Ductal carcinoma in situ of the breast: the importance of morphologic and molecular interactions.

Ductal carcinoma in situ (DCIS) of the breast is a lesion characterized by significant heterogeneity, in terms of morphology, immunohistochemical staining, molecular signatures, and clinical expression. For some patients, surgical excision provides adequate treatment, but a subset of patients will experience recurrence of DCIS or progression to invasive ductal carcinoma (IDC). Recent years have seen extensive research aimed at identifying the molecular events that characterize the transition from normal epithelium to DCIS and IDC. Tumor epithelial cells, myoepithelial cells, and stromal cells undergo alterations in gene expression, which are most important in the early stages of breast carcinogenesis. Epigenetic modifications, such as DNA methylation, together with microRNA alterations, play a major role in these genetic events. In addition, tumor proliferation and invasion is facilitated by the lesional microenvironment, which includes stromal fibroblasts and macrophages that secrete growth factors and angiogenesis-promoting substances. Characterization of DCIS on a molecular level may better account for the heterogeneity of these lesions and how this manifests as differences in patient outcome and response to therapy. Molecular assays originally developed for assessing likelihood of recurrence in IDC are recently being applied to DCIS, with promising results. In the future, the classification of DCIS will likely incorporate molecular findings along with histologic and immunohistochemical features, allowing for personalized prognostic information and therapeutic options for patients with DCIS. This review summarizes current data regarding the molecular characterization of DCIS and discusses the potential clinical relevance

Implications of hobnail features in anaplastic thyroid carcinoma and precursor lesions

Anaplastic thyroid carcinoma (ATC) has the poorest prognosis of all thyroid cancers. Morphologically, it is characterized by pleomorphic undifferentiated cells. In some cases, a differentiated precursor lesion, either papillary thyroid carcinoma (PTC) or follicular thyroid carcinoma, can be identified adjacent to the anaplastic component. There are certain morphological variants of PTC that are known to be associated with more aggressive behavior, but a recently described, understudied variant is the hobnail variant. It is characterized histologically by micropapillary structures lined by cells with abundant eosinophilic cytoplasm and apically-placed bulging nuclei. The aim of this study was to evaluate the frequency of hobnail cells in ATC and associated precursor lesions. Microscopic slides from 21 cases of ATC diagnosed at Thomas Jefferson University Hospital between 2014 and 2017 were studied. 11 cases had an identifiable differentiated component, 8 of which were PTC. Hobnail cells were identified within the precursor PTC lesion in 5/8 of these cases. The high frequency of hobnail features in PTC precursor lesions associated with ATC suggests that hobnail features are an indicator of tumor aggressiveness. Further study is warranted to determine the prognostic value of hobnail cells in thyroid neoplasms

Two Cases of Sinonasal Non-Intestinal-Type Adenocarcinoma with Squamoid Morules Expressing Nuclear β-Catenin and CDX2: A Curious Morphologic Finding Supported by Molecular Analysis

Sinonasal non-intestinal-type adenocarcinoma (non-ITAC) is a rare, morphologically diverse neoplasm of the head and neck. Squamoid morular metaplasia has recently been reported as an occasional finding in non-ITAC. Interestingly, these squamoid morules often show aberrant expression of CDX2 as well as nuclear expression of β-catenin, similar to other tumors that show this type of metaplasia, but the underlying mechanism responsible for this finding is not completely understood. We present two cases of low-grade non-ITAC with squamoid morules coexpressing CDX2 and nuclear β-catenin by immunohistochemistry, both of which were found to harbor a mutation in CTNNB1, the gene encoding β-catenin. This finding provides support that an alteration in the β-catenin pathway, including mutations in the β-catenin gene itself, is responsible for this recently described morphologic phenomenon in non-ITAC

Diagnostic Options and Challenges for Dengue and Chikungunya Viruses.

Dengue virus (DENV) and Chikungunya virus (CHIKV) are arboviruses that share the same Aedes mosquito vectors and thus overlap in their endemic areas. These two viruses also cause similar clinical presentations, especially in the initial stages of infection, with neither virus possessing any specific distinguishing clinical features. Because the outcomes and management strategies for these two viruses are vastly different, early and accurate diagnosis is imperative. Diagnosis is also important for surveillance, outbreak control, and research related to vaccine and drug development. Available diagnostic tests are aimed at detection of the virus, its antigenic components, or the host immune antibody response. In this review, we describe the recent progress and continued challenges related to the diagnosis of DENV and CHIKV infections

Performance of Creatinine and Chloride on the epoc Analyzer

BACKGROUND The epoc Blood Analysis System (Alere, Orlando, FL) performs blood gases, electrolytes, and metabolites using a Blood Gas Electrolyte and Metabolite (BGEM) Test Card panel on 92 uL of whole blood. The BGEM test card uses potentiometric sensors to measure sodium, potassium, ionized calcium, pH, pCO2; amperometric sensors to measure pO2, glucose, and lactate; and a conductometric sensor to measure hematocrit. Results are available in 3-10 minutes, depending upon the time between calibration and patient testing. TJUH implemented the epoc in its ICUs in 2012 to provide Point of Care (POC) results. Alere recently added creatinine and chloride sensors to its BGEM cartridge. At the request of our Emergency Department, we evaluated creatinine and chloride on the epoc. Poster presented at: American Association for Clinical Chemistry Annual Scientific Meeting in Philadelphia PA.https://jdc.jefferson.edu/pacbposters/1005/thumbnail.jp

Succinate Dehydrogenase Deficiency in Sporadic Pituitary Adenomas: A Potential Mechanism for Tumorigenesis

In order to determine whether succinate dehydrogenase (SDH) deficiency plays a role in spor-adic, non-familial pituitary adenomas, we analyzed 80 pituitary adenomas for SDH deficiency from patients without familial tumor syndromes or without known SDH deficiency-associated neoplasms. SDH deficiency was determined by immunohistochemical (IHC) stains for SDHB since the loss of any of the four SDH subunits results in the loss of SDHB expression. Three pituitary adenomas showed complete loss of SDHB staining, and of these two also showed loss of SDHA staining. We further characterized these adenomas by looking at Ki67, IGF1R, and 5-hmC levels via IHC. SDHx-deficient (non-SDHA deficient) tumors had a Ki67 proliferation index higher than non-SDH deficient pituitary tumors while SDHA-deficient tumors had Ki67 indices similar to non-SDH deficient tumors. IGF1R IHC staining was similar across all subsets. All SDH-deficient subtypes showed a loss of 5-hydroxymethylcytosine nuclear IHC staining. These findings suggest that SDH deficiency promotes tumorigenesis of pituitary adenomas through accumulation of succinate resulting in changes in the epigenome, specifically resulting in a hypermethylated state

Phosphaturic mesenchymal tumor of the nasal cavity: Clinicopathologic correlation is essential for diagnosis

Phosphaturic mesenchymal tumor (PMT) is a rare neoplasm in which the tumor cells produce fibroblast growth factor 23 (FGF23), leading to oncogenic osteomalacia and thus a distinct clinical presentation. However, the pathologic findings of PMT are often non-specific and variable, especially in tumors occurring in the head and neck. We present a case of a 66-year-old female who presented with osteomalacia-related symptoms and was found to have a nasal cavity mass. Histopathologic examination was suggestive of PMT but certain characteristic features were lacking, requiring confirmation of the diagnosis by chromogenic in situ hybridization (CISH) assay for FGF23 mRNA. The patient's symptoms and laboratory abnormalities resolved upon resection of the tumor. Keywords: Phosphaturic mesenchymal tumor, Sinonasal, Endoscopic endonasal resection, Tumor induced osteomalacia, Hypophosphatemia, FGF2