Carranza’s

Clinical
Periodontology
Twelfth Edition

MICHAEL G. NEWMAN, DDS, FACD PERRY R. KLOKKEVOLD, DDS, MS, FACD

Professor Emeritus, Section of Periodontics Associate Professor, Section of Periodontics
School of Dentistry Director, Postgraduate Periodontics Residency
University of California School of Dentistry
Los Angeles, California University of California
Los Angeles, California
HENRY H. TAKEI, DDS, MS, FACD
Distinguished Clinical Professor, Section of Periodontics EDITOR EMERITUS
School of Dentistry
FERMIN A. CARRANZA, DR ODONT, FACD
University of California
Professor Emeritus, Section of Periodontics
Los Angeles, California
School of Dentistry
University of California
Los Angeles, California
3251 Riverport Lane
St. Louis, Missouri 63043

CARRANZA’S CLINICAL PERIODONTOLOGY, 12TH EDITION ISBN: 978-0-323-18824-1

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CHAPTER 16

Gingival Enlargement
Fermin A. Carranza and Eva L. Hogan

CHAPTER OUTLINE
Inflammatory Enlargement Enlargements Associated with Neoplastic Enlargement (Gingival
Drug-Induced Gingival Enlargement Systemic Diseases Tumors)
Idiopathic Gingival Enlargement False Enlargement

An increase in size of the gingiva is a common feature of gingival • Diffuse: Involving the marginal and attached gingivae and
disease. The accepted current terms for this condition are gingival papillae
enlargement and gingival overgrowth. These are strictly clinical • Discrete: An isolated sessile or a pedunculated, tumorlike
descriptive terms, and they avoid the erroneous pathologic con- enlargement
notations of terms used in the past, such as hypertrophic gingivitis The degree of gingival enlargement can be scored as follows16:
and gingival hyperplasia. • Grade 0: No signs of gingival enlargement
• Grade I: Enlargement confined to interdental papilla
• Grade II: Enlargement involves papilla and marginal gingiva
The many types of gingival enlargement can be classified according • Grade III: Enlargement covers three quarters or more of the
to etiologic factors and pathologic changes as follows: crown
I. Inflammatory enlargement
A. Chronic Inflammatory Enlargement
B. Acute Gingival enlargement may result from chronic or acute inflamma-
II. Drug-induced enlargement tory changes, although chronic changes are much more common.
A. General information In addition, inflammatory enlargements are usually a secondary
B. Anticonvulsants complication of any of the other types of enlargement, thereby
C. Immunosuppressants creating a combined gingival enlargement. In these cases, it is
D. Calcium channel blockers important to understand the double etiology and to treat both causes
III. Enlargements associated with systemic diseases or conditions adequately.
A. Conditioned enlargement
1. Pregnancy Chronic Inflammatory Enlargement
2. Puberty Clinical Features. Chronic inflammatory gingival enlarge-
3. Vitamin C deficiency ment originates as a slight ballooning of the interdental papilla and
4. Plasma cell gingivitis marginal gingiva. In the early stages, it produces a life-preserver–
5. Nonspecific conditioned enlargement (pyogenic shaped bulge around the involved teeth. This bulge can increase
granuloma) in size until it covers part of the crowns. The enlargement may
B. Systemic diseases that cause gingival enlargement be localized or generalized; it progresses slowly and painlessly,
1. Leukemia unless it is complicated by acute infection or trauma (Figures 16-1
2. Granulomatous diseases (e.g., Wegener’s granulomatosis, and 16-2).
sarcoidosis) Occasionally, chronic inflammatory gingival enlargement
IV. Neoplastic enlargement (gingival tumors) occurs as a discrete sessile or pedunculated mass that resembles a
A. Benign tumors tumor. It may be interproximal or on the marginal or attached
B. Malignant tumors gingiva. The lesions are slow-growing masses, and they are usually
V. False enlargement painless. They may undergo a spontaneous reduction in size that
is followed by exacerbation and continued enlargement. Painful
ulceration sometimes occurs in the fold between the mass and the
With the use of the criteria of location and distribution, gingival adjacent gingiva.
enlargement is designated as follows:
• Localized: Limited to the gingiva adjacent to a single tooth or Histopathology. Chronic inflammatory gingival enlargements show
group of teeth the exudative and proliferative features of chronic inflammation (Figure
• Generalized: Involving the gingiva throughout the mouth 16-3). Lesions that are clinically deep red or bluish red are soft and
• Marginal: Confined to the marginal gingiva friable with a smooth, shiny surface, and they bleed easily. They also
• Papillary: Confined to the interdental papilla have a preponderance of inflammatory cells and fluid, with vascular

232

Figure 16-1 Chronic inflammatory gingival enlargement localized
to the anterior region.
Figure 16-2 Chronic inflammatory gingival enlargement.
Figure 16-3 Survey section of chronic inflammatory gingival
enlargement showing the inflamed connective tissue core and
strands of proliferating epithelium.
engorgement, new capillary formation, and associated degenerative
changes. Lesions that are relatively firm, resilient, and pink have a
greater fibrotic component with an abundance of fibroblasts and colla-
gen fibers.
Etiology. Chronic inflammatory gingival enlargement is caused
by prolonged exposure to dental plaque. Factors that favor plaque
accumulation and retention48 include poor oral hygiene, irritation
by anatomic abnormalities, and improper restorative and orthodon-
tic appliances.
Gingival Changes Associated with Mouth Breath-
ing. Gingivitis and gingival enlargement are often seen in patients
who are mouth breathers. The gingiva appears red and edematous,
with a diffuse surface shininess of the exposed area. The maxillary
CHAPTER 16 Gingival Enlargement 233
Figure 16-4 Gingival enlargement in a mouth breather. Note the
lesion that is sharply circumscribed to the anterior marginal and
papillary areas.
Figure 16-5 Gingival abscess on the facial gingival surface in the
space between the cuspid and the lateral incisor, unrelated to the
gingival sulcus area.
anterior region is the common site of such involvement. In many
cases, the altered gingiva is clearly demarcated from the adjacent
unexposed normal gingiva (Figure 16-4). The exact manner in
which mouth breathing affects gingival changes has not been dem-
onstrated. Its harmful effect is generally attributed to irritation from
surface dehydration. However, comparable changes could not be
produced by air drying the gingiva of experimental animals.66
Acute Inflammatory Enlargement
Gingival Abscess. A gingival abscess is a localized, painful,
rapidly expanding lesion that usually has a sudden onset (Figure
16-5). It is generally limited to the marginal gingiva or the inter-
dental papilla. In its early stages, it appears as a red swelling with
a smooth, shiny surface. Within 24 to 48 hours, the lesion usually
becomes fluctuant and pointed, with a surface orifice from which
a purulent exudate may be expressed. The adjacent teeth are often
sensitive to percussion. If permitted to progress, the lesion gener-
ally ruptures spontaneously.
Histopathology. The gingival abscess consists of a purulent focus
in the connective tissue surrounded by a diffuse infiltration of polymor-
phonuclear leukocytes, edematous tissue, and vascular engorgement.
The surface epithelium has varying degrees of intracellular and extracel-
lular edema, invasion by leukocytes, and sometimes ulceration.
Etiology. Acute inflammatory gingival enlargement results from
bacteria carried deep into the tissues when a foreign substance
(e.g., toothbrush bristle, piece of apple core, lobster shell fragment)
is forcefully embedded into the gingiva. The lesion is confined to
the gingiva and should not be confused with periodontal or lateral
abscesses.
Periodontal (Lateral) Abscess. Periodontal abscesses
involve the supporting periodontal tissues and generally produce
234 PART 1 Biologic Basis of Periodontology
A B
Figure 16-6 Gingival enlargement associated with phenytoin therapy. A, Facial view. Note the prominent papillary lesions and the firm,
nodular surface. B, Occlusal view of the upper jaw.
Figure 16-7 Phenytoin gingival enlargement in a 5-year-old child
covering most of the clinical crowns of the teeth.
enlargement of the gingiva. For a detailed description of periodon-
tal abscesses, see Chapter 20.
Drug-Induced Gingival Enlargement
Gingival enlargement is a well-known consequence of the
administration of some anticonvulsants, immunosuppressants,
and calcium channel blockers. The condition may create speech,
mastication, tooth eruption, and aesthetic problems.
Clinical and microscopic features of the enlargements caused
by the different drugs are similar.19,86 These are presented
first, followed by a description of the particular features of
each drug.
General Information
Clinical Features. The growth starts as a painless, beadlike
enlargement of the interdental papilla that then extends to the facial
and lingual gingival margins (Figure 16-6). As the condition pro-
gresses, the marginal and papillary enlargements unite, and they
may develop into a massive tissue fold that covers a considerable
portion of the crowns; this may interfere with occlusion (Figure
16-7).
When uncomplicated by inflammation, the lesion is mulberry
shaped, firm, pale pink, and resilient, with a minutely lobulated
surface and no tendency to bleed. The enlargement characteristi-
cally appears to project from beneath the gingival margin, from
which it is separated by a linear groove. However, the presence of
the enlargement makes plaque control difficult, often resulting in
a secondary inflammatory process that complicates the gingival
overgrowth caused by the drug.
The resultant enlargement then becomes a combination of the
increase in size caused by the drug and the complicating inflam-
mation caused by bacteria. Secondary inflammatory changes not
Figure 16-8 Combined gingival enlargement resulting from the
inflammatory involvement of a phenytoin-induced overgrowth.
only add to the size of the lesion caused by the drug but also
produce a red or bluish-red discoloration, obliterate the lobulated
surface demarcations, and increase bleeding tendency (Figure
16-8).
The enlargement is usually generalized throughout the mouth,
but it is more severe in the maxillary and mandibular anterior
regions. It occurs in areas in which teeth are present (not in eden-
tulous spaces), and the enlargement disappears in areas from which
teeth have been extracted. Hyperplasia of the mucosa in edentulous
mouths has been reported but is rare.26,27
Drug-induced enlargement may occur in mouths with little or
no plaque, and it may be absent in mouths with abundant deposits.
However, some investigators believe that inflammation is a prereq-
uisite for development of the enlargement, which therefore could
be prevented by plaque removal and fastidious oral hygiene.22,37,78,101
Oral hygiene by means of toothbrushing or the use of a chlorhexi-
dine toothpaste90 reduces the inflammation but does not lessen or
prevent the overgrowth. Hassell and colleagues42,44 have hypothe-
sized that, in noninflamed gingiva, fibroblasts are less active or
even quiescent and do not respond to circulating phenytoin,
whereas fibroblasts within inflamed tissue are in an active state as
a result of the inflammatory mediators and the endogenous growth
factors that are present.
A genetic predisposition is a suspected factor45,83 for determin-
ing whether a person treated with phenytoin will develop gingival
enlargement.
The enlargement is chronic, and it slowly increases in size.
Even if it is surgically removed, it recurs. Spontaneous disappear-
ance occurs within a few months after the discontinuation of the
drug. See Chapter 58 for more information about the treatment of
gingival enlargements, including the substitution of drugs that do
not induce gingival overgrowth.
 CHAPTER 16 Gingival Enlargement 235

Figure 16-9 Microscopic view of gingival

enlargement associated with phenytoin therapy.
A, Hyperplasia and acanthosis of the epithelium
and densely collagenous connective tissue, with
evidence of inflammation in the area adjacent to
the gingival sulcus (pocket). B, High-power view
showing the extension of deep rete pegs into the
connective tissue.

A B

appears in the saliva. There is no consensus, however, regarding

Histopathology. Drug-induced gingival enlargement consists of a
pronounced hyperplasia of the connective tissue and epithelium (Figure
16-9). There is acanthosis of the epithelium, and elongated rete pegs
extend deep into the connective tissue, which exhibits densely arranged
collagen bundles with an increase in the number of fibroblasts and new
blood vessels.89 An abundance of amorphous ground substance has also
been reported.67 Structural changes in the outer epithelial cell surface
have been reported with cyclosporine-induced enlargements.3,94
The enlargement begins as a hyperplasia of the connective tissue
core of the marginal gingiva and increases by its proliferation and expan-
sion beyond the crest of the gingival margin. An inflammatory infiltrate
may be found at the bottom of the sulcus or pocket. Cyclosporine
enlargements usually involve more highly vascularized connective tissue,
with foci of chronic inflammatory cells (particularly plasma cells).74
The “mature” phenytoin enlargement has a fibroblast-to-collagen
ratio that is equal to that of normal gingiva from normal individuals,
which suggests that, at some point in the development of the lesion,
fibroblastic proliferation must have been abnormally high.43 Recurring
phenytoin enlargements appear as granulation tissue composed of
numerous young capillaries and fibroblasts and irregularly arranged col-
lagen fibrils with occasional lymphocytes.
Anticonvulsants
The first drug-induced gingival enlargements reported were those
produced by phenytoin (Dilantin). Dilantin is a hydantoin that was
introduced by Merritt and Putnam68 in 1938 for the treatment of all
forms of epilepsy, except petit mal seizures. Shortly thereafter, its
relationship with gingival enlargement was reported.35,57
Other hydantoins that are known to induce gingival enlarge-
ment are ethotoin (Peganone) and mephenytoin (Mesantoin). Other
anticonvulsants that have the same side effect are the succinimides
(ethosuximide [Zarontin], methsuximide [Celontin]) and valproic
acid (Depakene).38
Gingival enlargement occurs in about 50% of patients receiving
the drug,109 although different authors have reported incidences
from 3% to 84.5%.2,35,79 It occurs more often in younger patients.5
Its occurrence and severity are not necessarily related to the
dosage after a threshold level has been exceeded.96 Phenytoin
whether the severity of the overgrowth is related to the levels of
phenytoin in plasma or saliva.2,5,6,41,115 Some reports indicate a
relationship between the drug dosage and the degree of gingival
overgrowth.54,58
Tissue culture experiments indicate that phenytoin stimulates
the proliferation of fibroblast-like cells97 and epithelium.98 Two
analogs of phenytoin (1-allyl-5-phenylhydantoinate and 5-methyl
5-phenylhydantoinate) have a similar effect on fibroblast-like
cells.98 Fibroblasts from a phenytoin-induced gingival overgrowth
show increased synthesis of sulfated glycosaminoglycans in vitro.53
Phenytoin may induce a decrease in collagen degradation as a
result of the production of an inactive fibroblastic collagenase.42
Experimental attempts to induce gingival enlargement with
phenytoin administration in laboratory animals have only been
successful in the cat,50 the ferret, and the Macaca speciosa
monkey.103 In experimental animals, phenytoin causes gingival
enlargement that is independent of local inflammation.
In cats, one of the metabolic products of phenytoin is
5-(parahydroxyphenyl)-5-phenylhydantoin; the administration of
this metabolite to cats also induces gingival enlargement in some
cases. This led Hassell and colleagues43 to hypothesize that gingi-
val enlargement may result from the genetically determined ability
or inability of the host to deal effectively with the prolonged
administration of phenytoin.
The systemic administration of phenytoin accelerates the
healing of gingival wounds in nonepileptic humans100 and increases
the tensile strength of healing abdominal wounds in rats.25,99 The
administration of phenytoin may precipitate megaloblastic anemia65
and folic acid deficiency.104
In conclusion, the pathogenesis of gingival enlargement induced
by phenytoin is not known, but some evidence links it to a direct
effect on specific, genetically predetermined subpopulations of
fibroblasts; the inactivation of collagenase; and plaque-induced
inflammation.
Immunosuppressants
Cyclosporine is a potent immunosuppressive agent that is used to
prevent organ transplant rejection and to treat several diseases of
236 PART 1 Biologic Basis of Periodontology
A B
Figure 16-10 Cyclosporine-associated gingival enlargement. A, Mild involvement located particularly on the papillae between teeth #9 and
#10 and teeth #10 and #11. B, Advanced generalized enlargement.
Figure 16-11 Microscopic view of cyclosporine-associated gingi-
val enlargement. Note the epithelial hyperplasia and fibrous stroma
with abundant vascularization.
autoimmune origin.20 Its exact mechanism of action is not well
known, but it appears to selectively and reversibly inhibit helper T
cells, which play a role in cellular and humoral immune responses.
Cyclosporine A (Sandimmune, Neoral) is administered intrave-
nously or by mouth, and dosages of more than 500 mg/day have
been reported to induce gingival overgrowth.24
Cyclosporine-induced gingival enlargement is more vascular-
ized than phenytoin enlargement (Figures 16-10 and 16-11).85,91,117
Its occurrence varies, according to different studies, from 25% to
70%.88 It affects children more frequently, and its magnitude
appears to be related more to the plasma concentration than to
the patient’s periodontal status.95 Gingival enlargement is greater
in patients who are medicated with both cyclosporine and calcium
channel blockers.101,111,112
The microscopic finding of many plasma cells plus the presence
of an abundant amorphous extracellular substance has suggested
that the enlargement is a hypersensitivity response to the
cyclosporine.67
In experimental animals (rats), the oral administration of cyclo-
sporine was also reported to induce the abundant formation of new
cementum.4
In addition to gingival enlargement, cyclosporine induces other
major side effects such as nephrotoxicity, hypertension, and hyper-
trichosis. Another immunosuppressive drug, tacrolimus, has been
used effectively; it is also nephrotoxic, but it results in much less
severe hypertension, hypertrichosis, and gingival overgrowth.7,70,102
Calcium Channel Blockers
Calcium channel blockers are drugs that were developed for the
treatment of cardiovascular conditions such as hypertension, angina
pectoris, coronary artery spasms, and cardiac arrhythmias. They
inhibit calcium ion influx across the cell membrane of heart and
smooth muscle cells, thereby blocking the intracellular mobilization
of calcium. This induces the direct dilation of the coronary arteries
and arterioles and improves oxygen supply to the heart muscle; it
also reduces hypertension by dilating the peripheral vasculature.
These drugs are the dihydropyridine derivatives (amlodipine
[Lotrel, Norvasc], felodipine [Plendil], nicardipine [Cardene], ni­
fedipine [Adalat, Procardia]); the benzothiazine derivatives (diltia-
zem [Cardizem, Dilacor XR, Tiazac]); and the phenylalkylamine
derivatives (verapamil [Calan, Isoptin, Verelan, Covera HS]).38
Some of these drugs can induce gingival enlargement. Nifedi­
pine, which is one of the most often used,39,62,64,76 induces gingival
enlargement in 20% of patients.8 Diltiazem, felodipine, nitrendi­
pine, and verapamil also induce gingival enlargement.14,46 The
dihydropyridine derivative isradipine can replace nifedipine in
some cases; it does not induce gingival overgrowth.114
Nifedipine is also used with cyclosporine in kidney transplant
recipients, and the combined use of both drugs induces larger
overgrowths.13 Nifedipine gingival enlargement has been induced
experimentally in rats, where it appears to be dose dependent32; in
humans, however, this dose dependency is not clear. One report
indicates that nifedipine increases the risk of periodontal destruc-
tion in patients with type 2 diabetes mellitus.63
Idiopathic Gingival Enlargement
Idiopathic gingival enlargement is a rare condition of undetermined
cause. It has been designated by such terms as gingivostomatosis,
elephantiasis, idiopathic fibromatosis, hereditary gingival hyper-
plasia, and congenital familial fibromatosis.
General Information
Clinical Features. The enlargement affects the attached
gingiva as well as the gingival margin and the interdental papillae.
This is in contrast with phenytoin-induced overgrowth, which is
often limited to the gingival margin and the interdental papillae
(see Figure 16-6). The facial and lingual surfaces of the mandible
and maxilla are generally affected, but the involvement may be
limited to either jaw. The enlarged gingiva is pink, firm, and almost

A B
Figure 16-12 Idiopathic gingival enlargement in 14-year-old white male patient. A, Facial view. The gingiva is firm, with a nodular, pebbled
surface and partially covering the crowns of the teeth. B, Occlusal view of the lower jaw.
leathery in consistency, and it has a characteristic minutely pebbled
surface (Figure 16-12). In severe cases, the teeth are almost
completely covered, and the enlargement projects into the oral
vestibule. The jaws appear distorted as a result of the bulbous
enlargement of the gingiva. Secondary inflammatory changes are
common at the gingival margin.
Histopathology. Idiopathic gingival enlargement shows a bulbous
increase in the amount of connective tissue that is relatively avascular
and that consists of densely arranged collagen bundles and numerous
fibroblasts. The surface epithelium is thickened and acanthotic, with
elongated rete pegs.
Etiology. The cause is unknown, and thus the condition is des-
ignated as “idiopathic.” Some cases have a hereditary basis,28,118,119
but the genetic mechanisms involved are not well understood. A
study of several families found the mode of inheritance to be auto-
somal recessive in some cases and autosomal dominant in others.52,83
In some families, the gingival enlargement may be linked to the
impairment of physical development.56 The enlargement usually
begins with the eruption of the primary or secondary dentition, and
it may regress after extraction, which suggests that the teeth (or the
plaque attached to them) may be initiating factors. The presence of
bacterial plaque is a complicating factor.
Gingival enlargement has been described in tuberous sclerosis,
which is an inherited condition characterized by a triad of epilepsy,
mental deficiency, and cutaneous angiofibromas.106,110
Enlargements Associated with
Systemic Diseases
Many systemic diseases can develop oral manifestations that may
include gingival enlargement. These diseases and conditions can
affect the periodontium via two different mechanisms:
1. The magnification of an existing inflammation initiated by
dental plaque. This group of diseases, which are discussed in
the Conditioned Enlargements section, includes some hormonal
conditions (e.g., pregnancy, puberty), some nutritional diseases
(e.g., vitamin C deficiency), and some cases in which the sys-
temic influence is not identified (i.e., nonspecific conditioned
enlargement).
2. The manifestation of the systemic disease independently of
the inflammatory status of the gingiva. These mechanisms are
described in the Systemic Diseases that Cause Gingival Enlarge-
ment section and the Neoplastic Enlargement (Gingival Tumors)
section.
Conditioned Enlargements
Conditioned enlargements occur when the systemic condition of
the patient exaggerates or distorts the usual gingival response to
CHAPTER 16 Gingival Enlargement 237
dental plaque. The specific manner in which the clinical picture of
conditioned gingival enlargement differs from that of chronic gin-
givitis depends on the nature of the modifying systemic influence.
Bacterial plaque is necessary for the initiation of this type of
enlargement. However, plaque is not the sole determinant of the
nature of the clinical features.
The three types of conditioned gingival enlargement are hor-
monal (pregnancy, puberty), nutritional (associated with vitamin C
deficiency), and allergic. Nonspecific conditioned enlargement is
also seen.
Enlargement in Pregnancy. Pregnancy gingival enlarge-
ment may be marginal and generalized, or it may occur as a single
mass or multiple tumorlike masses (see Chapters 11 and 12).
During pregnancy, there is an increase in levels of both proges-
terone and estrogen, which by the end of the third trimester reach
levels 10 and 30 times the levels present during the menstrual
cycle, respectively.1 These hormonal changes induce changes in
vascular permeability, which leads to gingival edema and an
increased inflammatory response to dental plaque. The subgingival
microbiota may also undergo changes, including an increase in
Prevotella intermedia.60,82
Marginal Enlargement. Marginal gingival enlargement during
pregnancy results from the aggravation of previous inflammation,
and its incidence has been reported as 10%18 and 70%.120
The clinical picture varies considerably. The enlargement
is usually generalized, and it tends to be more prominent inter-
proximally than on the facial and lingual surfaces. The enlarged
gingiva is bright red or magenta, soft, and friable, and it has a
smooth, shiny surface. Bleeding occurs spontaneously or on slight
provocation.
Tumorlike Gingival Enlargement. The so-called pregnancy
tumor is not a neoplasm; it is an inflammatory response to bacterial
plaque, and it is modified by the patient’s condition. It usually
appears after the third month of pregnancy, but it may occur earlier.
The reported incidence is 1.8% to 5%.66
The lesion appears as a discrete, mushroomlike, flattened spher-
ical mass that protrudes from the gingival margin or more often
from the interproximal space, and it is attached by a sessile or
pedunculated base (Figure 16-13). It tends to expand laterally, and
pressure from the tongue and the cheek perpetuates its flattened
appearance. It is generally dusky red or magenta in color; it has a
smooth, glistening surface that often exhibits numerous deep-red,
pinpoint markings. It is a superficial lesion that usually does not
invade the underlying bone. The consistency varies; the mass is
usually semifirm, but it may have varying degrees of softness and
friability. It is usually painless unless its size and shape foster the
accumulation of debris under its margin or interfere with occlusion,
in which case painful ulceration may occur.
238 PART 1 Biologic Basis of Periodontology
Figure 16-13 Localized gingival enlargement in a 27-year-old
pregnant patient.
Figure 16-14 Microscopic view of gingival enlargement in preg-
nant patient showing an abundance of blood vessels and inter-
spersed inflammatory cells.
Although the microscopic findings are characteristic of gingival
enlargement during pregnancy, they are not pathognomonic,
because they cannot be used to differentiate pregnant and nonpreg-
nant patients.66
Histopathology. Gingival enlargement in pregnancy is called
angiogranuloma. Both marginal and tumorlike enlargements consist of
a central mass of connective tissue, with numerous diffusely arranged,
newly formed, and engorged capillaries lined by cuboid endothelial
cells (Figure 16-14) as well as a moderately fibrous stroma with varying
degrees of edema and chronic inflammatory infiltrate. The stratified
squamous epithelium is thickened, with prominent rete pegs and some
degree of intracellular and extracellular edema, prominent intercellular
bridges, and leukocytic infiltration.
Most gingival disease during pregnancy can be prevented by
the removal of plaque and calculus as well as by the institution of
fastidious oral hygiene at the outset. During pregnancy, treatment
of the gingiva that is limited to the removal of tissue without the
complete elimination of local irritants is followed by the recurrence
of gingival enlargement. Although spontaneous reduction in the
size of gingival enlargement typically follows the termination of
pregnancy, complete elimination of the residual inflammatory
lesion requires the removal of all plaque deposits and factors that
favor its accumulation. For additional information about gingival
disease during pregnancy, see Chapter 58.
Enlargement in Puberty. Enlargement of the gingiva is
sometimes seen during puberty (see Chapter 11). It occurs in both
male and female adolescents, and it appears in areas of plaque
accumulation.
Figure 16-15 Conditioned gingival enlargement during puberty in
a 13-year-old boy.
The size of the gingival enlargement greatly exceeds that
usually seen in association with comparable local factors. It is
marginal and interdental, and it is characterized by prominent
bulbous interproximal papillae (Figure 16-15). Often, only the
facial gingivae are enlarged, and the lingual surfaces are relatively
unaltered; the mechanical action of the tongue and the excursion
of food prevent a heavy accumulation of local irritants on the
lingual surface.
Gingival enlargement during puberty has all of the clinical
features that are generally associated with chronic inflammatory
gingival disease. It is the degree of enlargement and its tendency
to recur in the presence of relatively scant plaque deposits that
distinguish pubertal gingival enlargement from uncomplicated
chronic inflammatory gingival enlargement. After puberty, the
enlargement undergoes spontaneous reduction, but does not disap-
pear completely until the plaque and calculus are removed.
A longitudinal study of 127 children between the ages of 11 and
17 years demonstrated a high initial prevalence of gingival enlarge-
ment that tended to decline with age.107 When the mean number of
inflamed gingival sites per child was determined and correlated
with the time at which the maximum number of inflamed sites was
observed and with the oral hygiene index at that time, a pubertal
peak in gingival inflammation unrelated to oral hygiene factors
clearly occurred. A longitudinal study of the subgingival microbi-
ota of children between the ages of 11 and 14 years and their
association with clinical parameters implicated Capnocytophaga
species in the initiation of pubertal gingivitis.71 Other studies have
reported that hormonal changes coincide with an increase in the
proportion of Prevotella intermedia and Prevotella nigrescens.73,116
Histopathology. The microscopic appearance of gingival enlarge-
ment during puberty is chronic inflammation with prominent edema and
associated degenerative changes.
Enlargement in Vitamin C Deficiency. The enlarge-
ment of the gingiva is generally included in classic descriptions of
scurvy. Acute vitamin C deficiency itself does not cause gingival
inflammation, but it does cause hemorrhage, collagen degenera-
tion, and edema of the gingival connective tissue. These changes
modify the response of the gingiva to plaque to the extent that the
normal defensive delimiting reaction is inhibited and the extent
of the inflammation is exaggerated,33,34 thereby resulting in the
massive gingival enlargement seen in patients with scurvy (Figure
16-16) (see Chapter 27).
Gingival enlargement with vitamin C deficiency is marginal;
the gingiva is bluish red, soft, and friable, and it has a smooth,
shiny surface. Hemorrhage that occurs either spontaneously or on
slight provocation as well as surface necrosis with pseudomem-
brane formation are common features.

Histopathology. In patients with vitamin C deficiency, the gingiva
has a chronic inflammatory cellular infiltration with a superficial acute
response. There are scattered areas of hemorrhage with engorged capil-
laries. Marked diffuse edema, collagen degeneration, and a scarcity of
collagen fibrils and fibroblasts are striking findings.
Plasma Cell Gingivitis. Plasma cell gingivitis consists of a
mild marginal gingival enlargement that extends to the attached
gingiva. The gingiva appears red, friable, and sometimes granular,
and it bleeds easily; usually it does not induce a loss of attachment
(Figure 16-17). This lesion is located in the oral aspect of the
attached gingiva and therefore differs from plaque-induced
gingivitis.
Histopathology. In patients with plasma cell gingivitis, the oral
epithelium shows spongiosis and infiltration with inflammatory cells;
ultrastructurally, there are signs of damage in the lower spinous layers
and the basal layers. The underlying connective tissue contains a dense
infiltrate of plasma cells that also extends to the oral epithelium, thereby
inducing a dissecting type of injury.75
An associated cheilitis and glossitis have been reported.55,93
Plasma cell gingivitis is thought to be allergic in origin and pos-
sibly related to components of chewing gum, dentifrices, or various
diet components. The cessation of exposure to the allergen brings
resolution of the lesion.
In rare instances, marked inflammatory gingival enlargements
with a predominance of plasma cells can appear; these are associ-
ated with rapidly progressive periodontitis.77
Figure 16-16 Gingival enlargement in a patient with vitamin C
deficiency. Note the prominent hemorrhagic areas. (Courtesy Dr.
Gerald Shklar, Boston, MA.)
A B
Figure 16-17 Plasma cell gingivitis. A, Diffuse lesions on the facial surface of the anterior maxilla. B, Mandibular lesions. (Courtesy Dr.
Kim D. Zussman, Thousand Oaks, CA.)
CHAPTER 16 Gingival Enlargement 239
A solitary plasma cell tumor or plasmocytoma has been
described in the nasopharynx and rarely in the oral mucosa.12,91 It
is a slow-growing pedunculated tumor with a pink and smooth
surface, and it is composed of normal plasma cells. It is usually
benign; however, in rare cases, it can be an oral manifestation of
multiple myeloma, which is a malignant tumor of the bone marrow.
Nonspecific Conditioned Enlargement (Pyogenic
Granuloma). Pyogenic granuloma is a tumorlike gingival
enlargement that is considered an exaggerated conditioned response
to minor trauma (Figure 16-18). The exact nature of the systemic
conditioning factor has not been identified.11 Pyogenic granuloma
is similar in clinical and microscopic appearance to the conditioned
gingival enlargement seen during pregnancy. The differential diag-
nosis is based on the patient’s history.
Treatment consists of the removal of the lesions plus the elimi-
nation of irritating local factors. The recurrence rate is about 15%.
Systemic Diseases that Cause
Gingival Enlargement
Several systemic diseases may result in gingival enlargement by
different mechanisms. These are uncommon cases, and they are
only briefly discussed.
Leukemia. Leukemic gingival enlargement may be diffuse or
marginal and localized or generalized (see Chapter 11). It may
appear as a diffuse enlargement of the gingival mucosa, an over-
sized extension of the marginal gingiva (Figure 16-19), or a dis-
crete tumorlike interproximal mass.
Clinical Features. In patients with leukemic enlargement, the
gingiva is generally bluish red, and it has a shiny surface. The
consistency is moderately firm, but there is a tendency toward
friability and hemorrhage that occur either spontaneously or with
slight irritation. Acute painful necrotizing ulcerative inflammatory
involvement may occur in the crevice formed at the junction of the
enlarged gingiva and the contiguous tooth surfaces.
Patients with leukemia may also have a simple chronic inflam-
mation without the involvement of leukemic cells, and they may
present with the same clinical and microscopic features seen in
patients without the systemic disease. Most cases, however, reveal
features of both simple chronic inflammation and leukemic
infiltrate.
True leukemic enlargement often occurs with acute leukemia,
but it may also be seen with subacute leukemia. It seldom occurs
with chronic leukemia.
240 PART 1 Biologic Basis of Periodontology
Figure 16-18 Pyogenic granuloma. (Courtesy Dr. Silvia Oreamuno,
San José, Costa Rica.)
Figure 16-19 Leukemic gingival enlargement (acute myelocytic
leukemia). (Courtesy Dr. Spencer Wolfe, Dublin, Ireland.)
Histopathology. Gingival enlargements in leukemic patients show
various degrees of chronic inflammation. Mature leukocytes and areas
of connective tissue are infiltrated with a dense mass of immature and
proliferating leukocytes, the specific nature of which varies with the type
of leukemia. Engorged capillaries, edematous and degenerated connec-
tive tissue, and epithelium with various degrees of leukocytic infiltration
and edema are found. Isolated surface areas of acute necrotizing inflam-
mation with a pseudomembranous meshwork of fibrin, necrotic epithe-
lial cells, polymorphonuclear leukocytes, and bacteria are often seen.
Granulomatous Diseases.
Wegener’s Granulomatosis. Wegener’s granulomatosis is a
rare disease that is characterized by acute granulomatous necrotiz-
ing lesions of the respiratory tract, including nasal and oral defects.
Renal lesions develop, and acute necrotizing vasculitis affects the
blood vessels. The initial manifestations of Wegener’s granuloma-
tosis may involve the orofacial region and include oral mucosal
ulceration, gingival enlargement,47 abnormal tooth mobility, exfo-
liation of teeth, and delayed healing response.17
The granulomatous papillary enlargement is reddish purple and
bleeds easily on stimulation (see Figure 19-30).
Histopathology. Chronic inflammation involves scattered giant
cells, foci of acute inflammation, and microabscesses covered by a thin,
acanthotic epithelium. Vascular changes have not been described with
gingival enlargement in patients with Wegener’s granulomatosis, prob-
ably because of the small size of the gingival blood vessels.51
The cause of Wegener’s granulomatosis is unknown, but the
condition is considered an immunologically mediated tissue
injury.23 At one time, the usual outcome for patients with this condi-
tion was death from kidney failure within a few months, but more
recently the use of immunosuppressive drugs has produced pro-
longed remissions in more than 90% of patients.59
Sarcoidosis. Sarcoidosis is a granulomatous disease of unknown
etiology. It starts in individuals during their twenties or thirties, it
predominantly affects blacks, and it can involve almost any organ,
including the gingiva, in which a red, smooth, painless enlargement
may appear.
Histopathology. Sarcoid granulomas consist of discrete, noncase-
ating whorls of epithelioid cells and multinucleated, foreign-body–type
giant cells with peripheral mononuclear cells.87
Neoplastic Enlargement (Gingival Tumors)
This section provides only a brief description of some of the more
common neoplastic and pseudoneoplastic lesions of the gingiva.
The reader is referred to oral pathology texts for more comprehen-
sive coverage.87,91
Benign Tumors of the Gingiva
Epulis is a generic term that is used clinically to designate all
discrete tumors and tumorlike masses of the gingiva. It serves to
locate the tumor but not to describe it. Most lesions referred to by
this term are inflammatory rather than neoplastic.
Neoplasms account for a comparatively small proportion of
gingival enlargements, and they make up a small percentage of the
total number of oral neoplasms. In a survey of 257 oral tumors,
approximately 8% occurred on the gingiva.69 In another study of
868 growths of the gingiva and palate (of which 57% were neo-
plastic and the remainder inflammatory), the following incidences
of tumors were noted: carcinoma, 11.0%; fibroma, 9.3%; giant cell
tumor, 8.4%; papilloma, 7.3%; leukoplakia, 4.9%; mixed tumor
(salivary gland type), 2.5%; angioma, 1.5%; osteofibroma, 1.3%;
sarcoma, 0.5%; melanoma, 0.5%; myxoma, 0.45%; fibropapil-
loma, 0.4%; adenoma, 0.4%; and lipoma, 0.3%.9
Fibroma. Fibromas of the gingiva arise from the gingival con-
nective tissue or from the periodontal ligament. They are slow-
growing spherical tumors that tend to be firm and nodular but that
may be soft and vascular. Fibromas are usually pedunculated. Hard
fibromas of the gingiva are rare; most of the lesions that are diag-
nosed clinically as “fibromas” are inflammatory enlargements.92
Histopathology. Fibromas are composed of bundles of well-formed
collagen fibers with scattered fibrocytes and variable vascularity.
The so-called giant cell fibroma contains multinucleated fibro-
blasts. In another variant, mineralized tissue (bone, cementum-like
material, and dystrophic calcifications) may be found; this type of
fibroma is called peripheral ossifying fibroma.
Papilloma. Papillomas are benign proliferations of surface
epithelium that are, in many (but not all) cases, associated with
the human papillomavirus (HPV). Gingival papillomas appear as
solitary wartlike or cauliflower-like protuberances (Figure 16-20).
They may be small and discrete, or they may be broad, hard eleva-
tions with minutely irregular surfaces.
Histopathology. The papilloma lesion consists of fingerlike projec-
tions of stratified squamous epithelium that are often hyperkeratotic,
with central cores of fibrovascular connective tissue.
Peripheral Giant Cell Granuloma. Giant cell lesions
of the gingiva arise interdentally or from the gingival margin;
they occur most frequently on the labial surface, and they may be
sessile or pedunculated. They vary in appearance from smooth,
regularly outlined masses to irregularly shaped, multilobulated

protuberances with surface indentations (Figure 16-21). The ulcer-
ation of the margin is occasionally seen. The lesions are painless,
they vary in size, and they may cover several teeth. They may be
firm or spongy, and their color varies from pink to deep red or
purplish blue. There are no pathognomonic clinical features
whereby these lesions can be differentiated from other forms of
gingival enlargement. Microscopic examination is required for
definitive diagnosis.
The prefix peripheral is needed to differentiate them from com-
parable lesions that originate within the jawbone (i.e., central giant
cell granulomas).
In some cases, the giant cell granuloma of the gingiva is locally
invasive and causes destruction of the underlying bone (Figure
16-22). Complete removal leads to uneventful recovery.
Figure 16-20 Papilloma of the gingiva in a 26-year-old man.
Figure 16-21 Gingival giant cell granuloma.
A B
Figure 16-22 A, Microscopic survey of a peripheral giant cell granuloma. B, High-power study of the lesion demonstrating the giant cells
and the intervening stroma that make up the major portion of the mass.
CHAPTER 16 Gingival Enlargement 241
Histopathology. The giant cell granuloma has numerous foci of
multinuclear giant cells and hemosiderin particles in a connective
tissue stroma (see Figure 16-22). Areas of chronic inflammation are
scattered throughout the lesion, with acute involvement occurring at
the surface. The overlying epithelium is usually hyperplastic, with
ulceration at the base. Bone formation occasionally occurs within the
lesion (Figure 16-23).
Central Giant Cell Granuloma. Giant cell lesions arise
within the jaws and produce central cavitation. They occasionally
create a deformity of the jaw that makes the gingiva appear
enlarged.
Mixed tumors, salivary gland types of tumors, and plasmacy-
tomas of the gingiva have also been described but are not often
seen.
Leukoplakia. Leukoplakia is a strictly clinical term defined by
the World Health Organization as a white patch or plaque that does
not rub off and that cannot be diagnosed as any other disease. The
cause of leukoplakia remains obscure, although it is associated with
the use of tobacco (smoke or smokeless). Other probable factors
are Candida albicans, HPV-16 and HPV-18, and trauma. Leuko-
plakia of the gingiva varies in appearance from a grayish white,
flattened, scaly lesion (Figure 16-24) to a thick, irregularly shaped,
keratinous plaque.
Most leukoplakias (80%) are benign; the remaining 20% are
malignant or premalignant, and only 3% of these are invasive
carcinomas.31 The biopsy of all leukoplakias is necessary, with the
most suspicious area being selected, to arrive at a correct diagnosis
and to then institute proper therapy.31,91
Histopathology. Leukoplakia exhibits hyperkeratosis and acantho-
sis. Premalignant and malignant cases have a variable degree of atypical
epithelial changes that may be mild, moderate, or severe, depending on
the extent of involvement of the epithelial layers. When dysplastic
changes involve all layers, it is diagnosed as a carcinoma in situ, and
this may become invasive carcinoma when the basement membrane
is breached.31 Inflammatory involvement of the underlying connective
tissue is a common associated finding.
Gingival Cyst. Gingival cysts of microscopic proportions are
common, but they seldom reach a clinically significant size.72
When they do, they appear as localized enlargements that may
involve the marginal and attached gingiva. The cysts occur in the
242 PART 1 Biologic Basis of Periodontology
mandibular canine and premolar areas, most often on the lingual
surface. They are painless, but, with expansion, they may cause
erosion of the surface of the alveolar bone. The gingival cyst should
be differentiated from the lateral periodontal cyst (see Chapter 20),
which arises within the alveolar bone adjacent to the root and
which is developmental in origin. Gingival cysts develop from
odontogenic epithelium or from surface or sulcular epithelium trau-
matically implanted in the area. Removal is followed by uneventful
recovery.
Figure 16-23 Bone destruction in the interproximal space between
the canine and lateral incisor caused by the extension of a periph-
eral giant cell reparative granuloma of the gingiva. (Courtesy Dr.
Sam Toll.)
Figure 16-24 Leukoplakia of the gingiva.
A B
Figure 16-25 Squamous cell carcinoma of the gingiva. A, Facial view. Note the extensive verrucous involvement. B, Palatal view. Note
the mulberry-like tissue emerging between the second premolar and the first molar.
Histopathology. A gingival cyst cavity is lined by a thin, flattened
epithelium with or without localized areas of thickening. Less frequently,
the following types of epithelium can be found: unkeratinized stratified
squamous epithelium, keratinized stratified squamous epithelium, and
parakeratinized epithelium with palisading basal cells.16
Other Benign Masses. Other benign tumors have also
been described as rare or infrequent findings in the gingiva. They
include nevus,10 myoblastoma,36 hemangioma,108 neurilemoma,31
neurofibroma,81 mucus-secreting cysts (mucoceles),113 and
ameloblastoma.105
Malignant Tumors of the Gingiva
Carcinoma. Oral cancer accounts for less than 3% of all malig-
nant tumors in the body, but it is the sixth most common cancer in
males and the twelfth most common in females.74 The gingiva is
not a frequent site of oral malignancy, accounting for only 6% of
oral cancers.61
Squamous cell carcinoma is the most common malignant tumor
of the gingiva. It may be exophytic, presenting as an irregular
outgrowth, or ulcerative, appearing as flat, erosive lesions. It is
often symptom free, going unnoticed until complicated by inflam-
matory changes that may mask the neoplasm but cause pain; some-
times it becomes evident after tooth extraction. These masses are
locally invasive, and they involve the underlying bone and peri-
odontal ligament of adjoining teeth and the adjacent mucosa
(Figure 16-25). Metastasis is usually confined to the region above
the clavicle; however, more extensive involvement may include the
lung, liver, or bone.
Malignant Melanoma. Malignant melanoma is a rare oral
tumor that tends to occur in the hard palate and maxillary gingiva
of older persons.74,84 It is usually darkly pigmented, and it is often
preceded by localized pigmentation.21 It may be flat or nodular, and
it is characterized by rapid growth and early metastasis. It arises
from melanoblasts in the gingiva, cheek, or palate. Infiltration into
the underlying bone and metastasis to cervical and axillary lymph
nodes are common.
Sarcoma. Fibrosarcoma, lymphosarcoma, and reticulum cell
sarcoma of the gingiva are rare; only isolated cases have been
described in the literature.40,109 Kaposi’s sarcoma often occurs in
the oral cavity of patients with acquired immunodeficiency syn-
drome, particularly in the palate and the gingiva (see Chapter 26).
Metastasis. Tumor metastasis to the gingiva occurs infrequently.
Such metastasis has been reported with various tumors, including
adenocarcinoma of the colon,49 lung carcinoma, melanoma,30 renal

A B
Figure 16-26 A, Apparent gingival enlargement associated with bone augmentation in a patient with fibrous dysplasia. B, Radiograph of
the case shown in A depicting a ground-glass, mottled pattern.
cell carcinoma,15 hypernephroma,80 chondrosarcoma,109 and tes-
ticular tumor.29
The low incidence of oral malignancy should not mislead the
clinician. Ulcerations that do not respond to therapy in the usual
manner as well as all gingival tumors and tumorlike lesions
must be biopsied and submitted for microscopic diagnosis (see
Chapter 34).
False Enlargement
False enlargements are not true enlargements of the gingival
tissues, but they may appear as such as a result of increases in the
size of the underlying osseous or dental tissues. The gingiva usually
presents with no abnormal clinical features except the massive
increase in the size of the area.
Underlying Osseous Lesions
Enlargement of the bone subjacent to the gingival area occurs most
often with tori and exostoses, but it can also occur with Paget’s
disease, fibrous dysplasia, cherubism, central giant cell granuloma,
ameloblastoma, osteoma, and osteosarcoma. Figure 16-26 shows
fibrous dysplasia (florid type) in a 38-year-old black woman that
induced an osseous enlargement in the mandibular molar area that
appeared to be a gingival enlargement. The gingival tissue can
appear normal, or it may have unrelated inflammatory changes.
Underlying Dental Tissues
During the various stages of eruption, particularly of the primary
dentition, the labial gingiva may show a bulbous marginal distor-
tion caused by the superimposition of the bulk of the gingiva on
the normal prominence of the enamel in the gingival half of the
crown. This enlargement has been called developmental enlarge-
ment, and often persists until the junctional epithelium has migrated
from the enamel to the cementoenamel junction.
In a strict sense, developmental gingival enlargements are
physiologic, and they usually present no problems. However,
when such enlargement is complicated by marginal inflammation,
the composite picture gives the impression of extensive gingival
enlargement (Figure 16-27). Treatment to alleviate the marginal
inflammation—rather than resection of the enlargement—is suffi-
cient for these patients.
CHAPTER 16 Gingival Enlargement 243
Figure 16-27 Developmental gingival enlargement. The normal
bulbous contour of the gingiva around the incompletely erupted
anterior teeth is accentuated by chronic inflammation.
NOTE: Chapter 85 in the online version of this book presents
numerous examples of gingival enlargements.
Suggested Readings
Aas E: Hyperplasia gingivae diphenylhydantoinea, Oslo, 1963,
Universitetsforlaget.
Fowler CB: Benign and malignant neoplasms of the periodontium. Peri-
odontol 2000 21:33, 1999.
Hallmon WW, Rossmann JA: The role of drugs in the pathogenesis of
gingival overgrowth. Periodontol 2000 21:176, 1999.
Kuffer R, Lombardi T: Premalignant lesions of the oral mucosa. A discus-
sion about the place of oral intraepithelial neoplasia (OIN). Oral Oncol
38:125, 2002.
Nuki K, Cooper SH: The role of inflammation in the pathogenesis of
gingival enlargement during the administration of diphenylhydantoin
sodium in cats. J Periodontal Res 7:91, 1972.
Rees TD: Drugs and oral disorders. Periodontol 2000 18:21, 1998.
Sapp JP, Eversole LR, Wysocki GP: Contemporary Oral and Maxillofacial
Pathology, ed 2, 2004, Mosby, Elsevier.
Seymour RA, Thomason JM, Ellis JS: The pathogenesis of drug-induced
gingival overgrowth. J Clin Periodontol 23:165, 1996.
References
References for this chapter are found on the companion
website www.expertconsult.com.

References
1. Amar S, Chung KM: Influence of hormonal variation on the periodon-
tium in women. Periodontol 2000 6:79, 1994.
2. Angelopoulos AP, Goaz PW: Incidence of diphenylhydantoin gingival
hyperplasia. Oral Surg 34:898, 1972.
3. Ashrafi SH, Slaski K, Thu K, et al: Scanning electron microscopy of
cyclosporine-induced gingival overgrowth. Scan Microsc 10:219,
1996.
4. Ayanoglou CM, Lesty C: New cementum formation induced by
cyclosporin A: a histological, ultrastructural and histomorphometric
study in the rat. J Periodontol 32:543, 1997.
5. Babcock JR: Incidence of gingival hyperplasia associated with Dilan-
tin therapy in a hospital population. J Am Dent Assoc 71:1447, 1965.
6. Babcock JR, Nelson GH: Gingival hyperplasia and Dilantin content
of saliva. J Am Dent Assoc 68:195, 1964.
7. Bader G, Lejeune S, Messner M: Reduction of cyclosporine-induced
gingival overgrowth following a change to tacrolimus: a case history
involving a liver transplant patient. J Periodontol 69:729, 1988.
8. Barclay S, Thomason JM, Idle JR, et al: The incidence and severity
of nifedipine-induced gingival overgrowth. J Clin Periodontol
19:311, 1992.
9. Bernick S: Growth of the gingiva and palate. II. Connective tissue
tumors. Oral Surg 1:1098, 1948.
10. Bernier JL, Tiecke RW: Nevus of the gingiva. J Oral Surg 8:165,
1950.
11. Bhaskar SN, Jacoway JR: Pyogenic granuloma: clinical features,
incidence, histology and result of treatment. J Oral Surg 24:391,
1966.
12. Bhaskar SN, Levin MP, Frisch J: Plasma cell granuloma of periodon-
tal tissues: report of 45 cases. Periodontics 6:272, 1988.
13. Bökenkamp A, Bohnhorst B, Beier C, et al: Nifedipine aggravates
cyclosporine A—induced hyperplasia. Pediatr Nephrol 8:181, 1994.
14. Brown RS, Sein P, Corio R, et al: Nitrendipine-induced gingival
hyperplasia. Oral Surg 70:593, 1990.
15. Buchner A, Begleiter A: Metastatic renal cell carcinoma in the gingiva
mimicking a hyperplastic lesion. J Periodontol 51:413, 1980.
16. Buchner A, Hansen AS: The histomorphologic spectrum of the gin-
gival cyst in the adult. Oral Surg 48:532, 1979.
17. Buckley DJ, Barrett AP, Bilous AM, et al: Wegener’s granulomatosis—
are gingival lesions pathognomonic? J Oral Med 42:169, 1987.
18. Burket LW: Oral medicine, Philadelphia, 1946, Lippincott.
19. Butler RT, Kalkwarf KL, Kaldhal WB: Drug-induced gingival hyper-
plasia: phenytoin, cyclosporine and nifedipine. J Am Dent Assoc
114:56, 1987.
20. Calne R, Rolles K, White DJ, et al: Cyclosporin-A initially as the only
immunosuppressant in 34 recipients of cadaveric organs: 32 kidneys,
2 pancreas and 2 livers. Lancet 2:1033, 1979.
21. Chaudry AP, Hampel A, Gorlin RJ: Primary malignant melanoma of
the oral cavity: a review of 105 cases. Cancer 11:923, 1958.
22. Ciancio SG, Yaffe SJ, Catz CC: Gingival hyperplasia and diphenyl-
hydantoin. J Periodontol 43:411, 1972.
23. Cotran RS, Kumar V, Robbins SL: Robbins’ pathologic basis of
disease, ed 4, Philadelphia, 1989, Saunders.
24. Daley TD, Wysocki GP, Day C: Clinical and pharmacologic correla-
tions in cyclosporine-induced gingival hyperplasia. Oral Surg 62:417,
1986.
25. DaCosta ML, Regan MC, al Sader M, et al: Diphenyl hydantoin
sodium promotes early and marked angiogenesis and results in
increased collagen deposition and tensile strength in healing wounds.
Surgery 123:287, 1988.
26. Dallas BM: Hyperplasia of the oral mucosa in an edentulous epileptic.
NZ Dent J 59:54, 1963.
27. Dreyer WP, Thomas CJ: DPH-induced hyperplasia of the masticatory
mucosa in an edentulous epileptic patient. Oral Surg 45:701, 1978.
28. Emerson TG: Hereditary gingival hyperplasia: a family pedigree of
four generations. Oral Surg 19:1, 1965.
29. Fantasia JE, Chen A: A testicular tumor with gingival metastasis. Oral
Surg 48:64, 1979.
CHAPTER 16 Gingival Enlargement 243.e1
30. Ferreti Bonan PR, Laranjeira AL, Martelli H, Jr, et al: Synchronous
metastatic melanoma presenting as gingival and facial swelling:
a case report and review of the literature. J Periodontol 79:2371,
2008.
31. Fowler CB: Benign and malignant neoplasms of the periodontium.
Periodontol 2000 21:33, 1999.
32. Fu E, Nieh S, Hiao CT, et al: Nifedipine-induced gingival overgrowth
in rats: brief review and experimental study. J Periodontol 69:765,
1988.
33. Glickman I: The periodontal tissues of the guinea pig in vitamin C
deficiency. J Dent Res 27:9, 1948.
34. Glickman I: The effect of acute vitamin C deficiency upon the
response of the periodontal tissues of the guinea pig to artificially
induced inflammation. J Dent Res 27:201, 1948.
35. Glickman I, Lewitus M: Hyperplasia of the gingiva associated with
Dilantin (sodium diphenyl hydantoinate) therapy. J Am Dent Assoc
28:1991, 1941.
36. Hagen JD, Soule EH, Gores RJ: Granular cell myoblastoma of the
oral cavity. Oral Surg 14:454, 1961.
37. Hall WB: Dilantin hyperplasia: a preventable lesion. J Periodontal
Res 4(Suppl):36, 1969.
38. Hallmon WW, Rossmann JA: The role of drugs in the pathogenesis
of gingival overgrowth. Periodontol 2000 21:176, 1999.
39. Hancock RH, Swan RH: Nifedipine-induced gingival overgrowth.
J Clin Periodontol 19:12, 1992.
40. Hardman FG: Secondary sarcoma presenting clinical appearance of
fibrous epulis. Br Dent J 86:109, 1949.
41. Hassell TM: Epilepsy and the oral manifestations of phenytoin
therapy. In Monographs in Oral Science, New York, 1981, S Karger.
42. Hassell TM: Evidence for production of an inactive collagenase by
fibroblasts from phenytoin-enlarged human gingiva. J Oral Pathol
11:310, 1982.
43. Hassell TM, Burtner AP, McNeal D, et al: Oral problems and genetic
aspects of individuals with epilepsy. Periodontol 2000 6:68, 1994.
44. Hassell TM, Page RC: The major metabolite of phenytoin (Dilantin)
induces gingival overgrowth in cats. J Periodontal Res 13:280, 1978.
45. Hassell TM, Page RC, Lindhe J: Histologic evidence of impaired
growth control in diphenylhydantoin gingival overgrowth in man.
Arch Oral Biol 23:381, 1978.
46. Heijl L, Sundin Y: Nitrendipine-induced gingival overgrowth in dogs.
J Periodontol 60:104, 1989.
47. Hernandez G, Serrano C, Porras L, et al: Strawberry-like gingival
tumor as the first clinical sign of Wegener’s granulomatosis. J Peri-
odontol 79:1297, 2008.
48. Hirschfeld I: Hypertrophic gingivitis: its clinical aspect. J Am Dent
Assoc 19:799, 1932.
49. Humphrey AA, Amos NH: Metastatic gingival adenocarcinoma from
primary lesion of colon. Am J Cancer 28:128, 1936.
50. Ishikawa J, Glickman I: Gingival response to the systemic administra-
tion of sodium diphenyl hydantoinate (Dilantin) in cats. J Periodontol
32:149, 1961.
51. Israelson H, Binnie WH, Hurt WC: The hyperplastic gingivitis of
Wegener’s granulomatosis. J Periodontol 52:81, 1981.
52. Jorgenson RJ, Cocker ME: Variation in the inheritance and expression
of gingival fibromatosis. J Periodontol 45:472, 1974.
53. Kantor ML, Hassell TM: Increased accumulation of sulfated glycos-
aminoglycans in cultures of human fibroblasts from phenytoin-
induced gingival overgrowth. J Dent Res 62:383, 1983.
54. Kapur RN, Grigis S, Little TM, et al: Diphenylhydantoin-induced
gingival hyperplasia: its relation to dose and serum level. Dev Med
Child Neurol 15:483, 1973.
55. Kerr DA, McClatchey KD, Regezi JA: Allergic gingivostomatitis
(due to gum chewing). J Periodontol 42:709, 1971.
56. Kilpinen E, Raeste AM, Collan Y: Hereditary gingival hyperplasia
and physical maturation. Scand J Dent Res 86:118, 1978.
57. Kimball O: The treatment of epilepsy with sodium diphenylhydanto-
inate. JAMA 112:1244, 1939.
58. Klar LA: Gingival hyperplasia during Dilantin therapy: a survey of
312 patients. J Public Health Dent 33:180, 1973.
243.e2 PART 1 Biologic Basis of Periodontology
59. Kornblut AD, Wolff SM, de Fries HE, et al: Wegener’s granulomato-
sis. Laryngoscope 90:1453, 1980.
60. Kornman KS, Loesche WJ: The subgingival microbial flora during
pregnancy. J Periodontal Res 15:111, 1980.
61. Krolls SO, Hoffman S: Squamous cell carcinomas of the oral soft
tissues: a statistical analysis of 14,253 cases by age, sex and race of
patients. J Am Dent Assoc 92:571, 1976.
62. Lederman D, Lummerman H, Reuben S, et al: Gingival hyperplasia
associated with nifedipine therapy. Oral Surg 57:620, 1984.
63. Li X, Luan Q, Wang X, et al: Nifedipine intake increases the risk
of periodontal destruction in subjects with type 2 diabetes mellitus.
J Periodontol 79:2054, 2008.
64. Lucas RM, Howell LP, Wall RA: Nifedipine-induced gingival hyper-
plasia: a histochemical and ultrastructural study. J Periodontol
56:211, 1985.
65. Lustberg A, Goldman D, Dreskin OH: Megaloblastic anemia due to
Dilantin therapy. Ann Intern Med 54:153, 1961.
66. Maier AW, Orban B: Gingivitis in pregnancy. Oral Surg 2:334, 1949.
67. Mariani G, Calastrini C, Carinci F, et al: Ultrastructural features
of cyclosporine A—induced gingival hyperplasia. J Periodontol
64:1092, 1993.
68. Merritt H, Putnam T: Sodium diphenylhydantoinate in the treatment
of convulsive disorders. JAMA 111:1068, 1938.
69. McCarthy FP: A clinical and pathological study of oral disease. JAMA
116:16, 1941.
70. Mihatsch MJ, Kyo M, Morozumi K, et al: The side-effects of
cyclosporine-A and tacrolimus. Clin Nephrol 49:356, 1988.
71. Mombelli A, Lang NP, Burgin WB, et al: Microbial changes associ-
ated with the development of puberty gingivitis. J Periodontal Res
25:331, 1990.
72. Moskow BS: The pathogenesis of the gingival cyst. Periodontics
4:23, 1966.
73. Nakagawa S, Fujii H, Machida Y, et al: A longitudinal study from
prepuberty to puberty of gingivitis: correlation between the occur-
rence of Prevotella intermedia and sex hormones. J Periodontol
21:658, 1994.
74. Neville BW, Damm DD, Allen CM, et al: Oral and maxillofacial
pathology, Philadelphia, 1995, Saunders.
75. Newcomb GM, Seymour GJ, Adkins KF: An unusual form of chronic
gingivitis: an ultrastructural, histochemical and immunologic investi-
gation. Oral Surg 53:488, 1982.
76. Nishikawa S, Tada H, Hamasaki A, et al: Nifedipine-induced gingival
hyperplasia: a clinical and in vitro study. J Periodontol 62:30, 1991.
77. Nitta H, Kameyama Y, Ishikawa I: Unusual gingival enlargement with
rapidly progressive periodontitis: report of a case. J Periodontol
64:1008, 1993.
78. Nuki K, Cooper SH: The role of inflammation in the pathogenesis of
gingival enlargement during the administration of diphenylhydantoin
sodium in cats. J Periodontal Res 7:91, 1972.
79. Panuska HJ, Gorlin RJ, Bearman JE, et al: The effect of anticonvul-
sant drugs upon the gingiva: a series of 1048 patients. J Periodontol
32:15, 1961.
80. Persson PA, Wallenino K: Metastatic renal carcinoma (hyperne-
phroma) in the gingiva of the lower jaw. Acta Odontol Scand 19:289,
1961.
81. Pollack RP: Neurofibroma of the palatal mucosa: a case report.
J Periodontol 61:456, 1990.
82. Raber-Durlacher JE, van Steenbergen TJM, van der Velde U, et al:
Experimental gingivitis during pregnancy and postpartum: clinical,
endocrinological and microbiological aspects. J Clin Periodontol
21:549, 1994.
83. Raeste AM, Collan Y, Kilpinen E: Hereditary fibrous hyperplasia of
the gingiva with varying penetrance and expressivity. Scand J Dent
Res 86:357, 1978.
84. Rapini RP, Golitz LE, Greer RO, Jr: Primary malignant melanoma of
the oral mucosa. Cancer 55:1543, 1985.
85. Rateitschak-Pluss EM, Hefti A, Lortscher R, et al: Initial observation
that cyclosporin A induces gingival enlargement in man. J Clin
Periodontol 10:237, 1983.
86. Rees TD: Drugs and oral disorders. Periodontol 2000 18:21, 1998.
87. Rees TD: Disorders affecting the periodontium. Periodontol 2000
21:145, 1999.
88. Romito GA, Pustiglioni FE, Saraiva L, et al: Relationship of subgin-
gival and salivary microbiota to gingival overgrowth in heart trans-
plant patients following cyclosporine A therapy. J Periodontol 75:918,
2004.
89. Rostock MH, Fry HR, Turner JE: Severe gingival overgrowth associ-
ated with cyclosporine therapy. J Periodontol 57:294, 1986.
90. Russell BJ, Bay LM: Oral use of chlorhexidine gluconate toothpaste
in epileptic children. Scand J Dent Res 86:52, 1978.
91. Sapp JP, Eversole LR, Wysocki GP: Contemporary oral and maxil-
lofacial pathology, St Louis, 2004, Elsevier.
92. Schneider LC, Weisinger E: The true gingival fibroma: an analysis of
129 fibrous gingival lesions. J Periodontol 49:423, 1978.
93. Serio FG, Siegel MA, Slade BE: Plasma cell gingivitis of unusual
origin: a case report. J Periodontol 49:423, 1978.
94. Seymour RA, Jacobs DJ: Cyclosporine and the gingival tissues. J Clin
Periodontol 19:1, 1992.
95. Seymour RA, Smith DG, Rogers SR: The comparative effects of
azathioprine and cyclosporine on some gingival health parameters of
renal transplant patients. J Clin Periodontol 14:610, 1987.
96. Seymour RA, Thomason JM, Ellis JS: The pathogenesis of drug-
induced gingival overgrowth. J Clin Periodontol 23:165, 1996.
97. Shafer WG: Effect of Dilantin sodium analogues on cell proliferation
in tissue culture. Proc Soc Exp Biol Med 106:205, 1960.
98. Shafer WG: Effect of Dilantin sodium on various cell lines in tissue
culture. Proc Soc Exp Biol Med 108:694, 1961.
99. Shafer WG, Beatty RE, Davis WB: Effect of Dilantin sodium on
tensile strength of healing wounds. Proc Soc Exp Biol Med 98:348,
1958.
100. Shapiro M: Acceleration of gingival wound healing in nonepileptic
patients receiving diphenylhydantoin sodium. Exp Med Surg 16:41,
1958.
101. Slavin J, Taylor J: Cyclosporine, nifedipine and gingival hyperplasia.
Lancet ii:739, 1987.
102. Spencer CM, Goa KL, Gillis JC: Tacrolimus: an update of its phar-
macology and drug efficacy in the management of organ transplanta-
tion. Drugs 54:925, 1997.
103. Staple PH, Reed MJ, Mashimo PA: Diphenylhydantoin gingival
hyperplasia in Macaca arctoides: a new human model. J Periodontol
48:325, 1977.
104. Stein GM, Lewis H: Oral changes in a folic acid deficient patient
precipitated by anticonvulsant drug therapy. J Periodontol 44:645,
1973.
105. Stevenson ARL, Austin BW: A case of ameloblastoma presenting as
an exophytic gingival lesion. J Periodontol 61:378, 1990.
106. Stirrups D, Inglis J: Tuberous sclerosis with nonhydantoin gingival
hyperplasia: report of a case. Oral Surg 49:211, 1980.
107. Sutcliffe P: A longitudinal study of gingivitis and puberty. J Periodon-
tal Res 7:52, 1972.
108. Sznajder N, Dominguez FV, Carraro JJ, et al: Hemorrhagic heman-
gioma of the gingiva: report of a case. J Periodontol 44:579, 1973.
109. Taicher S, Mazar A, Hirschberg A, et al: Metastatic chondrosarcoma
of the gingiva mimicking a reactive exophytic lesion: a case report.
J Periodontol 623:223, 1991.
110. Thomas D, Rapley J, Strathman R, et al: Tuberous sclerosis with
gingival overgrowth. J Periodontol 63:713, 1992.
111. Thomason JM, Seymour RA, Rice N: The prevalence and severity of
cyclosporine and nifedipine-induced gingival overgrowth. J Clin
Periodontol 20:37, 1993.
112. Thomason JM, Seymour RA, Ellis JS, et al: Determinants of gingival
overgrowth severity in organ transplant patients. J Clin Periodontol
23:628, 1996.
113. Traeger KA: Cyst of the gingiva (mucocele): report of a case. Oral
Surg 14:243, 1961.
114. Westbrook P, Bednarczyk EM, Carlson M, et al: Regression of
nifedipine-induced gingival hyperplasia following switch to a same
class calcium channel blocker, isradipine. J Periodontol 68:645, 1997.
 CHAPTER 16 Gingival Enlargement 243.e3

115. Westphal P: Salivary secretion and gingival hyperplasia in
diphenylhydantoin-treated guinea pigs. Sven Tandlak Tidskr 62:505,
1969.
116. Wojcicki CJ, Harper DS, Robinson PJ: Differences in periodontal-
disease associated microorganisms in prepubertal, pubertal and post-
pubertal children. J Periodontol 58:219, 1987.
117. Wysocki G, Gretsinger HA, Laupacis A, et al: Fibrous hyperplasia of
the gingiva: a side effect of cyclosporin A therapy. Oral Surg 55:274,
1983.
118. Zackin SJ, Weisberger D: Hereditary gingival fibromatosis. Oral Surg
14:828, 1961.
119. Ziskin DE, Zegarelli E: Idiopathic fibromatosis of the gingivae. Ann
Dent 2:50, 1943.
120. Ziskin DE, Blackberg SM, Stout AP: The gingivae during pregnancy.
Surg Gynecol Obstet 57:719, 1933.