. Step 28 of 41
Clinical Stem 3
A patient with right upper lobe adenocarcinoma progressing on biomarker-directed therapy

Answer B
Slides can be prepared and internally interpreted by cytotechnologists to ensure an adequate specimen for molecular testing. This may reduce time, effort, and complications. Physicians and their staff should be familiar with the process of smear preparation. Cytologic sampling is limited by the amount of tissue obtained because a small number of passes are made through the lesion. Often, all the aspirated material is expressed onto a single or small number of slides. Any type of cytologic sample and preparation may be used, including stained or unstained smears, automated Thin Prep slides and cytospin. Cell-block is commonly used for molecular analysis. The proportion of unsatisfactory cytology specimens for molecular analyses varies significantly with the type of cytological specimen. Obtaining core tissue should be attempted but is not always successful.

When cell blocks are planned, only a few slides might be needed for Diff-Quick and Papanicolau smear. The rest of the specimen is saved for cell-block preparation. Material obtained from additional sampling of the lesion or lymph node is expulsed from the needle into a solution such as Cytolyt. This is rendered into a pellet which is embedded in paraffin. This preparation may not represent the underlying tissue architecture, but is adequate for special stains and molecular analysis. Because there is some debate whether alcohol fixation is appropriate for FISH testing, techniques should be discussed with the institution's pathologist.

EBUS-TBNA and pleural fluid are more suitable than BAL because a larger number of tumor cells are usually retrieved, and there is greater possibility to make a cell-block.

Molecular testing for EGFR, K-RAS, BRAF, ALK and PIK3CA on cytology specimens provides results that are equivalent to those obtained from histology specimens in about 80% of cases.

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References:
  1. Burlingame OO, Kesse KO, Silverman SG, et al. On-site adequacy evaluations performed by cytotechnologists: correlation with final interpretations of 5241 image-guided fine needle aspiration biopsies. Cancer Cytopathol 2011.
  2. Colt HG, Murgu S. BronchAtlas. Smear preparation and bronchoscopic needle aspiration video available on YouTube (BronchOrg channel) 6/26/12.
  3. Muley T, Herth FJF, Schnabel P, Dienemann H, Meister M. From tissue to molecular phenotyping: Pre-analytical requirements Heidelberg Experience. Transl Lung Cancer Res 2012;1(2):111-121.
  4. Smouse JH, Cibas ES, Janne PA et al. EGFR mutations are detected comparably in cytologic and surgical pathology specimens of nonsmall cell lung cancer. Cancer 2009; 117: 67-72.
  5. Billah S, Stewart J, Staerkel G et al. EGFR and KRAS mutatiaons in lung carcinoma: molecular testing by using cytology specimens. Cancer Cytopathol 2011; 119:111-117.
  6. Schuurbiers OC, Looijen-Salamon MG, Liqtenberg MJ et al. A brief retrospective report on the feasibility of epidermal growth factor receptor and KRAS mutation analysis in transesophageal ultrasound and endobronchial ultrasound-guided fine needle cytological aspirates. J Thorac Oncol 2010; 5: 1664-1667).
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