Castleman disease: a case report of an unusual adrenal incidentaloma and literature review.

Adrenal incidentaloma (AI) is an incidental detection of an adrenal mass on an image not performed for a suspected adrenal problem. AI has become a commonly encountered lesion that requires further investigations for evidence of hormonal hypersecretion or malignancy potential. According to guidelines, surgical intervention is the standard of care for unilateral AI. We report on a case of a 64-year-old female who presented with a nonfunctional adrenal mass associated with compressive symptoms, which was revealed to be a mixed hyaline vascular and plasma cell variant Castleman disease (CD) after surgical resection. Although hyaline vascular variant and plasma cell variant of CD has been identified in adrenal glands, this is the first report of a mixed hyaline vascular and plasma cell variant in an adrenal mass.

Thyroid surgery in 103 children in a single institution from 2000-2014.

BACKGROUND: Data on thyroid surgery in children are scarce. OBJECTIVE: Analyze outcome data on thyroid surgery in a pediatric population. DESIGN: Medical record review. SETTING: Tertiary health care institution. PATIENTS AND METHODS: We collected demographic and clinical data on patients 18 years or younger who had thyroid surgery in the period 2000 to 2014. Descriptive data are presented. MAIN OUTCOME MEASURES: Indications for thyroidectomy, thyroid pathology, complications, length of stay, and radioactive iodine treatment and recurrences. SAMPLE SIZE: 103. RESULTS: Of 103 patients who underwent 112 thyroidectomy procedures, 80 (78%) were females and the mean age at operation was 13.2 years. and 17 (16%) were associated with multiple endocrine neoplasia type 2. There was no history of radiation exposure. Eighty-one patients (78%) had fine needle aspiration (FNA) which correlated with the final histopathology in 94% of cases. Sixty-six patients (64%) had malignant cancer (61 papillary), 44 (74.6%) of 59 patients who had neck dissection had lymph node metastasis and 7 (11%) had distant metastases to the lung. Procedures included total thyroidectomy (50%), hemithyroidectomy (17%), completion (31%), and subtotal thyroidectomy (2%). Twenty-three patients (22%) developed hypocalcemia (3 permanent) and 6 (5.8%) had unilateral recurrent laryngeal nerve injury (3 permanent). Patients were followed up for a mean duration of 71.7 months (median 60 months). Of 66 patients with thyroid cancer, 43 (65%) received radioactive iodine, and 10 (15%) had recurrence. CONCLUSION: Malignancy is the commonest indication for thyroid surgery in children and FNA is highly diagnostic. Hypocalcemia and recurrent laryngeal nerve injury are significant complications. The recurrence rate in thyroid cancer is 15%. LIMITATIONS: Retrospective. CONFLICT OF INTEREST: None.

c-Met inhibitor synergizes with tumor necrosis factor-related apoptosis-induced ligand to induce papillary thyroid carcinoma cell death.

The Met receptor tyrosine kinase is overexpressed and/or activated in variety of human malignancies. Previously we have shown that c-Met is overexpressed in Middle Eastern papillary thyroid carcinoma (PTC) and significantly associated with an aggressive phenotype, but its role has not been fully elucidated in PTC. The aim of this study was to determine the functional link between the c-Met/AKT signaling pathway and death receptor 5 (DR5) in a large cohort of PTC in a tissue microarray format followed by functional studies using PTC cell lines and nude mice. Our data showed that high expressions of p-Met and DR5 were significantly associated with an aggressive phenotype of PTC and correlated with BRAF mutation. Treatment of PTC cell lines with PHA665752, an inhibitor of c-Met tyrosine kinase, inhibited cell proliferation and induced apoptosis via the mitochondrial pathway in PTC cell lines. PHA665752 treatment or expression of c-Met small interfering (si)RNA resulted in dephosphorylation of c-Met, AKT and its downstream effector molecules. Furthermore, PHA665752 treatment upregulated DR5 expression via generation of reactive oxygen species in PTC cell lines, and synergistically potentiated death receptor-induced apoptosis with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Finally, cotreatment with PHA665752 and TRAIL caused more pronounced effects on PTC xenograft tumor growth in nude mice. Our data suggest that the c-Met/AKT pathway may be a potential target for therapeutic intervention for treatment of PTC refractory to conventionally therapeutic modalities.

Demethylation of TMS1 gene sensitizes thyroid cancer cells to TRAIL-induced apoptosis.

CONTEXT: TMS1 is a tumor suppressor gene that encodes for caspase recruitment domain containing regulatory protein and has been shown to be hypermethylated in various cancers. However, its methylation status has not been investigated in thyroid cancer. Therefore, we studied the methylation of TMS1 and its functional consequence in thyroid cancer. DESIGN: The methylation status of the promoter region of the TMS1 gene was determined using methylation-specific PCR in 40 papillary thyroid cancer samples, 10 normal thyroid tissue, and seven thyroid cancer cell lines. RT-PCR and Western blot analysis were used to assess the expression levels. 5-aza-2'-deoxycytidine was used to demethylate the thyroid cancer cell lines. Cell viability and apoptosis was determined by dimethylthiazoldiphenyltetra-zoliumbromide and flow cytometry. RESULTS: Twenty-three percent of the papillary thyroid carcinoma samples were found to be methylated for the TMS1 gene. Two of seven thyroid cell lines were either completely or partially methylated for the TMS1 gene. The treatment of methylated thyroid cancer cell lines with 5-aza-2'-deoxycytidine resulted in the demethylation of the TMS1 gene leading to the restoration of its expression. After demethylation, treatment of cells with TNF-related apoptosis-inducing ligand (TRAIL) led to the induction of apoptosis via activation of caspases-8, caspase-3, and poly(ADP-ribose) polymerase. Interestingly, gene silencing of TMS1 using TMS1-specific small interfering RNA prevented TRAIL-mediated apoptosis. CONCLUSION: Our results demonstrated that the TMSI gene is methylated in thyroid cancer cells and repression of methylation by 5-aza-2'-deoxycytidine restored expression of the TMS1 gene and sensitized cells to TRAIL-induced apoptosis. These findings suggest that the TMS1 gene can be targeted by combination of demethylating agents with TRAIL to induce efficient apoptosis in thyroid cancer cells.