Thyroid fine-needle aspiration (FNA) is used to assess appropriate management of nodular thyroid lesions safely, but Bethesda category III (atypia of undetermined significance/follicular lesion of undetermined significance) and category IV (follicular neoplasm/suspicious for follicular neoplasm) lesions are problematic. This study aimed to evaluate the Afirma Gene Expression Classifier (GEC) results for lesions in those categories.Medical records of patients with thyroid FNA and GEC results were obtained from archived material. Results were compared to thyroidectomy histologic diagnoses.Among 66 patients with FNA results (47 women and 19 men aged 26-89 years [mean, 59.4 years]), surgical reports were available for 38. Afirma GEC results were "nondiagnostic" for 10 of 66 (15.2%), "benign" for 22 (33.3%), and "suspicious" for 34 (51.5%). Surgical diagnosis was available for 38 of 66 patients (57.6%); GEC results for 6 (15.8%) of these were "nondiagnostic," 27 (71.0%) were "suspicious," and 5 (13.2%) were "benign." One of 6 (16.7%) samples with "nondiagnostic" results, 1 of 5 (20%) with "benign" results, and 15 of 27 (55.6%) with "suspicious" results were malignant on histology. Papillary carcinoma was the most common tumor type (15 of 38; 39.5%).Afirma GEC results minimize the number of unnecessary operations. Afirma GEC testing may be reserved for FNAs with a category III diagnosis on follow-up cytologic examination. We recommend a conservative approach for "suspicious" Afirma GEC results if Hürthle cells are seen with FNA.
Benign breast disease (BBD) is diagnosed in 1-2 million women/year in the US, and while these patients are known to be at substantially increased risk for subsequent development of breast cancer, existing models for risk assessment perform poorly at the individual level. Here, we describe a DNA-microarray-based transcriptional model for breast cancer risk prediction for patients with sclerosing adenosis (SA), which represent ¼ of all BBD patients. A training set was developed from 86 patients diagnosed with SA, of which 27 subsequently developed cancer within 10 years (cases) and 59 remained cancer-free at 10 years (controls). An diagonal linear discriminate analysis-prediction model for prediction of cancer within 10 years (SA TTC10) was generated from transcriptional profiles of FFPE biopsy-derived RNA. This model was tested on a separate validation case-control set composed of 65 SA patients. The SA TTC10 gene signature model, composed of 35 gene features, achieved a clear and significant separation between case and control with receiver operating characteristic area under the curve of 0.913 in the training set and 0.836 in the validation set. Our results provide the first demonstration that benign breast tissue contains transcriptional alterations that indicate risk of breast cancer development, demonstrating that essential precursor biomarkers of malignancy are present many years prior to cancer development. Furthermore, the SA TTC10 gene signature model, which can be assessed on FFPE biopsies, constitutes a novel prognostic biomarker for patients with SA.
Extraosseous Ewing's sarcoma (EES) involving the central nervous system is rare, but can be diagnosed and distinguished from other primitive neuroectodermal tumors (PNET) by identification of the chromosomal translocation (11;22)(q24;q12). We report EES arising from the spinal intradural extramedullary space, based on imaging, histopathological, and molecular data in two men, ages 50 and 60 years old and a review of the literature using PubMed (1970–2009). Reverse transcriptase polymerase chain reaction (RT-PCR) identified the fusion product FL1-EWS. Multimodal therapy, including radiation and alternating chemotherapy including vincristine, cyclophosphamide, doxorubicin and ifosfamide and etoposide led to local tumor control and an initial, favorable therapeutic response. No systemic involvement was seen from the time of diagnosis to the time of last follow-up (26 months) or death (4 years). This report confirms that EES is not confined to the earliest decades of life, and like its rare occurrence as an extra-axial meningeal based mass intracranially, can occasionally present as an intradural mass in the spinal canal without evidence of systemic tumor. Gross total resection followed by multimodal therapy may provide for extended progression free and overall survival.
18 Background: Benign breast disease (BBD) is diagnosed in 1-2 million women/year in the US, and while these patients are known to be at substantially increased risk for subsequent development of breast cancer, existing models for risk assessment perform poorly at the individual level. Here, we describe a DNA-microarray-based transcriptional model for breast cancer risk prediction for patients with sclerosing adenosis (SA), a lesion found in ¼ of all BBD patients that is characterized by epithelial proliferation, disordered acinar architecture, and stromal fibrosis. Methods: A training set was developed from 86 patients diagnosed with sclerosing adenosis (SA), of which 27 subsequently developed cancer within 10 years (cases) and 59 remained cancer-free at 10 years (controls). A diagonal linear discriminate analysis (DLDA)-prediction model for prediction of cancer within 10 years (SA TTC10) was generated from transcriptional profiles of formalin fixed, paraffin-embedded (FFPE) biopsy-derived RNA. This model was tested on a separate validation case-control set composed of 65 SA patients. Results: The SA TTC10 gene signature model, composed of 35 gene features, achieved a clear and significant separation between case and control with receiver operating characteristic area under the curve of 0.913 in the training set and 0.836 in the validation set. Conclusions: Our results provide the first demonstration that benign breast tissue contains transcriptional alterations that indicate risk of breast cancer development, and that essential precursor biomarkers of malignancy are present many years prior to cancer development. Furthermore, the SA TTC10 gene signature model, which can be assessed on FFPE biopsies, constitutes a novel prognostic biomarker for patients with SA.
The Breast Journal is a multidisciplinary publication with an equal partnership of different specialties and a focused approach toward enhancing our understanding of breast disease.The Breast Journal's editorial philosophy recognizes the increasing cooperation and interdependence of specialists who diagnose and treat diseases of the breast.Manuscripts will be considered in the form of editorials, original articles, fi rst time case reports, short communications, breast images, and letters to the editor.Submission of a paper implies that it reports unpublished work, except in abstract form, and is not being submitted simultaneously to another publication.
