanding endometriosis. Fertil Steril 2000;73:179–180. Brosens and Steeno recommended the reading of the manuscript of Daniel Schroen [note different spelling] published by Krebs in Jena in 1690. Ivo Brosens, the doyen of Belgian gynecology, is an internationally recognized scholar and authority on endometriosis and adenomyosis.

124

Benagiano G, Brosens I. History of adenomyosis. Best Pract Res Clin Obstet Gynaecol 2006;20:449–63: 450.

125

Ronald E. Batt. A compass for understanding endometriosis. Fertil Steril 2000;73:179. Questions asked of Professor Knapp: “What were the ages at menarche and at autopsy? Under what circumstances did these women come to autopsy? Were they ‘executed criminals or recently deceased indigents’? Absence of endometriotic lesions in Douglas’ pouch is unusual, because this is a common site for peritoneal endometriosis. Were the observations made in situ at autopsy or after removal of the reproductive organs from the body? Were the 17th and 18th century authors physician-professors and surgeons as described by Roger? Did the authors perform the autopsies? [Professor Knapp stated: ‘What is remarkable about this epistemology is that virtually every published investigator of the time said exactly the same thing.’] Did they make reference to each other? Did they make reference to even earlier authors?”

126

This conclusion is drawn from evidence in the literature, but with the caveat that at some time in the future all the “Knapp manuscripts” should be examined by a team consisting of eighteenth-century scholars and linguists as well authorities on endometriosis in order to establish a definitive judgment.

127

Benagiano G, Brosens I. Who identified endometriosis? Fertil Steril 2011;95:13–16.

128

Emge LA. The elusive adenomyosis of the uterus: its historical past and its present state of recognition. Am J Obstet Gynecol 1962;83:1541–1563. Ludwig A. Emge spent his professional life time studying adenomyosis, beginning shortly after Cullen published Adenomyoma of the Uterus in 1908. On the occasion of the 100th anniversary of Rokitansky’s description of adenomyosis, Emge presented his lifelong experience with the disease and recounted its history and pathogenesis and etiology at the eleventh Joseph L. Baer Lecture of the Chicago Gynecological Society in 1960 at which time he discussed both its pathogenesis and etiology. Even appendicitis was an unsolved problem at this time. Rickman John Godlee, Lord Lister [Oxford: Clarendon Press, 1924], 123. For the history of the recognition of appendicitis, see Smith DC. A historical overview of the recognition of appendicitis – Part I. NY State J Med 1986;86:571–83. Smith DC. A historical overview of the recognition of appendicitis – Part II. NY State J Med 1986;86:639–47. Smith DC. Appendicitis, appendectomy, and the surgeon. Bull Hist Med 1996;70:414–41.

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