1990, The British Journal of Radiology, 63, 206-208

Radiotherapy of Morbus Gorham-Stout: the biological value of low irradiation dose By L Handl-Zeller, M D and G. Hohenberg, M D Department of Radiotherapy and Radiobiology, University of Vienna, Alser Strasse 4, A-1090 Vienna, Austria

(Received July 1989 and in revised form August 1989)

Abstract. Morbus Gorham-Stout is a very rare disease. A patient with this disease was treated at the University Clinic of Radiobiology in Vienna. The clinical and radiological findings place special emphasis on the radiotherapeutic treatment, and the biological basis of the recommended dose is discussed.

The first case of progressive bone osteolysis combined with a soft-tissue tumour was reported in the Boston Medical and Surgical Journal (Jackson, 1838), with a follow-up in the same journal (Jackson, 1872). This was the only case observed before Xrays were discovered. Another case was reported by Branch (1945), and an overview of patients with vanishing bones was made by Gorham and Stout (1955). They concluded that the progressive osteolysis is always associated with an angiomatosis of the blood and sometimes angiomas of lymphatic vessels. The use of radiotherapy and the appropriate radiation doses are controversial, as discussed in the literature (Hoffman et al, 1980; Bek et al, 1981; Polivy & Zimbler, 1983). In our view, radiotherapy in Morbus Gorham-Stout is the preferable treatment. Here we attempt to answer the question as to why a relatively low dose of irradiation can be effective in this disease. Clinical and radiological findings

The disease may imitate a locally aggressive tumour, involving bones and adjacent tissues, although there are no other attributes of neoplastic disease or inflammatory process. The disease is neither inherited nor congenital. Fractures and pain in the bones may be present (Hambach et al, 1958; Sage & Allen, 1974; Heyden et al, 1977; Ross et al, 1978; Listewnik et al, 1986). In a few of the reported cases, radiographs depict early massive osteolysis. Johnson and McClure (1958) distinguished between an intraosseous and an extraosseous stage: in the early intraosseous stage, massive osteolysis resembles a "non-descript patchy osteoporosis", but later its appearance becomes that of any expanding non-sclerosing intramedullary lesion. There is no neoplastic osteogenesis or significant reactive bone formation. Having produced a disruption in the cortex of the encasing bone, the angioma invades and proliferates in the surrounding soft tissues. Bony resorption continues, but is now caused by the extraosseous as well as by the intraosseous component of the angioma. Confirmation of the roentgen diagnosis of 206

massive osteolysis can be achieved by arteriography and phlebography. It has been stated that irradiation can stop the osteolysis, but the disease may be arrested spontaneously too (Johnson & McClure, 1958; Campbell et al, 1975; Heyden et al, 1977; Ross et al, 1978; Feigel et al, 1981; Kolar et al, 1981; Len & Brunner, 1981). Therapeutic treatment

In most cases, bone resorption stops spontaneously. Many treatment modalities have been reported in cases of progressing disease. The two principal ones are surgical resection and radiotherapy. Other treatments which have been used include vitamin D, parathyroid hormone, androgens, calcium, adrenal extracts, vitamin B12 and others. Sympathectomy was used in one patient without any effect on the disease (Leriche, 1937). Surgical treatment of massive osteolysis has consisted of amputation and local resection, with and without replacement prostheses or bone grafts. Attempts at bone grafting have met with variable success (Aston, 1958; Butler et al, 1958; Halliday et al, 1964). There are also several reports showing involvement of grafts by the osteolytic process (Aston, 1958). In recent years the use of early radiotherapy has become more popular, in some instances with remarkable success (Murphy, 1978; Henck, 1979; Hoffman et al, 1980; Bek et al, 1981; Polivy & Zimbler, 1983). Despite the fact that many cases of bone resorption stop spontaneously, radiotherapy should be carried out as soon as possible after diagnosis, giving the destruction no time to spread. In planning a radiotherapy treatment, the volume should include not only the affected bones but also the surrounding soft tissues showing clinical or, better still, angiographic or computed tomographic signs of angiomatous invasion. Normally anteroposterior fields are used. If photons of higher energy (1 MeV) are unavailable or anteroposterior diameter is greater than 22 cm, a multiple field technique should be used. One should avoid the perineum or block parts of the vulva or scrotum if possible. The British Journal of Radiology, March 1990

Radiotherapy of Morbus Gorham-Stout

Recalcification, if it occurs, takes 4 months to become evident (Libschitz & Hortobagyi, 1981). Biological basis of applied radiation dose

Endothelial cells of proliferating capillaries or capillary-like vessels are extremely radiosensitive (Reinhold & Buisman, 1973; Reinhold, 1974). The classic histological appearance of vessel lesion in irradiated tissue is well documented. It is similar to the abnormalities found as a consequence of hypertension; hypertension and irradiation damage to vessels would appear to be linked in some way. Byrom (1963) reported the presence of irregularly spaced areas of constriction and dilation in the vessels of hypertensive animals. It has been suggested that similar changes could occur in irradiated blood vessels (Hopewell, 1968; Hopewell & Wright, 1970), the constrictions being formed by clones of vessel wall elements, i.e. endothelial or muscle cells. These clones of cells originate from the irregularly spaced reproductively viable cells that remain after irradiation. At the time of irradiation the majority of cells in the vessels are rendered reproductively non-viable. Cell loss occurs as these cells attempt to divide, stimulating the viable cells to produce irregularly spaced clones of cells along the length of a blood vessel. If the radiation dose increases, the number of viable cells is reduced until no occlusive reactions are possible (Hopewell, 1974). The observation of a maximum reduction in blood flow in mouse tail skin after 30 Gy and no modification after higher doses could be explained by the absence of proliferative endothelial cells (de Ruiter & van Piitten, 1975). Case report The patient, born in 1964, was admitted to the University Clinic for Radiotherapy in 1980 because of increasing pain in the right hip and seat which had continued for 2 years. A radiograph obtained elsewhere in March 1980 revealed quite discernible osteolytic destruction of the right os ilium with evidence of pathological fracture of the right os ischium. A bone survey disclosed no other areas of damage. On removal of a bone sample from the tuber ischii, serous fluid exuded from the tissues immediately outside the tuber ischii, giving the impression that a cystic process was present in the abdominal cavity. A contrast medium injection in this area by means of the inserted radon drain showed a massive colouring right into the retroperitoneal cavity. These results helped to establish the presence of a lymphangioma. Specimens of the partially destroyed bone showed an increased content of thinwalled vessels, some containing erythrocytes. In April 1980 the angiectatic tumour and also some retroperitoneal enlarged lymph nodes were resected at the orthopaedic department. Histologically the lymph nodes showed no evidence of disease. A post-operative lymphangiogram was normal, as was a subsequent aortogram. No obvious connection with the vascular or lymphatic circulation was noted. Postoperatively the patient was free from complications, and used crutches to ease the strain. The patient was kept under observation at the orthopaedic department. Subsequent radiographic check-ups continued to show a relatively rapid progression of osteolytic changes. For this reason, radiotherapy of the affected pelvic bones was started.

Vol. 63, No. 747

In our patient's case, radiotherapy was started at the time of demonstrable clinical and roentgenological progression. Our patient received 30.6 Gy yrays via opposing 22/14 cm ports in 17 days (single dose: 180 cGy, target volume-skin distance: 8 cm) ventral and dorsal, with sufficient margin of tissues. At the end of the radiation treatment the pains in the area of the right hip were considerably relieved. The only symptom present was slight pain due to pressure of weight. Following radiotherapy, our patient's radiograph showed slight recalcification. The arrest of the osteolytic process can therefore be regarded as an effect of radiotherapy. Discussion

There is a controversy concerning different treatment modalities for Morbus Gorham-Stout, especially in the area of radiotherapy. Poilleux and Codron (1960) report a patient for whom no active therapy was attempted. This ended in the devastation of the pelvic bones with a large number of pathological fractures and the patient's invalidity. Because of the rarity of this disease, the longterm effectiveness of radiation therapy cannot as yet be critically evaluated. An analysis of the literature reveals different opinions concerning the effect of radiotherapy: authors describing radiotherapy as ineffective used total doses ranging from a few cGy up to 20 Gy. Where a higher total dose was applied: up to 30 Gy or more, the effect was quite remarkable, as with our patient. Arrest of the osteolytic process and partial recalcification of the destroyed bone could be seen (Knoch, 1963; Heyden et al, 1977). The radiation dose therefore seems to be essential. In most cases the greatest part of the soft-tissue tumour is removed. Moreover, a dose of about 40 Gy is regarded as sufficient for benign tumours. Biological considerations give a hint as to what total dose should be used in this disease. On increasing the radiation dose, the number of viable cells is reduced until no occlusive reactions are possible. The observation by Casarett (1964) that vascular occlusive changes by endothelial cells are inhibited and parenchymal damage reduced after exposure to high doses in polonium irradiated rat kidneys can be explained on the basis that only a negligible number of viable cells remain to form clones under these conditions. A similar explanation was used to explain the reduction in vascular damage in rat brains treated with 4000 R as compared with those receiving 3000 R (Hopewell, 1974). This would also explain why hypertension loses its "radiosensitizing" effect, although it has been suggested that endotheJiaJ cells are responsible for vessel occlusion and vascular spasm (as is suggested for hypertension). This is supported by Bosniak et al (1969) who reported vascular spasm in irradiated vessels using an arteriographic technique. Bullough (1971) agrees that radiation therapy would appear to be a rational approach to the treatment of Gorham's disease but one has to bear in mind the inherent dangers of inducing sarcoma. Megavoltage irradiation, which produces equal absorption of energy in bone and soft tissue, induces 207

L. Handl-Zeller and G. Hohenberg

fewer bone sarcomas than orthovoltage irradiation, which has a higher absorption in bone compared with soft tissue (Tountas et al, 1979). The dose used in Morbus Gorham-Stout is the same as in juvenile angiofibroma, and the risk of radiationinduced cancer following treatment of juvenile angiofibroma is very low. None of 47 angiofibroma patients irradiated at the Radiumhemmet who were followed for between 10 and 40 or more years developed a radiation-induced cancer (Jereb et al, 1970) and there were no instances among 45 irradiated patients at Princess Margaret Hospital with from 2 to 20 years of follow-up (Fitzpatrick, 1970, Fitzpatrick et al, 1980). In conclusion, Gorham-Stout's syndrome is a rare and clinically serious disease, which, if untreated, can be mutilating despite the fact that spontaneous arrest can occur. Early irradiation of the appropriate selected volume of tissues using adequate doses of radiation can stop osteolysis and can achieve at least partial recalcification of the destroyed bone tissue. References ASTON, J. N., 1958. A case of massive osteolysis of the femur. Journal of Bone and Joint Surgery, 40B, 514. BEK,

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The British Journal of Radiology, March 1990

Radiotherapy of Morbus Gorham-Stout: the biological value of low irradiation dose.

Morbus Gorham-Stout is a very rare disease. A patient with this disease was treated at the University Clinic of Radiobiology in Vienna. The clinical a...
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