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.

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.