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Ovarian neoplasms: Their pathologic and surgical significance
OVARIAN
NEOPLASMS: THEIR PATHOLOGIC SURGICAL SIGNIFICANCE* VIRGIL S. COUNSELLER, Division of Surgery, ROCHESTER,
0
AND
M.D.
The Mayo Clinic MINNESOTA
VARIAN neopIasms beIong to the group of most common Iesions encountered in the practice of medicine and surgery. Some are more important than others, yet not one, even if it is benign, can exist for very Iong without the Ioss of ovarian function and IinaIIy compIete destruction of the organ. The resuIts of treatment of both the benign and the maIignant types are often disappointing. In addition, the pathoIogic characteristics of these neopIasms, it seems to me, have not been suffrcientIy stressed. A cIear conception of the type of tissue being deaIt with is the fundamenta1 basis for the appIication of correct surgica1 principIes in treatment. The ovary is one of the most compIex organs in the human body in that it not onIy is an organ of reproduction but aIso produces hormones of interna secretion which profoundIy reguIate many physioIogic processes of the femaIe. Many of the functions of the ovary are known but I am certain that others are not known and are not even suspected. These probabIy wiI1 not be discovered unti1 more intense study is made in the physioIogic chemistry of the various ceIIs in the ovary. In this connection it is of interest that onIy recentIy a cIose reIation between caIcium metaboIism in muscIe and ovarian function was reported. That factors other than reproduction are reIated to the ovary is shown by the fact that cancer of the breast is rare among castrated women. Cancer of the body of the uterus has Iikewise not been encountered among patients whose ovaries have been removed before the onset of the natura1 menopause. This does not hoId true for patients who have been given radium or
Roentgen therapy sufhcient to produce a menopause, but in whom the ovary has not been removed or compIeteIy destroyed. At present, no one knows how much irradiation is required to produce the same effect as biIatera1 oophorectomy. These observations are cited mereIy to stimuIate interest in the complexity of the functions of the ovary and to emphasize that Iesions of the ovary, whether benign or maIignant, shouId receive more carefu1 consideration. SurgicaI treatment of ovarian Iesions shouId be undertaken with meticuIous care and onIy after due consideration. The indiscriminate remova of the ovary for simpIe cystic conditions or for so-caIIed ovarian pain whether proved or not, shouId be condemned. The consistency of ovarian tissue in different individuaIs has a great range of norma variation as to size, irreguIarities of the surface, thickness of the cortex and the number of retained foIIicuIar cysts. AIso, the appearance of the organ varies tremendousIy according to the phase of the menstrua1 cycIe. For exampIe, there may be a bIood cIot of moderate size adjacent or adherent to a corpus Iuteum; yet this may be entireIy normaI. OccasionaIIy both ovaries may be sIightIy eIongated and irreguIar as a resuIt of retained foIIicIes, and yet be norma for the particuIar patient, who has, very IikeIy, sought treatment for periodic attacks of pain in the right and Ieft Iower abdomina1 quadrants. In most instances of this type attacks are due to rupture of a retention cyst or 0ccasionaIIy to sIight oozing of bIood from the waI1 of the cyst. Not infrequentIy such patients are submitted to an appendectomy and if
* Read before the meeting of the AnnuaI Post-Collegiate AssembIy, Ohio State University, 4, 1939.
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this does not give evidence of acute disease, the ovary often is removed as the cause of the pain. For some uncertain reason the ovary may never function properIy, or if once it has functioned normally, its function may become arrested. Yet to all gross appearances it is normaI. Occasionally this derangement is secondary to fauIty function of some other organ cIoseIy related to the generative organs; for example, the thvroid grand. This condition during the third decade of life is a very rear probIem to the patient and to the physician. Young women in this group are subjected to many varied types of therapy; some respond we11 to proper management whereas some do not. Radium therapy has been prescribed with the idea of producing temporary abeyance of ovarian function, thereby controIIing uterine hemorrhage. This procedure brings about in a young woman a temporary artificia1 menopause which seems to me absoIuteIy contraindicated. If the bIeeding cannot be controIIed by any type of substitution therapy in an otherwise norma individua1, I am of the opinion that abdomina1 hysterectomy with preservation of the ovaries is justified and is the Iogical surgica1 treatment. It is true that the ovaries sometimes become cystic and require surgica1 removal, but not a11 of them wiI1 require it by any means. The percentage of surviva1 of the ovaries after h)-sterectomy is determined for the most part by the extent of the interference with their bIood suppIy. The ovarian branches of the uterine arteries usuaIIy are destroyed, but the main ovarian artery and vein are not disturbed. However, if these vesseIs in the ovarian pedicIe are Ieft under considerable tension the vessels wiI1 graduaIIy become thrombosed and the ovary as a resuIt wiI1 become cystic or atrophic. It is important to distinguish between menstrua1 disturbances that arise from abnorma1 function of the ovary and those attending ovarian neopIasms. The histoIogic picture of the endometrium in both instances mav be identica1 and in cases of
NeopIasms
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functional bleeding aIone there is no objective evidence of Iesions of the ovary. NeopIasms usuaIIy disturb norma ovarian function but not in every instance and not aIways to the same extent. To understand the ovarian disturbance in the endometrium it is necessary to be familiar with the physioIogic and pathologic variations in the endometrium. 2 Briefly it is sufhcient to say that the endometrium is the most active tissue in the human body and that there is no socaIIed resting stage. In norma conditions the endometrium compIeteIy changes itself every twenty-eight days. The first fourteen days are designated as the proliferative phase, changes being brought about through the action of the foIIicIe. The Iast fourteen days are designated the differentiative stage, controIIed by the corpus Iuteum. Whenever failure of formation of the corpus Iuteum supervenes or if there is an excessive foIIicuIar effect, the endometrium becomes cystic. This has not been suffkientIy stressed; it deserves attention since it denotes ovarian faiIure from some cause. A cystic endometrium in the past has been aIIuded to as hyperpIastic, although it is not hyperpIastic at aI1, but on the contrary, is evidence of degeneration. One other point of extreme importance in this connection is that activity of the endometrium may be arrested at any point in the menstrua1 cycle; therefore, it may be designated pathoIogicaIIy as the persistent proIiferative or persistent differentiative phase of the menstrua1 cycIe, resulting in periodic menstrua1 bIeeding or periodic amenorrhea. A correIation of these findings in the endometrium with those of benign ovarian neopIasms, such as cystadenoma and adenomyoma, is often advantageous in pIanning surgica1 treatment. The cystadenoma is an outstanding exampIe of a benign ovarian neopIasm. It arises in the substance of the ovary in contradistinction to the simpIe foIIicuIar cyst, and so when, as frequentIy happens, it reaches considerabIe size, the ovary usuaIIy is destroyed. Second, these neoDIasms mav be uniIatera1 but unfortu-
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nateIy a high percentage are biIatera1, if not at the time of operation then Iater in Iife. If the endometrium reveaIs beginning ovarian faiIure with menstrua1 irreguIarities associated with a benign cystadenoma of one ovary, there are most IikeIy smaI1 muItiIocuIated cysts within the substance of the remaining ovary and the prognosis for correction of the disturbances of menstruation by removal of the one cystadenoma is not good. On the other hand, if the endometrium does not show degenerathe prognosis should be tive changes exceIIent. A Iarge ovarian tumor that compIeteIy fiIIs the abdomen of a young woman is usuaIIy of this type. It is not maIignant, in contradistinction to the papiIIary cystadenoma which is maIignant. I wish to pIace considerabIe emphasis on the word “papiIIary” in this connection. i fee1 that it is pathoIogicaIIy sound to regard and to treat as maIignant any tumor which resuIts in the formation of papiIIary epitheIium. To do otherwise is to court disaster. PapiIIary epitheIium behaves in characteristic fashion regardIess of where it is situated. For exampIe, if it appears in the urinary bIadder it may or may not be quiescent but if it is disregarded, eventuaIIy it wiI1 kiI1 the patient. Endometriosis (adenomyoma) is another benign Iesion of the ovary important because of its frequency, its appearance in earIy aduIt Iife, its effect on steriIity, the physica disabiIity and the disturbance of ovarian function attending it. This Iesion is not confined to the ovary, but the activity of any associated adenomyomas is entireIy dependent on the ovary. Roentgen rays or radium therapy sufficient to bring about arrest of ovarian function wiI1 render a11 lesions inactive unIess the ovary partiaIIy regains its function after such treatment. The disturbance of ovarian function in this type of disease is a factor which is in need of very carefuI study. It has been my beIief for considerabIe time that endometriosis of itself does not affect, to any appreciabIe degree at Ieast, the function of the ovary, since most patients who have this condition have associated Iesions of the
Neoplasms
AUGUST,,940
uterus or ovary which couId suffIcientIy expIain the menstrua1 irreguIarities. In a recent series of 308 cases I discovered that in 65.6 per cent menorrhagia, metrorrhagia or both occurred; this was approximateIy the same as the number of associated pathoIogic Iesions of the uterus and ovary. However, the endometria1 lesion may be the chief factor of the menstrual disturbance or an incident in a sequence of events resuIting from ovarian faiIure. Some evidence which wouId tend to cIarify this point might be found in a study of the incidence and distribution of endometria1 Iesions in cases of so-caIIed functiona uterine bIeeding. With regard to the effect on ovarian function, I have recentIy been impressed with the high incidence of cystic changes in the endometrium, ranging from a miId to a severe degree, among patients who have been subjected to operation primariIy for endometriosis. Furthermore, the extent of cystic change seems to bear a definite reIation to the amount of endometria1 disease and hemorrhagic cysts of the ovary. There is considerable disagreement among students of this subject in regard to whether hemorrhagic cysts (chocolate cysts) of the ovary are the resuIt of endometria1 ovarian Iesions. CertainIy in many cases of Iarge hemorrhagic cysts there is no pathoIogic evidence of endometriosis in the ovary or waI1 of the cyst but endometria1 Iesions usuaIIy are identifiabIe on the posterior surface of the broad Iigament adjacent to the ovary, aIthough certainIy not in great amount. When endometriosis is the outstanding abnorma1 condition present, the hemorrhagic cysts are usuaIIy very smaI1 but often muItipIe. Some of the cysts contain bIood of recent origin and in some it is tarry as a resuIt of decomposition of Iong standing. We have observed aIso that when endometriosis is the predominant abnorma1 dysmenorrhea is the condition present, but when chocolate prnicipa1 symptom, cysts are predominant, menstrua1 disturbance is the chief symptom. Pain and menstrua1 disturbance together usuaIIy denote
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rather extensive involvement by both types of Iesions. The treatment of these Iesions seems to me to be primarily surgica1 unIess the rectovagina1 septum is involved extensiveIy by endometrioma, in which case radium therapy sufficient to arrest ovarian function wouId invoIve considerabIy Iess risk. However, if the peIvis is fiIIed with Iarge chocoIate cysts it is wiser to perform biIatera1 oijphorectomy and Ieave the Iesion in the rectovagina1 septum undisturbed. In the case of a young woman who suffers predominantIy from these Iesions, the best treatment is to excise the invoIved structures and preserve the menstrua1 or the reproductive function or both. Such procedures are indicated onIy for patients whose lesions are not extensive or are confined onIy to one adnexa1 region because the incidence of recurring symptoms in cases of more extensive invoIvement is quite high. Sterility, of course, is a prominent compIaint and is often the symptom which induces the patient to seek medica advice. There is associated with this disease an absoIute steriIity in about 32 per cent of cases, but to correct it surgicaIIy is not aIways possibIe. In 56.2 per cent of a group of patients who had been treated by conservative surgica1 measures pregnancy occurred, but 16.8 per cent of these pregnancies resuIted in miscarriages. Hope is eterna1 in some women with regard to reproduction and if they can Iive under the impression that they can reproduce they have much more peace of mind. If the evidence of ovarian faiIure is strong, as exempIified by menstrua1 irreguIarities and cystic endometrium, I fee1 that the patient wiI1 be better cared for by a subtota1 hysterectomy and by excision of the ovarian Iesions, without compIete abIation of ovarian function. It has been my observation that the activity of smaI1 Iesions which may remain in the peIvis is considerabry reduced if the patient does not menstruate, aIthough the ovarian tissue remains. RadicaI treatment is required for extensive Iesions of this tvDe which excessiveIv d ./I
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ot’Surgery
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invoIve the ovaries of patients who are in the Iatter part of the fourth decade of Iife. AIso, considerabIe subacute peIvic distress due either to dacterial invasion or to the chemica1 action of blood pigment is more safeIy eIiminated in this manner. The significance of maIignant Iesions of the ovary is such that the question of preservation of ovarian function must be disregarded except in some uniIatera1 carcinomatous cysts of a low grade of maIignancy. It is unusua1 to find a maIignant cyst in a woman under 35, but it does occur sufficiently often to keep one constantIy Iooking for it. The maIignant cysts which occur in the ovary are carcinomatous cystadenomas, papiIIary, nonpapiIIary or mixed. From the standpoint of pathology these cysts shouId not be such a serious matter, because the majority grow very sIowIy and often remain confined to the ovary for months. UnfortunateIy a great number deveIop after the menopause and the onIy associated symptom is enIargement of the abdomen. If they occur during the menopausa1 period, the menstrua1 irreguIarity is regarded too frequentIy as a norma process. Later when the cysts reach huge proportions the cyst waI1 becomes thinned, especiaIIy at the sites of greatest pressure, and finaIIy becomes perforated. The maIignant process then rapidIy spreads and the condition approaches the inoperabIe stage. CompIete surgica1 remova of a11 peIvic organs is the procedure of choice for patients 40 years of age or oIder, even if the cyst is uniIatera1. However, 50 per cent are biIatera1 at the time of operation. If the cyst has become perforated and there are secondary impIants these may be heId in check by Roentgen therapy. True carcinomas of the ovary are of two types, the papiIIary adenocarcinoma and the soIid adenocarcinoma. In this group of cases symptoms frequently are absent during the earIy or favorabIe operative period. Some of these growths can be discovered, however, by routine peIvic examinations, and often the patient is amazed to Iearn that there is something wrong with
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her peIvic organs. PapiIIary adenocarcinomas originate as a ruIe from the surface of the ovary and, unfortunateIy, are of a high grade of maIignancy. Since they extend from the surface of the ovary, they become attached earIy to adjacent structures and shortIy assume such proportions that they become inoperabIe. FIuid in the abdomen is the ruIe and extension to other structures occurs in a few months. It is known that the prognosis is generaIIy poor for cancers of this type, aIthough many of the secondary growths become quiescent, as is the case in maIignant cysts, if the parent growth is removed and the procedure is foIIowed by the use of radium and Roentgen therapy. In my experience, the Iongest duration of Iife in such a case after this method of treatment was twenty years. It is important to note aIso that there is a high incidence of biIatera1 invoIvement, so that it is advisabIe to remove a11 the peIvic generative organs even if the growth is confined to onIy one ovary. SoIid carcinomas of the ovary represent a much smaIIer group than papiIIary adenocarcinomas, and they aIso vary in their rate of growth. Their presence is usuaIIy not suspected, and consequentIy there is a high incidence of peIvic attachment and extension to distant Iymph nodes. FIuid in the abdomen is a frequent finding, and an undesirabIe one in reIation to prognosis. The seriousness of this group of cancers was reveaIed in a recent study which showed that of the patients who had soIid carcinoma, grade 3 or 4, more than 75 per cent succumbed within a few months due to recurrences. The method of treating ovarian cancer is earIy surgica1 remova foIIowed by radium and Roentgen therapy. In some cases of carcinoma, grade I, confined to the ovary, irradiation is omitted. In many cases the Iesions are definiteIy not amenabIe to surgica1 treatment but are treated, if the patient’s condition wiI1 permit, by intensive radium and Roentgen therapy. Some time ago, I2 investigated a recent series of 143 patients at the ciinic. These patients had cancer of the ovary and were
NeopIasms
AUGUST, 19zw
treated with surgica1 procedures aIone; 65.4 per cent of them were Iiving five or more years after treatment. One hundred and eighteen patients received intensive irradiation in addition to surgica1 treatment and of this number 50.5 per cent were Iiving five or more years Iater. Thirty-six patients had extensive Iesions and were suitabIe for irradiation only; 16.7 per cent of them Iived five years or more after such treatment. UNUSUAL
NEOPLASMS
Another smaI1 group of infrequent ovarian neopIasms must be considered in this connection. The first of these is the arrhenoblastoma, or mascuIinizing tumor of the ovary. The cIinica1 syndrome which foIIows the onset of this tumor is a change toward a maIe type of habitus and a deveIopment of the secondary sexua1 characteristics of the maIe. The main physica features of the Cushing syndrome are absent. These growths are recognized easiIy both from the surgica1 and pathoIogic standpoints. If a patient who has previousIy had normal menstruation, experiences the sIow deveIopment of amenorrhea pIus the distribution of hair simiIar to that of maIes, enIargement of the cIitoris and changes of the voice to the mascuIine type, the possibiIity that an arrhenobIastoma is present is indicated. PathoIogicaIIy the tumor cIoseIy resembIes the seminiferous tubuIes of the testis. For this reason it was first caIIed “adenoma tubuIare testicuIare.” It is of interest that this tumor varies in its differentiation from norma testicuIar tissue to a type that is hardIy recognized as such. These ceIIs secrete a hormone which inff uences secondary sexua1 characteristics in a mascuIine direction. Furthermore, the tumors that have the Ieast resembIance pathoIogicaIIy to testis show the greatest mascuIinizing effect. It foIIows, therefore, that when these tumors are highIy differentiated the mascuIine effect is greatIy reduced and often unnoticed cIinicaIIy. This neopIasm frequentIy is cIassed as maIignant but very rarely has metastasis been noted. If present, metastatic lesions
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CounseIIer-Ovarian
can be destroyed or rendered inactive by Roentgen therapy as the celIs are very sensitive to Roentgen rays. The Iesion is always uniIatera1 and, since it extends but rarely beyond its initia1 site of origin, cure can be obtained by IocaI excision. This is of especia1 importance because these tumors are seen during the menstrual Iife of the patient. Another very interesting tumor is the granuIosa cel1 tumor or feminizing tumor. This hardIy can be said to be a rare tumor as about 400 have been reported. Sixty per cent of these tumors occur after the menopause and 30 per cent between puberty and the menopause; 5 to IO per cent occur before the age of adolescence. The inff uence of these tumors differs for the three age groups just mentioned. For exampIe, among young individuaIs the tumor produces precocious menstruation with earIy sexual and somatic deveIopment. In middle Iife the tumor produces either amenorrhea of itseIf or amenorrhea foIIowed by profuse and continuous menses. However, after the menopause, this neopIasm gives rise to a periodic pseudomenstrua1 type of bIeeding in 90 per cent of cases. The syndromes produced at the various ages are expIained by the effects of the large quantity of estrin eIaborated by these tumors. This hormone can be identified in both the bIood and urine of patients who have granuIosa-cel1 neopIasm and in aImost unbeIievabIe amounts in extracts of the tumor tissue. Its effect on the uterus is exactIy what one wouId expect from excessive activity of estrin-hyperpIasia of the myometrium and a thick, boggy, proliferative type of endometrium, usuaIly containing cysts. Why the effect of estrin among young peopIe is different from its effect on patients of more advanced ages is not clearly understood. PathoIogicalIy, 90 per cent of these tumors are said to be malignant but of a very low grade; therefore they rareIy extend beyond the IocaI initial site of origin. About 90 per cent of the Iesions are uniIateraI and they are usuaIIy cIassified as
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solid tumors. Different ceI1 types are recognized but are not of particuIar interest. Since these tumors are usuaIIy uniIatera1 and are of a low grade of maIignancy, conservative surgica1 measures can be safeIy and IogicaIly followed. After the menopause, however, panhysterectomy is usuaIIy in order. The next two tumors of special interest are the dysgerminoma and Brenner’s tumor, neither of which produces a hormone. The dysgerminoma is a very interesting Iesion because, aIthough pathologically maIignant, clinicaIIy it runs a very benign course. This tumor is said to correspond to the seminoma of the testis with the exception that the Iatter behaves as its degree of malignancy wouId indicate. The tumor usuaIIy occurs in girls and young women who are Iess than 20 years of age. It is frequentIy biIatera1 and is associated with hypoplasia of the genita1 organs. It is said that this is the most common lesion observed in pseudohermaphrodites and in individuaIs who have poorIy developed gonads. It may be best cIassified as occupying a “neutra1” position between the masculinizing arrhenobIastoma and the granuIosa ceI1 feminizing tumor. AIthough this lesion appears to be of a high grade of malignancy, cure is obtained by remova of the affected adnexa. When both ovaries are invoIved (35 per cent) compIete hysterectomy with remova of both adnexa is indicated. Brenner’s tumor is a soIid, non-hormoneproducing tumor of the ovary aIthough it may be found in association with ovarian cysts. It is characterized by sIow growth and is similar to ovarian fibromas in Iacking specific symptomatoIogy. It resembles somewhat a granuIosa ceI1 tumor and microscopicaIIy it resembres a metastatic epitheIioma. SurgicaI remova effects compIete cure, REFERENCES I. COUNSELLER, V. S. The surgical treatment of cancer of the generative organs of women. Texas State J. Med., 33: 560, 1937. 2. COUNSELLER, V. S., and HERRELL, IV. E. Some changing concepts regarding the endometrium and their significance. J. Indiana M. A., 29: 57, 1936.
NEOPLASMS: THEIR PATHOLOGIC SURGICAL SIGNIFICANCE* VIRGIL S. COUNSELLER, Division of Surgery, ROCHESTER,
0
AND
M.D.
The Mayo Clinic MINNESOTA
VARIAN neopIasms beIong to the group of most common Iesions encountered in the practice of medicine and surgery. Some are more important than others, yet not one, even if it is benign, can exist for very Iong without the Ioss of ovarian function and IinaIIy compIete destruction of the organ. The resuIts of treatment of both the benign and the maIignant types are often disappointing. In addition, the pathoIogic characteristics of these neopIasms, it seems to me, have not been suffrcientIy stressed. A cIear conception of the type of tissue being deaIt with is the fundamenta1 basis for the appIication of correct surgica1 principIes in treatment. The ovary is one of the most compIex organs in the human body in that it not onIy is an organ of reproduction but aIso produces hormones of interna secretion which profoundIy reguIate many physioIogic processes of the femaIe. Many of the functions of the ovary are known but I am certain that others are not known and are not even suspected. These probabIy wiI1 not be discovered unti1 more intense study is made in the physioIogic chemistry of the various ceIIs in the ovary. In this connection it is of interest that onIy recentIy a cIose reIation between caIcium metaboIism in muscIe and ovarian function was reported. That factors other than reproduction are reIated to the ovary is shown by the fact that cancer of the breast is rare among castrated women. Cancer of the body of the uterus has Iikewise not been encountered among patients whose ovaries have been removed before the onset of the natura1 menopause. This does not hoId true for patients who have been given radium or
Roentgen therapy sufhcient to produce a menopause, but in whom the ovary has not been removed or compIeteIy destroyed. At present, no one knows how much irradiation is required to produce the same effect as biIatera1 oophorectomy. These observations are cited mereIy to stimuIate interest in the complexity of the functions of the ovary and to emphasize that Iesions of the ovary, whether benign or maIignant, shouId receive more carefu1 consideration. SurgicaI treatment of ovarian Iesions shouId be undertaken with meticuIous care and onIy after due consideration. The indiscriminate remova of the ovary for simpIe cystic conditions or for so-caIIed ovarian pain whether proved or not, shouId be condemned. The consistency of ovarian tissue in different individuaIs has a great range of norma variation as to size, irreguIarities of the surface, thickness of the cortex and the number of retained foIIicuIar cysts. AIso, the appearance of the organ varies tremendousIy according to the phase of the menstrua1 cycIe. For exampIe, there may be a bIood cIot of moderate size adjacent or adherent to a corpus Iuteum; yet this may be entireIy normaI. OccasionaIIy both ovaries may be sIightIy eIongated and irreguIar as a resuIt of retained foIIicIes, and yet be norma for the particuIar patient, who has, very IikeIy, sought treatment for periodic attacks of pain in the right and Ieft Iower abdomina1 quadrants. In most instances of this type attacks are due to rupture of a retention cyst or 0ccasionaIIy to sIight oozing of bIood from the waI1 of the cyst. Not infrequentIy such patients are submitted to an appendectomy and if
* Read before the meeting of the AnnuaI Post-Collegiate AssembIy, Ohio State University, 4, 1939.
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this does not give evidence of acute disease, the ovary often is removed as the cause of the pain. For some uncertain reason the ovary may never function properIy, or if once it has functioned normally, its function may become arrested. Yet to all gross appearances it is normaI. Occasionally this derangement is secondary to fauIty function of some other organ cIoseIy related to the generative organs; for example, the thvroid grand. This condition during the third decade of life is a very rear probIem to the patient and to the physician. Young women in this group are subjected to many varied types of therapy; some respond we11 to proper management whereas some do not. Radium therapy has been prescribed with the idea of producing temporary abeyance of ovarian function, thereby controIIing uterine hemorrhage. This procedure brings about in a young woman a temporary artificia1 menopause which seems to me absoIuteIy contraindicated. If the bIeeding cannot be controIIed by any type of substitution therapy in an otherwise norma individua1, I am of the opinion that abdomina1 hysterectomy with preservation of the ovaries is justified and is the Iogical surgica1 treatment. It is true that the ovaries sometimes become cystic and require surgica1 removal, but not a11 of them wiI1 require it by any means. The percentage of surviva1 of the ovaries after h)-sterectomy is determined for the most part by the extent of the interference with their bIood suppIy. The ovarian branches of the uterine arteries usuaIIy are destroyed, but the main ovarian artery and vein are not disturbed. However, if these vesseIs in the ovarian pedicIe are Ieft under considerable tension the vessels wiI1 graduaIIy become thrombosed and the ovary as a resuIt wiI1 become cystic or atrophic. It is important to distinguish between menstrua1 disturbances that arise from abnorma1 function of the ovary and those attending ovarian neopIasms. The histoIogic picture of the endometrium in both instances mav be identica1 and in cases of
NeopIasms
American
Journal
of Surgerv
285
functional bleeding aIone there is no objective evidence of Iesions of the ovary. NeopIasms usuaIIy disturb norma ovarian function but not in every instance and not aIways to the same extent. To understand the ovarian disturbance in the endometrium it is necessary to be familiar with the physioIogic and pathologic variations in the endometrium. 2 Briefly it is sufhcient to say that the endometrium is the most active tissue in the human body and that there is no socaIIed resting stage. In norma conditions the endometrium compIeteIy changes itself every twenty-eight days. The first fourteen days are designated as the proliferative phase, changes being brought about through the action of the foIIicIe. The Iast fourteen days are designated the differentiative stage, controIIed by the corpus Iuteum. Whenever failure of formation of the corpus Iuteum supervenes or if there is an excessive foIIicuIar effect, the endometrium becomes cystic. This has not been suffkientIy stressed; it deserves attention since it denotes ovarian faiIure from some cause. A cystic endometrium in the past has been aIIuded to as hyperpIastic, although it is not hyperpIastic at aI1, but on the contrary, is evidence of degeneration. One other point of extreme importance in this connection is that activity of the endometrium may be arrested at any point in the menstrua1 cycle; therefore, it may be designated pathoIogicaIIy as the persistent proIiferative or persistent differentiative phase of the menstrua1 cycIe, resulting in periodic menstrua1 bIeeding or periodic amenorrhea. A correIation of these findings in the endometrium with those of benign ovarian neopIasms, such as cystadenoma and adenomyoma, is often advantageous in pIanning surgica1 treatment. The cystadenoma is an outstanding exampIe of a benign ovarian neopIasm. It arises in the substance of the ovary in contradistinction to the simpIe foIIicuIar cyst, and so when, as frequentIy happens, it reaches considerabIe size, the ovary usuaIIy is destroyed. Second, these neoDIasms mav be uniIatera1 but unfortu-
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nateIy a high percentage are biIatera1, if not at the time of operation then Iater in Iife. If the endometrium reveaIs beginning ovarian faiIure with menstrua1 irreguIarities associated with a benign cystadenoma of one ovary, there are most IikeIy smaI1 muItiIocuIated cysts within the substance of the remaining ovary and the prognosis for correction of the disturbances of menstruation by removal of the one cystadenoma is not good. On the other hand, if the endometrium does not show degenerathe prognosis should be tive changes exceIIent. A Iarge ovarian tumor that compIeteIy fiIIs the abdomen of a young woman is usuaIIy of this type. It is not maIignant, in contradistinction to the papiIIary cystadenoma which is maIignant. I wish to pIace considerabIe emphasis on the word “papiIIary” in this connection. i fee1 that it is pathoIogicaIIy sound to regard and to treat as maIignant any tumor which resuIts in the formation of papiIIary epitheIium. To do otherwise is to court disaster. PapiIIary epitheIium behaves in characteristic fashion regardIess of where it is situated. For exampIe, if it appears in the urinary bIadder it may or may not be quiescent but if it is disregarded, eventuaIIy it wiI1 kiI1 the patient. Endometriosis (adenomyoma) is another benign Iesion of the ovary important because of its frequency, its appearance in earIy aduIt Iife, its effect on steriIity, the physica disabiIity and the disturbance of ovarian function attending it. This Iesion is not confined to the ovary, but the activity of any associated adenomyomas is entireIy dependent on the ovary. Roentgen rays or radium therapy sufficient to bring about arrest of ovarian function wiI1 render a11 lesions inactive unIess the ovary partiaIIy regains its function after such treatment. The disturbance of ovarian function in this type of disease is a factor which is in need of very carefuI study. It has been my beIief for considerabIe time that endometriosis of itself does not affect, to any appreciabIe degree at Ieast, the function of the ovary, since most patients who have this condition have associated Iesions of the
Neoplasms
AUGUST,,940
uterus or ovary which couId suffIcientIy expIain the menstrua1 irreguIarities. In a recent series of 308 cases I discovered that in 65.6 per cent menorrhagia, metrorrhagia or both occurred; this was approximateIy the same as the number of associated pathoIogic Iesions of the uterus and ovary. However, the endometria1 lesion may be the chief factor of the menstrual disturbance or an incident in a sequence of events resuIting from ovarian faiIure. Some evidence which wouId tend to cIarify this point might be found in a study of the incidence and distribution of endometria1 Iesions in cases of so-caIIed functiona uterine bIeeding. With regard to the effect on ovarian function, I have recentIy been impressed with the high incidence of cystic changes in the endometrium, ranging from a miId to a severe degree, among patients who have been subjected to operation primariIy for endometriosis. Furthermore, the extent of cystic change seems to bear a definite reIation to the amount of endometria1 disease and hemorrhagic cysts of the ovary. There is considerable disagreement among students of this subject in regard to whether hemorrhagic cysts (chocolate cysts) of the ovary are the resuIt of endometria1 ovarian Iesions. CertainIy in many cases of Iarge hemorrhagic cysts there is no pathoIogic evidence of endometriosis in the ovary or waI1 of the cyst but endometria1 Iesions usuaIIy are identifiabIe on the posterior surface of the broad Iigament adjacent to the ovary, aIthough certainIy not in great amount. When endometriosis is the outstanding abnorma1 condition present, the hemorrhagic cysts are usuaIIy very smaI1 but often muItipIe. Some of the cysts contain bIood of recent origin and in some it is tarry as a resuIt of decomposition of Iong standing. We have observed aIso that when endometriosis is the predominant abnorma1 dysmenorrhea is the condition present, but when chocolate prnicipa1 symptom, cysts are predominant, menstrua1 disturbance is the chief symptom. Pain and menstrua1 disturbance together usuaIIy denote
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rather extensive involvement by both types of Iesions. The treatment of these Iesions seems to me to be primarily surgica1 unIess the rectovagina1 septum is involved extensiveIy by endometrioma, in which case radium therapy sufficient to arrest ovarian function wouId invoIve considerabIy Iess risk. However, if the peIvis is fiIIed with Iarge chocoIate cysts it is wiser to perform biIatera1 oijphorectomy and Ieave the Iesion in the rectovagina1 septum undisturbed. In the case of a young woman who suffers predominantIy from these Iesions, the best treatment is to excise the invoIved structures and preserve the menstrua1 or the reproductive function or both. Such procedures are indicated onIy for patients whose lesions are not extensive or are confined onIy to one adnexa1 region because the incidence of recurring symptoms in cases of more extensive invoIvement is quite high. Sterility, of course, is a prominent compIaint and is often the symptom which induces the patient to seek medica advice. There is associated with this disease an absoIute steriIity in about 32 per cent of cases, but to correct it surgicaIIy is not aIways possibIe. In 56.2 per cent of a group of patients who had been treated by conservative surgica1 measures pregnancy occurred, but 16.8 per cent of these pregnancies resuIted in miscarriages. Hope is eterna1 in some women with regard to reproduction and if they can Iive under the impression that they can reproduce they have much more peace of mind. If the evidence of ovarian faiIure is strong, as exempIified by menstrua1 irreguIarities and cystic endometrium, I fee1 that the patient wiI1 be better cared for by a subtota1 hysterectomy and by excision of the ovarian Iesions, without compIete abIation of ovarian function. It has been my observation that the activity of smaI1 Iesions which may remain in the peIvis is considerabry reduced if the patient does not menstruate, aIthough the ovarian tissue remains. RadicaI treatment is required for extensive Iesions of this tvDe which excessiveIv d ./I
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American
Journal
ot’Surgery
287
invoIve the ovaries of patients who are in the Iatter part of the fourth decade of Iife. AIso, considerabIe subacute peIvic distress due either to dacterial invasion or to the chemica1 action of blood pigment is more safeIy eIiminated in this manner. The significance of maIignant Iesions of the ovary is such that the question of preservation of ovarian function must be disregarded except in some uniIatera1 carcinomatous cysts of a low grade of maIignancy. It is unusua1 to find a maIignant cyst in a woman under 35, but it does occur sufficiently often to keep one constantIy Iooking for it. The maIignant cysts which occur in the ovary are carcinomatous cystadenomas, papiIIary, nonpapiIIary or mixed. From the standpoint of pathology these cysts shouId not be such a serious matter, because the majority grow very sIowIy and often remain confined to the ovary for months. UnfortunateIy a great number deveIop after the menopause and the onIy associated symptom is enIargement of the abdomen. If they occur during the menopausa1 period, the menstrua1 irreguIarity is regarded too frequentIy as a norma process. Later when the cysts reach huge proportions the cyst waI1 becomes thinned, especiaIIy at the sites of greatest pressure, and finaIIy becomes perforated. The maIignant process then rapidIy spreads and the condition approaches the inoperabIe stage. CompIete surgica1 remova of a11 peIvic organs is the procedure of choice for patients 40 years of age or oIder, even if the cyst is uniIatera1. However, 50 per cent are biIatera1 at the time of operation. If the cyst has become perforated and there are secondary impIants these may be heId in check by Roentgen therapy. True carcinomas of the ovary are of two types, the papiIIary adenocarcinoma and the soIid adenocarcinoma. In this group of cases symptoms frequently are absent during the earIy or favorabIe operative period. Some of these growths can be discovered, however, by routine peIvic examinations, and often the patient is amazed to Iearn that there is something wrong with
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her peIvic organs. PapiIIary adenocarcinomas originate as a ruIe from the surface of the ovary and, unfortunateIy, are of a high grade of maIignancy. Since they extend from the surface of the ovary, they become attached earIy to adjacent structures and shortIy assume such proportions that they become inoperabIe. FIuid in the abdomen is the ruIe and extension to other structures occurs in a few months. It is known that the prognosis is generaIIy poor for cancers of this type, aIthough many of the secondary growths become quiescent, as is the case in maIignant cysts, if the parent growth is removed and the procedure is foIIowed by the use of radium and Roentgen therapy. In my experience, the Iongest duration of Iife in such a case after this method of treatment was twenty years. It is important to note aIso that there is a high incidence of biIatera1 invoIvement, so that it is advisabIe to remove a11 the peIvic generative organs even if the growth is confined to onIy one ovary. SoIid carcinomas of the ovary represent a much smaIIer group than papiIIary adenocarcinomas, and they aIso vary in their rate of growth. Their presence is usuaIIy not suspected, and consequentIy there is a high incidence of peIvic attachment and extension to distant Iymph nodes. FIuid in the abdomen is a frequent finding, and an undesirabIe one in reIation to prognosis. The seriousness of this group of cancers was reveaIed in a recent study which showed that of the patients who had soIid carcinoma, grade 3 or 4, more than 75 per cent succumbed within a few months due to recurrences. The method of treating ovarian cancer is earIy surgica1 remova foIIowed by radium and Roentgen therapy. In some cases of carcinoma, grade I, confined to the ovary, irradiation is omitted. In many cases the Iesions are definiteIy not amenabIe to surgica1 treatment but are treated, if the patient’s condition wiI1 permit, by intensive radium and Roentgen therapy. Some time ago, I2 investigated a recent series of 143 patients at the ciinic. These patients had cancer of the ovary and were
NeopIasms
AUGUST, 19zw
treated with surgica1 procedures aIone; 65.4 per cent of them were Iiving five or more years after treatment. One hundred and eighteen patients received intensive irradiation in addition to surgica1 treatment and of this number 50.5 per cent were Iiving five or more years Iater. Thirty-six patients had extensive Iesions and were suitabIe for irradiation only; 16.7 per cent of them Iived five years or more after such treatment. UNUSUAL
NEOPLASMS
Another smaI1 group of infrequent ovarian neopIasms must be considered in this connection. The first of these is the arrhenoblastoma, or mascuIinizing tumor of the ovary. The cIinica1 syndrome which foIIows the onset of this tumor is a change toward a maIe type of habitus and a deveIopment of the secondary sexua1 characteristics of the maIe. The main physica features of the Cushing syndrome are absent. These growths are recognized easiIy both from the surgica1 and pathoIogic standpoints. If a patient who has previousIy had normal menstruation, experiences the sIow deveIopment of amenorrhea pIus the distribution of hair simiIar to that of maIes, enIargement of the cIitoris and changes of the voice to the mascuIine type, the possibiIity that an arrhenobIastoma is present is indicated. PathoIogicaIIy the tumor cIoseIy resembIes the seminiferous tubuIes of the testis. For this reason it was first caIIed “adenoma tubuIare testicuIare.” It is of interest that this tumor varies in its differentiation from norma testicuIar tissue to a type that is hardIy recognized as such. These ceIIs secrete a hormone which inff uences secondary sexua1 characteristics in a mascuIine direction. Furthermore, the tumors that have the Ieast resembIance pathoIogicaIIy to testis show the greatest mascuIinizing effect. It foIIows, therefore, that when these tumors are highIy differentiated the mascuIine effect is greatIy reduced and often unnoticed cIinicaIIy. This neopIasm frequentIy is cIassed as maIignant but very rarely has metastasis been noted. If present, metastatic lesions
Nr
CounseIIer-Ovarian
can be destroyed or rendered inactive by Roentgen therapy as the celIs are very sensitive to Roentgen rays. The Iesion is always uniIatera1 and, since it extends but rarely beyond its initia1 site of origin, cure can be obtained by IocaI excision. This is of especia1 importance because these tumors are seen during the menstrual Iife of the patient. Another very interesting tumor is the granuIosa cel1 tumor or feminizing tumor. This hardIy can be said to be a rare tumor as about 400 have been reported. Sixty per cent of these tumors occur after the menopause and 30 per cent between puberty and the menopause; 5 to IO per cent occur before the age of adolescence. The inff uence of these tumors differs for the three age groups just mentioned. For exampIe, among young individuaIs the tumor produces precocious menstruation with earIy sexual and somatic deveIopment. In middle Iife the tumor produces either amenorrhea of itseIf or amenorrhea foIIowed by profuse and continuous menses. However, after the menopause, this neopIasm gives rise to a periodic pseudomenstrua1 type of bIeeding in 90 per cent of cases. The syndromes produced at the various ages are expIained by the effects of the large quantity of estrin eIaborated by these tumors. This hormone can be identified in both the bIood and urine of patients who have granuIosa-cel1 neopIasm and in aImost unbeIievabIe amounts in extracts of the tumor tissue. Its effect on the uterus is exactIy what one wouId expect from excessive activity of estrin-hyperpIasia of the myometrium and a thick, boggy, proliferative type of endometrium, usuaIly containing cysts. Why the effect of estrin among young peopIe is different from its effect on patients of more advanced ages is not clearly understood. PathoIogicalIy, 90 per cent of these tumors are said to be malignant but of a very low grade; therefore they rareIy extend beyond the IocaI initial site of origin. About 90 per cent of the Iesions are uniIateraI and they are usuaIIy cIassified as
NeopIasms
American
Journal
of Surgery
289
solid tumors. Different ceI1 types are recognized but are not of particuIar interest. Since these tumors are usuaIIy uniIatera1 and are of a low grade of maIignancy, conservative surgica1 measures can be safeIy and IogicaIly followed. After the menopause, however, panhysterectomy is usuaIIy in order. The next two tumors of special interest are the dysgerminoma and Brenner’s tumor, neither of which produces a hormone. The dysgerminoma is a very interesting Iesion because, aIthough pathologically maIignant, clinicaIIy it runs a very benign course. This tumor is said to correspond to the seminoma of the testis with the exception that the Iatter behaves as its degree of malignancy wouId indicate. The tumor usuaIIy occurs in girls and young women who are Iess than 20 years of age. It is frequentIy biIatera1 and is associated with hypoplasia of the genita1 organs. It is said that this is the most common lesion observed in pseudohermaphrodites and in individuaIs who have poorIy developed gonads. It may be best cIassified as occupying a “neutra1” position between the masculinizing arrhenobIastoma and the granuIosa ceI1 feminizing tumor. AIthough this lesion appears to be of a high grade of malignancy, cure is obtained by remova of the affected adnexa. When both ovaries are invoIved (35 per cent) compIete hysterectomy with remova of both adnexa is indicated. Brenner’s tumor is a soIid, non-hormoneproducing tumor of the ovary aIthough it may be found in association with ovarian cysts. It is characterized by sIow growth and is similar to ovarian fibromas in Iacking specific symptomatoIogy. It resembles somewhat a granuIosa ceI1 tumor and microscopicaIIy it resembres a metastatic epitheIioma. SurgicaI remova effects compIete cure, REFERENCES I. COUNSELLER, V. S. The surgical treatment of cancer of the generative organs of women. Texas State J. Med., 33: 560, 1937. 2. COUNSELLER, V. S., and HERRELL, IV. E. Some changing concepts regarding the endometrium and their significance. J. Indiana M. A., 29: 57, 1936.