Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Introduction: Papillary thyroid cancer (PTC) is the most common endocrine malignancy. More than 98% of patients achieve an excellent response with no evidence of clinical, biochemical, or structural disease after initial treatment. In these patients structural recurrence is rare, more frequently diagnosed in the first 5 years from initial treatment and almost invariably localized in neck lymph nodes. Patient: We report the case of a woman affected by PTC who presented with rapidly rising anti-thyroglobulin antibodies (TgAb) level after 10 years from clinical, morphological and biochemical remission. Diagnosis and Treatment: In 2003, a 56 year old patient was treated with total thyroidectomy and radioiodine remnant ablation (RRA) for a PTC (2 cm) with minimal extrathyroidal extension (T3N1aM0 according to the 6th AJCC TNM staging system) associated with diffuse lymphocytic thyroiditis. In 2004 the patient was free of disease defined as undetectable Tg after recombinant human TSH administration in the absence of TgAb and structural disease. Since February 2012 the appearance and progressive increase of TgAb titer was observed and in 2014 a 18FDG-PET scan documented three hypermetabolic lesions suggestive of lung micrometastases. The lung lesions were cytologically confirmed as PTC metastases. Both the primary tissue and the lung metastasis were positive for BRAF V600E mutation. The patient was treated with 131-radioiodine that showed radioiodine avid lung lesions that lose the ability to take up iodine at the following treatment. The patient is still alive and the lung lesions are growing slowly. Conclusions: Structural recurrence in patients that demonstrated an excellent response after initial treatment for PTC is extremely rare, and distant metastases exceptional but possible. This case is peculiar because recurrence was early identified after 10 years from initial treatment for the presence of detectable TgAb in a patient that had an histological diagnosis of lymphocytic thyroiditis but with an atypical clinical presentation (normal thyroid at neck ultrasound and undetectable TgAb and anti-thyroid peroxidase antibodies). For this reason TgAb should be tested with Tg in patients with a history of lymphocytic thyroiditis, either histological or humoral, also when TgAb is in the normal range and not suggestive of autoimmune thyroiditis.
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PMID:Lung Recurrence of Papillary Thyroid Cancer Diagnosed With Antithyroglobulin Antibodies After 10 Years From Initial Treatment. 3035 57

Immunocytochemistry in a 78-year-old man diagnosed as having systemic metastatic cancer of unknown primary origin revealed atypical cells positive for napsin A and TTF-1, suggesting adenocarcinoma of the lung. However, there was no evidence of a primary lesion in the lung on positron emission tomography/computed tomography or at autopsy. Meanwhile, both the left and right thyroid lobes were firm and grayish white with marked fibrosis. Histology identified a diffuse sclerosing variant of papillary thyroid carcinoma that was positive for TTF-1 and napsin A but negative for PAX8. This disease entity is often misdiagnosed clinically as chronic thyroiditis. This is the first report of napsin A-positive and PAX8-negative thyroid carcinoma and highlights the pitfalls of clinicopathological diagnosis.
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PMID:Occult carcinoma confirmed to be a diffuse sclerosing variant of papillary thyroid carcinoma with unusual immunohistochemical features: A pitfall of clinicopathological diagnosis. 3165 81

Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are increasingly recognized, characterized by prolonged survival even with metastatic disease. Their medical treatment is complex involving various specialties, necessitating awareness of treatment-related adverse effects (AEs). As GEP-NENs express somatostatin receptors (SSTRs), long-acting somatostatin analogs (SSAs) that are used for secretory syndrome and tumor control may lead to altered glucose metabolism. Everolimus and sunitinib are molecular targeted agents that affect glucose and lipid metabolism and may induce hypothyroidism or hypocalcemia, respectively. Chemotherapeutic drugs can affect the reproductive system and water homeostasis, whereas immunotherapeutic agents can cause hypophysitis and thyroiditis or other immune-mediated disorders. Treatment with radiopeptides may temporarily lead to radiation-induced hormone disturbances. As drugs targeting GEP-NENs are increasingly introduced, recognition and management of endocrine-related AEs may improve compliance and the quality of life of these patients.
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PMID:Endocrinological Toxicity Secondary to Treatment of Gastroenteropancreatic Neuroendocrine Neoplasms (GEP-NENs). 3183 42

Pembrolizumab, a programmed death 1 inhibitor, has been shown to have clinically significant efficacy in different types of cancer, providing long-term survival benefit for patients with lung cancer. Herein, we report the development of a primary thyroid cancer in a lung cancer patient that was being treated with pembrolizumab. Primary thyroid malignancy (and not only metastatic disease or immunotherapy-induced thyroiditis) should be considered in patients with lung cancer being treated with immune checkpoint inhibitors who develop new incidental thyroid lesions on imaging studies.
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PMID:Development of Thyroid Carcinoma During Treatment With Pembrolizumab in a Lung Cancer Patient. 3184 39

Background: Pediatric papillary thyroid carcinoma (PTC) is a rare malignancy, but with increasing incidence. Pediatric PTCs have distinct clinical and pathological features and even the molecular profile differs from adult PTCs. Somatic point mutations in pediatric PTCs have been previously described and studied, but complex information about fusion genes is lacking. The aim of this study was to identify different fusion genes in a large cohort of pediatric PTCs and to correlate them with clinical and pathological data of patients. Methods: The cohort consisted of 93 pediatric PTC patients (6-20 years old). DNA and RNA were extracted from fresh frozen tissue samples, followed by DNA and RNA-targeted next-generation sequencing analyses. Fusion gene-positive samples were verified by real-time polymerase chain reaction. Results: A genetic alteration was found in 72/93 (77.4%) pediatric PTC cases. In 52/93 (55.9%) pediatric PTC patients, a fusion gene was detected. Twenty different types of RET, NTRK3, ALK, NTRK1, BRAF, and MET fusions were found, of which five novel, TPR/RET, IKBKG/RET, BBIP1/RET, OPTN/BRAF, and EML4/MET, rearrangements were identified and a CUL1/BRAF rearrangement that has not been previously described in thyroid cancer. Fusion gene-positive PTCs were significantly associated with the mixture of classical and follicular variants of PTC, extrathyroidal extension, higher T classification, lymph node and distant metastases, chronic lymphocytic thyroiditis, and frequent occurrence of psammoma bodies compared with fusion gene-negative PTCs. Fusion-positive patients also received more doses of radioiodine therapy. The most common fusion genes were the RET fusions, followed by NTRK3 fusions. RET fusions were associated with more frequent lymph node and distant metastases and psammoma bodies, and NTRK3 fusions were associated with the follicular variant of PTC. Conclusions: Fusion genes were the most common genetic alterations in pediatric PTCs. Fusion gene-positive PTCs were associated with more aggressive disease than fusion gene-negative PTCs.
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PMID:RET, NTRK, ALK, BRAF, and MET Fusions in a Large Cohort of Pediatric Papillary Thyroid Carcinomas. 3249 21

A 58-year-old man with previous melanoma of the left leg underwent whole-body F-FDG PET/CT to stage metastatic disease prior to commencing pembrolizumab. Follow-up FDG PET/CT after 3 months of treatment showed partial metabolic response of soft tissue and nodal metastases and diffuse increased thyroid and colonic uptake, suggestive of thyroiditis and colitis. Pembrolizumab was ceased, and a repeat FDG PET/CT scan showed regression of uptake in the thyroid gland and colon, in keeping with resolution of inflammatory change. Immune-related adverse events induced by Immune checkpoint inhibitors, such as pembrolizumab, should be recognized-cessation of treatment often leads to resolution.
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PMID:Pembrolizumab-Induced Thyroiditis and Colitis-Presentation and Resolution on Serial FDG PET/CT. 3296 9


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