THE AMERICAN JOURNAL OF CANCER

A Continuation of The Journal of Cancer Research

VOLUME XXXV JANUARY, 1939 NUMBER 1

MESONEPHROMA OVARII

WALTER SCHILLER, M.D.

(Cook County Hospital, Chicago, Ill.)

Recent investigations on the solid ovarian neoplasias have contributed much to our knowledge of the structure and development of such tumors as the disgerminoma and the arrhenoblastoma. Little advance, however, has been made in the study of the cystic tumors. Current classification methods do not differ essentially from those formerly employed, by which the cystade- nomata were divided into serous or pseudomucinous, simple or papillary, uni- .locular or multilocular, and benign or malignant types. The evolution of theit epithelial components is evidence of abnormal developmental potentialities contained in the cells lining the small cysts originating in the inclusions of the superficial epithelium. This development coincides with the physiological differentiation of the epithelium of Muller’s duct, which is derived, as is the surface epithelium of the ovary, from the cells lining the celomic cavity. On this basis a simple system of classification is possible: the ciliated serous cysts are said to correspond with tubal epithelium; endometrioma with the endo- metrium ; pseudo-mucinous cysts with the cylindrical mucus-secreting epi- thelium of the cervical canal.

At times, however, atypical growths are encountered for which this general method of classification proves inadequate. The epithelium in certain papil- lary tumors may show definite differences from the type observed in the com- mon form. Normally, the cylindrical cells lining the cystic cavities are so grouped that they form a more or less regular horizontal boundary between the epithelial layer and the cystic space. In occasional papillary tumors, how- ever, the epithelial cells appear flattened, as is commonly seen only in the dilated subdivisions of multilocular cystomas or in edematous portions of papillomatous tumors. In the latter location such findings are incidental and depend wholly upon local conditions. In the atypical papillary tumors, on the other hand, the cells are basically of the flat type, and frequently are wider than they are high. More striking is the difference in the cavity lining, which here takes the form of an irregular wavy line formed by the surface of cells

1

2 WALTER SCHILLER

each with a prominent projecting nucleus and a narrow rim of cytoplasm. The nuclei of the common cystadenoma are situated centrally in the cells and are surrounded by a large amount of relatively resistant, well stained cyto- plasm. The large, round, deeply staining nuclei of the atypical form, whether of the cells in one layer or of those in skveral layers, are more conspicuous, whereas the cytoplasm is reduced in amount, shrunken, and poorly stained. Where the epithelium consists of a single layer, it gives the impression of being constituted by a chain of loosely arranged, dark nuclei separated by incom- pletely filled internuclear spaces (Fig. 1). The differences in the epithelium of the two forms of papillary cystomas is sufficient to warrant their separation into two groups (Fig. 2 ) .

FIG. 1. EPITHELIUM OF THE WALL OF A CYSTIC CAVITY (CASE VI) The large dark nucleus of each cell produces a button-like projection into the lumen. Contact

between the cytoplasm of the cells is either absent or very slight. X 800

The question immediately arises as to the derivation of the epithelium present in the more unusual type of cystic tumor. Neither the epithelial cells nor their arrangement on the underlying stroma is characteristic of a normal glandular epithelium. Cells with projecting nuclei occur in endothelium; therefore, an endothelial or even a perithelial origin is theoretically possible. However, the often purely papillary type of growth, the absence of any areas having a structure comparable to blood vessels, and the differences from endo- theliomata arising in other sites make the diagnosis of endothelioma appear unlikely. That these tumors are simple collections of lymph spaces or lym- phangiomas is also improbable. An endothelioma must show evidence of neoplastic proliferation of endothelial cells : whether a tumor actually de- veloping from the endothelium of blood or lymph vessels exists is doubtful. Tumors commonly accepted as endotheliomata have their origin in the cells lining the serous cavities. Such investigators as Kaufmann, Kermauner and

MESONEPHROMA OVARII 3

Robert Meyer deny the occurrence of true endothelioma in the female genital tract. The histological picture of the tumors in question does not conform to the morphoIogy commonly associated with perithelioma, where the prolif - erating cells are found about the adventitia of the blood vessels. This type of tumor has been described in the ovary, but more careful examination usually reveals such growths to be necrotic sarcoma or carcinoma in which only the well nourished cells about the blood vessels are retained.

Differences in the papillary structure of the common form of cystadenoma and the tumor in question are evident. The branching papillary processes of the common type are relatively small in comparison with the cystic spaces into which they project. In tumors of the type under consideration the cavities in

FIG. 2. EPITHELIUM OF (a) SIMPLE SEROUS CYSTOMA; (b) PSEUDOMUCINOUS CYSTOMA; (c)

(h, i , k) MESONEPHROMA PAPILLARY SEROUS CYSTOMA; (d, e, f ) P'aPlLLARY CARCINOMA; (8 ) STRUMA OVARII;

extensive portions are smaller and, as a result, the slender papillary projections appear to be relatively larger or at least longer. Their length often equals the diameter of the cyst. Although usually no more than two papillary processes are found in a cavity, they appear to fill the cystic spaces quite completely. Grossly, the soft, friable, light-colored and easily compressed tumor tissue has a consistency not unlike that of soft solid tumors.

The cells lining both the small cystic spaces and the papillary portions have a morphologic resemblance to endothelium ; however, when proliferation is particularly active, there is an approach to an epithelial form. If the ques- tion is raised where cavities are normally to be found lined by endothelid-like cells and containing processes which are also covered with endothelial-like epithelium, there is but one answer-the glomerulus of the kidney. The nor- mal glomerulus consists of a cavity lined by the outer layer of Bowman's capsule and capillary tufts or loops covered by the inner layer, the cells of which show an endothelial-like character. The nuclei project in a button-like fashion toward the lumen and are separated by a relatively wide interval in

4 WALTER SCHILLER

FIG. 3. TUMOR PARENCHYMA WITH GLOMERULAR FORMATION (RIGHT) BORDERING ON A LARGE THIN-WALLED VEIN (LEFT) (CASE I ) . x 140

FIG. 4. TUMOR PARENCHYMA CONSISTING OF SMALL CYSTIC SPACW CORRESPONDING TO GLOMERULI, EACH CONTAINING A CAPILLARY LOOP. x 140

which the cytoplasm shrinks away toward the basal membrane. In view of their epithelial-like morphology and their accepted mesodermal origin, these flat cells lining the visceral layer of Bowman’s capsule are classified by many histologists as endothelium. Mollendorf considers them allied to the adven- titial cells or pericytes which surround the precapillary arterioles.

MESONEPHROMA OVARII

FIG. 5 . FIVE-MILLIMETER EMBRYO, SHOWING BILATERAL MESONEPHRIC GLOMERULI The invaginated process, containing a capillary loop, is lined by tall epithelium with prominent

nuclei. The vessel lumen contains nucleated red cells. X 120

FIG. 6. FEMALE FETUS MEASURING 40 M X . FROM CROWN OF H E A D TO COCCYX

The ovary is completely pedunculated; involution of the mesonephros has begun. glomerular tufts appear as papillary processes. X 140

The

Isolated structural units, recalling glomeruli, occur at rare intervals in cer- tain of the papillary growths in question (Fig. 3 ) . In others they occupy in a compact fashion areas of sufficient amplitude to produce a homogeneous tumor parenchyma (Fig. 4). But while the normal glomerulus contains forty or fifty capillary loops, there are but one or two-at most three-papillary projections

G WALTER SCHILLER

in the tumors. The further question therefore arises as to whether glomeruli with this minimal number of capillaries occur physiologically in man. This question can be answered in the affirmative if it is recalled that the glomerular structures of the wolffian body or mesonephros contain only a few capillaries, lined by relatively tall cells (Fig. 5 ) . Involution of the wolffian body usually

FIG. 7 . HOMOGENEOUS TUMOR PARENCHYMA CONTAINING A LARGE GLOMERULAR-LIKE STRUCTURE, IN WHICH THE CELLS LINING TIfE VISCERAL LAYER ARE SEPARATED FROM THE CAPILLARY

(CASE IV). X 140

begins at approximately the time when a change of the tall cylindrical capsular cells to the cuboidal form is indicated (Fig. 6 ) . In the metanephros, develop- ment proceeds farther, and is characterized by continued reproduction of the capillaries of the tuft accompanied by a flattening of the lining cells, though occasionally, as a result of a developmental anomaly, tall cells occur in the metanephric glomeruli also. That the cells lining the papillary processes of the tumors which are being considered here are in general flat would indicate a more advanced stage in development, not accompanied, however, by a multi- plication of the capillaries, which remain few in number. The abortive glo- merular structures in the tumors may be observed to best advantage in the areas where the ultimate degree of neoplastic proliferation has not as yet been attained. The flat or cuboidal epithelium of the glomerular-like structures in the tumors is frequently separated by a space from the underlying capillary loops (Fig. 7 ) , as is frequently observed in the mesonephric glomeruli.

In contrast to the well developed connective tissue which encloses the small blood vessels in the papillary processes of the common type of cystic tumor, the processes in the tumors described in the present paper consist of a capillary system surrounded by a layer of cells, but without connective tissue. Tissue reconstruction based on serial sections affords further evidence of the glo- merular nature of the cystic spaces, but distortions in their structure fre- quently appear in areas contiguous to rapidly proliferating tumor tissue (Fig. 8). At times the capillaries may become dilated and filled with blood, and

MESONEPHROMA OVARII 7

their lining cells may be increased to several layers in depth. Such formations are five to ten times as large as a normal glomerulus and they may bear a superficial resemblance to a perithdiomatous formation. The fact that the capillaries lie in a space which is lined by parietal cells similar to those situated centrally reveals the true nature of the structure.

FIG. 8. SERIAL SECTION RECONSTRUCTION OF A GLOMERULAR-LIKE STRUCTURE (CASE 11). x 130 V, to V12 show the ascending capillary branch ; VII, the descending branch. The capillary bend

is shown in VI, and VI,.

The glomerular elements of the tumors may be classified according to the differentiation of the " parietal and visceral " layers of the cystic spaces.l Corresponding to the earliest stage of development of the wolffian body, at the time of invagination of the mesonephric vesicle by a branch of the meso-

1As compared to the differentiation of the analogous elements of the fetal glomerulus in the mesonephros.

8 WALTER SCHILLER

nephric artery, is the smallest type, containing a glomerular tuft lined by a single row of cuboidal or low cylindrical epithelium. The endothelial char- acter of the cells is as yet not apparent (Fig. 5 ) . The glomerular structures in the next stage are somewhat larger, the capillaries have increased to several in number and they are now enclosed by an interrupted layer of flatter, endo- thelial-like cells (Fig. 9). The largest formations, containing several layers of cylindrical cells on the visceral and parietal surfaces, which are observed as a result of frank neoplastic transformation, have no direct morphslogic rela- tionship to the structures of the wolffian body, but the presence in the tumors

FIG. 9. EMBRYO 9.5 MM. LONG To the right of the mesonephric glomeruli is the first adage of the gonads. The nuclei of the

epithelium about the capillary loop of the lowest glomerulus project into the lumen. X 120

of intermediary stages of development permits an identification of their glo- merular origin (Fig. 7 ) .

The possibility of the derivation of the tumors from the pronephros ap- pears remote. This structure is rudimentary in man, and indeed is not de- veloped in every embryo. I t bears no topographical relationship to the gonads and has long since undergone involution when gonadal development begins. The metartephros develops from metanephric tissue at relatively too great a distance from the site of the origin of the gonads. The mesonephros, which remains by a process of exclusion, lies in such intimate relationship to the gonads that cellular inclusions of mesonephric tissue in the gonadal pa- renchyma and consequent possible heterotopic tumor development do not ap- Jear improbable. v. Recklinghausen attempted to prove that endometrioid

MESONEPHROMA OVARII 9

neoplasms situated at the uterine extremity of the fallopian tubes develop from cellular rests of the wolffian body, but this view has subsequently been aban- doned. The gonads and the wolffian body develop in such proximity that, even during relatively late embryonic stages, the juxtaposition of mesenchymal gonadal tissue and fully developed glomeruli of the wolffian body is frequently observed. Growth of the genital grooves produces a separation of the two organs (Fig. lo), and after the development of the ovarian ligament this be- comes complete (Fig. 6). Should the genital grooves be located more pe- ripherally, that is, closer to the mesonephros, the result would be an inclusion

FIG. 10. FIFTEEN-MILLIMETER EMBRYO SHOWING INDENTATION OF BOTH FOLDS OF THE MESONEPHRIC RIDGE. X 175

The gonadal parenchyma borders directly on a mesonephric glomerulus.

of mesonephric elements in the ovary. A tumor developing from such cellular rests may appropriately be called a mesonephroma by analogy with Albrecht and Trappe’s designation “ nephroma ” for an adenosarcoma arising in em- bryonal rests of the metanephros. In order to differentiate such growths from parovarian cysts, which likewise develop from mesonephric tissue, it might be advisable to add some designative adjective as glomerular, pseudo-cystic, or endotheliomatous. The paper of Hansmann and Budd on 1 7 cases of mas- sive unattached retroperitoneal tumors included a description of several growths derived from rests of the wolffian body.

Since the mesonephros also gives rise to renal tubules, it is logical to as- sume that analogous tumor formations would be represented in the meso- nephroma. The assumption is warranted, as short narrow canals lined by a moderately tall cylindrical epithelium with large nuclei were observed in the loose stroma of one tumor of the present series. These areas may represent carcinomatous degeneration of mesonephric tubules (Fig. 15). The rarity of

10 WALTER SCHILLER

tubular tissue is difficult to explain, as rests of mesonephric tissue certainly must contain elements capable of tubule formation since the glomerular and tubular portions are not developmentally distinct.

No similarity of the tumor in question to carcinoma arising in the meta- nephros exists, since the mesonephroma arises in undifferentiated embryonal rests, and the carcinoma in renal tissue which has progressed considerably in its differentiation.

The mesonephric inclusions are probably formed when the wolffian body is in an undifferentiated state, Differentiated wolffian remnants have not been observed in the hilus of the ovary of the new-born or in young children. Simi- larly, granulosa-cell tumors are believed to arise in undifferentiated mesen- chyme, and not in the granulosa-cell tissue proper. But since the gonads develop later than the mesonephros, it is logical to assume that the cells form- ing the mesonephric inclusions are probably laid down in the region of the celomic epithelium, where the gonads subsequently arise. The rarity of tubules in tumor tissue may depend upon an absence of the physiological stimulus to their differentiation present in organized embryonic tissue. They develop normally from the mesonephric vesicles adjacent to the wolffian duct, into which they empty. I t would not be at variance with current biological opinion to assume that the wolffian duct, by its presence and function, acts as an inducing agent or stimulus to the development of the tubules. The tumor contains no duct tissue; in consequence, the growth of tubular structures is generally in abeyance.

I n these tumors transitions occur from the characteristic glomerular struc- tures to a complex system of cystic cavities of varying dimensions lined by the parietal layer of endothelial cells, but in which the capillary tuft has failed to develop. The glomerular tufts may be distorted by the proliferation of acces- sory capillary loops or an abnormality in their size. Tumors with large cystic spaces and many papillary processes resemble the common cystadenoma, but examination of the finer histologic structure of the papillary and parietal portion usually suffices to establish a correct diagnosis. Extensive prolifera- tion of the endothelial-like cells does not produce solid homogeneous cellular masses, but instead gives rise to a loose network of cells with large, round, dis- tinct nuclei separated by narrow rims of cytoplasm. These portions, con- taining fine connective-tissue fibrils as a supporting stroma, infiltrate the cystic spaces and fill them either partially or completely. Infrequently the cells in solid tumor areas contain a larger amount of vesicular cytoplasm. Small quantities of fat are found secondary to degenerative phenomena.

Additional proof of this theory of the origin of the tumors is their occa- sional occurrence at a site corresponding to the normal location of the wolffian body; for example, in the ovarian ligament or in the area of its attachment as peripheral displacement of the ovary occurs after the formation of its pedicle, and in the parovarium. Rests of the wolffian body form the normal con- stituents of the parovarium, situated between the folds of the broad ligament. One example of extra-ovarian and intraligamentary localization of a meso- nephroma is included in the following series of cases (Case I) .

MESONEPHROMA OVARII 11

CASE HISTORIES CASE I: A patient forty-three years of age gave a history of pain in the sacral, anal,

and bladder regions for two years. Examination revealed a mass the size of a child’s head, immediately to the left of the uterus. It was adherent and tore slightly when removed

FIG. 11. CASE I: POSTERIOR VIEW (ABOVE) AND CROSS-SECTION (BELOW) OF TUMOR In the posterior view the elongated and narrowed tube is seen extending along the capsule of

the intraligamentary tumor. Note the uninvolved ovary. In the upper portion of the cross- section are seen a number of cystic spaces; the lower portion has a medullary, pseudo-solid appearance.

through an abdominal incision. The patient received postoperative radiation and was symptom-free two years later.

The uterus was not enlarged. An intraligamentary tumor, in the area where paro- varian cysts are commonly found, displaced the ovary downward (Fig. 11). The narrowed tube extended along the margin of the mass. The upper half of the tumor was cystic, and large, coarse papillary processes were present on the internal surface of its thick wall; the

12 WALTER SCHILLER

tissue of the lower solid half was friable and light-colored. Histologically, the tumor con- sisted of cystic cavities of various sizes lined by cells resembling endothelium. There were numerous characteristic glomerular formations with dilated capillary tufts (Fig. 12) . Fol- lowing proliferation of the endothelial cells in many areas, loose masses of cells were formed which completely filled the smaller cystic spaces. This is an example of a meso- nephroma that has developed on the normal anatomical site of the mesonephros.

A similar tumor infiltrating the vagina to the hymen was observed in the second patient, but its exact point of origin could not be determined. Since tumors arising in the ovary rarely extend in this direction, it is possible that this growth developed from intraligamentary mesonephric tissue situated close to the pelvic wall or from retroperitoneal rests,

FIG. 12. CASE I: TUMOR PARENCHYMA WITH GLOMERULAR FORMATIONS. x 140

CASE 11: A well developed child of eight months had for several weeks had a bloody vaginal discharge. Histologic examinstion of friable tissue masses curetted from the region of the hymen revealed the typical structure of a mesonephroma. The cystic spaces were small and contained typical capillary loops (Fig. 4). The endothelial cells in active pro- liferation showed signs of marked polymorphism. Portions of the tumor were necrotic, hemorrhagic and infiltrated with leukocytes. The renal origin of this tumor was especially evident, as extensive areas consisted of closely packed structures with a characteristic re- semblance to glomerular formations.

The child was treated with radium and x-rays for three weeks, but no apparent benefit ensued. The treatment was interrupted and death occurred five months later. An autopsy was not obtained.

The tumors in the following 6 patients undoubtedly developed in ovarian parenchyma.

CASE 111: Examination of a twenty-year-old patient disclosed a pelvic tumor extending to the umbilicus, and at operation a pedunculated mass attached to the right ovary was removed. There was no evidence of metastasis or ascites. No recurrence was discovered upon examination six months later.

MESONEPHROMA OVARII 13

FIG. 13. CASE 111: CYSTIC SPACES LINED BY ENDOTHELIAL-LIKE EPITHELIUM OF IRREGULAR HEIGHT AND PENETRATED BY CAPILLARY VESSELS. x 140

FIG. 14. CASE 111: D~FFUSE, LOOSE TUMOR PARENCHYMA WITH BEGINNING GLOMERULAR FORMATIONS

The tumor consisted of a cystic and a relatively solid portion composed, however, of numerous very small cystic spaces, irregularly filled with proliferating endothelial cells of the parietal layer (Fig. 13). The connective tissue was loose and edematous. Atypical and well differentiated glomerular-like structures were present. I n some areas the cavities were either partially or completely filled with a fine network of cells projecting from the walls (Fig. 14).

14 WA1,TER SCHILLER

CASE IV: A thirteen-year-old girl who had never menstruated complained of abdominal swelling and pain in the sacral region for eight days prior t o admission. A palpable, freely movable tumor the size of a child’s head was removed surgically from the left ovarian re- gion. A large amount of ascitic fluid was present. The abdominal enlargement recurred after two months, Rectal examination revealed a firm, irregular mass, the size of a fist, attached to the right side of the pelvis. I t was sensitive to pressure and produced a con- striction of the rectal canal. A second laparotomy was performed and the ascitic fluid proved to be hemorrhagic. The tumor displaced the uterus anteriorly, but the right ovary was normal and situated independently of and superior to the mass. There were isolated peritoneal nodules in the vesico-uterine space and in the greater omentum, but no recurrence in the left ovarian region. The patient died the day after the operation, and necropsy re- vealed extensive peritoneal deposits.

The tumor removed at the first operation contained many large and small cysts filled with clear yellow or bloody fluid; in some areas it was of a solid consistency. Histologically, structures analogous to glomeruli were observed, and in many there was evidence of pro-

FIG. 15. CASE Iv: NODTJLE COXSISTING OF TUBULES WITII CYLINDRICAL EPITHELIUM

liferation of the cells lining the parietal layer. In the cells lining the capillary tufts it was sufficiently extensive to produce a configuration resembling perithelioma (Fig. 7). The metastases on the uterine serosa were formed of a network of fine papillary processes. The tumor contained abortive structures reproducing renal tubules (Fig. 15).

CASE V: A woman of sixty-nine, some nineteen years past the menopause, gave a his- tory of hiccoughs and obstipation of two months’ duration, without vomiting. Three weeks prior to admission she began to notice progressive abdominal enlargement and loss of weight. Examination revealed a firm, partially fixed mass in the right lower abdomen ex- tending to the umbilicus. The cervix was atrophic and the uterine body difficult t o distin- guish, but there were no masses in the pouch of Douglas. A laparotomy was performed; the peritoneal cavity contained several liters of clear fluid, and diffuse carcinomatous nodules covered the thickened peritoneum. An ovarian tumor, the size of a child’s head, adherent to the walls of the pelvis and the intestines, was incompletely extirpated. I t had extended into the intraligamentary region. The uterine tube and its mesentery were attached to the mass. The tumor consisted of a dense external zone from which round papillary processes, varying in diameter from 0.75 to 2.5 cm., projected into a cystic space and united to form focal areas of a solid nature (Fig. 16).

The structure of the microscopic cystic cavities was evident on histologic examination.

MESONEPHROMA OVARII 15

FIG. 16. CASE V: OVARIAN TUMOR On the right, in the lower view, is the free portion of the tumor with smooth surface, separated

from the intraligamentary portion on the left by the tube, which extends from the lower left to the upper right of the figure. Note the fimbriated end of the tube in the upper right. The upper view is a cross-section showing pseudo-solid areas and cystic spaces.

The parietal endothelial cells were large and stained deeply; numerous cysts containing papillary processes alternated with others in which these were lacking (Fig, 1 7 ) . The rare glomerular formations are atypical. Numerous cells of the tumor parenchyma elaborated a considerable amount of mucous secretion.

Seven years previously a par- tial resection of the internal genitalia was performed for a tumor of the right ovary, diag- nosed as carcinoma. After several months abdominal enlargement and intestinal dis- turbances reappeared, and an intraligamentary adherent mass, the size of a child’s head, was removed at a second operation. The patient has remained without further recurrence.

The second tumor removed was a unilocular cyst. Isolated and confluent papillary

CASE V I : The patient was a woman of fifty-two years.

16 WALTER SCHILLER

FIG. 17. CASE v: TUMOR PARENCHYMA CONSISTING OF SMALL CYSTS LINED BY ENDOTIIELIAL-LIKE CELLS. X 140

FIG. 18. CASE VI: CYSTIC TUMOR SHOWING PAPILLARY STRUCTURE. X 140

processes projected into its cavity, which contained a yellow serous fluid. Despite the lack of frank similarity of the cystic and papillary portions to glomeruli, the general architecture of the tumor did not differ essentially from that described in Case I (Fig. 18). There were areas of secondary degeneration or more extensive necrosis and leukocytic infiltration.

CASE VII : A woman of forty gave a history of an operation for prolapse four years previously. Her present illness began five or six weeks prior to admission, with enlargement of the abdomen, urinary incontinence, painful defecation, and pain in the sacral and ap- pendicular regions. There was dullness over the upper portion of the sternum and over the left apex of the lung. A roentgenogram showed a sharply defined non-pulsating shadow in that area, subperiosteal sternal thickening and elevation of the diaphragm on the left.

MESONEPHROMA OVARII 17

Three weeks later evidence of thoracic disease disappeared. The blood count was as fol- lows: red cells 3,710,000; white cells 5,500 (polymorphonuclears 80 per cent; small lympho- cytes 11 per cent; large lymphocytes 4 per cent; eosinophils 2 per cent; monocytes 3 per cent). The cervix was normal, the uterine body not distinctly palpable. A firm immobile tumor filled the lower abdomen and extended into the pouch of Douglas. At operation a mass the size of a child’s head, with papillary processes on its external surface, was found replacing the left ovary. The right ovarian region contained a second, smaller tumor ex- tending into the pouch of Douglas and forming adhesions between the uterus and the rectum. The tubes were not involved, but the uterus appeared moderately enlarged. The peritoneum of the lower abdomen contained numerous carcinomatous nodules, the peritoneal cavity two liters of clear yellow fluid. A total hysterectomy was performed. Grossly, soft friable excrescences were observed on the walls of the multilocular cystic tumors, extending in- ternally into the smaller subdivisions and externally to the broad ligament, the serosa of the uterine tubes, and the posterior surface of the uterus (Fig. 19).

FIG. 19. CASE VII: RIGHT OVARY The surface (left) shows peritoneal adhesions. I n the upper right of this view are small,

warty implantation metastases on the peritoneum of the tube. In cross-section (right) the lower pole shows an area of hemorrhagic necrosis, the middle portion soft, light-colored pseudo-solid tumor tissue. There is a large, smooth-walled cystic space in the upper left.

In areas where the cystic spaces were lined by a single layer of flat cells, the histologic structure was characteristic ; numerous cavities, however, were filled with large masses of proliferating cells. The tumor is certainly malignant, but sufficient time has not elapsed since the operation to forecast the ultimate fate of the patient.

CASE VIII : A woman of thirty-eight gave a history of abdominal discomfort, loss of weight, and difficulty in urination for six months. Examination disclosed a firm, immobile mass in the right posterior adnexal region, extending into the pouch of Douglas, displacing the uterus to the left and anteriorly. At operation additional, smaller, degenerated tumor masses were found extending from the lower pelvis to the region above the sacrum. Total hysterectomy was performed. The cystic tumor, as large as a child’s head, showed the characteristic gross and microscopic structure described in previous cases (Fig. 20).

The last two cases of the series are of an unusual nature, since the meso- nephroma in one was associated with a dermoid tumor and in the other with an embryoma.

18 WALTER SCHILLER

CASE I X : A twenty-one-year-old patient complained of recent enlargement of the lower abdomen. A round, hard mass extending from the symphysis to the costal margin, re- placing the right ovary, and metastatic deposits in the vesico-uterine space, in the pouch of Douglas, and on the left ovary were excised. Death occurred six months later as a result of extensive carcinosis.

The tumor was multilocular and many of its cavities were filled with deposits of hair and fat. In other cavities the parietal layer formed irregular friable papillary projections. Areas of cornified squamous epithelium with sebaceous and sweat glands were present and tooth and bone structure were observed in the septa and in the central solid portions of the growth. The papillary and solid areas had the characteristic structure of a mesonephroma. There were numerous dilated capillaries and glomerular structures (Fig. 21), but no glomeruli were found in the metastases (Fig. 22).

CASE X : Following a throat infection a woman of twenty-six had irregular vaginal bleeding over a period of several weeks. The abdomen became enlarged, and on admission the patient complained of a slight rise in temperature, anorexia, and loss of weight. A cystic

FIG. 20. CASE VIII: PAPILLARY AND CYSTIC TUMOR. x 140 To the left of the mid-portion is a glomerulus almost completely filled by proliferating cells.

mass arising from the right ovary extended from the pelvis to the umbilicus; it was adherent to the parietal peritoneum and large intestine. The left ovary was slightly enlarged and also cystic. A total hysterectomy was performed. Portions of the right ovarian tumor were nodular and firm, but hemorrhagic and friable necrotic zones occurred frequently. The thick-walled cystic spaces contained a clear, greenish fluid,

The mass was composed of different types of tumor tissue. Portions showed the char- acteristic histology of a disgerminoma, with areas of secondary degeneration, lymphocytic infiltration, and giant-cell formation in the stroma. Other fragments had the typical struc- ture of an embryoma with solid areas containing glandular tissue, loose and fibromatous connective tissue, cartilage and nerve tissue, and glial elements. Interspersed in these zones were the small cystic cavities lined by flat cells and many glomerular formations of a mesonephroma (Fig. 23) .

Five months later 6.4 liters of hemorrhagic fluid were removed from the abdomen. Further irradiation proved of no avail; the ascites recurred, the patient became cachectic, and death ensued seven weeks later. Autopsy revealed a chronic purulent peritonitis in the lower abdomen, multipIe metastases in the pelvis, on the posterior surface of the bladder, and in the upper abdomen,

Six postoperative radiation treatments were given.

MESONEPHROMA OVARII 19

Fic. 21. CASE IX: LOOSE NETWORK OF TUMOR PAREXCHYMA WITH SMALL GLOMERULI. X 140

FIG. 22. CASE IX: METASTASIS ON THE LEFT OVARY. X 140 The tunica albuginea is in the upper portion ; the lower is formed of a spindle-cell homogeneous

tumor parenchyma.

and a subdiaphragmatic tumor the size of a man’s head, displacing the liver to the left. The histologic nature of the metastatic nodes was not determined.

The malignant destructive nature of the mesonephroma in Case IX caused added difficulty in the interpretation of the histologic sections, but the possi- bility that it developed from primary inclusions of renal tissue among the heterotopic elements of the dermoid appears remote. The extensive descrip-

20 WALTER SCHILLER

tions by Kermauner, Sternberg and other authors contain no mention of simi- lar inclusions in dermoids. More logical is the assumption that two coordi- nated abnormalities in tissue development existed. The condition differs, however, in Case X. Accompanying the inclusions of other tissues, from which the embryoma will later develop, are inclusions of renal tissue. Whether they are mesonephric or metanephric in origin cannot be deter- mined, but the tumor elements morphologically are comparable to those of the growths previously described in this paper.

Clinically, the mesonephroma must be considered a malignant tumor, as demonstrated by the findings and course in 7 of the 10 cases described. Suffi- cient time has not elapsed in one of the remaining 3 cases to permit a final deter- mination of the type of growth, which at operation appeared to be benign.

FIG. 23. CASE X: TUMOR PARENCHYMA CONSISTING OF SMALL CYSTS AND GLOMERULAR FORMATIONS. X 140

The age of the patients ranged from eight months to sixty-nine years. The right ovary was more often involved than the left. In 6 cases there was a definite right-sided tumor, in 2 a similar location was probable, and a purely left-sided lesion occurred only once. The number of cases is too few, how- ever, for this finding to be of great significance, especially as no embryogenetic explanation is available. The ovary in birds develops on the right side, but in man the gonads and wolffian body are bilateral and symmetrical. Sympto- matologicdly, the mesonephroma does not differ from other benign or ma- lignant ovarian papillary cystadenomata. That 10 cases could be collected in a relatively short time is proof that this type of tumor is not rare.'

NOTE: I wish to express my appreciation to Professor P. Werner for Cases I and VI; to Dr. Loffler and Dr. Bergglas for Case 11; to Prof. Mahnert (Graz) and Dr. Joachimowicz for Case 111; to Prof. Jos. Novak for Case IX; to Dr. Steinhardt for Case X, and to Dr. Pollitzer, Director of the Embryological Institute of Vienna, for Figs. 6, 9, and 10.

2 Since completion of this paper I have 9 additional cases of mesonephroma ovarii.

MESONEPHROMA OVARII 21

REFERENCES

HANSMANN, G. H., AND BUDD, J. W.: J. A. M. A. 98: 6, 1932. KERMAUNER, F.: I n Veit-Stoeckel: Handbuch der Gynak. vol. 7, 1932, p. 206. MEYER, ROBERT: Virchows Arch. f . path. Anat. 204: 94, 1911; Centralbl. f . allg. Path. u.

v. MOLLENDORF, W.: Ztschr. f . Zellforsch. u. mikr. Anat. 6: 441, 1927; Handbuch der

STERNBERG, C.: I n Halban-Seitz: Biologie und Pathologie der Weibs, V/2, 1926, p. 702. TRAPPE, M.: Frankfurt. Ztschr. f . Path. 1: 130, 1907.

path. Anat. 30: 291, 1919; Arch. f . Gynak. 113: 454, 1920; 116: 638, 1923.

mikroskopischen Anatomie, VII/l, 1930.