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IASLC ATLAS OF ALK TESTING IN LUNG CANCER
of nonepithelial malignancy (such as lymphoma or sarcoma) and/or the possibility that a cancer, especially adenocarcinoma, is not lung metastasis from another organ (Kerr 2013b). Most often, this step can be done easily, based on the evaluation of adequate clinical and radiographic information accompanying the sample and the basic H & E-based morphologic assessment. A lack of clinical information, however, may lead to unnecessary ancillary IHC testing on the sample in an attempt to exclude possible extrathoracic sources for an adenocarcinoma, which may leave insufficient material for molecular testing. Assuming the tumor is primary lung cancer, the next step is to distinguish small cell lung cancer (SCLC) from other types, as advanced SCLC is treated differently from NSCLC. This discrimination can usually be made with high accuracy on the basis of morphologic characteristics (Burnett 1994), but IHC may be required. Most cases that are not SCLC can be accurately and consistently classified morphologically as squamous cell carcinoma, adenocarcinoma or, rarely, another NSCLC type. In 25% to 40% of cases, however, depending on the sample type and case mix, morphologic features are not adequate for accurate and consistent NSCLC subtype classification; such cases should be initially designated NSCLC not otherwise specified (NOS) (Chuang 1984). Diagnostic IHC can then be used to predict the likely NSCLC subtype (Loo 2010, Travis 2011, Travis 2013). This approach, using a limited IHC panel, can reduce the proportion of NSCLC-NOS cases to less than 10% and predict the NSCLC subtype in most NOS cases with an accuracy of more than 80% (Loo 2010). Cases reported in conjunction with this use of IHC should be described by the recommended terminology (e.g., NSCLC, favor adenocarcinoma) in a morphologically undifferentiated case, where IHC predicts adenocarcinoma (Travis 2011, Kerr 2013a).
Conclusion
The identification of patients with therapeutically targetable molecular drivers in their tumors is now a standard of care. The need for extra molecular testing, beyond that required for initial morphologic diagnosis and refinement of tumor classification by IHC when necessary, makes the acquisition, handling, processing, and judicious use of diagnostic tumor tissue of crucial importance. Every effort must be made to ensure that a sufficient amount of tumor tissue is available for a subsequent diagnostic step. However, lack of sufficient tissue may be inevitable in some cases and will have the greatest impact on molecular tests that follow the tumor diagnosis. When the amount of tissue is insufficient, repeat biopsy is increasingly being done.