A differential diagnosis of inherited endocrine tumors and their tumor counterparts

Toledo, S. P. A.; Lourenço, Delmar M.; Toledo, Rodrigo A.

doi:10.6061/clinics/2013(07)24

Cited by 15 publications

(11 citation statements)

References 199 publications

(477 reference statements)

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“…The clinical diagnosis of MEN1 was defined as previously established (1,5,27). Familial MEN1 was characterized by the combined presence of a MEN1 index case and at least one first-degree family member with one or more main MEN1-related tumors (HPT, PET, PIT).…”

Section: Patientsmentioning

confidence: 99%

“…Genetic testing should be also offered for several sporadic cases with MEN1-related tumors, such as multiglandular parathyroid disease, gastrinoma and multiple PET at any age; parathyroid hyperplasia (<40 years); recurrent HPT; several atypical MEN1-related phenotypes (5) and, more recently, PIT macroadenoma identified at a young age, adding a substantial number of cases to be genetically tested (26). This goal should be pursued as genetic diagnosis provides an opportunity for earlier treatment, avoiding comorbidities as those associated with HPT, PIT macroadenomas or PETs (3,4,5,6,7,8,9,10,11,12,13,14,24,25,26,27).…”

Section: Introductionmentioning

confidence: 99%

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Germline mutation landscape of multiple endocrine neoplasia type 1 using full gene next-generation sequencing

Carvalho¹,

Urtremari²,

Jorge³

et al. 2018

European Journal of Endocrinology

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Background Loss-of-function germline MEN1 gene mutations account for 75–95% of patients with multiple endocrine neoplasia type 1 (MEN1). It has been postulated that mutations in non-coding regions of MEN1 might occur in some of the remaining patients; however, this hypothesis has not yet been fully investigated. Objective To sequence for the entire MEN1 including promoter, exons and introns in a large MEN1 cohort and determine the mutation profile. Methods and patients A target next-generation sequencing (tNGS) assay comprising 7.2 kb of the full MEN1 was developed to investigate germline mutations in 76 unrelated MEN1 probands (49 familial, 27 sporadic). tNGS results were validated by Sanger sequencing (SS), and multiplex ligation-dependent probe amplification (MLPA) assay was applied when no mutations were identifiable by both tNGS and SS. Results Germline MEN1 variants were verified in coding region and splicing sites of 57/76 patients (74%) by both tNGS and SS (100% reproducibility). Thirty-eight different pathogenic or likely pathogenic variants were identified, including 13 new and six recurrent variants. Three large deletions were detected by MLPA only. No mutation was detected in 16 patients. In untranslated, regulatory or in deep intronic MEN1 regions of the 76 MEN1 cases, no point or short indel pathogenic variants were found in untranslated, although 33 benign/likely benign and three new VUS variants were detected. Conclusions Our study documents that point or short indel mutations in non-coding regions of MEN1 are very rare events. Also, tNGS proved to be a highly effective technology for routine genetic MEN1 testing.

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Section: Patientsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Germline mutation landscape of multiple endocrine neoplasia type 1 using full gene next-generation sequencing

Carvalho¹,

Urtremari²,

Jorge³

et al. 2018

European Journal of Endocrinology

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“…Germline mutations that cause familial predisposition to pituitary tumors, including multiple endocrine neoplasia (MEN) type 1 (MEN1), MEN4, Carney complex and familial isolated pituitary adenoma, as well as mutations in genes encoding succinate dehydrogenase (SDHB, SDHC and SDHD) [42], have also been linked with a tendency to present with a more aggressive clinical course than sporadic adenomas [43,44,45]. …”

Section: Evolving Biomarkers Of Pituitary Tumor Aggressivenessmentioning

confidence: 99%

Aggressive Pituitary Tumors

et al. 2015

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Pituitary adenomas are common intracranial tumors that are mainly considered as benign. Rarely, these tumors can exhibit an aggressive behavior, characterized by gross invasion of the surrounding tissues, resistance to conventional treatment leading to early and frequent recurrences. Even more rarely, pituitary tumors can give rise to cerebrospinal or systemic metastases qualifying as pituitary carcinomas according to the latest WHO definition. In the same classification, a subset of tumors with relatively distinct histopathological features was identified and defined as atypical adenomas designated to follow a more aggressive clinical course. This classification, although clinically useful, does not provide an accurate correlation between histopathological findings and the clinical behavior of these tumors, neither is it adequate to convey the precise features of ‘aggressive' tumors. Thus, ‘aggressive' pituitary adenomas need to be properly defined with clinical, radiological, histological and molecular markers in order to identify patients at increased risk of early recurrence or subsequent tumor progression. At present, no single marker or classification system of pituitary tumor aggressiveness exists, and clinically useful information in the literature is insufficient to guide diagnostic and therapeutic decisions. Treatment of patients with aggressive pituitary tumors is challenging since conventional treatments often fail, necessitating multiple surgical procedures with additional radiotherapy. Although traditional chemotherapy applied in other neuroendocrine tumors has not been shown to be efficacious, newer agents, particularly temozolomide, have shown promising results and are currently used despite the lack of data from a randomized prospective trial. Molecular targeted therapies such as mTOR and epidermal growth factor inhibitors have also been applied and might prove to be useful in the management of these patients. In the present review, we provide information regarding the epidemiology and clinical, histopathological and molecular features of aggressive pituitary tumors using recent employed definitions. In addition, we review currently employed therapeutic means providing a therapeutic algorithm and highlight the need to identify more specific disease-related and prognostic markers and the necessity for central registration of these tumors.

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“…Pituitary tumors in MEN1 patients are present from 10 to 60% and they can be the first clinical manifestation in up to 15% of the cases. Pituitary adenomas associated with MEN1 differ from sporadic ones ( 18 ). In MEN1, they are usually diagnosed at earlier ages, frequently macroadenomas, often resistant to medical therapy and with high recurrence rates ( 18 ).…”

Section: Progress In Classificationmentioning

confidence: 95%

Progress in the Diagnosis and Classification of Pituitary Adenomas

et al. 2015

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Pituitary adenomas are common neoplasms. Their classification is based upon size, invasion of adjacent structures, sporadic or familial cases, biochemical activity, clinical manifestations, morphological characteristics, response to treatment and recurrence. Although they are considered benign tumors, some of them are difficult to treat due to their tendency to recur despite standardized treatment. Functional tumors present other challenges for normalizing their biochemical activity. Novel approaches for early diagnosis, as well as different perspectives on classification, may help to identify subgroups of patients with similar characteristics, creating opportunities to match each patient with the best personalized treatment option. In this paper, we present the progress in the diagnosis and classification of different subgroups of patients with pituitary tumors that may be managed with specific considerations according to their tumor subtype.

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A differential diagnosis of inherited endocrine tumors and their tumor counterparts

Cited by 15 publications

References 199 publications

Germline mutation landscape of multiple endocrine neoplasia type 1 using full gene next-generation sequencing

Germline mutation landscape of multiple endocrine neoplasia type 1 using full gene next-generation sequencing

Aggressive Pituitary Tumors

Progress in the Diagnosis and Classification of Pituitary Adenomas

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