Publications (29) View all
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Article: Carcinoma of the Thyroid With Ewing Family Tumor Elements: A Tumor With Unknown Histogenesis.
International Journal of Surgical Pathology 05/2013; · 1.00 Impact Factor -
Article: Carcinoma of the Thyroid With Ewing Family Tumor Elements and Favorable Prognosis: Report of a Second Case.
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ABSTRACT: The rare reports of primary, nonneuroendocrine small cell carcinomas of the thyroid have not provided enough evidence to support the recognition of these tumors as an entity or to understand their etiopathogenesis. We report the second case of a primary, nonneuroendocrine small cell carcinoma of the thyroid displaying diffuse expression of cytokeratins, CD99, and p63, in the absence of vimentin expression, in a 24-year-old male who is alive without any signs of disease 13 years after total thyroidectomy and radioactive iodine. The tumor disclosed the EWSR1-FLI1 rearrangement, and we propose to designate it as a carcinoma of the thyroid with Ewing family tumor elements.International Journal of Surgical Pathology 05/2013; · 1.00 Impact Factor -
Article: Cribriform-Morular Variant of Papillary Thyroid Carcinoma Displaying Poorly Differentiated Features.
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ABSTRACT: Cribriform-morular variant of papillary thyroid carcinoma (CMVPTC) usually occurs in the setting of familial adenomatous polyposis (FAP) although it can rarely arise sporadically. Poorly differentiated thyroid carcinoma (PDTC) is a follicular cell-derived neoplasm with more aggressive behavior than well-differentiated carcinomas such as CMVPTC. We report the case of a 35-year-old woman without FAP history who presented a left neck mass and complained of back pain. Imagiological examinations revealed a nodule in the left lobe of thyroid and multiple nodular lesions in the bone and lungs suggestive of metastases. The patient was submitted to total thyroidectomy and radioactive iodine. The tumor was composed of CMVPTC and PDTC components that shared the same somatic APC gene mutation (p.Cys520Tyr_fsX534). Besides this mutation, no CTNNB1, BRAF, N-RAS, and H-RAS gene mutations were detected in any of the 2 components. To the best of our knowledge, this is the first report of a sporadic CMVPTC with transformation into PDTC. Although the majority of CMVPTCs carry an indolent clinical outcome, the coexistence of poorly differentiated areas may justify the aggressiveness of the CMVPTC reported here.International Journal of Surgical Pathology 01/2013; · 1.00 Impact Factor -
Article: TGF-beta/Smad pathway and BRAF mutation play different roles in circumscribed and infiltrative papillary thyroid carcinoma.
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ABSTRACT: Poorly circumscribed growth pattern, extra-thyroid extension and high intratumoural lymph vessel density are significantly associated to nodal metastatization in papillary thyroid carcinoma (PTC). It was also shown that transforming growth factor beta (TGF-beta)/Smad-dependent pathway activity is associated with local invasion, nodal metastatization and BRAF-mutated PTCs. We analysed the immunoexpression of TGF-beta, Smad2/Smad3, Smad4 and Smad7 in a series of 42 cases of classic PTC and 33 cases of follicular variant of PTC with known clinico-pathological and follow-up data, as well as BRAF and RAS status. The 75 PTCs were divided into poorly circumscribed (PCPTC) (n = 53) and well circumscribed (WCPTC) (n = 22) according to their borders. Nodal metastases were not detected in any WCPTC regardless of the presence of immunoexpression for TGF-beta, Smad2/Smad3, Smad4 and Smad7 and occurrence of BRAF mutation (in 20 % of WCPTCs). Increased cytoplasmatic expression of TGF-beta at the periphery of PCPTC was associated to morphological features of invasiveness, featuring the so-called epithelial-to-mesenchymal transition (EMT), and presence of nodal metastases, as well as to the occurrence of BRAF mutation which did not significantly alter, per se, the frequency of nodal metastases. The nuclear expression of Smad7 was more frequent in WCPTCs than in PCPTCs and was associated with unicentricity and absence of extra-thyroid extension, vascular invasion and nodal metastases. We conclude that nodal metastases are associated to poorly circumscribed, locally invasive PTCs that exhibit low levels of nuclear Smad7 and a peripheral EMT phenotype displaying TGF-beta overexpression, regardless of the occurrence of BRAF mutation.Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 04/2012; 460(6):587-600. · 2.49 Impact Factor -
Article: RET/PTC rearrangement is prevalent in follicular Hürthle cell carcinomas.
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ABSTRACT: de Vries M M, Celestino R, Castro P, Eloy C, Máximo V, van der Wal J E, Plukker J T M, Links T P, Hofstra R M W, Sobrinho-Simões M & Soares P (2012) Histopathology RET/PTC rearrangement is prevalent in follicular Hürthle cell carcinomas Aims: The molecular alterations underlying follicular Hürthle cell carcinomas (FHCCs) are largely unknown. In an attempt to clarify this issue, we analysed a series of Hürthle cell tumours for the presence of RET/PTC and PAX8/PPARG rearrangements and BRAF, HRAS and NRAS mutations. Methods and results: We investigated a series of 20 follicular Hürthle cell tumours [17 FHCCs and three follicular Hürthle cell adenomas (FHCAs)]. RET/PTC rearrangements were found in 33% of FHCAs and in 38% of FHCCs. All RET/PTC-positive FHCCs had a solid pattern of growth. PAX8/PPARG rearrangement was present in 27% of the FHCCs which displayed, in most cases, a follicular architecture. NRAS mutation was detected in one FHCC. An FHCC with a solid/microfollicular growth pattern scored positive for both RET/PTC and PAX8/PPARG rearrangement. Conclusions: Our study has shown a significant association between RET/PTC rearrangements and FHCCs with a solid growth pattern, thus raising the possibility of using tyrosine kinase inhibitors for the treatment of patients with FHCCs, which are often refractory to radioiodine treatment.Histopathology 04/2012; · 3.08 Impact Factor
