Risk of second malignancies among survivors of pediatric thyroid cancer.

BACKGROUND: Thyroid carcinoma is a very rare tumor in the pediatric age group, accounting for only 1.5-3% of childhood carcinomas in the United States and Europe. We aimed to identify the risk of a second malignancy among pediatric thyroid cancer survivors. METHODS: The cohort analysis consisted of pediatric cancer patients aged less than 20 years, diagnosed with a primary thyroid cancer, identified by site code ICD-0-3: C739, and reported to the SEER 9 database between 1973 and 2013. They were followed up until December 31, 2013; the end of the study period, or up to death if earlier. RESULTS: Out of 1769 patients diagnosed primarily with thyroid carcinoma, 42 patients had a total of 45 incidences of subsequent malignancies. The mean age of patients at the initial diagnosis of thyroid cancer was 16 years. Females (90.5%) had a significantly higher incidence of second malignancies (SM) than males (9.5%). The overall Standardized Incidence Ratio (SIR) of SM in the study patients was higher than expected (SIR = 1.48). Some specific sites showed significantly higher incidences: the salivary glands (SIR = 33.95), the gum and other parts of the mouth [excluding the lips, tongue, salivary glands and floor of the mouth] (SIR = 24.53)*** and the kidneys (SIR = 5.72). The overall risk of SM in patients who had received radioactive iodine was higher than expected (SIR = 4.41). The cumulative incidence of SM after treatment of thyroid cancer in children increases steadily over 40 years (11.92%). CONCLUSIONS: Race, gender, histological subtypes, and radioactive iodine are potentially significant prognostic factors for the development of SM among pediatric thyroid cancer survivors. Identification of underlying mechanisms that raise the risk of SM is important for both treatment and follow-up strategies.

Follicular thyroid carcinoma metastasis to the facial skeleton: a systematic review.

BACKGROUND: Follicular thyroid carcinoma (FTC) metastasis to the facial skeleton is exceedingly rare. A case of FTC metastasizing to the mandible is presented and a systematic review of the literature describing thyroid metastasis to the facial skeleton is performed. CASE PRESENTATION: A 73-year-old female presented with metastatic FTC to the mandible and underwent total thyroidectomy, segmental mandibulectomy, bone impacted fibular free flap reconstruction, and adjuvant radioactive iodine treatment. The PubMed database was searched for literature describing thyroid cancer with facial skeleton metastasis using the key words "thyroid," "cancer," "carcinoma," "metastasis," and "malignancy" with "oral cavity," "maxilla," "mandible," "sinus," "paranasal," and "orbit." Reports that only involved the soft tissues were excluded. Systematic review revealed 59 cases of well-differentiated thyroid cancer with facial skeleton metastasis: 35 mandibular metastases (21 = FTC), 6 maxilla metastases (2 = FTC), 9 orbital metastases (4 = FTC), and 11 paranasal sinus metastases (7 = FTC). Treatment included surgery, RAI, external beam radiotherapy (XRT), or a combination of these modalities. The one, two, and five-year survival rates were 100%, 79%, and 16%, respectively. CONCLUSION: Facial skeleton metastasis of FTC is a rare clinical challenge. Optimal treatment appears to include total thyroidectomy and resection of involved structures with or without adjuvant treatment.

Early and late adverse effects of radioiodine for pediatric differentiated thyroid cancer.

BACKGROUND: Radioiodine-131 (I131) therapy for differentiated thyroid cancer (DTC) is generally a safe and effective treatment, but it has some potential side effects, which have been well described in adults but less analyzed in children. Our aim was to describe early and late adverse events of radioactive I131 in pediatric patients. METHODS: All consecutive patients ≤18 years treated for DTC in the period 1980-2015 were retrospectively analyzed for early and late side effects of radioiodine. Early side effects include nausea/emesis, radiation thyroiditis, sialadenitis, dry mouth, and transient bone marrow (BM) suppression. Late complications include permanent salivary gland dysfunction, permanent BM suppression, pulmonary fibrosis, second cancers, and fertility problems. RESULTS: One hundred five pediatric patients were treated with I131 for DTC in our department for a total amount of 302 radioiodine treatments. In total, 127 early complications were recorded: 44 episodes of nausea/emesis; 30 sialoadenitis, 24 thyroiditis, 18 dry mouth, and 11 transient BM suppression. Early side effects were correlated with the amount of radioactivity administered in any treatment. Twelve children developed ≥1 late complication for a total of 20 complications: two permanent salivary gland dysfunction, four permanent BM suppression, five pulmonary fibrosis, four second malignancies, and five fertility alterations. Late events, except fertility alterations, were correlated with the number of therapies and cumulative activities of I131. CONCLUSIONS: In conclusion, early side effects of I131 are associated with the amount of administrated activities of each treatment, while the late effects are correlated with the number of treatments and cumulative activities of radioiodine, except for fertility problems.

Metastatic follicular thyroid carcinoma: a case report.

OBJECTIVE: A case of oral metastatic follicular thyroid carcinoma is presented. BACKGROUND: Metastatic tumours are more frequent in older individuals and can be the only sign/symptom of an undiagnosed primary malignancy. CASE REPORT: A 69-year-old lady presented with an enlarging mandibular swelling. Incisional biopsy and imaging studies were suggestive of metastatic follicular thyroid carcinoma. CONCLUSION: Metastatic tumours should be considered in the differential diagnosis of mandibular swellings especially in older individuals.

[Isolated metastasis of the ascending ramus of the mandible of thyroid follicular carcinoma: a case report].

The mandibular metastatic spread of carcinoma from the thyroid gland is exceedingly rare. Follicular thyroid carcinoma is the second most common type of thyroid carcinoma，accounting for approximately 10% to 15% of all thyroid cancers. The prognosis of FTC is relatively satisfactory. Due to its rich blood transport, it is easy to metastasize hematological, with the main sites of metastasis are bone and lung. However，mandibular metastasis of thyroid follicular carcinoma is rare. We report a case of thyroid follicular carcinoma that metastasized to the ascending ramus of the mandible 21 years after surgery.The operation was successfully completed, and there was no recurrence during postoperative follow-up. Due to the absence of obvious clinical symptoms in the patient, the diagnosis and treatment were challenging. We have provided detailed radiographic and pathological images to facilitate understanding and discussion of the disease.

Toxicology and carcinogenesis studies of N,N-dimethyl-p-toluidine (CAS No. 99-97-8) in F344/N rats and B6C3F1/N mice (gavage studies).

N,N-dimethyl-p-toluidine was nominated for toxicology and carcinogenesis studies by the National Cancer Institute based on the potential for human exposure through its use in dental materials and bone cements and the lack of toxicity and carcinogenicity data. Male and female F344/N rats and B6C3F1/N mice were administered N,N-dimethyl-p-toluidine (greater than 99% pure) in corn oil by gavage for 3 months or 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium and Escherichia coli, mouse peripheral blood, and mouse and rat liver. 3-MONTH STUDY IN RATS: Groups of 10 male and 10 female rats were administered 0, 62.5, 125, 250, 500, or 1,000 mg N,N-dimethyl-p-toluidine/kg body weight in corn oil by gavage, 5 days per week for 14 weeks. Additional groups of 10 male and 10 female rats (clinical pathology study) were administered the same doses, 5 days per week for 25 days. On day 88, blood was collected from core study rats for hemoglobin and methemoglobin analyses only. All 1,000 mg/kg male and female rats and one 500 mg/kg male rat died by study day 3. Mean body weights of all surviving dosed groups of males and females were significantly less than those of the vehicle controls. Clinical findings associated with exposure to N,N-dimethyl-p-toluidine included cyanosis, abnormal breathing, and lethargy in groups administered 250 mg/kg or greater. Methemoglobinemia appeared to be the primary hematologic toxic response, and many other lesions could be explained as secondary to methemoglobin formation including Heinz body formation; a macrocytic, hypochromic, responsive anemia; and increased hematopoietic cell proliferation in the spleen and bone marrow. In general, hematologic changes were dose-related and occurred at both evaluated timepoints in all dosed groups. Anemia was evidenced by decreases in hematocrit values, hemoglobin concentrations, and erythrocyte counts; erythrocyte macrocytosis was characterized by increases in mean cell volume and mean cell hemoglobin values; erythrocyte hypochromia was evidenced by decreases in mean cell hemoglobin concentration values; and an erythropoietic response to the anemia was characterized by substantially increased reticulocyte and nucleated erythrocyte counts. Liver weights of all surviving dosed groups of males and females were significantly greater than those of the vehicle controls. Kidney weights of all surviving dosed groups of females were significantly greater than those of the vehicle controls. There were significant decreases in left cauda epididymis and left epididymis weights in 250 mg/kg males. There was a dose-related decrease in the number of cycling females, with only four females in the 250 mg/kg group having regular cycles and females in the 125 and 250 mg/kg groups spending a significantly higher proportion of time in extended diestrus compared to the vehicle control group. In the surviving groups of rats, there were significantly increased incidences of pigmentation in the liver of all dosed groups, hepatocyte hypertrophy in groups administered 125 mg/kg or greater, and hepatocyte necrosis in 62.5, 250, and 500 mg/kg females. In the olfactory epithelium of the nose, there were dose-related increases in the incidences and severities of degeneration in all dosed groups and significantly increased incidences of metaplasia in the 250 and 500 mg/kg groups. In the respiratory epithelium of the nose, there were significantly increased incidences of hyperplasia and squamous metaplasia in all of the groups administered 125 mg/kg or greater. The incidences of glandular hyperplasia of the nose were significantly increased in males and females administered 125, 250, or 500 mg/kg. In the spleen, there were significantly increased incidences of capsule fibrosis, congestion, mesothelial hypertrophy, and lymphoid follicle atrophy primarily in groups administered 125 mg/kg or greater. Hematopoietic cell proliferation and pigmentation were increased in severity in treated groups. In the kidney, there were significantly increased incidences of nephropathy (females), pigmentation (males and females), papillary necrosis (males and females), and mineralization (males). Other treatment-related lesions included inflammation of the forestomach in males, mesenteric lymph node atrophy in females, and bone marrow hyperplasia in males and females. 3-MONTH STUDY IN MICE: Groups of 10 male and 10 female mice were administered 0, 15, 30, 60, 125, or 250 mg N,N-dimethyl-p-toluidine/kg body weight in corn oil by gavage, 5 days per week for 14 weeks. All 250 mg/kg male and female mice (except for one male mouse) died before day 10, and three males and two females administered 125 mg/kg died before the end of the study. The final mean body weight of 125 mg/kg males and the mean body weight gains of 125 mg/kg males and females were significantly less than those of the vehicle controls. Clinical findings associated with administration of N,N-dimethyl-p-toluidine included abnormal breathing, thinness, lethargy, cyanosis, and ruffled fur in 125 and 250 mg/kg males and females. Methemoglobinemia appeared to be the primary hematologic toxic response; however there were less severe erythron changes compared to the 3-month study in rats. In females, no erythron changes were detected up to 125 mg/kg. In males, inconsistent and minor decreases in hematocrit values, hemoglobin concentrations, and erythrocyte counts, and increased reticulocyte counts occurred in groups administered 60 mg/kg or greater. Methemoglobin values were minimally increased in males and females administered 30 mg/kg or greater. Heinz bodies were slightly increased in 60 mg/kg females, 125 mg/kg males and females, and the one surviving 250 mg/kg male; Heinz body formation was considered secondary to methemoglobin formation. Liver weights of all dosed groups of mice were significantly greater than those of the vehicle controls. In the surviving groups of mice, there were significantly increased incidences of bronchiolar epithelium degeneration, bronchiolar epithelium regeneration, and peribronchiolar chronic active inflammation in the lung of 125 mg/kg groups, and histiocytic infiltrates of the alveoli in 125 mg/kg females. In the nose, there were significantly increased incidences of glandular hyperplasia and olfactory epithelium metaplasia in the 125 mg/kg groups and olfactory epithelium degeneration in 60 mg/kg females and 125 mg/kg males and females. In the thymus, the incidences of thymocyte necrosis in the 125 mg/kg groups were significantly increased. In the liver, the severities of cytoplasmic vacuolization of the hepatocytes were increased in dosed groups of males and females. 2-YEAR STUDY IN RATS: Groups of 50 male and 50 female rats were administered 0, 6, 20, or 60 mg N,N-dimethyl-p-toluidine/kg body weight in corn oil by gavage, 5 days per week for 104 or 105 weeks. Additional groups of 10 male and 10 female rats (clinical pathology study) were administered the same doses for 86 days. Survival of 60 mg/kg males was significantly less than that of the vehicle controls. Mean body weights of 60 mg/kg males and females were more than 10% less than those of the vehicle controls after week 61 and week 33, respectively. Clinical findings included signs of pallor in 60 mg/kg females and hyperactivity and boxing behavior in 20 mg/kg females and 60 mg/kg males and females. The hematology findings at the 3-month timepoint were consistent with those in the 3-month study in rats which indicated that methemoglobinemia was the primary hematologic toxic response. In the 20 and 60 mg/kg groups, there were dose-related decreases in hematocrit values, hemoglobin concentrations, and erythrocyte counts. There were similar trends toward erythrocyte macrocytosis and hypochromia and increased erythropoiesis as seen in the 3-month study. While the magnitudes of the erythron decreases were not sufficient to classify the responses as anemias, the patterns of the erythron changes were identical to those in the 3-month study. In the liver of 60 mg/kg males and females, there were significantly increased incidences of hepatocellular carcinoma and hepatocellular adenoma or hepatocellular carcinoma (combined). Numerous nonneoplastic liver lesions occurred in dosed males and females primarily in the 20 and 60 mg/kg groups. In the nose, there were significantly increased incidences of transitional epithelium adenoma and transitional epithelium adenoma or carcinoma (combined) in 60 mg/kg males; transitional epithelium adenoma also occurred in female rats administered 6 or 60 mg/kg. In the nose, there were significantly increased incidences of nonneoplastic lesions in the olfactory, respiratory, and transitional epithelia of dosed rats. These lesions occurred with the greatest incidence and severity in the 60 mg/kg groups. The incidences of inflammation and nerve atrophy were significantly increased in males and females administered 60 mg/kg. There were increased incidences of follicular cell adenoma or carcinoma (combined) of the thyroid gland in all dosed groups of males, and an increased incidence of follicular cell adenoma in 20 mg/kg females. In the spleen, there were significantly increased incidences of hematopoietic cell proliferation in all dosed groups of males and females. The incidences of congestion and mesothelial hypertrophy of the capsule were significantly increased in 60 mg/kg males and all dosed groups of females. There were also significantly increased incidences of capsular fibrosis and atrophy of the lymphoid follicle in the 60 mg/kg groups. The incidences of pigmentation were significantly increased in all dosed groups of males and in 60 mg/kg females. In all dosed groups of female rats, there were significantly increased incidences of nephropathy. (ABSTRACT TRUNCATED)

Bilateral thyroid follicular compact-cellular carcinoma in a llama.

An 18-y-old female llama (Lama glama) in Saskatoon, Saskatchewan was examined during a routine herd check, and a mass was detected in the ventral cervical area just below the angle of the jaw. No clinical signs were evident except for the mass and chronic loss of body condition. Postmortem examination revealed bilateral enlargement of the thyroid gland with multiple cysts. Histopathology of the thyroid gland revealed follicular compact-cellular carcinoma lesions, with infiltration of neoplastic thyroid follicular cells in regional lymph nodes.

Fine needle aspiration cytology of mixed medullary-follicular thyroid carcinoma: a case report.

BACKGROUND: Mixed medullary-follicular thyroid carcinoma (MMFTC) is a rare tumor that has been regarded as a clinicopathologic variant of medullary thyroid carcinoma. MMFTC represents a diagnostic challenge by fine needle aspiration cytology (FNAC). CASE: A 77-year-old woman had a palpable mass on the left side of the neck. It was diagnosed as follicular neoplasm by FNAC; she underwent total thyroidectomy. Pathology revealed follicular carcinoma. Radioactive iodine was administered. An enlarging mass was present in the left mandible later. FNAC showed suspicious follicular neoplasm with predominance of oncocytic cells. Pathology revealed follicular carcinoma with parafollicular cell differentiation. Immunohistochemical analysis demonstrated positive status for thyroglobulin and calcitonin. Simultaneous expression of thyroglobulin and calcitonin within the same neoplastic cell was considered. She underwent several courses of radioactive iodine therapy without significant effect. Interestingly, her serum calcitonin level was not elevated. CONCLUSION: Coexpression of thyroglobulin and calcitonin in the same cell is very rare. The component of medullary carcinoma should be considered when encountering an atypical thyroid carcinoma with predominance of cells showing oncocytic changes on FNAC and with clinically poor response to conventional treatment. Immunohistochemistry and pathologic analyses are helpful to confirm the diagnosis, especially in the absence of elevated serum calcitonin level.

Two case reports on Mandibular metastases.

Metastatic tumours of the oral cavity are not common. The most common site for bone metastases in the head and neck region is the mandible. Metastatic lesion of the mandible most commonly originate from the lungs in men and breast in women, and these lesions (or tumours) usually are carcinomas rather than sarcomas. We report two cases of metastatic lesions in the mandible: (1) A 19year old male with right mandibular swelling and a nodular swelling in the distal two-third of the right tibia. Radiograghs revealed sclerotic lesion with a sunburst appearance in both the jaw and tibia. Histology of the jaw lesion confirmed a metastatic osteosarcoma of the mandible. (2) A 51year old female with a right mandibular swelling with associated swelling in the anterior neck, right shoulder and right parietal region of the skull. Computerised tomography scan (CT) of the jaws showed an osteolytic lesion of the right mandible. CT scan of the brain also showed a large lytic lesion seen in the posterior aspect of the right parietal bone. Histology of the jaw mass confirmed a metastatic follicular carcinoma from the thyroid. Mandibular metastasis may be the first presenting feature of underlying occult malignancy of another primary site. Therefore, clinicians should maintain a high level of suspicion while evaluating patients with a history of cancer presenting with oral lesions.

Percutaneous vertebroplasty in the treatment of pain caused by metastatic tumor.

Percutaneous vertebroplasty is a radiologically guided therapeutic procedure that consists of percutaneous injection of polymethylmetacrylate (PMMA) into pathologic vertebral bodies. It is a minimally invasive procedure that is effective in the treatment of pain resulting from bone metastasis. This procedure has the advantage of providing rapid pain relief and spinal stabilization. A patient with severe, aggressive pain from metastatic lumbar spinal tumor of thyroid follicular carcinoma is presented herein. Despite treatment with analgesic agents, external beam radiation therapy, radioiodine therapy, and posterior fusion surgery, the pain reemerged and progressed. After percutaneous vertebroplasty, definite pain relief was achieved. Vertebroplasty would be useful as an additional or alternative pain relief method in patients with metastatic vertebral tumors.

Metastasis of thyroid carcinoma to the mandible. Case report.

Metastatic tumours to the jaw bones are uncommon. The incidence of jaw bone metastasis is difficult to assess accurately since the usual method to determine the distribution of a metastatic tumour has been by a radiographic skeletal survey in which the jaws are rarely included. At times, metastatic lesions of the orofacial region may be the first evidence of dissemination of a known tumour from its primary site. A case of metastatic follicular carcinoma of the thyroid to the mandible is presented. The present case emphasizes the importance of considering metastasis in the differential diagnosis of a radiolucent lesion in the mandible in a patient with a history of any malignant disease.

Metastatic follicular thyroid carcinoma to the body of the mandible mimicking an odontogenic tumor.

Metastatic tumors to the jawbones are uncommon. Metastatic lesions to the oro-facial region may be the first evidence of dissemination of an unknown tumor from its primary site. Follicular thyroid carcinoma rarely presents initially as a distant metastatic lesion within the mandible. This case of metastatic follicular thyroid carcinoma is presented to emphasize its unusual initial presentation within the body of the mandible, which mimicked an odontogenic tumor. It's important to detect the carcinoma early so that it can be treated successfully and also improves the prognosis of the patient. The histopathological features and immunohistochemical findings are also discussed.

Metastatic follicular thyroid carcinoma to the mandible.

Metastatic tumors are of great significance since few cases may represent the only symptom of an undiscovered underlying malignancy. Metastatic tumors rarely metastasize to the oral region despite the fact that many common primary neoplasms frequently metastasize to bone. The true incidence of metastatic tumors in the bones of the jaw is unknown, as jaws are not always included in radiographic skeletal surveys for metastasis. Sometimes oral metastasis may be the first evidence of metastasis from its primary site. A case of metastatic follicular thyroid carcinoma to the mandible is presented here, along with the discussion of clinical and histological features. The present case not only emphasizes the importance of considering metastasis in the differential diagnosis of a radiolucent lesion in the mandible, but also emphasizes in the improvement of the overall survival rate and treatment results by an early detection of metastatic disease.