Keratin formation may occasionally be seen in radicular cysts, but when present it affects only part of the cyst wall (Figure 3.14a). Browne and Smith (1991 ) stated that 2% of radicular cysts may show some keratinisation and that orthokeratin with evidence of a granular cell layer is most common. More recently, Maheswaran et al. (2014 ) analysed 38 radicular cysts and 9 residual cysts using Papanicolaou stain and found evidence of keratinisation in 12 (31.6%) radicular cysts and 6 (66.7%) residual cysts. Orthokeratin was only found in 1 residual cyst and only 2 cysts showed typical parakeratin. In all other cases the keratin was described as focal. However, little detail was given and the findings were not illustrated. We interpret this to mean that the Papanicolaou technique revealed occasional superficial orange‐stained cells. Although this may suggest early keratinisation, it should be noted that this technique is primarily a cytological stain and may not be as reliable as a routine haematoxylin and eosin (H&E) stain for identification of keratin in histological sections (Rao et al. 2015 ). A more cautious interpretation of Maheswaran et al.'s data may suggest that only three of their cysts showed clearly identifiable keratinisation (6.4%). Our experience would support this, since we rarely see true keratinisation in radicular cysts, and when present it affects only a small section of the lining. This, and attention to the clinical and radiological findings (association with a non‐vital tooth), should prevent the lesion being misinterpreted as odontogenic keratocyst. Also, when present the parakeratin seen in a radicular cyst is different morphologically from that seen in keratocysts, since it lacks the typical corrugated surface and affects only a small portion of the lesion.
Table 3.3 Characteristic histopathological features found in radicular cysts, with their approximate frequency (see text for explanation).
| Feature | Frequency (%) |
|---|---|
| Keratinisation | 2 |
| Ciliated cells | 10 |
| Hyaline bodies | 10 |
| Foamy histiocytes | 10 |
| Mucous cells | 20 |
| Cholesterol | 30 |
Metaplastic changes, in the form of mucous cells or ciliated cells, are frequently found in the epithelial linings of radicular cysts (Table 3.3; Shear 1960b ; Browne 1972 ; Browne and Smith 1991 ; Slabbert et al. 1995 ; Takeda et al. 2005 ; Tsesis et al. 2016 ). Mucous cells are seen in the surface layer of the stratified squamous epithelial lining, either as a continuous row (Figure 3.14d) or as scattered cells (Figure 3.14c). Ciliated cells may also be seen, but are always found in association with mucous cells and together they sometimes form quite well‐developed respiratory‐type (pseudostratified columnar ciliated) epithelium (Figure 3.14b).
Figure 3.14 Cellular changes in the lining of radicular cysts. (a) A portion of the lining showing a focal area of orthokeratinisation. (b) Respiratory‐type epithelium with cilia and occasional mucous (goblet) cells. (c, d) Mucous cells in the surface layer may be scattered (c) or may form a continuous row (d).
Browne (1972 ) examined 402 radicular cysts and found mucous cells in 159 (39.6%), but cilia were only found in 3 cases (0.7%). Takeda et al. (2005 ) found mucous cells in 18% of radicular cysts, and in most cases they were arranged along the surface of the epithelium, but occasional intraepithelial gland‐like structures were also noted, most often in areas where the epithelium was hyperplastic. Browne (1972 ) found no difference in frequency of mucous cells between mandibular and maxillary lesions, but Takeda et al. (2005 ) found that they were more common in maxillary lesions (21%) than mandibular lesions (14%). In an analysis of 711 radicular cysts, Tsesis et al. (2016 ) found mucous cells in 5.3% and 7.4% of mandibular and maxillary lesions, respectively, but this difference was not significant. They also found that mucous cells were significantly more likely to be found in residual (23.5%) than radicular (5.8%) cysts, and were also more frequent in asymptomatic cysts and in cysts with well‐demarcated radiographic margins. This suggests that metaplasia takes time and is more likely to be encountered in well‐established or older cysts. This view is supported by the observation of Browne (1972 ) that there was an increasing frequency of mucous cells with age, at the rate of 7% per decade.
Slabbert et al. (1995 ) studied 154 mandibular radicular and residual cysts and found unequivocal mucous metaplasia in 15 (10%). In many cases they found that the mucous cells were associated with vacuolated cells, many of which were empty, but some contained fine granules or networks of periodic acid–Schiff (PAS)–positive material. The authors observed that the vacuolated cells resembled those described by Fell (1957 ) in the process of metaplasia from stratified squamous to ciliated epithelium in explants of chick embryo skin grown under the influence of excess vitamin A. By analogy to Fell's findings, Slabbert et al. (1995 ) suggested that the vacuolated cells represented an intermediate stage in the process of mucous metaplasia. Takeda et al. (2005 ) found similar clear cells and agreed with Slabbert et al. (1995 ) that mucous cell differentiation is a process of metaplasia. This view is also supported by the fact that mucous cells are found in mandibular lesions. Some have suggested that an origin from antral mucosa (see below) may explain mucous cells in radicular cysts. This may happen on occasion, but the mucous cells in mandibular lesions are almost certainly explained by true metaplasia, and provide good evidence for the metaplastic potential of odontogenic epithelium. Browne (1972 ) also found mucous cells in dentigerous cysts and lateral periodontal cysts, with a similar frequency between mandibular and maxillary lesions.
Cilia are found in radicular cysts with reported frequencies of 0.7% (Browne 1972 ), 11.4% (Takeda et al. 2005 ), 4.8% (Tsesis et al. 2016 ), and 8.2% (Ricucci et al. 2014 ). In his careful ultrastructural studies, Nair examined 39 cysts and found 3 (7.6%) that were lined by ciliated columnar epithelium (Nair et al. 2002 ). All were found in the maxilla and he suggested that the cyst linings were derived in part from cell rests of Malassez, but also from antral mucosa. However, although cilia do appear to be more common in the maxilla, ciliated epithelium has also been found in cysts in the anterior and posterior regions of the mandible. In the study of Takeda et al. (2005 ), ciliated cells were found overall in 11% of radicular cysts, but in 12% and 9% of maxillary and mandibular lesions, respectively. Tsesis et al. (2016 ) found cilia in 4.8% of 711 cysts, but only in 2 (0.2%) mandibular lesions compared to 32 (8.9%) maxillary lesions. Furthermore, 16 were found in the maxillary molar regions, 12 in the anterior region, and 4 associated with premolars. Browne (1972 ) also found that cilia were more frequently encountered in the maxilla, with 2 of 3 being of maxillary origin.
Gao et al. (1988b ) and Lu et al. (2002 ) investigated cytokeratin (CK) expression in radicular cysts. Gao et al. showed strong CK19 expression in rest cells of Malassez and in the epithelium of periapical granulomas and radicular cysts, supporting an odontogenic origin for the cyst lining. As an early change, proliferating epithelium in periapical granulomas also uniformly and strongly expressed CK14 and subsequently CK13 and CK4. Further epithelial changes to form a cyst lining were associated with a more clearly differentiated phenotype of non‐keratinised stratified squamous epithelium expressing CK8 and CK18. Lu et al. (2002 ) confirmed some of these findings