Original Article

Clinicopathological comparison of periapical cyst

and periapical granuloma in a cohort of Tamil
population
Jeswin Immanuel, Deepak Pandiar, Reshma Poothakulath Krishnan
Department of Oral Pathology and Microbiology, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical
Sciences, Saveetha University, Chennai, Tamil Nadu, India

Abstract
Aim: The aim of this study was to present and analyze detailed clinicopathological data of periapical cysts (PCs) and periapical
granuloma (PG) in a cohort of 135 cases from the South Indian Population.
Methodology: The present study included 135 cases of PC and PG out of 2696 biopsies submitted over 3 years. The
clinicodemographic data which included age, gender, location, radiographic appearance, and treatment were collected along
with the histopathological examination of the biopsied specimen. Data were entered in a Microsoft Excel spreadsheet, 2021,
and analyzed using SPSS software ver. 26.
Results: There were 71 cases of PG and 64 cases of PC. The mean age of occurrence in PG was slightly lower than cases
in PC. Irrespective of the group, there was a clear male preponderance, and maxillary permanent central incisors were most
commonly affected. However, no significant difference was noted. Radiographically, PC significantly showed more well‑defined
corticated radiolucent lesions compared to PG where most cases were ill‑defined (69.01%). Histologically, all cases showed
classic features for diagnosis with additional histological characteristics which may aid in diagnosis.
Conclusion: PG was more common than PC. There was a predilection for the male gender in both lesions. The actual
incidence of these lesions would be actually high, as some cases are lost to private practitioners, and not all the lesions are
submitted for histopathological examination.
Keywords: Cyst; granuloma; periapical; radiolucent

INTRODUCTION the tissue provides the definitive diagnosis and is regarded

as the “gold‑standard test,” and thus predicts and may at
Periapical radiolucencies are commonly encountered by times change the course of the treatment plan. Among
a clinician, with a wide range of differential diagnoses these periapical radiolucencies, periapical cysts (PCs) and
ranging from commonly inflammatory cystic lesions to granulomas, always associated with nonvital teeth, are the
comparatively uncommon odontogenic pathologies.[1] It has most common inflammatory lesions formed secondary to
been widely accepted that histopathological examination of insult to the pulp, most commonly due to dental caries.[2‑4]
History of trauma may be elucidated in many other cases,
Address for correspondence: particularly in children and young adults.[5,6] However, in
Dr. Deepak Pandiar, some cases, with large carious lesions in children with
Department of Oral Pathology and Microbiology, Saveetha
Dental College and Hospitals, Saveetha Institute of Medical and good host immune response, instead of necrosis, the pulp
Technical Sciences, Saveetha University, Chennai, Tamil Nadu, shows hyperplasia which is regarded as pulp polyp/chronic
India. hyperplastic pulpitis.[7]
E‑mail: [email protected]
Date of submission : 28.03.2024 This is an open access journal, and articles are distributed under the terms
Review completed : 02.04.2024 of the Creative Commons Attribution‑NonCommercial‑ShareAlike 4.0
Date of acceptance : 03.04.2024
License, which allows others to remix, tweak, and build upon the work
Published : 10.05.2024
non‑commercially, as long as appropriate credit is given and the new
Access this article online creations are licensed under the identical terms.
Quick Response Code: For reprints contact: [email protected]
Website:
https://journals.lww.com/jcde
How to cite this article: Immanuel J, Pandiar D, Krishnan RP.
Clinicopathological comparison of periapical cyst and periapical
DOI: granuloma in a cohort of Tamil population. J Conserv Dent Endod
10.4103/JCDE.JCDE_160_24
2024;27:524-8.

524 © 2024 Journal of Conservative Dentistry and Endodontics | Published by Wolters Kluwer - Medknow
 Immanuel, et al.: PG and PC in tamil population

Despite being common gnathic cystic lesions, there RESULTS

are only a few published studies pertaining exclusively
to PC and granulomas from the Indian population, Sample characteristics
many comprising the class of all odontogenic cysts Two thousand and two hundred twenty‑six oral and
collectively.[8‑10] The aim of the present study was thus maxillofacial biopsies were received in the department
to present detailed clinicopathological data of PC and during 3 years, out of which 135 cases of PG and PC were
periapical granuloma (PG) in a cohort of 135 cases from included in the study (5.14% of all the pathology specimens
the South Indian population. Furthermore, a comparison submitted). Eight cases of paradental cysts, the closest
was made with a relatively uncommon variant of PC, the histological mimicker of PC, were excluded after clinical
residual cyst. and radiographic correlation. For comparison, 11 cases
of residual cysts were also included during the course of
METHODOLOGY the study. There were 64 cases (47.41%, 64/135) of PC and
71 cases (52.59%, 71/135) of PG. The mean age for PG was
Study design and sample selection 29.80 ± 10.68 years (median 29 years, range 7–59 years),
The present retrospective cross‑sectional study was which was lower than the cases of PC 32.69 ± 12.24 (median
conducted in the Department of Oral Pathology and 31.5 years, range 7–62 years). The cases of residual cysts
Microbiology, after seeking approval from the Institutional were seen at even higher age (mean 34.45 ± 15.81;
Human Ethical Clearance Board (IHEC/SDC/FACULTY/22/ median‑33 years). No statistically significant difference
OPATH/011). Records of all the patients were screened was noted between the study groups. There was overall
and reviewed during 3 years (January 2021 to December marked preponderance for the male gender (90M:45F;
2023), who demonstrated periapical radiolucencies ratio 2:1). A similar trend was noted when both pathologies
associated with nonvital tooth. Inclusion criteria were: (a) were analyzed individually (PG‑1.63M:1F; PC‑2.56M:1F).
However, no statistically significant difference was seen
availability of complete clinical and demographic
between the two groups with regard to gender (P value
profile, (b) presence of an associated nonvital tooth as
0.150). With regard to residual cysts, cases were almost
tested by physical or electric pulp testing, (c) availability
equally distributed among males and females (6M:5F).
of radiographs and radiographic evidence of a periapical
There was an associated carious lesion or history of
radiolucency, and (d) histopathological confirmation of
trauma in 63/71 cases of PG and 49/64 cases of PC, and
PG/PC.
no relevant history could be retrieved for the remaining
cases. Although not significant, the lesions in the anterior
All the cases where the histopathological diagnosis
segment were more frequently associated with a positive
was nonspecific (including chronic inflammatory
history of trauma.
lesions), or diagnosis other than PC/PG (such as any named
odontogenic development cyst or a tumor) was rendered,
With regard to the site, most cases were seen in the
or the formalin‑fixed paraffin‑embedded tissue blocks maxilla (93/135, 68.9%) compared to 31.1% of cases in the
or slides were not available for re‑evaluation were lower jaw (42/135). Irrespective of the lesion, the maxillary
excluded from the study. The clinicodemographic data anterior segment was the most frequently affected segment;
which included age, gender, location, radiographic 48/71, 67.61% of PG and 64.06% (41/64 cases) of PC. For
appearance, and treatment were collected along with PG, the mandibular anterior segment was the second most
the histopathological examination of the biopsied commonly affected site (16/71, 22.53%), but the mandibular
specimen. For ease of categorization, the cases were posterior segment was the second most commonly
divided into anterior (teeth #1‑3) and posterior affected site for PC (11/64, 17.2%). However, there was no
segments (teeth #4‑8) for both jaws. Furthermore, statistically significant difference noted between the two
reported cases of residual cysts were also included for study groups with regard to location (P value 0.280). All
comparison. the cases were seen in permanent dentition except four
cases (1 PG and 3 PC). Maxillary central incisors showed
Statistical analysis maximum incidence of PG and PC among anterior teeth.
The results were tabulated, and entered in a Microsoft
Excel spreadsheet 2013 (Microsoft Corporation, Redmond, Radiographic data were available for all 135 cases
Washington, United States). Descriptive analyses were and included mainly intraoral periapical radiographs;
done for the demographic and clinical data. Finally, orthopantomograms were available for occasional
we generated a database using the IBM SPSS Statistics cases. Radiographically, all cases were single unilocular
for Windows, Version 26.0 (Released 2019; IBM Corp., radiolucencies. The borders of the radiolucent lesions
Armonk, New York, United States) software. Statistical were segregated into ill‑defined borders without
analysis was done using the Chi‑square test, and P ≤ 0.05 cortication and well‑defined lesions with cortication. PC
was considered significant statistically. showed a significantly higher number of well‑corticated

Journal of Conservative Dentistry and Endodontics | Volume 27 | Issue 5 | May 2024 525
Immanuel, et al.: PG and PC in tamil population

lesions (53/64, 82.8%) in comparison to 22/71 cases lymphoplasmacytic infiltrate and a more peripheral densely
PG (P value 0.000). Detailed features and comparative collagenous wall devoid of inflammation. 29 cases showed
values are shown in Table 1. arcading of the epithelium (45.31%), Rushton bodies were
noted in 3 (4.69%) cases, 18 showed ciliated epithelium (all
Histopathological features maxillary), 39 cases had evidence of cholesterol clefts with
All seventy‑one cases of PGs showed three features: (1) the foreign body‑type multinucleated giant cells (60.93%), and
presence of dense mixed/chronic inflammatory reaction 17 cases showed Russell bodies in the wall [Figure 2b‑d].
in fibrous connective tissue, (2) the presence of foamy All residual cysts showed nonkeratinized odontogenic
macrophages in sheets or focal clusters, and (3) areas epithelium with minimal inflammatory infiltrate in the
of hemorrhage [Figure 1]. Additional histopathological adjacent wall.
features were noted in a few cases. Six cases (8.46%) showed
evidence of lumenization/cystification, 4 (5.63%) cases Treatment and follow‑up
demonstrated fragments of spongiotic nonkeratinized All cases were managed by root canal therapy with
epithelium, and 14 (19.72%) cases showed clusters of enucleation/excision of lesions with or without apicectomy
cholesterol clefts with foreign body‑type multinucleated and retrograde restoration. None of the cases recurred.
giant cells.
DISCUSSION
The presence of an epithelium‑lined lumen with an
inflamed cyst wall was a consistent feature of all 64 cases; Inflammatory cysts of jaws are a heterogeneous group of
the epithelial lining was nonkeratinized stratified cystic lesions that arise resultant to epithelial proliferation
squamous epithelium [Figure 2a]. A stratification of cyst within loci of inflammatory cells and could be the result
was noted in 52 (81.25%) cases. Starting at the lumen, the of a number of variegated causes. Inflammatory cysts
cysts were nonkeratinized odontogenic epithelium, with
an inflamed subepithelial wall moderately or densely by

a b

c d
Figure 2: Photomicrographs of H and E‑stained sections
a b of periapical cyst showing (a) nonkeratinized odontogenic
Figure 1: Photomicrographs of H and E‑stained sections of epithelium lining the cyst cavity (×40), (b) arcading
periapical granuloma showing dense chronic inflammatory of epithelium, (c) cholesterol clefts, and (d) Rushton
reaction (a, ×100) and sheets of foamy macrophages (b, ×400) bodies (×400)

Table 1: Details of comparative clinicodemographic features of periapical cysts and periapical granuloma
Parameter Periapical granuloma (n=71) PC (n=64) P
Age (years) 29.80±10.68 32.69±12.24 0.149#
Gender Males: 44 Males: 46 0.150#
Females: 27 Females: 18
Ratio: 1.63 male: 1 female Ratio: 2.56 male: 1 female
Location, n (%) Maxillary anterior: 48 (67.61) Maxillary anterior: 41 (64.06) 0.280#
Mandibular anterior: 16 (22.53) Mandibular anterior: 10 (15.62)
Maxillary posterior: 2 (2.82) Maxillary posterior: 2 (3.12)
Mandibular posterior: 5 (7.04) Mandibular posterior: 11 (17.2)
Radiographic feature, n (%) Ill‑defined: 49 (69.01) Ill‑defined: 11 (17.2) 0.000*
Well‑defined: 22 (30.99) Well‑defined: 53 (82.8)
*Statistically significant, #Nonsignificant. PC: Periapical cyst, PG: Periapical granuloma

526 Journal of Conservative Dentistry and Endodontics | Volume 27 | Issue 5 | May 2024
 Immanuel, et al.: PG and PC in tamil population

other than PC were not included in the study, which differ necrosis (nutritional deficiency theory) or the proliferating
in localization and etiology from the commoner PC. PC, epithelium surrounds the abscess cavity (abscess theory).[22]
synonymously known as radicular cysts, comprise 35%– The cyst then enlarges by osmosis, increasing the intracystic
87% of all odontogenic cysts and arise from the epithelial pressure (phase of enlargement).[21] Numerous cytokines,
remnants of periodontal ligament following necrosis of the cells, and enzymes are involved in this step. Inflammatory
pulp.[11‑13] Little information is available regarding PC and cells like polymorphonuclear neutrophils are known to play
granuloma from the Indian cohort;[8‑10] thus, the present an important role in cyst enlargement. These cells form
study was conducted to demonstrate clinicodemographic channels along the entire length of the epithelium, to reach
and histopathological features of these common the central cystic cavity and cause enlargement.[23] Cytokines,
inflammatory periapical lesions. namely, interleukin (IL)‑1, IL‑6, and tumor necrosis factor‑α,
are identified in the keratinocytes of the cyst lining and
A definite preponderance was noted for both for the result in bone resorption.[24] Furthermore, Leonardi et al.
male gender. This is in concordance with the previous reported that the extracellular matrix also takes part in
Indian studies.[8‑10] The higher prevalence in males in the the pathogenesis of these two lesions.[25] Upregulation
present study could be justified by the fact that in most of MMP‑13 plays an important role in the formation of
cases, particularly in the anterior, there was a previous radicular cysts from the PG.[25] Disequilibrium between
history of trauma which could be directly correlated with TIMP‑1 and MMP‑1 further assists the expansion of this
more indulgence of boys in outdoor sports, a common cystic space.[26]
source of dentoalveolar injuries. It is worth noting that
a reverse trend was noted in the data available from Histological examination of the excised tissue is the gold
other countries where females were more commonly standard for diagnosis, although radiographic appearance
affected.[11,14,15] Other studies showed almost an equal could serve a clue. We found a significant difference
ratio.[16,17] In line with previous studies, we found between the radiographic appearance of PG and PC, the
that the anterior region of the maxilla was the most latter being more well corticated than PG supporting the
frequently affected site for both PG and PC.[11] Maxillary prevailing concept of an indolent course of the development
central incisors were the most commonly affected tooth of PC through PG. Leite et al. could demonstrate more
in our study; however, in a study from Brazil, Tavares inflammatory cells in the cases of PG compared to cysts and
et al. showed that the upper lateral incisor was the opined that there is a higher antigenic stimulation in PG.[27]
most affected tooth.[11] Alotaibi et al. and Chen et al. Apart from the main diagnostic histopathological features
also showed a slightly higher incidence in the lateral for the diagnosis of PG and PC, we could demonstrate some
incisors.[18,19] The authors were of the opinion that the unusual features that may not be of clinical significance but
higher prevalence of periapical lesions in the maxillary are important for understanding the pathogenesis of these
lateral incisors could be due to the higher frequency
lesions, such as epithelized PG, early cystification of PG or
of caries, trauma, and wide anatomical variation in
the presence of Rushton/Russell bodies in PC, collectively
the tooth morphology. Overall, the maxillary anterior
serve clue in etiopathogenesis, chronic nature, and role of
segment was affected more than the mandibular for
inflammatory chemokine or cytokines in the generation
both PG and PC, while, akin to the data presented by
of these lesions. The incidence of Rushton bodies was
Tavares et al., the mandibular posterior segment showed
much lower in our study than previously explained.[19,28]
a second higher frequency for a PC.[11] Other authors also
Irrespective, root canal therapy with or without apicectomy
demonstrated similar results.[15‑17] Results in our study
is the treatment of choice.[29,30]
were not significant, possibly due to a comparatively
lower number of cases than in the aforementioned study.
CONCLUSION
It is believed that the PG is a precursor of the PC. A balance
between cell death and proliferation is involved in the The results of the present study showed that PG was more
pathogenesis of these two lesions. PG arises from chronic common than PC. There is a male predilection for both
inflammatory stimuli resulting from pulpal necrosis, lesions. The actual incidence of these lesions would be
microbial interaction, or a periapical abscess. The actually high, as some cases are lost to private practitioners,
inflammatory cells in the PG activate the cell rests, causing and not all the lesions are submitted for histopathological
their proliferation and eventually leading to the formation examination.
of PC.[20] The pathogenesis of PC is best explained in
three phases. Under the influence of bacterial antigens, Financial support and sponsorship
endotoxins, and inflammation, the dormant epithelial Nil.
cell rests of Malassez begins to proliferate (phase of
initiation).[21] This is followed by the phase of cyst formation, Conflicts of interest
where the central cells undergo liquefactive degeneration/ There are no conflicts of interest.

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Immanuel, et al.: PG and PC in tamil population

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