Context.-Lung carcinoma is the result of sequential accumulation of genetic and epigenetic changes. Lung adenocarcinoma is a heterogeneous disease with diverse somatic mutations, and several of them include the socalled driver mutations, which may serve as ''druggable'' therapeutic targets. Thus, development of personalized approaches for the treatment of non-small cell lung carcinoma (NSCLC) mandates that pathologists make a precise histologic classification inclusive of routine molecular analysis of such tumors.Objective.-To address the molecular mechanisms underlying NSCLC and how this knowledge reflects the multidisciplinary approach in the diagnosis and management of these patients. We will also summarize the current available and investigational personalized therapies for patients with resectable early-stage, unresectable locally advanced, and metastatic NSCLC.Data Sources.-Peer-reviewed published literature and personal experience.Conclusions.-There are multiple mechanisms involved in the pathogenesis of lung cancer, which operate in parallel and involve pathways of activation and inhibition of various cellular events. Further research is essential to characterize the histologic and mutational profiles of lung carcinomas, which will ultimately translate into improved and more personalized therapeutic management of patients with lung cancer.(Arch Pathol Lab Med. 2013;137:481-491; doi: 10.5858/ arpa.2012-0287-RA) L ung cancer is the leading cause of cancer-related mortality in both men and women in the United States. It is projected that in 2012, lung cancer will account for 26% and 29% of cancer-related deaths in the female and male population, respectively.1 Historically, lung cancer has been divided into 2 major categories based on the histologic features and response to conventional therapies, and they include non-small cell lung carcinoma (NSCLC) and small cell lung carcinoma. NSCLC includes 3 cell types (adenocarcinoma, squamous cell carcinoma, and large cell carcinoma), and these can be further divided into various subtypes or variants.2 NSCLC accounts for most (~80%) of the lung cancers, with lung adenocarcinoma being the most common subtype in the United States. Despite significant improvements in radiologic imaging, supportive care, availability of newer antineoplastic agents, and multimodality therapy, the 5-year relative survival rate for lung cancer in the United States remains dismal, that is, at only 16% in 2007 compared to 12% in 1975, thus indicating little improvement in survival rate over a period of 3 decades.

Sarcomatoid (spindle cell) carcinoma of the pancreas is a rare, high-grade epithelial malignancy composed predominantly or exclusively of spindle cells demonstrating evidence of epithelial derivation, but no features indicative of a specific line of mesenchymal differentiation. The current study presents the case of an 85-year-old Caucasian male with a tumor mass in the body of the pancreas. The individual subsequently underwent a distal pancreatectomy, splenectomy and partial gastrectomy. Microscopic examination of the 3.3-cm mass located in the body of the pancreas revealed a small, but high-grade, adenocarcinomatous component that blended imperceptibly with malignant spindle cells. No light microscopic or immunohistochemical evidence of specific mesenchymal differentiation was identified, and the spindle cells, as in the case of the carcinoma, were diffusely keratin-positive. Sarcomatoid (spindle cell) carcinoma defined in this way rarely presents in the pancreas, with, to the best of our knowledge, only six cases reported in the English literature.

No abstract

Abstract. Plexiform fibromyxoma is a rare, benign mesenchymal neoplasm that predilects the gastric antrum and has potential for misdiagnosis as a gastrointestinal stromal tumor (GIST). The histology of the tumor is characterized by interwoven fascicular growth of cytologically bland spindled cells within a variably myxoid stroma. The current study reports the clinicopathological and immunohistochemical findings of a plexiform fibromyxoma resected from a 28-year-old Vietnamese female. The patient presented with acute, severe abdominal pain and worsening anemia. The initial fine-needle aspiration and needle core biopsy of the gastric antral mass led to an initial diagnosis of GIST. The subsequent distal partial gastrectomy revealed a 5.5-cm transmural antral mass that ulcerated the overlying mucosa and grew as variably elongated, myxoedematous, polypoid (cotyledon-like) excrescences from the serosal surface. Microscopically, the tumor demonstrated plexiform and multinodular growth of cytologically bland spindled cells proliferating in an abundant myxocollagenous stroma with a prominent capillary network. Tumor cells immunohistochemically expressed smooth muscle actin and CD10, but did not express CD117, Discovered on GIST-1 or nuclear β-catenin. Follow-up evaluation 23 months post surgery revealed no evidence of residual tumor. A review the cases of this rare entity reported in the English language literature is also provided.

No abstract

Context.-Kirsten-RAS (KRAS) mutations play an important role in the carcinogenesis of a subset of lung adenocarcinomas and are associated with poorer prognosis.Objective.-To investigate the relationship of KRAS mutation status to the histologic subtype of adenocarcinoma according to the recent classification, patient demographics, tumor size, predominant histologic subtype, nodal status, and visceral pleural invasion, in an attempt to uncover the reason for the worse prognosis associated with KRAS mutation.Design.-A total of 187 consecutive resected lung adenocarcinomas from our institution from 2008 to 2011 that were diagnosed according to the new International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification and screened for KRAS mutations were included in the study.Results.-A total of 32% of the adenocarcinomas harbored the KRAS mutation. The median age in the KRAS mutation group was 69 years (range, 43-86 years), and male to female ratio was 1:2.3. The proportion of heavy smokers was significantly higher in tumors with KRAS mutation compared with wild type (83% versus 62%; P ¼ .01). A total of 27% of tumors with KRAS mutation had pleural invasion versus 11% of tumors without KRAS mutation (P ¼ .009). A total of 59 tumor samples were positive for KRAS mutation (25 for G12C, 14 for G12A, 8 for G12V, 7 for G12D, 3 for G12S, and 1 for G12T), and only 3 tumors harbored codon 13 mutations (G13C). Two tumors had double mutations.Conclusions.-KRAS mutations are more common in heavy smokers, and lung adenocarcinomas with KRAS mutation are more likely to invade the visceral pleura. Increased frequency of visceral pleural invasion may explain in part the worse prognosis associated with KRAS mutations.

We describe the first cytology case report of an intraductal oncocytic papillary neoplasm (IOPN) of the liver. A 51-year-old male presented with recurrent cholangitis. Magnetic resonance imaging and endoscopic retrograde cholangiopancreatogram revealed a 1.1 × 0.9 cm polypoid lesion within the left intrahepatic bile duct. Fine-needle aspiration and needle core biopsy (NCB) revealed nests, 3-dimensional or papillary clusters of columnar or cuboidal cells with loss of polarity. The nuclei were uniform with even chromatin, and cytoplasm was granular or vacuolated. No mitosis or necrosis was seen. The cytologic and histologic diagnosis was "consistent with Intraductal Oncocytic Papillary Neoplasm (IOPN), intermediate grade (borderline)." The patient then underwent a left lateral liver segmentectomy. Microscopic examination showed histology similar to the NCB with no stromal invasion identified. Hepatic IOPN poses a diagnostic challenge due to its broad differential diagnoses. Both malignant and non-malignant IOPNs may present with similar clinical symptoms, pathology, histology, cytomorphology, and immunohistochemistry. Hepatic IOPN should be excised as it is a precursor lesion of adenocarcinoma.

No abstract