CARCINOMA EX PLEOMORPHIC ADENOMA INPAROTID GLAND – CASE REPORT

INTRODUCTION

Pleomorphic adenoma, also know as benign mixed

tumor because of the presence of both epithelial and

mesenchymal tissue, are the most common tumors of

the major salivary glands. (1,2). These tumors occurs

most frequently in the parotid gland. Most pleomorphic

adenomas of parotid gland develop in the superficial

parotid lobe. Generally they presents as a well-deliniated,

solitary, painless mass with slow growth. (3). Although

205

Journal of Experimental Medical & Surgical Research

Cercetãri Experimentale & Medico-Chirurgicale

Year XVII · Nr.3/2010 · Pag. 205 - 209E x p e r i m e n t a l

M e d i c a l S u r g i c a l

R E S E A R C H

J O U R N A L o f

Correspondence to: Dr. Anamaria Mag, Clinica ORL Timiºoara, Bd. Revoluþiei No. 6, Telefon: 0740 43 47 40, Email: anamariamag@yahoo.com

SUMMARY:Carcinoma ex pleomorphic adenoma is defined as a pleomorphic adenoma from whichderived an epithelial malignancy. This tumor develops in primary or recurrent pleomorphicadenoma. Carcinoma ex pleomorphic adenoma is rare and comprises approximately 3.6%of all salivary tumors. The authors present a case of carcinoma ex pleomorphic adenoma,which is one of the 6 cases of carcinomas ex pleomorphic adenoma that have beenoperated in ENT Department Timiºoara over the last 10 years, emphasizing diagnostic steps taken and therapeutic methods. We present the case of a 63 year old female from urbanarea who was admitted to hospital for a mass in the parotid region, witch appeared so, afterseven months, gradually increasing in size. At MRI examination appeared an expansivepolilobulated tumor mass with axial diameters of 4/5 cm, in the left parotid gland projection.We performed total left parotidectomy with facial nerve preservation and lateral neckdissection Level II – IV. Histopathological exam revealed mucoepidermoid carcinoma expleomorphic adenoma. The evolution of this tumor presents a high aggressiveness, thepatient undergone postoperative radiotherapy, respectively.

Key Words: carcinoma ex pleomorphic adenoma, malignant parotid tumor, parotidectomy

CARCINOM EX ADENOM PLEOMORF PAROTIDIAN – PREZENTARE DE CAZ

Rezumat:Carcinomul ex adenom pleomorf este definit ca adenom pleomorf în care apar elementemaligne strict epiteliale. Acesta se dezvoltã în adenom pleomorf primar sau recurent.Carcinomul ex adenom pleomorf este rar ºi reprezintã aproximativ 3,6% din toate tumorileglandelor salivare. Autorii prezintã un caz de carcinom ex adenom pleomorf, dintre cele 6cazuri diagnosticate ºi operate în Clinica ORL Timiºoara în ultimii 10 ani, subliniind etapelediagnostice parcurse, precum ºi modalitatea terapeuticã utilizatã. Prezentãm cazul uneipaciente în vârstã de 63 de ani din mediu urban, ce a fost internatã în Clinica ORL Timiºoarapentru o formaþiune tumoralã în regiunea parotidianã stângã, apãrutã, afirmativ, în urmã cuaproximativ ºapte luni înaintea internãrii, crescând treptat în dimensiuni. Examinarea RMN a evidenþiat o masã tumoralã expansivã cu contur polilobulat cu diametrele axiale maximede 4/5 cm., în proiecþia glandei parotide stângi. S-a efectuat parotidectomie totalã stângã cu conservarea nervului facial ºi evidare ganglionarã funcþionalã selectivã parþialã stângã(ariile II-IV). Examenul histopatologic a relevat: carcinom mucoepidermoid ex adenompleomorf. Evoluþia acestei tumori prezintã o agresivitate crescutã, motiv pentru care s-aindicat efectuarea de radioterapie postoperator.Cuvinte-cheie: carcinom ex adenom pleomorf, neoplasm parotidian, parotidectomie totalã.

A. Mag1

S. Cotulbea1

A. H. Marin1

C. Doros1

D. Neamtu1

N. Balica1

A. Ruja2

M. Preda3

Received for publication: 01.05.2010

Revised: 21.07.2010

1. - ENT Department, University of Medicine and Pharmacy Timiºoara2. - Clinic of Odontotherapiy, Faculty of Dentistry, University of Medicine and Pharmacy Timiºoara3. - Clinic of General and Oncologic Surgery, University of Medicine and Pharmacy Timiºoara

benign, as many as 25% undergo carcinomatous

transformation, if left untreated. (2). Pleomorphic

adenoma can sometimes to recur, metastasizes or suffer

malignant degeneration. (3). Carcinoma ex pleomorphic

adenoma is usually a more poorly circumscribed mass

than the benign pleomorphic adenoma. Carcinomas ex

pleomorphic adenoma are prone to frequent recurrence

and commonly metastasize. (3).

We made a study of all malignant tumors of parotid

gland tumors treated in ENT Department Timiºoara

between 2002 to 2009. From 26 cases of malignant

parotid tumors, only six represented carcinomas ex

pleomorphic adenoma. We decided to make this case

report because of the rarity of carcinoma ex pleomorphic

adenoma in malignant tumoral pathology of parotid

gland.

CASE PRESENTATION

S.M. patient, aged 63 years, from urban area, was

admitted in the ENT Department Timiºoara in August

2008 for a mass in the parotid region, which appeared,

after seven months, gradually increasing in size. We have

to mention that the patient did not present at admission

facial palsy or ear sensory disturbances.

E.N.T. Clinical Exam:

Inspection: deformation of the left parotid gland region

by a tumor with size of 4/5 cm.

Palpation: reveals a tumor size of 4/5 cm, well

circumscribed with hard consistency, fixed to deep

planes, sensitive to palpation. The superjacent skin

aspect was normal. (Fig. 1)

Bucopharyngoscopy, anterior and posterior

rhynoscopy, indirect laryngoscopy, nasal endoscopy,

hypopharingo-laryngo-endoscopy with 70 degree

endoscope revealed no pathological evidence.

General examination reveals no pathology.

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Fig. 1 Left parotid tumor

Fig. 2(a) MRI

Fig. 2(b) MRI

Laboratory examination reveals a minor anemia but no

other change in biological constants. Chest X-ray shows

no active or disabling pleuropulmonary lesions.

MRI examination (Fig. 2a end 2b) is performed and

reveals an expansive, polilobulated tumor mass with

axial diameters of 4/5 cm, in the left parotid gland

projection; the formation shows heterogeneous

hypo-signal in T1, with fluid signal infracentrimetric areas

(necrosis) co-existing with hemorrhage lesions on T1

hyper-signal; in T2 nonhomogeneous hyper-signal,

heterogeneous gadolinophilly of areas with

parenchymatous signal and the absence of signal in

areas of necrosis contrast intake.

With these clinical and laboratory data we establish

presumptive diagnosis of left parotidian tumor, possibly

malignant.

Regarding differential diagnosis, other diseases that

could enter into discussion are: secondary lymph node

from septic processes of the mouth, chronic parotitis,

syphilis, tuberculosis and actinomicosis, Hodgkin’s

disease, lymphosarcoma, metastatic tumors, primary or

metastatic melanoma, angiomatosis tumor,

neurofibroma.

Based on these data, with patient consent, surgical

intervention is decided. Total parotidectomy was

performed with preservation of facial nerve and left

lateral neck dissection II-IV. (Fig. 4a and 4b)

Postoperative evolution, under antibiotic therapy and

daily wound toilet, was good with healing per primam.

The tumor removed was sent to hystopathological

examination which revealed a microscopic structure of

mucoepidermoid carcinoma ex pleomorphic adenoma

associated with small fragments of salivary gland with

lesion of pleomorphic adenoma; tumor is invasive in

adjacent tissues of glandular lodge, for which

postoperative radiotherapy was indicated.

Immunohistochemical study revealed for Ki 67 a positive

immune reaction. (Fig. 3).

The particularity of the case is represented by the

rapid evolution of the tumor mass (seven months), since

the most studies, highlights most often, a significantly

longer evolution.

DISCUSSIONS

Pleomorphic adenoma is the most common benign

tumor that affects salivary glands (1,2), occuring on

60%-70% of cases. Pleomorphic adenoma is

characterized by proliferation of epithelial-mesenchymal

tissue of the salivary gland.

Occasionally pleomorphic adenoma may undergo

malignant transformation resulting carcinoma ex

pleomorphic adenoma or respectively carcinosarcoma.

Very occasionally however, metastatic lesions are

identified in patients with a history of pleomorphic

adenoma which, on detailed pathological evaluation, are

found to exhibit all the histological hallmarks of the

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Fig. 3 Area of mucoepidermoid carcinoma ex pleomorphicadenoma immunopozitive for Ki67

Fig. 4a Intraoperative aspect Fig. 4b. Intraoperative aspect

preceding benign lesion. This “enigmatic” entity has been

termed the metastasizing pleomorphic adenoma. (4).

In recent years appeared datas about non-invasive (in

situ or intracapsular) carcinoma ex pleomorphic

adenoma. (5). They are carcinomas occurring in the

pleomorphic adenoma without penetrating the capsule.

Although encapsulation of tumor proved to be a indicator

of benign character, Felix et al. (5) recently reported a

case in which a fully encapsulated carcinoma ex

pleomorphic adenoma presented regional lymph nodes.

Carcinoma ex pleomorphic adenoma usually occurs in

men in six decade of life. (6).

Approximately 80% are located in major salivary

glands and 20% in small salivary glands. (7). Most cases

(81,7%) occur in the parotid gland, while a 18%,

respectively 0,3% appear in submandibular and

sublingual gland. (8). Most series show a female to male

ratio of 1.2 to 3.1. (9). Carcinoma ex pleomorphic

adenoma rarely occurs before age of 20 years. (10).

Usually presents as a mass with a long evolution that

shows a sudden increase in size. In 12-55% of cases this

rapid increase in size may be accompanied by pain, facial

nerve palsy and fixation to the surrounding soft tissue. A

small percentage of patients may have tumors with rapid

growth, without any symptoms. (10). Zbaren et al. in a

group of 24 patients with carcinoma ex pleomorphic

adenoma noted a percentage of 33% (8 cases), when

tumor was in parotid deep lobe. (11).

Eneroth and Zetterberg’s studies support the

hypothesis that the risk of carcinomatous transformation

in a adenoma increases with the age of the tumor. (12).

Histological features of carcinoma ex pleomorphic

adenoma are: the capsule invasion, hemorrhage,

necrosis alternating with areas presenting classical

features of pleomorphic adenoma. (13). Recent studies

have shown that the most frequently encountered

histological types in a carcinoma ex pleomorphic

adenoma are: highly malignant adenocarcinoma or

undifferentied carcinoma, although many other types

were found such as squamous cell carcinoma,

mucoepidermoid carcinoma, adenoid cystic carcinoma,

papillary carcinoma and terminal duct carcinoma. (14).

Carcinoma ex pleomorphic adenoma treatment is

surgical – parotidectomy with neck dissection.

Some authors (15,16) recommended surgery and

postoperative radiotherapy, which is also our opinion in

treatment of this tumors. Chen and colab. (15) have

obtained a better local tumor control from 49% to 75% by

combining surgery with postoperative radiotherapy in 63

patients diagnosed with carcinoma ex pleomorphic

adenoma.

Features associated with an unfavorable prognosis

include: high tumor grade, large size, soft tissue invasion,

perineural invasion and lymph node metastases.

According to LiVolsi and Perzin (17) the extent of tumor

infiltration beyond the capsule is the most reliable

prognostic marker. Carcinoma ex pleomorphic adenoma

metastasizes exclusively as a carcinoma. Distant

metastases occur more frequently than regional

metastases. Distant metastases seem to show a

particular affinity for lung and bone, especially the

vertebral column. (18).

Zbaren et al. (11) observed in 24 cases of carcinoma

ex pleomorphic adenoma studied, a survival rate of 76%

at 5 years and a recurrence rate of 25% (six of 24

patients). Luers et al. (19) retrospectively analyzed 22

cases of carcinoma ex pleomorphic adenoma, found that

about half of patients had evidence of a parotid mass of

up to 1 year only while maximum of the others was 48

years. Both 5-year disease-specific and overall survival

were 60%. Recurrence-free survival after 5 years was

85%.

CONCLUSIONS

The fact that pleomorphic adenomas are classified as

benign tumors should not overshadow the wide range of

biologic behaviors associated with these tumors.

Because of the potential for malignant transformation,

surgical treatment must be properly performed.

Surgery followed by postoperative radiation should be

considered the standard of care for patients with

carcinoma ex pleomorphic adenoma.

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