ENDOMETRIAL CHANGES IN UTERINE MYOMA

by B. D. BARUAH*' M.B.B.S., Ph.D. and D. BARKAKATI* *' M.B.B.S.

Uterine myoma, variously called explain this have yielded a diversity fibromyoma, myofibroma, or collo­ of opinions. Several factors have been quially "fibroid", is the most common put forward to explain this haemor­ - benign tumour of smooth muscle rhage. They are: (1) Increased size origin in women. These tumours are of the uterine cavity leading to in­ responsible for at least one-third of creased bleeding surface, particularly all gynaecological admissions to hos­ in the submucous type. pitals and are found in the general (2) Mechanical obstacle caused population in about 1 in 10 women in by the tumour to muscular contrac­ r active reproductive life. tion of the uterus, which is an im­ I Although often asymptomatic, they portant factor in arresting menstrual are commonly associated with ab­ bleeding under normal conditions. normal and excessive uterine bleed­ ( 3) The change in the vascular ' .,. I ing, which does not conform to pattern of the endometrium. The a constant pattern, but varies bet­ coiled arteries of the mucosa overly­ ween hypermenorrhoea and poly­ ing the tumour are changed into menorrhoea. The amount of blood small sclerotic arteries with stasis of loss varies enormously. Bleeding is blood. Thus the atrophied mucosa dependent upon the situation rather tends to bleed longer than the normal than the size of the growth. Tumours endometrium because of the arterial of large size may exist without it, defect and venous congestion. while excessive or even dangerous ( 4) Formation of myomatous polyp ..I haemorrhage may be produced by undergoing degeneration, infection others quite small in size. It is more or malignant change. common in submucous growths. In­ ( 5) Erosion of the endometrium terstitial tumours occupy an inter­ over the submucous myoma with mediate position as regards their ten­ subsequent ulceration and haemor­ dency to produce haemorrhage. rhage. Of theoretical and practical im­ (6) Dysfunctional bleeding asso­ portance is the consideration of the ciated with hyperplasia of the endo­ mechanism of bleeding. Attempts to metrium. Thus, according to some, the bleed­ *Professor of Pathology. ing is purely mechanical, but re­ **Department of Pathology, Assam cently a large number of workers Medical College, Dibrugarh, Assam. are attempting to establish a direct

• 0 ENDOMETRIAL CHANGES IN UTERINE MYOMA 247

relationship between uterine bleeding plasia with myoma. Wattenwyl et al. and hyperoestrinism, based on his­ ( 1946) studied· endometrial res­ topathologic study of the endomet­ ponse in myomatous uteri from spe­ rium and hormonal assay. cimens removed both surgically and Although the literature is full of by curettage and concluded that al­ data concerning the gross and micro­ most two-thirds showed evidence of scopic analysis of uterine myomas as overproduction of oestrogens in the well as some experimental work re­ first half of the cycle and decreased garding their aetiology, very little progesterone production in the second has appeared in the English litera-­ half. Mayer (1948) examined 44 ture in regard to the correlation of cases of myomas requiring hysterec­ endometrial changes in the presence tomy and the endometrium showed: of myomas as well as other uterine (a) Glandular cystic hyperplasia or adnexal pathology, which might in 20 cases ( 45}'; ) . be the causative factors for endo­ (b) Simple cystic hyperplasia in metrial abnormalities. 19 cases ( 44 % ). The reported occurrence of differ­ (c) Mucosa of atrophic type in -1 ent endometrial changes in ut er in '~ case (9% ). myoma varies widely. Wyder (1878) (d) Complicating uterine adeno­ was the first to describe the endome-­ carcinoma in 1 case. trial change in uterine myoma. In a Jorgensen and Oram (1949) re­ subsequent paper (1887) he dealt ported a frequency of 55 cases of with the atrophic endometrium. Von endometrial hyperplasia in 100 Campe, in 1884, found inucosal uterine myomas. Zachariae (1954) hypertrophy in 16 cases_. Semb found 9 cases of hyperplasia (Swiss (1893) reported mucosal hypertro­ cheese) of the endometrium in 108 phy in most cases of myomas, with myomas in curettage. Henderson ob­ subsequent secondary changes due to served hyperplasia in only 6.5 j ~) pressure. The most detailed descrip­ of a series of 727 cases. Jacobson tion of pressure atrophy was by and Enzer (1956) found hyperplasia Frankl -(1912). King (1933) repcrt­ in 23 uteri in 103 uterine myomas ed 114 cases of myomas, 71 % of (22.3 ); ~ ). Timonen and Purola 1960) which exhibited hyperplasia of the found the histological picture in endometrium. Witherspoon (1936) patients with myoma dominated by reported the association of endome­ a high frequency of various hyper­ trial hyperplasia associated with plastic endometrial conditions (63% ) myomas in 55 % of his cases. Brewer and endometriosis ( 24 % ) . and Jones ( 1941) found hyperplasia From these it is clear that the cri­ in only 1 out of 100 cases. Torpin teria of "hyperplasia" must have et al (1942) compared the endome­ varied widely. A few workers have trial findings in 100 myomatous uteri emphasized that no · endometrial and fo·und · no - essential difference change is specific for uterine myoma. with · relatively the same percentage In the routine work however, one of hyp~rplasia present in both groups cannot help observing that certain :and-concluded :that there was no spe­ -changes are . more . common: and cial association of endom2trial hyper- characteristic. 14

t 248 JOURNAL OF OBSTETRICS AND GYNAECOLOGY OF INDIA

With this background in mind, this were taken to be normal. The en­ study was undertaken with the fol­ dometrial tissue for study was ob­ lowing purposes: tained by curettage from the remov­ ( 1) To determine the pattern of ed uterus. Sections were taken the endometrium and associated from different parts of the tumour, pathological changes in other organs uterus, ovary, tubes and cervix. in uterine myoma. ) (2) To correlate the endometrial Results changes with uterine bleeding, as The distribution of uterine myoma this will surely guide the future line according to age is shown in Table I of treatment. TABLE I (3) To throw some light on the Distribution of Uterine Myoma hormonal relationship with the aetio­ according to Age logy of uterine myoma. Age in years Incidence of Methods and Materials uterine myoma The present material comprises of 0-10 Nil 53 specimens of myoma uteri, remov­ 11-20 1 ed in the Gynaecology Department, 21-30 29 31-40 17 Assam Medical College and other 41-50 5 outside Hospitals in the state of 51-60 1 Assam. These were sent to the De­ 61-70 1 partment of Pathology for pathologi­ .J Total 54 cal examination. 1 The following points were noted in the clinical history in each case and varied from 18 years to 65 years. and in the naked eye appearance of The majority (54%) of these cases the specimens. fell in the group between 21 to 30 (1) Age, parity and complaints of years. the patient and specially the nature The symptoms are shown in Table of bleeding when present. II according to the type of myoma. (2) Size, number, position and It is apparent that haemorrhage was type of myoma. commonly associated with the sub­ ( 3) Presence of enlargement of mucous type. t distortion of the uterine cavity. Changes in Endometrium. The 1 ( 4) Gross observation concerning ·various histological changes in the the endometrium, thin or thick, pale endometrium and other organs are or injected, haemorrhagic, oedema­ summarized in Table III. It can be taus, polypoid or ulcerated. seen that 19 out of 53 cases (36% ) of ( 5) Gross appearance of ovary, uterine myoma were associated with tube and cervix. hyperplasia of the . endometrium. Our survey of ovarian pathology Majority of these patients ( 16 out of was limited only to the specimen re­ 19) had one symptom common to all, moved at operation. And for all prac­ i.e. excessive and irregular uterine tical purposes the unremoved ovaries bleeding, The hyperplasia was asso- ENDOMETRIAL CHANGES IN UTERlNE MYOMA 249

TABLE II Occurrence of Various Symptoms according to Types of Uterine Myoma

Types of myoma Symptoms Submucous Intramural Subserous Multiple mixed

Haemorrhage 22 4 6 6 Sterility 2 0 1 1 Backache 1 0 1 3 Mass over the abdomen 6 4 4 3 Amenorrhoea . . 2 0 0 0

TABLE III Histological Changes in Different Organs in Uterine Myoma

Types of uterine myoma Associated changes in other organs

.... I -0 §"' 0 "' ...... E >. +> "'t> . ~ 'iii"' § E"' >. 0 ;g C1l "'t> 0 C1l '"ii1 I'< "' 'J:: jj 'bD 0 I'< ;g >...... t> ;:l 0 ll~ C1l ,g ;:l I'< E E C1l "C1 1 E I': C1l .~ ~ > g 0 '"ii1 I'< "' ~~ C1l t> ] ....."' ~cd ...:io "C1 .!ll':: '3 ..."' ;:l ~ -~ 0 > ...... "' "C1 r.f). .s r.f). ~ r:..o Uo Jj~ < ~ ~] ~ ~ A. Endo- Hyperpla- ~ "' metrium sia 14 3 1 1 3 3 19 36% Post-mens- trual 3 2 8 1 7 3 1 1 1 14 26.5% Secretory 0 0 0 0 0 0%

Atrophied 5 7 0 2 2 1 14 26.5% Chronic en dome- tritis 6 0 0 0 1 6 11%

B. Ovary Follicu- lar cyst 7 2 3 1 13 24.6%

( C.L. haema- toma 0 1 1 1 3 5.7% Serous cyst 0 0 1 0 1 1.9%

C. Associat-Endome- ed changes triosis 0 0 1 0 1 1.9% Adeno- myosis 2 1 0 0 3 5.7 % Tubal infla- mmation 0 0 1 1 2 3.8% "" • 0"'

TABLE IV

Age in . Type of Uterine Associated . Sr. No. Parity Complamts 't Ovary h Histopatho 1ogy years myoma cav1 y c anges

55./51 40 0 Irregul ar Single Distorted Normal Nil (1) Fibromyoma bleeding submucous (2) Slight hyperplasia with P. V. - adenomyosis 1 year '-< 0 964/ 56 40 7 Irregular Single Eplarged Cystic Nil (1) Fibromyoma C 1 bleeding submucous (2) Hyperplasia of endo- S2 P. V. - metrium ~ 3 months (3) Single follicular cyst :of ~ overy ~

~ I 0 ;707 / 57 35 3 Irregular Single Dist01-ted Cystic Nil (1) Fibromyoma : ~ bleeding submucous (2) Endometrial hyperplasia t;a P. V. - (3) Multiple follicular cysts ;d 10 months of ovary n r.n

1749/59 30 0 (1) Primary Single Normal Cystic Uterus (1) Fibromyoma ~ amenor rhoea submucou s didelphys (2) Endometrial hyperplasia t1 (2) Pain in , and adenomyosis ~ the lower ! (3) Multiple follicular cysts z abdomen of ovary t;; 0 o · 1839/60 32 0 Irregul ar Sing!~ Normal Normal Nil (1) Fibromyoma b bleeding intramular (2) Slight hyperplasia with 0 P. V. - adenomyosis ><

6 months i ' ~-

>~ I ., i I ._....,._ -~

.... ENDOMETRIAL .CHANGEs IN UTERINE." MYOMA 251

eiated with 14: cases of submucous, 3 intramural, 1 subserous and 1 mixed type of myoma. The hyperplasia was associated with follicular cysts of ovary and adenomyosis in 3 in­ stances. There was no definite re'" lationship between. the number, size and type of myomas to. endometrial hyperplasia. In none of the · endo­ metrium of these 53 cases was there any evidence of secretory activity.

Changes in Other Organs The ovary showed single ·or multi­ Fig. 2. ple follicular cysts in 13 cases Section of the endometrium fr om a myoma uteri (24.6% ). Four cases showed endome­ showing marked endom etrial hyperplasia. triosis (7.5% ). Haematoxylin & Eosin X 180 .. In 5 cases, there were 3 or more pathological lesions in the same speci­ men, i.e. myoma uteri, hyperplasia of the endometrium, follicular cysts of . the ovary and adenomyosis. · The detailed descriptions of these cases are given in Table IV (Figs. 1, 2, .3, 4).

Fig. 3. Section .from the same uterus showing adeno­ myosis. The islets of endometrium exhibit also hyperplasia. H. & E. X 180.

Fig. 1. . change is specific for uterine myoma, Uterine myoma (mixed type) associated with while others have shown a marked multiple follicular cyst of the ovary. increase in the incidence of endome­ trial hyperplasia. Our study revealed Discussion that 36 % of' myomata were associ­ It has been stated that some wor­ ated with hyperplasia of the endo­ kers believe that no endometrial metrium and the symptom common 252 JOURNAL OF OBSTETRICS AND GYNAECOLOGY OF INDIA

stimulation. In this study the dia­ gnosis of hyperplasia has been res­ tricted to strict histological ·criteria. Adenomyosis of the uterus ( endo­ ~etriosis .interna) is considered to be due to exaggerated proliferative activity of the uterine mucosa and muscularis, which might be the re­ sult of abnormal functional activity of the ovaries. But this is not yet sci­ entifically established. In many cases there is also hyperplasia of these ectopic endometrial glands associated with hyperplasia of the uterine endometrium. In hyperpla­ Fig. 4. sia of the endometrium and myoma Section from the ovary from the same specimen showing multiple follicular cysts. of the uterus there is a high inci­ H. & E. X 120. dence of endometriosis ( 30 % ) (Witherspoon, 1939) and he sug­ to all in these cases was excessive gested that these 3 conditions might and irregular uterine bleeding. This possibily have a common back­ frequent association of hyperplastic ground. In a subsequent report it endometrium seems to be much more has been found that ovarian and than a mere coincidence. uterine endometriosis are associated There have been varying reports with hyperplasia of the endometrium on the frequency of hyperplastic and uterine myomas in 64 % of the changes in the endometrium in 44 cases studied, a figure far too high patients with uterine myoma and in to indicate a mere coincidence most series such changes have been (Witherspoon, 1939). more frequent than normal (King, Other authors likewise have 1933; von Wattenwyl, 1946; Mayer, called attention to the frequent 1948; J jtirgensen and Oram, 1949; association of hyperplasia of the Witherspoon, 1939; Jacobson and endometrium, endometriosis and J Enzer, 1956; Timonen and Purola, uterine myoma. In Jeffcoate's series 1960). According to King ( 1933) the of 113 cases of endometriosis, 79 frequency of hyperplasia associated women (71% ) presented hyperpla­ with uterine myoma would surely ex­ sia of the endometrium, while 31 clude its being a chance relationship. (28% ) presented uterine myomata. It is more commonly found in con­ Allen in his study of endometriosis nection with the smaller tumours, was impressed with the _high inci­ as the larger ones, by stretching and dence of the association of this con­ f pressure, are more likely to produce dition with menstrual irregularities endometrial atrophy. due to hyperplasia of the endome­ It is generally accepted that endo­ trium (70% ) and uterine myomata l metrial hyperplasia is a reflector of ( 41% ) and the prevalence of rela­ excessive and prolonged oestrogenic tive sterility. Smith in 159 cases of j I _ j ENDOMETRIAL CHANGES IN UTERINE MYOMA 253

endometriosis noted associated hyper­ not all uteri with hyperplasia bleed. plasia of the endometrium in 42 % This work further throws some and uterine myomata m 52 % of the light on the aetiology of uterine patients. Mayer (1948) found that myoma. After a prolonged contro­ 38 ovaries out of 44 cases of myoma versy, it has been now generally ac­ were sclerocystic. Timonen and Puro­ cepted that myoma arises from the la ( 1960) found the histological pic­ immature muscle cells in the uterine ture in patients with myoma dominat­ wall, lying in the vicinity of the blood ed by a high frequency of various vessels. But very little is known as l hyperplastic endometrium ( 63 % ). to the underlying cause for the deve­ The frequency of endometriosis was lopment of uterine myoma. Many also high, 24 % , and polycystic ova­ theories have been advanced as to ries, 21 % . Conversely, in a series the stimulus for its growth. collected during the same period by Recently the hormone theory has these authors, 42 % of 381 patients received considerable support _and with endometriosis had myomata, an excessive oestrogen activity over a observation which agrees with that prolonged period is thought to be published by earlier workers. the responsible agent. Witherspoon We have found 24.6% of myoma ( 1939) particularly has concluded uteri cases showing single or multiple emphatically that excessive ovarian follicular cysts of ovary. This is a follicular hormone stimulation is the frequency too conspicuous to be igniting factor that causes cellular overlooked. metaplasia of certain uterine muscle According to Novak (1952) bleed­ cells which, if the hormonal stimula­ ing in the presence of uterine myoma tion continues, develop into uterine is not necessarily the result of myoma and also may evoke some myoma. This may be due to very hyperplastic and neoplastic condi­ different intrauterine conditions, or tions in female sex organs like breast associated ovarian dysfunction and and uterus. This hypothesis is of constitutional or systemic disorders. interest and certainly merits further The finding of a high percentage study. Evidences in support of of hyperplasia of the endometrium hyperoestrogenic activity are experi­ together with the follicular cysts of mental and deduction from human ovary and adenomyosis in patients survey. with complaint of excessive and irre­ gular uterine bleeding, must have a Experimental certain bearing on this syn~ptom in ( i) Lacassagne ( 1935), Nelson these cases and this indicates that ( 1937, 1939), Burrows ( 1940), Lips­ hyperoestrinism is an important fac­ chutz (1950) experimentally suc­ tor responsible for haemorrhage in ceeded in the production of fibro­ uterine myoma. In these cases the myomatous growth in female guinea oestrogenic hormonal influence is so pigs, rabbits and mice by prolonged strikingly apparent that one would and continued administration of o~s­ be loath to associate other mechani­ trogens, accompanied in all by cystic cal causes in explanation of this glandular hyperplasi!J. and concluded bleeding. It is also equally true that that the causative factor ·of uterine

. ' 254 JOURNAL OF OBSTETRICS AND GYNAECOLOGY OF INDIA myoma is excessive oestrogenic sti­ cess of oestrogen, due to failure of mulation. the liver to inactivate oestrogen. . (ii) Anti-estrogenic substances ( ix) High incidence of uterine (testosterone and progesterone) in-· myoma in women of coloured races in hibit the tumorigenic action of oestro­ U.S.A. (9 times as frequent as in the gens and even cause reg1~ession of White women) probably is due to fre­ tumour, once they are formed .. quency of pelvic inflammation, which (iii) Rats exposed to a vitamin E causes ovarian hyperaemia and con­ deficient diet develop fibromJ.'omas of sequently its increased activity the uterus (Vitamin E ha:s anti­ (Witherspoon, 1939). oestrogenic properties). Although not determined, certainly there are some arguments against Human Survey this oestrogenic theory. Many women with even large tumours (i) Uterine myoma develops only have a perfectly normal cyclic during the active reproductive life of menstrual function, . are known to women. ovulate and are fertile. Following (ii) Women with myoma often myomectomy, the · recurren.ce of the reach menopause 2-10 years later tumour is very small and many of than normal women. these . cases do become pregnant. (iii) Uterine myoma tends to re­ Severt=~l workers (Brewer and gress after menopause, removal of Jones, 1941; Torpin et al, 1942) the ovary or after radiation castra­ from the study of the endometrium tion. in myomatous uteri found no uniform (iv) Uterine myomas are prone to evidence of hyperplasia. On the increase rather rapidly in size in the other hand, some authors claim that presence of a spontaneous or thera­ the incidence of ovarian follicular peutic increase of oestrogens. cyst and endometrial hyperplasia is (v) Appearance of sporadic re­ no higher than that .found in women ports that administration of testoster·· with myoma. According to Meyer one causes a decrease in size of the ( 1930) autoregression of uterine tumour. myoma which occurs after meno­ (vi) Frequent association of hyper­ pause can be more logically attribut­ plasia of the endometrium and folli­ ed to the diminished blood supply ac­ cular cyst of the ovary in patients companying cessation of ovarian with uterine myoma. function than to mere· withdrawal of (vii) These tumours are not hormones themselves. Further ex­ rarely associated with thecomas or perimentally produced tumours are granulosa cell tumour of the ovary. not really comp;;1rable -to myomas as (viii) Among the Bantus and they are . in fact fibromas and not some other races a fatty degeneration muscle · tumours. · Besides, they do of the liver with cirrhosis, caused by not involve the uterus, but are exten­ malnutrition, is a widespread malady, sively distributed throughout · the accompanied by an abnormally large peritoneal cavity:. However, . stHl the incidence of uterine myoma (Wither­ analogy between human apd ex:oe.ri­ spoon, 1935a), attributable to an ex- mental tumours can be drawn from

. . __ / . ENDOMETRIAL CHANGES IN UTERINE MYOMA 255

two points. Firstly, both depend upon Other supportive evidences, like oestrogenic activity and secondly, hormonal assay in the blood or urine, Loth arise from mesoblastic tissue. have been carried out by several Novak (1952) argues that myoma workers, but the results are not quite occurs in many parts of the body convincing. Biochemical examina­ other than genital organs, though tion of myomatous tissue has indicat­ certainly most commonly in the ed its oestrogen content to be negli­ uterus. But no one would invoke gible. This finding, however, must a hormonal cause of myoma of the be accepted with caution, since stomach or intestine though its struc­ normal myometrial tissue, which is ture is quite similar to that of uterme known to react to oestrogen, is like­ myoma. wise almost free of the hormone. The persistence of hyperplasia of Very recently Timonen and Purola the endometrial glands is a sure sign ( 1960) by using a cytological hor­ of excessive oestrogenic effect. The mone assessment method revealed a role of multiple follicular cysts of the hyperoestrogenic condition in 56 % of ovary resulting in hyperoestrinisrn is the uterine myomas. This picture well established. Since myoma tends approximately corresponds to the fre­ to grow slowly, this abnorwal quency of hyperplasia ( 63 % ). They oestrogenic stimulus would produce concluded that oestrogens probably immediate hyperplasia of the endo­ are of decisive importance in myoma­ metrium and would gradually deve­ genesis. lop myomas, provided the stimulus is That the three conditions, hyper­ prolonged sufficiently. Witherspoon plasia of the endometrium, uterine ( 1933, 1935b) studied 44 women myoma and endometriosis, may with endometrial hyperplasia and occur in combination, suggest tha:t in none was a uterine myoma dis­ there is a common denominator, covered, although in 20 of the women which on the basis of present know­ a laparotomy was carried out and in ledge could be the oestrogenic hor­ every one of these the ovaries con­ mone. The fundamental cause has tained numerous, small transparent its origin in excessive stimulation by cysts. Nevertheless, after an average ovarian follicular hormone, elaborat­ interval of 5 years, each of these ed by the cystic ovaries. Our results, patients was operated on for myoma showing a high percentage of endo­ of the uterus. .In an extensive in­ metrial hyperplasia, associated with quiry, cystic ovarian follicles were follicular cysts of the ovary and endo­ seen in every one of 124 women metriosis, also poi:rit to the idea that operated on for uterine myomas. If hyperoestrinism may be an aetiologic this is correct, in medical practice an factor. The presence of corpus early recognition of hyperplasia of tuteum in a few cases in no way the endometrium, usually by the exa­ contradicts this hypothesis. mination of fragments removed by It cannot be explained, however, curettage, is essential because a why myomata do not occur in 100 ~; continuance of the oestrogenic effect of the experimental animals, or why which it indicates, may lead to neo­ an increased oestrogen secretion or a plasm at some later date. demonstrable relative hyperoestrin- ]5

.. 256 JOURNAL OF' OBSTETRICS AND GYNAECOLOGY OF INDIA

ism does not always lead to myoma­ metria! hyperplasia, associated with genesis, but may produce entirely a follicular cysts of the ovary (24.6%) different disturbance, or have no and endometriosis (7.5%), points to r effect at all. Probably, the condition the possible relationship of hyper­ I of the substrate or the inherent sus­ oestrinism with the development of I ceptibility of the various tissues may uterine myoma. govern the response to a common J stimulus. Acknowledgment l The exact nature of the action of We wish to express our thanks to the oestrogenic principle upon the the Principal and Superintendent of uterine muscle is still only partially the Assam Medical College for per­ understood. It has been stated that mission to publish this paper. ' myoma arises from the muscle of References blood vessels. Uterine muscle cells possess an inherent growth capacity Allen: Cited by Witherspoon, 1939. different from that of smooth muscles Brewer J. I. and Jones H. 0.: Amer. in other parts of the body. Oestro­ Jour. Obst. and Gyn.; 41, 733-751, 1941. gen possesses a selective action on the Burrows H.: J. Path. and Bact.; 51, 385, muscle of the blood-vessels, ovarian 1940. and uterine. Hyperplasia of uterin-:: Campe V.: Ztschr. Geburtsh. u. Gynak.; vessels is an accompanying feature 10, 356-358, 1884. of endometrial hyperplasia. The Frankl 0.: Arch. f. Gynak.; 95, 269-343, 1912. vessels in small myoma show marked I proliferation (Schwaz and Wissner, Henderson: Cited by Macleod D. H. and - I 1950). A myoma with scattered foci Read C. in Gynaecology, 5th ed., 1955, of growth, which represent myoma J. & A. Churchill Ltd., London. · in early stages, show probably the Jacobson F. J. and Enzer N.: Obst. and origin from the arterioles. Gyn.; 7, 206-210, 1956. Jeffcoate: Cited by Witherspoon, 1939. From this work it is concluded that Jrgensen G. and Oram V.: Nord. Med.; hyperplasia of the endometrium is an 41, 1024-1027, 1949. important factor in the production of King J. E.: Amer. Jour. Obst. and Gyn.; uterine bleeding in uterine myoma and hyperoestrinism may be con­ 26, 582, 1933. Lacassagne A.: Comp. rend. Soc. de sidered to be one of the principal ' . biol.; 120, 685, 1935. aetiologic factors in myomagenesis. Lipschutz A.: Steroid Hormones and Tumours; Baltimore, Williams & Wil­ Summary kins, 1950. 53 specimens of uterine myomas Mayer C.: Acta Chirurgica Belgica, have been subjected to histopatho­ Brussels;· 47, 404-417, 1948. . logical study. 36% cases showed Mayer R.: Die pathologische Anatomie hyperplasia of the endometrium, der Gebarmutter. Henke-Lubarsch which may explain the irregular and Handb. der spez. Path. Anat. u. Risto­ excessive uterine bleeding in these logie. Bd. Vii, Erstes Theil, Julim· cases. Springer, Berlin, 1930. The hi~h percentage o£ endo- Nelson W. Q.; · Anat. Rec.; 68, 99, 1937. ENDOMETRIAL CHANGES IN UTERINE MYOMA 257

Nelson W. 0.: Endocrinology; 24, 50, Witherspoon J. T.: Endocrinology; 17, 1939. 621, 1933. Novak E.: Gynaecologic and Obstetric Witherspoon J. T.: Amer. Jour. Cancer; Pathology, 3rd ed.; W. B. Saunders & 24, 402, 1935 (a). Co., 1952. Witherspoon J. T.: Surg. Gyn. and Obst.; Schwarz 0. H., and Wissner S.: Amer. 61, 743, 1935 (b). Jour. Obst. and Gyn.; 58, 1133, 1949. Semb 0.: Arch. f. Gynak.; 43, 200, 1893. Witherspoon J. T.: Clinical Pathological Smith: Cited by Witherspoon, 1939. Gynaecology; Henry Kimpton, London, Tirnonen S. and Purola E.: Acta Obstet. 1939. Gynec. Scand.; 39, 153-168, 1960. Wyder Th.: Arch. F. Gynak.; 13, 35, 1878. Torpin R., Fund E. and Peeples W. J.: Wyder Th.: Arch. f. Gynak.; 29, 1-42, Amer. Jour. Obsl and Gyn.; 44, 569, 1887. 1942. Wattenwyl H. v., Muller J. H. and Hacki Zachariae F.: Acta Path. Microbial J.: Gynaecologia; 122, 282-291, 1946. Scand.; 34, 437-444, 1954.

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