Negar Rassaei

Glucose transporter-1 in pulmonary neuroendocrine carcinomas: expression and survival analysis

Glucose transporter-1 (GLUT-1) mediates the transport of glucose across the cellular membrane. Its elevated levels and/or activation have been shown to be associated with malignancy. The aim of this study was to investigate GLUT-1 expression in pulmonary neuroendocrine carcinomas. Tissue microarray-based samples of 178 neuroendocrine carcinomas, including 48 typical carcinoids, 31 atypical carcinoids, 27 large cell neuroendocrine carcinomas and 72 small cell carcinomas from different patients, were studied immunohistochemically for GLUT-1 expression. Forty-seven percent (75/161) of pulmonary neuroendocrine carcinomas were immunoreactive with GLUT-1. GLUT-1 was observed in 7% (3/46) of typical carcinoid, 21% (6/29) of atypical carcinoid, 74% (17/23) of large cell neuroendocrine carcinoma and 78% (49/63) of small cell carcinoma. GLUT-1 expression correlated with increasing patient age (P=0.01) and with neuroendocrine differentiation/tumor type (P<0.001), but not with gender, tumor size or stage. GLUT-1 expression was seen in a characteristic membranous pattern of staining along the luminal borders or adjacent to necrotic areas. GLUT-1 expression was associated with an increased risk of death for neuroendocrine carcinomas as a group (risk ratio=2.519; 95% confidence interval=1.519–4.178; P<0.001) and carcinoids (risk ratio=4.262; 95% confidence interval=1.472–12.343; P=0.01). In conclusion, GLUT-1 is expressed in approximately half of the pulmonary neuroendocrine carcinomas and shows a strong correlation with neuroendocrine differentiation/grade, but not with other clinicopathologic variables. Further studies appear plausible to elucidate the prognostic significance of GLUT-1 expression in pulmonary carcinoids.

Proteomic profiling of human plasma identifies apolipoprotein E as being associated with smoking and a marker for squamous metaplasia of the lung

Biomarkers to identify subjects at high‐risk for developing lung cancer will revolutionize the disease outlook. Most biomarker studies have focused on patients already diagnosed with lung cancer and in most cases the disease is often advanced and incurable. The objective of this study was to use proteomics to identify a plasma biomarker for early detection of lung lesions that may subsequently be the harbinger for cancer. Plasma samples were obtained from subjects without lung cancer grouped as never, current, or ex‐smokers. An iTRAQ‐based proteomic analysis was performed on these pooled plasma samples. We identified 31 proteins differentially abundant in current smokers or ex‐smokers relative to never smokers. Western blot and ELISA analyses confirmed the iTRAQ results that demonstrated an increase of apolipoprotein E (APOE) in current smokers as compared to both never and ex‐smokers. There was a strong and significant correlation of the plasma APOE levels with development of premalignant squamous metaplasia. Additionally, we also showed that higher tissue levels of APOE are seen with squamous metaplasia, supporting a direct relationship. Our analysis reveals that elevated plasma APOE is associated with smoking, and APOE is a novel predictive protein biomarker for early morphological changes of squamous metaplasia in the lung.

Occult primary parotid gland acinic cell adenocarcinoma presenting with extensive lung metastasis.

Acinic cell adenocarcinoma is a malignant salivary gland neoplasm with a relatively low rate of lymphangitic spread to regional lymph nodes. Distant metastases are rare and their occurrence typically indicates an unfavorable outcome. We encountered an unusual example of acinic cell adenocarcinoma that initially presented in the lung, whereas the primary parotid carcinoma, despite extensive clinical evaluation, only became apparent 1 year after initial diagnosis. The histologic, immunohistochemical, and ultrastructural features of the tumor in the parotid gland and lung were similar. The tumor displayed an aggressive behavior resulting in death within 2 years of the initial presentation. This presentation is unique, showing that peripheral lung tumors of salivary gland type are likely to be metastatic, and careful clinical evaluation is warranted in establishing their primary site of origin.

Deposition of calcium salts in a case of pulmonary zygomycosis: histopathologic and chemical findings☆

We report a case of pulmonary zygomycosis associated with unusual deposition of calcium salt crystals. The patient was a 75-year-old female who had onset of cough and shortness of breath. She was treated for community-acquired pneumonia but died despite intensive therapy. Postmortem examination revealed diffuse alveolar damage and multifocal necrotizing pneumonia associated with herpes simplex infection and invasive zygomycosis. Birefringent particles were seen associated with fungal elements in the lung parenchyma, within bronchial cartilage, and in blood vessel walls. By infrared spectroscopy, the birefringent particles in the pulmonary parenchyma and within bronchial cartilage had spectral characteristics of calcium oxalate dihydrate and calcium oxalate monohydrate, respectively. The birefringent crystals within vascular walls were identified as calcium carbonate. This case documents the chemical composition and location of 3 different calcium salt crystals in pulmonary zygomycosis. It also shows that among pulmonary fungal infections, calcium oxalate deposition is not restricted to aspergillosis.

Frozen Section Interpretation of Pancreatic Margins: Subspecialized Gastrointestinal Pathologists Versus General Pathologists

Intraoperative assessment of pancreatic parenchymal margin during pancreatectomies is challenging and misinterpretation by the pathologist is a cause of incorrect frozen section (FS) diagnosis. Although the current literature supports that pancreatic margin FS diagnosis and its accuracy has no impact on the patient outcome for pancreatic ductal adenocarcinoma (PDAC) patients and reexcision in an attempt to achieve a negative intraoperative pancreatic margin after positive FS is not associated with increased overall survival; still it remains a routine practice in many institutions. To this end, we sought to assess the interobserver variation and accuracy of FS diagnosis between subspecialized gastrointestinal/pancreatobiliary (GI) and general pathologists. Seventy seven consecutive pancreatic parenchymal margin FSs performed on pancreatectomies for PDAC from 2010 to 2013 were retrieved at our institution. These were retrospectively evaluated by 2 GI and 2 general pathologists independently without knowledge of the original FS diagnosis or the final diagnosis. The specificity, sensitivity, positive predictive value, negative predictive value, and accuracy of GI versus general pathologist was 97.8% versus 87.5%, 61.1% versus 66.7%, 78.6% versus 41.4%, 95% versus 95.2%, and 93.5% versus 85.1%, respectively. The interobserver agreement between GI and general pathologists was fair (κ = .337, P < .001). The interobserver agreement between 2 GI pathologists was fair (κ = .373, P = .0005) and between 2 general pathologists was slight (κ = .195, P = .042). Although overall accuracy of subspecialized GI pathologists was higher than that of general pathologists, none had an accuracy of 100%. Our study reaffirms the challenging nature of these FSs.

Photo Quiz. A 59-Year-Old Man With Multiple Liver Lesions, Rash, and Uveitis.

A 59-year-old man with a medical history significant for earlystage chronic lymphocytic leukemia (CLL), diagnosed 6 years prior, was referred for infectious diseases evaluation due to rash and liver lesions. The patient’s pertinent clinical history began 8 months prior when he experienced 1–2 weeks of night sweats and fatigue, followed by transient numbness and pain in his hands, abdomen, and back, then severe bilateral back pain for several weeks and weight loss of at least 10 pounds. A diffuse nonpruritic rash also developed. Computed tomographic (CT) scan of his chest, abdomen, and pelvis raised concerns for metastatic disease in his liver and possible lytic lesions in his iliac bones. Consequently, he was given a poor prognosis with 6 months to live. The patient had been temporarily residing in Florida, so he returned home to Pennsylvania to be with family. After returning to Pennsylvania, the patient underwent additional studies, including magnetic resonance imaging of his abdomen. This showed multiple, rounded, enhancing lesions of varying sizes in the liver, compatible with metastatic disease (Figure 1). Further investigations suggested that the abnormalities in his iliac bones likely were related to his CLL. CT-guided biopsy of a focal liver lesion demonstrated fibroblastic tissue with moderate mixed inflammatory infiltrate with no evidence of malignancy. He continued to feel unwell, with severe fatigue, generalized weakness, anorexia, and progressive weight loss, and over the ensuing months became almost bedridden. Approximately 6 months following the onset of his initial symptoms, he developed bilateral eye redness and pain with a gritty sensation and blurred vision. Ophthalmologic evaluation revealed uveitis and episcleritis, and he was started on topical cyclopentolate and prednisolone with gradual amelioration. Two empiric courses of oral prednisone were prescribed at about this time, and each course led to a sense of overall improvement by the patient, as well as transient reduction of his rash. Several physicians had examined the rash Figure 1. Enhanced abdominal magnetic resonance imaging (liver protocol). Coronal (A) and transverse (B) T1-weighted images of the liver obtained 20 minutes after administration of Eovist gadolinium-based contrast.

Pleuroparenchymal Fibroelastosis With Long History of Asbestos and Silicon Exposure

Pleuroparenchymal fibroelastosis (PPFE) is an uncommon interstitial lung disease. PPFE is characterized by fibroelastosis involving the pleura and subjacent parenchyma with a predominantly upper lobe distribution. While different possible environmental and familial etiologies have been postulated in the literature, the etiology of this disease remains essentially unclear and most cases are considered as idiopathic. In this report, we describe a rare case of PPFE with multiple lung lobe involvements and prolonged asbestos and silica exposure. Our goal is to investigate the exposure of asbestos and silica and try to identify their possible association with PPFE.

The Role of Race and Economic Characteristics in the Presentation and Survival of Patients With Surgically Resected Non-Small Cell Lung Cancer

Background Little is understood regarding the inter-relation between economic, marital, and racial/ethnic differences in presentation and survival of surgically resected lung cancer patients. Our investigation will assess these differences in addition to known therapeutic, patient, and histopathologic factors. Methods A retrospective review of the Surveillance Epidemiology and End Reporting database was conducted through the years 2007–2012. The population was split into nine different ethnic groups. Population differences were assessed via chi-square testing. Multivariable analysis (MVA) were used to detect overall survival (OS) differences in the total surgical population (TS, N = 35,689) in an ear (T1–T2 < 4 cm N0) surgical population [early-stage resectable (ESR), N = 17,931]. Lung cancer-specific survival (LCSS) was assessed in the ESR. Results In the TS population, as compared to Whites, Blacks, and Hispanics presented with younger age, more adenocarcinomas, lower rates of marriage, lower rates of insurance, less stage I tumors, and had less nodes examined, but their type of surgical procedures and OS/LCSS were the same. MVA demonstrated that lower OS and LCSS were associated with males, single/divorced/widowed partnership, lower income (TS only), and Medicaid insurance. MVA also found that Blacks and Hispanics had a similar OS/LCSS to Whites and that all ethnic groups were associated with a similar or better outcomes. The 90-day mortality and positive nodes were correlated with not having insurance and not being married, but they were not associated with ethnicity. Conclusion In TS and ESR groups, OS was not different in the two largest ethnic groups (Black and Hispanic) as compared to Whites, but was related to single/widowed/divorced status, Medicaid insurance, and income (TS group only). Nodal positivity was associated with patients who did not have a married partner or insurance suggesting that these factors may impact disease biology. Economic and psychosocial variables may play a role in survival of ear lung cancer in addition to standard histopathologic and treatment variables.

A case of vasculopathy of unknown etiology associated with fatal hydrops fetalis and review of the literature on intimomedial mucoid degeneration

Non-immune hydrops fetalis (NIHF) has a high mortality rate [1]. Many etiologies of NIHF have been identified, including cardiovascular abnormalities, severe anemia, and genetic defects. In patients with cardiovascular etiology, structural malformations lead to fluid accumulation resulting in increased intravascular hydrostatic pressure. We report a fatal case of NIHF in a 31 week gestational age, Caucasian neonate with heart remodeling associated with a stenotic vasculopathy of the right pulmonary artery. The artery revealed partial occlusion with vascular wall abnormalities, including disarrayed smooth muscle fibers, hyperplasia within the tunica media, and myxoid change within the media and intima. Identical vasculopathy was also identified within a mesenteric artery, and this contributed to hemorrhage and early ischemic necrosis of the small intestine, discovered on postmortem examination.

Population-based differences in the outcome and presentation of lung cancer patients based upon racial, histologic, and economic factors in all lung patients and those with metastatic disease

To investigate the interrelation between economic, marital, and known histopathologic/therapeutic prognostic factors in presentation and survival of patients with lung cancer in nine different ethnic groups. A retrospective review of the SEER database was conducted through the years 2007–2012. Population differences were assessed via chi‐square testing. Multivariable analyses (MVA) were used to detect overall survival (OS) differences in the total population (TP, N = 153,027) and for those patients presenting with Stage IV (N = 70,968). Compared to Whites, Blacks were more likely to present with younger age, male sex, lower income, no insurance, single/widowed partnership, less squamous cell carcinomas, and advanced stage; and experience less definitive surgery, lower OS, and lung cancer‐specific (LCSS) survival. White Hispanics presented with younger age, higher income, lower rates of insurance, single/widowed partnership status, advanced stage, more adenocarcinomas, and lower rates of definitive surgery, but no difference in OS and LCSS than Whites. In the TP and Stage IV populations, MVAs revealed that OS was better or equivalent to Whites for all other ethnic groups and was positively associated with insurance, marriage, and higher income. Blacks presented with more advanced disease and were more likely to succumb to lung cancer, but when adjusted for prognostic factors, they had a better OS in the TP compared to Whites. Disparities in income, marital status, and insurance rather than race affect OS of patients with lung cancer. Because of their presentation with advanced disease, Black and Hispanics are likely to have increased benefit from lung cancer screening.