Thyroid paraganglioma. Report of 3 cases and description of an immunohistochemical profile useful in the differential diagnosis with medullary thyroid carcinoma, based on complementary DNA array results

Castelblanco, Esmeralda; Gallel, Pilar; Ros, Susana; Gatius, Sonia; Valls, Joan; De-Cubas, Aguirre A.; Maliszewska, Agnieszka; Yebra-Pimentel, M. Teresa; Menarguez, Javier; Gamallo, Carlos; Opocher, Giuseppe; Robledo, Mercedes; Matias-Guiu, Xavier

doi:10.1016/j.humpath.2011.08.022

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Thyroid paraganglioma. Report of 3 cases and description of an immunohistochemical profile useful in the differential diagnosis with medullary thyroid carcinoma, based on complementary DNA array results☆

Esmeralda Castelblanco, BSc
- Department of Pathology and Molecular Genetics, Hospital Universitari Arnau de Vilanova, University of Lleida, IRBLLEIDA, 25198 Lleida, Spain
- Department of Surgery, Hospital Universitari Arnau de Vilanova, University of Lleida, IRBLLEIDA, 25198 Lleida, Spain
- Department of Research Laboratory, Hospital Universitari Arnau de Vilanova, University of Lleida, IRBLLEIDA, 25198 Lleida, Spain
Pilar Gallel, MD
- Department of Pathology and Molecular Genetics, Hospital Universitari Arnau de Vilanova, University of Lleida, IRBLLEIDA, 25198 Lleida, Spain
- Department of Surgery, Hospital Universitari Arnau de Vilanova, University of Lleida, IRBLLEIDA, 25198 Lleida, Spain
- Department of Research Laboratory, Hospital Universitari Arnau de Vilanova, University of Lleida, IRBLLEIDA, 25198 Lleida, Spain
Susana Ros, MD
- Department of Pathology and Molecular Genetics, Hospital Universitari Arnau de Vilanova, University of Lleida, IRBLLEIDA, 25198 Lleida, Spain
- Department of Surgery, Hospital Universitari Arnau de Vilanova, University of Lleida, IRBLLEIDA, 25198 Lleida, Spain
- Department of Research Laboratory, Hospital Universitari Arnau de Vilanova, University of Lleida, IRBLLEIDA, 25198 Lleida, Spain
Sonia Gatius, MD
- Department of Pathology and Molecular Genetics, Hospital Universitari Arnau de Vilanova, University of Lleida, IRBLLEIDA, 25198 Lleida, Spain
- Department of Surgery, Hospital Universitari Arnau de Vilanova, University of Lleida, IRBLLEIDA, 25198 Lleida, Spain
- Department of Research Laboratory, Hospital Universitari Arnau de Vilanova, University of Lleida, IRBLLEIDA, 25198 Lleida, Spain
Joan Valls, PhD
- Department of Pathology and Molecular Genetics, Hospital Universitari Arnau de Vilanova, University of Lleida, IRBLLEIDA, 25198 Lleida, Spain
- Department of Surgery, Hospital Universitari Arnau de Vilanova, University of Lleida, IRBLLEIDA, 25198 Lleida, Spain
- Department of Research Laboratory, Hospital Universitari Arnau de Vilanova, University of Lleida, IRBLLEIDA, 25198 Lleida, Spain
Aguirre A. De-Cubas, BSc
- Centro Nacional de Investigaciones Oncológicas (CNIO), 28029 Madrid, Spain
Agnieszka Maliszewska, BSc
- Centro Nacional de Investigaciones Oncológicas (CNIO), 28029 Madrid, Spain
M. Teresa Yebra-Pimentel, MD
- Hospital Juan Canalejo, 15006 La Coruña, Spain
Javier Menarguez, MD
- Hospital Gregorio Marañon, 28007 Madrid, Spain
Carlos Gamallo, MD
- Hospital de la Princesa, 28006 Madrid, Spain
Giuseppe Opocher, PhD
- Familial Cancer Clinic, Veneto Institute of Oncology, 35128 Padova, Italy
- Department of Medical and Surgical Sciences, University of Padova, 35122 Padova, Italy
Mercedes Robledo, PhD
- Centro Nacional de Investigaciones Oncológicas (CNIO), 28029 Madrid, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), 28029 Madrid, Spain
Xavier Matias-Guiu, MD, PhD
- Department of Pathology and Molecular Genetics, Hospital Universitari Arnau de Vilanova, University of Lleida, IRBLLEIDA, 25198 Lleida, Spain
- Department of Surgery, Hospital Universitari Arnau de Vilanova, University of Lleida, IRBLLEIDA, 25198 Lleida, Spain
- Department of Research Laboratory, Hospital Universitari Arnau de Vilanova, University of Lleida, IRBLLEIDA, 25198 Lleida, Spain
- Corresponding author. Department of Pathology and Molecular Genetics, Hospital Universitari Arnau de Vilanova, Av. Alcalde Rovira Roure 80, 25198 Lleida, Spain

Received 22 June 2011; received in revised form 12 August 2011; accepted 18 August 2011. published online 03 January 2012.
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Summary

Thyroid paraganglioma is a rare disorder that sometimes poses problems in differential diagnosis with medullary thyroid carcinoma. So far, differential diagnosis is solved with the help of some markers that are frequently expressed in medullary thyroid carcinoma (thyroid transcription factor 1, calcitonin, and carcinoembryonic antigen). However, some of these markers are not absolutely specific of medullary thyroid carcinoma and may be expressed in other tumors. Here we report 3 new cases of thyroid paraganglioma and describe our strategy to design a diagnostic immunohistochemical battery. First, we performed a comparative analysis of the expression profile of head and neck paragangliomas and medullary thyroid carcinoma, obtained after complementary DNA array analysis of 2 series of fresh-frozen samples of paragangliomas and medullary thyroid carcinoma, respectively. Seven biomarkers showing differential expression were selected (nicotinamide adenine dinucleotide dehydrogenase 1 alpha subcomplex, 4-like 2, NDUFA4L2; cytochrome c oxidase subunit IV isoform 2; vesicular monoamine transporter 2; calcitonin gene-related protein/calcitonin; carcinoembryonic antigen; and thyroid transcription factor 1) for immunohistochemical analysis. Two tissue microarrays were constructed from 2 different series of paraffin-embedded samples of paragangliomas and medullary thyroid carcinoma. We provide a classifying rule for differential diagnosis that combines negativity or low staining for calcitonin gene-related protein (histologic score, <10) or calcitonin (histologic score, <50) together with positivity of any of NADH dehydrogenase 1 alpha subcomplex, 4-like 2; cytochrome c oxidase subunit IV isoform 2; or vesicular monoamine transporter 2 to predict paragangliomas, showing a prediction error of 0%. Finally, the immunohistochemical battery was checked in paraffin-embedded blocks from 4 examples of thyroid paraganglioma (1 previously reported case and 3 new cases), showing also a prediction error of 0%. Our results suggest that the comparative expression profile, obtained by complementary DNA arrays, seems to be a good tool to design immunohistochemical batteries used in differential diagnosis.

Keywords: cDNA arrays, Differential diagnosis, Immunohistochemistry, Medullary thyroid carcinoma, Thyroid paraganglioma, Tissue microarray

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☆ Supported by grants 2009SGR794, RD06/0020/1034, FIS PI080883, Fundación Mutua Madrileña AP2775/2008, and programa de intensificación de la investigación ISCIII. E. C. holds a predoctoral fellowship from AGAUR 2010FI-B01057. A. A. d. C. and A. M. are predoctoral fellows from La Caixa Fundation. Tumor samples were obtained with the support of Xarxa Catalana de Bancs de Tumors, the Tumor Banc Platform of RTICC and RD09/0076/00059, as well as the Spanish Tumor Bank Network coordinated by CNIO.

PII: S0046-8177(11)00375-3

doi:10.1016/j.humpath.2011.08.022

« BackHuman Pathology

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