Archives of pathology & laboratory medicine
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Crizotinib (Xalkori), the first inhibitor of both anaplastic lymphoma kinase (ALK) and c-Met receptor kinases, has been approved in the United States, Korea, and other countries for the treatment of ALK-positive non-small cell lung cancer (NSCLC). This approval came within just 4 years of the discovery of rearrangements in the ALK gene in a subset of patients with NSCLC. Oral crizotinib 250 mg twice daily showed excellent efficacy in patients with advanced ALK-positive NSCLC, with objective response rates of 61% and 51% in ongoing phase I and II studies, respectively. ⋯ Phase III studies investigating crizotinib for the first- and second-line treatment of advanced ALK-positive NSCLC, versus current standards of care, are ongoing. Crizotinib represents a new standard of care for patients with ALK-positive NSCLC and highlights the importance of the role of the pathologist, as molecular profiling becomes a part of initial workups for newly diagnosed patients with NSCLC. This approach will ensure effective individualized treatment for patients with NSCLC.
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Arch. Pathol. Lab. Med. · Oct 2012
ReviewUpdate for pathologists on idiopathic interstitial pneumonias.
Idiopathic interstitial pneumonias are a subset of diffuse pulmonary interstitial diseases classified by international consensus in 2002 as idiopathic pulmonary fibrosis, nonspecific interstitial pneumonia, cryptogenic organizing pneumonia, acute interstitial pneumonia, respiratory bronchiolitis interstitial lung disease, desquamative interstitial pneumonia, and lymphoid interstitial pneumonia. Each is associated with a characteristic histopathologic pattern. In 2011, updated consensus guidelines were released for diagnosis and management of idiopathic pulmonary fibrosis. The entire group of idiopathic interstitial pneumonias is currently undergoing refinement, with updates expected in a forthcoming consensus classification. Many of these recent and anticipated changes are relevant to pathologists. ⋯ Diagnosis of idiopathic interstitial pneumonias by multidisciplinary discussion among clinicians, radiologists, and pathologists is now strongly encouraged. Diagnosis of idiopathic pulmonary fibrosis no longer requires surgical lung biopsy; high-resolution computed tomography is an acceptable surrogate. In the context of clinical trials, pathologists are being asked to assign levels of confidence for histologic diagnosis of usual interstitial pneumonia in patients with idiopathic pulmonary fibrosis. Acute exacerbation of idiopathic pulmonary fibrosis is now accepted and should be considered when acute lung injury is superimposed on a background of usual interstitial pneumonia. The updated classification of idiopathic interstitial pneumonias will include a separate category for rare entities, including lymphoid interstitial pneumonia and idiopathic pleuroparenchymal fibroelastosis.
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Although improvements in genomic technologies during the past decade have greatly advanced our understanding of the genomic alterations that contribute to lung cancer, and the disease has (to a degree) become a paradigm for individualized cancer treatment in solid tumors, additional challenges must be addressed before the goal of personalized cancer therapy can become a reality for lung cancer patients.
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Arch. Pathol. Lab. Med. · Aug 2012
Review Case ReportsClear cell tumors of the central nervous system: a case-based review.
Clear cell tumors of the central nervous system (CNS) encompass a variety of tumor subtypes that are challenging to diagnose given their similar morphologic features. Here, I use a case-based approach to review the clinicopathologic and radiologic features to help guide the general pathologist in the diagnosis of clear cell tumors of the CNS. First, the reader is invited to study 6 images of different CNS tumors with clear cell morphology. ⋯ A brief discussion follows with up-to-date diagnostic tools. Finally, I propose an immunohistochemical algorithm to navigate through the complex features that characterize clear cell tumors of the CNS. This review aims to provide a comprehensive approach to diagnosing clear cell neoplasms of the CNS based on improved assessment of the clinicopathologic and radiologic features of each entity.