I read with great interest the paper by Kaczmarzyk et al. The authors should be commended for their mammoth task of reviewing the existing literature on this topic and trying to put the results of the many retrospective case series into perspective. At the same time, however, I was somewhat taken aback by the harsh tone of their paper suggesting that all 168 papers reviewed, except two, had not contributed to existing knowledge on the recurrence tendency of keratocystic odontogenic tumour (KCOT). That certainly is not the case and does not acknowledge all the authors who have struggled with this intriguing pathological entity. They do present a complete review of the literature, however, and as such the paper is worth reading. The authors are also correct in saying that future research should focus on the true KCOT or parakeratotic keratocyst, as it is referred to in the old terminology. The orthokeratotic (kerato)cyst does behave less aggressively and should be considered as a different entity, although I have personally seen cysts that had the histological characteristics of both.
With all due respect, however, there are some important points missing in the discussion of this article that need to be addressed.
First, all papers the authors have reviewed are of a retrospective nature and thus lack pertinent information, for instance, regarding how the diagnosis was ascertained. In a prospective study, which included 25 years of careful registering of all clinical and radiographic characteristics, it became clear that as many as 40% of the OKCs, as they were known in those days, were inconspicuous unilocular looking cysts located mainly in the dentate area of the jaws, often in a lateral follicular or lateral periodontal configuration. In other words, many of these cysts were treated as regular cysts, i.e. by enucleation and/or curettage. This aspect is not covered in most papers reviewed. This in itself presents a giant bias because it is unlikely that this would not have happened in other case series. In other words, retrospective studies that claim a uniform treatment protocol have to be taken with a grain of salt.
Second, the authors have focused their research on the method of treatment used without questioning what the reason for a recurrence may be. This is certainly strange as it should play a major role in the assessment of the various treatment options. This aspect is commonly included in papers discussing the recurrences of other tumours, for instance, ameloblastoma. The KCOT is not just a cyst but should be regarded as a tumour. In most cases, tumour islands and microcysts are found in the wall of the cyst and, as shown in our research, are almost always located in the mucosa attached to the cyst. It is currently well accepted that the origin of KCOT stems not only from remnants of the dental lamina but also from offshoots of the oral mucosa. As pointed out in several studies, our research has also clearly shown that there are two reasons for these recurrences. There is no doubt that incomplete removal of the cyst membrane may lead to a true recurrence, because a new cyst may develop from the active cells left behind. This is probably the reason why marsupialisation has a high recurrence rate, despite the metaplasia that occurs in the original cyst lining, seemingly changing the nature of the epithelial lining. The other reason, most likely, is equally important and that is that the origin of the cyst is left behind in the mucosa attached to the cyst when the cyst is enucleated, while the attached mucosa is not included in the treatment. It then hardly matters whether the defect is treated with Carnoy’s solution, since recurrences develop from the epithelial islands left in the mucosa. This explains why a high percentage of recurrences are seen when the cyst is enucleated but the defect is treated with Carnoy’s solution. Stoelinga, in a study of 5 recurrent OKCs, all of the parakeratotic type, clearly showed the presence of multiple epithelial islands and microcysts in the attached, overlying mucosa of the recurrent cysts all located in the ascending ramus of the mandible. Hence, the design of the prospective study to include the attached overlying mucosa in connection with the cyst, as reported in 2001 and reiterated in 2005. In more than 50% of the KCOTs diagnosed in advance in the 2001 study, this was affirmed by histological examination. It follows that any treatment that leaves this mucosa behind will leave behind the possible source of a new cyst. It also explains why resection will result in zero recurrence. This is only true when the mucosa is included in the resection. Several case reports, from times before microsurgical reconstruction existed, have shown recurrences to appear in free bone grafts. These bone grafts were inserted via an extra oral approach without perforating the oral mucosa, so as to avoid contamination by the oral flora.
One question remains to be answered: why do some recurrences appear even after excision of the mucosa and proper treatment of the bony defect? The answer may be threefold. The excision may not have included all tumour nests in the mucosa, or some new epithelial offshoots from the basal layer of the oral epithelium have developed. Histological examinations of some of our fresh cases were very indicative of the latter. The remote possibility always remains that despite treatment with Carnoy’s solution or cryotherapy some active epithelial cells survive. Yet, I fully agree with the authors that resection of part of the jaw is not warranted for a benign lesion often appearing in relatively young patients. Recurrences are manageable provided they are diagnosed in a timely manner. The above mentioned facts, however, mean that any discussion on treatment, without taking into account the pathogenesis of the recurrences, is virtually senseless.
Third, the summary of the authors’ findings is confusing and may cause misinterpretations by future authors who will refer to this paper. They report 50% recurrence after enucleation and treatment with Carnoy’s solution, based on two cases and 40% after marsupialisation based on 10 cases. The percentages of other modes of treatment were also based on rather small numbers. Since this paper is a meta-analysis, these figures will tend to be regarded as cemented in stone, particularly since they appear in the summary as overall recurrence rates. Admittedly, the authors discuss the merit of these figures in the discussion and tone down their importance, but that is not the case in the abstract, which may mislead the readers.
Fourth, they claim that my 2001 paper did not qualify for their meta-analysis. I fail to see the reasons why, since all the data provided in that study were of a prospective nature, while the 7 orthokeratotic cysts were discussed separately – one of those did recur. They also mistakenly used my name for a paper (no. 128) which was actually written by Worral.
In summary, this meta-analysis shows the flaws of all retrospective studies that do not connect the mode of treatment with the pathogenesis of recurrent KCOTs. It also shows that it will be difficult to come up with evidence based data when no precise clinical, radiological and histological features are included, let alone that a double blind study will be possible, comparing two modes of treatment. The relative frequency of this tumour is simply too low to acquire enough cases within a reasonable timeframe to carry out such a study. The best option will be to begin multicentre prospective studies, using strict protocols, and to compare results over periods ranging from 5 to 20 years or more. That will require organization and loyal participants. Since the authors are right about recurrences of KCOTs that may occur after a long period of time, an extended period of follow-up will be necessary to come up with meaningful figures.