The Significance of RAS-Like Mutations and MicroRNA Profiling in Predicting Malignancy in Thyroid Biopsy Specimens.

In cytologically indeterminate thyroid nodules undergoing molecular testing, estimated risk of malignancy is variable. Identification of a non-cancer-specific mutation (RAS-like) confirms a neoplastic process but does not differentiate between benign, malignant, and low-risk neoplasms. This study aims to retrospectively evaluate institutional experience of Interpace (ThyGeNEXT® and ThyraMIR®; Pittsburgh, PA) testing and to determine the rate of malignancy in resected nodules, stratified by mutational analysis and microRNA profile. Of 1917 fine need aspirations, 140 (7.3%) underwent Interpace testing: 47 (33.6%) were molecular-not-benign (harbored mutation, fusion, and/or positive miRNA) and 93 (66.4%) were molecular-benign (no mutations or fusions and negative microRNA). Surgery was spared in 79.6% of molecular-benign and 61.4% of all tested patients. Fifty-four (38.6%) underwent resection. Seventeen (89.5%) of the resected molecular-benign were benign and 2 were malignant. Thirteen (37.1%) of the resected molecular-not-benign were benign, 7 (20%) were noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), and 15 (42.9%) were malignant (p < 0.05, negative predictive value (NPV) 89.4-95.6%, positive predictive value (PPV) 22.3-42.8%). Most molecular-not-benign (72.3%) had RAS-like mutation. Twenty-three were resected: 3 were malignant and 7 were NIFTP. Nodules with non-RAS-like mutations (BRAF V600E-like, others) were more likely to be malignant than RAS-like (H/N/KRAS, BRAF K601E) (p < 0.05, NPV 86.9-96.5%, PPV 100%). Most nodules had RAS-like mutations and most were benign or low-risk neoplasms (NIFTP). This study supports the role of histologic examination in the distinction of malignancy in RAS-like thyroid neoplasms and underscores the role of molecular testing in risk stratification, patient counseling, and operative management.

Synchronous and Metastatic Papillary and Follicular Thyroid Carcinomas with Unique Molecular Signatures.

Despite the relatively high prevalence of thyroid cancer, the occurrence of multiple synchronous, distinct subtypes of primary thyroid carcinoma is uncommon. The incidental finding of papillary thyroid microcarcinoma in a gland with a biologically relevant follicular or medullary carcinoma is more frequent than the synchronous occurrence of multiple clinically significant carcinomas. We report a case of synchronous papillary and follicular thyroid carcinomas metastatic to lymph node and bone, respectively. Next generation sequencing showed BRAF V600E mutation in the primary papillary carcinoma and NRAS Q61R mutation in the primary follicular carcinoma and bony metastasis. To our knowledge, this is the first reported case of synchronous and metastatic primary papillary and follicular carcinomas, and the first report of synchronous BRAF V600E mutated papillary and NRAS mutated follicular carcinoma.

Clinical presentation and response to therapy in patients with massive prolactin hypersecretion.

Prolactin hypersecretion from a pituitary adenoma usually results in a serum prolactin level less than 1,000 ng/ml. During therapy with a dopamine agonist, prolactin levels usually normalize and the tumors shrink substantially. In the past few years, we have seen three men who presented with serum prolactin levels greater than 10,000 ng/ml. All presented with large tumors, visual field deficits, and hypogonadotropic hypogonadism. All other pituitary hormones were normal. In all three patients, significant tumor shrinkage was achieved with improvement or resolution of headaches and visual field deficits. None of our patients has been able to achieve a normal prolactin or testosterone. A literature review identified 32 patients with prolactin levels of more than 10,000 ng/ml. Twenty-six (81%) were males. Most had large tumors, headaches and visual field defects. Even with the addition of surgery and/or radiation therapy to medical therapy, normalization of serum prolactin occurred in only six patients (19%) and only one man achieved a normal testosterone. We conclude that in patients with massive prolactin hypersecretion, therapy with a dopamine agonist will lead to tumor shrinkage and improvement of mass effects, but usually does not normalize prolactin or testosterone. Rather than waiting for maximal prolactin reduction, we would recommend early institution of testosterone replacement therapy.

Long-term risks for thyroid cancer and other neoplasms after exposure to radiation.

Radiation-related thyroid cancer continues to be a clinical concern for two reasons: the risks associated with the widespread use of radiation treatments for benign conditions in the middle of the last century persist for decades after exposure; and radiation continues to be an effective component of the treatment of several childhood malignancies. Patients who were irradiated in the head and neck area need to be evaluated for thyroid cancer, benign thyroid nodules, hyperparathyroidism, salivary-gland neoplasms and neural tumors, including acoustic neuromas. Radiation-related thyroid cancers appear to have the same clinical behavior as other thyroid cancers, but many irradiated patients are entering the age range when more aggressive neoplasms occur. In this paper, we review how to approach the clinical management of a patient with a history of radiation exposure in the thyroid area, and how to treat radiation-exposed patients who develop related neoplasms, especially thyroid cancer.