Pediatric Articles
ADRENOCORTICAL CARCINOMA IN A CHILD WITH SPECIFIC PEDIGREE OF FAMILY ASSOCIATED WITH CANCER AGGREGATION
TAIJI TSUKAMOTO, YOSHIAKI KUMAMOTO, ATSUSHI TAKAHASHI, KEIGO AKAGASHI, NAOKI ITOH, AKIHITO NANBU AND MASAAKI SATO
From the Department of Urology and Pathology, Sapporo Medical College, Sapporo, Japan
ABSTRACT
We report on a 5-year-old boy with functioning adrenocortical carcinoma as a proband of a specific pedigree with several young family members who had cancer. Most of the members who died of cancer had early onset of osteosarcoma, hepatoblastoma or malignant lymphoma. The finding of cancer aggregation in the family corresponded to the criteria for the cancer family syndrome.
KEY WORDS: carcinoma; neoplastic syndromes, hereditary; adrenal cortex diseases; hereditary diseases
Recent advances in molecular biology have revealed a genetic predisposition in some childhood cancers, such as retinoblas- toma in which the RB gene has a major role in the pathogenesis of this disease.1 In the family with a young child who has evidence of a specific cancer the other family members have been demonstrated to have a higher predisposition for various cancers. The specific family with cancer aggregation is de- scribed as having the cancer family syndrome2 or SBLA syn- drome.3 We report on a 5-year-old boy with adrenocortical carcinoma and a strong predisposition for cancer in the family.
CASE HISTORY
A 5-year-old boy was referred to the urology clinic on Novem- ber 4, 1989 because of a painless scrotal swelling discovered by his mother. He was the product of a full-term gestation, and had good mental and physical growth corresponding to age before the hospital visit. There were no congenital diseases at birth nor any medical problems during the fetal period. In addition to scrotal swelling, which was diagnosed as bilateral hydrocele of the testis, physical examination revealed a 10 cm. solid mass with an irregular surface in the right flank. Hirsut- ism and enlargement of the penis were also found, indicating precocious puberty. He had no clinical abnormalities, such as hemihypertrophy, hepatomegaly and/or nephromegaly suggest- ing the Beckwith-Wiedemann syndrome.
The patient was the fourth child of the father and the first child of the mother. The father was 43 years old and the mother was 38 years old when the patient was born. Family history was remarkable for cancer (fig. 1). Of the 3 half siblings 1 died of malignant lymphoma at the age of 10 years and 1 died of hepatoblastoma at the age of 5 years. Both tumors were verified by histopathological examination.4 The patient with hepato- blastoma had hypoglycemic episodes that were caused by an insulin-like substance secreted from the tumor. The father of our patient died of lung carcinoma when he was 45 years old. Of the father’s 5 siblings 2 died of cancer (1 had osteosarcoma and died during childhood, while 1 died of breast cancer but the age was not identified). Moreover, 1 of the patient’s cousins also died of osteosarcoma during childhood. Lung cancer in the father, osteosarcoma and breast cancer in the father’s siblings and osteosarcoma in the cousin were all verified by family history. No specific cancer aggregation was recorded on the
maternal side of the family or in that of the mother of his half siblings.
Computerized tomography and magnetic resonance imaging revealed a 13 cm. solid abdominal mass in the left suprarenal area. A low density area in the liver was also discovered, suggesting a metastatic focus. The left kidney with a normal collecting system was displaced downward by the mass as shown by excretory urography (IVP). No other abnormalities were found on the IVP. Serum cortisol, adrenal androgens (dehydroepiandrosterone and its sulfate derivative), testoster- one and estradiol were all markedly elevated. Urinary 17- hydroxycorticosteroids and 17-ketosteroids were also elevated.
Since clinical features suggested the left functioning adre- nocortical carcinoma, an operation through a thoracoabdom- inal approach was attempted on December 20. The mass was removed completely and histopathological examination showed pleomorphic cells with eosinophilic cytoplasm, nuclear pleo- morphism and atypia, and abundant mitoses (fig. 2). Invasion of the cells to the capsule and vessels was also found. These findings indicated adrenocortical carcinoma. After recovery from the operation the patient was begun on 1.0 gm. op’- dichlorodiphenyldichloroethane daily, which was gradually in- creased to 6.0 gm. daily. However, the drug did not inhibit growth of the liver metastasis. The patient died of multiple
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Accepted for publication May 24, 1991.
liver and lung metastases on March 26, 1990. An autopsy confirmed multiple organ and lymph node metastases.
DISCUSSION
Adrenocortical carcinoma is rare in any age group, with the incidence being estimated at 0.02% of all malignancies in the United States.5 This carcinoma accounts for 0.2 to 0.3% of all pediatric malignancies in the United States.6 The cases of adrenocortical carcinoma are often associated with hemihyper- trophy, the Beckwith-Wiedemann syndrome or congenital mal- formations of the urinary tract.7,8 The patients are also predis- posed to have secondary malignancies at a later date when they recover from the adrenocortical carcinoma.9 These findings may support the idea that some genetic alterations would affect the occurrence of adrenocortical carcinoma. Indeed, recent studies have demonstrated a loss of heterozygosity at several chromosomes in human adrenocortical carcinoma. Yano et al found a loss of heterozygosity at the 17p, 11p and 13q sites, while benign adrenal tumors and hyperplasia have not exhib- ited any deletions in chromosomes.1º Henry et al suggested that a gene for predisposition to adrenocortical carcinoma lies in the region of 11p.11
Moreover, a high frequency of cancer has been reported in the family of the proband with adrenocortical carcinoma. The specific family with such a cancer aggregation is said to have the cancer family syndrome as proposed by Li et al.2, 12 Although the syndrome has not been defined in detail, the recent criteria of the syndrome by Li are that the family should have a proband with sarcoma that occurs at an age of less than 45 years and that at least 2 young relatives in the family should have cancer.12 Also, cancer in the family should consist mostly of soft tissue sarcoma occurring primarily in childhood and breast cancer occurring at an early age. Osteosarcoma, brain tumor, leukemia and adrenocortical carcinoma occurring in children and young adults should be considered 4 additional cancer components of the family. Multiple primary cancers found in the family should be included in this syndrome.
Li et al surveyed cancers according to tumor types and patient age at diagnosis in 151 patients among 24 cancer families and documented that soft tissue or bone sarcoma accounts for 36% of the total, followed by breast carcinoma in 24%, brain tumor in 9% and leukemia in 6%.2 Adrenocortical carcinoma accounted for 3% of the 151 patients. It is notewor- thy that in the cancer-aggregate family all adrenocortical car- cinomas occurred during childhood. Thus, compared to distri- bution of tumor types other than sarcoma and breast carcinoma in 41 family members at an age of less than 45 years, adreno- cortical carcinoma occupied 10% of the total, which was dis-
tinctly higher than the incidence of carcinoma in the general population of the United States (approximately less than 1%).
A similar type of syndrome, the SBLA syndrome, has been reported by Lynch et al.3 In this syndrome the specific types of cancer, that is, sarcoma, breast carcinoma (or brain tumor), leukemia (laryngeal carcinoma or lung carcinoma) and adre- nocortical carcinoma, are accumulated in the specific family. Lynch et al found a specific pedigree of the family with the SBLA syndrome.13 In the 5 generation families in 1 pedigree a total of 26 cancer syndrome cases was identified. The tumors included 6 sarcomas (2 of which occurred in children), 4 breast carcinomas all with early onset, 7 brain tumors (5 in children), 3 lung carcinomas, 1 laryngeal carcinoma and 3 leukemias (3 in children). Two adrenal carcinomas (1 in a child) also were found in the families. Thus, it is remarkable that 14 of 26 tumors occurred in children or young adults. The researchers have further extended the investigation focusing on the specific branch of the family.14 The family was identified to have a lineage of new syndrome cancers and of an excess of childhood syndrome cancers. These cancers appeared to be transmitted to a sixth generation.
In the cancer family syndrome and the SBLA syndrome adrenocortical carcinoma is one of the specific tumors consist- ently found in a cancer-accumulation family. Among the family members of our patient 5 of the 8 relatives who died of cancer had early onset of the disease during childhood. Consequently, the family shares characteristics found in the cancer family syndrome. Because of the rarity of this disease no systematic clinical trials have been attempted to obtain improvement in the clinical course of the patient. A recent extensive series by Bodie et al indicated that the 5-year survival rate is 25%, which is totally dependent on an extension of the disease at diagno- sis.15 They also noted that op’-dichlorodiphenyldichloroethane did not improve the survival of patients with metastasis. Thus, the prognosis of patients with this disease remains poor when there is distant metastasis at diagnosis as in our patient.
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