Small-cell lung cancer in never-smokers: A case series
Introduction
Lung cancer is the leading cause of cancer-related death and the second most commonly diagnosed cancer in women [1]. Small-cell lung cancer (SCLC) represents a particularly aggressive subtype that accounts for 15–20% of all lung cancers, with an incidence that has been progressively declining as the smoking rate has declined [2], [3]. In fact, SCLC is strongly correlated to tobacco smoking and, despite the fact that lung cancer in never-smokers is approximately the seventh most important cause of cancer-related mortality after smoking [1], [4], [5], [6], it is very rare to find reports describing SCLC in never-smoking patients [7], [8], [9], [10], [11], [12]. The aetiology and pathogenicity of SCLC in these contexts are still unclear; this is mostly due to the paucity of cases and lack of solid research, especially compared to the research developed among non-small cell lung cancer (NSCLC) in patients with no smoking-history [13], [14].
We present four cases of non-smoker patients diagnosed with SCLC in the Pulmonology Unit of Coimbra University Hospital accounting for 11.4% of all SCLC at follow-up during the same period. Each non-smoker patient completed a detailed telephone questionnaire which addressed, firstly, second-hand smoking habits and, secondly, occupational exposure to carcinogens including asbestos, chromium, arsenic, cadmium, silica, nickel, and polycyclic aromatic hydrocarbons. Five patients diagnosed with SCLC, all females, had never smoked and had had no significant exposure to environmental tobacco smoke (ETS) or other known carcinogenic agents. The cumulative dose of ETS was assessed as the sum of the number of exposure years at home, social gatherings and/or workplace, similar to what has been previously reported [15]. Those with significant cumulative ETS were considered to be passive smokers and thus excluded from our study.
Section snippets
Case 1
A 75-year-old female was referred to our Unit for a 3-month history of productive cough, hemoptoic sputum, left chest pain, asthenia and anorexia. Computed tomography (CT) revealed a pulmonary mass in the upper left lobe. Transbronchial biopsies diagnosed SCLC: sheets of small cells with focal nuclar crushing in scarce hyaline stroma, where trabecular pattern was also evident. There the cells revealed positive staining for AE1/AE3, cytokeratin (CK) 7, thyroid transcription factor-1 (TTF1) and
Discussion
The four never-smoking patients, with the diagnosis of SCLC were treated in the Pulmonology Unit. The histological diagnosis were obtained by transbronchial and bronchial biopsy and confirmed with immunohistochemical staining (Ki-67 staining was not interpretable in one of the cases due to lack of material).
To the best of our knowledge, this is the first report to definitely exclude smoking, either active or passive, as the underlying cause of SCLC in all the patients in the subset. Previously
Conflict of interest
The authors have no conflict of interests to declare.
Acknowledgments
To Dr. Tiago Alfaro, for his guidance and support.
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