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Review Article: A Reevaluation of the Clinical Significance of Histological Subtyping of Non—Small-Cell Lung Carcinoma: Diagnostic Algorithms in the Era of Personalized Treatments

`Division of Pathologic Anatomy, Azienda Ospedaliero-Universitaria Policlinico, Modena

Giuseppe Pelosi, MD

Division of Pathologic Anatomy, European Institute of Oncology and University of Milan School of Medicine, Milan, giuseppe.pelosi{at}ieo.it

Paolo Graziano, MD

Division of Pathologic Anatomy, Forlanini Hospital, Rome

Mattia Barbareschi, MD

Division of Pathologic Anatomy, Santa Chiara Hospital, Trento

Mauro Papotti, MD

4 Division of Pathologic Anatomy, San Luigi Hospital and University of Turin, Orbassano Italy

The classification of lung cancer has always been primarily based on the morphologic assessment of routinely stained histological sections, but this approach may be difficult or even unfeasible in cytological preparations or small biopsies. Moreover, the simplistic dichotomization between small-cell carcinoma and non-small cell carcinoma (NSCLC) should be overcome, as new drugs have been discovered that are effective in specific subtypes of lung cancer. A more accurate characterization of NSCLC, however, may be hard in carcinomas lacking clear-cut signs of differentiation. The incorporation into the diagnostic algorithm of poorly differentiated carcinomas of an immunohistochemical panel including markers of squamous (high-molecular-weight cytokeratins, p63) and glandular (TTF-1, cytokeratin 7) cell differentiation seems the most promising approach. The evaluation of lung cancer for gene mutations, gene amplification, tumor-related angiogenesis, expression levels of DNA repair genes and genomic or proteomic profiles represents an exciting challenge for the pathologist in the near future.

Key Words: non—small cell lung carcinoma • small cell lung carcinoma • morphology • immunohistochemistry • antibody panel • gene • mutation • amplification • DNA repair

International Journal of Surgical Pathology, Vol. 17, No. 3, 206-218 (2009)
DOI: 10.1177/1066896909336178


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