2 Pathology Research International (a) (b) (c) Figure 1: The characteristic morphologic patterns of tumor in smears. (a) SQC carcinoma showing ﬂat sheet of polygonal, atypical cells and (b) orangeophilia on Pap stain demonstrating keratinization. (c) ADC with typical cytomorphology and formation of glandular structures. classiﬁcation, prognostic makers, and use of ancillary tech- niques. 2. Clinical Advances in the Management of Patients with Pulmonary Carcinoma The current classiﬁcation of lung cancer recognizes four major histological subtypes, namely, squamous cell carci- noma (SQC), adenocarcinoma (ADC), large-cell carcinoma (LCC), and small cell lung carcinoma (SCLC). Until recently, most of the cytological diagnosis of lung carcinoma was based on distinguishing SCLC from other tumors generally designated as nonsmall cell carcinoma (NSCLC), because these two categories were the most relevant for directing therapy. However, advances in thoracic medical oncology have led to a paradigm shift in NSCLC diagnosis, resulting in a new emphasis on accurate NSCLC subtyping. Speciﬁcally, two novel agents have challenged NSCLC as clinically relevant diagnostic category. It has been demonstrated that patients with the diagnosis of SQC are at increased risk for life-threatening complications if treated with bevacizumab, a humanized antibody against vascular endothelial growth factor (VEGF) [3]. In addition, in the case of pemetrexed, an antifolate that inhibits multiple enzymes in purine and pyrimidine synthesis, patients with SQC showed no response to the drug in comparison to a good response observed in patients with the diagnosis of non-squamous cell carcinoma [4]. For these reasons, these two new drugs are only recommended for use in patients with a diagno- sis of non-squamous cell carcinoma. Other developments include the identiﬁcation of genetic alterations which have been described almost exclusively in adenocarcinoma that confer susceptibility to therapeutic agents or resistance to chemotherapeutic drugs. For example, tumors with epider- mal growth factor (EGFR) mutations have a better outcome and respond to the tyrosine kinase inhibitors erlotinib and geﬁtinib, as a ﬁrst-line therapy, whereas patients without EGFR mutations seem to have a better outcome with standard chemotherapy [5]. Furthermore, translocation in the EML4-ALK gene has been described predominantly in adenocarcinomas. This translocation confers susceptibility to speciﬁc inhibitor, crizotinib that is currently undergoing clinical testing [6]. These advances in the understanding of molecular mechanisms underlying lung cancer and the development of new targeted therapies challenge the traditional diagnostic dichotomization between SCLC and NSCLC and prompt a more speciﬁc characterization of NSCLC into squamous or adenocarcinoma category. Traditionally, NSCLC sub- classiﬁcation has been based on morphologic assessment of routine H&E-stained histological specimens. Because cytology specimens, such as FNAB, diﬀer in preparation and technique from traditional histology, the accuracy of subtyping these specimens has been challenged, yet there is considerable evidence supporting the utility of cytology in both subtyping NSCLC and providing material for predictive and prognostic studies. 3. Role of Immediate Assessment in the Accuracy of Lung FNA Cytological Diagnosis Published reports reveal that the sensitivity of FNAB for the diagnosis of lung cancer ranges from 56 to over 90% whereas speciﬁcity is close to 100%. In nearly all these studies, the overall positive predictive value is nearly 99%. While the false positive rate is generally less than 1%, a negative result is less reliable with most studies reporting a false negative rate of around 10% [7, 8]. The major contribution to the relatively high false negative rate is failure to obtain diagnostic material, most commonly due to sampling error. Studies have shown that immediate on- site assessment is valuable in minimizing false negative diagnoses due to nondiagnostic material [9, 10]. Published series by Austin and Cohen show that immediate on-site assessment during FNAB was associated with a statistically signiﬁcant increased diagnostic accuracy compared to cases without immediate assessment, 100% versus 80%, respec- tively [11]. During on site adequacy determination, smears from the aspirate are rapidly stained and are evaluated by a cytopathologist or cytotechnologist for cellularity and diagnostic yield. On-site adequacy evaluation also pro- vides real-time communication of information including appropriate tissue triage recommendations for ancillary tests such as molecular testing, ﬂow cytometry, cytoge- netics, electron microscopy, and so forth. This interaction directly impacts clinical management during the critical