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A 22-year-old women developed breast cancer 15 years after radiotherapy to the lung for metastatic Wilms tumor. Her 32-year-old mother died of bilateral breast cancer, suggesting a genetic predisposition to radiogenic cancer. Recent improvements in the survival of children with certain cancers necessitate long-term surveillance for iatrogenic neoplasia, particularly when familial susceptibility is evident.
A 35-year-old man who received radiation for thymic enlargement as a child and subsequently developed both thyroid and breast cancer is reported. This appears to be the first case in which this association has been reported in a male.
Many more children with cancer are being cured, often as a result of aggressive treatment regimens. These employ several modalities and multiple chemotherapeutic agents. The acute complications resulting from this type of treatment are relatively well known. Those that develop later are becoming better understood; some are formidable. The challenge in pediatric oncology lies in developing better treatment strategies with a view to minimizing normal tissue damage while achieving higher cure rates. The cooperative clinical trial mechanism is well-suited to testing new treatment regimens designed to achieve these goals.
A patient who received postoperative radiation therapy for the treatment of a chromophobe adenoma developed a fibrosarcoma of the pituitary gland region 10 years later. A single course of irradiation was given with a total dose to the pituitary of 4092 rad in 21 fractions and 29 days using Cobalt 60 radiation at a source to skin distance of 80 cm.
A case is reported of a patient who developed a histologically unusual sarcoma in the axilla and chest wall 8 years after receiving radiation therapy (6500 rad) for carcinoma of the breast. This sarcoma showed light- and electron-microscopic features of a malignant fibrous histiocytoma, a tumor not documented among 24 previously reported cases of postirradiation sarcoma following the diagnosis of breast carcinoma. In addition, the literature is reviewed and discussed regarding postirradiation sarcoma in general following breast carcinoma.
Potential posttreatment complications for patients with the lymphomas and leukemia include: 1) impairment of growth and development in children, 2) CNS disturbances encompassing psychologic, intellectual and neurologic expressions, 3) gonadal effects--endocrine, reproductive, teratogenic and genetic, 4) dysfunction of other organs and structures, such as the thyroid, lung and heart and 5) oncogenesis. Many of these adversities are occasioned by radiation therapy, but chemotherapy also can be responsible for some long-term deleterious consequences. The results of combined chemo- and radiaton therapy are becoming better understood, and require further elucidation because earlier stages of the disease are being managed by combined chemo- and radiation therapy regimens.
Previous reports of radiation-related neoplasia have relied primarily upon patients treated by orthovoltage to low doses for benign disease. This survey is believed to be the first to assess the incidence of second neoplasms following megavoltage therapy. The source was the records of all long-term pediatric survivors (88 patients) who were treated with megavoltage radiation (cobalt 60) at the University of Minnesota. There was an average follow-up period of 14 years during which 7 second neoplasms were discovered (8%). Five were not associated with prior radiation. Both radiation-related neoplasms were associated with low doses and one was without significant morbidity. Two of the seven neoplasms were malignant; one was not associated with radiation while the other was associated with prolonged chemotherapy and low dose radiation (1%). The only fatal second neoplasm was not associated with radiation but developed 5 years after prolonged chlorambucil treatment. This review reveals the tendency of childhood cancer victims to develop other neoplasms regardless of radiation. The finding of neoplasia induction only at low radiation doses supports the Gray hypothesis of decreased tumor induction at high doses through increased cell killing.
A patient who developed an immunoblastic leukemia of T-cell type two and one half years after initial diagnosis of mixed cellularity Hodgkin's disease, stage IIIB, is described. The patient's course was characterized by an initial 15-months remission following radiation therapy. A relapse of Hodgkin's disease was treated with intensive chemotherapy. Thirteen months later the patient entered a rapid terminal course with multiple organ infiltrates and a leukemic peripheral blood. The leukemic phase was characterized by a 55,000 WGC with 48% immunoblasts, greater than 90% of which marked as T-cells. Although acute myelogenous leukemia, acute lymphocytic leukemia, lymphosarcoma cell leukemia and other tumors have been described in Hodgkin's disease after intensive therapy, this is the first report of the unusual association of a T-cell immunoblastic leukemia with Hodgkin's disease.
Lymphangioma circumscriptum, a rare long-term complication of chronic lymphedema, has been described only twice following radical mastectomy. The case discussed in this report developed 25 years after radical mastectomy and radiation therapy. Both this condition and lymphangiosarcoma, its malignant counterpart, may arise in lymphedematous extremities regardless of the etiology of the lymphatic obstruction.
Long-term observations were made for the development of secondary neoplasms following radiotherapy of animal tumors. Experimental tumors were 3rd generation isotransplants of a mammary carcinoma which arose spontaneously in a C3Hf/He mouse. A single dose of TCD20-TCD98 was followed by weekly observations. Most recurrences were observed in the first 150 days, while only a few were seen in the subsequent 150 days. Secondary neoplasms developed frequently following this period, i.e., 41 out of 67 animals surviving more than 300 days developed secondary neoplasms. They were osteogenic and soft tissue sarcomas, and half the new tumors were found within 490 days after radiotherapy. The results obtained were compared with literature reports of secondary neoplasms following postoperative radiotherapy for carcinoma of the breast and treatment of retinoblastomas. Most of these secondary human neoplasms were nonepithelial sarcomas as in the present study. Secondary carcinomas have been reported following radiotherapy of carcinoma in other locations, i.e., the cervix or head and neck; however, only a limited number of studies have been reported.
Ten cases of irradiation induced sarcoma of bone which fulfilled Cahan's criteria were seen in a twenty year period at the Princess Margaret Hospital. The overall incidence of this complication is 0.035% of all irradiated five year survivors. Combining our data with three other large series presented in the literature, a dose complication curve could be deduced. On the basis of the human and animal data reviewed, it was concluded that the risk of radiation induced sarcoma is so low in the dose range of modern radiotherapeutic practise that it does not represent a contraindication to the use of radiation therapy.
Thyroid neoplasms occurred in two patients 14 and 18 years after treatment with radiation for medulloblastoma. One patient has a papillary cancer and the other patient had multiple adenomas and a Hurthle cell adenoma. In addition, the latter case had foci of hyperplasia plus a microfollicular transformation, which has not been described in association with prior thyroid irradiation. The radiation doses delivered to the thyroid through posterior cervical spinal ports (2000--3000 roentgens) fall within the upper range of radiation dosage associated with induction of neoplastic changes within the thyroid.
Evaluation of radiation therapy for a given neoplasm includes consideration of possible treatment complications as well as potential benefit. A 43-year-old male with a glomus jugular tumor or the right middle ear had received 4480 rad to the right middle and inner ear and temporal bone. Eight years later, he developed an anaplastic astrocytoma of the right cerebellar hemisphere. At this time a third neoplasm, a left carotid body tumor, was demonstrated angiographically. Although radiation can be implicated in the genesis of the glial neoplasm, the presence of two neural crest derived tumors suggests that a lowered threshold for neoplastic transformation in neuroectodermal cells may have been an additional factor. Long-term follow-up of large numbers of patients with glomus jugulare tumors will be necessary to determine if multiple paragangliomas predispose to radiation-associated gliomas.
Two patients with anaplastic carcinoma of the thyroid following irradiation for Hodgkin's disease are presented, and the previously reported cases briefly reviewed. The risk of late development of thyroid carcinoma is life-long and high-dose irradiation in patients with prolonged life expectancy may result in anaplastic carcinoma as well as less malignant histological forms.
The difficulties encountered in establishing a diagnosis of a malignant peritoneal mesothelioma are emphasized in a patient who developed the lesion 16 years after radiation therapy for a seminoma of the testis. Historically, histologically, electron microscopically, and by microincineration, there was no evidence of asbestos exposure. We believe that present lesion may be a consequence of prior radiation therapy.
We report a 60-year-old woman with a history of x-ray therapy for generalized hirsutism at 20 years of age who at the age of 37 years developed the first of numerous basal cell epitheliomas on her trunk, including chest, on a background of radiation damaged skin. At the age of 51 years one of the basal cell epitheliomas was biopsied and an incidental histologic finding was a breast carcinoma. The basal cell epithelioma is clearly linked with x-ray exposure; breast cancer is less so although there is impressive epidemiologic evidence supporting an association between human breast cancer and radiation exposure. In view of an association between thyroid cancer and dermatologic x-ray therapy, further investigation of such an association with breast cancer should be considered. It may be wise to evaluate patients who received dermatologic x-ray exposure to their breasts for possible breast cancer and to consider radiation induced skin damage on or near the skin overlying the thyroid or breasts as a cutaneous marker of internal malignancy or potential internal malignancy.
Two cases of plexiform tumor of the uterus are presented. Both were incidental microscopic findings in leiomyomatous uteri and had the typical branching cords of small, polygonal cells with scanty cytoplasm and vesicular nuclei. Ultrastructurally the cells had features of smooth muscle differentiation such as actin-like filaments, dense bodies, peripheral dense plaques, pinocytotic vesicles, and incomplete basal lamina. Their close relationship to capillaries resembled the structure of glomus tumor and vascular leiomyoma and suggested histogenetic kinship among these neoplasms.
This paper reports a case of angiosarcoma of the terminal ileum in a 66-year-old female. This angiosarcoma developed 8 years after postoperative irradiation for ovarian carcinoma. This case appears to be the sixth case of angiosarcoma arising at the site of therapeutic irradiation thus far reported in the literature. The fact that the angiosarcomas in these cases developed in anatomic sites, which are unusual for angiosarcomas in general, suggests that there is a cause-and-effect relationship between irradiation and angiosarcoma. Apart from the direct carcinogenic effect of irradiation, prolonged stimulation for tissue repair resulting from tissue damage secondary to irradiation-induced vascular changes may also play an etiologic role in the development of angiosarcomas in these cases.