A STUDY BY (From
OF THE VERY R. W.
DECIDUA ND. Hop7:ins
0 DETERMINE the presence of a very early pregnancy from examination of the uterine curettiqs is a task which not infrequently the gynecologic pathologist. is called upon to perform. When bits of the trophoblast are seen, the diagnosis of pregnancy is certain, but when one is not fortunate enough to see portions of the very early products of conception the determination of the presence of pregnancy may be very difficult. Jn fact, as will be shown by consideration of the cases below, if the pregnancy is early enough, its diagnosis may be impossible. The uterus may be currttrd in early preqiancy and the site of implantat,ion of the ovum missed or, if removed with the curette, it may fail to appear in the sections of curettings studied. In such cases a thorough knowledge of the earliest changes in the cndometrium is essential for a histologic diagnosis. Through what may be termed a clinical accident, the author has obtained some histolopic data on the early qavid endometrium, coupled with an exact clinical history. It is with the hope of adding to our exact knowledge of the histologic picture of the very early decidua that this case is presented. 011 June 30, x woman, nged twenty-three, prewnted herself complaining of severe, lower abdominal, cramp-like pains which WCI’C particularly screre in the right lower IIcr previous mrnsttw~l l&tory indieatrd that her periods had begun quadmnt. nt twrlvr years of nge :lnd haul never been lwrfcctlg regular, the interval being twenty-right to thirty-six days. The usual duration was fvc to six days and the periods were associated lvith severe :rbdomiu:~l ctxmps. The present cramps mere much more severethan those usually associated wit11 1~~~ periods. IIer last menstrwll period had begun 011 May 26 and ended on May 29. She WIS married on May 28 and ceased menstruating tile nest day. On June 23 she hrg:~n having severe lower abdominal craml)-like pains, particularly on the right side. These continued with increasing severity and she consulted me on June 30. Pelvic esamimttion revealed a smooth, film cervix, high in the vagina and a uterus normal in size, consistence, and position. To the right of the uterus one could feel a very tenilcr, cystic mass about (i cm. in diameter, from which the ovary could not be ditIcrrntintcd. Ju view of the prrseucr of this mass, and its association with right-sided pain, in a woman a few d:~ys past the date of her experted lwiod, it was felt that the susl)icion of a tubal pregnancy should be confirmed or ruled out by an examinatiou under ether. Upon making this examination the author felt certain that the small, right-sided mass was a small ovarian cyst and did not, feel justified in performing a Inparotomy. In view of the history of dysmenorrhea, how-ever, it was thought advisable to take advantage of the anesthesia and perform a dilatation and curettngc in the hope of relieving her pain. Aerordingly, 011 July 1 a curettage W:IS done and a normal amount of endometrium was obtained which, macroscopically, showed no abnormality. The 809
histologic picture of this cndometrium wis that of the late l~rcmenstrual pattern. The patient, after her discharge from the liosl~ital, from time to time suffered On reexamination, August 1, the uterus was found to from raginal I~cmtrrrl~:~gcs. be softened and synmrctric:~Ily cnlargctl to :~pl~roxim:~tely the size of a six or tight weeks’ pregnancy. The pticnt was put to bed but coutinucd to hurt rec~urrillg cr:lrnps ant1 llrnlor~l!:rgrs. Fin:illy, on Scptcmbcr 3, since she was bleeding l~rofuscly ant1 the hemoglobin 11:rtl dropl~ed from S.5 per ctnt to 6.S per cent, it was felt that it would be unwise to sul,,jcct I~cr to further loss of blood and that there was littlo clmncc of the l~rcgnancy going to term. The I~morrlu~ges had been so frequent that it sccmccl inlprol~:~hIc tint tlrc fetus could be ;Iliw. Accordingly, the cervix was dilated with gre:it difficulty aud the fetus remorcd in pieces. To our surprise thn fetus sl~owcd no evidence of necrosis. &cause of the right-sided mass, ;L laparotomy vas done anil tlic right clr:iry, which colit:titicd :I dermoid cyst of about 6 cm. in diameter and the rorl,us Iutcum of l,r~‘gn:rncy, together with the :ilywidis were removetl. (‘!lnIxI~wcwrc~ \\:,s !~llc?Y~iltfr!l.
I.-Low-power field weeks’ pregnancy.
of the spongy Note the wicle
of the cmlomc~trium awl aermtecl outlines
of our of the
case of glan:ls.
Upon ex:in~iiintioi~ of tlic arm 0B the fetus alid carefnll~~ comparing it vith sperimens of different :,:;es in tlic collection of the (‘arnegsie Embrplogical Institute, Dr. George Streeter was able to tix the mcnstrwl age of the fetus obtained September 3 at thirteen to fourtccu wrecks. \Vith tliis tlxctl age as a starting point for our calculation it is obvious tlmt the lniticnt must 11:ivc become pregnant at her first ovulation ‘after her n~arriage. Since ovulation occurred between June 9 and 15 and the saml~le of endonietrium s11own brie was ol~txi~~ctl July 1, it is obviously a decidux of a little over two week::. The endometrium is comlrosed of two fairly distinct layers, the superficial eornpa da and the subadjxecnt spongiosa. The sections having been madc from eurettings, the basalis is absent. The compacta is a thin zone composed of stroma cells and traversed by the necks of the utcrinc glands. The spongiosa is composed of the dilat,ed glands of tile premcnstru:~l type coutaining much less stroma than the coml~~cln (Fig. I). These glands are markedly tortuous and have wide luminn. lined with cI~ithclium in a serrated pttrrn. Eosinstaining secretion is present in most of the glands. The rather light-staining el~ithelium lining the glands is lor the most part moderately lo\\. columnar with :I frayed border due to the secretion
Fig. 3.-Lower-power fiehl of a lor,gitudinnl section of the spongy layer of a pregnant endomc~trium (Miller), The #lards are somewhat dilated and serrated, but on the whole these features, usuxlly consi~ler’ctl characteristic of the pregravid and, in a more exagger:rtetl form,, characteristic of the gravill cndometrium. are actually less,marked in this emlumetrlum than in the pregr’nvirl cn~lometrium shown in Fig. 1. type but with less exaggerated premenstrual (*11:1ractcristics than in tither t,he pregnant endomrtrium shown in Fig. 1 or the late premenstrual endometrium in Fig. 2. A comparison of Fig. 3 with Fig. 1 will show that thr prcmenstru:rl pattern is more exaggerated in the twenty-six-day I~wrucnstru:ll c~n(lonwtrium than in the Mille’r endomctrium. In fact, the lapse of time from the onset, of the last menstrual period in the case of the Miller pregnancy is less than in either of the other two
C:LSCS. The endometrium in the Miller cnw was obtuinrtl twenty-one days after the onset of the last menstrual period and the pregnancy t.o be of ten to eleven days duration. The endometrium of pregnancy was obtuinrd thirtp-six days after the onset of the last menstrual pwmenstrual rndometrium sl~own above was obtained twenty-six onset of the last menstrual period. The lumina of the glands of contain the srerction cmbryotrophe and the epithclial lining is of acter :ts that of our t7yT.O weks decidw and the In tc l)wmcnstrual
to t\Tenty-two was estimated reported above period and the days after the the Miller cuse the s3mc charspwimen.
Fig. 4.-Longitudinal section of the spongy layer of the same premenstrual endometrium shown in Fig. 2. The magnification of Fig. 3 :~n(l Fig. 4 is the same. Note the wider lumina and more marked serration of the alamls in Fig. 4 than of those of Fig. 3.
Fig. S.-High-power field of stroma of cornpacta of endomctrium of nancy reported above. showing slight d~cidua-like change of the stroma change, however, is less marked than in the menstruating rndometrium Fig. 6.
early pr&gcells. The shown in
The stroma tolls of the early drcidw of our case arc interesting in comparison with those of thr late premenstrual or menstrual cndomctrium aud the endometrium of the Miller decidun. The stroma cells of the compacta are rather large, lightly staining polygonal cells with abundant lightly staining cytoplasm, and large, round or slightly oval nuclei (Fig. 5). In other I\-or& they 11:lre br~gun to bpar some
resemblance to the classical d&dun ~11. Comparing them with the stromn cells of the compaeta of a menstruating endometrium, we find the same type of “decidualike” cells in the menstruating endomctrium (Fig. 6). It is not uncommon in the late premenstrual or menstruating endomentrium to fintl tlw stroma cells of the compxcta taking on changes characteristic of the yonng decidua cell. In Fig. 6 the same type of decidun-like cell is scrn, hut the cells of thr menstruating endomctrium actually appear mow like the classical tlrcidw cells t,ll:ln do those of the wrlp
Fig. ti.-High-power decitlua-like changes what more marked
Fig. ‘I.-High-power ten to eleven days). decidua cells except
Aeld of compacta of menstruating of the cells. The resemblance to typical than in the pregnant enclometrium shown
field of compacta The stroma cells the immediate
entlometrium, decidua cells in Fix. $.
showing is some-
of very early pregnant endometrium (Miller, of thr enrlomrtrium bear no rcsemblancc to proximity of the ovum as shown in Fig. 8.
pregnancy. Coml~aring thcsr cells with the stroma cells of a still earlier pregnancy (Miller, ten to eleven clays) we find not eren the slightest wsembla~~ee of the stroma cells in the compacta of the Miller deciilua to the classical decidua cell (Fig. 7). In the immediate region of the implanted Miller OT-~1x1, on the other hand, there is a narrow zone within which the cells have taken on a slight but definite d&dual In another wry early pregnant endometrium, that of Kteinhans change (Fig. 8).
pregnmt en(lometrium Fig. X.-High-power field of early phoblast (b). The stroma cells (n) in close proximity to the on clelinite tlc~cidua-like charactrristlcs.
Fi?. Y.-Endometrium of the Kleinhans case, showing trophoblastic The stroma CC&S (n) bear no resemblance the adjacent endometrium. even in the proximity of the ovum.
tissue (b) and to decidua cells
3’ig. 9 sho~~-s troplrobhtstic tissue and adjacent the immediate vicinity of the ovum. Unfortunately, although stroma, but the latter hears no resrmblnncc to decidaa. it is very early, the actual age of the Kleinhans specimen could not be determined. The stroma cells of the spongy layer of the cndomctrium of all of the above cases show no d&dual changes.
iufiltr:ltion In our early pregnancy spccimerl there is :I slight throughout the vndomet~ium, most mnrkcd in the compact layer where l~ol~n~0~l~l~onuelc:~r leucocytc is seen. The prcmenstrxtl specimen more cxtcnsire infiltration with round and I~ol~moi~l~l~o~~ucIc:~~ cells, the comp:l~‘t~ hty”‘. This infiltration is the usu:~l fillding for two bci‘ore menstruntion ant1 is :I lxcrursor of the dcgrncrativc process of menstruation. III the Miller dccidua thclc is :I slmrsc sprinkling hut :I greater number of them arc seen in the immediate region Sumelous an:111 blood vessels :IW found through all the I:lycrs of the tllcre being no cssentinl diffuence bctnern tile blood x~sscls of this :~ud those of the late l~remenstrual endonlerltriuin.
round cells an occ:tsion:il shows an even particularly in or three d:lys charnrtrristic of rom~d cells, of the ovum. early dcvidua, e:uly tlccidu:~
A study of the above description in conjunction with the photomicrographs will show that there is no essential difference between the early decidua of ten or fourteen days and the pregravid endometrium. There is no evidence to show that the presence of a fertilized ovum embedded in the endometrium brings about any changes in the glands or stroma cells of the endometrium during the first two weeks except in the immediate vicinity of the ovum (Fig, 8, Miller ovum). The morphology of the glands and stroma in the Miller case and in our case of pregnancy corresponds to that of premenstrual nongravid endometrium of the same period of time since the last menstrual period. The premenstrual changes are less marked in the Miller case of pregnancy, in which a curettage was done twenty-one to twenty-two days after the onset of the last menstrual period, than in the premenstrual, nonpregnant case in which the patient was curetted on the twentysixth day of the menstrual cycle. On the other hand, there are slight but definite decidua-like changes in the stroma cells in the vicinity of the fertilized ovum which are entirely absent from the rest of the endometrium. These facts assume some clinical importance and indicate that, in our present state of knowledge, unless actual trophoblast is seen, the diagnosis of pregnancy cannot be made from curettings of a uterus pregnant two weeks or less. Exactly how soon the changes in the stroma and glands become sufficiently marked to determine pregnancy with certainty from the histologic picture of the endometrium can only be determined by placing on record exact histologic data of early decidua of definitely known age. Perhaps it will be shown that, there are individual variations, within certain limits, of the histologic changes taking place in the endometrium early in pregnancy and in the time at which these changes occur. Certainly one learns from t.he study of many curettings obtained during the various phases of the menstrual cycle that there are individual differences in the response which endometria make to the influence of corpora lutea in the premenstrual phase, as evidenced by different degrees of histologic change. Our case illustrates also a fact of some clinical interest inasmuch as it shows t,o what extent the endometrium can be injured even
to the extent of a curettage embedded ovum.
OF OBSTETRIC‘S AND (:YNECOLOCY
of the growth
11: conclusion, I wish to express my tllnllks to Dr. George Stvectcr of the C:wnc$e Embryologir:il Institute for his cooperation and hrlpful suggwtions in the pwpaT:lt,ion of this papw, and to l\lr. Oeborne Heard for tlw exerllrrlt pllotomierogr:tplls. REFERENCES GrossPr, Otto: Ztschr. f. d. ges. Anat. 11. I Abt. 66: 179, 1922. Hitschnman, F.u. Adler: Mon:ltsrhr. f. Geburtsll. u. Gynsk. 22: 1, 1908. Millrr, F. IV.: Rerl. Klin. Wrhnschr. No. II). 81 reetcr, George: Contributions to Embryology No. 92 18: 31, Carnegie Institute of ‘\l;nsllington. 1107 ST. Parr,
l3ODY OF THE UTERUS”
A. WOLFE, M.D., F.A.C.S., Dqmtnw~~t nf Pathology of the ihng
BY SAMUEL (From.
IXED tumors as defined by Ewing are growths comprised of embryonal elements in which blastomatous or malignant features are prominent. As first classically demonstrated by Wilms, these tumors are bidermal or tridermal teratomatas reproducing the stamp of the t,issues of the locality in which they occur. They differ, however, from true teratomas by the absence of complex structures or production of rudimentary organs. In the mixed tumors, the blastomatous process may effect the derivatives of one or more layers so that adenosarcoma or carcinosarcoma may be reproduced. More commonly, however, the sarcomatous change predominates. Classical examples of mixed tumors are those of the salivary glands of which the parotid group is best known. They produce basal cell carcinoma coexisting with mucoid tissue, bone or cartilage derived from the mesoderm. In the breast similar tumors arise from aberrant ectoderm and mesoderm. The kidney is most frequently the seat of mixed tumors reproducing derivatives of the sclerotome and myotome. As described by Wilms, these tumors contain glands, striated muscle, cart,ilage, bone and fat; all elements are embryonal in type. Similar tumors have been noted in the bladder, testicle and prostate. The admixture of various mesodermal elements was at first assumed to result by metaplasia. &lore recently, however, advances in teratology have produced sufficierit evidence to warrant belief that diEerent,iation of residual embryonal cells is the parent source of such tissues. In the genital tract of the female, similar tumors are not unknown. In a most comprehensive and thorough review of such tumors, Wilfred The vagina furnishes a group Shaw notes three sit,es of predilection. qead