C H O R I O N - C A R C I N O M A I N T H E M I D L A N D S *

WILFRID MILLS, F.R.C.S., F.R.C.O.G.

United Birmingham Hospitals, Birmingham

CHEMOTHERAPY for cancer will undoubtedly be one of the major benefits that the second half of the twentieth century will give to medicine and chorion-carcinoma may well prove to be one of the most sensitive tumours. Consequently the publication of a series of cases in which metho- trexate and similar drugs have not been used will soon become impossible, and it may be forgotten what could be accomplished prior to their intro- duction. It seemed relevant to collect records of twenty-three gynaecological cases reported to the Birmingham Follow-up Department from various units in the Midland region between 1946 and 1960, so that their results might serve as a basis for comparison with those following in the chemo- therapy era.

The interpretation of results in chorion-carcinoma is exceptionally difficult as the condition is not always easy to classify in respect of malignancy. The distinction histologically between benign hydatidiform mole, invasive mole, metastasising mole and chorion-carcinoma may in some cases be more quantitative than qualitative, and there used to be some justification for revising the diagnosis of a case labelled chorion-carcinoma if it were cured by surgery. In common with other gynae- cologists we have experience of a case of doubtful malignancy that was provisionally classified as chorion-carcinoma when multiple metastases ap- peared in the chest, only to have the diagnosis reversed when they faded and disappeared spon- taneously. Similarly Brews (1939) in his classic account of one hundred moles and twenty-four chorion-carcinomata describes a case with vaginal metastases that disappeared spontaneously after hysterectomy. It is this possibility of spontaneous regression of borderline tumours, coupled with the difficulty of exact histological classification, that tends to invalidate the apparent success of any new method of treatment. Gordon King (1956) with great experience of this type of tumour in the Far East, discusses the problem in detail and refuses to accept any borderline case as being malignant. Out of his first fifteen post-war cases accepted as chorion-carcinoma only three survived, and these all followed hydatidiform moles. The Hong Kong material was reviewed by Chan (1962) when forty-

one cases were analysed. Despite the fact that these include the beginning of the chemotherapy era they will be used as a comparison with the Midland cases.

MATERIAL

The twenty-three cases were drawn from a wide area during a fifteen-year period during which there must have been approximately one million births, giving a ratio of roughly 1:43,000; this is in com- plete contrast with the Hong Kong ratio of 1:1,331 deliveries. Ages at diagnosis ranged from nineteen to forty-eight (Hong Kong twenty-two to forty- eight) with twelve between nineteen and thirty, seven between thirty-one and forty, and four over forty. This suggests a parallel with fertility rather than with age as an aetiological factor.

There were nine tumours associated with or following a hydatidiform mole. The fact that this figure (39 per cent) agrees tolerably well with the Hong Kong 44 per cent (eighteen out of forty-one) and with Hertig (1950) who quotes 50 per cent, suggests reasonable uniformity in classification and diagnosis. One of these patients had had three children and three hydatidiform moles, the last being two years previous to this tumour, while another had an interval of six years between hysterectomy for a supposedly benign mole and the diagnosis ofchorion-carcinoma from pulmonary secondaries. There was only one case that followed within six months of a successful pregnancy, but four that occurred shortly after an abortion, and one in association with an ectopic tubal pregnancy. The remaining eight cases did not show any close relationship with a preceding pregnancy.

The diagnosis in the above cases was usually made from the examination of curettings when bleeding persisted following childbirth, abortion or hydatidiform mole. In four other cases it was made from curettings taken from patients with unexplained uterine bleeding. There do not appear to have been examples of 'false negative curettings' (three out of nine possible Hong Kong cases) due to the growth being localised in the myo- metrium and not projecting into the uterine cavity. In three other patients an advanced abdominal mass was the first indication of trouble, while in

* Presented at the Autumn Meeting of the Faculty of Radiologists in Birmingham, on 5th October 1963

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C H O R I O N - C A R C I N O M A I N T H E M I D L A N D S 261

ooe other case an apparently spontaneous cerebral haemorrhage proved to be the presenting symptom.

The use of biological tests (such as Ascheim- Zondek or Hogben) did not figure largely in making the diagnosis, except in the surveillance of patients who had expelled a hydatidiform mole. In two patients the positive Hogben test (which had previously been negative) was the first sign that chorion-carcinoma had developed as a metastasis. In the Hong Kong cases Chan (1960a) comments that the positive test may indicate either a benign or a malignant recurrence, while the test may remain negative even in the presence of recurrent malig- nancy.

The common sites for metastatic tumour proved to be the lungs (nine), liver (five), and vagina (five), with cerebral secondaries recorded in only three cases. The Hong Kong series was similar with twenty-nine out of forty-one patients recorded as having pulmonary metastases (including 100 per cent of those coming to autopsy), thirteen cerebral, eleven hepatic and only seven vaginal tumours.

RESULTS

Out of the twenty-three patients in the series, eleven died of the disease and eleven survive apparently cured, while one (aged forty-eight) eventually died of coronary artery disease and no malignancy could be demonstrated at autopsy. Whether the anxiety and physical strain of pelvic surgery was a factor in her death is opento question, but she will be included statistically in the 'apparent cures' of the disease.

Of the twelve patients apparently cured (and with between three and seventeen years follow-up) two were treated by nothing more than curettage and observation after the passage of a mole that the pathologist had classified as malignant. Two others had been treated by hysterectomy for a local recurrence in the uterus and in one case hysterectomy had been followed by the regression of vaginal metastases without any ancilliary treatment. It might be contended that some revision of the diagnosis would be permissible in one or other of these cases.

The other seven had received irradiation although two of these patients had already undergone pelvic surgery that might have been successful without the D.X.R. In the remaining five cases, however, the irradiation appeared to have been directly responsible for the involution and cure of metastatic lesions that had been diagnosed beyond reasonable doubt. The sites of these lesions were the vagina (two patients), the uterus (once), the lungs (once)

and in the final patient there appeared to be com- plete regression of malignant lesions in the uterus, the vagina and the lungs.

Of the eleven deaths, nine had received no irradia- tion. These included three patients whose diagnosis was made only by the discovery of inoperable abdominal masses, and three others diagnosed by curettage who were then found to have such advanced secondary deposits of turnout that they died before treatment could be started. One other suffered cerebral haemorrhage from a secondary in the brain as the first intimation of the disease, while one presented with haemoptysis six years after the passage of a hydatidiform mole and the diagnosis was achieved too late for treatment. Finally, there was a girl of nineteen who was still bleeding from the uterus four weeks after the birth of her first baby, and who was dead in two months from chorion-cancer in the uterus, liver and lungs.

There appear to be only two patients treated unsuccessfully by irradiation. The former was diagnosed in 1950 by curettage for uterine bleeding, following six pregnancies of which three had been hydatidiform moles (thelast in 1947). Hysterectomy was followed by irradiation, but she died with massive growth in lungs and the upper abdomen. The other of these unsuccessful cases is particularly instructive. A married woman of thirty, who had miscarried two of her previous three pregnancies, was seen with five months amenorrhoea, sickness and a vaginal tumour. The uterus was barely enlarged, the A-Z test was strongly positive, the vaginal tumour proved to be chorion-cancer and her chest was full of secondaries. Irradiation was commenced following a blood transfusion and she made splendid progress, the vaginal tumour shrinking rapidly and the pulmonary shadows melting away, but on the last day of treatment she suddenly died from cerebral haemorrhage. Autopsy showed a large metastasis that had been unsuspected in the brain, while the uterine primary and pul- monary secondaries had undergone marked re- gression following irradiation.

DISCUSSION

The unpredictable course of tumours classified as chorion-carcinoma leads inevitably to difficulty in the assessment of the value of treatment in isolated cases, for a favourable result might be due either to response to therapy or to inaccurate classification. The above series is strongly sug- gestive that irradiation conveys benefits in respect of involution of metastatic growth in sufficient

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262 C L I N I C A L R A D I O L O G Y

cases to have made it an essential part of the routine treatment in the decade that ended in 1960. Its limitation is shown only too clearly in the case that died of undiagnosed cerebral meta- stases while undergoing successful treatment to other parts of the body.

In the last few years a number of alternative methods of treatment have been suggested, and in particular the use of the folic acid antagonist methotrexate. This has been used with some success by Chan (1962b), Hertz (1961), Manahan (1961), Manly (1961) and Buckle (1961). Nitrogen mustard has been used by Webb (1962), while Chambers (1961) reported successful treatment of vaginal and pulmonary secondaries following pituitary destruction by Yttrium 90. Finally, the possibility of immunological treatment, based upon the creation of homograf t immunity against the husband's leucocytes, has been explored without much success by Hackett and Beech (1961) and commented upon by Schmidt and Hertz (1961).

I t would appear that the present decade represents the dawn of a new era in the treatment of chorion. carcinoma, but the value of all these new and exciting remedies must be measured against the proven success of irradiation as carried out previously.

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68, 280; CHAN, D. P. C. (1962a). Brit. reed. J. 2, 953. CHAN, D. P. C. (1962b). Brit. med. J. 2, 957. HACKETT, E. & BEECH, M. (1961). Brit. med. J. 2, 1123. HERTZ, R., LEWIS, J. & LIPSETT, M. B. (1961). Amer. &

Obstet. Gynec. 82, 631. KING, G. (1956). Proc. R. Soc. Med. 49, 381. MANLY, G. A. (1961). J. Obstet. Gynaee. Brit. Emp. 68, 277. MANAHAN, C. P., BENITZ, I. & ESTRELLA, F. (1961). Amer. J.

Obstet. Gynec. 82, 641. SCHMIDT, P. J. & HERTZrR. (1961). Amer. J. Obstet. Gynee.

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