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

In 1987, Carney et al reported 11 thyroid tumors with the following features: circumscription or encapsulation, trabecular architecture with intratrabecular hyalin and colloid, polygonal and spindle cells, nuclei with frequent grooves and cytoplasmic inclusions, occasional psammoma bodies, and a low mitotic rate. The neoplasms did not recur or metastasize during a follow-up period that averaged 10 years, and they were titled hyalinizing trabecular adenomas. Subsequently, the nuclear features of the neoplasm led to the introduction of 2 modified titles for it, hyalinizing trabecular tumor and hyalinizing trabecular neoplasm. Later, discovery of RET/PTC mutations in the tumor resulted in it being designated as a type of papillary thyroid carcinoma. We studied 119 neoplasms of the type outlined, collected over a 20-year period, for invasion, recurrence and metastasis, and obtained follow-up in 96% of the cases. One hundred eighteen tumors showed no evidence of aggressive behavior (capsular, vascular, and parenchymal invasion), local recurrence, or metastasis. One tumor showed vascular and capsular invasion, and pulmonary metastasis. We conclude that the overwhelming majority of hyalinizing trabecular tumors of the thyroid behave as benign neoplasms and that, at this time, hyalinizing trabecular adenoma is the most appropriate title for them.
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PMID:Hyalinizing trabecular tumors of the thyroid gland are almost all benign. 1881 21

Non-medullary thyroid carcinoma (NMTC) is mostly sporadic, but familial clustering is described. We aimed to compare the features of patients with sporadic and familial NMTC (FNMTC) patients and to assess whether FNMTC patients with parent-child relationship exhibit the 'anticipation' phenomenon (earlier age at disease onset and increased severity in successive generations). Among 300 NMTCs followed in the Section of Endocrinology (University of Siena, Italy), 34 (11.3%) patients, all with the papillary histotype, (16 kindred), met the criteria of FNMTC. Twenty-seven of them (79.4%) exhibited a parent-child relationship and seven (20.6%) a sibling relationship. These patients were compared with 235 patients with sporadic papillary thyroid cancer (PTCs). To analyze the features of FNMTC of the first and second generations, we cumulated the series of Siena with 32 additional FNMTC patients (15 kindred) from the Department of Endocrinology-Endocrine Oncology, Thessaloniki, Greece. Significant difference between sporadic PTC and FNMTC patients included more frequent tumor multifocality (P=0.001) and worse final outcome in FNMTC patients (P=0.001). Among 47 FNMTC with parent-child relationship, we found an earlier age at disease presentation (P<0.0001), diagnosis (P<0.0001), and disease onset (P=0.04) in the second generation when compared with the first generation. Patients in the second generation were more frequently males (P=0.02); their tumors were more frequently multifocal (P=0.003) and bilateral (P=0.01), had higher rate of lymph node metastases at surgery (P=0.02) and worse outcome (P=0.04) when compared with the first generation. In conclusion, FNMTC displays the features of clinical 'anticipation' with the second generation acquiring the disease at an earlier age and having more advanced disease at presentation.
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PMID:Familial non-medullary thyroid carcinoma displays the features of clinical anticipation suggestive of a distinct biological entity. 1883 44

RET/PTC rearrangements are initiating events in the development of a significant proportion of papillary thyroid carcinomas. Activated RET/PTC mutations are thought to be restricted to thyroid disease, but this study proposes that these events may also occur in nonthyroid tumors. A total of 57 nonthyroid papillary tumors were examined for RET/PTC rearrangements using interphase fluorescence in situ hybridization, Taqman reverse transcriptase polymerase chain reaction, and immunohistochemistry. Taqman single nucleotide polymorphism detection was used to analyze for expression of mutated BRAF T1799A. In all, 20% (3/15) of primary peritoneal carcinoma had detectable RET/PTC1 rearrangements by all 3 methodologies. A further case of similar histotype had an alternate RET/ PTC rearrangement. No RET/PTC1 rearrangements were detected in the remaining tumor cohort. All 57 tumors were homozygous for wild-type BRAF. The results indicate that RET/PTC rearrangements occur in a small subset of nonthyroid papillary tumors. These rearrangements may not be directly implicated in tumor growth; rather representing "passenger" mutations reflecting RET instability in secondary tumor subclones.
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PMID:RET/PTC rearrangement occurring in primary peritoneal carcinoma. 1914 13

Capillary thyroid carcinoma (PTC) is the most common neoplasm of thyroid. It usually grows slowly and is clinically indolent; although rare, its aggressive forms with local invasion or distant metastases can occur. Metastatic thyroid carcinoma rarely involves the orbit. We reported an uncommon case of orbital metastasis of PTC. A 66-years-old woman presented proptosis of the right eye. The biopsy of the tumor in orbit revealed metastatic thyroid carcinoma. The ultrasensitive TSH level was 1,34 mUI/L and free T4 level was 1,65 ng/dL. A total thyroidectomy was performed and histopathological analysis of the nodule revealed follicular variant of papillary thyroid carcinoma. Currently, the patient has been receiving palliative chemotherapy with Clodronate Disodium. The importance of the case is due to its unusual presentation, which emerged as a primary clinical manifestation. Although rare, thyroid carcinoma should be suspected in orbit metastasis.
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PMID:Orbital metastasis as primary clinical manifestation of thyroid carcinoma--case report and literature review. 1919 59

Metastatic lesions from differentiated thyroid cancer (DTC) are usually seen in the cervical lymph nodes, lungs, or bones. Skeletal muscle, especially erector spinae metastasis from DTC, is extremely rare. In this report, 2 cases of DTC metastasizing to the erector spinae incidentally found by I-131 whole-body scanning and low-dose I-131 SPECT/CT scan are described. One is a PTC and the other is the follicular variant of PTC. I-131 whole-body scan is indispensable for the management of patients with DTC. However, precise localization of the foci of I-131 uptake is formidable because of the lack of anatomic landmarks. Low-dose integrated SPECT/CT allows for better location and definition of I-131 whole-body scan findings for residual or metastases in DTC. Metastases to skeletal muscle in DTC may be incidental findings and are more common on I-131 whole-body scans combined with SPECT/CT scans.
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PMID:Erector spinae metastases from differentiated thyroid cancer identified by I-131 SPECT/CT. 1935 73

In endocrine malignancies (thyroid carcinoma, parathyroid carcinoma, adrenocortical carcinoma, malignant pheochromocytoma) surgery is currently the treatment of choice, in case of differentiated thyroid carcinomas followed by 131-I-radioiodine administration. This approach is often successful in early disease; however, treatment options for advanced endocrine malignancies remain unsatisfactory and prognosis is poor. In particular, cytotoxic chemotherapy and radiation therapy often show only limited and transient efficacy and are associated with significant toxicity. Thus, new treatment options are urgently needed. Advances in the understanding of the molecular pathology of endocrine malignancies has recently led to identification of key events in endocrine oncogenesis (e.g. oncogenic RET mutations in medullary thyroid carcinoma or RET/PTC rearrangements in papillary thyroid carcinoma). These new insights are increasingly matched by new compounds (e.g. tyrosine kinase inhibitors) targeting signaling pathways essential for tumor cell survival, proliferation and metastases. Accordingly, a rapidly growing number of preclinical investigations and early clinical trials in endocrine malignancies have been initiated. First results of "targeted therapies" in medullary and differentiated thyroid carcinoma are impressive: phase II trials targeting RET or VEGF receptor kinases led to objective tumor response in up to 50% of patients. This review covers these recent molecular and clinical advances which most likely will dramatically alter the treatment of endocrine malignancies within the coming decade.
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PMID:New targets and therapeutic approaches for endocrine malignancies. 1937 19

Patients with poorly differentiated thyroid cancers (PDTC), anaplastic thyroid cancers (ATC), and radioactive iodine-refractory (RAIR) differentiated thyroid cancers have a high mortality, particularly if positive on [(18)F]fluorodeoxyglucose (FDG)-positron emission tomography (PET). To obtain comprehensive genetic information on advanced thyroid cancers, we designed an assay panel for mass spectrometry genotyping encompassing the most significant oncogenes in this disease: 111 mutations in RET, BRAF, NRAS, HRAS, KRAS, PIK3CA, AKT1, and other related genes were surveyed in 31 cell lines, 52 primary tumors (34 PDTC and 18 ATC), and 55 RAIR, FDG-PET-positive recurrences and metastases (nodal and distant) from 42 patients. RAS mutations were more prevalent than BRAF (44 versus 12%; P = 0.002) in primary PDTC, whereas BRAF was more common than RAS (39 versus 13%; P = 0.04) in PET-positive metastatic PDTC. BRAF mutations were highly prevalent in ATC (44%) and in metastatic tumors from RAIR PTC patients (95%). Among patients with multiple metastases, 9 of 10 showed between-sample concordance for BRAF or RAS mutations. By contrast, 5 of 6 patients were discordant for mutations of PIK3CA or AKT1. AKT1_G49A was found in 9 specimens, exclusively in metastases. This is the first documentation of AKT1 mutation in thyroid cancer. Thus, RAIR, FDG-PET-positive metastases are enriched for BRAF mutations. If BRAF is mutated in the primary, it is likely that the metastases will harbor the defect. By contrast, absence of PIK3CA/AKT1 mutations in one specimen may not reflect the status at other sites because these mutations arise during progression, an important consideration for therapies directed at phosphoinositide 3-kinase effectors.
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PMID:Mutational profile of advanced primary and metastatic radioactive iodine-refractory thyroid cancers reveals distinct pathogenetic roles for BRAF, PIK3CA, and AKT1. 1948 99

The 5 main types of thyroid cancer (papillary, PTC, follicular, FTC, poorly differentiated, PDTC undifferentiated, UTC, medullary, MTC) not only differ regarding morphology, pathogenesis, genetics,and pathophysiology (iodine metabolism, thyroglobulin and calcitonin production), but also concerning tumor biology, metastatic behavior (lymphogenous, locally invasive and hematogenous routes) and prognosis. Knowledge of these features is the basis of the surgical concept of one or two-stage thyroidectomy, the exceptions and the concept of locoregional lymph node dissection. Lymph node surgery plays an important role in those cancers exhibiting mainly lymph node metastases (PTC, MTC) not only due to frequent recurrences but also due to its potential curative intent. Differentiated carcinomas may have an acceptable prognosis despite local invasion of the cervical aerodigestive system, thus resections are justified when technical prerequisites are given.
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PMID:[Surgery of thyroid carcinoma]. 1990 89

Differentiated thyroid carcinoma is the most frequent neoplasm of the endocrine system. Although thyroid cancer usually has an excellent prognosis, no therapeutic options are available for patients that develop metastases and are or became resistant to radioiodine therapy. The deeper knowledge of molecular aberrations that characterize tumor growth has provided novel targets in cancer therapy. Several proteins have been implicated as having a crucial role in the carcinogenesis of differentiated thyroid cancer, such as those involved in RET/PTC-RAS-RAF-MAPK pathway. Moreover, vascular aberrations and angiogenesis equilibrium have also been related to tumor growth. The development of new, targeted therapies and their encouraging initial results have opened a hopeful opportunity of treatment for these orphan therapy tumor patients.
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PMID:Targeted therapies in thyroid cancer. 1990

Completion operations after thyroid surgery due to incidental postoperative diagnosis of thyroid cancer are indicated in differentiated thyroid cancer with tumor size > 1 cm, extrathyroidal invasion, multifocality, angioinvasion or metastases. By thorough preoperative clinical work-up of nodular goiter (ultrasonography, fine needle aspiration cytology the frequency of completion thyroidectomies are aimed to be less than 10% of all thyroid cancer operations. To facilitate postoperative radioiodine ablation prophylactic completion operations can be postponed to 3 months postoperatively to minimize surgical morbidity, if not performed during the early postoperative period. Prophylactic central node dissection as part of the completion operation is reserved for papillary (PTC) and medullary carcinomas (MTC) but not for follicular cancer. Lateral node dissection is recommended in nodal-positive MTC and in PTC with more than 5 lymph node metastases in the central compartment.
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PMID:[Thyroid carcinoma found incidentally after thyroidectomy: postoperative strategy]. 1994 Dec 36


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