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Year : 2012  |  Volume : 8  |  Issue : 6  |  Page : 111-115

Minor salivary gland tumors of the oral cavity: A case series with review of literature

1 Department of Head and Neck Surgery, Tata Memorial Hospital, Mumbai, India
2 Department of Pathology, Tata Memorial Hospital, Mumbai, India

Date of Web Publication24-Jan-2012

Correspondence Address:
G H Pantvaidya
Department of Head and Neck Surgery, Tata Memorial Centre, Parel, Mumbai - 400 012
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0973-1482.92224

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 > Abstract 

Background: Minor salivary gland tumors (MSGTs) are unusual, accounting for only 15-20% of all salivary gland tumors. The commonest site of MSGTs of the head and neck is oral cavity.
Aims: To describe our experience with MSGTs of oral cavity seen over a period of one decade and elucidate their prognostic factors.
Materials and Methods: Over a period of 10 years, from 1991 to 2000, all MSGTs of oral cavity were analyzed. All demographic, treatment and survival data were recorded. Kaplan-Meier curves were used to find the survival. Multivariate analysis was performed using Cox regression.
Results: We treated 104 patients with curative intent. The commonest site was hard palate, accounting for 54.8% of all sites. The commonest histology was adenoid cystic carcinoma (45.2%). There were 17 (16.34%) pleomorphic adenoma cases, while the remaining 87 (83.66%) were minor salivary gland malignancies. Treatment was surgical in 91.3% of patients. Adjuvant radiotherapy was administered in 38.5% of patients. The median follow-up was 50 months. Recurrences were seen in 22 (25.3%) of the 87 malignant cases. Using Kaplan-Meier analysis, the expected 10-year overall and disease-free survivals were 75.2 and 65.8%, respectively. Survivals were better in non-adenoid cystic tumors (non-ACC). On multivariate analysis, T status, tumor grade and adjuvant therapy were independent prognostic factors for disease-free survival.
Conclusions: MSGTs of oral cavity have good overall survival despite recurrences. T stage, adjuvant radiotherapy and grade are independent prognostic factors for disease-free survival. Adenoid cystic tumors have worse outlook than non-ACC.

Keywords: Adenoid cystic carcinoma, minor salivary glands, minor salivary gland tumors, salivary gland tumors

How to cite this article:
Vaidya A D, Pantvaidya G H, Metgudmath R, Kane S V, D'Cruz A K. Minor salivary gland tumors of the oral cavity: A case series with review of literature. J Can Res Ther 2012;8, Suppl S2:111-5

How to cite this URL:
Vaidya A D, Pantvaidya G H, Metgudmath R, Kane S V, D'Cruz A K. Minor salivary gland tumors of the oral cavity: A case series with review of literature. J Can Res Ther [serial online] 2012 [cited 2021 May 8];8:111-5. Available from: https://www.cancerjournal.net/text.asp?2012/8/6/111/92224

 > Introduction Top

Salivary gland tumors account for only 3-5% of all head and neck cancers. Of these, only 15-20% tumors arise in the minor salivary glands. [1],[2] A large majority of these tend to be malignant. [3],[4] The minor salivary gland tumors (MSGTs) constitute a heterogenous group of pathologies, with varying tumor biology and hence exhibit varied clinical behavior. The commonest site of head and neck MSGTs is the oral cavity. [3] The relative rarity of these tumors is borne out by the fact that there are scarce publications detailing them. This poses a difficulty in the elucidation of the frequency, distribution, behavior and prognostic factors of these tumors. We present our experience with MSGTs of the oral cavity over a period of 10 years. The aim of the present study was to study the demographic features, site distribution, pathology, prognostic factors and the survival of MSGTs of the oral cavity.

 > Materials and Methods Top

We carried out a retrospective chart review of all patients presenting with MSGTs of the oral cavity from the year 1991 to 2000. Patients were identified from the hospital registry for this time period.

Demographic, clinico-radiological and pathological data were obtained from the hospital records. All the patients were treated with curative intent. The type of surgical procedure, margin status, recurrence and outcomes were analyzed. Pathological diagnosis of all patients was confirmed by an independent head and neck pathologist at our institute.

Statistical analysis was carried out using the SPSS 14.0 software (SPSS Inc., Chicago, Ill., USA). Kaplan-Meier curves were used to find the disease-free survival (DFS) and the overall survival (OAS). Univariate analysis was performed to identify the factors that were deemed pertinent to prognosis and survival. Multivariate analysis was performed using the Cox proportional hazards model to identify independent prognostic markers for DFS and OAS.

Included in this series are only tumors of the oral cavity proper. MSGTs of the oropharyngeal sites, such as tonsil and tongue base, were not included since they belong to a different site.

 > Results Top

There were 104 patients with oral MSGTs who were treated with a curative intent during a 10-year period from 1991 to 2000. The median age of presentation was 45 years with a range of 11-74 years. There was no gender predilection, with a male to female ratio of 1:1 (51 male patients and 53 female patients). The details of patient characteristics are given in [Table 1].
Table 1: Details of patient characteristics

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Of the 104 MSGTs, 87 were recognized as malignant, while 17 were benign tumors. All of these 17 benign MSGTs were pleomorphic adenomas. Amongst the malignant tumors, the most common pathology was adenoid cystic carcinoma. The details of pathology are given in [Table 2].
Table 2: Pathology of oral cavity MSGTs

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The most common site of the oral MSGTs was the hard palate, being the site of involvement in 57 patients (54.8%).

Of the malignant MSGTs (87 patients), 13 patients (14.9%) had neck nodes on presentation.

Of the 104 patients, 68 (65.4%) were treated per primum at our center. The remaining 36 patients (34.6%) had received some prior treatment elsewhere. Majority of the patients in this series (95 patients, 91.3%) were treated by surgery, followed by postoperative radiation where required. Five patients who were operated elsewhere were treated with adjuvant radiotherapy (RT) alone, while four were observed without further treatment as they had received adequate treatment prior to consulting our institute.

Ninety-five patients were treated with surgery. Surgery included wide excisions of the palate, buccal mucosa or lip, infrastructure maxillectomies, palatectomies, marginal mandibulectomies and a segmental mandibulectomy. Amongst the cases where the resection status was recorded intraoperatively, an R0 resection, that is a complete gross and microscopic resection of the tumor, was achieved in 71 cases (74.7%) and an R1 resection (gross total resection, but seemingly positive microscopic margins) was achieved in 24 patients (25.3%), while no patients were recorded to have gross residual disease at surgery. Cut margins were negative (>5 mm away and free) in 67 (70.5%) cases, close (<5 mm away and free) in 8 (8.5%) cases and involved in 20 cases (21%).

Postoperative radiotherapy (PORT) was advised in 43 patients (41.4%), but 40 (38.5%) received it. Indications for adjuvant RT were close or positive cut margins, node positive tumors, T3, T4 tumors and recurrent tumors.

There were 17 patients with benign pleomorphic adenomas in the present study. These were most commonly seen in the palate (10 patients), followed by buccal mucosa and lip. There were no cases with neck nodes on presentation. All of these tumors were treated with a complete R0 resection. All resections had clear-cut margins on final histopathology. No adjuvant treatment was instituted for these benign tumors. There were no recurrences in the benign group of MSGTs. Hence, they were neither considered for survival analysis nor included in the multivariate analysis. The further discussion of results is therefore limited to malignant MSGTs.

Of the 87 malignant tumors, locoregional recurrences were seen in 16 (18.4%) cases. When the adenoid cystic tumors (ACC) were compared to non-adenoid cystic tumors (non-ACC), recurrences occurred in 12 of 47 (25.5%) ACC as compared to 4 of 40 (10%) non-ACC tumors (Chi-square, P = 0.05). There were six cases of distant recurrences, of which five were ACC.

For estimating survival, only the 87 patients of malignant tumors were taken into consideration. With a median follow-up of 50 months, the estimated 5- and 10-year OAS and DFS were 87.3 and 75.2%, and 77.2 and 65.8%, respectively [Figure 1] and [Figure 2]. When the DFS of ACC and non-ACC tumors was compared, the estimated 5- and 10-year DFS were 66.1 and 44.1%, respectively (for ACC tumors), and 89.4 and 81.3%, respectively (for non-ACC tumors). This difference was statistically significant (logrank test, P = 0.02). Similarly, the estimated 5- and 10-year OAS was also better in non-ACC tumors (94.4 and 85.9%, respectively) as compared to those of ACC tumors (80.8 and 60.6%, respectively; logrank test, P = 0.04) [Figure 3] and [Figure 4].

We performed univariate and multivariate analysis to identify factors that were pertinent to DFS. The prognostic factors included were T status (T1, T2 vs. T3, T4), presence of nodes (positive vs. negative) intraoperative R status (R0 vs. R1), cut margins (positive or close vs. negative), grade of tumor and adjuvant radiation (yes vs. no).
Figure 1: Kaplan– Meier curve showing overall survival of malignant minor salivary gland tumors

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Figure 2: Kaplan– Meier curve showing disease-free survival of malignant minor salivary gland tumors

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Figure 3: Kaplan– Meier curve showing comparison of disease-free survivals between adenoid cystic carcinomas and non-adenoid cystic carcinomas

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Figure 4: Kaplan– Meier curve showing comparison of overall survivals between adenoid cystic carcinomas and non-adenoid cystic carcinomas

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Multivariate analysis was done using Cox regression method. On Cox regression multivariate analysis, the factors prognostic of DFS were T stage (P = 0.029), adjuvant RT (P = 0.043) and grade of tumor (P = 0.05). Patients with T1 or T2 tumors did significantly better than those with T3 or T4 tumors. With respect to grade, there was significant difference in the DFS between low-and high-grade (P = 0.01) tumors as well as between intermediate- and high-grade (P = 0.01) tumors [Figure 5]. Also, patients who had received adjuvant RT had better DFS as compared to those who had not.
Figure 5: Kaplan– Meier curve showing comparison of disease-free survivals according to grade of tumor

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Univariate and multivariate analysis was also done separately for the 47 patients of ACC tumors, where perineural invasion (PNI) was also included as a prognostic factor in addition to the above factors. PNI was found to be a significant prognostic factor for DFS on univariate analysis (P = 0.02), but showed a non-significant trend for better DFS on multivariate analysis (P = 0.06).The independent significant prognostic factors for DFS of ACC on multivariate analysis were grade (P = 0.05) and adjuvant RT (P = 0.01).

The results of univariate and multivariate analysis are given in [Table 3].
Table 3: Univariate and multivariate analysis of prognostic factors for disease free survival

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 > Discussion Top

MSGTs, though most commonly found in oral cavity, are still a relatively rare entity. [3] The varied histology, clinical presentation and behaviour implies varied prognosis of these tumors. In the absence of level-one evidence and given the rarity of these tumors, the treatment decisions will have to be based on retrospective studies which have looked at the survival and prognostic factors. The present study was a single institution experience of 104 cases over a period of 10 years, which has included a detailed survival analysis and multivariate analysis of prognostic factors.

The median age of presentation in our study was 45 years. This is in agreement with literature, where the commonest age group for MSGTs was found to be in 4 th to 7 th decades. [5],[6],[7] Some studies have reported a slight female predilection, [3],[5],[7],[8] while others have reported a slight male predominance. [9],[10],[11] In our study, however, the tumors were equally found in both genders.

The commonest site of the MSGTs was hard palate (54.8%), a finding similar to that described in literature. [3],[5],[7],[10],[11]

In large studies that have included both benign and malignant MSGTs, the proportion of malignant tumors was found to be 63-82%. [2],[12] In the present study, 87 patients (83.65%) had malignant tumors. This high incidence of malignant MSGTs could perhaps be attributed to referral bias, as ours is a tertiary cancer referral institution.

Literature has shown that the two most common malignant salivary gland tumors are ACC and muco-epidermoid carcinoma (MEC). Some studies reported ACC to be the commonest, [4],[8],[12],[13] while most others found MEC to be the commonest. [5],[7],[11],[14],[15] Buchner et al. postulate that geographical and ethnic differences probably play a role in the relative frequency of ACC and MEC. [5]

Surgery is the mainstay of treatment of oral cavity MSGTs; [5],[7],[14],[16] and in the present study, all patients had undergone surgical resection. Wide local excision with adequate free surgical margins is necessary for better prognosis and outcome. [17]

Positive surgical margins have widely varied in literature, ranging from 3.4 to 40%. [17] In our study, positive margins were present in 21% of the cases. Some authors have reported free surgical margins as an important prognostic factor; [18],[19] however, we found only a non-significant trend toward better DFS with clear surgical margins on multivariate analysis (P = 0.07).

The role of adjuvant RT is less well defined, and is extrapolated from evidence in major salivary gland tumors. [9] In our institution, adjuvant RT was offered for T3 and T4 tumors, high-grade tumors, close or positive cut margins, presence of metastatic nodes and in case of perineural infiltration. On Cox regression analysis, we found adjuvant RT to be a significant prognostic factor predicting DFS, and hence emphasize the need for multimodality therapy even in oral MSGTs. Literature review revealed that ours was the only study where adjuvant RT was found to be a prognostic factor on multivariate analysis.

We performed survival analysis using the Kaplan-Meier method. We found that OAS was uniformly better than DFS; this indicates that though there were recurrences after treatment, these could be salvaged with a good OAS. When the DFS was compared between the ACC and non-ACC pathologies, we found that DFS was significantly better in non-ACC tumors. Kakarala et al. found similar significant difference in OAS and DFS based on tumor histology on univariate and multivariate analysis. [7] However, Spiro et al. reported their 45-year experience treating 459 patients with minor salivary gland cancer and found that histologic subtype did not independently predict survival. [20]

On Cox regression multivariate analysis, we found that T stage, grade of tumor and adjuvant RT were independent risk factors for DFS. Carillo et al., in a multivariate model, identified tumor size, grade, surgical margins and lymph node status significant for DFS. [19] Kakarala et al., in a SEER database review of 639 oral MSGTs, found T and N stage as the most significant predictors of survival. [7] Mucke et al., in a review of 95 cases, found T stage, N stage, UICC stage and resection margin status as the independent factors predicting OAS. [17] Apart from the present study, only one previous study by Carillo et al.[19] found prognostic significance and good stratification regarding grade in multivariate analyses for oral MSGTs.

We found PNI to be an important prognostic factor for ACC tumors for DFS on univariate, but not on multivariate analysis. The importance of PNI in ACC tumors was pointed out by several authors. [21],[22] Agarwal et al., in a multivariate analysis, found PNI to be an independent prognostic factor of DFS in ACC tumors. [23]

This was a retrospective study with its attendant shortcomings. However, in the absence of large prospective studies due to the rarity of these tumors, evidence would have to be sought from the analysis of similar such studies.

 > Conclusions Top

MSGTs of the head and neck are most commonly found in the oral cavity. Despite this, they comprise an unusual entity and exhibit a varied pathology, clinical presentation and prognosis. We found that these tumors have a good OAS, despite increased incidence of locoregional recurrence, thereby making a case for aggressive salvage of recurrent tumors. On multivariate analysis, we found T stage, grade of tumor and adjuvant RT to be the important prognostic factors for DFS. This underlines the importance of multimodality therapy consisting of upfront surgery followed by PORT in high-stage, high-grade tumors or those with high-risk factors on histopathology.

 > References Top

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12.Ito FA, Ito K, Vargas PA, de Almeida OP, Lopes MA. Salivary gland tumors in a Brazilian population: a retrospective study of 496 cases. Int J Oral Maxillofac Surg 2005;34:533-6.  Back to cited text no. 12
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19.Carrillo JF, Maldonado F, Carrillo LC, Ramirez-Ortega MC, Pizano JG, Melo C, et al. Prognostic factors in patients with minor salivary gland carcinoma of the oral cavity and oropharynx. Head Neck 2011;33:1406-12.  Back to cited text no. 19
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21.Garden AS, Weber RS, Morrison WH, Ang KK, Peters LJ. The influence of positive margins and nerve invasion in adenoid cystic carcinoma of the head and neck treated with surgery and radiation. Int J Radiat Oncol Biol Phys 1995;32:619-26.  Back to cited text no. 21
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23.Agarwal JP, Jain S, Gupta T, Tiwari M, Laskar SG, Dinshaw KA, et al. Intraoral adenoid cystic carcinoma: prognostic factors and outcome. Oral Oncol 2008;44:986-93.  Back to cited text no. 23


  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]

  [Table 1], [Table 2], [Table 3]

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