PATHOLOGY

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Acute Primary Actinomycosis Involving theHard Palate of a Diabetic Patient

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, Brazil

*PhD St

entist

yResideentist

zProfesentistr

xProfeskProfesntistry.

Ana Luiza Dias Leite de Andrade, DDS, MSc,* M�arcio Menezes Novaes, DDS,yAdriano Rocha Germano, DDS, MSc, PhD,z Kleber Giovanni Luz, MD, MSc, PhD,x

Roseana de Almeida Freitas, DDS, MSc, PhD,k and

H�ebel Cavalcanti Galv~ao, DDS, MSc, PhD{

Actinomycosis is a relatively rare infection caused by saprophytic bacteria of the oral cavity and gastro-

intestinal tract that can become pathogenic. The chronic hyperglycemia of diabetes mellitus inducesevents that promote structural changes in various tissues and are associated with problems in wound

healing. This infection remains largely unknown to most clinicians because of its different presentations,

and palatal involvement is extremely rare. This report describes the case of a 46-year-old woman who

was diagnosed with actinomycosis involving the hard palate. The main clinical, histopathologic, and

therapeutic characteristics and differential diagnosis of actinomycosis are reviewed. To date, 3 cases

of actinomycosis involving the hard palate have been reported.

� 2014 American Association of Oral and Maxillofacial Surgeons

J Oral Maxillofac Surg 72:537-541, 2014

Actinomycosis is a slowly progressing infection caused

by anaerobic or microaerophilic, gram-positive, non–

spore-forming, non–acid-fast bacteria of the genus Ac-

tinomyces. The species most frequently isolated is Ac-

tinomyces israelii. Three distinct clinical forms of the

disease have been described: cervicofacial, abdomino-

pelvic, and thoracopulmonary, with the first being the

most common.1,2

Oral and cervicofacial diseases are commonly asso-

ciated with dental caries and extractions, gingivitis

and gingival trauma, infection in erupting secondary

teeth, chronic tonsillitis, otitis or mastoiditis, diabetes

mellitus, immunosuppression, malnutrition, and local

tissue damage caused by surgery, neoplastic disease, or

irradiation.3 The chronic hyperglycemia of poorly con-

trolled diabetes mellitus induces events that promotestructural changes in various tissues and are associated

rom the Federal University of Rio Grande do Norte, Natal,

.

udent, Oral Pathology Postgraduate Program, Department

ry.

nt, Division of Oral and Maxillofacial Surgery, Department

ry.

sor, Division of Oral and Maxillofacial Surgery, Department

y.

sor, Division of Infectology, Giselda Trigueiro Hospital.

sor, Oral Pathology Postgraduate Program, Department of

537

with problems in wound healing and a greater suscep-

tibility to infections.4-6

Actinomycosis mimics different diseases and ex-

hibits different symptoms, a fact that makes its diagno-

sis difficult.3 Most commonly, it presents as a slowly

progressive, indolent, indurated infiltrationwithmulti-

ple abscesses, fistulas, and sinuses. A less common

form is acute and rapidly progressive, with fever anda fluctuating swelling that resembles a typical pyo-

genic infection.7,8 The differential diagnosis includes

tuberculosis (scrofula), fungal infections, nocardiosis,

suppurative infections by other organisms, and

neoplasms.3

Microscopic analysis shows an outer zone of granu-

lation tissue consisting of collagen fibers around cen-

tral purulent loculations that contain abundantneutrophils that surround multiple ‘‘sulfur granules.’’

{Professor, Oral Pathology Postgraduate Program, Department of

Dentistry.

Address correspondence and reprint requests to Dr de Andrade:

Departamento de Odontologia, Universidade Federal do Rio Grande

do Norte, Av Senador Salgado Filho, 1787, Lagoa Nova, Natal, RN,

Brasil CEP 59056-000; e-mail: ana_luiza_dla@hotmail.com

Received July 8 2013

Accepted August 7 2013

� 2014 American Association of Oral and Maxillofacial Surgeons

0278-2391/13/01032-X$36.00/0

http://dx.doi.org/10.1016/j.joms.2013.08.006

538 ACUTE PRIMARY ACTINOMYCOSIS IN DIABETES

These granules appear as a basophilic mass with a radi-

ating border of eosinophilic clubs after routine

staining.3,9

This report describes the fourth case of primary ac-

tinomycosis involving the hard palate and discusses

the main clinical, histopathologic, and therapeutic

characteristics and differential diagnosis of this rare

presentation of the disease.

FIGURE2. Panoramic view showing colonies of filamentous bacte-ria (hematoxylin and eosin stain; magnification, �40).

de Andrade et al. Acute Primary Actinomycosis in Diabetes. J OralMaxillofac Surg 2014.

Report of Case

A 46-year-old woman was seen at the Department ofOral and Maxillofacial Surgery, Federal University of

Rio Grande doNorte (Natal, Brazil) with a 4-day history

of a painful lesion on the hard palate that caused dys-

phagia. The patient had a 3-year medical history of

poorly controlled type 2 diabetes mellitus and was be-

ing treated with metformin, although she reported dis-

continuing the treatment 2 months before the

appearance of the lesion. The patient had beena smoker for 20 years, consuming 1 pack of cigarettes

per day.

Intraoral examination showed an ulcerative lesion

on the left side of the hard palate that measured ap-

proximately 1 cm in diameter and exhibited bone

destruction and exposure with an overlying yellow-

white slough (Fig 1). Several teeth were missing and

the patient presented extensive carious lesions, supra-and subgingival dental calculi, extensive root expo-

sure caused by gum recession, and a coated tongue.

The patient denied episodes of bleeding, purulent dis-

charge, headache, heaviness of the cheeks, coughwith

expectoration, respiratory distress, epistaxis, fatigue,

anorexia, weight loss, fever, or more cardinal signs of

inflammation. No lesion or symptom was identified

in the oropharynx or hypopharynx or in any other re-gion of the body, and there was no evidence of cervical

lymphadenopathy.

FIGURE 1. Ulcerative lesion showing bone destruction with anoverlying yellow-white slough.

de Andrade et al. Acute Primary Actinomycosis in Diabetes. J OralMaxillofac Surg 2014.

Based on the clinical presentation, the diagnostic

hypotheses were necrotizing sialometaplasia, salivary

gland neoplasm, and oral squamous cell carcinoma.

An incisional biopsy was performed and histopatho-

logic analysis showed the presence of microscopic ag-

gregates of tangled filaments characterized by a central

eosinophilic mass from which numerous peripheralbasophilic rays extended (Figs 2 through 4). The

surrounding connective tissue was dense and fibrous

and contained a discrete inflammatory infiltrate

consisting of neutrophils, lymphocytes, and plasma

cells. Some foreign body–type multinucleated giant

cells and areas of necrosis also were identified.

Based on the microscopic findings, material was col-

lected for culture and identification of the microbialagent. However, because the culture result was nega-

tive, a new sample was collected, seeded onto sheep

blood agar, and incubated under anaerobic conditions.

FIGURE 3. Numerous microscopic aggregates of tangled bacte-rial filaments in mildly inflamed connective tissue (hematoxylinand eosin stain; magnification, �100).

de Andrade et al. Acute Primary Actinomycosis in Diabetes. J OralMaxillofac Surg 2014.

FIGURE4. Sulfur granules present a central eosinophilic mass withperipheral basophilic rays (hematoxylin and eosin stain; magnifica-tion, �400).

de Andrade et al. Acute Primary Actinomycosis in Diabetes. J OralMaxillofac Surg 2014.

DE ANDRADE ET AL 539

The resulting colonies consisted of gram-positive ba-

cilli that were negative by Ziehl-Neelsen staining. No

b-hemolysis was observed. Next, the material was ex-

amined using the VITEK automated identification

system (bioM�erieux, Marcy l’Etoile, France), which

identified Actinomyces naeslundii with 97% agree-

ment. Some laboratory tests were performed (Table 1)to confirm the efficacy of the equipment. The diagnosis

of actinomycosis was thus confirmed.

The patient was treated orally with amoxicillin (500

mg) 3 times per day for 4 weeks, which resulted in

complete regression of the lesion.

Discussion

Actinomyces species are saprophytic bacteria of the

oral cavity and gastrointestinal tract. The bacteria ex-

hibit a low degree of virulence and are commonly

found in the saliva and in dental plaque. However, un-

der certain circumstances that compromise anatomic

barriers and host susceptibility, their pathogenic

form can cause actinomycosis.10,11

In addition to precarious oral hygiene, the present

patient had diabetes mellitus. It is believed that the

high concentration of glucose in the wound fluid of pa-

tientswith diabetes is themain reason for the increased

Table 1. BIOCHEMICAL TESTS PERFORMED TOCONFIRM THE DIAGNOSIS OF ACTINOMYCOSIS

Biochemical Tests Result

Hydrogen sulfide +

Bile esculin +

Urease +

Catalase �de Andrade et al. Acute Primary Actinomycosis in Diabetes. J OralMaxillofac Surg 2014.

bacterial growth seen in these patients.5,12,13 According

to Hirsch et al,5 nondiabetic patients can resist bacterial

invasion much more efficiently, whereas diabetic pa-

tients are more likely to succumb to the bacterial chal-

lenge. In addition, it is well known, although not

completely understood, that diabetes mellitus impairs

wound healing.

The typical actinomycosis infection is chronic in na-ture; however, it may be atypical with subacute or

acute clinical manifestations.8 Samuels and Martin14

described 3 distinct presentations of the disease: acute

painful swellings with duration shorter than 1 month;

chronic long-standing infections with duration longer

than 3 months; and unsuspected microbiologically

proved actinomycotic lesions. Although the present

patient did not show all signs and symptoms of acuteinflammation, according to the classification of Sam-

uels and Martin,14 the case can be categorized as the

acute type of actinomycosis as a result of the presence

of a painful lesion that occurred within a short period.

Actinomycosis involving the hard palate is ex-

tremely rare, and only 3 cases have been reported in

the literature7 (Table 2). The first case was a cocaine

user who had a circular and necrotic defect in thehard palate without nasal communication on prob-

ing.15 The second case presented a necrotic ulceration

along the hard palate with overhanging yellow-green

slough, in addition to perilesional erythema and boggi-

ness with reactive swelling of the upper lip.11 The

third case was characterized by a firm, infiltrative ul-

cerated plaque and significant tissue destruction and

deformity, with an overlying yellow-white slough.7

The clinical diagnosis of actinomycosis is difficult

because its onset is not specific and the differential di-

agnosis covers a wide range of diseases.16 Its variable

clinical presentations are generally considered repre-

sentative of malignancy rather than of an infectious

process,3 as seen in the present case. From this per-

spective, the diagnosis of actinomycosis on admission

is correct in fewer than 10% of cases.15

Different pathologic entities were considered in the

differential diagnosis of the present case. Necrotizing

sialometaplasia, a benign reactive necrotizing inflam-

matory process involving the minor salivary glands

of the hard palate,17 was one of them. The most com-

monly proposed and generally accepted etiology for

this condition relates to ischemia and, although not

all cases will be correlated with an obvious etiologicevent, clinical history is helpful in its diagnosis.18

The present case denied any surgical procedure or

other traumatic injuries that could be considered

potential predisposing factors. Moreover, the micro-

scopic features of necrotizing sialometaplasia (pseu-

doepitheliomatous hyperplasia of the overlying epi-

thelium, squamous metaplasia of the salivary ducts,

and acinar necrosis) were not found.

Table 2. CASES OF ACTINOMYCOSIS INVOLVING THE HARD PALATE REPORTED IN THE LITERATURE

Reference Year

Age (yr)/

Gender Duration Condition Signs and Symptoms Treatment

Rubin and Krost15 1995 58/M — cocaine snorting nasal congestion,

yellow sputum, and

purulence

intravenous aqueous

penicillin + oral

clindamycin;

intravenous

penicillin

Herman et al11 1998 65/F 2 wk chronic lymphocytic

leukemia

pain, malaise,

generalized

prostration,

difficulty eating and

swallowing

intravenous penicillin

De et al7 2011 32/M 2 yr normal — intravenous

crystalline

penicillin G

Present case 2013 46/F 4 days diabetes mellitus dysphagia and pain penicillin

Abbreviations: F, female; M, male.

de Andrade et al. Acute Primary Actinomycosis in Diabetes. J Oral Maxillofac Surg 2014.

540 ACUTE PRIMARY ACTINOMYCOSIS IN DIABETES

Because the palate is one of the most common sites

for the development of primary salivary gland neo-

plasms, a malignant salivary gland tumor was included

in the differential diagnosis of the present case. The

most likely candidates based on frequency of occur-

rence are mucoepidermoid carcinoma, adenoid cystic

carcinoma, and polymorphous low-grade adenocarci-noma.11 However, although more aggressive tumors

such as salivary duct carcinoma should be considered,

the development of a tumor of the reported extent and

bone destruction within such a short period would be

highly unlikely.

The propensity of actinomycosis to mimic squa-

mous cell carcinoma is well known.16 In agreement

with this aspect, the authors also hypothesized thatthe present lesion was an epithelial malignant tumor

based on the rapidly destructive evolution of the dis-

ease and the fact that the patient had been a smoker

for 20 years. However, carcinomas of the hard palate

often present as a papillary or exophytic growth rather

than a flat or ulcerated lesion,19 as observed in the

present case.

Although not pathognomonic, histologic features ofactinomycosis are the presence of sulfur granules

whose centers exhibit basophilic staining with eosino-

philic rays and that are surrounded by neutrophils.3

The present case differs from previously reported

cases by exhibiting microscopic aggregates that did

not show the established pattern when stained by rou-

tine techniques. In addition, neutrophilic inflamma-

tion was scarce. To the authors’ knowledge, this isthe first case exhibiting this staining pattern, which

could not be clarified satisfactorily. The mild intensity

of the inflammatory infiltrate was probably due to the

short duration of the lesion and the systemic condition

of the patient. Leukocyte dysfunction is common in

patients with diabetes mellitus, and the metabolic

anomalies of the disease associated with decreased

chemotaxis cause inadequate migration of neutrophilsand macrophages to the site of aggression.20,21

Culture results are negative in more than 50% of

cases of actinomycosis and an incisional biopsy is fre-

quently necessary for diagnosis of the disease.22 In

view of the difficulty in identifying themicrobial agent,

2 bacterial cultures were necessary in the present

case, because the first culture result was negative.

The second culture identified A naeslundii as thecausative agent of the infection. In the oral cavity,

this micro-organism plays an important role in dental

biofilm formation and gingival inflammation. It is be-

lieved that this bacterium can induce the destruction

of soft and hard tissues through root canals and the gin-

gival sulcus, playing a key role in the onset of peri-

odontal disease or in the transition from gingivitis to

periodontitis.23

Treatment of the present case consisted of the oral

administration of penicillin as recommended in the lit-

erature,7,11,15 and the patient presented complete

regression of the lesion.

In conclusion, the diagnosis of infection with Acti-

nomyces species in oral tissues represents a challenge

because of the variable clinical manifestations of the

disease. However, health care professionals shouldbe aware of the presence of ulcerative, destructive

DE ANDRADE ET AL 541

oral lesions because they can mimic malignant condi-

tions. Among the previously reported cases of actino-

mycosis of the hard palate, this is the first report in

which A naeslundii was identified as the causa-

tive agent.

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