Breast metastasis from medullary thyroid carcinoma mimicking ductal carcinoma with neuroendocrine differentiation.

BACKGROUND: Medullary thyroid carcinoma very rarely metastasizes to the breast. Hematogenous spread to the liver, lungs, or mediastinum is more common. CASE: We describe the morphologic and immunohistochemical features of a 63-year-old woman who presented with a BIRADS-5 category nodule in the right breast and enlarged axillary lymph nodes. Core biopsy showed suggested breast cancer with neuroendocrine or apocrine differentiation. The immunohistochemical profile showed (RE-/RP-/HER-2-) and Ki67 10%. Chromogranin and synaptophysin were positive; AR and GCDFP-15 were negative. On reviewing the patient's clinical history, it was discovered that she had been treated for medullary thyroid carcinoma 15 years earlier. Additional stains showed positivity for TTF-1, CEA, and calcitonin. These findings were consistent with a diagnosis of breast metastasis from medullary thyroid carcinoma. We discuss briefly the morphologic features and the possible key features in order to make an accurate diagnosis. CONCLUSION: This case highlights the importance of investigating a history of cancer in patients with discordant or unusual histologic or immunohistochemical findings, as this can help avoid misdiagnosis and inappropriate treatment.

Contribution of molecular analysis to the typification of the non-functioning pituitary adenomas.

AIM: The WHO Classification of Tumours of Endocrine Organs considers the inmunohistochemical characterization of pituitary adenomas (PA) as mandatory for patient diagnosis. Recent advances in the knowledge of the molecular patterns of these tumours could complement this classification with gene expression profiling. METHODS: Within the context of the Spanish Molecular Registry of Pituitary Adenomas (REMAH), a multicentre clinical-basic research project, we analysed the molecular phenotype of 142 PAs with complete IHC and clinical information. Gene expression levels of all pituitary hormones, type 1 corticotrophin-releasing hormone receptor, dopamine receptors and arginine vasopressin receptor 1b were measured by quantitative real-time polymerase chain reaction. In addition, we used three housekeeping genes for normalization and a pool of nine healthy pituitary glands from autopsies as calibration reference standard. RESULTS: Based on the clinically functioning PA (FPA: somatotroph, corticotroph, thyrotroph and lactotroph adenomas), we established the interquartile range of relative expression for all genes studied in each PA subtype. That allowed molecularly the different PA subtypes, including the clinically non-functioning PA (NFPA). Afterwards, we estimated the concordance of the molecular and immunohistochemical classification with clinical diagnosis in FPA and between them in NFPA. The kappa values were higher in molecular than in immunohistochemical classification in FPA and showed a bad concordance in all NFPA subtypes. CONCLUSIONS: According to these results, the molecular characterization of the PA complements the IHC analysis, allowing a better typification of the NFPA.

Prevalence of Lynch syndrome among patients with newly diagnosed endometrial cancers.

BACKGROUND: Lynch syndrome (LS) is a hereditary condition that increases the risk for endometrial and other cancers. The identification of endometrial cancer (EC) patients with LS has the potential to influence life-saving interventions. We aimed to study the prevalence of LS among EC patients in our population. METHODS: Universal screening for LS was applied for a consecutive series EC. Tumor testing using microsatellite instability (MSI), immunohistochemistry (IHC) for mismatch-repair (MMR) protein expression and MLH1-methylation analysis, when required, was used to select LS-suspicious cases. Sequencing of corresponding MMR genes was performed. RESULTS: One hundred and seventy-three EC (average age, 63 years) were screened. Sixty-one patients (35%) had abnormal IHC or MSI results. After MLH1 methylation analysis, 27 cases were considered suspicious of LS. From these, 22 were contacted and referred for genetic counseling. Nineteen pursued genetic testing and eight were diagnosed of LS. Mutations were more frequent in younger patients (<50 yrs). Three cases had either intact IHC or MSS and reinforce the need of implement the EC screening with both techniques. CONCLUSION: The prevalence of LS among EC patients was 4.6% (8/173); with a predictive frequency of 6.6% in the Spanish population. Universal screening of EC for LS is recommended.

Adenocarcinoma y tumor carcinoide pulmonares sincrónicos. Presentación de dos casos / Two cases of synchronous adenocarcinoma and carcinoid tumour of the lung

La asociación de tumor carcinoide y carcinoma broncopulmonar en forma de tumores de aparición sincrónica es excepcional y sólo ha sido publicada en diez ocasiones. En el presente trabajo se describen los hallazgos en 2 pacientes con adenocarcinoma pulmonar en los que en el estudio de la pieza quirúrgica se identificó un tumor carcinoide típico. El hallazgo de un segundo nódulo en un paciente con un carcinoma broncopulmonar, situación cada vez más frecuente por la incorporación de técnicas de imagen con mayor sensibilidad, plantea la necesidad de su evaluación patológica para una correcta estadificación. Un problema adicional es la identificación de segundos nódulos en el curso de la intervención quirúrgica, lo que obliga al estudio intraoperatorio. La correcta valoración de los parámetros morfológicos y su comparación con los del tumor principal puede ser determinante en un correcto diagnóstico y evitar la sobrestadificación(AU)

The association of carcinoid tumour and bronchopulmonary carcinoma is very rare, with only 10 cases published to date. We present two cases of pulmonary adenocarcinoma in which a typical carcinoid tumour was an incidental finding on microscopy of the surgical specimen. The improved sensitivity of imaging techniques increases the possibility of detecting the presence of secondary nodules during the work-up for bronchopulmonary carcinoma, indicating further intraoperatory investigation. A correct morphological assessment and comparison with the main tumour could prove to be a key diagnostic factor, avoiding incorrect overstaging(AU)

Oncocytic transformation in pituitary adenomas: immunohistochemical analyses of 65 cases.

CONTEXT: Oncocytic change in pituitary adenomas has been evaluated by electron microscopy and more recently by immunohistochemistry. The clinical significance of this change is not well known, although some reports suggest a relationship with more aggressive behavior. OBJECTIVE: To assess the frequency of oncocytic change in pituitary adenomas and to correlate this finding with clinicopathologic factors. DESIGN: We studied oncocytic change in a series of 65 pituitary adenomas by immunohistochemistry. According to the percentage of oncocytic cells stained by antimitochondrial antibody, adenomas were classified in 3 groups: 50% or more, 10% to 49%, and 1% to 9% of oncocytic cells. RESULTS: Eight cases (12.3%) showing at least 50% of oncocytic cells were classified as oncocytic adenomas: 6 were gonadotroph adenomas and 2 were null-cell adenomas. Among the remaining cases, 9 (14%; all gonadotroph adenomas) showed 10% to 49% oncocytic cells, and in 14 cases (21.5%; 5 gonadotroph adenomas, 6 somatotroph adenomas, 2 corticotroph adenomas, and 1 thyrotroph adenoma) between 1% and 9% were shown. Patients with adenomas that showed oncocytic change presented more frequently at a higher average age (P =.05), but no relationship with extrasellar extension or proliferative activity measured by Ki-67 was observed. In somatotroph adenomas, cases with oncocytic change showed higher percentages of Ki-67 (P =.05) but no correlation with extrasellar extension or cytokeratin staining (dot pattern versus perinuclear) was found. CONCLUSION: Adenomas with oncocytic change present more frequently in older patients, but they are not clinically more aggressive. In addition, somatotroph adenomas with oncocytic cells show similar cytokeratin pattern and higher proliferative activity, which is not correlated with local aggressiveness.

Tratamiento quirúrgico de los tumores neuroendocrinos de localización broncopulmonar / Surgical treatment of bronchopulmonary neuroendocrine tumors

Introducción: El objetivo de este trabajo es revisar nuestra experiencia con los tumores neuroendocrinos de localización broncopulmonar, en especial el tipo de tratamiento quirúrgico aplicado en función del tipo histológico. Material y métodos: Hemos realizado un estudio retrospectivo sobre 45 pacientes: 35 casos de carcinoides típicos, 6 de carcinoides atípicos, 1 oat cell y 3 de carcinomas de células grandes. Los tumores fueron clasificados siguiendo los criterios de Travis. Resultados: El tratamiento quirúrgico practicado fue: 4 neumonectomías, 23 lobectomías, 6 bilobectomías, 3 resecciones atípicas por videocirugía, 7 broncoplastias con lobectomía y 2 broncoplastias sin resección pulmonar. En el 86 por ciento de los casos el estadio fue tipo I (9 IA y 30 IB), clasificándose 5 pacientes como IIIA, y 1 como IIIB. El estudio rutinario de los pacientes incluyó: radiología de tórax, analítica completa, tomografía computarizada toracoabdominal y broncoscopia. El seguimiento medio ha sido de 46,09 meses. Conclusiones: La gran mayoría de tumores neuroendocrinos tratables con cirugía son de bajo grado de agresividad (carcinoides típicos). El tratamiento quirúrgico también es el de elección en la mayoría de los carcinoides atípicos, aunque en éstos el grado de agresividad es mayor, al provocar diseminación ganglionar locorregional o metástasis en mayor proporción que los anteriores. En los carcinomas de célula grande con diferenciación neuroendocrina y en los cacinomas de células pequeñas, el tratamiento óptimo no está bien definido, aunque la cirugía parece ser una opción que debe plantearse siempre que sea posible, combinada o no con otras terapias (AU)