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Two decades of lung cancer through the pages of Cancer Cytopathology

In the mid-1990s, we in cytopathology thought we were at the pinnacle of lung cancer diagnosis. We were an integral part of the lung cancer clinical team, attended transthoracic fine-needle aspirates (FNAs) in radiology suites to perform immediate evaluations, handled aspirated or exfoliated pulmonary and bronchial material in the laboratory, were responsible for mighty decisions regarding lung masses, and gave the magic required code word assessment of “small” or “non-small.” We knew that our word dictated subsequent clinical management whether surgical, oncologic, or palliative, and we took inner pride in knowing that our thin needle sampling alone had saved many patients from purely diagnostic thoracic surgery. If we had any problems, they were perhaps in the realm of primary versus metastatic adenocarcinomas, the dogma being to give the patient the benefit of the doubt if comparison with prior tissue did not help. There also were those non-small cell samples in which there was some doubt as to whether there was glandular or squamous differentiation, or both. In this dilemma, we were assured by our oncologist colleagues that it did not really matter to them or to prognosis; they would use pretty much the same cocktails anyway. There were no antibodies specific to glandular or squamous lung cancer; no thyroid transcription factor 1 (TTF1), napsin A, p40, or p63; no endobronchial ultrasound guidance; no staging required of us; and no molecular targeting of lung cancers. Oh what a very long way we had yet to travel. Looking back over 20 years in the annals of Cancer Cytopathology, 3 developments have undoubtedly carried the pulmonary cytopathologist into the modern arena of lung cancer diagnosis, staging, and prognosis. Immunocytochemical testing to more specifically determine accurate cell typing in non-small cell lung cancer was introduced pari passu with the need of oncologists to treat glandular and squamous carcinomas differently. Confirmation of neuroendocrine differentiation by immunochemistry was an added safety measure in what was then still widely called “small cell” or even “oat cell” carcinoma. The availability of an increasing armamentarium of antibodies assisted immeasurably in the previously mentioned concern regarding primary and metastatic carcinomas, whether intrapulmonary, gastrointestinal, colorectal, breast, prostatic, or other. Not insignificant was the ability, through a changing spectrum of favored antibodies, to accurately distinguish epithelial lung tumors from mesothelial primaries in both FNA and fluid samples. Pleural fluid samples in the diagnosis of lung cancer are quite possibly the simplest, most useful, practical, and valuable specimens to process. Not only is the diagnosis and subtyping of neoplasia sensitive, specific, and accurate in good hands, but any adjunctive studies including culture, immunochemistry, fluorescence in situ hybridization (FISH), flow cytometry, and molecular analysis may be performed readily on the fluid itself or on cell blocks created. Staging is assured and inoperability confirmed by the very existence of pleural