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Ovarian Tumors
Ovarian Tumors A. E. KANTER, M.D, F.A.C.S. *
THE problems of histogenesis of both primary and secondary tumors of the ovary are many and varied. Histopathologists, because of their many interpretations, have made it difficult to adopt a universal classification. The problems involved are many for there are benign and malignant tumors, both primary and secondary; cystic and solid tumors and those with both cystic and solid components; soro.e tumors have benign histopathology with a malignant course; of some we know the embryologic origin and of others we do not; some have hormonal effect and others do not. In order to discuss these interesting tumors more intelligently I would like to incorporate the workable classification described by Pfannenstiel many years ago with our present knowledge of these tumors into a reasonably modern conception. MODIFIED PFANNENSTIEL CLASSIFICATION
A. N onproliferative Tumors Follicle cysts (single) Multiple follicle cysts Theca lutein cysts Corpus luteum cysts a. Solitary cyst b. Multiple corpora lutea 5. Germinal inclusion cysts 1. 2. 3. 4.
B. Proliferative Cysts
I. Stromal in origin 1. Fibroma 2. Sarcoma II. Parenchymal in origin From the Department of Obstetrics and Gynecology, University of Illinois College of Medicine, The Presbyterian Hospital of the City of Chicago and Mt. Sinai Hospital, Chicago.
* Clinical Professor of Obstetrics and Gynecology (Rush), University of Illinois College of Medicine;' Attending Obstetrician and Gynecologist, Presbyterian H'Ospital 'Of the City of ChicagIF,and Mj. Sinai Hospital, Chicago. 279
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280 1. Cystadenomas a. Papillary cystadenoma, benign and malignant b. Pseudomyxomatous cystadenoma 2. Primary carcinoma of the ovary a. Solid carcinoma b. Adenocarcinoma c. Medullary carcinoma d. Plexiform carcinoma 3. Ovigenous tumors a. Benign teratoma (dermoid) b. Malignant teratoma 1. Diffuse , 2. Mesonephroma of the ovary 3. Struma ovarii 4. Hormone-producing tumors a. Male hormone-producing tumors 1. Arrhenoblastoma or andreoblastoma 2. Masculinovoblastoma 3. Teratoma containing male gonad elements b. Female hormone-producing tumors 1. Granulosa cell tumor 2. Theca cell tumor 5. Metastatic tumor of the ovary a. Secondary to contiguous carcinoma b. Krukenberg tumor c. Secondary to cancer of breast d. Endometrioma 6. Tumors from undifferentiated sex cells a. Dysgerminoma 7. Brenner tumor of the ovary NONPROLIFERATIVE TUMORS
The nonproliferative tumors make up the largest group. They are merely the changes in the normal structures present in the ovary that are associated with the physiologic changes. In this category are the "disappearing tumors" of the ovary which may be present on one examination and absent at a later investigation. An inexperienced operator may perform an oophorectomy when actually these tumors will resolve without surgery. In most instances these ovarian tumors are symptomless unless there is torsion of the pedicle or rupture with hemorrhage into the abdominal cavity. The solitary corpus luteum cyst may, on occasion, produce large amounts of progesterone stimulating a very heavy pregravid endometrium. Amenorrhea followed by a very severe uterine hemorrhage may occur. This is most often diagnosed as a spontaneous abortion. Treatment of a corpus luteum cyst is removal of the cyst while conserving .the ovary.. The multiple corpora lutea cysts associated with hydatidiform mole or chorioepithelioma may present an ovary as large as a fist. The en-
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largement is due to the lutenization effect of the chorionic gonadotropin plus the storage of this hormone in the ovary. Upon removal of the mole the ovaries go back to their normal size. On rare occasions, one of these large ovaries may twist upon itself, producing an acute abdominal crisis necessitating surgery. I have had this experience in 2 instances. Bilateral small cystic disease of the ovary may in some instances produce the Stein-Leventhal syndrome. The syndrome consists of amenorrhea or oligomenorrhea, sterility and palpable large cystic ovaries. Occasionally obesity, hirsutism, small underdeveloped breasts, and pelvic pain are noted. When, after every attempt has been made to correct the syndrome by hormonal therapy, weight reduction and correction of nutritional disturbances to no avail, then and only then should one resort to a cuneiform section of both ovaries. In most instances the surgery will not be needed. A diagnosis of these cysts can be made by history, palpation and/or pneumoperitoneum, culdoscopy and colpotomy studies. PROLIFERATIVE CYSTS
Fibroma of the ovary is much less common than the uterine fibroid. It is most often unilateral and solitary. The fibroid may be pea sized or the ovary with tumor may be as large as a five to six months' pregnancy. An interesting grouping of signs known as Meig's syndrome is seen in about one-fourth of the cases. It is characterized by ascites and unilateral or bilateral hydrothorax. This is also seen rarely with other benign solid tumors of the ovary, such as the thecoma and Brenner cell tumor. The exact pathogenesis of the collected fluid is unknown and many theories have been expounded. When there is ascites there is frequently intercellular edema of the fibroid tissue. Though ascites with pelvic malignant tumors is very common, one must not overlook the possibility of the ascites coexisting with a benign tumor of the ovary and not deny a patient the benefits of abdominal surgery. In case of the benign tumors, the ascites and hydrothorax will disappear when the ovarian tumor is removed. Sarcoma of the ovary is very rare, it may be seen at any age, it is usually primary but may be secondary to a fibroma. The diagnosis is usually made by the pathologist. When a lobulated tumor of the ovary shows a tendency to degeneration with intertwihing soft and hard masses one should suspect a sarcoma. PARENCHYMAL TUMORS
Serous Cystadenoma
The serous cystadenomas comprise about 15 per cent of all ovarian neoplasms. They are bilateral in about 30 per cent of cases and are usually seen between the ages of 20 and 50. They may be moderate or large
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in size. The small ones are usually unilocular but the large ones may be lobulated and multilocular. Cauliflower projections are seen in both the everting and inverting types. The contents of the cyst is watery and may be chocolate colored from blood elements. Most of these tumors are cystic but solid types are met with. Histologically, the epithelial cells may be benign or malignant. Clinically all those with a malignant picture run a malignant course and even the benign histologic ones may on occasion show peritoneal implantation with ascites accompanied by a malignant clinical course. For this reason the prognosis must be guarded. Spontaneous regression occurs occasionally when the pathology is of a malignant character. These tumors are silent ones until they have reached a large size or when they have associated ascites. Treatment consists of removal of the involved ovaries with extreme care to prevent contamination of the peritoneal cavity. The age of the patient and involvement of one or both ovaries determines the extent of the surgery. If the papillary excrescences are intracystic and only one ovary is involved, in younger individuals the other ovary may be saved. If botp. ovaries are involved and particularly in extracystic growths, the uterus with the ovaries should be removed irrespective of age. Pseudomucinous Cystadenoma
This entity makes up about 15 per cent of all ovarian tumors. It is one of the most rapidly growing tumors known and may reach enormous size. About 5 per cent are malignant. They are usually unilateral. The tumor consists of locules of various size. On cut surface the locules have unusual coloration brought about by cholesterol and blood pigments. Grossly the surface is smooth, of a white or bluish white color. They rarely become adherent to contiguous surfaces. There may be spontaneous rupture, spilling the contents into the abdominal cavity, producing pseudomyxoma peritonaei. With the accumulation of the material, the abdomen is filled with the gelatinous substance which persists after the removal of the primary tumor. In 10 to 25 per cent of the cases the appendix is also involved with a similar tumor, the so-called mucocele of the appendix. . The treatment is removal of the cyst without rupture, for spilling the contents may produce a pseudomyxoma peritonaei. In young women with a normal ovary on the one side the healthy ovary may be saved. In women past the menopause or close to it both adnexa and uterus should be removed. Careful inspection of the appendix should be made and it .should be removed if it is involved with a .similar tumor.
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Primary Carcinoma of the Ovary
Besides the papillary cystadenocarcinoma and malignant pseudomucinous tumors there is a group of solid or solid cystic carcinomas of the ovary. They vary in size from very small to large. The tumor is round, ovoid or kidney shaped. The consistence of the tumor depends upon the amount of epithelial, fibrous or cystic degeneration. There is a great tendency for both ovaries to be involved in more than 50 per cent of the cases. The papillary form is called adenocarcinoma, the very cellular with little fibrous structure, medullary, with a large amount of fibrous structure, scirrhous, and when arranged in cords, plexiform carcinoma of the ovary. :JThese tumors give no symptoms until well advanced. There may be increased weight in the abdomen, pressure and vaginal discomfort, and as the tumor grows, loss of weight, ascites and urinary difficulty, and finally pain. When these tumors occur during menstrual life there may be no alteration in the cycle. When the menopause is present uterine bleeding may occur, due to extension to the uterus, the pelvic congestion, and the effect of the tumor on the endometrium. A silent ascites in an elderly woman most frequently means ovarian malignancy. The treatment depends upon the advancement of the malignancy and the surgical risk of the patient. If there is a possibility of removal without leaving extensive metastatic masses in the abdomen, a removal of the uterus and adnexa should be accomplished. If this cannot be done, x-ray therapy and irradiated colloidal gold therapy should be instituted without great hope of stemming the growth. Ovigenous Tumors (Dermoid Cysts)
These are tumors which are usually found during the reproductive period and are the common tumors found in young individuals. Contrary to the old conception, tissues found in dermoids are derived from the three primary germ layers and not only ectodermal elements. They are bilateral in about 15 per cent of the cases and are not infrequently multiple. They are occasionally recognized for the first time during pregnancy. The contents of the cyst is usually lipoid material, hair (not necessarily the same shade as the host) and the epithelial plug. One may also find bone, teeth and cartilage. The outer wall of the cyst is quite thick and when a flat plate is taken one can frequently make a diagnosis of the tumor because of the thickened capsule and the radiolucent interior ofthe mass. If teeth and jaw bone are present they show up well on x-ray. Treatment. The spilling of the contents of the cyst into the abdominal
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cavity may produce a very irritating peritonitis. When possible the cyst should be removed intact. Dermoids should be treated surgically. The ovary or part of the ovary should be removed, and careful study of the contralateral ovary should be made because of the possibility of the presence of seed dermoids. The seed dermoids should be enucleated Only about 5 per cent of dermoids show malignant changes in the epi thelial plug. Teratoma or Malignant Dermoid
In these tumors there is a heterogenicity of tissues and parts. Brain, spinal column, intestine, muscle, notochord tissues, mesonephros and many other parts have been described. These tumors are seen in young individuals, usually are small but may grow quite large. The cut surface varies according to its histologic structure. There is a great tendency for it to perforate its capsule and grow into adjacent structures and distant organs. These tumors are highly malignant. Special forms of teratoma may occur, such as mesonephroma, struma ovarii, and arrhenoblastoma with teratoma, which Kanter and Klawans described in the literature in 1946. The mesonephroma was suggested by Schiller because of the presence of glomerular-like structure of cystic spaces containing capillary loops covered by endothelium. In some cases structures are present which duplicate fetal glomeruli with one capillary loop covered by a single layer of columnar epithelium. These tumors are highly malignant and symptomatically do not differ from other malignant papillary cystadenomas. Struma ovarii is a teratoma in which the main structure resembles thyroid tissue with typical acini showing varying amounts of colloid tissue. Chemical analysis (iodine) identifies these tumors as thyroid tissue. Many teratomas histologically show small amounts of thyroid tissue. In struma ovarii, most of the mass is made up of the thyroid tissue. In about 5 per cent of the cases there are symptoms of hyperthyroidism. Ascites is not infrequently associated. PERSONAL CASE. Mrs. J. D., in May 1929, at the age of 24, was hospitalized for hyperemesis gravidarum. In 1932, during the second pregnancy she developed hyperemesis followed by a spontaneous abortion. Five months later a supravaginal hysterectomy was performed for marked dysmenorrhea and menorrhagia. In June, 1941, the patient, now 36 years old, was again hospitalized with a four month history of tremor of the hands, palpitation, dizziness, emotional instability with crying spells, headache, heat intolerance, excessive sweating, dyspnea on exertion, and a loss of 40 pounds in the four month period. Physical examination revealed a moderate bilateral exophthalmos without lid lag or widening of the palpebral fissure. There was a coarse tremor of both hands. The thyroid gland was bilaterally enlarged, smooth, firm and movable. The pulse was 120 and of good quality and regular in rhythm. The blood pressure was 120 systolic and 70 diastolic. On June 23, the basal metabolic rate was plus 57. The
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Kahn reaction was negative, the eythrocytes 4,030,000. leukocytes 5860 with a normal differential, and the blood cholesterol 159 mg. per 100 cc. On July 1, 1941, a subtotal thyroidectomy was performed with complete removal of the isthmus. The gland was very friable and bleeding was profuse. Microscopic sections of the gland revealed a colloid goiter which was incompatible with the toxic manifestations. Following surgery there was a mild thyroid crisis which rapidly subsided with intravenous iodides and sedation. One week postoperatively the basal metabolic rate was plus 40 and there was no abatement of the symptoms. The following four years were punctuated by frequent admissions to hospitals and clinics because of persistence of the above symptoms. At these institutions she had various trials with Lugol's and thiouracil to which she failed to respond and in the spring of 1945 a second thyroidectomy was performed in another city
Fig. 29. Cut section of struma ovarii. and was followed by roentgen therapy which produced no appreciable benefit. It was evident now, because of the impotence of surgery, radiation, iodine and thiouracil, that her difficulty was extrinsic to the thyroid gland. In December, 1945, the patient began to complain of pain in the left lower quadrant. Bimanual examination revealed a mass in the left cul-de-sac, grapefruit sized, nontender, freely movable, and fairly solid in consistency (Fig. 29). On February 7, 1946, the pelvis was explored and a teratoma of the left ovary was removed. Microscopic examination confirmed the impression of the surgeon that the mass consisted chiefly of hyperplastic thyroid tissue which was verified histologically. Two days before surgery the basal metabolic rate was plus 35 and two weeks later it had dropped to plus 1 and the pulse was 76. Four months postoperatively the basal metabolic rate was plus 1 and the pulse 72, with a marked improvement in the patient's general physical condition.
Hormone-Producing Tumors
In this group are male and female hormone-producing tumors. The former type is the arrhenoblastoma or andreoblastoma, and the masculin-
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ovoblastoma (hypernephroma, luteoma, adrenal rest). Robert Meyer described three types of arrhenoblastoma, namely the highly differentiated form (testiculoma ovarii Pick), the highly undifferentiated form which resembles the sarcoma and the intermediate group with tubule formation and occurrence of the interstitial cells of Leydig. These tumors are rare and in most instances are benign. The symptoms depend upon the production of androgenic hormone. If the hormoneproducing cells are not functioning there will be no symptoms of masculinization. We may have defeminization, such as atrophy of breasts,
A
B
Fig. 30. Patient before operation, showing in A, male type of hair distribution, flatness of breasts, and extent of abdominal tumor; in B, beard growth (four days) and masculine facial characteristics. (Kanter, A. E., and Klawans, A. H., in American_IIournal of Cancer, Volume 40, 1940.)
amenorrhea, redistribution of fat, broadening of the shoulders and changes in facial contour (Fig. 30). These changes are followed by masculinization with three cardinal symptoms, male hirsutism, enlarged clitoris, and hypertrophic laryngitis with hoarse voice. When these tumors are removed, the patient reverts back to her normal physiologic status, menstruating and bearing children (Fig. 31). The histologic picture is shown in Figures 32 to 35. The female hormone-producing tumors are the granulosa cell and theca cell tumors. The granulosa cell tumors are more common than the theca cell tumors. They may occur at any age and are usually unilateraL Granulosa cell tumors are malignant in about 20 per cent of the cases. The theca cell
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Fig. 31. Same patient three months after operation, eleven days after shaving. Note also increase in size of breasts. (Kanter, A. E., and Klawans, A. R., in American Journal of Cancer, Volume 40, 194O.)
Fig. 32. Cystic portion of teratomatous arrhenoblastoma. (Kanter, A. E., and Klawans, A. R., in American Journal of Cancer, Volume 40, 194O.)
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288 Fig. 33.
Fig. 34. Fig. 33. Mesenchyme and cartilage. Fig. 34. Area of tumor showing classical structure of arrhenoblastoma. (Kanter, A. E., and Klawans, A. H., in American Journal of Cancer, Volume 40, 1940.)
tumor is rarely malignant. Granulosa cell tumors vary in size from very small to size large enough to occupy most of the abdomen. They are ovoid or kidney shaped with a smooth capsule. The cut surface is of a granular consistency, may be solid or solid with cystic cavities. His-
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tologically there is a diffuse parenchymatous, follicular pattern, and a trabeculated cylindroid type. The theca cell tumors were first described in this country by Melnick and Kanter. They are unilateral hard tumors with a smooth capsule. The cut surface resembles a fibroid with a distinct yellow or orange tinge. Histologically there are fusiform cells with many areas of cell nests, assuming an epithelioid appearance. The symptoms of the estrin-producing tumors depend upon the amount of hormone produced and the age of the patient. In the young
Fig. 35. Embryonic rete.
a precocious puberty may occur with more or less regular bleeding from the uterus. During reproduction period there ~ay be irregular periOds, oligomenorrhea or amenorrhea. During the menopause the ut~~us is enlarged, the endometrium is hypertrophied, the vaginal mucous membrane is thickened and there is more or less regular uterine bleeding; Upon removal of the tumor, when not malignant, the patient reverts back to her normal physiological somatic age. Repeating, these tumors may be present without producing any symptoms .because the hormone cells are not functioning. Treatment should be surgical removal, conservation of the ovaries in the young, and more.radicl!-l operation in older people and when malig~ nancy is found to exist.
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Metastatic: Tumors of the Ovary These tumors may arise because of the contiguity of the ovary to tube, uterus and large bowel. Carcinoma in any of these structures may metastasize to the ovaries. Also carcinoma of the stomach, intestine and breast may metastasize to the ovaries. The tumor of the ovary histologically resembles the primary tumor. The most interesting of these tumors is the Krukenberg tumor with its characteristic signet ring cells which are not invariably present. The ovary is symmetrically enlarged but retains its normal form with a smooth surface. The treatment is radical removal of the uterus, tubes and ovaries, and careful investigation of the stomach and duodenum before closing the abdomen, for the patient may harbor carcinoma in these organs without a~ symptoms. A Krukenberg tumor should be thought of when a patient hastad a longstanding gastric ulcer or when a carcinoma of the stomach had been operated upon previously. The endometrioma, chocolate cyst or Sampson's tumor may be unilateral or bilateral. The tumor is characterized by having chocolate material in the cyst cavity with endometrial elements proven histologically. Every tumor of the ovary filled with chocolate material is not an endometrioma. As these tumors grow larger there is a tendency to perforate so that they adhere to the uterus, tube, broad ligament, uterosacral ligaments and the rectosigmoid. In freeing these adherent tumors there is always a spill oJ"'hick chocolate colored fluid. There may be no symptoms but when present there is a characteristic dysmenorrhea with pain beginning some days before the onset of menses, lasting throughout and several days beyond the end of the period. Sterility frequently is a complaint of these patients. Treatment. These tumors occur frequently in the young so whenever possible the normal ovary should be retained. If the pathologic changes have destroyed both ovaries and there is much involvement of bowel and adjacent structures ablation of all pelvic organs may be necessary. Conservation in many instances has permitted the patient to have a family even though a second operation may be necessary in ·the future. Presacral neurectomy is useful in these cases when the uterus is not removed in the presence of severe dysmenorrhea. Dysgerminoma This appellation was given by Robert Meyer because these tumors arise from undifferentiated germ cells before the cells have male or female attributes. The identical tumor has been described in the testicle under the name of seminoma. These are unilateral but may be bilateral and are seen most frequently before the age of 30. They vary widely in size, grow quite rapidly and ha~e a high degree of malignancy. Their spread simulates the metastases of all ovarian malignancies.
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Grossly they have a smooth dense capsule and at times are nodular. The cut surface is grayish pink and has fibrillations simulating the sulci in the brain. Microscopically there is abundant cytoplasm with large nuclei arranged in alveolar form separated by fibrous tissue septa with marked lymphocytic infiltration. There are many mitotic figures and occasional giant cells with the nuclei at the periphery. These tumors are commonly seen in pseudohermaphrodites or in women with poor gonadal development. The removal of the tumor does not change the pseudohermaphrodite nor improve the subnormal gonadal development. There are cases on record of pregnancy following the removal of this neoplasm. In general, the treatment of these tumors is radical surgery plus x-ray when the lesion is limited to the pelvis. When extensive metastases have occurred in the liver, lymph glands, omentum and other vital structures it is questionable whether surgery is indicated. Exception to the above rule may be made when the dysgerminoma is limited to one ovary in a young woman with no evidence of the tumor breaking through its capsule. Brenner Tumor
These are relatively rare tumors named after the man who first described them accurately. They are seen most frequently during the menopause. They vary greatly in size, most of them are solid, some have cystic areas. Occasionally they are found in the wall of a pseudomucinous cyst. They are not uncommonly bilateral. There are no characteristic symptoms. They do not produce any hormone yet a few Brenner tumors have been associated with postmenopausal bleeding. There is no evidence that the tumor produced the hormone to initiate the bleeding from the endometrium. The tumor is benign. Occasionally one finds Meigs' syndrome associated with this neoplasm. Most characteristic is the histologic picture wherein are nests of epithelial cells surrounded by fibromatous connective tissue. The cells are large, polyhedral, quite uniform with small ovoid nuclei. There is a tendency to degeneration of the center of the cell nests. Also there is a tendency for the superficial layer of cells in the cystic cavities to assume a pseudomucinous appearance. For this reason some workers believe that these tumors may be the origin of the pseudomucinous tumors. Treatment. Removal of the tumor is all that is necessary in the young. During the menopause all the pelvic generative organs should be removed. 'PRACTICAL ASPECTS OF OVARIAN TUMORS
Whenever an ovarian neoplasm is present at repeated examinations several weeks apart it should be investigated even in the absence of
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symptoms. About 15 per cent of the proliferation tumors are malignant so it is necessary to study these tumors, grossly and microscopically. This can be accomplished only by surgical intervention, although other methods, such as x-ray, pneumoperitoneum and culdoscopy, may be helpful. When a benign tumor is diagnosed, normal ovarian tissue should be conserved. If possible all tumors of the ovary should be removed intact even if it necessitates the large incisions. When a malignant tumor is unilateral, both the adnexa and uterus should be removed. Eighty per cent of the ovarian tumors are cystic and are mostly benign; 20 per cent are solid tumors and are mostly malignant. The question as to removing the ovaries at a certain age when hysterectomy is done is still unsettled. Some gynecologists give an arbitrary age of 43 or 45, while others believe in leaving in one ovary if it is still functioning. It has been my experience that rarely does a patient return with an ovarian neoplasm at a future date following a hysterectomy. However, when there is any suspicion of serious pathology in the contralateral ovary, it should be removed disregarding the patient's age. In ovarian tumors discovered in early pregnancy indications for immediate operation are torsion of the pedicle, intracystic hemorrhage, signs of infection, signs of malignancy, overdistention of the abdomen and cysts adherent in the cul-de-sac. If there is no immediate haste for surgery one should wait until the fourth month. When the diagnosis of a tumor mass is first made just before the viability of the fetus, if delay is not harmful one should wait until the child is viable or preferably observe the patient until term so that cesarean section and removal of tumor can be accomplished at the same time. There is a fairly high incidence of carcinoma of the endometrium associated with granulosa and theca cell tumors especially when they occur during the menopause. The incidence is much higher than chance alone. The hormone produced by these tumors produces a hyperplasia of the endometrium and there is a direct relationship between hyperplasia and adenocarcinoma of the body of the uterus. For this reason radical surgery is indicated. Because malignant tumors of the ovary produce no symptoms until they have grown considerably, and many times the patient when first seen is beyond cure by any means at hand today, one asks whether there are really any effective prophylactic methods against ovarian carcinoma. A routine bilateral oophorectomy in women past 40 undergoing a pelvic laparotomy will certainly prevent carcinoma of the ovary. One must weigh the sudden menopause with its attendant symptoms against the natural menopause. In my experience sudden ablation of the gonads disturbs the patient less than the natural menopause. Also we have at
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hand today therapy which combats the untoward symptoms. If ablation of the ovaries is not to be done, a very careful inspection of these organs must be carried out whether the surgery is done by the abdominal or vaginal route. Finally in the surgical repair of procidentia where the uterus is conserved, an inspection of the ovaries should be made either through an anterior or posterior colpotomy incision. One of the big advantages in doing a hysterectomy as part of the procedure in the cure of procidentia is the opportunity to study the ovaries for neoplastic growth. Following operation for malignancy of the ovary and in the inoperable cases a course of x-ray therapy is indicated. Today most workers show a 15 per cent increased salvage rate in the five year period following treatment. Occasionally a case that seems hopeless improves sufficiently under radiation therapy to warrant the use of surgery. Colloidal isotope gold is used intraperitoneally when ascites is associated with malignancy of the ovary. In some patients the formation of the fluid is retarded so that there is less necessity for tapping the abdomen. The course of the disease is not altered. Male hormone therapy has been used in inoperable cancer of the ovary and uterus and although there is a feeling of well-being, the therapy does not alter the course of the disease. REFERENCES Novak, Emil: Gynecological and Obstetrical Pathology, Philadelphia, W. B. Saunders Company, 1947. Dockerty, M. B.: Ovarian Neoplasms. A Collected Review. Int. Abst. Surg. 81: 3,179-204. Barzilai, Y.: Atlas of Ovarian Tumors. New York, Grune & Stratton, 1943. Kanter, A. E. and Klawans, A. H.: Arrhenoblastoma of the Ovary. Am. J. Cancer 42 (4): 470-486 (Dec.) 1940. Kanter, A. E. and Ragins, A. B.: Arrhenoblastoma of Ovary. Am. J. Obst. & Gynec. 42: 1061-u5 (Dec.) 1941. Melnick, P. J. and Kanter, A. E.: Theca Cell Tumors of the Ovary. Am. J. Obst. & Gynec. 27: (1): 41-53, 1934. Walter, R. I., Bachman, A. L. and Harris', W.: Treatment of Carcinoma of the Ovary: Improvement of Results with Postoperative Radiotherapy. Am. J. Roentj1;enol. J.5: 403--411 (March) 1941.
THE problems of histogenesis of both primary and secondary tumors of the ovary are many and varied. Histopathologists, because of their many interpretations, have made it difficult to adopt a universal classification. The problems involved are many for there are benign and malignant tumors, both primary and secondary; cystic and solid tumors and those with both cystic and solid components; soro.e tumors have benign histopathology with a malignant course; of some we know the embryologic origin and of others we do not; some have hormonal effect and others do not. In order to discuss these interesting tumors more intelligently I would like to incorporate the workable classification described by Pfannenstiel many years ago with our present knowledge of these tumors into a reasonably modern conception. MODIFIED PFANNENSTIEL CLASSIFICATION
A. N onproliferative Tumors Follicle cysts (single) Multiple follicle cysts Theca lutein cysts Corpus luteum cysts a. Solitary cyst b. Multiple corpora lutea 5. Germinal inclusion cysts 1. 2. 3. 4.
B. Proliferative Cysts
I. Stromal in origin 1. Fibroma 2. Sarcoma II. Parenchymal in origin From the Department of Obstetrics and Gynecology, University of Illinois College of Medicine, The Presbyterian Hospital of the City of Chicago and Mt. Sinai Hospital, Chicago.
* Clinical Professor of Obstetrics and Gynecology (Rush), University of Illinois College of Medicine;' Attending Obstetrician and Gynecologist, Presbyterian H'Ospital 'Of the City of ChicagIF,and Mj. Sinai Hospital, Chicago. 279
A. E. Kanter
280 1. Cystadenomas a. Papillary cystadenoma, benign and malignant b. Pseudomyxomatous cystadenoma 2. Primary carcinoma of the ovary a. Solid carcinoma b. Adenocarcinoma c. Medullary carcinoma d. Plexiform carcinoma 3. Ovigenous tumors a. Benign teratoma (dermoid) b. Malignant teratoma 1. Diffuse , 2. Mesonephroma of the ovary 3. Struma ovarii 4. Hormone-producing tumors a. Male hormone-producing tumors 1. Arrhenoblastoma or andreoblastoma 2. Masculinovoblastoma 3. Teratoma containing male gonad elements b. Female hormone-producing tumors 1. Granulosa cell tumor 2. Theca cell tumor 5. Metastatic tumor of the ovary a. Secondary to contiguous carcinoma b. Krukenberg tumor c. Secondary to cancer of breast d. Endometrioma 6. Tumors from undifferentiated sex cells a. Dysgerminoma 7. Brenner tumor of the ovary NONPROLIFERATIVE TUMORS
The nonproliferative tumors make up the largest group. They are merely the changes in the normal structures present in the ovary that are associated with the physiologic changes. In this category are the "disappearing tumors" of the ovary which may be present on one examination and absent at a later investigation. An inexperienced operator may perform an oophorectomy when actually these tumors will resolve without surgery. In most instances these ovarian tumors are symptomless unless there is torsion of the pedicle or rupture with hemorrhage into the abdominal cavity. The solitary corpus luteum cyst may, on occasion, produce large amounts of progesterone stimulating a very heavy pregravid endometrium. Amenorrhea followed by a very severe uterine hemorrhage may occur. This is most often diagnosed as a spontaneous abortion. Treatment of a corpus luteum cyst is removal of the cyst while conserving .the ovary.. The multiple corpora lutea cysts associated with hydatidiform mole or chorioepithelioma may present an ovary as large as a fist. The en-
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largement is due to the lutenization effect of the chorionic gonadotropin plus the storage of this hormone in the ovary. Upon removal of the mole the ovaries go back to their normal size. On rare occasions, one of these large ovaries may twist upon itself, producing an acute abdominal crisis necessitating surgery. I have had this experience in 2 instances. Bilateral small cystic disease of the ovary may in some instances produce the Stein-Leventhal syndrome. The syndrome consists of amenorrhea or oligomenorrhea, sterility and palpable large cystic ovaries. Occasionally obesity, hirsutism, small underdeveloped breasts, and pelvic pain are noted. When, after every attempt has been made to correct the syndrome by hormonal therapy, weight reduction and correction of nutritional disturbances to no avail, then and only then should one resort to a cuneiform section of both ovaries. In most instances the surgery will not be needed. A diagnosis of these cysts can be made by history, palpation and/or pneumoperitoneum, culdoscopy and colpotomy studies. PROLIFERATIVE CYSTS
Fibroma of the ovary is much less common than the uterine fibroid. It is most often unilateral and solitary. The fibroid may be pea sized or the ovary with tumor may be as large as a five to six months' pregnancy. An interesting grouping of signs known as Meig's syndrome is seen in about one-fourth of the cases. It is characterized by ascites and unilateral or bilateral hydrothorax. This is also seen rarely with other benign solid tumors of the ovary, such as the thecoma and Brenner cell tumor. The exact pathogenesis of the collected fluid is unknown and many theories have been expounded. When there is ascites there is frequently intercellular edema of the fibroid tissue. Though ascites with pelvic malignant tumors is very common, one must not overlook the possibility of the ascites coexisting with a benign tumor of the ovary and not deny a patient the benefits of abdominal surgery. In case of the benign tumors, the ascites and hydrothorax will disappear when the ovarian tumor is removed. Sarcoma of the ovary is very rare, it may be seen at any age, it is usually primary but may be secondary to a fibroma. The diagnosis is usually made by the pathologist. When a lobulated tumor of the ovary shows a tendency to degeneration with intertwihing soft and hard masses one should suspect a sarcoma. PARENCHYMAL TUMORS
Serous Cystadenoma
The serous cystadenomas comprise about 15 per cent of all ovarian neoplasms. They are bilateral in about 30 per cent of cases and are usually seen between the ages of 20 and 50. They may be moderate or large
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in size. The small ones are usually unilocular but the large ones may be lobulated and multilocular. Cauliflower projections are seen in both the everting and inverting types. The contents of the cyst is watery and may be chocolate colored from blood elements. Most of these tumors are cystic but solid types are met with. Histologically, the epithelial cells may be benign or malignant. Clinically all those with a malignant picture run a malignant course and even the benign histologic ones may on occasion show peritoneal implantation with ascites accompanied by a malignant clinical course. For this reason the prognosis must be guarded. Spontaneous regression occurs occasionally when the pathology is of a malignant character. These tumors are silent ones until they have reached a large size or when they have associated ascites. Treatment consists of removal of the involved ovaries with extreme care to prevent contamination of the peritoneal cavity. The age of the patient and involvement of one or both ovaries determines the extent of the surgery. If the papillary excrescences are intracystic and only one ovary is involved, in younger individuals the other ovary may be saved. If botp. ovaries are involved and particularly in extracystic growths, the uterus with the ovaries should be removed irrespective of age. Pseudomucinous Cystadenoma
This entity makes up about 15 per cent of all ovarian tumors. It is one of the most rapidly growing tumors known and may reach enormous size. About 5 per cent are malignant. They are usually unilateral. The tumor consists of locules of various size. On cut surface the locules have unusual coloration brought about by cholesterol and blood pigments. Grossly the surface is smooth, of a white or bluish white color. They rarely become adherent to contiguous surfaces. There may be spontaneous rupture, spilling the contents into the abdominal cavity, producing pseudomyxoma peritonaei. With the accumulation of the material, the abdomen is filled with the gelatinous substance which persists after the removal of the primary tumor. In 10 to 25 per cent of the cases the appendix is also involved with a similar tumor, the so-called mucocele of the appendix. . The treatment is removal of the cyst without rupture, for spilling the contents may produce a pseudomyxoma peritonaei. In young women with a normal ovary on the one side the healthy ovary may be saved. In women past the menopause or close to it both adnexa and uterus should be removed. Careful inspection of the appendix should be made and it .should be removed if it is involved with a .similar tumor.
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Primary Carcinoma of the Ovary
Besides the papillary cystadenocarcinoma and malignant pseudomucinous tumors there is a group of solid or solid cystic carcinomas of the ovary. They vary in size from very small to large. The tumor is round, ovoid or kidney shaped. The consistence of the tumor depends upon the amount of epithelial, fibrous or cystic degeneration. There is a great tendency for both ovaries to be involved in more than 50 per cent of the cases. The papillary form is called adenocarcinoma, the very cellular with little fibrous structure, medullary, with a large amount of fibrous structure, scirrhous, and when arranged in cords, plexiform carcinoma of the ovary. :JThese tumors give no symptoms until well advanced. There may be increased weight in the abdomen, pressure and vaginal discomfort, and as the tumor grows, loss of weight, ascites and urinary difficulty, and finally pain. When these tumors occur during menstrual life there may be no alteration in the cycle. When the menopause is present uterine bleeding may occur, due to extension to the uterus, the pelvic congestion, and the effect of the tumor on the endometrium. A silent ascites in an elderly woman most frequently means ovarian malignancy. The treatment depends upon the advancement of the malignancy and the surgical risk of the patient. If there is a possibility of removal without leaving extensive metastatic masses in the abdomen, a removal of the uterus and adnexa should be accomplished. If this cannot be done, x-ray therapy and irradiated colloidal gold therapy should be instituted without great hope of stemming the growth. Ovigenous Tumors (Dermoid Cysts)
These are tumors which are usually found during the reproductive period and are the common tumors found in young individuals. Contrary to the old conception, tissues found in dermoids are derived from the three primary germ layers and not only ectodermal elements. They are bilateral in about 15 per cent of the cases and are not infrequently multiple. They are occasionally recognized for the first time during pregnancy. The contents of the cyst is usually lipoid material, hair (not necessarily the same shade as the host) and the epithelial plug. One may also find bone, teeth and cartilage. The outer wall of the cyst is quite thick and when a flat plate is taken one can frequently make a diagnosis of the tumor because of the thickened capsule and the radiolucent interior ofthe mass. If teeth and jaw bone are present they show up well on x-ray. Treatment. The spilling of the contents of the cyst into the abdominal
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cavity may produce a very irritating peritonitis. When possible the cyst should be removed intact. Dermoids should be treated surgically. The ovary or part of the ovary should be removed, and careful study of the contralateral ovary should be made because of the possibility of the presence of seed dermoids. The seed dermoids should be enucleated Only about 5 per cent of dermoids show malignant changes in the epi thelial plug. Teratoma or Malignant Dermoid
In these tumors there is a heterogenicity of tissues and parts. Brain, spinal column, intestine, muscle, notochord tissues, mesonephros and many other parts have been described. These tumors are seen in young individuals, usually are small but may grow quite large. The cut surface varies according to its histologic structure. There is a great tendency for it to perforate its capsule and grow into adjacent structures and distant organs. These tumors are highly malignant. Special forms of teratoma may occur, such as mesonephroma, struma ovarii, and arrhenoblastoma with teratoma, which Kanter and Klawans described in the literature in 1946. The mesonephroma was suggested by Schiller because of the presence of glomerular-like structure of cystic spaces containing capillary loops covered by endothelium. In some cases structures are present which duplicate fetal glomeruli with one capillary loop covered by a single layer of columnar epithelium. These tumors are highly malignant and symptomatically do not differ from other malignant papillary cystadenomas. Struma ovarii is a teratoma in which the main structure resembles thyroid tissue with typical acini showing varying amounts of colloid tissue. Chemical analysis (iodine) identifies these tumors as thyroid tissue. Many teratomas histologically show small amounts of thyroid tissue. In struma ovarii, most of the mass is made up of the thyroid tissue. In about 5 per cent of the cases there are symptoms of hyperthyroidism. Ascites is not infrequently associated. PERSONAL CASE. Mrs. J. D., in May 1929, at the age of 24, was hospitalized for hyperemesis gravidarum. In 1932, during the second pregnancy she developed hyperemesis followed by a spontaneous abortion. Five months later a supravaginal hysterectomy was performed for marked dysmenorrhea and menorrhagia. In June, 1941, the patient, now 36 years old, was again hospitalized with a four month history of tremor of the hands, palpitation, dizziness, emotional instability with crying spells, headache, heat intolerance, excessive sweating, dyspnea on exertion, and a loss of 40 pounds in the four month period. Physical examination revealed a moderate bilateral exophthalmos without lid lag or widening of the palpebral fissure. There was a coarse tremor of both hands. The thyroid gland was bilaterally enlarged, smooth, firm and movable. The pulse was 120 and of good quality and regular in rhythm. The blood pressure was 120 systolic and 70 diastolic. On June 23, the basal metabolic rate was plus 57. The
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Kahn reaction was negative, the eythrocytes 4,030,000. leukocytes 5860 with a normal differential, and the blood cholesterol 159 mg. per 100 cc. On July 1, 1941, a subtotal thyroidectomy was performed with complete removal of the isthmus. The gland was very friable and bleeding was profuse. Microscopic sections of the gland revealed a colloid goiter which was incompatible with the toxic manifestations. Following surgery there was a mild thyroid crisis which rapidly subsided with intravenous iodides and sedation. One week postoperatively the basal metabolic rate was plus 40 and there was no abatement of the symptoms. The following four years were punctuated by frequent admissions to hospitals and clinics because of persistence of the above symptoms. At these institutions she had various trials with Lugol's and thiouracil to which she failed to respond and in the spring of 1945 a second thyroidectomy was performed in another city
Fig. 29. Cut section of struma ovarii. and was followed by roentgen therapy which produced no appreciable benefit. It was evident now, because of the impotence of surgery, radiation, iodine and thiouracil, that her difficulty was extrinsic to the thyroid gland. In December, 1945, the patient began to complain of pain in the left lower quadrant. Bimanual examination revealed a mass in the left cul-de-sac, grapefruit sized, nontender, freely movable, and fairly solid in consistency (Fig. 29). On February 7, 1946, the pelvis was explored and a teratoma of the left ovary was removed. Microscopic examination confirmed the impression of the surgeon that the mass consisted chiefly of hyperplastic thyroid tissue which was verified histologically. Two days before surgery the basal metabolic rate was plus 35 and two weeks later it had dropped to plus 1 and the pulse was 76. Four months postoperatively the basal metabolic rate was plus 1 and the pulse 72, with a marked improvement in the patient's general physical condition.
Hormone-Producing Tumors
In this group are male and female hormone-producing tumors. The former type is the arrhenoblastoma or andreoblastoma, and the masculin-
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ovoblastoma (hypernephroma, luteoma, adrenal rest). Robert Meyer described three types of arrhenoblastoma, namely the highly differentiated form (testiculoma ovarii Pick), the highly undifferentiated form which resembles the sarcoma and the intermediate group with tubule formation and occurrence of the interstitial cells of Leydig. These tumors are rare and in most instances are benign. The symptoms depend upon the production of androgenic hormone. If the hormoneproducing cells are not functioning there will be no symptoms of masculinization. We may have defeminization, such as atrophy of breasts,
A
B
Fig. 30. Patient before operation, showing in A, male type of hair distribution, flatness of breasts, and extent of abdominal tumor; in B, beard growth (four days) and masculine facial characteristics. (Kanter, A. E., and Klawans, A. H., in American_IIournal of Cancer, Volume 40, 1940.)
amenorrhea, redistribution of fat, broadening of the shoulders and changes in facial contour (Fig. 30). These changes are followed by masculinization with three cardinal symptoms, male hirsutism, enlarged clitoris, and hypertrophic laryngitis with hoarse voice. When these tumors are removed, the patient reverts back to her normal physiologic status, menstruating and bearing children (Fig. 31). The histologic picture is shown in Figures 32 to 35. The female hormone-producing tumors are the granulosa cell and theca cell tumors. The granulosa cell tumors are more common than the theca cell tumors. They may occur at any age and are usually unilateraL Granulosa cell tumors are malignant in about 20 per cent of the cases. The theca cell
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Fig. 31. Same patient three months after operation, eleven days after shaving. Note also increase in size of breasts. (Kanter, A. E., and Klawans, A. R., in American Journal of Cancer, Volume 40, 194O.)
Fig. 32. Cystic portion of teratomatous arrhenoblastoma. (Kanter, A. E., and Klawans, A. R., in American Journal of Cancer, Volume 40, 194O.)
A. E. Kanter
288 Fig. 33.
Fig. 34. Fig. 33. Mesenchyme and cartilage. Fig. 34. Area of tumor showing classical structure of arrhenoblastoma. (Kanter, A. E., and Klawans, A. H., in American Journal of Cancer, Volume 40, 1940.)
tumor is rarely malignant. Granulosa cell tumors vary in size from very small to size large enough to occupy most of the abdomen. They are ovoid or kidney shaped with a smooth capsule. The cut surface is of a granular consistency, may be solid or solid with cystic cavities. His-
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tologically there is a diffuse parenchymatous, follicular pattern, and a trabeculated cylindroid type. The theca cell tumors were first described in this country by Melnick and Kanter. They are unilateral hard tumors with a smooth capsule. The cut surface resembles a fibroid with a distinct yellow or orange tinge. Histologically there are fusiform cells with many areas of cell nests, assuming an epithelioid appearance. The symptoms of the estrin-producing tumors depend upon the amount of hormone produced and the age of the patient. In the young
Fig. 35. Embryonic rete.
a precocious puberty may occur with more or less regular bleeding from the uterus. During reproduction period there ~ay be irregular periOds, oligomenorrhea or amenorrhea. During the menopause the ut~~us is enlarged, the endometrium is hypertrophied, the vaginal mucous membrane is thickened and there is more or less regular uterine bleeding; Upon removal of the tumor, when not malignant, the patient reverts back to her normal physiological somatic age. Repeating, these tumors may be present without producing any symptoms .because the hormone cells are not functioning. Treatment should be surgical removal, conservation of the ovaries in the young, and more.radicl!-l operation in older people and when malig~ nancy is found to exist.
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Metastatic: Tumors of the Ovary These tumors may arise because of the contiguity of the ovary to tube, uterus and large bowel. Carcinoma in any of these structures may metastasize to the ovaries. Also carcinoma of the stomach, intestine and breast may metastasize to the ovaries. The tumor of the ovary histologically resembles the primary tumor. The most interesting of these tumors is the Krukenberg tumor with its characteristic signet ring cells which are not invariably present. The ovary is symmetrically enlarged but retains its normal form with a smooth surface. The treatment is radical removal of the uterus, tubes and ovaries, and careful investigation of the stomach and duodenum before closing the abdomen, for the patient may harbor carcinoma in these organs without a~ symptoms. A Krukenberg tumor should be thought of when a patient hastad a longstanding gastric ulcer or when a carcinoma of the stomach had been operated upon previously. The endometrioma, chocolate cyst or Sampson's tumor may be unilateral or bilateral. The tumor is characterized by having chocolate material in the cyst cavity with endometrial elements proven histologically. Every tumor of the ovary filled with chocolate material is not an endometrioma. As these tumors grow larger there is a tendency to perforate so that they adhere to the uterus, tube, broad ligament, uterosacral ligaments and the rectosigmoid. In freeing these adherent tumors there is always a spill oJ"'hick chocolate colored fluid. There may be no symptoms but when present there is a characteristic dysmenorrhea with pain beginning some days before the onset of menses, lasting throughout and several days beyond the end of the period. Sterility frequently is a complaint of these patients. Treatment. These tumors occur frequently in the young so whenever possible the normal ovary should be retained. If the pathologic changes have destroyed both ovaries and there is much involvement of bowel and adjacent structures ablation of all pelvic organs may be necessary. Conservation in many instances has permitted the patient to have a family even though a second operation may be necessary in ·the future. Presacral neurectomy is useful in these cases when the uterus is not removed in the presence of severe dysmenorrhea. Dysgerminoma This appellation was given by Robert Meyer because these tumors arise from undifferentiated germ cells before the cells have male or female attributes. The identical tumor has been described in the testicle under the name of seminoma. These are unilateral but may be bilateral and are seen most frequently before the age of 30. They vary widely in size, grow quite rapidly and ha~e a high degree of malignancy. Their spread simulates the metastases of all ovarian malignancies.
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Grossly they have a smooth dense capsule and at times are nodular. The cut surface is grayish pink and has fibrillations simulating the sulci in the brain. Microscopically there is abundant cytoplasm with large nuclei arranged in alveolar form separated by fibrous tissue septa with marked lymphocytic infiltration. There are many mitotic figures and occasional giant cells with the nuclei at the periphery. These tumors are commonly seen in pseudohermaphrodites or in women with poor gonadal development. The removal of the tumor does not change the pseudohermaphrodite nor improve the subnormal gonadal development. There are cases on record of pregnancy following the removal of this neoplasm. In general, the treatment of these tumors is radical surgery plus x-ray when the lesion is limited to the pelvis. When extensive metastases have occurred in the liver, lymph glands, omentum and other vital structures it is questionable whether surgery is indicated. Exception to the above rule may be made when the dysgerminoma is limited to one ovary in a young woman with no evidence of the tumor breaking through its capsule. Brenner Tumor
These are relatively rare tumors named after the man who first described them accurately. They are seen most frequently during the menopause. They vary greatly in size, most of them are solid, some have cystic areas. Occasionally they are found in the wall of a pseudomucinous cyst. They are not uncommonly bilateral. There are no characteristic symptoms. They do not produce any hormone yet a few Brenner tumors have been associated with postmenopausal bleeding. There is no evidence that the tumor produced the hormone to initiate the bleeding from the endometrium. The tumor is benign. Occasionally one finds Meigs' syndrome associated with this neoplasm. Most characteristic is the histologic picture wherein are nests of epithelial cells surrounded by fibromatous connective tissue. The cells are large, polyhedral, quite uniform with small ovoid nuclei. There is a tendency to degeneration of the center of the cell nests. Also there is a tendency for the superficial layer of cells in the cystic cavities to assume a pseudomucinous appearance. For this reason some workers believe that these tumors may be the origin of the pseudomucinous tumors. Treatment. Removal of the tumor is all that is necessary in the young. During the menopause all the pelvic generative organs should be removed. 'PRACTICAL ASPECTS OF OVARIAN TUMORS
Whenever an ovarian neoplasm is present at repeated examinations several weeks apart it should be investigated even in the absence of
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symptoms. About 15 per cent of the proliferation tumors are malignant so it is necessary to study these tumors, grossly and microscopically. This can be accomplished only by surgical intervention, although other methods, such as x-ray, pneumoperitoneum and culdoscopy, may be helpful. When a benign tumor is diagnosed, normal ovarian tissue should be conserved. If possible all tumors of the ovary should be removed intact even if it necessitates the large incisions. When a malignant tumor is unilateral, both the adnexa and uterus should be removed. Eighty per cent of the ovarian tumors are cystic and are mostly benign; 20 per cent are solid tumors and are mostly malignant. The question as to removing the ovaries at a certain age when hysterectomy is done is still unsettled. Some gynecologists give an arbitrary age of 43 or 45, while others believe in leaving in one ovary if it is still functioning. It has been my experience that rarely does a patient return with an ovarian neoplasm at a future date following a hysterectomy. However, when there is any suspicion of serious pathology in the contralateral ovary, it should be removed disregarding the patient's age. In ovarian tumors discovered in early pregnancy indications for immediate operation are torsion of the pedicle, intracystic hemorrhage, signs of infection, signs of malignancy, overdistention of the abdomen and cysts adherent in the cul-de-sac. If there is no immediate haste for surgery one should wait until the fourth month. When the diagnosis of a tumor mass is first made just before the viability of the fetus, if delay is not harmful one should wait until the child is viable or preferably observe the patient until term so that cesarean section and removal of tumor can be accomplished at the same time. There is a fairly high incidence of carcinoma of the endometrium associated with granulosa and theca cell tumors especially when they occur during the menopause. The incidence is much higher than chance alone. The hormone produced by these tumors produces a hyperplasia of the endometrium and there is a direct relationship between hyperplasia and adenocarcinoma of the body of the uterus. For this reason radical surgery is indicated. Because malignant tumors of the ovary produce no symptoms until they have grown considerably, and many times the patient when first seen is beyond cure by any means at hand today, one asks whether there are really any effective prophylactic methods against ovarian carcinoma. A routine bilateral oophorectomy in women past 40 undergoing a pelvic laparotomy will certainly prevent carcinoma of the ovary. One must weigh the sudden menopause with its attendant symptoms against the natural menopause. In my experience sudden ablation of the gonads disturbs the patient less than the natural menopause. Also we have at
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hand today therapy which combats the untoward symptoms. If ablation of the ovaries is not to be done, a very careful inspection of these organs must be carried out whether the surgery is done by the abdominal or vaginal route. Finally in the surgical repair of procidentia where the uterus is conserved, an inspection of the ovaries should be made either through an anterior or posterior colpotomy incision. One of the big advantages in doing a hysterectomy as part of the procedure in the cure of procidentia is the opportunity to study the ovaries for neoplastic growth. Following operation for malignancy of the ovary and in the inoperable cases a course of x-ray therapy is indicated. Today most workers show a 15 per cent increased salvage rate in the five year period following treatment. Occasionally a case that seems hopeless improves sufficiently under radiation therapy to warrant the use of surgery. Colloidal isotope gold is used intraperitoneally when ascites is associated with malignancy of the ovary. In some patients the formation of the fluid is retarded so that there is less necessity for tapping the abdomen. The course of the disease is not altered. Male hormone therapy has been used in inoperable cancer of the ovary and uterus and although there is a feeling of well-being, the therapy does not alter the course of the disease. REFERENCES Novak, Emil: Gynecological and Obstetrical Pathology, Philadelphia, W. B. Saunders Company, 1947. Dockerty, M. B.: Ovarian Neoplasms. A Collected Review. Int. Abst. Surg. 81: 3,179-204. Barzilai, Y.: Atlas of Ovarian Tumors. New York, Grune & Stratton, 1943. Kanter, A. E. and Klawans, A. H.: Arrhenoblastoma of the Ovary. Am. J. Cancer 42 (4): 470-486 (Dec.) 1940. Kanter, A. E. and Ragins, A. B.: Arrhenoblastoma of Ovary. Am. J. Obst. & Gynec. 42: 1061-u5 (Dec.) 1941. Melnick, P. J. and Kanter, A. E.: Theca Cell Tumors of the Ovary. Am. J. Obst. & Gynec. 27: (1): 41-53, 1934. Walter, R. I., Bachman, A. L. and Harris', W.: Treatment of Carcinoma of the Ovary: Improvement of Results with Postoperative Radiotherapy. Am. J. Roentj1;enol. J.5: 403--411 (March) 1941.