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A case of chorionepithelioma of the lung
A CASE OF CHORIONEPITHELIOMA IJI?ON G:ERIN-LA-JOIE,F.R.C.S.
(cl), F.A.C.S.,
OF THE LUNG MONTREAL, QUEBEC
having its origin during pregnancy C HORIONEPITHELIOMA dealt with by the obstetrician and gynecologist. Its evolution
may be and marphology have become so complex, however, that he now has often to call upon specialists in other fields, e.g., the biologist, the pathologist, the radiologist, the surgeon specialized in the removal of metastases to other anatomical regions of the body. Conversely, the gynecologist is sometimes called upon as consultant. This was the situation in which the case now to be reported was seen. The rarity of the disease makes it nearly impossible for one man or even a group of men of the same opinion to report on any appreciable number of cases. Most of the reviews can only he collections of single reported cases. Any reviewer will remove a number of cases from any previous author’s list. producing a discrepancy in the number of available cases. This discrepancy is perhaps especially evident when we try to evaluate the part played by the hydatidiform mole in the production of chorionepithelioma. Some authors have attributed to the hydatidiform mole the develop ment of all choriocarcinomas. Others have asserted that all hydatidifortn moles are destined to degenerate into chorionepithelioma., unless an immediate removal is accomplished. Others declare that the hydatidiform mole. when diagnosed, may already have invaded distant parts of the body. It is well first to sum up briefly the history of the varying opinions ill YPgard to the morphology and evolut,ion of chorionepithelioma. f[istoricaZ Data.Tn 1867, R. Volkman first described what, was probably a malignant hydatidiform mole. He called it a “destructive placental polyp.” Tlater Ewing named it a “chorioadenoma destruens.” In 1888. Sanger ascribed a maternal origin t,o the chorionepithelioma, but in 1894, Gottschalk attributed it to a fetal origin. It remained for Marchand t,o establish, in 1895, the precise origin by meticulous cytologica,l study of the ectoblastic covering of the placenta. The cases studied up to this time had all been chorionepitheliomas secondary to uterine pregnancy. It was logical to expect similar relationships for ovarian and tubal pregnancies, such as were actually described in 1902 by Rleinha.ns and in 1905 by Risel. One must also remember the possibility of the ectopic choriocarcinomas developed in chorionic villi transported outside t,he genital sphere and tardily developed after a pregnancy or even the menopause. 391
Definitiorz.-
(~!horinc~arcinolna is not easy to clcfirle. II ronld be cited as *'. a vawnc)nlat,ous proliferation of the trc~l~hol)last. al)pcarirlg (luring (11’ afirr prcgnancp and l>r(>l>agiatetl hp the I~loocl strcanl through t’rrc whc~lr l)o~I~~,In+inci-pall,V t0 the IUllgS, tll? brain, thP livc~r iillcl tile splwtl.“” These tumors IIP’VPI’bar-e a,ny stroltla. ‘l’li(~y ill)])t’iL1’ essrntially dcstruc*tivc in their histological ch;lracteristics antI do noi elicit, any colinccdti\.e tissur rep the l)r~,lifrratioris of action. The difficulty in diagnosis lies in differrntiatin t,he ~l~r~l~al placellta fron1 t,hoxc of the (‘h~l’i~~(.i~t’ciIl~lna. rind Fwqztr)fc,y of the (‘hol,iocc(~cilro?~~(l.-The origin of t,he c~hol,ioeat,cinonl;1. is most frequently in the uterine cavit..v. Tt may occasionally tlcvc~lol) 011 the I~lacenta during pregnancy. Generally it occurs on retained placental drl)ris following delivery after all incomplete curettage. RaGtics va 1-y on the frequent a;; of the ~lro~~ic~nepithelionl~~. Tn retahulating indepentlent statisticas thti followilrg pr’ol)oriions appear to lw thr joule : Oriqilz
LzTfollow I$; follow $$ ‘follow
hydatidifol*nr rr101e an abortion ; nor~nial prcgnancg
:
and confinement.
According to Novak, hydatidiform mole appears once in 2300 pregnancies and of these only fro~rr 1 to 5 per cent l)ecorne choriocarcinomas. Choriocarcinomas are said, however. to he encountered once in 4,000 pregnancies. Cli?ZiCd Sym)jtonu.It is nearly impossible clinically to diagnose a choriocarcinoma at its onset. The first and most, frequent sign is recurring hemorrhage, lmt this is also characteristic of hydatidiform mole, threatened abortion, or incomplete ahortion. The unusual enlargement of the uterus in relation to the history of the duration of t,he pregnancy should suggest the l)ossibility of hydatidiform mole. The absence of movement of the fetus and the inabilit,y to palpate t,he head, breech, and limbs add to the necessity of considering molar t,ransformation. In such cases diagnosis can readily be confirmecl hy a simple roentgenogram of the abdomen. It is also well to rcmcmher that the recurrencde of hemorrhage from one to five weeks following an abortion. a delivery. or a curettage should lead to the suspicion of a transformation intcb a c.hol.ioc;trcillc,nla. l’olycgsti~ ovaries are frequently associated with hydatitliform mole and cllorioc~~r~cinoaIn, but more frequently with the former. Hormonal
E’ncto,rs
rmd Biologicnl
Tests.--
The hormonal biological tests are indispensable, although their interpreIf Aschheim-Zondek or Friedmantation is sometimes subject to controversy. Brouha tests are carried out systematically after a pregnancy they become negative very rapidly, seldom later than thirty da.ys. In hydat,idiform mole, Payne has noted tha.t, in 36 cases, 66 per cent have become negative in less than thirty days, and 95 per cent in less than three months. Moreover, Merger’” has established the fact that the prolonged persistence of a small quantity of
Prolan B after the expulsion of a mole or a placenta, indicates the persistence of molar remnants or the malignant transformation of mole. l’his is especially true if the quantitative values are stationary or increasing. It is imperative to follow these cases regularly, from the clinical point of view, but biological tests must also be made every three or four weeks. It, should be remembered that in addition to a normal pregnancy, hydatidiform mole, or a choriocarcinoma, there are some other lesions than can occasionally give a positive Aschheim-Zondek or Friedman-P,rouha reaction. Indications for the Asckheiw~-Zondek or Priedw~an-Brouha TPst.s.T One of these tests should be used in the following instances : A. In prolonged hemorrhage after a confinement, or an abortion. B. Following the expulsion of hydatidiform molt, cvcry three weeks for three months and then every three months for one year. C. Following an operation for a choriocarcinoma, on the schedule followetl for hydatidiform mole for one year and at yearly intervals thereafter. D. In all cases where a tumor of the adrenal cortex or of the ant,erior pituitary is suspected, or in cliseases of the hypothalamus, and in cases with intracranial hypertension. Factors lkading to Errol in th.r Aschheim-Zonclrk or FriedwlamBrouhn Tests.As in any other laboratory test there are possibilities of error which must be taken into account. Erroneous reports have been encountered clue to the following factors: (a) hormonal disorders in the test animal; (b) faulty administration of the hormone ; (c) the possibility of the hormone-producing tumor being enclosed in a fibrous capsule preventing the hormone from entering the circulation ; (cl) (I egeneration or necrosis of the tumor; (e) faulty renal function preventing the appearance of the hormone in the urine. Physiological Metastases of Pregnancy.It has been definitely established that trophoblastic tissues of clecidual cells and even villi enter the maternal blood stream ancl reach the lungs as emboli or metastases, where they may remain in a latent state until the end of the pregnancy. At delivery these metastatic cells or emboli are eliminated by an unknown substance with a specific histolytic power. Schmor18 has found such trophobIast.ic tissues in autopsies of women who had died of eclampsia or after delivery. Poten goes so far as to state that trophoblastic cells circulate freely in the blood stream in all cases of pregnancy. It is possible that in hydatidiform mole or chorionepithelioma these metastases may occur still more easily. Malignancy of the Choriocar&oqna.Choriocarcinoma is considered as the most malignant of all carcinomas of the pelvis. Its dissemination occurs through the blood stream rather than by the lymphatics or through local invasion. The lungs are m.ost frequently involved, followed in order by the brain, the liver, the spleen, and finally the kidneys.
GfiHIX-T,AJOJE
394
rim
i Ob>t & Gym. Jxly, 1954
It is difficult to establish accurat,e statistics on the outcome: for a great mmber of cures originally reported in malignant cases now stem doubt fill AS to t ltclir malignancy. Most statistics give a 70 to 80 I)ILI’ c~ont mortality, lull SIIL-;~.~“’is VI t,he opinion that it is closer to 90 11t’r cecnt it’ XVPdq~cnd l~l)ojl 1 Iltl (+l*iti+ IJI Ilcrtig’!’ for diagnosis. ,Metastases are often diagnosed orrly after cleat11 which usually occurs li1.r Only yawlg ~10 we encounter c~hnriocar*c4to six months following delivery. Nevertheless fTofflt~an, nomas wil.hout any trace of the primar)- lesion. Schmitz, Novak. and others relate a wrt.aitl II~~II~~WI~ of surh rases. HC~/?TSSi#11
of
P117111011nr~/
AIPfcrst,rsrs.---
11 is difficult. to ~)IYJTV the regression of mrtnst.ases in chorioca~ci~roula. yc.1 twenty cases have IJWII reported in the literature of which twelve concern IJUISuch cases havc~ l~cen &cd by Mazer,14 and Peight.al.‘” mnnary metastases. Although proof is difficult to est;llJlish it is possible t.hat following t,he early removal of t,he primn.ry ttutlor’ cnncealetl metastases may often disappear, as :I result of the same histolytic preps that produces the disappearance of the physiological metastnsrs after no~~tnal pregnancy. I;& ~hlW!lO~,?,l”lt f)f f’cJ?fli?t d~ftflSf(iXQ.Y.111 most cases. metastases W~Jllt?ill' it few weeks or at most a few months after the ~wnoval of the primary turtlcbr. The Hinglais”” have insistetl that the metsstases occur at the same t,imc as i hc clevelopment of the primary tumor and that t.hese may disappear spontantously rollowing the rert~oaal of the tumor if the hysterectomy is done soon enough. Evidence against this theor>is foun~l in some cases in which metnxtases appear, not only many months, Imf rven years after the removal of t,he lxirnary tumor. Feinerl” reports 47 cases with an interval of from I to 1G years. Lynch: reports one case aftei- :;l years. To explain suc~h cases we must suppose that the histolytic substance did not coml)lete its destructive effect upon the meNo douljt. some metastases at the time of the removal of the primary tumor. tastases are left dormant. On the occasion of a, new pregnancy, or an abortion, or a trauma, or from an unknown hormonnl fa.ctor, these latent met.astatic cells may later be revived. Case Report MaieP reported the observation of a woman .32 years of age who developed a choriocarcinoma of the Iun g three years following a hydatidiform molr. His patient survived for at least three more years after panhysterectomy, lobectomy, and x-ray therapy. In conclusion, the author wrote: “The pulmonary metastases of choriocarcinomas are frequent; they grow rapidly and terminate generally by death. A few cases with pulmonary metastases atypical in evolntion were cured by radiotherapy following hysterectomy.” We have personally observed a case similar to that of Maier.27 Some of t,he data are incomplete ancl depentl upon reports from a hospital nearly a thousand miles from Montreal. versity
Mrs. of
A. L.,
No.
4306.53,
Montreal, FacuIty
29 years of age, was of Medicine on April
admitted
to Notre-Dame
25, 1953, for a “tumor
Hospital, of the lung”
Uniand
Volume 68
Number
CASE
I
directed to cough over and nausea;
the chest a month; nocturnal
Gynecological
OF
CHOXIONEX’lTHELTOMMh
OF
LVNG
395
clinic. Her complaints were: grippe syndrome with dry and persistent thoracic pains in the right supero-anterior region; asthenia, anorexia, and the loss of i pounds in weight in the last month. sweating; History.-
She menstruated for the first time at the age of 1.5, and had a regular cycle of 30 days until her marriage at the age of 33 years. Thereafter, the cycle was four weeks, the periods having a duration of from 3 to 4 days. On June 24, 1948, she was admitted to the HGtel-Dieu of St. Joseph of Campbelton, N. B., for uterine hemorrhage following a period of amenorrhea of four months. A roentgenogram of the abdomen showed no visible signs of a fetus. A uterine curettage revealed the presence of a hydatidiform mole which eventually required two more curettages before the hleeding could be stopped. She was discharged from the hospital on July 13, 1945, in good condition. In the following three years, she gave birth to three normal babies at term. Since her last confinement in March, 1951, she had enjoyed good health except for a prolongation of the meuses up to a duration of 6 to 8 days.
Fig.
l.-Roentgenogram
of
lungs
on
arrival.
Tumor
easily
discernible
in
At the beginning of March, 1953, she developed “grippe” with a cough cine could relieve. She consulted her physician who advised a roentgenogram which proved to be negative. Her menstruation was then delayed for 10 days. to 19 she had profuse uterine bleeding which continued as a reddish discharge. meek of April, her cough became more severe. A second roentgenogram now of the right lung which caused her physician to send her to the Chest Clinic Hospital. Upon arrival, the patient appeared tired and clinical examination revealed an absolute dullness right upper lobe. Bronchoscopy revealed an extrinsic segment of the right upper lobe.
UPPW
right
lobe.
which no mediof the lungs From April 10 In the third showed a lesion at Notre-Dame
pale. Her weight was 103 pounds. The with absence of breath sounds in the obstruction of the bronchus of the apic.al
On April 27, a roentgenogram report read ‘ ‘ . , . presence of a segmentary opacity occupying the apical and anterior segments of the superior lobe. There seems also to exist a thickening of the apical pleura as well as a small effusion at the right base with obliteration of the cul-de-sac. From the past history, this is probably a metastasis. (Dr. J. L. LCgcr.)” (Fig. 1.)
Called in consultation on April 30, we noted slight bleeding from the utcrns. The eel’vix was eroded, soft, and slightly dilated. The body of the uterus was of normal size an11 position, mobile, and nonpainful. The :cdnc~~:~ were palpal~lr, slight.ly enl:lrg:t~,l 011 I he rig111 side. In vic>w of the complcs gyncc~ological history, \v,’ sugg,rc~4i~l tllat tlll*rts l111gl11 181~:I I:L~I, The excessive trauma sufforc~l at the tiulr pulmonary metastasis of a chorionepithelioma. of the repeated curettages for hydatidiform mole, followed by three successive term Jnregnancies in three years, may have contributed to the dissemination of troplroblaxtic tissue ill the lung and the late malignant transformation of a comlition perhaps primarily benign. Before confirming or eliminating this possible hypothesis we had a srritss i)V yll:llitittiV~~ and quantitative Friedman-Brouha tests made. These shon~l the followmg : May May May
2, 19X-Undiluted: 6, 1953-Diluted 8, 19X-Diluted
l/10: 3 /166
positive; positive; : J~ositivc~.
A biopsy-curettage was then carried out, although without much Hope ful information. The curettings showed a ’ ’ mucosa at thtl proliferative stage, taining lymphocytes, plasmocytes, and polymorphonuclrar leukocytes without r:horiocarcinomatous debris. ”
Fig. Fig. Fig.
Z.-Front J.--Rack
view view
2.
1‘3s.
of
ohtnining
use’-
the stroma con czlrori:rl vilJi nor
3.
of tumor. of turnor.
On May 16, Dr. Ed. Gagnon performed a right thoracotomy. A very hard mass, adherent to the parietal pleura, was found replacing the superior lobe of the right lung. The tumor was isolated by extrapleural decorticat.ion, although the pleura was found to be inti mately atta(>hc4 to thcl sup(xrior vena cava. .Z fragment of the lattflr was r~riov~~l for Iliopsy, and then a pneumonectomy was carried out. The pathologist’s examination of the specimen disclosed the following: The tumor measured 6 by 11 cm., was of a dark red color and very hard consistency. The cut section was multi-colored aud hemorrhagic (Figs. 3 and 3). On microscopic examination, the tumor was found to contain numerous areas of necrosis, recent and old hemorrhage, and strands of The tumor tissue, dispersed throughout these necrotic and hemorrhagic hyaline sclerosis. areas, was composed of small, richly vascularized cellular islands. The cells themselves were
CASE
OF
CHORIONEPITHELIOMA
OF
397
LTJNG
acidophilic or nearly colorless, their shape usually polygonal, their nuclei variably shaped. These rellular elements recalled the Langhans cells of the placenta. In most places the but in a few areas there existed only capillaries were covered by a normal endothelium, The diagnosis was choriocarcinoma of the a blood sinus covered by cells of syncytial type. right lung (Fig. 4).
Fig.
Fig.
4.-High-power
5.-Roentgenog-ram
photomicrograph
of
lungs
showing
one month developing
The fragment taken from the superior similar choriocarcinomatous tissue. The postoperative course was relatively operation and the physical condition of the test was negative. Another made thirteen hut a third one done on the twenty-third day
characteristic
after in left
vena
removal lung.
cava
choriocarcinomatous
of
was
right
found
lung.
cells.
Metastases
to be diffusely
are
invaded
hy
left
A gynecological the impression
normal considering the seriousness patient. A week later an undiluted days after the operation was also was positive.
examination done on the that the ovaries, particularly
twenty-fourth the right
of the Friedman negative,
postoperative day, June 11, one, were enlarged and might
\I,!
~:fiRl.~-r,A.IoIF:
398
be polycyst,ic. The general condition decided to remove the uterus and the rectomy were performed on June 15. visible or palpable metastases.
I Ol>
of the patient htking considerably improvrd. it KXP adncsa. A t(ot:tl hystcreetonly and lrilate~al n~~phr~ The rxploration of the abdominal c,ar-ily shon-~1 nib
The pathologic study showed that thr uterus n~~a~ured S cm. in length ;~ntl that t11r. ‘ivkil’dright ovary contained a c?-st 4 cm. in diannri pr. St~ri:rl swt ions of :I I I *lwcinlrns studied. I\‘o choriocarcinoma was found in the erl~l~)rlrt~trium or myometrillrrl. or iti t11v (‘PI \-is, tubes, or ovaries. The ovarian cyst W:IS of 1hc1 lnteirl type. Postoperative recovery was again urlcvvntful. On June undiluted Friedman test was still positive. on July 2, it was posit,ive m-hen dilut,ed l/100. Roentgenograms appeared in the left
Tel: days 29 it was
following positive
thv
whv11
tlilutwl
ion
the
l,itc~;
of the lungs had been negative urlt il mid-
On July 5, the patient asked to return hrme. IIer family p11ysician thcari saw llrl regularly and wrote to 11s describing her ~rarlua1 dc-clink> with (lyspnea, hemopt,vsis. grrv era1 weakness, and pain in the lower limbs. Dys~~nr~a and cschexia became larogressivrl! was no autolr~y. ‘I’llr~t~ was ItlOre pronounced and t,he patient dird on Aug. 20, 1955:Z. There no doubt that death was due to lung metasiascs of :I cllorioc~arcirlonla.
The special interest of this history lies in ihe fact, that there have I)ee:ll few cases of choriocarcinoma of the lun,: without the presence of a l)riinary gcnital lesion. +Since 1942, eight cases of true c~hol~ioc;lrci~lolnn have lwm well ilt Sot.rcDame Hospital. The reported case is the only one of the eight, ihilt has cntlecl fatally. All t,he others were operated upon within fire weeks front thfl iiine 01 delivery or curettage, sn.ve one which was referred 16 weeks after R normal labor. Four cases followed hyclatidiform mole, including the one rcl)ort WI here, t,hree followed abortion, and one, a full-term delivery. Table I is disconcerting. It, represent,s some cases rel)ortetl in the lit ct.ature where choriocarcinoms appeared a 1011g time after any known l)regnattc*y. It seems therefore possible for ;i llII?tilSt:Iti~ tuflio~ to dt~vclop tar*(lily. NeYthl,theless, some authors dill maintain that Ihrrf> is always :ln unknow11 prrqnancy in the da.ys preceding this niillignil~~l tl’R~lSf’~~l’~~liltiO~l. It \vns JIOSsibly so in our case, when a menstrllal tleln,v 01’ ten d;Ivs oc~~u~tl in March before t,he onset of the final illness. Yet the curritage done a month I;llcr gx\.(x no evidence of recent pregnancy. Park and Lees”” report the apprarance of a ~horioca~~t?inoit~~ in ;I \\‘oman 55 years of age three years after the menopause. We concur with t,he hypolhesis of Schmorl and Novak8 t,hat 1he melastwtic elements frown the nomnl placenta have less tentlcncy to proliferate than those of the hydatitlifornl nlola that, give evidence of t’urthel growth after their tlistant mrtastases. It is IMIS-. sihle that distant mtdastnsis of the benign hy(lntidiforrrl mole oecut’s al t hc time of the curettage and becomcls malignant mn~h later. Alternatively. il is sometimes true, as Mat,hieu has ::uggestetl, tflat c~horioearcincnna develops simultaneously with mole and that it is transpc~rted to the lung as a malignant tumor remaining in a latent state for many months or even years after a curettage. The case here reported seems to favor such a hypothesis.
Volume 68 Number I TABLE
I.
CASE LATE
AGE OF PAAUTHOR
TIENT
OF
APPEARANCE
PARITY
OF
TYPE OF PRECEDING PREGNANCY
Dorr and Cutler'?
?
Menopause
nrownzo
i
a
CHORIONEPITHELIOMA CHORIOOARCINOMA FROM DIFFERENT INTERVAL BETWEEN DELIVERY AND OPERATION
A-Z TEST
OF FOLLOWING AUTHORS
PATHOLOGY AT HYSTERECTOMY
LUNG
399
PREGNANCY.
A-Z TEST
INTERVAL BETWEEN IAST PREGNANCY AND OPERATION
B
?
Hydatidiform mole Abortion
L’ years
Negative
9 years
5 months
Hydatidiform mole Hydatidiform
3 years
Malcolmso
09
1
Hydatidiform mole
1
Herbert30
32
ii
Hydatidiform mole
4 years
Siegles40
34
Hydatidiform mole
Sieglesao
19
Hiegles40
23
SiegleW
33
SiegleW
38
30
years
CASES
TAKEN
RESULT
GenerDead. alized chorioearcinoma Dead. Pulmonary metastases Dead. Generalized metastases
4 years
Dead. Cerebral metastases
Negative
4 years
4 months
Chorioearcinoma
4 months
Abortion
5 months
Choriorarcinoma
5 months
Hydatidiform mole Abortion
24 years
Negative
24 years
1 year
Negative
1 year
6 months
Choriocarcinoma
1 year
Alive after lobectomy for choriocarcinoma Dead. Metastases in lungs, bladder, brain Dead. Metastases in lungs and brain Dead. Pulmonary metastases Dead. Pulmonary metastases Dead. Pulmonary metastases
mole
Hydatidiform mole
37 The choice of treatment varies according to the authors. The HinglaiP favor the early removal of the original lesion, by panhysterectomy, in all cases of hydatidiform mole. If metastases are inoperable, radiotherapy should be Others maintain the uselessness of tried, locally, or as teleroentgentherapy. radiotherapy in cases where the risk of operation is too great. Others report some improvement in the symptoms of metastases with the use of estrogens.
Conclusions 1. There are different degrees of malignancy in hydatidiform mole and choriocarcinoma, which explains the difference in evolution of the disease in different cases. 2. The rare cases of spontaneous regression or cure are due to certain histolytic substances and to the defensive action of the decidual cells. 3. The reported incidence of the change of hydatidiform mole to a malignant tumor varies according to the care with which the histological study is made.
ii;<, 4. Choriocarcinoma may appear ilt a.ny a.ge between puI)c~1~i~-illIt mcnopausc 01’ even after the menopausal. 5. Multiparas seem more prone 1.0 the disease than primipal*as. 6. The Aschheim-Zondek ant1 I~‘riedluan-l:rouha t.ests h:tr-cl ;I II itltlisl)c3fl sahlc value and dilution studies shoul~l 1~ VarricLd ollt Ior* at I(w~ 1’ \v(‘(‘]is j’(fllowing the operation or delivery.
$fortality 8. Early diagnosis is most: important. the delay in performing the operation. 9. Opinions vary as to the value of radiotherapy.
is it1 tlirec,t I~~,oI)ortiol~ to
Summary A case is reported of a chorionepithelioma of the lung in a woman who five years previously had had a hydatidifolxl mole. During the interval betw:cet~ mole and choriocarcinoma there had been three normal pregnancies. the last one two years prior to the appearance of the malignant lesion of t.he Lund The probable source of the choriocarcinoma and the significance of the latenl period are discussed. I would like here to express my thanks to the rrwmhcrs of my staff who the chest surgeon, I’. Brodeur, radiologist the case, to Drs. Ed. Gagnon, C Simard, pathologist and his staff, and Roger Lapointe, my resident, SO helpful in the editing of this paper and in allowing me to publish their interesting case. in L.
took an inttxrwt o,nd his st:tff,
\rho have I~rt‘rt reports on this
References Poten, W.: Arch. f. Gyn;ik. 66: 590, 1902. Ewing, J.: Surg., Gynec. & Obst. 10: 366, 1910. Surg., Gynec. & Obst. 16: 362, 1913. Cary, E.: Outerbridge, G. W.: Am. J. Obst. 72: 952, 19lri. Taylor, H. C.: Am. J. Obst. 75: 671, 1917. Cottalorda, J.: Gyn&. et obst. 4: 119, 1921. S. Clin. North America 2: 577, 1922. Lynch, F. W.: Schmorl, G., and Novak, E.: J. A, M. A. 78: 1771, 19’“. Masson, P.: Tumeurs-diagnostics histologiques, in SerFeut, S., Ri~)ac~eau-l)ulllas, I,.. and Babonneix, L., editors: Traiti: de pathologie medicale et de thPraprlltil{ue WI). pliqube, Paris, 1928, A. Maloine Pt fils, vol. 27, part 2, p. 525. Novak, E., and Roff, A. K.: AM. J. O&ST. & GYNEG. 20: 481, 1930. Anspach, B. M., and Hoffman, J.: AM. J. OBST. & GYNEC. 22: 239, 1931. Dorr, W. R., and Cutler, 0. I.: California & West. Med. 37: 247, 1932. Merger, R. : Contribution a 1’6tude du chorio-bpitheliome maiin, Paris ‘I’hesis, I!i:iJ. AM. J. OBST. & GYNEC. 26: 195, 1933. Mazer, C. : 1.5. Peightal, T. C.: AM. J. OBST. & GYNFX. 28: 435, 193-2. 16. Feiner, D. : AM. J. OBST. & GYNEC. 29: 840, 1935. 17. Mathieu, A. : Surg., Gynec. & Obst. 64: 1021, 1937. Simard, L. C.: Am. J. Cancer 30: 2, 1937. ii: Gey, G. O., Seeger, G. E., and Hellman, L. M.: Science 88: 306, 1938. 20. Brown, A. F.: Am, J. Cancer 38: 564, 1910. 21. Brindeau, A., Hinglais, H., and Hinglais, M.: Paris m6d. 31: 74, 1941. 22. Gerin-Lajoie, L., Laberg!, A., and Gauthier, J.: Union m&l. du Canada 70: IS, 1941. 23. Lyons, W. R.: Essays III Biology in Honor of Herbert M. Ev;rns, Rerke1e.y and Los Angeles, 1943, University of California Press, p, 315. 24. Cole, H. H., and Goss, H.: Essays in Biology in Honor of Herbert M. Evar~s, Berkeley and LOS Angeles, 1943, University of California Press, p. 105. 1.
2.
‘T: c
2
7:
i:
IO. 11. 12.
13. 14.
.
voiurne 68 Number
2.5. Best. 26. 27.
2% 29. 30. 31. X
33 X: 35. 3.i. 37. 38. 39. 40.
CASE
1
C. H.. ‘Baltimore, Gerin-Lajoie,
and
OF
CITORIONEPITHELIOMA
OF
LUNG
401
Tavlor. N. B.: The Phvsioloeical Basis of Medical Practice. ed. 4, 1945,“,Williams and Wilkins Comcany, p. 758. I,.: Unwon med. du Canada 75: 1350, 1946. Maier, If. C.: Aw J. OBST. & GYNEC. 53: 674,1947. Selve. H.: Textbook of Endocrinoloev. Montreal. Canada. I 1947. , Universite de Mon” keal, pp. 209, 221, 254, 918. -” ’ Hertig, A. T., and Novak, E. : AM. J. OBST. & GYNEC. 59: 1355, 1950. Park, W. W., and Lees, J. C.: Arch. Path. 49: 73, 205, 1950. Schmorl, G.: Cited by Park and Lees.30 Iiassianow. K. E.: Cited bv Park and Lees.ao Veit “J . Cited bv Park agd Lees.su H&la&, H., and” Hinglais, M.: (lompt. rend. Sot. de biol. 145: 1752, 1951. Levi, L. M., and Haig, P. V.: Radiology 56: 73, 1951. Novak, E.: Grnecological and Obstetrical Pathology, ed. 3, Philadelphia, 1952, W. B. Saunders Company, p. 503. Hinglais, H., and Hinglais, M.: Presse med. 64: 1359. 1952. Rcaile, G., and Briant; M.: Gynec. et obst. 52: 34, 1953. Hinglais, H., and Hinglais, M.: La Remaine d. Hop. de Paris 29: 7, 1953. Sieglrr, Samuel T,., et al.: Am. .I. Obst. & G!-net. 60: 586, 1950.
(cl), F.A.C.S.,
OF THE LUNG MONTREAL, QUEBEC
having its origin during pregnancy C HORIONEPITHELIOMA dealt with by the obstetrician and gynecologist. Its evolution
may be and marphology have become so complex, however, that he now has often to call upon specialists in other fields, e.g., the biologist, the pathologist, the radiologist, the surgeon specialized in the removal of metastases to other anatomical regions of the body. Conversely, the gynecologist is sometimes called upon as consultant. This was the situation in which the case now to be reported was seen. The rarity of the disease makes it nearly impossible for one man or even a group of men of the same opinion to report on any appreciable number of cases. Most of the reviews can only he collections of single reported cases. Any reviewer will remove a number of cases from any previous author’s list. producing a discrepancy in the number of available cases. This discrepancy is perhaps especially evident when we try to evaluate the part played by the hydatidiform mole in the production of chorionepithelioma. Some authors have attributed to the hydatidiform mole the develop ment of all choriocarcinomas. Others have asserted that all hydatidifortn moles are destined to degenerate into chorionepithelioma., unless an immediate removal is accomplished. Others declare that the hydatidiform mole. when diagnosed, may already have invaded distant parts of the body. It is well first to sum up briefly the history of the varying opinions ill YPgard to the morphology and evolut,ion of chorionepithelioma. f[istoricaZ Data.Tn 1867, R. Volkman first described what, was probably a malignant hydatidiform mole. He called it a “destructive placental polyp.” Tlater Ewing named it a “chorioadenoma destruens.” In 1888. Sanger ascribed a maternal origin t,o the chorionepithelioma, but in 1894, Gottschalk attributed it to a fetal origin. It remained for Marchand t,o establish, in 1895, the precise origin by meticulous cytologica,l study of the ectoblastic covering of the placenta. The cases studied up to this time had all been chorionepitheliomas secondary to uterine pregnancy. It was logical to expect similar relationships for ovarian and tubal pregnancies, such as were actually described in 1902 by Rleinha.ns and in 1905 by Risel. One must also remember the possibility of the ectopic choriocarcinomas developed in chorionic villi transported outside t,he genital sphere and tardily developed after a pregnancy or even the menopause. 391
Definitiorz.-
(~!horinc~arcinolna is not easy to clcfirle. II ronld be cited as *'. a vawnc)nlat,ous proliferation of the trc~l~hol)last. al)pcarirlg (luring (11’ afirr prcgnancp and l>r(>l>agiatetl hp the I~loocl strcanl through t’rrc whc~lr l)o~I~~,In+inci-pall,V t0 the IUllgS, tll? brain, thP livc~r iillcl tile splwtl.“” These tumors IIP’VPI’bar-e a,ny stroltla. ‘l’li(~y ill)])t’iL1’ essrntially dcstruc*tivc in their histological ch;lracteristics antI do noi elicit, any colinccdti\.e tissur rep the l)r~,lifrratioris of action. The difficulty in diagnosis lies in differrntiatin t,he ~l~r~l~al placellta fron1 t,hoxc of the (‘h~l’i~~(.i~t’ciIl~lna. rind Fwqztr)fc,y of the (‘hol,iocc(~cilro?~~(l.-The origin of t,he c~hol,ioeat,cinonl;1. is most frequently in the uterine cavit..v. Tt may occasionally tlcvc~lol) 011 the I~lacenta during pregnancy. Generally it occurs on retained placental drl)ris following delivery after all incomplete curettage. RaGtics va 1-y on the frequent a;; of the ~lro~~ic~nepithelionl~~. Tn retahulating indepentlent statisticas thti followilrg pr’ol)oriions appear to lw thr joule : Oriqilz
LzTfollow I$; follow $$ ‘follow
hydatidifol*nr rr101e an abortion ; nor~nial prcgnancg
:
and confinement.
According to Novak, hydatidiform mole appears once in 2300 pregnancies and of these only fro~rr 1 to 5 per cent l)ecorne choriocarcinomas. Choriocarcinomas are said, however. to he encountered once in 4,000 pregnancies. Cli?ZiCd Sym)jtonu.It is nearly impossible clinically to diagnose a choriocarcinoma at its onset. The first and most, frequent sign is recurring hemorrhage, lmt this is also characteristic of hydatidiform mole, threatened abortion, or incomplete ahortion. The unusual enlargement of the uterus in relation to the history of the duration of t,he pregnancy should suggest the l)ossibility of hydatidiform mole. The absence of movement of the fetus and the inabilit,y to palpate t,he head, breech, and limbs add to the necessity of considering molar t,ransformation. In such cases diagnosis can readily be confirmecl hy a simple roentgenogram of the abdomen. It is also well to rcmcmher that the recurrencde of hemorrhage from one to five weeks following an abortion. a delivery. or a curettage should lead to the suspicion of a transformation intcb a c.hol.ioc;trcillc,nla. l’olycgsti~ ovaries are frequently associated with hydatitliform mole and cllorioc~~r~cinoaIn, but more frequently with the former. Hormonal
E’ncto,rs
rmd Biologicnl
Tests.--
The hormonal biological tests are indispensable, although their interpreIf Aschheim-Zondek or Friedmantation is sometimes subject to controversy. Brouha tests are carried out systematically after a pregnancy they become negative very rapidly, seldom later than thirty da.ys. In hydat,idiform mole, Payne has noted tha.t, in 36 cases, 66 per cent have become negative in less than thirty days, and 95 per cent in less than three months. Moreover, Merger’” has established the fact that the prolonged persistence of a small quantity of
Prolan B after the expulsion of a mole or a placenta, indicates the persistence of molar remnants or the malignant transformation of mole. l’his is especially true if the quantitative values are stationary or increasing. It is imperative to follow these cases regularly, from the clinical point of view, but biological tests must also be made every three or four weeks. It, should be remembered that in addition to a normal pregnancy, hydatidiform mole, or a choriocarcinoma, there are some other lesions than can occasionally give a positive Aschheim-Zondek or Friedman-P,rouha reaction. Indications for the Asckheiw~-Zondek or Priedw~an-Brouha TPst.s.T One of these tests should be used in the following instances : A. In prolonged hemorrhage after a confinement, or an abortion. B. Following the expulsion of hydatidiform molt, cvcry three weeks for three months and then every three months for one year. C. Following an operation for a choriocarcinoma, on the schedule followetl for hydatidiform mole for one year and at yearly intervals thereafter. D. In all cases where a tumor of the adrenal cortex or of the ant,erior pituitary is suspected, or in cliseases of the hypothalamus, and in cases with intracranial hypertension. Factors lkading to Errol in th.r Aschheim-Zonclrk or FriedwlamBrouhn Tests.As in any other laboratory test there are possibilities of error which must be taken into account. Erroneous reports have been encountered clue to the following factors: (a) hormonal disorders in the test animal; (b) faulty administration of the hormone ; (c) the possibility of the hormone-producing tumor being enclosed in a fibrous capsule preventing the hormone from entering the circulation ; (cl) (I egeneration or necrosis of the tumor; (e) faulty renal function preventing the appearance of the hormone in the urine. Physiological Metastases of Pregnancy.It has been definitely established that trophoblastic tissues of clecidual cells and even villi enter the maternal blood stream ancl reach the lungs as emboli or metastases, where they may remain in a latent state until the end of the pregnancy. At delivery these metastatic cells or emboli are eliminated by an unknown substance with a specific histolytic power. Schmor18 has found such trophobIast.ic tissues in autopsies of women who had died of eclampsia or after delivery. Poten goes so far as to state that trophoblastic cells circulate freely in the blood stream in all cases of pregnancy. It is possible that in hydatidiform mole or chorionepithelioma these metastases may occur still more easily. Malignancy of the Choriocar&oqna.Choriocarcinoma is considered as the most malignant of all carcinomas of the pelvis. Its dissemination occurs through the blood stream rather than by the lymphatics or through local invasion. The lungs are m.ost frequently involved, followed in order by the brain, the liver, the spleen, and finally the kidneys.
GfiHIX-T,AJOJE
394
rim
i Ob>t & Gym. Jxly, 1954
It is difficult to establish accurat,e statistics on the outcome: for a great mmber of cures originally reported in malignant cases now stem doubt fill AS to t ltclir malignancy. Most statistics give a 70 to 80 I)ILI’ c~ont mortality, lull SIIL-;~.~“’is VI t,he opinion that it is closer to 90 11t’r cecnt it’ XVPdq~cnd l~l)ojl 1 Iltl (+l*iti+ IJI Ilcrtig’!’ for diagnosis. ,Metastases are often diagnosed orrly after cleat11 which usually occurs li1.r Only yawlg ~10 we encounter c~hnriocar*c4to six months following delivery. Nevertheless fTofflt~an, nomas wil.hout any trace of the primar)- lesion. Schmitz, Novak. and others relate a wrt.aitl II~~II~~WI~ of surh rases. HC~/?TSSi#11
of
P117111011nr~/
AIPfcrst,rsrs.---
11 is difficult. to ~)IYJTV the regression of mrtnst.ases in chorioca~ci~roula. yc.1 twenty cases have IJWII reported in the literature of which twelve concern IJUISuch cases havc~ l~cen &cd by Mazer,14 and Peight.al.‘” mnnary metastases. Although proof is difficult to est;llJlish it is possible t.hat following t,he early removal of t,he primn.ry ttutlor’ cnncealetl metastases may often disappear, as :I result of the same histolytic preps that produces the disappearance of the physiological metastnsrs after no~~tnal pregnancy. I;& ~hlW!lO~,?,l”lt f)f f’cJ?fli?t d~ftflSf(iXQ.Y.111 most cases. metastases W~Jllt?ill' it few weeks or at most a few months after the ~wnoval of the primary turtlcbr. The Hinglais”” have insistetl that the metsstases occur at the same t,imc as i hc clevelopment of the primary tumor and that t.hese may disappear spontantously rollowing the rert~oaal of the tumor if the hysterectomy is done soon enough. Evidence against this theor>is foun~l in some cases in which metnxtases appear, not only many months, Imf rven years after the removal of t,he lxirnary tumor. Feinerl” reports 47 cases with an interval of from I to 1G years. Lynch: reports one case aftei- :;l years. To explain suc~h cases we must suppose that the histolytic substance did not coml)lete its destructive effect upon the meNo douljt. some metastases at the time of the removal of the primary tumor. tastases are left dormant. On the occasion of a, new pregnancy, or an abortion, or a trauma, or from an unknown hormonnl fa.ctor, these latent met.astatic cells may later be revived. Case Report MaieP reported the observation of a woman .32 years of age who developed a choriocarcinoma of the Iun g three years following a hydatidiform molr. His patient survived for at least three more years after panhysterectomy, lobectomy, and x-ray therapy. In conclusion, the author wrote: “The pulmonary metastases of choriocarcinomas are frequent; they grow rapidly and terminate generally by death. A few cases with pulmonary metastases atypical in evolntion were cured by radiotherapy following hysterectomy.” We have personally observed a case similar to that of Maier.27 Some of t,he data are incomplete ancl depentl upon reports from a hospital nearly a thousand miles from Montreal. versity
Mrs. of
A. L.,
No.
4306.53,
Montreal, FacuIty
29 years of age, was of Medicine on April
admitted
to Notre-Dame
25, 1953, for a “tumor
Hospital, of the lung”
Uniand
Volume 68
Number
CASE
I
directed to cough over and nausea;
the chest a month; nocturnal
Gynecological
OF
CHOXIONEX’lTHELTOMMh
OF
LVNG
395
clinic. Her complaints were: grippe syndrome with dry and persistent thoracic pains in the right supero-anterior region; asthenia, anorexia, and the loss of i pounds in weight in the last month. sweating; History.-
She menstruated for the first time at the age of 1.5, and had a regular cycle of 30 days until her marriage at the age of 33 years. Thereafter, the cycle was four weeks, the periods having a duration of from 3 to 4 days. On June 24, 1948, she was admitted to the HGtel-Dieu of St. Joseph of Campbelton, N. B., for uterine hemorrhage following a period of amenorrhea of four months. A roentgenogram of the abdomen showed no visible signs of a fetus. A uterine curettage revealed the presence of a hydatidiform mole which eventually required two more curettages before the hleeding could be stopped. She was discharged from the hospital on July 13, 1945, in good condition. In the following three years, she gave birth to three normal babies at term. Since her last confinement in March, 1951, she had enjoyed good health except for a prolongation of the meuses up to a duration of 6 to 8 days.
Fig.
l.-Roentgenogram
of
lungs
on
arrival.
Tumor
easily
discernible
in
At the beginning of March, 1953, she developed “grippe” with a cough cine could relieve. She consulted her physician who advised a roentgenogram which proved to be negative. Her menstruation was then delayed for 10 days. to 19 she had profuse uterine bleeding which continued as a reddish discharge. meek of April, her cough became more severe. A second roentgenogram now of the right lung which caused her physician to send her to the Chest Clinic Hospital. Upon arrival, the patient appeared tired and clinical examination revealed an absolute dullness right upper lobe. Bronchoscopy revealed an extrinsic segment of the right upper lobe.
UPPW
right
lobe.
which no mediof the lungs From April 10 In the third showed a lesion at Notre-Dame
pale. Her weight was 103 pounds. The with absence of breath sounds in the obstruction of the bronchus of the apic.al
On April 27, a roentgenogram report read ‘ ‘ . , . presence of a segmentary opacity occupying the apical and anterior segments of the superior lobe. There seems also to exist a thickening of the apical pleura as well as a small effusion at the right base with obliteration of the cul-de-sac. From the past history, this is probably a metastasis. (Dr. J. L. LCgcr.)” (Fig. 1.)
Called in consultation on April 30, we noted slight bleeding from the utcrns. The eel’vix was eroded, soft, and slightly dilated. The body of the uterus was of normal size an11 position, mobile, and nonpainful. The :cdnc~~:~ were palpal~lr, slight.ly enl:lrg:t~,l 011 I he rig111 side. In vic>w of the complcs gyncc~ological history, \v,’ sugg,rc~4i~l tllat tlll*rts l111gl11 181~:I I:L~I, The excessive trauma sufforc~l at the tiulr pulmonary metastasis of a chorionepithelioma. of the repeated curettages for hydatidiform mole, followed by three successive term Jnregnancies in three years, may have contributed to the dissemination of troplroblaxtic tissue ill the lung and the late malignant transformation of a comlition perhaps primarily benign. Before confirming or eliminating this possible hypothesis we had a srritss i)V yll:llitittiV~~ and quantitative Friedman-Brouha tests made. These shon~l the followmg : May May May
2, 19X-Undiluted: 6, 1953-Diluted 8, 19X-Diluted
l/10: 3 /166
positive; positive; : J~ositivc~.
A biopsy-curettage was then carried out, although without much Hope ful information. The curettings showed a ’ ’ mucosa at thtl proliferative stage, taining lymphocytes, plasmocytes, and polymorphonuclrar leukocytes without r:horiocarcinomatous debris. ”
Fig. Fig. Fig.
Z.-Front J.--Rack
view view
2.
1‘3s.
of
ohtnining
use’-
the stroma con czlrori:rl vilJi nor
3.
of tumor. of turnor.
On May 16, Dr. Ed. Gagnon performed a right thoracotomy. A very hard mass, adherent to the parietal pleura, was found replacing the superior lobe of the right lung. The tumor was isolated by extrapleural decorticat.ion, although the pleura was found to be inti mately atta(>hc4 to thcl sup(xrior vena cava. .Z fragment of the lattflr was r~riov~~l for Iliopsy, and then a pneumonectomy was carried out. The pathologist’s examination of the specimen disclosed the following: The tumor measured 6 by 11 cm., was of a dark red color and very hard consistency. The cut section was multi-colored aud hemorrhagic (Figs. 3 and 3). On microscopic examination, the tumor was found to contain numerous areas of necrosis, recent and old hemorrhage, and strands of The tumor tissue, dispersed throughout these necrotic and hemorrhagic hyaline sclerosis. areas, was composed of small, richly vascularized cellular islands. The cells themselves were
CASE
OF
CHORIONEPITHELIOMA
OF
397
LTJNG
acidophilic or nearly colorless, their shape usually polygonal, their nuclei variably shaped. These rellular elements recalled the Langhans cells of the placenta. In most places the but in a few areas there existed only capillaries were covered by a normal endothelium, The diagnosis was choriocarcinoma of the a blood sinus covered by cells of syncytial type. right lung (Fig. 4).
Fig.
Fig.
4.-High-power
5.-Roentgenog-ram
photomicrograph
of
lungs
showing
one month developing
The fragment taken from the superior similar choriocarcinomatous tissue. The postoperative course was relatively operation and the physical condition of the test was negative. Another made thirteen hut a third one done on the twenty-third day
characteristic
after in left
vena
removal lung.
cava
choriocarcinomatous
of
was
right
found
lung.
cells.
Metastases
to be diffusely
are
invaded
hy
left
A gynecological the impression
normal considering the seriousness patient. A week later an undiluted days after the operation was also was positive.
examination done on the that the ovaries, particularly
twenty-fourth the right
of the Friedman negative,
postoperative day, June 11, one, were enlarged and might
\I,!
~:fiRl.~-r,A.IoIF:
398
be polycyst,ic. The general condition decided to remove the uterus and the rectomy were performed on June 15. visible or palpable metastases.
I Ol>
of the patient htking considerably improvrd. it KXP adncsa. A t(ot:tl hystcreetonly and lrilate~al n~~phr~ The rxploration of the abdominal c,ar-ily shon-~1 nib
The pathologic study showed that thr uterus n~~a~ured S cm. in length ;~ntl that t11r. ‘ivkil’dright ovary contained a c?-st 4 cm. in diannri pr. St~ri:rl swt ions of :I I I *lwcinlrns studied. I\‘o choriocarcinoma was found in the erl~l~)rlrt~trium or myometrillrrl. or iti t11v (‘PI \-is, tubes, or ovaries. The ovarian cyst W:IS of 1hc1 lnteirl type. Postoperative recovery was again urlcvvntful. On June undiluted Friedman test was still positive. on July 2, it was posit,ive m-hen dilut,ed l/100. Roentgenograms appeared in the left
Tel: days 29 it was
following positive
thv
whv11
tlilutwl
ion
the
l,itc~;
of the lungs had been negative urlt il mid-
On July 5, the patient asked to return hrme. IIer family p11ysician thcari saw llrl regularly and wrote to 11s describing her ~rarlua1 dc-clink> with (lyspnea, hemopt,vsis. grrv era1 weakness, and pain in the lower limbs. Dys~~nr~a and cschexia became larogressivrl! was no autolr~y. ‘I’llr~t~ was ItlOre pronounced and t,he patient dird on Aug. 20, 1955:Z. There no doubt that death was due to lung metasiascs of :I cllorioc~arcirlonla.
The special interest of this history lies in ihe fact, that there have I)ee:ll few cases of choriocarcinoma of the lun,: without the presence of a l)riinary gcnital lesion. +Since 1942, eight cases of true c~hol~ioc;lrci~lolnn have lwm well ilt Sot.rcDame Hospital. The reported case is the only one of the eight, ihilt has cntlecl fatally. All t,he others were operated upon within fire weeks front thfl iiine 01 delivery or curettage, sn.ve one which was referred 16 weeks after R normal labor. Four cases followed hyclatidiform mole, including the one rcl)ort WI here, t,hree followed abortion, and one, a full-term delivery. Table I is disconcerting. It, represent,s some cases rel)ortetl in the lit ct.ature where choriocarcinoms appeared a 1011g time after any known l)regnattc*y. It seems therefore possible for ;i llII?tilSt:Iti~ tuflio~ to dt~vclop tar*(lily. NeYthl,theless, some authors dill maintain that Ihrrf> is always :ln unknow11 prrqnancy in the da.ys preceding this niillignil~~l tl’R~lSf’~~l’~~liltiO~l. It \vns JIOSsibly so in our case, when a menstrllal tleln,v 01’ ten d;Ivs oc~~u~tl in March before t,he onset of the final illness. Yet the curritage done a month I;llcr gx\.(x no evidence of recent pregnancy. Park and Lees”” report the apprarance of a ~horioca~~t?inoit~~ in ;I \\‘oman 55 years of age three years after the menopause. We concur with t,he hypolhesis of Schmorl and Novak8 t,hat 1he melastwtic elements frown the nomnl placenta have less tentlcncy to proliferate than those of the hydatitlifornl nlola that, give evidence of t’urthel growth after their tlistant mrtastases. It is IMIS-. sihle that distant mtdastnsis of the benign hy(lntidiforrrl mole oecut’s al t hc time of the curettage and becomcls malignant mn~h later. Alternatively. il is sometimes true, as Mat,hieu has ::uggestetl, tflat c~horioearcincnna develops simultaneously with mole and that it is transpc~rted to the lung as a malignant tumor remaining in a latent state for many months or even years after a curettage. The case here reported seems to favor such a hypothesis.
Volume 68 Number I TABLE
I.
CASE LATE
AGE OF PAAUTHOR
TIENT
OF
APPEARANCE
PARITY
OF
TYPE OF PRECEDING PREGNANCY
Dorr and Cutler'?
?
Menopause
nrownzo
i
a
CHORIONEPITHELIOMA CHORIOOARCINOMA FROM DIFFERENT INTERVAL BETWEEN DELIVERY AND OPERATION
A-Z TEST
OF FOLLOWING AUTHORS
PATHOLOGY AT HYSTERECTOMY
LUNG
399
PREGNANCY.
A-Z TEST
INTERVAL BETWEEN IAST PREGNANCY AND OPERATION
B
?
Hydatidiform mole Abortion
L’ years
Negative
9 years
5 months
Hydatidiform mole Hydatidiform
3 years
Malcolmso
09
1
Hydatidiform mole
1
Herbert30
32
ii
Hydatidiform mole
4 years
Siegles40
34
Hydatidiform mole
Sieglesao
19
Hiegles40
23
SiegleW
33
SiegleW
38
30
years
CASES
TAKEN
RESULT
GenerDead. alized chorioearcinoma Dead. Pulmonary metastases Dead. Generalized metastases
4 years
Dead. Cerebral metastases
Negative
4 years
4 months
Chorioearcinoma
4 months
Abortion
5 months
Choriorarcinoma
5 months
Hydatidiform mole Abortion
24 years
Negative
24 years
1 year
Negative
1 year
6 months
Choriocarcinoma
1 year
Alive after lobectomy for choriocarcinoma Dead. Metastases in lungs, bladder, brain Dead. Metastases in lungs and brain Dead. Pulmonary metastases Dead. Pulmonary metastases Dead. Pulmonary metastases
mole
Hydatidiform mole
37 The choice of treatment varies according to the authors. The HinglaiP favor the early removal of the original lesion, by panhysterectomy, in all cases of hydatidiform mole. If metastases are inoperable, radiotherapy should be Others maintain the uselessness of tried, locally, or as teleroentgentherapy. radiotherapy in cases where the risk of operation is too great. Others report some improvement in the symptoms of metastases with the use of estrogens.
Conclusions 1. There are different degrees of malignancy in hydatidiform mole and choriocarcinoma, which explains the difference in evolution of the disease in different cases. 2. The rare cases of spontaneous regression or cure are due to certain histolytic substances and to the defensive action of the decidual cells. 3. The reported incidence of the change of hydatidiform mole to a malignant tumor varies according to the care with which the histological study is made.
ii;<, 4. Choriocarcinoma may appear ilt a.ny a.ge between puI)c~1~i~-illIt mcnopausc 01’ even after the menopausal. 5. Multiparas seem more prone 1.0 the disease than primipal*as. 6. The Aschheim-Zondek ant1 I~‘riedluan-l:rouha t.ests h:tr-cl ;I II itltlisl)c3fl sahlc value and dilution studies shoul~l 1~ VarricLd ollt Ior* at I(w~ 1’ \v(‘(‘]is j’(fllowing the operation or delivery.
$fortality 8. Early diagnosis is most: important. the delay in performing the operation. 9. Opinions vary as to the value of radiotherapy.
is it1 tlirec,t I~~,oI)ortiol~ to
Summary A case is reported of a chorionepithelioma of the lung in a woman who five years previously had had a hydatidifolxl mole. During the interval betw:cet~ mole and choriocarcinoma there had been three normal pregnancies. the last one two years prior to the appearance of the malignant lesion of t.he Lund The probable source of the choriocarcinoma and the significance of the latenl period are discussed. I would like here to express my thanks to the rrwmhcrs of my staff who the chest surgeon, I’. Brodeur, radiologist the case, to Drs. Ed. Gagnon, C Simard, pathologist and his staff, and Roger Lapointe, my resident, SO helpful in the editing of this paper and in allowing me to publish their interesting case. in L.
took an inttxrwt o,nd his st:tff,
\rho have I~rt‘rt reports on this
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