Christopher Sebastiano

Mucosal eosinophilia: Prevalence and racial/ethnic differences in symptoms and endoscopic findings in adults over 10 years in an urban hospital

Background: Eosinophilic esophagitis is a chronic inflammatory disease with mucosal accumulation of eosinophils. There is a paucity of data among racial/ethnic groups other than white patients. Aim: To determine if racial/ethnic differences exist in clinical presentation, endoscopic appearance, and biopsy results in adult patients (age ≥18 y) with mucosal eosinophilia and examine the prevalence of mucosal eosinophilia at an urban hospital over a 10-year period. Methods: Pathology reports searched at Temple University Hospital 2000 to 2009; key words: “eosinophils”, “esophagus”, and “biopsy”. Clinical and endoscopic records reviewed on patients with ≥15 eosinophils/high power field. Results: A total of 64 adults (average age, 41 y; 62% male patients; 81% white, 12% black, and 6% Hispanic). White patients were significantly younger (P=0.03). Adult mucosal eosinophilia diagnosis increased by 833% (3 in 2000 to 25 in 2009); black/Hispanic diagnosis increased by 500% (1 in 2000 to 5 in 2009). Solid food dysphagia was more common among white patients (72% vs. 0.33%, P=0.02). Reflux symptoms were more common in black/Hispanic patients (42% vs. 22%, P=0.16). Normal endoscopy (42% vs. 13%, P=0.04) and reflux changes (41% vs. 21%, P=0.16) were more common in black/Hispanic patients. Furrows (42% vs. 8%, P=0.04) and rings (46% vs. 0%, P=0.002) were more common in white patients. Average eosinophil counts did not vary between groups. Conclusions: Mucosal eosinophilia presents with significant differences between racial/ethnic groups in age at onset, symptoms at presentation, and endoscopic features. Differences may reflect different phenotypes of the same disease or separate disease entities.

Breast intraductal papillomas without atypia in radiologic‐pathologic concordant core‐needle biopsies: Rate of upgrade to carcinoma at excision

The surgical management of mammary intraductal papilloma without atypia (IDP) identified at core‐needle biopsy (CNB) is controversial. This study assessed the rate of upgrade to carcinoma at surgical excision (EXC).

Cystic lesions of the adrenal gland: our experience over the last 20 years ☆

Cystic lesions of the adrenal gland are uncommon, often presenting with nonspecific clinical and radiologic findings, and are thus underrecognized. They are occasionally associated with malignant neoplasms, which can greatly mimic benign lesions and carry detrimental clinical consequences if misdiagnosed. Here we present our 20-year experience (1992-2012) with these lesions at an academic medical center. Among more than 4500 adrenal gland specimens, 31 cases of adrenal lesions with a predominant cystic component were identified in 30 patients with an age range of 34 to 86 years (median, 55.5 years) and a male/female ratio of 13:17. Macroscopic descriptions, available histologic and immunostain slides, and available radiologic records were reviewed for all included cases. Radiologic studies and gross examination correlated well, and hemorrhage (26 cases; 84%) and encapsulation (25 cases; 81%) appeared to be nonspecific radiologic/gross features shared across histologic subtypes. Microscopic review identified 12 cases (39%) of pseudocysts, 2 cases (6%) of endothelium-derived cysts, and 17 cases (55%) of epithelium-derived cysts. Among these 31 cystic adrenal lesions, 2 cases (6%) were malignant neoplasms (1 epithelioid angiosarcoma, 1 adrenocortical carcinoma). Radiologic impression and histopathologic diagnosis were concordant in 11 (73%) of the 15 cases for which radiologic records were available. This study represents the second largest case series to date on cystic adrenal lesions and presents a comprehensive review on their demographic, clinical, radiologic, and gross and microscopic pathologic features, as well as their differential diagnoses.

Systems biology perspectives on the carcinogenic potential of radiation

This review focuses on recent experimental and modeling studies that attempt to define the physiological context in which high linear energy transfer (LET) radiation increases epithelial cancer risk and the efficiency with which it does so. Radiation carcinogenesis is a two-compartment problem: ionizing radiation can alter genomic sequence as a result of damage due to targeted effects (TE) from the interaction of energy and DNA; it can also alter phenotype and multicellular interactions that contribute to cancer by poorly understood non-targeted effects (NTE). Rather than being secondary to DNA damage and mutations that can initiate cancer, radiation NTE create the critical context in which to promote cancer. Systems biology modeling using comprehensive experimental data that integrates different levels of biological organization and time-scales is a means of identifying the key processes underlying the carcinogenic potential of high-LET radiation. We hypothesize that inflammation is a key process, and thus cancer susceptibility will depend on specific genetic predisposition to the type and duration of this response. Systems genetics using novel mouse models can be used to identify such determinants of susceptibility to cancer in radiation sensitive tissues following high-LET radiation. Improved understanding of radiation carcinogenesis achieved by defining the relative contribution of NTE carcinogenic effects and identifying the genetic determinants of the high-LET cancer susceptibility will help reduce uncertainties in radiation risk assessment.

Densely Ionizing Radiation Acts via the Microenvironment to Promote Aggressive Trp53-Null Mammary Carcinomas

Densely ionizing radiation, which is present in the space radiation environment and used in radiation oncology, has potentially greater carcinogenic effect compared with sparsely ionizing radiation that is prevalent on earth. Here, we used a radiation chimera in which mice were exposed to densely ionizing 350 MeV/amu Si-particles, γ-radiation, or sham-irradiated and transplanted 3 days later with syngeneic Trp53-null mammary fragments. Trp53-null tumors arising in mice irradiated with Si-particles had a shorter median time to appearance and grew faster once detected compared with those in sham-irradiated or γ-irradiated mice. Tumors were further classified by markers keratin 8/18 (K18, KRT18), keratin 14 (K14, KRT14) and estrogen receptor (ER, ESR1), and expression profiling. Most tumors arising in sham-irradiated hosts were comprised of both K18- and K14-positive cells (K14/18) while those tumors arising in irradiated hosts were mostly K18. Keratin staining was significantly associated with ER status: K14/18 tumors were predominantly ER-positive, whereas K18 tumors were predominantly ER-negative. Genes differentially expressed in K18 tumors compared with K14/18 tumor were associated with ERBB2 and KRAS, metastasis, and loss of E-cadherin. Consistent with this, K18 tumors tended to grow faster and be more metastatic than K14/18 tumors, however, K18 tumors in particle-irradiated mice grew significantly larger and were more metastatic compared with sham-irradiated mice. An expression profile that distinguished K18 tumors arising in particle-irradiated mice compared with sham-irradiated mice was enriched in mammary stem cell, stroma, and Notch signaling genes. These data suggest that carcinogenic effects of densely ionizing radiation are mediated by the microenvironment, which elicits more aggressive tumors compared with similar tumors arising in sham-irradiated hosts.

Benign Vascular Lesions of the Breast Diagnosed by Core Needle Biopsy Do Not Require Excision

Surgical excision of all benign vascular lesions of the breast identified by core needle biopsy has been recommended in the past to rule out a more serious lesion. In this study we investigated the clinical, radiological and pathological findings in patients diagnosed with a benign vascular lesion at our institution to assess whether excision may be spared for lesions without atypia.