Effects of prepubertal indole-3-carbinol treatment on development of N-methyl-N-nitrosourea-induced mammary carcinomas in female Sprague-Dawley rats.

BACKGROUND: Indole-3-carbinol (I3C), which is present in cruciferous vegetables, has been shown to prevent the development of mammary cancer when administered to adult animals. However, no studies have been reported on the effects of prepubertal short-term I3C treatment on N-methyl-N-nitrosourea (MNU)-induced mammary carcinogenesis. MATERIALS AND METHODS: Prepubertal female Sprague-Dawley rats were administered the vehicle (Group 1) or I3C (Group 2, 250 mg/kg/day at 15 and 16 days of age; Group 3, 50 mg/kg/day at 15 and 16 days of age; Group 4, 50 mg/kg/day at 15, 16, 29 and 30 days of age; Group 5, 50 mg/kg/day at 29 and 30 days of age). All rats were administered 50 mg/kg MNU at 22 days of age. Rats were sacrificed at 34 weeks of age or when their largest mammary tumor reached a diameter of > or =1 cm. Body weight gain, vaginal opening, estrous cyclicity and mammary carcinogenesis were compared between the groups. RESULTS: Rats administered 250 mg/kg I3C exhibited acute toxicity, and 40% of that group died soon after administration of I3C. There was no significant difference in body weight and relative uterine-ovarian weight of surviving rats between groups at the end of the experiment. However, rats from Group 2 and Group 3 exhibited earlier vaginal opening and prolonged estrous cyclicity, respectively. I3C treatment before and after MNU administration (Group 4) tended to reduce mammary carcinoma incidence (percentage of mammary carcinomas with a diameter of > or =1 cm) and multiplicity (number of all-sized mammary carcinomas per rat), and prolonged the latency (time from MNU administration to point when mammary tumors grew to a diameter of > or =1 cm) compared with the vehicle (control) group. Mammary carcinogenesis was not altered by other I3C treatments. CONCLUSION: Prepubertal I3C treatment before and after carcinogen exposure appeared to provide an insignificant protection against MNU-induced mammary carcinogenesis.

An autopsy case of primary mixed choriocarcinoma and mature teratoma located in the thymic region associated with elevated human chorionic gonadotropin levels and characteristic testicular changes.

An autopsy case of a 19-year-old male Japanese student with a primary mixed choriocarcinoma and mature teratoma in the thymic region is reported. The patient died 7 days after he first noticed fever and dyspnea. On autopsy, an anterior mediastinal mass was found to be in contact with the thymic gland. The mass weighed 270 g and measured 12.5 cm x 10 cm x 5 cm. The left thoracic cavity contained 2200 ml bloody pleural effusion and 200 g coagula due to hemorrhage from the tumor. Metastasized choriocarcinoma was seen in both lungs and the liver. High serum levels of human chorionic gonadotropin (HCG, 1 634 000 mIU/ml) and a decreased weight of the testes (2.0 g each) with Leydig cell hyperplasia/hypertrophy and the seminiferous tubules with hyaline ghost tubules or Sertoli cell only tubules were seen; other male reproductive organs were histologically normal. Although the serum testosterone level was within the normal range (5.75 ng/ml), luteinizing hormone (LH, 0.1 mIU/ml) and follicle-stimulating hormone (FSH, 0.3 mIU/ml) levels were decreased. High serum levels of HCG and characteristic testicular changes are drscribed.

Diagnostic cytopathology in type II angiosarcoma of the breast: a case report.

BACKGROUND: The rare occurrence of angiosarcoma of the breast is reflected in limited descriptions of fine needle aspiration (FNA) cytomorphologic findings in this neoplasm. We present a case of angiosarcoma of the breast and discuss the pitfalls in diagnostic cytopathology that can potentially lead to incorrect diagnoses in such cases. CASE: A 45-year-old woman presented with a 2-year history of a right-sided breast mass. FNA cytology revealed a hypocellular smear composed of cohesive ductal epithelial cells; isolated or loosely arranged, round to spindle-shaped fibroblastlike cells; and projectile growths of round, oval and polygonal cells on loose tangles of connective tissue. The background was hemorrhagic, with scattered foam cells. The overall cytologic diagnosis was inconclusive but suggested phyllodes tumor (of borderline malignancy). Excisional biopsy was performed, followed by simple mastectomy. Histologic features were consistent with angiosarcoma, a diagnosis that was supported by immunohistochemical studies. CONCLUSION: On FNA smear, 49.1% of isolated atypical cells were positive for the endothelial marker CD34; however, cytomorphologic appearance of these cells resembled that of CD34-negative active mesenchymal cells. Angiosarcoma rarely occurs in the breast, and a definitive diagnosis is difficult based on cytologic examination of hypocellular smears alone. However, the presence of atypical round, oval and polygonal cells on loose tangles of connective tissue, suggesting sheared vasculature, can be an important diagnostic feature.

Effects of prepubertal zeranol exposure on estrogen target organs and N-methyl-N-nitrosourea-induced mammary tumorigenesis in female Sprague-Dawley rats.

BACKGROUND: There are no previous reports of the effects of prepubertal exposure to zeranol, an estrogenic substance, on estrogen-responsive reproductive organs and mammary glands in rats, or its effects on N-methyl-N-nitrosourea (MNU)-induced mammary tumorigenesis in rats. MATERIALS AND METHODS: Prepubertal female Sprague-Dawley rats were treated daily with either 0, 0.1 or 10 mg/kg body weight of zeranol between 15 and 19 days of age. They were given 50 mg/kg body weight MNU at 28 days of age, and were monitored for occurrence of mammary tumors > or = 1 cm in diameter. Body weight gain, structures and functions of estrogen target tissues, and mammary carcinogenesis were compared between dosage groups. RESULTS: Zeranol did not affect body weight gain. At 28 days of age, zeranol-treated and -untreated rats showed similar development of reproductive organs and mammary glands. However, both low- and high-dose zeranol treatment caused significantly earlier vaginal opening, irregularity of estrous cycle (high frequency of prolonged estrous or prolonged diestrous) at 8 to 11 weeks of age, and anovulatory ovary (ovaries without newly formed corpora lutea). At 37 weeks of age, the high-dose zeranol-treated group exhibited increased relative uterine-ovarian weight, but mammary gland development was comparable to that of untreated rats. Mammary carcinogenesis was not affected by low- or high-dose zeranol treatment. CONCLUSION: Short-duration zeranol treatment in the prepubertal period severely damaged ovarian functions and structure, but mammary carcinogenesis was not affected. The present results suggest that ingestion of foods containing zeranol in the infantile period can cause dramatic endocrine disruption in later life.