Shear's Cysts of the Oral and Maxillofacial Regions. Paul M. Speight

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Shear's Cysts of the Oral and Maxillofacial Regions - Paul M. Speight

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were restored 3–7 days after aspiration, suggesting that there was constant movement of fluid into the cyst lumen.

      This pioneering work on the role of hydrostatic pressure in the growth of odontogenic cysts was mostly undertaken during the 1970s, but it has not been superseded or refuted by more contemporary experiments. Nair (1998 , 2004 ) has suggested that osmotic pressure as a factor in the development of radicular cysts has been ‘eliminated’. As evidence for this he cites the fact that the lumen of pocket or bay cysts is open to the root canal, and cannot therefore sustain an increased internal pressure. He suggests that cyst growth is sustained by molecular mechanisms. This is undoubtedly correct – a cascade of biological factors underpins the processes of epithelial proliferation, extracellular matrix destruction, and bone resorption, but there is still good evidence that there is increased pressure within the cyst lumen, and that osmosis is the driving force. This does not exclude other factors, although it should be noted that even in pocket cysts it is unlikely that the root canal remains empty and that the lumen is truly open to the oral cavity. It is also well recognised that release of this pressure, through decompression, has long been and still is a common and effective form of treatment (Castro‐Núñez 2016 ). More recently this issue has been re‐evaluated, but the outcome remains that hydrostatic pressure is still considered to be of primary importance in the growth of all cyst types. Kubota et al. (2004 ) measured the intracystic fluid pressure of odontogenic keratocysts, dentigerous cysts, and radicular cysts. They confirmed the earlier results of Toller (1970b ) and Skaug (1976a ), that the pressure was greater than the local blood pressure and that there were no differences between the three cyst types. They also measured cyst volume and showed that volume correlated to the area of the cysts measured on panoramic radiographs. They correlated the pressure to the areas of the cysts and found pressures of 337.6 ± 126.0, 258.2 ± 160.9, and 254 ± 157.3 mmHgcm−2 for keratocysts, dentigerous cysts, and radicular cysts, respectively. Furthermore, these authors showed that the intracystic pressure in all cyst types was inversely correlated to the cyst size. They therefore concluded that increased pressure played a pivotal part in early cyst growth.

      Ward et al. (2004 ) used mathematical modelling to simulate odontogenic cyst growth. They assumed a spherical cyst lined by a semi‐permeable membrane and with a central osmotic pressure as a result of accumulation of degraded cellular material. The model supported the conclusions of the early experimental work, that osmotic pressure played an important part in cyst growth. Interestingly, the model also confirmed the findings of Kubota et al. (2004 ), and suggested that as the cyst became larger, osmotic pressure played a lesser part and cell proliferation became more important.

      Osmotic pressure must be maintained by a high concentration of soluble proteins in the cyst fluid. Electrophoretic studies (Toller and Holborow 1969 ; Toller 1970a ) demonstrated that radicular cyst fluids contained small molecular‐sized albumin and β1‐globulin in quantities comparable with the patient's serum, but had fewer, if any, of the larger protein molecules. α‐ and β2‐ globulins were greatly diminished or absent, and γ‐globulins (mainly immunoglobulins) varied greatly in quantity, but were most often found in inflamed cysts. They showed that more than half display levels of immunoglobulins much higher than the patient's own serum. In 19 cyst fluids in which levels of IgG, IgA, and IgM were measured independently, all three were significantly raised in most of the non‐keratinising cysts. Immunofluorescent staining showed that lymphoid cell aggregates in the walls of radicular cysts often included numerous plasma cells.

      Skaug (1973 , 1974 , 1976b , 1977 ) confirmed that fluid from non‐keratinising jaw cysts contained high concentrations of proteins, including immunoglobulins, but supported the view that accumulation of cyst fluid resulted essentially from inadequate lymphatic drainage of the cyst cavity. He suggested that plasma protein exudate and hyaluronic acid, as well as the products of cell breakdown, contributed to the high osmotic pressure of the cyst fluid.

      These data suggest that the accumulation of proteins in the cyst lumen is a combination of a serum exudate, an inflammatory exudate, and breakdown products of cells, including luminal epithelial cells and inflammatory cells. It is likely therefore that the luminal pressure, necessary for cyst expansion, is greatest when the cyst is most inflamed, at earlier stages of development. As a cyst gets larger and matures, inflammation may subside, the rate of growth will slow, and a state of equilibrium may be reached. This is supported by the study of Kubota et al. (2004 ) and the model proposed by Ward et al. (2004 ), who both show that pressure and the rate of growth decrease with size of the lesion.

Photo depicts a long-standing radicular cyst.

      The next crucial element of cyst growth is degradation of the connective tissues. Among the most important and widely studied factors are the matrix metalloproteinases (MMPs). These are a large family of calcium‐dependent and zinc‐containing proteases, capable of degrading a wide range of extracellular matrix proteins. A number of studies have shown expression of MMPs in odontogenic cysts, including the gelatinases (MMP‐2 and MMP‐9; Teronen et al. 1995a ; Kubota et al. 2000 ; D'addazio et al. 2014 ; Alvares et al. 2017 ; Andrade et al. 2017 ) and collagenases (MMP‐1, MMP‐8, and MMP‐13; Teronen et al. 1995b ; Lin et al. 1997 ; Wahlgren et al. 2001 ; D'addazio et al. 2014 ; Andrade et al. 2017 ), suggesting a role for these enzymes in cyst growth and development. Furthermore, MMP activity increases with the intensity of inflammation and is often more prominent in periapical granulomas than in established cysts (Lin et al. 1997 ; Andrade et al. 2017 ). In keeping with this, inflammatory cytokines, especially IL‐1, up‐regulate active MMP‐9 in odontogenic cysts (Kubota et al. 2000 ) and increased numbers of mast cells are associated with MMP activation in odontogenic cysts (Teronen et al. 1996 ; Rodini et al. 2008 ; Andrade et al. 2017 ). Inflammation in radicular cysts is also associated with secretion of neutrophil collagenase (MMP‐8) and with increased expression of plasminogen activator (Tsai et al. 2004 ), which indirectly forms plasmin that may also activate MMPs.

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