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ORIGINAL ARTICLE

A retrospective review of 139 major and minor salivary gland tumorsMarija Trenkić Božinović1, Dragan Krasić2,3, Vuka Katić2, Miljan Krstić2,4

1Ophthalmology Clinic, University Medical Center, 2University of Niš, School of Medicine, 3Clinic of Maxillofacial Surgery, 4Institute of

Pathology, University Medical Center; Niš, Serbia

Corresponding author:

Marija Trenkić Božinović

Department of Ophthalmology,

University Medical Center

Dr. Zorana Djindjica 48, 18000 Niš, Serbia

Phone +381 18 4232 367;

Fax: +381 18 4534545;

E-mail: marija.trenkic@gmail.com

Original submission:

31 July 2014;

Revised submission:

30 October 2014;

Accepted:

16 December 2014.

Med Glas (Zenica) 2015; 12(1):73-78

ABSTRACT

Aim To describe demographic and histomorphological characte-ristics of 139 patients with epithelial salivary gland tumors in the Southeastern Serbia population.

Methods A total number of 139 patients with epithelial tumors arising in major and minor salivary glands in the period 2010-2012 was evaluated. After standard tissue proceeding, the routine haematoxylin-eosin (HE) and histochemical alcian blue-periodic acid-Schiff (AB - PAS) methods were used for histomorphological examination.

Results Among 139 patients, 102 (73.38%) had benign, and 37 (26.62%) malignant tumors. The majority of tumors were loca-lized in the parotid gland, in 117 (84.17%) patients. Among be-nign tumors there were 50 (49.02%) pleomorphic adenoma, 48 (47.06%) Warthin’s tumor, two (1.96%) myoepithelioma, and two (1.96%) oncocytoma. In the group of malignant tumors the most common was mucoepidermoid carcinoma, in 12 (32.43%) pati-ents, carcinoma ex pleomorphic adenoma in six (16.22%), adeno-id cystic carcinoma in five (13.51%), and oncocytic carcinoma in three (8.11%) patients.

Conclusion Benign tumors were more common than malignant ones, with predominance of pleomorphic adenoma. Malignant tu-mors are less common than benign in the large salivary glands, and more common in the minor salivary glands. Histochemical AB-PAS method helps in the diagnosis of mucinous salivary gland carcinoma.

Key words: benign, carcinoma, epidemiology, histopathology.

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INTRODUCTION

Salivary gland tumors can show a striking ran-ge of morphological diversity among different tumor types and sometimes within an individual tumorous mass. In addition, hybrid tumors, de-differentiation and propensity for some benign tumors to progress to malignancy can confound histopathological interpretation. These features, together with the relative rarity of a number of tumors (1), can sometimes make diagnosis di-fficult. There is some geographic variation and among different ethnic groups according to the place of residence (2-5). Therefore, the global annual incidence, when all salivary glands tu-mors were considered, varied from 0.4–13.5 ca-ses per 100.000 population (6). The frequency of malignant salivary neoplasm range from 0.4–2.6 cases per 100.000 population (7). Between 64% and 80% of all primary tumors occur in the paro-tid gland, 7%–11% in the submandibular glands, and 9%–23% occur in the minor glands (6,8). Females are more frequently affected (2). The mean ages of patients with benign and malignant tumors is 46 and 47 years, respectively (3,9).The aim of this study was to investigate both de-mographic and histomorphological characteristi-cs of epithelial salivary gland tumors of 139 pati-ents over a period of three years, and to compare findings with results of other studies. The purpo-se of this paper is to contribute to more accurate diagnosis of a lesion of salivary glands.

PATIENTS AND METHODS

The study included 139 patients with epithelial salivary gland tumors arising in the major and minor salivary glands, selected from the medi-cal files of the University Hospital, Department of Maxillofacial Surgery, and the Institute of Pa-thology of the University Medical Center Niš, Serbia, from the beginning of 2010 to the end of 2012. The following parameters were analyzed: patient age and gender, distribution of tumors in relation to malignancy (benign or malignant), as well as the localization in salivary glands (minor glands, parotid gland, submandibular glands, su-blingual glands). After standard tissue proceeding, routine hae-matoxylin-eosin (HE) and histochemical alcian blue-periodic acid-Schiff (AB - PAS) methods

were used for histomorphological examination.The results were statistically analyzed using des-criptive and quantitative analysis, the arithme-tic mean (X) and standard deviation (SD). The difference in the average values was calculated using the t- test for two independent samples. The association between the two marks was measured using the χ2 test. The Pearson’s rank correlation test was used to determine a relation between the associated parameters. The threshold for statisti-cal significance was taken at p ≤ 0.05.

RESULTS

During the span of 3 years, 139 cases of salivary glands tumors were diagnosed. Among these, 73 (52.52%) patients were females (56 benign and 17 malignant), and 66 (47.48%) were males (46 beni-gn and 20 malignant); 102 (73.38%) were benign and 37 (26.62%) malignant tumors (Tables 1-3). The mean age of the patients was 51.2 ± 13.97 ye-ars for benign tumors, and 58.97 ± 10.35 years for malignant tumors. In the group of benign tumors, the youngest patient was a 16-year-old female with pleomorphic adenoma in the right parotid gland. The oldest patient was 80-year-old male with pleomorphic adenoma of the left parotid gland. In the series of malignant tumors, the yo-ungest patient was also female, 43-year old, with mucoepidermoid carcinoma of the right subman-dibular gland. The oldest patient was a 81-year-old male, who was diagnosed with adenoid cystic carcinoma of the right submandibular gland. Localization of tumors in the major (parotid, sub-mandibular and sublingual glands) and minor sa-livary glands is presented in Table 1.Examining the correlation between types of tu-mors (benign or malignant) and their localizati-on in the salivary glands (minor glands, parotid gland, submandibular glands, sublingual glands) a statistically significant difference was found (p<0.0001 ) (Table 1).

No (%) of patients

Type of tumor

Minor glands

Parotid gland

Subman-dibular glands

Sublin-gual

glandsTotal p

Benign 3(2.94%)

97 (95.10%)

2 (1.96%) 0 102

(73.38%)

<0.0001Malignant 11(29.73%)

20 (54.05%)

6 (16.22%) 0 37

(26.62%)

Total 14 (10.07%)

117 (84.17 %)

8 (5.76 %) 0 139

Table 1. Distribution of tumors in the salivary glands

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Trenkić Božinović et al. Major and minor salivary gland tumors

The most frequent tumors originated from the parotid gland (97 benign and 20 malignant), fo-llowed the submandibular gland (2 benign and 6 malignant) and minor salivary glands (benign 3 and malignant 11). The majority of tumors, both benign and malignant, was localized in the pa-rotid gland, 117 (84.17%). The most frequent tumors in minor salivary glands were malignant, 11 (78.57%). Benign lesions were localized in parotid gland, in 97 (95.10%) patients (69.78% of all tumors), and only 20 (54.05%) malignant lesions (14.39% of all tumors) were localized in the parotid gland. No tumor was implicated from sublingual mayor salivary gland. There was no statistically significant association between tumor type and gender (p>0.05). Pati-ents with malignant tumors were significantly ol-der than patients with benign tumors (p<0.05). In

both, benign and malignant tumors, there was no significant difference considering the localization (right/left) (p>0.05 ).Among 102 (73.38%) benign tumors, there were 50 (49.02%) pleomorphic adenoma, 48 (47.06%) Warthin’s tumor, and myoepithelioma and onco-cytoma, two (1.96%) of each (Table 2). The ma-

No (%) of patients

Type of tumorGender Localization Type of salivary gland

TotalMale Female Right Left Parotid Submandibular Sublingual Minor

Pleomorphic adenoma 14 (28.0) 36 (72.0) 25 (50.0) 25 (50.0) 47 (94.0) 1 (2.0) 0 2 (4.0) 50 (49.02)Warthin’s tumor 30 (62.5) 18 (37.5) 29 (60.42) 19 (39.58) 47 (97.92) 1 (2.08) 0 0 48 (47.06)Myoepithelioma 1 (50.0) 1 (50.0) 1 (50.0) 1 (50.0) 2 (100.0) 0 0 0 2 (1.96)Oncocytoma 1 (50.0) 1 (50.0) 2 (100.0) 0 1 (50.0 ) 0 0 1 (50.0) 2 (1.96)Total 46 (45.1) 56 (54.9 ) 57 (55.88) 45 (44.12) 97 (95.1) 2 (1.96) 0 3 (2.94) 102

Table 2. Histological types and other characteristics of benign salivary gland tumors

No (%) of patients

Type of tumor (Ca)

Gender Type of salivary gland Total

Male Fimale ParotidSub-

mandi-bular

Sublin-gual Minor

Mucoepi-dermoid

7(58.33)

5(41.67)

7(58.33)

4(33.33)

0 1(8.34)

12(32.43)

Ca ex PA 2(33.33)

4(66.67)

4(66.67)

2(33.33) 0 0 6

(16.22)Adenoid cystic

3(60.0)

2(40.0) 0 0 0 5

(100.0)5

(13.51)

Oncocytic 2(66.67)

1(33.33)

2(66.67) 0 0 1

(33.33)3

(8.11)Myoepit-helial

1(50.0)

1(50.0) 0 0 0 2

(100.0)2

(5.41)

Cystadeno 2(100.0) 0 0 0 0 2

(100.0)2

(5.41)Squamous cell

1(50.0)

1(50.0)

2(100.0) 0 0 0 2

(5.41)Basal cell adeno

0 2(100.0)

2(100.0) 0 0 0 2

(5.41)Mucinous adeno

1(100.0)

0 1(100.0) 0 0 0 1

(2.70)Salivary duct

1(100.0) 0 1

(100.0) 0 0 0 1(2.70)

Small cell type

0 1(100.0)

1(100.0) 0 0 0 1

(2.70)

Total 20(54.05)

17(45.95)

20(54.05)

6(16.22) 0 11

(29.73) 37

Table 3. Histological types and other characteristics of malig-nant salivary gland tumors

Ca, carcinoma

Figure 1. A) Pleomorphic adenoma: epithelial cells arranged in strands in mucoid background (HE, x 200); B) Warthin’s tumor: double-layered columns of cells with intervening lymphoid tis-sue (HE, x 200); C) Myoepithelioma: clear cell variant with mucoid surrounding stroma (AB- PAS, x 200); D) Oxyphilic ad-enoma: large polyhedral cells with finely granular cytoplasm; colagenous stroma is minimal – PAS positive (AB- PAS, x 300) (Katić, V, 2014)

A)

B)

C)

D)

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jority of the benign tumors were located in the parotid glands, in 97 (95.10%) cases. The most common histological types (overall prevalence was 62.16%, e.g., 23 cases) were mu-coepidermoid carcinoma which were reported in 12 (32.43%) cases, carcinoma ex pleomorphic adenoma in six (16.22%) cases, adenoid cystic carcinoma in five (13.51%) cases, followed by oncocytic carcinoma, in three (8.11%), myoepit-helial carcinoma in two (5.41%), cystadenocarci-noma in two (5.41%), squamous cell carcinoma in two (5.41%), basal cell adenocarcinoma in two (5.41%) cases. Small cell carcinoma, salivary duct carcinoma, and mucinous adenocarcinoma were uncommon, in one (2.70%) case each, respective-ly. Most of the tumors in the minor salivary glands were malignant, 11 (78.57%) (Table 1 and 3). The most common histologic appearance of be-nign and malignant tumors is presented in Figure 1 and 2.

DISCUSSION

This paper describes the epidemiological and histomorphological features of 139 epithelial tumors of the salivary glands, with reference to their surgical treatment. Our results are similar to other reports in relation to age, sex and localiza-tion of the tumors (2,9,10).In this series, the most common benign tumor was pleomorphic adenoma, localized mostly in the parotid glands, mostly affecting women. Ple-omorphic adenoma is a benign tumor, but recu-rrence appears very often (10). Recurrences can be explained by the growth of the tumor around the facial nerve, which complicates its surgical extirpation (11,12), or they arise as complicati-ons of multicentric growth of pleomorphic ade-noma (1). The recurrence increases the risk to malignant alteration of pleomorphic adenoma (11,13). Warthin’s tumor was more common in our series, localized in the parotid gland without malignant alteration. In some reports, this is one of rare variants of epithelial salivary gland tu-mors (14). The discrepancy in the frequency co-uld be explained by geographical, racial factors, as well as aggravated differential diagnosis with metastatic adenocarcinoma tumors in the lymph nodes, that is induced by its mixed lymphoid - glandular structure (3,4,15-17). Cancers of the salivary glands are less common than benign forms in this study. A higher inciden-ce of malignant tumors, compared to the results of other authors (14,18), could be explained by the profile of patients treated in our institution of tertiary level, as pointed out by the others (19). The microscopic pattern of malignant salivary gland tumors is sometimes very similar to beni-gn tumors, therefore, the differentiation is diffi-cult (6,8,20). The specific criteria of malignancy include anaplasia, infiltration of the capsule to surrounding tissue or the absence of a capsule, multiple foci of necrosis and hemorrhage, lymp-hangio invasion, as well as perineural invasion inside the tumor. The most important characte-ristic of malignant tumor is the involvement of the regional lymph nodes, that we found in our malignant salivary gland tumors (7). According to the results of this study, the most common was mucoepidermoid carcinoma, re-ported in 12 cases. Contrary to the literature that

Figure 2. A) Mucoepidermoid carcinoma: both solid and multi-cystic pattern, with syalomucin in cystic component (AB-PAS, x 200); B) Carcinoma ex pleomorphic adenoma: poorly differ-entiated adenocarcinoma (HE, x 200); C) Adenoid cystic carci-noma: multiple cystic spaces filled with acid mucin (AB- PAS, x 250) (Katić, V, 2014)

A)

B)

C)

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Trenkić Božinović et al. Major and minor salivary gland tumors

mucoepidermoid carcinoma is frequently located in the minor salivary glands (20), we have fo-und that the mucoepidermoid carcinoma is more frequently presented in the parotid gland and submandibular glands. Carcinoma ex pleomorp-hic adenoma was second in frequency, which is directly related to the long-standing pleomorphic adenoma and its recurrences. Inexplicable mani-festation of metastasizing benign mixed tumor with local or distant metastasis ( “metastasizing pleomorphic adenoma”) has been described in the new WHO histological classification of tu-mors of the salivary glands (1). Differential di-agnosis of the metastatic adenocarcinoma of surrounding organs from primary salivary gland adenocarcinoma is very difficult (21,22). Due to these characteristics, it is emphasized that patho-gnomonic finding of primary adenocarcinoma of the salivary gland is the presence of polymorphic adenoma or healthy salivary gland tissue in its vicinity (23). Adenoid cystic carcinoma reported in this study was localized in the small salivary glands, oncocytic carcinoma in the parotid glan-ds, and in the minor salivary glands. In terms of localization and frequency, this is in accordance with data from the literature (24,25).

Other cancers, myoepithelial carcinoma, cystade-nocarcinoma, squamous cell carcinoma and basal cell carcinoma were far less frequently found in this study. Myoepithelial carcinoma and cystade-nocarconoma were discovered in the minor sali-vary glands, while squamous and basal cell adeno-carcinoma were found in the parotid gland (5,25).In conclusion, this study is the first epidemiologi-cal study on salivary gland tumors performed on the population from Southeastern Serbia, based on the 2005 WHO tumor classification. The fin-dings of this study contribute significantly to the awareness of clinical and pathological features of salivary gland tumors in our region and can improve our understanding of significant diffe-rences in the global distribution of salivary gland tumors which have been reported. Although, the reason for these differences remains unclear, fur-ther investigations specifically searching for the possible causes, are greatly encouraged.

FUNDING

No specific funding was received for this study.

TRANSPARENCY DECLARATIONS

Conflict of interest: none to declare.

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Retrospektivni pregled 139 tumora malih i velikih pljuvačnih žlezdaMarija Trenkić Božinović1, Dragan Krasić2,3, Vuka Katić2, Miljan Krstić2,4

1Klinika za očne bolesti, Klinički centar Niš, 2Medicinski fakultet, Univerzitet u Nišu, 3Klinika za maksilofacijalnu hirurgiju, Niš, 4Institut za

patologiju, Klinički centar Niš; Niš, Srbija

SAŽETAK

Cilj Opisati demografske i histomorfološke karakteristike 139 slučajeva epitelijalnih tumora pljuvačnih žlezda u populaciji jugoistočne Srbije.

Metode Analizirano je 139 pacijenata s epitelnim tumorima malih i velikih pljuvačnih žlezda operisa-nih na Klinici za maksilofacijalnu hirurgiju u Nišu, u periodu od 2010. do 2012. godine. Posle standar-dne obrade tkiva za histomorfološko ispitivanje korišćena je rutinska hematoksilin-eozin (HE) metoda i histohemijska AB-PAS metoda.

Rezultati Studija je obuhvatila 139 slučajeva, odnosno 102 (73,38%) benigna tumora i 37 (26,62%) malignih lezija. Većina tumorâ bila je lokalizovana u parotidnim žlezdama, u 117 (84,17%) slučajeva. Među benignim tumorima bilo je 50 (49,02%) slučajeva pleomorfnog adenoma, 48 (47,06%) Warthino-vog tumora i po dva slučaja (1,96%) mioepitelioma i oncocitoma. U grupi malignih tumora najčešći je bio mukoepidermoidni karcinom, u 12 (32,43%) slučajeva, carcinoma ex pleomorphic adenoma u šest (16,22%), adenoidni cistični karcinom u pet (13,51%) i oncocitic carcinoma u tri (8,11%) slučaja.

Zaključak Benigni tumori pljuvačnih žlezda su češći nego maligni, uz dominaciju pleomorfnog ade-noma. Maligni tumori su se ređe od benignih javljali u velikim pljuvačnim žlezdama, a češće su bili lokalizovani u malim pljuvačnim žlezdama. Histohemijska AB-PAS metoda pomaže u dijagnozi muci-noznih karcinoma pljuvačnih žlezda.

Ključne reči: benigni, maligni, epidemiologija, histopatologija.