A major difference between this SR and the previously published non-SR syntheses on GOCs is that the former does not include case reports per se
and is inclusive of a report regardless of the community reported, language of publication and its source. Gardner32
criticized one such non-SR synthesis as he considered it not to be “an accurate source of such information as prevalence and incidence, racial predilection and recurrence rates”.
Although 12 SR-included reports were found by the “text-word” “glandular odontogenic cyst”, 15 were also captured by the only relevant MeSH “odontogenic cyst”. This MeSH was introduced in 1965 and is defined as “Cysts found in the jaws and arising from epithelium involved in tooth formation. They include follicular cysts (e.g.
primordial cyst, dentigerous cyst, multilocular cyst), lateral periodontal cysts, and radicular cysts. They may become keratinized (odontogenic keratocysts). Follicular cysts may give rise to ameloblastomas and, in rare cases, undergo malignant transformation.”33
Although this definition is clearly very outdated (follicular cyst is not even an “entry term” (synonym) for dentigerous cysts34
), the MeSH itself has a very high “recall” for GOC reports. As expected, there were no GOC reports published earlier than 1987, when Padayachee and Van Wyk35
first reported this lesion.
The necessity to include LILACS in the database search was discussed in an earlier SR.12
The absence of LILACS-indexed Latin American reports on GOC stood in sharp contrast to the four identified by MEDLINE. This suggested that LILACS was not an effective source for GOC reports in this global group. Although this discrepancy may have arisen, as observed in the SR on fibrous dysplasia,6
by not using the WHO's classification of odontogenic neoplasms, MEDLINE's MeSH with the out-of-date definition actually identified more reports than the “text-words”. This indicates that the definition had little or no effect on the MeSH's ability to recall those GOC reports indexed in MEDLINE. Only Piloni and co-authors' report20
had not been indexed under the MeSH “odontogenic cyst”, even though “odontogenic cyst” was their first keyword and thus should not have been overlooked by the indexer. A reason for this oversight may have been that the Spanish text preceded the English part of this bilingual report. MeSH indexing errors were certainly an issue when Piloni and co-authors' report was published.8
Kaplan and co-authors1
recently stated that “due to similarities in microscopic characteristics between GOC and lesions such as botryoid cyst, radicular and dentigerous cysts with mucous metaplasia and more importantly low-grade mucoepidermoid carcinoma, a definitive diagnosis can be difficult to make.” Nevertheless, they added that a diagnosis of GOC had to be based on the mandatory presence of the five major features. These are squamous epithelium, varying thickness, cuboidal eosinophilic (“hob-nail”) cells, mucous (goblet) cells and intraepithelial glandular or duct-like structures.1
Although it is unlikely that any reports used such strict criteria, this statement clearly indicates that the histopathology alone may be considered to be insufficiently specific in each and every case of GOC. Nevertheless, it does raise the possibility that GOCs were underreported in many if not all of the SR-included reports. This could have occurred because the histopathologists assigned a diagnosis of GOC only to those lesions that they were absolutely satisfied fulfilled the requirements of this diagnosis.
To give a better indication of the mean annual incidence the reported community may have experienced, the “number of cases per year” was given rather than the “relative period prevalence” used by many reports, in particular those reporting more than one lesion.22,28
Such “relative period prevalences” are dependent upon the classification in vogue.
In , although men predominated overall and for most decades, women predominated in the fifth decade, which was also the decade with the overall peak incidence for the SR. This anomaly may reflect the hormonal changes occurring in females during the perimenopause or menopause. As a gynaecological and/or obstetric history is unlikely to feature in history-taking in most dental facilities, there are few data to develop this discussion at the present.
88% of GOCs first presented with swelling, whereas 9% were discovered as incidental findings. The wide range of periods of prior awareness in the two, albeit very small, West European reports14
was not easy to explain, as the patients in both reports should have had easy access to socialized medicine.
GOCs displayed a predilection for the mandible, and for the anterior sextants of both jaws. Therefore, their minimal association with unerupted teeth can be readily understood, as the majority are distant from the third molars, which account for the great majority of unerupted teeth. Furthermore, Noffke and Raubenheimer23
remarked that their cases had no association with unerupted teeth, but rather displaced erupted teeth. This and the first presentation of GOCs, largely during the third to fifth decades, suggest a predilection for the individual in the prime of his/her life, long after the majority of the adult dentition has erupted.
The multilocular expansile radiological presentation in the anterior sextant recalls that of the general dispositions of both the central giant cell lesion and the solid (multilocular) type of ameloblastoma. 50% of mandibular and 75% of maxillary central giant cell lesions in a recent large Dutch case series were sited in the anterior sextant.36
Although the central giant cell lesion may be readily distinguished from GOCs by their younger mean age at first presentation,36
mean age does not assist in differentiating between the GOC and the solid type of ameloblastoma. Piloni and co-authors20
reported that, out of their 10 GOCs, 4 were thought to be ameloblastomas prior to biopsy; the GOC was not considered in a single case. In one of the most detailed case series of ameloblastomas,37
the solid type of ameloblastoma first presented in the second half of the fourth decade, whereas the GOC in this SR first presented in the later fourth decade and first half of the fifth decade. Furthermore, both lesions displaced teeth and caused root resorption and had little association with unerupted teeth. In the light of the discussion in the preceding paragraph this last feature is not surprising.
Manor and co-authors'31
review of all cases and case series reported in the literature clearly indicated that the primary conventional radiograph for most GOCs is the panoramic radiograph. Some others were imaged solely by periapical radiographs. A single lateral projection was supplemented by an occlusal in only 4 out of the 51 cases they included in their synthesis. This paucity of occlusal radiographs may have contributed to the lack of comment with regards not only to buccolingual expansion, but also to the perforation of the cortex. Five of Manor and co-authors'31
GOCs were also imaged by CT, which displayed these perforations. Nevertheless, they suggested that CT should be “reserved for large lesions, especially multilocular or lesions involving extragnathic structures, such as the sinuses, floor of the nose or the orbital floor”. Although Hisatomi and co-authors38
were able to correlate the presentations of a range of radiological modalities, including MRI in a case of GOC associated with ameloblastoma, in another report they determined that MRI images of a GOC could not be distinguished from those of dentigerous, radicular and nasopalatine cysts.39
Interestingly, distinguishing between these very lesions on the basis of conventional radiology would have presented little trouble in most cases. The GOC's infrequent association with unerupted teeth would have distinguished it from the dentigerous cyst. As the majority of GOCs were multilocular they would have been readily distinguished from the others, which were almost exclusively unilocular. For those GOCs which are unilocular, there was the frequent root resorption to distinguish them.
Several reports included measurements of the GOCs. Only measurements made on CT alone can be considered accurate.40
Noffke and Raubenheimer's23
measurements, made on panoramic radiographs, could be compromised by the distortion inherent in this modality. Measurements on panoramic radiographs are subject to “unequal magnification and geometric distortion across the image”.41
Furthermore, Noffke and Raubenheimer's23
report made no mention of adjustment for their machines' magnification factor, which can be considered only reasonably reliable for those measurements made vertically. Manor and co-authors'31
measurements were made clinically, which means that they are likely to have been smaller than the actual lesion's full extent within the jawbones, which will only be apparent radiologically. Nevertheless, the potential overestimate of the former and the underestimate of the latter did not result in a significant difference between them.
Although Kaplan and co-authors1
reported 85% occurrence of perforation of cortical plate in their non-SR synthesis, this is at variance with the 61% of this SR. A reason for this disagreement has already been expounded in the first paragraph of the discussion.
Not one SR-included report considered a downward expansion of the lower border of the mandible. The only report that did was the SR-excluded double case report by Koppang and co-authors.42
Although 17.5% of GOCs recurred globally, not one GOC recurred in the sub-Saharan African global group, whereas one-third recurred in the Western global group. Even taking into account the Black South African's younger mean age at first presentation, the WHO life expectancy is 50 and 53 years for men and women, respectively.43
Thus, it may be that the individual could have died from other causes before the lesion recurred, whereas the life expectancy in the UK (supplier of most Western cases) is 75 and 80 years for men and women, respectively; 44
the life expectancy in Latin America (Argentina)45
and East Asia (China)46
is 72/78 and 72/75 years respectively. Therefore, there is still ample time for recurrence in these global groups.
Long-term follow-up of GOCs should be undertaken, until risk factors for recurrence, if they exist, can be identified. Although, Kaplan and co-authors24
recommend that GOCs should be followed up for at least 3 years, preferably 7 years, one of Shen and co-authors'25
cases recurred after 3 years and one of Hussain and co-authors'18
recurred after 7 years. Thor and co-authors47
followed up a GOC for 13 years; they treated 11 recurrences during the first 10 years. After the GOC was marginally resected, there were no subsequent recurrences.
Kaplan and co-authors24
stated that the risk of a recurrence increases with size and multilocular appearance. The type of treatment also affects recurrence. So far, resection resulted in no recurrence, reinforcing Thor and co-authors'47