. Step 39 of 41
Clinical Stem 3
A patient with right upper lobe adenocarcinoma progressing on biomarker-directed therapy

Answer D
Results of molecular tests can alter therapy. In this case, the patient could be enrolled in a clinical trial using a monoclonal antibody against c-MET. An IHC panel can aid in sub-classifying NSCLC. Multiple IHC stains, however, may reduce the quantity of tissue available for molecular analysis. Tissue conservation is crucial so that tissue is available for potential molecular testing.

Pathologists should minimize the number of IHC preparations used to sub-classify a lesion. When morphology is equivocal and there is no clear glandular or squamous differentiation, IHC using a panel of antibodies; typically TTF-1, p63 and p40, cytokeratin 7 and cytokeratin 5/6 may be used on previously stained smears, automated slides, and cell-blocks.

Rapid On-Site Evaluation (ROSE), while not available everywhere, is an important complement to needle aspiration. ROSE helps improve the accuracy of the procedure, but does not necessarily improve yield. By using ROSE, the cytopathologist can confirm that the specimen is adequate and representative of the targeted lesion. For example, a significant number of lymphocytes should be found when a lymph node is targeted. ROSE also helps confirm that sufficient material is obtained for a definitive final diagnosis and molecular testing. ROSE thus optimizes future allocation and processing of specimens for specific analyses according to suspected or known diagnosis.
Results of IHC usually favor a single diagnosis. Adenocarcinomas of pulmonary origin are typically reactive for TTF-1 and cytokeratin 7 and non-reactive for p63 and cytokeratin 5/6. Squamous cell carcinomas are typically reactive for p63 and cytokeratin 5/6 but non-reactive for TTF-1 and cytokeratin 7. The concordance between needle aspirate and biopsy in NSCLC subtyping is very high (96%), especially when analysis of material in cell blocks can be performed.

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References:
  1. Travis WD, Rekhtman N. Pathological diagnosis and classification of lung cancer in small biopsies and cytology: strategic management of tissue for molecular testing. Semin Respir Crit Care Med. 2011;32:22?31.
  2. Griffin AC, Schwartz LE, Baloch ZW. Utility of on-site evaluation of endobronchial ultrasound-guided transbronchial needle aspiration specimens. Cytojournal 2011; 8: 20.
  3. Pusztaszeri M Soccal PM, Mach N et al. Cytopathological Diagnosis of Non Small Cell Lung Cancer: Recent Advances Including Rapid On-Site Evaluation, Novel Endoscopic Techniques and Molecular Tests. J Pulmonar Respirat Med 2012; S5:002.
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