CASE REPORT
Mucous Metaplasia in a Radicular Cyst Lining An Update and a
Case Report
Priya N S,1 Uma K,2 Ashwin D P, 3 Kavita Rao4
ABSTRACT
Radicular cyst is the most common inflammatory cyst in the oral
cavity. Approximately, 40% of non-keratinizing odontogenic cysts
show mucous metaplasia in their linings. A case of radicular cyst
with mucous metaplasia is presented with a description of the
phenomenon of metaplasia and the mechanism of cholesterol
cleft formation. The cystic fluid in the radicular cyst exhibits a
variety of substances which may contribute to the pathogenesis of
the cyst. The composition of the cyst fluid is described briefly.
Radicular cysts also occur in primary dentition, accounting for 0.5-
33% of the total number of cases. Differences between the
radicular cysts arising from primary and permanent dentitions are
considered. Certain immunochemical markers which play a key
role in understanding the pathogenesis of the cyst are highlighted.
KEYWORDS: Radicular cyst, metaplasia, cholesterol clefts, cyst
fluid.
. pain in the right upper front teeth region since one
Introduction
The term cyst is derived from the Greek word Kystis
meaning sac or bladder.1 The radicular cyst is the most
common cystic lesion in the jaws which is always
associated with a non-vital tooth. It arises from the
epithelial residues within the periodontal ligament as a
result of inflammation.
Histomorphological changes in the cystic lining of the
radicular cyst occur, which include metaplasia,
degeneration, dysplasia and malignant transformation.
The incidence of mucous metaplasia in the epithelial
lining is common in maxillary cysts. The biological
significance of this phenomenon is not well understood.
But, the presence of metaplasia can throw light on the
pathogenetic events in cyst formation. Also, the concept
of desired metaplasia can bring in the possibility of new
IJCD JANUARY, 2012 3(1)
organ or tissue formation.
2012 Int. Journal of Contemporary
of desired metaplasia can bring in the possibility of new
organ or tissue formation.
Radicular cyst can exist in two structurally distinct forms
(Simon 1980)1
1. Periapical true cyst: Cavities are
completely enclosed by the epithelial
lining.
2. Periapical pocket cyst/ Bay cyst:
Epithelium-lined cavities are open to the
root canal.
The cyst fluid in a radicular cyst is a simple dialysate of
blood which passes through a semi-permeable lining into
the lumen. The diverse molecular components in the
fluid which may play a role in cyst expansion are
considered. The differences in radicular cysts of primary
and permanent dentition are also looked at.
Case Report
A 26 year-old male patient was referred from a private
dental clinic to the Department of Oral and Maxillofacial
Pathology, VS Dental College, with a complaint of mild
month. There was reported history of trauma to the
upper front teeth four years ago. Pain was associated
with a swelling in the labial region of 11, 12 & 13.
Oral examination of the swelling revealed a well
circumscribed, firm, sessile swelling, measuring 2cm in
diameter present in the maxillary labial vestibule of 11,
12 & 13. No pus discharge from the swelling was evident.
General physical examination did not reveal any
significant findings.
The orthopantomogram showed a unilocular
radiolucency with well defined margins in the right
anterior maxilla involving the apices of 11, 12 & 13 (Fig
1). A clinical diagnosis of radicular cyst was considered.
Fine needle aspiration cytology revealed clear straw
colored fluid with shimmering cholesterol crystals.
Patient was scheduled for enucleation of cyst.
Perforation of labial cortex was evident during the
surgical procedure. The lesion shelled out intact. Grossly
the cystic specimen showed smooth inner and outer
walls
with focal nodular thickenings. The lumen10was
Dentistry
completely filled with a cholesterol granuloma.
 CASE REPORT
Fig 1: OPG showing well defined unilocular radiolucency
involving the apices of 11, 12 & 13.
Fig 5: Giant cells (H & E 40X)

Fig 2: Cyst lining with a focal arcade and cholesterol clefts in

the lumen (H & E - 10X)

Fig 6 : Mucous cells in the epithelial lining (PAS- 10X)

Fig 3: Mucous cells in the superficial layer of the epithelium

(H & E 40X)

Fig 7: Mucin droplets within the mucous cells (PAS- 40X)

Fig 4: Cholesterol clefts associated with giant cells (H & E -

10X)

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11 2012 Int. Journal of Contemporary Dentistry

the cystic specimen showed smooth inner and outer
walls with focal nodular thickenings. The lumen was
completely filled with a cholesterol granuloma.
Microscopic examination showed a cystic lining
comprising of non-keratinized stratified squamous
epithelium with a focal arcade. Mucous metaplasia in
the lining was observed. A continuous layer of mucous
cells was seen in the superficial layer. Cholesterol clefts
associated with multinucleated giant cells were seen in
the lumen. The dense fibrous wall was largely devoid of
inflammatory components, though a few diffusely
distributed inflammatory cells, predominantly
lymphocytes were seen in focal areas. (Fig 2, 3 4 & 5)
The sections were also stained with PAS (periodic acid-
Schiff) and the mucous cells showed positive
expression. Few cells were present singly with densely
packed mucin granules. (Fig 6& 7)
A diagnosis of radicular cyst with mucous metaplasia
was made.
Discussion
What is metaplasia?
Metaplasia is derived from the Greek word metaplasis
meaning change in form. It is also referred to as
transdifferentiation2.
It is the reversible replacement of one differentiated
cell type with another mature differentiated cell type
(transdifferentiation). It is a change seen as a cellular
adaptability to an abnormal stimulus. Another school of
thought is that metaplasia is brought about by stem
cells that reprogram differentiation of cells rather than
by transdifferentiation. Stem cells are nudged along a
different pathway of differentiation by cytokines and
growth factors in the cell's environment3.
Some examples of epithelial metaplasia are squamous
metaplasia, glandular metaplasia and mucous
metaplasia.Metaplasia is not restricted to epithelial
tissue. It can also occur in connective tissue, eg. osseous
metaplasia2.
Why metaplasia?
Metaplasia is a cellular adaptation induced by direct
stimulation of cells2. The stimulus can be
Chronic irritation in the form of
smoking or stone formation in
salivary ducts
Vitamin A deficiency
Mutation
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2012 Int. Journal of Contemporary Dentistry
CASE REPORT
Slack (1985)4 has proposed that metaplasia represents
the mammalian equivalent of homeotic mutations that
occur in invertebrates. These consist of mutations in
master regulatory genes that allow the respecification
of a developing body part.
The mechanism of mucous metaplasia in odontogenic
cysts is not known clearly. Vacuolated cells are
observed in the lining along with mucous cells.
Vacuolated cells represent a stage in the histogenesis of
mucous metaplasia. It is postulated that in the initial
process of metaplasia, the keratinocytes became
vacuolated, and then some vacuoles accumulated
mucin granules, ultimately forming mucous cells.
Mucous cells are round, or flat sometimes, vary in size
and shape and change their position in the epithelium
at times. These cells can be present singly or in groups
within the superficial layers except the basal layer.
Mucous cells are densely packed with mucin granules
which are dispersed through out the cytoplasm5.
Significance of metaplasia in odontogenic cysts:
Mucous secretions from the goblet cells
influence the consistency of cyst fluid giving it a
viscous / mucinous consistency.
Goblet cells secrete glycoconjugates including
GAG ( glycosaminoglycans ) & glycoproteins into
the cyst lumen , which may account partly for
the cyst expansion. These contribute to the
osmolality of the fliud.6
Desired metaplasia:
A new phenomenon in which the adult developed
mammalian / human body, can neo-regenerate its own
tissue / organs in vivo, is recognized as desired
metaplasia. This new phenomenon has been critically,
analytically and scientifically studied and discussed in
the literature7.
New organ and tissue formation is possible with the
help of autogenous pluripotent stem cells if exposed to
the proper environment and functional need, provided
the tissues are embryologic neighbors8.
How are cholesterol clefts formed?
Cholesterol clefts associated with giant cells are usually
seen within the lumen and in the connective tissue wall
of a radicular cyst. The length of a cholesterol cleft can
vary from 0.2-1.3 mm6.
The possible mechanisms suggested for their formation
are6
Breakdown of RBCs ( plasmalemma contains
cholesterol)
12
 CASE REPORT
Ingestion of RBCs by macrophages leading to
intracellular formation of cholesterol esters
Deposition of hemosiderin Poor lymphatic drainage leading to
Foam cells resulting from local metabolic accumulation of cholesterol
activity
Table 1: Compostion of radicular cyst fluid9

Serum proteins Albumin

1 globulin
2 globulin
globulin
globulin

Immunoglobulins
Ig G
Ig A
Ig M
Proteases & Inhibitors
Collagenases (latent form)
2 macroglobulin
1 antitrypsin

Keratin & other antigens Prealbumin (Traces)

Lactoferrin

GAG & Proteoglycans Hyaluronic acid

Dermatan Sulfate
Chondrotin Sulfate
Heparin/Heparan sulfate
Glycoproteins
Fucose (Fucomucins)
Lipids Cholesterol
1& 1 lipoproteins

Table 2: Differences in radicular cysts arising from primary & permanent teeth10.

Features Radicular cyst arising from primary Radicular cyst arising from
teeth permanent teeth
Terminology Periradicular cyst Periapical cyst
Etiology Caries is the common etiologic Trauma, caries & old
factor silicate restorations
Clinical features Mandibular teeth are commonly Maxillary teeth are
affected commonly affected
Radiologic features Radiolucency in inter radicular area Radiolucency adjacent to
and around the roots because of the apex
short and partially resorbed roots
and existence of accessory canals in
roots of primary molars

Histopathology Similar in both Similar in both

Cholesterol crystals are rare Cholesterol crystals are

common (30%)

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2012 Int. Journal of Contemporary Dentistry
 CASE REPORT
Table 3: Immunohistochemical markers of importance in radicular cyst

Markers Importance
11
Apoptosis related factors Apoptosis

12
Cyclo-oxygenase-2 (PG E2) Bone resorption

12
MMP-1 & 2 Bone resorption

13
HSP 27 Epithelial cell growth & differentiation
14
Keratinocyte growth factor Epithelial cell growth & differentiation

15
CD 57+ Immuno modulator

VEGF/VPF(Vascular Endothelial Cyst expansion ( vascular permeability &

Growth Factor/ Vascular angiogenesis
16
Permeability Factor)

Inducible nitric oxide synthase Epithelial proliferation

17
(iNOS)

At the sites of inflammation in the wall of the cyst, plasma proteins. Such channels are
there are repeated small hemorrhages. Foamy absent in the odontogenic keratocyst
macrophages play an important role here. They Inflammation has an effect on the
engulf extravasated RBCs. The cholesterol esters protein levels
from cell membranes of RBCs are presented to Presence of bacteria in fluid and blood
lysosomes of foam cells and are hydrolyzed into contamination during aspiration may
cholesterol and fatty acids by the action of acid also influence the protein levels6
lipase. This stage is said to occur in the first
cellular compartment; then, cholesterol passes
into the second cellular compartment where it is
re-esterified by microsomal enzymes and is stored
Conclusion
in lipid droplets in the cytoplasm. Off-loading of Radicular cyst, although common among the jaw
cholesterol occurs when suitable acceptors are lesions, exhibits a wide range of histomorphological
found in the external environment. So cholesterol changes which impacts the pathogenesis. Biochemical
is handled by macrophages by feedback studies have speculated the contribution for better
mechanisms and at times the crystals are expelled understanding of the cyst composition which shows
into tissue spaces6. the molecular heterogeneity. The progress in the field
of immunohistochemistry provides the base for the
Composition of cyst fluid in radicular cyst: pathogenetic events in the cyst formation. An attempt
is made to document the biology of metaplasia and
The radicular cyst fluid is hypertonic compared to concepts related to it.
serum and contains the following substances6
(Table1) References

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 CASE REPORT

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About the Authors
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E-mail: dr_priyans@yahoo.com

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15 2012 Int. Journal of Contemporary Dentistry