as well as CK13. Of relevance to the above discussion, they compared keratin protein and mRNA expression in radicular cysts to normal nasal and oral epithelium. They showed that a CK18+/CK8+/CK13– phenotype was only found in nasal epithelium. Only three cysts showed this phenotype and all three were large maxillary lesions protruding into the maxillary sinus. They concluded that occasional maxillary radicular cysts may not be odontogenic in origin, but that their epithelium may derive from nasal or antral respiratory mucosa.
From these studies, it seems certain that some maxillary cysts may derive at least part of their epithelial lining from the antral mucosa, and this may explain the occurrence of mucous and ciliated cells or respiratory‐type epithelium found in maxillary cysts. Such an occurrence could also be deduced from the radiological appearance of large maxillary cysts, which often clearly protrude into the maxillary sinus. However, the presence of secretory and ciliated epithelium in mandibular radicular cysts also confirms that mucous and ciliated cells may arise as a result of metaplasia.
Hyaline Bodies
In approximately 10% of radicular cysts, hyaline bodies are found in the epithelial linings (Figure 3.15). Although initially noted by Dewey in 1918, they were first described in detail by Rushton (1955 ) and are often referred to as Rushton bodies. They measure up to about 0.1 mm and are described as having two morphological patterns. The first pattern appears like linear, straight, or curved rods, sometimes with a ‘hairpin’ shape (Figure 3.15b). These may have a pale centre and a darker eosinophilic or basophilic periphery. Serial sections, however, will show that these are not actually rods, but are folded sheets. The second pattern is of circular or polycyclic bodies (Figure 3.15), which often have a clear or pale centre, surrounded by concentric laminations that are variably eosinophilic or basophilic. Both patterns may exist together, as can be seen in Figure 3.15. Hyaline bodies are brittle and frequently fracture during histological processing, so that only small fragments may be seen. Occasionally they may form masses that protrude into the cyst lumen (Figure 3.15a), but only very rarely are they seen in the fibrous capsule. The presence of hyaline bodies may be suspected if, on examination of the gross specimen, the pathologist sees small, smooth, white, dome‐shaped swellings of the epithelial surface protruding into the cyst cavity.
Although they are typically seen in radicular cysts, they may also be encountered in dentigerous cysts or odontogenic keratocysts, but are always associated with areas of inflammation. Lam and Chan (2000 ) reported hyaline bodies in 7% of a series of 69 odontogenic keratocysts and Lin et al. (2013 ) found them in 11% of dentigerous cysts. Ide et al. (1996 ) reported an unusual glandular odontogenic cyst with hyaline bodies, and Takeda et al. (1985 ) described their presence in a plexiform ameloblastoma. They are, however, specific to odontogenic epithelium and have not been reported in non‐odontogenic cysts. Occasionally similar structures may be found associated with epithelial rests in dental follicles.
Figure 3.15 Hyaline bodies in the epithelial lining of a radicular cyst. (a) The bodies accumulate in the epithelial lining and form nodules that protrude into the lumen. (b) The bodies are eosinophilic and form circular, folded, and curved ‘rod’ shapes.
Hyaline bodies are intriguing and enigmatic, but they have little diagnostic or prognostic significance. More than 100 years after they were first noted, the origin and pathogenesis of these bodies is still debated and no consensus has been reached. There have been two competing theories of their origin: first, that they derive from epithelium; and second, that they are of haematogenous origin. Rushton (1955 ) believed that the hyaline bodies resembled, in appearance and the liability to fracture, the keratinised secondary enamel cuticle of Gottlieb. Wertheimer (Wertheimer et al. 1962 ; Wertheimer 1966 ) directly compared enamel cuticle and hyaline bodies and showed similar staining for a number of histochemical stains, also concluding that the bodies represented a keratin‐like epithelial product equivalent to dental cuticle.
A number of other studies, which have included electron microscopy and X‐ray microanalysis, have also supported an epithelial origin (Allison 1974 , 1977a , 1977b ; Jensen and Erickson 1974 ; Morgan and Johnson 1974 ; Morgan and Heyden 1975 ; Rühl et al. 1989 ; Philippou et al. 1990 ). Morgan and Johnson (1974 ) also found cell debris and particulate matter and concluded that the bodies are a secretory product of odontogenic epithelium that is deposited on a hard surface in a manner analogous to the formation of dental cuticle on the unerupted portions of enamel surfaces. X‐ray microanalysis and scanning electron microscopic studies (Rühl et al. 1989 ; Philippou et al. 1990 ) also found that the bodies were associated with cell debris, suggesting that foreign material may irritate the epithelium to form a cuticle‐like substance. These findings are consistent with the observation that hyaline bodies are always associated with areas of chronic inflammation. In a rarely cited paper dating back to 1943, Bauer described the histology of the enamel cuticle associated with an unerupted third molar overlying the carious roots of the second molar (Bauer 1943 ). There was a periapical granuloma containing proliferating epithelium that was in continuity with the reduced enamel epithelium of the unerupted tooth. Within the epithelium Bauer described ‘bands, rods, rings, and spherically shaped bodies’, which were continuous with the primary enamel cuticle of the unerupted tooth and with the ‘dental cuticle’ surrounding the cementum of the decayed roots. He referred to these structures as ‘horny hyaline‐like bodies’ and his illustrations show structures identical to what we now regard as hyaline bodies. Bauer also noted that these bodies were associated with proliferating epithelial strands that were a ‘product’ of chronic inflammation. These simple, but careful, observations are consistent with the more detailed later studies described above and provide good evidence that hyaline bodies can derive from odontogenic epithelium and are similar to enamel cuticle.
Others, however, have believed that hyaline bodies are of haematogenous origin (Bouyssou and Guilhem 1965 ; Sedano and Gorlin 1968 ; El‐Labban 1979 ). Although the mechanism is not clear, these studies suggest that the bodies derive from thrombi or degenerate red blood cells within vessels that have become entrapped in the proliferating epithelial lining of the cyst. Browne and Matthews (1985 ) tested this hypothesis using immunohistochemistry to stain cysts for keratin, factor VIII‐related antigen, haemoglobin, and fibrinogen. The hyaline bodies were negative for all these antigens, but fibrinogen was detected in the cores of some circular and polycyclic forms. Browne and Matthews concluded that hyaline bodies were not keratinous in nature, nor did they arise from erythrocytes or capillary endothelium. They tentatively proposed that the presence of fibrinogen in the cores of some hyaline bodies could support the notion of a haematogenous origin.
Although we agree that the circular or polycyclic forms are sometimes of a morphology that suggests a transversely sectioned blood vessel, there are some puzzling features about their distribution if they were of vascular or haemotogenous origin. For one thing, they are often seen in epithelium overlying connective tissue devoid of any blood vessels. For another, they are very rarely found in the fibrous capsules, and we have never seen them in this situation. Third, if their pathogenesis is as described, it is most surprising that they are only found in lesions of odontogenic origin.
More recently a novel solution to the debate has been suggested. Sakamoto et al. (2012 ) proposed that hyaline bodies are of both haematogenous and epithelial origin. They carried out immunohistochemistry for anti‐hair keratin (CK40; AE13), CK17, CK19, and anti‐haemoglobin alpha chain on 10 cysts containing hyaline bodies. They found that hair keratin and haemoglobin alpha chain were specifically expressed in all the hyaline bodies, but not in adjacent epithelium. Hyaline bodies were also positive for orcein and Congo red and occasionally for Prussian blue. Sakamoto