Salivary Gland Neoplasms A Histopathological and Statistical Study
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1 Med. J. Cairo Univ., Vol. 8, No., December: , 23 Salivary Gland Neoplasms A Histopathological and Statistical Study GINA A. NAKHLA, M.D.; HALA N. HOSNI, M.D.; MOHAMMED FAISAL DARWEESH, M.D.; AHMED A. SOLIMAN, M.D. and MARWA A.M. HASSANIN, M.Sc. The Department of Pathology, Faculty of Medicine, Cairo University, Egypt Abstract Salivary gland neoplasms represent only about 3 to 4% of all head and neck tumors. This study shows a registry of cases showing salivary gland neoplasms received by the department of Pathology, Kasr El Aini Hospital, during the period from January 26 till December 2. This work also comprises the determination of the frequency and distribution of these tumors as a group in a sample of Egyptian patients. Statistical evaluation of clinical and patient data and that of the pathological findings available in the request sheet is done to analyze these data. Material and Methods: This work includes 4 cases of salivary gland neoplasms obtained through collection of all archived cases of salivary gland tumors during the period from January, 26 till December 3, 2 from the Pathology Department, Faculty of Medicine, Cairo University, Kasr El Aini Hospital. The available archived H&E. Glass slides were obtained and revised. The paraffin blocks were cut 5u thick and stained by hematoxylin and eosin for histopathogical examination. Results: 4 cases were collected. The patient s age ranged from 6 to 84 years with male predominance 76 (54%), 99 cases (7.7%) were of parotid origin, 3 cases (2.4%) were of minor salivary gland origin and cases were submandibular in origin (7.9%). The predominant histopathologic type was pleomorphic adenoma 6 cases (43.6%). Conclusion: Many variations were seen between the results of salivary gland neoplasms in Egyptian patients and those obtained by other studies in different parts of the world. However, many clinical characteristics of the diseases were in agreement with most studies all over the world. Key Words: Salivary gland neoplasms Histopathological Statistical. Introduction SALIVARY gland tumors are specific neoplasms in the oral and maxillo-facial area. However, morphological heterogeneity and low frequency make it considerably difficult to histologically classify these tumors [,2]. Correspondence to: Dr. Ahmed Abd-El Moneim Soliman, drahmedsoliman@yahoo.com The frequency of salivary gland neoplasms varies from.4 to 3.5 annual cases per, inhabitants in various populations. Of all diagnosed neoplasms, salivary gland tumors constitute 3% of those in the head and neck area [3]. Salivary gland tumors are more frequent in adults than in children [4]. Among all salivary gland tumors, the most frequently reported benign tumor is pleomorphic adenoma [,3]. Considering the malignant salivary gland neoplasms, reports of the most commonly seen tumors varies but, in general, mucoepidermoid carcinoma [5-7] and adenoid cystic carcinoma [8-] were reported. While tumors of the salivary glands can appear at any age, the maximum incidence is in the fourth decade of life for benign lesions and in the fifth decade for malignant tumors [7,]. Classically, these lesions have been reported to be more frequent in women, although the proportion varies according to the histological type of tumor [2]. Material and Methods This work included 4 cases of salivary gland neoplasms obtained through collection of all archived cases of salivary gland tumors during the period from January, 26 till December 3, 2 from the Pathology Department, Faculty of Medicine, Cairo University, Kasr El Aini Hospital. Data obtained from pathology sheet are: - Age and sex of patient. - Symptoms and duration. - Site of salivary gland tumors. 967
2 968 Salivary Gland Neoplasms a Histopathological & Statistical Study - Diagnosis of salivary gland tumors and histopathologic subtypes. - Gross pathological features e.g. size, tumor ulceration and lymph node status. All collected cases were: - The available archived H&E. glass slides. - The paraffin blocks which were cut of 5u and stained by hematoxylin and eosin stains for histopathogical examination. Histopathological evaluation: Revision of all available slides were done, reclassified according to the most recent staging systems and photographed with a digital camera attached an Olympus microscopic model BX5. Statistical methods: Data were analyzed using SPSS (Statistical program for social science version 7). Numerical data were summarized as means and standard deviations (SD) or medians and ranges as appropriate. While qualitative data were described as frequencies and percentages. Results 4 cases of salivary gland tumors received by Pathology Department at Kasr El Aini Hospital during the last five years (26-2) were included in this study. The median age at presentation was 47 years with a range of (6-84) years with male predominance of 76 patients in a ratio.2: respectively (M: F ratio). Sex distribution of salivary gland tumors showed male predominance (54%). The mean age of the benign cases was 44.6 years± 3 compared to 44.7 years for malignant cases±8.2. Of the 4 patients collected, 96 patients had a benign pathology with a male predominance of 64.6%. On the other hand, 68.2% of malignant cases were females. The peak incidence of both benign and malignant tumors was in the fifth decades followed by six decades. Benign tumors outnumbered malignant tumors in all decades except in females in st, 2nd, 7th and 8th decades. Presentation: Most of the patients presented with more than one symptom. A mass was the main presenting symptom (95%) followed by palpable lymph nodes (33.6%). Pain was common feature (7.%). Table (.3). Facial nerve paralysis was found in (27.3%) of malignant cases whereas it was not noted in patients of benign tumors, skin infiltration was noted in (22.7%) of malignant cases. Pain was a common feature in (34. %) of malignant tumors, whereas only (9.4%) of patients of benign tumors had pain. (Table.4). Tumor site: Concerning the tumor site, the majority were in parotid gland (7.7%), followed by minor salivary glands (2.4%). Benign tumors were more commonly encountered in the parotid while malignant tumors were most common in minor salivary glands. Minor salivary gland tumors affected females more than males (9/3 cases), also in females the malignant tumors in minor salivary glands were predominant (73.7%). The most common site of minor salivary gland tumors was palate (6 cases). Twenty cases showed recurrence of the tumor, further analysis revealed (6.2%) were benign (2 cases were pleomorphic adenoma and 4 cases were warthin s tumor) while (9. %) in malignant cases (3 cases adenoid cystic carcinoma and one case acinic cell tumor). Pathological data: Perineural invasion was seen in 7/44 cases of malignant tumors (5.9%). Four cases of mucoepidermoid carcinoma, two cases of adenoid cystic carcinoma and one case only of acinic cell carcinoma. Dissected lymph nodes were positive for metastasis in 8/35 cases only (22.9%). Pleomorphic adenoma was the commonest benign salivary gland tumors (43.6%) followed by warthin s tumor (2.4%) while the most common malignant salivary gland tumor was mucoepidermoid carcinoma (.4%) followed by adenoid cystic carcinoma (8.6%). Table (.5). The most common benign tumor in parotid was pleomorphic adenoma (45.6%) while Mucoepidermoid carcinoma was the commonest malignant tumor (%) while adenoid cystic carcinoma was the commonest malignant tumor in minor salivary gland (36.7%). Table (.5).
3 Gina A. Nakhla, et al. 969 Table (. ): Age, Sex and tumor nature of cases of salivary gland tumors. Age group More than 8 Benign Malignant Male Female Total Male Female 2 (3.2%) 8 (2.9%) (6%) 9 (3.6%) 6 (25.8%) 4 (6.5%) 3 (4.8%) (2.9%) 7 (2.6%) 4 (.8%) 6 (47.%) 5 (4.7%) (2.9%) 3 (3.%) 5 (5.6%) 4 (4.6%) 35 (36.5%) 2 (2.9%) 4 (4.2%) 3 (3.%) (.%) (7.%) (7.%) (7.%) 3 (2.4%) 3 (2.4%) 3 (2.4%) 2 (4.3%) (3.3%) 3 () (6.6%) 4 (3.3%) 8 (26.6%) 5 (6.6%) 2 (6.6%) 2 (6.6%) Total Total 2 (4.5%) 4 (9.%) 6 (3.6%) 4 (9.%) (25%) 8 (8.2%) 5 (.4%) 4 (9.%) Table (.2): Frequency of presenting symptoms of salivary gland tumors. Clinical presentation Frequency Percentage (%) Mass Pain Facial nerve paralysis Firm induration Skin infiltration and ulceration 7. Palpable lymph nodes Table (.3): Correlation of the main presenting symptoms with the tumor nature. Clinical Benign Malignant presentation (n=96) (n=44) Mass 92 (95.8%) 4 (93.2%) Pain 9 (9.4%) 5 (34.%) Facial nerve paralysis 2 (27.3%) Firm induration 3 (3%) 9 (2.5%) Skin infiltration and ulceration (22.7%) Palpable lymph nodes 2 (2.5%) 35 (79.5%) p-value=. Table (.4): Frequency of histological types of salivary gland tumors. Tumor type Benign tumors: Pleomorphic adenoma Warthins tumor Myoepithelioma Schwannoma Haemangioma Basal cell adenoma Oncocytoma Malignant tumors: Mucoepidermoid carcinoma Adenoid cystic carcinoma Ca ex-pleomorphic adenoma Acinic cell carcinoma Adenocarcinoma (NOS) Clear cell carcinoma Epithelial-Myoepithelial carcinoma Lymphoma Metastatic renal cell carcinoma Squamous cell carcinoma Total Number Percentage (%) Table (.5): Frequency of different tumor types according to site of 4 salivary gland tumors. Histological type Parotid gland Submandibular gland Minor salivary gland Benign tumors: Pleomorphic adenoma Warthin's tumor Myoepithelioma Schwannoma Haemangioma Basal cell adenoma Oncocytoma Malignant tumors: Mucoepidermoid carcinoma Adenoid cystic carcinoma Carcinoma ex pleomorphic adenoma Acinic cell carcinoma Adenocarcinoma (NOS) Clear cell carcinoma Epithelial-myoepithelial carcinoma Lymphoma Metastatic renal cell carcinoma Squamous cell carcinoma (45.6%) 28 (28.4%) (%) (%) (%) 23 (%) (%) 2 (2%) 3 (3%) (%) (%) 3 (3%) (%) (%) 9 6 (54.5%) 2 (8.2%) (9.%) 2 (9.%) (9.%) (33.3%) (3.3%) 9 5 (6.7%) (36.7%) 2 (6.7%) (3.3%) Total 99 (%) (%) 3 (%)
4 97 Salivary Gland Neoplasms a Histopathological & Statistical Study Fig. (): Pleomorphic adenoma in submandibular gland (H & E x). Fig. (2): Warthin s tumor in parotid gland showing Luminal layer of palisaded oncocytic cells (H & E x2). Fig. (3): Adenoid cystic carcinoma, showing nests of cells with cylindromatous microcystic spaces, some filled with hyaline material (H & E x4). Fig. (4): Mucoepidermoid carcinoma showing mixture of epidermoid and intermediate cells, with tiny cystic space (H & E x4). Fig. (5): Squamous cell carcinoma in parotid gland, the cells showing nuclear pleomorphism and central keratinization in a desmoplastic stroma (H & E x4). Fig. (6): Acinic cell tumor showing acinar cells with basophilic granular cytoplasm and eccentric round nucleus (H & E x2).
5 Gina A. Nakhla, et al. 97 Fig. (7): Adenocarcinoma (Left) on top of pleomorphic adenoma (Right) (H & E x). Fig. (8): Basal cell adenoma showing basaloid cells in a solid and glandular pattern (H & E x). Discussion Salivary gland neoplasms represent only about 3 to 4% of all head and neck tumors. The salivary glands stand out as the tissue with probably the most diverse pathology in the human body. The WHO salivary gland tumour classification lists at least 38 subtypes of epithelial tumours alone, as well as several stromal types [3]. Regardless of this diversity, salivary gland tumours are rare; and most of them occur in the major glands (75-9%), []. The literature reports that the site of the tumours is distributed mainly between the parotid gland (about 8%) and submandibular gland (2%), while rarely are tumours found in the sublingual gland. Minor salivary gland tumours of the lips, oral cavity, pharynx, larynx, trachea, nasal mucosa, and paranasal sinuses are reported as uncommon (9-23%), [4]. The present study (received in the Pathology Department, Kasr El Aini Hospital) included 4 salivary gland tumors during the period between In our study, it was observed that benign tumors were the most frequent (68.6%), similar to most published series (6,5). Parotid major salivary glands were most commonly affected both in benign and malignant neoplasias, which is reported in the majority of the scientific series [3,5,6]. According to WHO, the average ages of patients with benign and malignant tumours are 46 and 47 years, respectively and the peak incidence is in the sixth and seventh decades [3]. In this study, the mean age was 44.7; the average age of patients with benign and malignant tumours was 44.6 and 44.7 years, respectively. The differ- ence was statistically insignificant and the peak incidence was in fifth and sixth decades. The mean age is in accordance with Al-Khateeb et al., [9] (4 years), Li et al., [] (4.38 years), Subhashraj, [] (46 years), Vargas et al., [5] (48 years), and Kamulegeya et al., [7] (34 years). In our study, there was a slight overall male predominance, with a male to female ratio of.2:; males. This finding coincides with some reports [7,], but differs from the majority of studies that showed a higher frequency among females [,5,9,7]. In our study, there was predominance of male in the fifth decades of life, which is different from studies by [7,8,9,2] which were in fourth decades. As regard the relation of sex to the nature of the tumor, in our study, benign tumors had a male predominance of 64.6%. On the other hand, 68.2% of malignant cases were females, which is highly significant. Although benign tumors were found to be more common in females [3,5,2], a few studies found an association between the male sex and benign tumours and the female sex and malignant tumours [8,22]. Concerning the aetiology of salivary gland tumours, the prevalence of pleomorphic adenoma and acinic cell carcinoma in women with a distinct peak in the 3rd decade of life, signalises a hormone influence, some studies have been performed in this subject [23], but without conclusive results. Among others, ethnicity and geographic locations have been proposed as having an effect on the frequency of occurrence of salivary gland tumours [24,25]. However, the data presently expressed, show similarities among those encountered all over the world [26-28], especially in relation to the sex,
6 972 Salivary Gland Neoplasms a Histopathological & Statistical Study mean age, and location. These findings may imply that common aetiologic agents might be acting regardless of ethnical and geographic location. Concerning the presenting symptoms, in our study, firm induration was found in 2.5% of patients with malignant lesions while 3% in benign cases, facial nerve palsy founded in 2% of the patients with malignant lesions and not detected in benign tumours. Skin ulceration was seen in 22.7% of malignant lesions. Thus, in agreement with [29], pain and firm induration were significant indicators of malignancy. Of all salivary gland tumors included in this study, 7.7% were located in the parotid gland, 7.6% in the submandibular gland, and 2.4% in the minor salivary glands. This result is similar to findings of most of the published reports [,9,]. In the study by Ito et al., [2], the parotid gland was the most frequent site, representing 7% of the cases, followed by the minor salivary glands and the submandibular gland with 22% and 8% of tumours, respectively. All large series of salivary gland tumours showed similar results [,3]. However, according to Vargas s et al., the submandibular gland is the most frequent site. In our study, 8.2% of benign tumors were in the parotid gland. In almost all published studies, the parotid gland was the predominant area of the benign tumors [,3]. 52% of malignant tumours were in the parotid gland followed by 43% in minor salivary glands. The most frequent malignant tumour of the parotid gland is mucoepidermoid carcinoma (3-5%), followed by adenoid cystic carcinoma (25%), carcinoma ex-pleomorphic adenoma (5%), and acinic cell carcinoma (5%) [2,3]. In our study, as regard the frequency of benign tumors, pleomorphic adenoma was the most commonly encountered type of salivary gland neoplasm (43.6%) followed by Warthin s tumor (2.4%), which is in agreement with findings from all of the published literature from all over world [,3]. The incidence of pleomorphic adenoma has been reported to range from between 4.8% and 7% [9]. On the other hand, the most common malignant salivary gland tumor was mucoepidermoid carcinoma.4% followed by adenoid cystic carcinoma 8.6%. The reports according to the prevalence of malignant salivary gland tumors were variable. Some authors (Yih et al., [6], Otoh et al., [7] & Vargas et al., [5]) have reported that mucoepidermoid carcinoma is the most frequent malignant salivary tumor, similar to our study, while adenoid cystic carcinoma was the most frequent malignant tumor found in other reports [8-,3,32]. In parotid gland, the present study confirms the findings of Wang et al., [3] and Li et al., [] that the pleomorphic adenomas (45.6%) are the most frequently seen tumor in parotid gland and representing 59.2% of benign parotid gland tumors. The most frequent malignant tumor in parotid gland was mucoepidermoid carcinoma representing /23 cases, (43.5%) followed by acinic cell carcinoma 3/23 cases (3%) of malignant parotid tumors. Although there is no consensus in the literature according to parotid gland malignancies, the majority of reports found that mucoepidermoid carcinoma is the most frequent parotid gland malignancy [2,5,]. According to Al-Khateeb and Ababneh, [9], the frequency of mucoepidermoid carcinoma and adenoid cystic carcinoma originating from the parotid gland was equal. On the other hand, other series have reported adenoid cystic carcinoma [32], carcinoma ex pleomorphic adenoma [], squamous cell carcinoma [7], and acinic cell carcinoma as the most common parotid gland malignancy. In the submandibular gland, we found that the most common benign tumor was pleomorphic adenoma 66.7%, which is consistent with the all of the previously published reports [5,7,32]. In this study, only two malignant cases were seen in this area, including, mucoepidermoid carcinoma, and lymphoma one case each. The adenoid cystic carcinoma is the most frequent malignant tumor of the submandibular gland by Al-Khateeb and Ababneh, (27) [9], Li LJ et al., (28) [] and Subhashraj, (28) []. The small number of cases in this site in our study may be the cause of such discrepancy. In our study, pleomorphic adenoma was the most frequent tumor of the minor salivary glands (33.3%), in agreement with Wang et al., [3] & Li et al., []. Adenoid cystic carcinoma was the most commonly encountered malignant tumor in the minor salivary glands /9 case (57.9%) followed by mucoepidermoid carcinoma 5/9 (26.3%). Although a great number of reports [,7-] corroborate our report, mucoepidermoid carcinomas
7 Gina A. Nakhla, et al. 973 were the most common malignant minor salivary gland tumors by Yih et al., [6] and Vargas et al., [5]. In the studies from outside of Japan, it has been reported that the most common malignant minor salivary gland tumours are adenoid cystic carcinomas and mucoepidermoid carcinomas. The incidence of adenoid cystic carcinomas and mucoepidermoid carcinomas has been reported to account for % and % of all tumours (.5-5.% and % of malignant tumours), respectively (8, 33). Similar to these findings, in our study adenoid cystic carcinoma represent 36.7% of all minor salivary gland tumors followed by mucoepidermoid carcinoma 6.7% (57.9% and 26.3% of malignant tumors) respectively. The discrepancies existing in the frequency and distribution of these tumours is possibly influenced by race and geographic location of the population in question. References - LI L.J., LI Y., WEN Y.M., LIU H. and ZHAO H.W.: Clinical analysis of salivary gland tumor cases in West China in past 5 years. Oral. Oncol., 44: 87-92, MINICUCCI E.M., De CAMPOS E.B., WEBER S.A., DOMINGUES M.A. and RIBEIRO D.A.: Basal cell adenoma of the upper lip from minor salivary gland origin. Eur. J. Dent., 2: 23-6, WANG D., LI Y., HE H., LIU L., WU L. and HE Z.: Intraoral minor salivary gland tumors in a Chinese population: A retrospective study on 737 cases. Oral. Surg. Oral. Med. Oral. Pathol. Oral. Radiol. Endod.,4: 94-, DHANUTHAI K., BOONADULYARAT M., JAENG- JONGDEE T. and JIRUEDEE K.: A clinico-pathologic study of 3 intraoral salivary gland tumors in Thais. J. Oral. Pathol. Med., 38: 495-5, VARGAS P.A., GERHARD R., ARAÚJO FILHO V.J. and De CASTRO I.V.: Salivary gland tumors in a Brazilian population: A retrospective study of 24 cases. Rev. Hosp. Clin. Fac. Med. Sao. Paulo., 57: 27-6, YIH W.Y., KRATOCHVIL F.J. and STEWART J.C.: Intraoral minor salivary gland neoplasms: Review of 23 cases. J. Oral. Maxillofac. Surg., 63: 85-, OTOH E.C., JOHNSON N.W., OLASOJI H., DANFILLO I.S. and ADELEKE O.A.: Salivary gland neoplasms in Maiduguri, north-eastern Nigeria. Oral. Dis., : 386-9, TOIDA M., SHIMOKAWA K., MAKITA H., KATO K., KOBAYASHI A., KUSUNOKI Y., et al.: Intraoral minor salivary gland tumors: A clinicopathological study of 82 cases. Int. J. Oral. Maxillofac. Surg., 34: , AL-KHATEEB T.H. and ABABNEH K.T.: Salivary tumors in north Jordanians: A descriptive study. Oral. Surg. Oral. Med. Oral. Pathol. Oral. Radiol. Endod., 3: e53-9, SUBHASHRAJ K.: Salivary gland tumors: A single institution experience in India. Br. J. Oral. Maxillofac. Surg., 46: 635-8, EVESON J.W. and CAWSON R.A.: A: Salivary gland tumours. A review of 24 cases with particular reference to histological histological types, site, age and sex distribution. J. Pathol., 46: 5-58, PONS VICENTE O., ALMENDROS MARQUÉS N., BERINI AYTÉS L. and GAY ESCODA C.: Minor salivary gland tumors: A clinicopathological study of 8 cases. Med. Oral. Patol. Oral. Cir. Bucal., 3: E582-8, BARNES L., EVESON J.W., REICHART P. and SIDRAN- SKY D.: (Eds), World Health Organization classification of tumours. Pathology and genetics of head and neck tumours. Lyon: IARC Press, 29-28, EVESON J.W. and CAWSON R.A.: B: Tumours of the minor (oropharyngeal) salivary glands: A demographic study of 336 cases. J. Oral. Pathol., 4: 5-59, PIRES F.R., PRINGLE G.A., ALMEIDA O.P. and CHEN S.Y.: Intra-oral minor salivary gland tumors: A clinicopathological study of 546 cases. Oral. Oncol., 43: 463-7, JABER M.A.: Intraoral minor salivary gland tumors: A review of 75 cases in a Libyan population. Int. J. Oral. Maxillofac. Surg., 35: 5-4, TIAN Z., LI L., WANG L., HU Y. and LI J.: Salivary gland neoplasms in oral and maxillofacial regions: a 23- year retrospective study of 6982 cases in an eastern Chinese population. Int. J. Oral. Maxillofac. Surg., 39: , JANSISYANONT P., BLANCHAERT J.R.R.H. and ORD R.A.: Intraoral minor salivary gland neoplasm: A single institution experience of 8 cases. Int. J. Oral. Maxillofac. Surg., 3: 257-6, VUHAHULA E.A.: Salivary gland tumors in Uganda: Clinical pathological study. Afr. Health Sci., 4 (): 5-23, ANSARI M.H.: Salivary gland tumors in an Iranian population: A retrospective study of 3 cases. J. Oral. Maxillofac. Surg., 65 (): , ITO F.A., ITO K., VARGAS P.A., ALMEIDA O.P. and LOPES M.A.: Salivary gland tumors in a Brazilian population: A retrospective study of 496 cases. Int. J. Oral. Maxillofac. Surg., 34: 533-6, MA AITA J., AL-KAISI N., AL-TAMIMI S. and WRAIKAT A.: Salivary gland tumors in Jordan: A retrospective study of 22 patients. Croat. Med. J., 4: , ABBEY L.M. and WITORSCH R.J.: Prolactin binding in minor salivary gland tumors. Oral. Surg. Oral. Med. Oral. Pathol., 6: 44-49, TAKEICHI N., HIROSE F., YAMAMOTO H., EZAKI H. and FUJIKURA T.: Salivary gland tumors in atomic bomb survivors, Hiroshima, Japan. II. Pathologic study and supplementary epidemiologic observations. Cancer, 52: , 983.
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