title: Diagnosis of anaplastic lymphoma kinase rearrangement in cytological samples through a fluorescence in situ hybridization-based assay: Cytological smears versus cell blocks.
abstract: Anaplastic lymphoma kinase (ALK) status analysis of lung cytological specimens should be successfully encouraged in routine practice because biopsy specimens are not always available. To date, the US Food and Drug Administration has approved both fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) as diagnostic tests for identifying ALK-positive patients eligible for treatment with crizotinib. Although ALK IHC is an optimal diagnostic tool, FISH becomes mandatory in equivocal cases. ALK FISH of paraffin-embedded tissue material is still the gold standard, whereas the cytological specimen assay has not yet been completely standardized. Many controversial data have been reported on the adequacy of cytology cell blocks (CBs) versus conventional smears for FISH testing. This review discusses some critical issues related to ALK FISH of cytological samples, including the triaging of collected specimens to optimize the material, the use of CBs versus conventional smears, and alternative methods for an ALK rearrangement diagnosis. Conventional smears have the advantages of an immediate evaluation, no probe tissue-related artifactual loss, no fixation-related alterations, and usually sufficient material for an analytic preparation. On the other hand, CBs have several advantages, including the appropriate conservation of the tissue architecture, an absence of problems related to cell overlapping, and the ability to evaluate neoplastic cells in a dark field. Cancer Cytopathol 2017;125:303-312. © 2017 American Cancer Society.
authors.affiliation: Pathology Unit, Istituto Nazionale Tumori Fondazione G. Pascale, Naples, Italy.|Pathology Unit, Luigi Vanvitelli University of Campania, Naples, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Zito Marino
authors.affiliation: Unit of Pathologic Anatomy, Azienda USL Valle d'Aosta, Aosta, Italy.
authors.forename: Giulio
authors.initials: G
authors.lastname: Rossi
authors.affiliation: Anatomic Pathology Section Department of Pathology, University of Verona, Verona, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Brunelli
authors.affiliation: Pathology Unit, Istituto Nazionale Tumori Fondazione G. Pascale, Naples, Italy.
authors.forename: Maria Gabriella
authors.initials: MG
authors.lastname: Malzone
authors.affiliation: Pathology Unit, Istituto Nazionale Tumori Fondazione G. Pascale, Naples, Italy.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Liguori
authors.affiliation: Section of Pathologic Anatomy, Sacro Cuore Don Calabria Hospital, Negrar, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Bogina
authors.affiliation: Medical Oncology Unit, Department of Thoracic Surgical and Medical Oncology, Istituto Nazionale Tumori Fondazione G. Pascale, Naples, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Morabito
authors.affiliation: Division of Thoracic Surgery, Department of Thoracic Surgical and Medical Oncology, Istituto Nazionale Tumori Fondazione G. Pascale, Naples, Italy.
authors.forename: Gaetano
authors.initials: G
authors.lastname: Rocco
authors.affiliation: Pathology Unit, Luigi Vanvitelli University of Campania, Naples, Italy.
authors.forename: Renato
authors.initials: R
authors.lastname: Franco
authors.affiliation: Pathology Unit, Istituto Nazionale Tumori Fondazione G. Pascale, Naples, Italy.
authors.forename: Gerardo
authors.initials: G
authors.lastname: Botti
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D000077548:Anaplastic Lymphoma Kinase; D000077547:Crizotinib; D003581:Cytodiagnosis / Q000379:methods; D015321:Gene Rearrangement; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence / Q000379:methods*; D008175:Lung Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D016612:Paraffin Embedding; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011720:Pyrazoles / Q000627:therapeutic use; D011725:Pyridines / Q000627:therapeutic use; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D013048:Specimen Handling
chemical_list: D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011725:Pyridines; D000077547:Crizotinib; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases
keywords: anaplastic lymphoma kinase (ALK); cell block; cytological smears; fluorescence in situ hybridization (FISH); lung cytology