Follicular carcinoma

FIGURE 10.11 Papillary thyroid carcinoma, follicular variant. Immunoperoxidase stain for CKl 9 demonstrates intense cytoplasmic reactivity. 

Follicular tumors with questionable features of papillary carcinoma (follicular tumors of uncertain malignant potential) often demonstrate intermediate and/or irregular patterns of staining for CK19, HBME-1, and galectin-3. 

Osborne-Mendel rats were fed technical-grade heptachlor (73%) males received TWA doses of 1.94 and 3.9 mg/kg/day and females received TWA doses of 1.28 and 2.56 mg/kg/day for 80 weeks (NCI 1977). The results of this study showed a statistically significant increase in follicular cell neoplasms in the thyroid (adenomas and carcinomas) in females fed the high dose compared to controls. This finding was discounted by the investigators, however, because the incidence rates were low and are known to be variable in the control rat population. Rates of tumor incidences in males were not increased. 

Gastrointestinal, pancreas, biliary, lung, transitional cell, sweat glands, mucosal squamous cell, mucinous carcinomas of female GU tract, medullary carcinoma of thyroid Breast, squamous cell, endometrioid, Brenner tumor Renal cell, hepatocellular, prostate, follicular thyroid, adrenal cortical, serous carcinomas of female GU tract, embryonal, yolk sac, mesothelioma... 

Spontaneous thyroid tumors derived from the thyroid follicular cell occur in l%-3% of laboratory rats (adenomas and carcinomas combined in a variety of strains of rats aged 2 or more years). 

In animal studies aldrin induced an increased incidence of hepatocellular carcinoma at two dietary doses in male mice the tumors showed a significant dose-response trend and were statistically significant at the high dose. Follicular cell tumors of the thyroid and adrenal cortical cell adenomas were increased in female rats in the low-dose group but not in the high-dose group the results could not be clearly associated with treatment. ... 

In 2-year drinking water studies, there was some evidence of carcinogenic activity in male rats based on increased incidences of renal tubule adenomas and carcinomas there was equivocal evidence of carcinogenicity in female mice based on increased incidences of follicular cell adenoma. ... 

At dosages above 30mg/kg in the diet, chlordane interfered with reproduction in rats and mice, but this effect was reversible after exposure ceased." Pre- and postnatal exposures to chlordane altered the development of the immune system in rodents. A dose-related increase in the incidence of hepatocellular carcinomas was found in male and female mice fed approximately 60mg/k chlordane for 80 weeks. In rats, increases in the incidences of thyroid follicular cell neoplasms were observed. ... 

Chronic oral exposure of rats and mice to MDA and its dihydrochloride is carcinogenic. Treatment-related increases in the incidences of thyroid follicular cell adenomas and hepatocellular neoplasms were observed in mice after chronic ingestion of MDA in drinking water. In rats, increases in the incidences of thyroid follicular cell carcinoma and hepatic nodules were observed in males and thyroid follicular cell ademonas occurred in females. Although not statistically significant, certain uncommon tumors such as bile duct adenomas, papillomas of the urinary bladder, and granulosa cell tumors of the ovary also were reported. These tumors are of low incidence in historical controls. In another report, MDA acted as a promoter of thyroid tumors in rats. °... 

Two-year studies were conducted by administering VCD in acetone by dermal application 5 days per week for over 100 weeks to groups of rats of each sex at 0, 15, or 30mg/animal and to groups of mice at 0, 2.5, 5, or lOmg/animal. Acanthosis and sebaceous gland hypertrophy of skin from the scapula were observed at increased incidences in both species. Squamous cell papillomas in male rats and squamous cell carcinomas in males and females were observed in exposed rats at an increased incidence. The combined incidence of basal cell adenomas or carcinomas was also increased in both sexes. Squamous cell carcinomas were found in the exposed mice. Follicular atrophy and tubular hyperplasia of the... 

Thyroid cancer Exogenous thyroid hormone may produce regression of metastases from follicular and papillary carcinoma of the thyroid and is used as ancillary therapy of these conditions with radioactive iodine. Larger doses than those used for replacement therapy are required. 

MM = multiple myeloma ATL = adult T-cell leukemia ALL = acute lymphoblastic leukemia CLL = chronic lymphocytic leukemia FCC = follicular center cell lymphoma DLC = diffuse large cell lymphoma TRB = T-cell rich B-cell lymphoma ALCL = anaplastic large cell lymphoma MALT = mucosa-associated lymphoid tissue-type lymphoma LC = lung cancer CMM = cutaneous malignant melanoma TCC = transitional cell carcinoma CSCC = cutaneous squamous cell carcinoma. 

Sebaceous gland adenomas and carcinomas or basal-cell tumours Follicular-cell adenomas and carcinomas Carcinomas... 

Reported estimated doses in the mice were 3,200 and 6,650 mg/kg/day in males and 3,760 and 7,780 mg/kg/day in females (NTP 1986). Hepatocellular adenoma or carcinoma (combined) occurred at significantly increased incidences in low-dose male mice (22/50, p=0.002) and high-dose male mice (18/50, p=0.019) in comparison to controls (8/50) and showed a positive dose-related trend (p=0.021). Incidences of hepatocellular carcinoma alone were not significantly increased in either the low- or high-dose male mice. Slightly elevated incidences of thyroid gland follicular cell adenoma or carcinoma (combined) were... 

Neoplastic effects in the NTP (1986) bioassay included increased incidences of neoplastic nodules in the liver in the male and female rats and hepatocellular adenoma or carcinoma (combined) in the male mice. Slightly elevated incidences of thyroid gland follicular cell tumors were additionally observed in exposed male mice, although the increases were equivocal. No exposure-related neoplastic changes were found in the chronic study of the 77.4% decaBDE mixture (Kociba et al. 1975 Norris et al. 1975a), but the power of this study to detect carcinogenic effects is limited by the very low dose levels in comparison to those tested in the NTP bioassay. 

A 71-year-old woman who had undergone total thyroidectomy with subsequent irradiation because of follicular carcinoma 3 years before (22). Since then, she had taken oral levothyroxine 0.15 mg and 0.2 mg on alternate days. When latent hypothyroidism became evident despite replacement therapy, the dose of levothyroxine was increased to 0.3 mg/day. Three weeks later, she had formed an acute posterior myocardial infarction, although she had no previous history of coronary artery disease. Subsequent coronary arteriograms revealed no evidence of disease of the major vessels. Myocardial scintigraphy 3 weeks after infarction still showed a persistent perfusion defect. 

In a prospective, observational cohort study in a tertiary-care hospital, there were abnormal serum TSH concentrations in 26 of 42 patients) who took sunitinib for renal cell carcinoma or GIST. Persistent primary hypothyroidism, isolated TSH suppression, and transient mild rises in TSH were found in 36%, 10%, and 17% of patients respectively. There appears to be a correlation between the duration of use of sunitinib and suppressed TSH concentrations as well as a risk of hypothyroidism. Whether sunitinib induces destructive thyroiditis through follicular cell apoptosis has not been fully elucidated (1078,1079,1080). 

M (CEL increased incidence of NTP 1982b thyroid follicular cell adenoma or carcinoma)... 

Interferons are proteins or glycoproteins that are produced either by animal cells or plant cells in response to stimuli or DNA recombinant technology. These drugs are active against malignant neoplasms and have immunomodulating effects. These are useful in chronic hepatitis B, hepatitis C, hairy cell leukemia, myeloid leukemia, follicular lymphoma, carcinoid tumor, multiple myeloma, renal cell carcinoma, multiple sclerosis, chronic granulomatous diseases, blood disorders, common cold, herpes simplex, inflammatory bowel disease, and leishmaniasis. 

Negative Renal cell, hepatocellular, prostate, follicular thyroid, adrenal cortical, serous carcinomas of female GU tract, embryonal, yolk sac, mesothelioma... 

Malignant diseases hairy cell leukemia, chronic myelogenous leukemia, cutaneous T cell lymphoma, follicular lymphoma, multiple myeloma, Kaposi s sarcoma, diffuse melanoma, renal cell carcinoma, carcinoid tumors Viral diseases condylomata acuminata, chronic active hepatitis B and C... 

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