Does Immunohistochemistry Represent a Robust Alternative Technique in Determining Drugable Predictive Gene Alterations in Non-Small Cell Lung Cancer?

Immunohistochemistry (IHC) is a widely-tested, low-cost and rapid ancillary technique available in all laboratories of pathology. This method is generally used for diagnostic purposes, but several studies have investigated the sensitivity and specificity of different immunohistochemical antibodies as a surrogate test in the determination of predictive biomarkers in non-small cell lung cancer (NSCLC), particularly for Epidermal Growth Factor Receptor (EGFR) gene mutations, Anaplastic Lymphoma Kinase (ALK) gene and ROS1 rearrangements. In this review, a critical examination of the works comparing the consistency of IHC expression and conventional molecular techniques to identify genetic alterations with predictive value in NSCLC is discussed. Summarizing, data on sensitivity and specificity of antibodies against ALK and ROS1 are very consistent and time has come to trust in IHC at least as a cost-effective screening tool to identify patients with rearranged tumors in clinical practice. On the other hand, mutant-specific antibodies against EGFR demonstrate a good specificity but a lowto- fair sensitivity, raising some cautions on their employment as robust predictive biomarkers. A brief comment on preliminary experiences with antibodies against BRAF, RET, HER2 and c-MET is also included.

Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia syndrome.

The term diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) may be used to describe a clinico-pathological syndrome, as well as an incidental finding on histological examination, although there are obvious differences between these two scenarios. According to the World Health Organization, the definition of DIPNECH is purely histological. However, DIPNECH encompasses symptomatic patients with airway disease, as well as asymptomatic patients with neuroendocrine cell hyperplasia associated with multiple tumourlets/carcinoid tumours. DIPNECH is also considered a pre-neoplastic lesion in the spectrum of pulmonary neuroendocrine tumours, because it is commonly found in patients with peripheral carcinoid tumours.In this review, we summarise clinical, physiological, radiological and histological features of DIPNECH and critically discuss recently proposed diagnostic criteria. In addition, we propose that the term "DIPNECH syndrome" be used to indicate a sufficiently distinct patient subgroup characterised by respiratory symptoms, airflow obstruction, mosaic attenuation with air trapping on chest imaging and constrictive obliterative bronchiolitis, often with nodular proliferation of neuroendocrine cells with/without tumourlets/carcinoid tumours on histology. Surgical lung biopsy is the diagnostic gold standard. However, in the appropriate clinical and radiological setting, transbronchial lung biopsy may also allow a confident diagnosis of DIPNECH syndrome.

Classification of different patterns of pulmonary adenocarcinomas.

The epidemic increase of adenocarcinoma histology accounting for more than 50% of primary lung malignancies and the advent of effective molecular targeted-therapies against specific gene alterations characterizing this tumor type have led to the reconsideration of the pathologic classification of lung cancer. The new 2015 WHO classification provided the basis for a multidisciplinary approach emphasizing the close correlation among clinical, radiologic and molecular characteristics and histopathologic pattern of lung adenocarcinoma. The terms 'bronchioloalveolar carcinoma' and 'mixed adenocarcinoma' have been eliminated, introducing the concepts of 'adenocarcinoma in situ', 'minimally invasive adenocarcinoma' and the use of descriptive predominant patterns in invasive adenocarcinomas (lepidic, acinar, papillary, solid and micropapillary patterns). 'Invasive mucinous adenocarcinoma' is the new definition for mucinous bronchioloalveolar carcinoma, and some variants of invasive adenocarcinoma have been included, namely colloid, enteric and fetal-type adenocarcinomas. A concise update of the immunomorphologic, radiological and molecular characteristics of the different histologic patterns of lung adenocarcinoma is reported here.