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alveolar rhabdomyosarcoma or a clear-cell sarcoma. Electron ... mesenchymal neoplasm (sarcoma). .... aneuploid cells in cultures of peripheral blood leuco-.
1987, The British Journal of Radiology, 60, 89-90

JANUARY

1987

Case reports Adrenal-cell carcinoma and rhabdomyosarcoma occurring in father and daughter: "SBLA" syndrome? By M. J. Tomlinson, M.R.C.P. and J. A. Bullimore, F.R.C.R. Bristol Radiotherapy and Oncology Centre, Horfield Road, Bristol

(Received March 1986 and in revised form June 1986)

The association of adrenal-cell carcinoma and softtissue sarcoma within the same family has been reported and may be an example of a hereditary cancer syndrome. A report is given of a further example of such a family.

acneiform rash for 3 weeks. She had excessive underarm sweating and had needed to use deodorants. She was also noted to be tearful. She had always tended to drink a lot, demanding drinks at night, and had polyuria. She had no headaches, had normal vision and had not had any vaginal bleeding. Apart from a febrile convulsion at age 17 months, her past history was unremarkable. She was a large child with height and weight on the 97th percentile. (Her father is 5 foot 10 inches and mother 5 foot 4 inches.) There was no breast development and no abdominal masses were palpable. She had marked clitoral hypertrophy, early pubic hair and rugose labia. There was no axillary hair but the axillae were moist. The initial diagnosis was virilisation due to congenital adrenal hyperplasia, but 17 hydroxy-progesterone levels were normal. There was, however, a high urinary androgen and cortisol level. The excretion of androgen was not suppressed by dexamethasone, and the excretion of cortisol was only partially suppressed. A skull radiograph was normal. Her bone age was 6 years and 5 months. Intravenous pyelography demonstrated a small area of curvilinear calcification in the region of the right adrenal gland, which did not enhance during the nephrogram stage. An inferior venocavogram showed a round mass, diameter 2 cm, above the right renal pole. A CT scan confirmed an adrenal mass with calcification. A right adrenalectomy was performed under hydrocortisone cover. A well encapsulated tumour was found to be arising from the adrenal gland. There were no clinically involved lymph nodes. The tumour was excised with its capsule apparently intact. Histology showed a lobulated adrenal tumour of variable histological appearance with infrequent mitoses but many tumour giant cells. In some areas the border of the lesion was poorly defined. The appearance was that of an adrenal cortical tumour, thought to be a carcinoma because of the nuclear pleomorphism and the clinical presentation. As the tumour was believed to be penetrating the capsule, and therefore may not have been completely excised, postoperative radiotherapy to the tumour bed and para-aortic region was advised, and was tolerated well. She is making good progress, her growth has slowed and the signs of precocious puberty have regressed. She has no signs of recurrence on clinical examination or on abdominal ultrasound, and 24 h urinary androgens have remained within normal limits. On enquiry, a further member of the family, the father's maternal aunt, has been treated for carcinoma of the breast, but no other history of familial cancer has been elicited.

CASE REPORT

A 34-year-old Caucasian man presented in March 1983 with a 3-month history of cramp in the left leg followed by the appearance of a painless lump. He had a 5 cm x 5 cm mass in the left calf which was firm and was not attached to the skin but tethered to deep tissues. Malignant mesenchymal cells suggestive of a rhabdomyosarcoma were apparent from fineneedle aspiration. Histology obtained at open biopsy revealed fragments of fibrous connective tissue extensively infiltrated by an undifferentiated, highly vascular malignant tumour with large areas of necrosis and occasional multinucleate tumour giant-cells. The histological appearances and the results of special staining techniques favoured a diagnosis of either an alveolar rhabdomyosarcoma or a clear-cell sarcoma. Electron microscopy confirmed the appearances of an undifferentiated mesenchymal neoplasm (sarcoma). A lymphogram showed metastatic involvement of the upper para-aortic lymph nodes. A chest radiograph appeared normal, but a computed tomography (CT) scan of the chest revealed several small, left-sided pulmonary metastases. Chemotherapy comprising vincristine, Adriamycin (Farmitalia Carlo Erba Ltd), cyclophosphamide and actinomycin D in a 3-weekly cycle was commenced, but response was not marked. There was no progress of intra-abdominal disease on a follow-up lymphogram, but a pulmonary metastasis became visible on a chest radiograph. Because of persisting discomfort in the calf, and the patient's reluctance to have further chemotherapy at that time, the primary lesion was irradiated using 60 Co y rays. The patient then accepted further chemotherapy and received cisplatinum 30 mg IV at 3-4weekly intervals. He tolerated this extremely well and was able to work fully between treatments. The erythema reduced and the mass became impalpable. Unfortunately, the pulmonary metastases, which had been static, recommenced growth and became visible bilaterally on a chest radiograph. They did not respond to increased doses of cisplatinum or to VP16 and ifosfamide, methotrexate l g IV with folinic acid rescue or mitozantrone. In September 1985 recurrence at the primary site was noted. The patient has a daughter who also presented in March 1983, aged 2 years and 4 months, with a history of rapid growth for the previous 4 months. (Height had been in the normal range at a routine 2-year examination.) She had developed pubic hair over the same period and had had an

DISCUSSION

Kenny et al (1968) described seven cases of virilising tumours of the adrenal cortex, in four of which there 89

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was a positive family history of malignancy. This was particularly striking in two families in which four other individuals had cancer. In one family the child's father and sister died of malignant bone tumours, the maternal grandfather died of cancer of the stomach and a maternal great-aunt had breast cancer. In the other family the mother had breast cancer, a maternal aunt had died of a malignant breast tumour, a maternal uncle had died of a brain tumour and a maternal cousin had died of an adrenal tumour. Both children died of metastatic disease from adrenal cortical carcinoma. An American 8-year nationwide survey (Miller, 1971) of deaths from childhood leukaemia and solid tumours, undertaken to ascertain cancer mortality during childhood in siblings, described two families in which one child had adrenocortical carcinoma and another had rhabdomyosarcoma. The frequency of these neoplasms is so low that only one such occurrence is expected by chance in the United States in 130 years. In one of these families a third child had brain cancer (cell type unavailable) and in the other the mother developed an astrocytoma at 30 years of age (Li & Fraumeni, 1969a). There have been other case reports of adrenocortical carcinoma and brain tumours in close relatives; these neoplasms have also been reported as double primaries (Fraumeni & Miller, 1967; Epstein et al, 1970). Bottomley and Condit (1968) reported a familial cancer aggregation of sarcoma, brain tumour, breast carcinoma, leukaemia and adrenal cortical carcinoma and suggested that the tendency to develop malignancy in this family was due to an autosomal dominant factor. In some relatives they found an increased percentage of aneuploid cells in cultures of peripheral blood leucocytes (Bottomley et al, 1971). Li and Fraumeni (1969b, 1975) studied similar families and defined the association as a syndrome. They too suggested that inheritance of the syndrome could be due to an autosomal dominant gene with variable expression. However, they thought that inheritance alone was probably insufficient to explain the range of neoplasms seen, and postulated an environmental influence such as an oncogenic virus. Lynch et al (1978) have designated this hereditary tumour complex as the "SBLA" cancer syndrome; S (sarcoma), B (breast and bone tumours), L (leukaemia, laryngeal carcinoma and lung cancer), A (adrenal cortical carcinoma). In their series, 16 tumours were available for pathological review (by light microscopy). Ten showed one or more of the following pathological features: multinucleate tumour giant cells, hypertrophied cells with large amounts of acidophilic

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cytoplasm, erythrophago-cytosis by tumour cells and three types of cellular inclusions. They suggested the possibility that these findings may have reflected viral injury, although they had no proof of this. They hypothesised that an oncogenic virus acting with a rare autosomal dominant gene had led to the production of highly specific histological varieties of malignant neoplasms (Lynch & Guirgis, 1979). The family reported in this case report has three members with cancer: the father with rhabdomyosarcoma, his maternal aunt with breast cancer and his daughter with adrenal cortical carcinoma. It is too early to say whether this family will show other features of the "SBLA" syndrome. ACKNOWLEDGMENTS

We wish to thank Dr M. G. Mott and Dr E. C. Whipp for permission to report on their patients. REFERENCES BOTTOMLEY, R H. & CONDIT, P. T., 1968. Cancer families.

Cancer Bulletin, 20, 22-24. BOTTOMLEY, R. H., TRAINER, A. L. & CONDIT, P. T., 1971.

Chromosome studies in a "cancer family". Cancer, 28, 519-528. EPSTEIN, L. I., BIXLER, D. & BENNETT, J. E., 1970. An incident

of familial cancer including 3 cases of osteogenic sarcoma. Cancer, 25, 889-891. FRAUMENI, J. F., JR & MILLER, R. W., 1967. Adrenocortical

neoplasms with hemihypertrophy, brain tumors, and other disorders. Journal of Pediatrics, 70, 129-138. KENNY, F. M., HASHIDA, Y., ASKARI, H. A., SIEBER, W. H. &

FETTERMAN, G. H., 1968. Virilizing tumours of the adrenal cortex. American Journal of Diseases oj Children, 115,445-458. Li, F. P. & FRAUMENI, J. F., JR, 1969a. Rhabdomyosarcoma in children: epidemiologic study and identification of a familial cancer syndrome. Journal of the National Cancer Institute, 43, 1365-1373. 1969b. Soft tissue sarcomas, breast cancer, and other neoplasms. A familial syndrome? Annals of Internal Medicine, 71, 747-752. 1975. Familial breast cancer, soft-tissue sarcomas and other neoplasms. Annals of Internal Medicine, 83, 833-834. LYNCH, H. T. & GUIRGIS, H. A., 1979. Childhood cancer and

the SBLA syndrome. Medical Hypotheses, 5, 15-22. LYNCH, H. T., MULCAHY, G. M., HARRIS, R. E., GUIRGIS,

H. A. & LYNCH, J. F., 1978. Genetic and pathologic findings in a kindred with hereditary sarcoma, breast cancer, brain tumors, leukemia, lung, laryngeal, and adrenal cortical carcinoma. Cancer, 41, 2055-2064. MILLER, R. W., 1971. Deaths from childhood leukemia and solid tumors among twins and other sibs in the United States, 1960-67. Journal of the National Cancer Institute, 46, 203-209.