J. clin. Path., 1970, 23, 676-680 Endometrial changes associated with myomata of the uterus L. DELIGDISH AND M. LOEWENTHAL From the Institute of Pathology, Municipal-Government Medical Centre, Tel-Aviv University Medical School, Israel SYNOPSIS The endometrium of 30 uteruses with myomata was studied at four standard sites. Glandular atrophy over a myoma or opposite a myoma was the most constant finding. At the margin of a myoma hyperplastic glands were frequently found, and distorted, elongated, or dilated glands were present at this site in half of all specimens. Other changes included adenomyosis and the separation of glands by muscle fibres from the basal layer of the endo- metrium. The coexistence of many of these findings in endometrial curettings can lead to the histological diagnosis of uterine myomata. Two factors, mechanical and hormonal, may be responsible and their mechanisms are discussed. The pathological changes of the endometrium that occur in the presence of uterine leiomyomata ('fibroids') have been studied with special refer- ence to submucous myomata. The recognition of similar changes in endometrial curettings can enable the presence of myomata to be suspected. It has been possible to show that some of the endometrial changes are due to the mechanical presence of a myoma, whilst other abnormalities appear to be the result of hormonal disturbances. Material and Methods Thirty uteruses with myomata, removed by total or subtotal hysterectomy, were examined. The patients' ages ranged between 31 and 54, with an average age of 45 years. Twenty specimens contained multiple submucous, intramural, and subserous myomata; in the remaining 10 there was a single submucous myoma. The changes in the endometrium were recorded in the follow- ing four constant areas of each uterus (Fig. 1): (1) the endometrium overlying a submucous myoma; (2) the endometrium opposite a myoma; (3) the endometrium at the margin of a sub- mucous myoma; (4) the endometrium from the Fig. 1 Diagram of the sites of the endometrium Received for publication 16 May 1969. that were examined. copyright. on January 16, 2020 by guest. Protected by http://jcp.bmj.com/ J Clin Pathol: first published as 10.1136/jcp.23.8.676 on 1 November 1970. Downloaded from
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J. clin. Path., 1970, 23, 676-680
Endometrial changes associated withmyomata of the uterus
L. DELIGDISH AND M. LOEWENTHALFrom the Institute ofPathology, Municipal-Government Medical Centre, Tel-Aviv University MedicalSchool, Israel
SYNOPSIS The endometrium of 30 uteruses with myomata was studied at four standardsites. Glandular atrophy over a myoma or opposite a myoma was the most constant finding.At the margin of a myoma hyperplastic glands were frequently found, and distorted, elongated,or dilated glands were present at this site in half of all specimens. Other changes includedadenomyosis and the separation of glands by muscle fibres from the basal layer of the endo-metrium. The coexistence of many of these findings in endometrial curettings can lead to thehistological diagnosis of uterine myomata. Two factors, mechanical and hormonal, may beresponsible and their mechanisms are discussed.
The pathological changes of the endometriumthat occur in the presence of uterine leiomyomata('fibroids') have been studied with special refer-ence to submucous myomata. The recognition ofsimilar changes in endometrial curettings canenable the presence of myomata to be suspected.It has been possible to show that some of theendometrial changes are due to the mechanicalpresence of a myoma, whilst other abnormalitiesappear to be the result of hormonal disturbances.
Material and Methods
Thirty uteruses with myomata, removed by totalor subtotal hysterectomy, were examined. Thepatients' ages ranged between 31 and 54, withan average age of 45 years. Twenty specimenscontained multiple submucous, intramural, andsubserous myomata; in the remaining 10 therewas a single submucous myoma. The changesin the endometrium were recorded in the follow-ing four constant areas of each uterus (Fig. 1):(1) the endometrium overlying a submucousmyoma; (2) the endometrium opposite a myoma;(3) the endometrium at the margin of a sub-mucous myoma; (4) the endometrium from the Fig. 1 Diagram of the sites of the endometriumReceived for publication 16 May 1969. that were examined.
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Endometrial changes associated with myomata of the uterus
fundus, or, in cases with a myoma in the uterinefundus region, from any other area unassociatedwith a myoma.The tissues were fixed in 10% formalin. Sec-
tions were stained with haematoxylin and eosin,van Gieson, and some with the periodic acid-Schiff techniques.
Results
The results are summarized in Table I. In theendometrium overlying a submucous myoma,there was total endometrial glandular atrophyin 17 (58%) of the 30 cases. Endometrial glandswere absent; the stroma was thin and fibrocyticwith oedema or haemorrhage in most of the
specimens. The surface epithelium was oftenmissing but, when present, usually consisted ofcuboidal or cylindrical cells with dark basalnuclei. In the same area eight specimens showedsubtotal atrophy of the endometrium. In thesethe endometrium was thin, with scattered glands,generally without any signs of a cyclical menstrualphase, whose shape was frequently distorted.There were haemorrhages in the stroma andflattening or loss of the surface epithelium (Fig. 2).Deposits of a basophilic substance, positive toPAS staining indicative of a high content ofmucopolysaccharides, were found in the stroma.Sometimes these focal stromal deposits pro-jected into the uterine cavity, forming smallpolyps covered by surface epithelium (Fig. 3).In one case there was a true polyp in this areaof the endometrium. Cyclical menstrual changes
Endometrium Total Subtotal Distorted, Cystic Polyposis Adenomyosis GlandsAtrophy Atrophy Dilated, Glandular Separated by
Elongated Hyperplasia Muscle FibresGlands
Overlying a sub-mucous myoma 17 8 1 0 1 3 4
Opposite asubmucous myoma 12 10 3 2 0 2 2
At margin ofa myoma 0 0 15 8 7 4 5
At fundus orother area 1 0 4 6 4 2
Table I Endometrial changes associated with uterine myomata in 30 cases
Fig. 3.
Fig. 2 Endometrium overlying a myoma showingsubtotal glandular atrophy. There is haemorrhagein the stroma and partial loss ofsurface epithelium.Haematoxylin and eosin. x 63.
Fig. 3 Endometrium overlying a myoma. A stromalpolyp is composed of basophilic PAS-positive material.Periodic acid-Schiff. x 160.
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were clearly recognizable in only three specimens(in two cases proliferative phase, and in one casesecretory phase).
In the endometrium directly opposite a myoma,12 cases with total atrophy and 10 with subtotalatrophy were found in the 30 examined. Distorted,dilated, and elongated glands were present inthree instances, and these frequently accompaniedsubtotal endometrial glandular atrophy. Cysticglandular hyperplasia was present in two casesand normal cyclical changes were clearly recogni-zable in only three instances (one proliferativephase, two secretory phase).
In the area at the margin of a myoma theendometrium did not show total or subtotalatrophy but other morphological changes werepresent. Distortion, elongation, and dilatation ofglands (Figs. 4, 5, and 6) were present in 15 of the30 cases. The glands in these specimens showedan irregular shape and were triangular or poly-gonal in transverse section, sometimes parallel
to the myometrium. Some glands were longer thannormal, without parallel distribution, and otherswere composed of flattened epithelium and con-tained mucus. In the remaining 15 specimens,seven showed polyposis and eight cystic glandularhyperplasia. At this site menstrual cyclicalchanges were present in 11 of the 30 cases (sevenproliferative, four secretory).
In the uterine fundus area and in other areasof the endometrium not related to myomata,atrophic changes were found in three cases (onetotal and two subtotal atrophy). In 10 cases therewere hyperplastic changes (cystic glandularhyperplasia in four and polyposis in six). Cyclicalchanges were recognizable in 15 of the 30areas examined; nine of them showed the pro-liferative phase and six the secretory phase.Adenomyosis was present in eight of the 30
cases. The islands of endometrial glands sur-rounded by cellular stroma were usually situatedin the inner third of the myometrium, and were
Fig. 4.
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9ZAFig. 6.
Fig. 4 Endometrium at margin of a myoma showingdistortion and elongation ofglands. Haematoxylinand eosin. x 63.
Fig. 5 Endometrium at margin of a myoma. Glandsvary in size and shape and, at the right, are parallelto the myometrium. Haematoxylin and eosin. x 100.
Fig. 6 Endometriunm at margin of a myoma witha cystic gland between secretory phase glands.Haematoxylin and eosin. x 160.
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Endometrial changes associated with myomata of the uterus
Fig. 7 Endometrium opposite a myoma. Distortedglands are parallel to the myometrium and a singlegland is separatedfrom the endometrium by musclefibres. Haematoxylin and eosin. x 160.
found to have an almost equal distribution inthe four areas examined.
Endometrial glands which were separated fromthe endometrial layer by muscle fibres werefound in 12 of the 30 cases (Figs. 7 and 8).These glands were solitary or in small groups,and did not show any recognizable cyclicalchanges. They were situated under the basallayer of the endometrium; their presence was notrelated to islets of adenomyosis, which were
situated much deeper in the myometrium andwere always surrounded by cellular stroma. Inthree cases they coexisted with adenomyosis,and in nine cases they were present withoutadenomyosis. Their distribution throughout thefour areas examined was nearly equal.
Discussion
Uterine myoma was first believed to be a purelylocal growth, due to local reasons, but by the endof the 19th century it became accepted thatmyomata of the uterus were related to hormonaldisturbances. In 1935, Witherspoon describedthree pathological changes, aetiologically closelyrelated: (1) myoma of uterus, (2) microcysticdegeneration of the ovary with incompleteluteinization, and (3) cystic glandular hyper-plasia of the endometrium. According to Bolck(1961), different authors reported that the asso-ciation between uterine myoma and endometrialhyperplasia varied between 6% and 80%.Granjon, Yanotti, and Cedard (1961) found highoestrogen levels in women with uterine fibroidsand believed that the endometrium played arole in the synthesis of oestrogens. Laitinen
17-~~
IM.~~~~~~-z--~~i -
_ _ -;r .... -_
Fig. 8 Endometrium from fundus of uterus. Groupsofglands are separatedfrom the basal layer of theendometrium by muscle fibres. Haematoxylin andeosin. x 160.
(1964) reported that hyperplasia was the mostcommon change in the endometrium belongingto a myomatous uterus, but endometrial oedemamay be confused with hyperplasia. Bolck (1961)described hyperplastic, normal, and atrophicareas in the endometrium of myomatous uterusesand an irregular excretion of oestrogens inthese patients.
Rechnitz and Domotori (1964) examined 1,255cases of myomatous uterus. They found in-creased oestrogenic activity in 59% of the casesin patients with an average age of 43 years,and atrophic changes in patients with an averageage of 52. Novak and Woodruff (1962) describedthe association between myoma and the non-ovulatory type of cycle with hyperplasia ofendometrium but suggested that the abnormalbleeding may be of dysfunctional origin and notdue to the presence of the myoma. Sehgal andHaskins (1960) studied the correlation betweenthe area of the endometrial surface and theamount of endometrial bleeding. He found thatthe normal endometrial surface area of 15 cm2was markedly increased by the presence ofmyomata, reaching 224-5 cm2, and explained themenorrhagia on this basis.The present study included a topographical
investigation of the pathological changes of theendometrium with special reference to the siteof myomata within the uterus. We suggest thatthe contradictory descriptions and interpretationsthat have been reported may be partly explainedby the varied changes in the endometrium in thedifferent topographical sites. These differentpathological patterns may be the result of amechanical factor and a hormonal factor. Atrophyof the endometrium, elongation, and distortionof the glands may result from mechanical pres-
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sure exerted by the nodular mass of the myomaon the overlying or nearby endometrium.Cystic glandular hyperplasia, polyposis, oedema,and haemorrhages can result from hormonaldisturbances, mainly hyperoestrogenism.The action of these two factors-mechanical
and hormonal-seems to be a complex one.Atrophy may result not only from mechanicalpressure but also from postmenopausal hormonalinsufficiency. Glandular hyperplasia or polyposis,mainly in the endometrium at the edge of amyoma, may not only be the expression of oestro-genic hyperactivity but also the result of mechani-cal forces upon the endometrium. Distortion,elongation, and dilatation of glands seems to bemore the result of pressure than of hormonaldisturbance. The development of small pseudo-polyps (Fig. 3) in an atrophic endometriumoverlying a submucous myoma represents anotherexample of the double action of both these factors.Mechanically, the endometrium is stretched andthinned until it is atrophic. Hormonally, deBrux (1960) has described an increased vascularpermeability due to hyperoestrogenism, causingthe deposition of protein and mucopolysaccha-rides in the stroma that form the basis of pseudo-polyps.
In postmenopausal age groups there wereinvolutional changes in the uterus with atrophyof the endometrium. Nevertheless, our study hasshown that atrophic changes of the endometriumwere the most constant morphological changesin the presence of uterine, mainly submucous,myoma (83 %). Total or subtotal glandularatrophy was present in all age groups and onlyfive women were postmenopausal. Other post-menopausal aspects, and all specimens showingendometritis, were not included in the presentstudy.There is wide agreement that the incidence of
adenomyosis is raised in the presence of myomata.Laitinen (1964) reported the association betweenadenomyosis in the cornua and sterility in womenwith myomata. In our cases, adenomyosis wasfound in eight specimens (27 %) and was presentin all four of the areas examined.The presence of endometrial glands, solitary
or in small groups, separated from the endome-trium by muscle fibres, does not represent adeno-myosis and we found no relationship betweenadenomyosis and the topography of these glands.
Hormann (1960) described an increased proli-ferative potentiality of some muscle groups ofthe myometrium in the presence of myomata,and we suggest that the presence of musclefibres between the endometrial glands can beexplained by a diffuse proliferation of musclefibres throughout the uterine wall.The endometrial changes that were found to
take place in association with myomata can berecognized in endometrial curettings. The pre-sence of myomata is suggested if curettings showa mixed picture of glandular atrophy, cysticglandular hyperplasia or polyposis, togetherwith many distorted, elongated, or dilated glands,and muscle fibres between glands.
Disturbances of normal cyclical changes in the30 specimens were most marked in the areaslying over or opposite the myoma. There wasa clearly recognizable cyclical phase at these twosites inonlythreecases. Thislackofcyclical activityseemed to be less marked at the margin of amyoma and least marked in the uterine fundusarea or in areas that were not related to myomata.We believe that alterations of the endometrialcycle in these 30 women were due to hormonalvariations which may represent a common causefor both the myomata and some of the endome-trial changes. The remaining endometrial abnor-malities appeared to have been due to mechanicalfactors that mainly affected the endometriumlying over, opposite, or close to the myoma.
References
Bolck, F. (1961). Die Pathologie der Uterusmyome. Arc/h.Gynak., 195, 166-177.
de Brux, J., and Dupre Froment, D. (1960). L'iperplasia endo-metriale. II. Studio istogenetico. Gazz. sanit. (Milano), 31,629.634.
Granjon, A., Yannotti, S., and Cedard, L. (1961). ContributionA 1'etude hormonale des fibromes: dosage des oestrogenesdans le sang. Les fibromes et les muqueuses uterines.Presse med., 69, 2191-2193.
Hormann, G. (1960). Zur Topographie und formalen Geneseder Uterusmyome. Geburtsch. u. Frauenheilk., 20, 942-953.
