Qing Kay Li

The utility of napsin‐A in the identification of primary and metastatic lung adenocarcinoma among cytologically poorly differentiated carcinomas

New developments in the treatment of lung cancer have necessitated the further histologic and cytologic subtyping of nonsmall cell lung carcinomas. Thyroid transcription factor‐1 (TTF‐1) long has served as the predominant marker for demonstrating lung origin. However, it is also expressed in a variety of other tumors, particularly neuroendocrine neoplasms and, to a much lesser degree, squamous cell carcinoma of the lung. Napsin‐A, which is expressed in lung tissue, is a relatively new marker for lung adenocarcinoma. In this study, the authors examined the utility of napsin‐A compared with TTF‐1 in cytologic specimens of primary and metastatic, poorly differentiated lung adenocarcinomas.

Cytology of endobronchial ultrasound-guided transbronchial needle aspiration: a retrospective study with histology correlation.

Endobronchial ultrasound (EBUS) is a relatively new modality that can be used to guide transbronchial needle aspiration (TBNA) of mediastinal and hilar lymph nodes and peripheral lung lesions. Few studies have investigated the cytological profile of EBUS‐TBNA specimens. In this study, we have reviewed the cytological profile of 135 consecutive cases, including 71 lymph node cases, 4 lung cases, and 60 cases of both lymph node and lung sampling. Our study contains the largest number of cases in the evaluation of cytomorphology.

Improvement of cellularity on cell block preparations using the so-called tissue coagulum clot method during endobronchial ultrasound-guided transbronchial fine-needle aspiration†

Cell block (CB) preparation during the endobronchial ultrasound‐guided transbronchial fine‐needle aspiration (EBUS‐TBNA) procedure plays an important role in the diagnosis of lung cancer and recovery of cellular material for molecular characterization of the tumor. However, the efficiency of the conventional method of CB preparation is suboptimal.

KEAP1 gene mutations and NRF2 activation are common in pulmonary papillary adenocarcinoma

Distinctive histological variants of lung cancer are increasingly recognized to have specific genetic changes that affect tumor biology and response to therapy. In this study, we evaluated true papillary adenocarcinoma of the lung, proposed as a distinct diagnostic category with relatively poor response to therapy, to determine whether these tumors also have specific molecular alterations that would affect sensitivity to chemotherapy. Specifically, we measured protein levels of P53, excision repair cross-complementation 1 (ERCC1) and ribonucleotide reductase M1 (RRM1) by immunohistochemistry and evaluated the Kelch-like erythroid cell-derived protein with cap-n-collar homology (ECH)-associated protein 1 (KEAP1) gene for mutations, correlating mutations of this gene with total and nuclear expression of the nuclear factor erythroid-2-related factor 2 (NRF2). We found high levels of P53 in 23 of the 55 specimens (41.8%), similar to the rate of P53 gene mutations observed in general for pulmonary adenocarcinoma, and levels of ERCC1 and RRM1 also showed distributions similar to those reported generally for non-small lung cell cancer (NSCLC). However, KEAP1 alterations were observed at a significantly higher frequency in papillary adenocarcinoma tumors (60%) than what has been reported previously for NSCLC (3–19%). These mutations of KEAP1 were associated with increased nuclear accumulation of NRF2 in tumors, as expected for functional alterations. Thus, high rates of KEAP1 mutations and NRF2 overexpression in true papillary adenocarcinoma could be related to poor prognosis and chemotherapy resistance. Furthermore, this distinctive molecular characteristic supports the recognition of true papillary adenocarcinoma as a diagnostic entity.

EGFR and KRAS mutations in metastatic lung adenocarcinomas

In primary lung adenocarcinoma, EGFR and KRAS mutations are found in approximately 10% to 20% and 20% to 30%, respectively. Few studies have investigated these mutations in metastases. Patients with EGFR mutations have a 70% to 80% response rate to tyrosine-kinase inhibitors therapy and a longer progression-free survival rate in contrast to patients with KRAS mutations that are associated with virtually no response tyrosine-kinase inhibitors. In this study, we have investigated EGFR and KRAS mutations in metastatic lung adenocarcinoma. Using Johns Hopkins Hospital archives, 1966 lung adenocarcinomas were found from January 2007 to May 2010. A total of 60 metastatic adenocarcinomas (28 cytologic and 32 surgical cases) with EGFR and KRAS studies were identified. In addition, 18 cases of primary and matched metastases were also included. Exons 18 to 21 of EGFR and exon 2 of KRAS (codons 12 and 13) were sequenced. In our study, EGFR and KRAS mutations were found in 21.7% (13 of 60 cases) and 28.3% (17 of 60 cases), respectively, and occurred more often with advanced stage of primary tumors. KRAS mutations were associated with poor prognosis and occurred exclusively in smokers in comparison with EGFR mutation. Of 9 pairs, mutations were concordant in 77.8%; 1 pair displayed acquisition of KRAS mutation, whereas 1 pair showed loss of EGFR mutation in the corresponding metastasis. Our findings suggest that EGFR and KRAS status should be tested in metastasis regardless of known mutations of the primary tumor. Additional studies are needed to further investigate the mechanisms of discordances in metastatic tumors.

Cytology of endobronchial ultrasound-guided transbronchial needle aspiration versus conventional transbronchial needle aspiration

Conventional endoscopic transbronchial needle aspiration (TBNA) is a common procedure used to obtain samples for diagnosing and staging lung lesions. Recently, endobronchial ultrasound‐guided transbronchial needle aspiration (EBUS‐TBNA) has been developed and increasingly used by clinicians. Clinical data suggest that EBUS‐TBNA has higher sensitivity and specificity than conventional TBNA in staging lung cancers. In this study, the authors have investigated the cytological features and compared the diagnostic yield of these procedures in lung cancer patients.

Application of glycoproteomics for the discovery of biomarkers in lung cancer

Lung cancer is the leading cause of cancer‐related deaths in the United States. Approximately 40–60% of lung cancer patients present with locally advanced or metastatic disease at the time of diagnosis. Lung cancer development and progression are a multistep process that is characterized by abnormal gene and protein expressions ultimately leading to phenotypic change. Glycoproteins have long been recognized to play fundamental roles in many physiological and pathological processes, particularly in cancer genesis and progression. In order to improve the survival rate of lung cancer patients, the discovery of early diagnostic and prognostic biomarkers is urgently needed. Herein, we reviewed the recent technological developments of glycoproteomics and published data in the field of glycoprotein biomarkers in lung cancer, and discussed their utility and limitations for the discovery of potential biomarkers in lung cancer. Although numerous papers have already acknowledged the importance of the discovery of cancer biomarkers, the systemic study of glycoproteins in lung cancer using glycoproteomic approaches is still suboptimal. Recent development in the glycoproteomics will provide new platforms for identification of potential protein biomarkers in lung cancers.

Glycoproteomic Analysis of Bronchoalveolar Lavage (BAL) Fluid Identifies Tumor-Associated Glycoproteins from Lung Adenocarcinoma

Cytological examination of cells from bronchoalveolar lavage (BAL) is commonly used for the diagnosis of lung cancer. Proteins released from lung cancer cells into BAL may serve as biomarkers for cancer detection. In this study, N-glycoproteins in eight cases of BAL fluid, as well as eight lung adenocarcinoma tissues and eight tumor-matched normal lung tissues, were analyzed using the solid-phase extraction of N-glycoprotein (SPEG), iTRAQ labeling, and liquid chromatography tandem mass spectrometry (LC-MS/MS). Of 80 glycoproteins found in BAL specimens, 32 were identified in both cancer BAL and cancer tissues, with levels of 25 glycoproteins showing at least a 2-fold difference between cancer and benign BAL. Among them, eight glycoproteins showed greater than 2-fold elevations in cancer BAL, including Neutrophil elastase (NE), Integrin alpha-M, Cullin-4B, Napsin A, lysosome-associated membrane protein 2 (LAMP2), Cathepsin D, BPI fold-containing family B member 2, and Neutrophil gelatinase-associated lipocalin. The levels of Napsin A in cancer BAL were further verified in independently collected 39 BAL specimens using an ELISA assay. Our study demonstrates that potential protein biomarkers in BAL fluid can be detected and quantified.

Intrapancreatic accessory spleen: A case report and review of literature

Intrapancreatic accessory spleen is not an uncommon entity and usually located in the tail of the pancreas. Most of them are asymptomatic and incidental findings on radiologic study or at autopsy. On imaging study, it appears to be a well‐defined, solitary, and hypervascular lesion; therefore, it may be confused with pancreatic neoplasms, such as neuroendocrine neoplasm, well‐differentiated adenocarcinoma, solid pseudopapillary tumor, or metastatic tumor to the pancreas. As such, the diagnostic fine‐needle aspiration biopsy of the lesion may be performed. Several case reports describing cytological features of the lesion have been published in recent years. Among them, the most commonly identified cytological findings are sheets of a heterogeneous population of lymphocytes and prominent traversing blood vessels. Herein, we report an unusual EUS‐FNA case of intrapancreatic accessory spleen. In addition to above previously well‐described cytological features, our case revealed many cells with fine granular chromatin and areas with pseudo rosette‐like architecture, mimicking and engendering the differential diagnosis of pancreatic neuroendocrine tumors. Although cytological findings of our case are rare, they may extend our current knowledge and provide additional differential diagnostic information for this entity. Diagn. Cytopathol. 2013.

Cytologic Diagnosis and Differential Diagnosis of Lung Carcinoid Tumors a Retrospective Study of 63 Cases with Histologic Correlation.

Neuroendocrine (NE) neoplasms of the lung are a spectrum of tumors including typical carcinoid (TC), atypical carcinoid tumor (ACT), small cell lung carcinoma (SCLC), and large cell NE carcinoma (LCNEC). Given the overlapping features within these tumors, misclassification is a known risk, with significant treatment consequences.