Apoptotic ciliated cells on sputum smear

Dear Dr. Bedrossian: Ciliated cells observed on sputum smears may be detached from airway epithelia of the nasal and tracheobronchial areas. Individually, and in well-preserved cells, we can point out as morphological features: columnar shape ending in a tail, cilia with a terminal plate at the apical end, and a nucleus (at the basal end) with a finely granular chromatin pattern. Ciliary arrangement is characteristic at the apical end, it being unidirectional and following the major axis to the cytoplasm. Because of degenerative changes caused by cellular exfoliation, these features may be absent and/or show significant modifications such as absence of cilia, existence of cytoplasmatic debris, and nuclear alterations (commonly hyperchromasia with a tendency to karyopicnosis and/or karyorrhexis). On the other hand, apoptosis is one of the main types of programed cell death by means of an orchestrated series of biochemical events due to a set of aspartate-specific proteases called caspases. In cancer, this biological mechanism is crucial because defects and/or fails in apoptosis are implicated in both tumorigenesis and chemotherapy drug resistence. Moreover, apoptosis is required for normal development and maintenance of tissue physiology, in addition to having a role as a defense mechanism to remove damaged and infected cells, and has also been postulated as a mechanism to restore homeostasis in hyperplastic epithelium after airway inflammation because of a reduction of cell numbers by programed cell death. In certain airway inflammatory diseases, such as bronchial asthma, excessive apoptosis may be a mechanism likely to be responsible for damage to, and sloughing off, of airway epithelial cells. Some in vitro and in vivo models have suggested that, in airway epithelial cells, apoptosis may be a mechanism to limit viral particle release and could be a potential mechanism for chronic airway epithelial damage induced by corticosteroids. Among the morphological features of apoptotic cells, it is possible to highlight nuclear alterations such as chromatin condensation, nuclear shrinkage, DNA fragmentation, and formation of apoptotic bodies. These changes are compatible with those observed in ultrastructural studies. Other pathological factors may cause morphological alterations in airway ciliated cells such as viral injury, causing phenomena such as ‘‘ciliocythopthoria’’ and aberrant ciliogenesis; smoking, with axonemal anomalies and shortened cilia; and chronic bronchitis, with ciliary membrane abnormalities. These alterations have been observed by means of light and electron microscopy both in cytology samples and biopsy specimens. The purpose of this letter is to report two images showing apoptotic ciliated cells on a sputum smear, stained by the Papanicolaou method, and corresponding to a spontaneous expectoration from a 59-year-old man, habitual smoker and diagnosed with chronic bronchitis who, 1 month ago, suffered from an acute clinical respiratory viral process. In both (Figs. 1A and B), we can observe isolated ciliated cells, columnar in shape, with a dense acidophilic cytoplasm, fragmented nucleus in a number of dark round corpuscles (apoptotic changes), and a weird ciliary arrangement alongside a large portion of the cytoplasmic outline. In one of the cells (A), it is possible to appreciate a dark line corresponding to the terminal bar, but in the other (B), the cytoplasmic outline is irregular (indented-like) and the terminal bar is not appreciable. Although in both cells the ciliary insertion seems regular, its disposition, in contrast, is very unusual in the majority of the airway epithelial ciliated cells observed on sputum smears. These cells, by means of an immunohistochemical technique and using the epithelial marker CAM 5.2 (1:50 dilution, Dako En Vision, Denmark), showed positivity for this antibody. *Correspondence to: Rafael Martı́nez-Girón, M.D., Ph.D., CF Anatomı́a Patológica y Citologı́a, Instituto de Piedras Blancas, Avda. Principal 33, 33450 Piedras Blancas, Asturias, Spain. E-mail: rmartinezgiron@hotmail.com Received 16 June 2010; Accepted 2 November 2010 DOI 10.1002/dc.21614 Published online 6 January 2011 in Wiley Online Library (wileyonlinelibrary.com)