SARCOMA FOLLOWING X-RAY THERAPY FOR GRAVES' DISEASE
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1 SARCOMA FOLLOWING X-RAY THERAPY FOR GRAVES' DISEASE By P. H. JAYES, M.B., B.S., F.R.C.S., and R. H. DALE, M.B., B.Chir., F.R.C.S.Ed. From the Plastic Surgery and Jaw Injuries Centre, East Grinstead IT is well known that malignant neoplasms are liable to develop as complications of irradiation burns of the skin. The majority of these growths are squamous-cell carcinomata. The appearance of a sarcoma is rare. In the case here described a sarcoma appeared in the tissues of the neck, which had been burned by X-rays in the treatment of Graves' disease. CASE HISTORY The patient is a married woman aged 61. Thirty years ago, in 1919, she was treated for thyrotoxicosis by X-rays at King's College Hospital, London. The details of the treatment are not available, but it apparently continued over a period of three years. The thyrotoxicosis was relieved, but the patient gradually developed a typical irradiation burn of the skin. In December 1948, twenty-nine years after the treatment, she first noticed a lump, situated just above and to the left of the sternal notch, within the area of burned skin. It gradually increased in size, and in May 1949 the skin over it broke down and an ulcer developed. She was admitted to this unit on ISth August 1949, when she presented the appearance shown in Fig. I. On examination there was an area of skin on the anterior surface of the neck, measuring 4½ by 3 in., which exhibited the typical appearance of an irradiation burn. It was pale, thin, dry, scaly, and hairless ; there were multiple telangiectases on the surface ; it was adherent deeply to scar tissue in the neck. Above and to the left of the sternal notch was a hard mass, with a raised fungating surface, roughly round in shape, measuring 2½ in. in diameter. There was no evidence of lymphatic spread. The tumour was diagnosed as an epithelioma, although there were several unusual features about the clinical appearance. It was much more fleshy and exuberant than the typical epithelioma arising in scar, and its rate of growth was unusually rapid. It was decided to excise the whole irradiated area, including the turnout, and to close the defect by means of a delayed transposed flap from the right side of the neck and chest. A flap measuring 8 by 3~ in. was designed and delayed in two stages, under local anmsthesia, at an interval of fourteen days (Figs. 2 and 3). During this time the tumour was seen to have increased considerably in size. On the eleventh day after the second delay operation the irradiated skin of the neck, together with the tumour, was excised down to and including the deep fascia. The infra-hyoid and sterno-mastoid muscles were found to be normal and not involved in the disease. The defect was closed by means of the transposed flap, the secondary defect being covered with a split-skin graft. 2 E ~ 147
2 148 BRITISH JOURNAL OF PLASTIC SURGERY FIG. I Appearance on admission. FIG. 2 After the first delay operation. FXG. 3 FIG. 4 After the second delay operation. Final appearance.
3 SARCOMA FOLLOWING X-RAY THERAPY FOR GRAVES' DISEASE 149 Pathological Report.--Grossly, the specimen consisted of an oval yellowish mass about 2½ in. in diameter and raised about ½ in. above the skin surface. Section (report by Professor H. A. Magnus, King's College Hospital).- " Sections (Figs. 5, 6, and 7) show a sarcoma with a uniform structure, the cells composing it being spindle-celled in shape. Mitotic figures are frequent, and the tumour is infiltrating fat and connective tissue. It contains little collagen, but very considerable quantities of reticulin fibre are present." The flap healed soundly (Fig. 4), and the patient has remained well since Fro. 5 Section of tumour stained with heematoxylin and eosin. I IO. operation. When last seen on Ioth January 1951, sixteen months after operation, she was in excellent health. There is no evidence of local or metastatic spread. DISCUSSION Soon after the discovery of X-rays, in 1895 by Roentgen, examples of irradiation burns, or chronic X-ray dermatitis, began to appear. By 19o2, within seven years of the discovery, cases of malignant disease supervening upon chronic X-ray dermatitis were being reported. The majority of turnouts were squamous-cell carcinomata, but occasional cases of sarcoma occurred. The latter were especially common following the X-ray treatment of lupus vulgaris. In animals spindle-cell sarcomata have been produced by irradiation of tissue, which has been made the site of chronic inflammation. It would seem that chronic inflammatory tissue is more susceptible than normal connective tissue to the development of sarcoma following exposure to X-rays (Willis, 1948 ; Michalowski, 1946 ; Silverstone, 1942 ).
4 150 BRITISH JOURNAL OF PLASTIC SURGERY FIG. 6 Section of tumour stained with h~ematoxylin and eosin FIG. 7 Section of tumour stained by silver impregnation~ showing reticulin. I2O.
5 SARCOMA FOLLOWING X-RAY THERAPY FOR GRAVES' DISEASE I5I It has been suggested that many of these tumours, whilst having the general appearance of spindle-cell sarcomata, are, in fact, atypical epitheliomata with a spindle-cell stroma ; that cell nests can be discovered on careful search of the whole tumour (Michalowski, 1946 ; Nuytten and Driessens, I939). This has not been confirmed by workers in this country. A small number of cases have been reported in which sarcomata have developed in the scars of thermal burns. Fleming and Rezek (1941) reported a case in which a spindle-cell sarcoma developed in a burn scar forty-nine years after burning. The tumour was highly malignant, and the patient died of multiple metastases nineteen months after it had been excised. Niedelman (1946) described a spindle-cell sarcoma arising in the scar of a thermal burn of the chest wall forty-two years after burning. This was a fungating ulcerative growth, very similar to the turnout described in this report. Niedelman recognised it as the " Fibrosarcoma Protuberans " described by Darier (1924) and Hoffman (I925). Such tumours are reputed to be of low malignancy and to be cured by surgical removal (Hertzler, 1926). Arnheim (I942) gave an account of a case, the history of which closely resembled that of the case reported in this paper. He claimed it to be the " first reported case of sarcoma of the neck following X-ray therapy for Graves' disease." The growth appeared twenty years after the exposure to X-rays. In this case, however, there was no ulceration of the skin. The tumour was excised, and five months later an operation was performed on an extension of the growth in the tissues of the neck. Two years later there had been no further recurrence. Section of the tumour showed it to be a spindle-cell sarcoma. CONCLUSION Spindle-cell sarcoma supervening upon chronic X-ray dermatitis is a rare condition. It has been shown that sarcoma is more likely to occur after the irradiation of chronically inflamed tissue, as in lupus vulgaris. The case reported in this paper is of interest in that a spindle-cell sarcoma appeared in an area of chronic X-ray dermatitis thirty years after the treatment of Graves' disease with X-rays. There was no evidence of any associated chronic inflammatory lesion. The tumour had the clinical characteristics of " fibrosarcoma protuberans." Insufficient cases have been described to justify any statistical conclusion. We are greatly indebted to Professor H. A. Magnus for his help and advice and for his report and photomicrographs of the section ; also to Mr Gordon Clemetson for the clinical photographs. REFERENCES ARNHEIM, E. (1942). J. A/It. Sinai Hosp., 9, 2. DARIER and FERRAND (I924). Ann. Derm. Syph. Paris, 5, 545. FLEMIIqG, R. M., and RrZEK, P. R. (I94I). Amer. J. Surg., 54, 2. HERTZLER, A. E. (1926). Amer. J. Surg., 84, 489. HorrMan, E. (x925). Derm. Z., 43, I. MICH~OWSKI, R. (1946). Acta Derm. Ven., 24, 3. NIEDELMAN, M. C. (1946). Ann. Surg., I23, 2. NOYTTEN and DRIESSENS (1939)- Quoted by R. Michalowski (I946). SILVERSTONE, S. M. (1942). J. Mr. Sinai Hosp., 9, 2. WILLIS (1948). " Pathology of Tumours." London : Butterworth & Co. Ltd.
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