Clinicopathological features of salivary and non-salivary adenoid cystic carcinomas

doi:10.1016/j.ijom.2011.12.022

International Journal of Oral and Maxillofacial Surgery

Volume 41, Issue 3, March 2012, Pages 354-360

https://doi.org/10.1016/j.ijom.2011.12.022 Get rights and content

Abstract

Adenoid cystic carcinoma (ACC), commonly from salivary glands, is known for its insidious local growth and usually protracted clinical course. ACC developing from non-salivary glands (i.e., non-salivary ACC) is heterogeneous, and its clinicopathological features remain poorly defined. Patients treated for ACC in a single institution between 1995 and 2007 were included in this study. Immunohistochemical evaluation of Ki-67, E-cadherin, p16, and cyclinD1 was performed. The prognostic significance of clinical and immunophenotypic markers was evaluated. 83 cases of salivary ACC and 24 cases of non-salivary ACC were included. The expression levels of Ki-67 (54.8%), E-cadherin (90.4%), p16 (32.9%), and cyclinD1 (19.2%) between ACCs present at various sites were not different. Sinonasal, lacrimal, and tracheobronchial ACCs had significantly worse outcomes than those of ACC of the major salivary glands. Postoperative radiotherapy reduced the recurrence rate of patients with a negative resection margin (P = 0.028). Older age (age >60 years), advanced stage, positive resection margin, high histological grade, and high expression of Ki-67 were significantly correlated with poor prognosis. In conclusion, the site of origin plays a role in the prognosis of ACC, in which positive resection margin and advanced stage are possible factors underlying the differences in outcomes.

Section snippets

Patients and clinical characteristics

Patients who were newly diagnosed with ACC of the head and neck and treated at National Taiwan University Hospital from 1995 to 2007 were selected from the Cancer Registry of National Taiwan University Hospital and were included in this study. ACC originating from salivary glands or secretory glands contributing to salivation within or near the oral cavity is defined as salivary ACC. ACC from secretory glands not contributing to salivation beyond the oral cavity of the head and neck is defined

Clinicopathological features

101 patients, with a median age of 49 years (range 16–86 years), met the inclusion criteria (Table 1). There were 44 male and 57 female patients. 32 patients had ACC of the major salivary gland, 51 of the minor salivary gland, and 18 of non-salivary glands. Minor salivary gland ACC included intraoral and sinonasal ACC, and non-salivary ACC was composed of ear, lacrimal, and tracheobronchial ACC. Histological grade 1 (61.4%), perineural invasion (70.3%), and positive resection margin (62.4%)

Discussion

In this study, the authors found that: the prognosis of sinonasal, lacrimal, and tracheobronchial ACC is worse than major salivary gland ACC; older age, advanced stage, positive resection margin, high histological grade, and higher expression of Ki-67 were associated with poor outcomes; and postoperative RT might improve EFS in ACC patients with negative resection margins.

The origin of ACC had been reported as playing a role in prognosis. Khan et al. reported that sinonasal ACC had worse

Competing interests

None declared.

Funding

Supported by grant FEMH-99-C-038.

Ethical approval

IRB approved, NTUH-REC No 200707037R.

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particularly, muscular denervation can be considered a secondary sign of nerve damage: firstly, in acute and subacute stages, oedema appears, while the chronic appearance is characterized by fatty replacement of muscle tissue and by muscular atrophy [17]. However, the possibility that many other conditions, such as infection, inflammation, trauma, vascular lesion, and hematoma can mimic a neoplasm of the head and neck region must be considered [19]. sensitivity of MRI is superior to CT scan (95% -to 100%) in detecting ACC's perineural spread along the skull base, but the sensitivity, when mapping the extent of disease, decreases to 63% [18].
Adenoid cystic carcinoma (ACC) represents approximately 10% of all epithelial salivary neoplasms and most commonly involves the parotid gland.
We report CT and MRI finding of a 38-year-old young man presented to our ENT department with 02 years history of an external auditory canal stenosis. Physical examination revealed bilateral parotid gland swelling with a complete stenosis of the left external auditory canal.
Temporal bone contrast enhanced CT-SCAN revealed is an isodense enhancing mass measuring 4 cm involving posterior and inferior external auditory canal wall, and invading the superficial lobe of the homolateral parotid gland. No bone erosion was noted. MRI investigation has shown a tumor process highly suspicious of malignancy centered on the left EAC involving the superficial lobe of the homolateral parotid gland. Adenoid cystic carcinoma (ACC) of the parotid gland was the final diagnosis, after surgical biopsy and histopathological examination. The Pre-operative check-up demonstrated multiple round shape lung lesions suggestive of multiple metastases. Considering the metastatic stage of the tumor, a collegial decision to adopt a palliative treatment approach based on chemotherapy was taken by the multidisciplinary oncology board.
Impact of tumor site on the prognosis of salivary gland neoplasms: A systematic review and meta-analysis
2021, Critical Reviews in Oncology/Hematology
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Different head and neck sites and histological types were compared. Twenty studies were included in the OS analysis (Hay et al., 2019; Ouyang et al., 2017; Lin et al., 2012; Gencturk et al., 2019; Kawakita et al., 2020; Amit et al., 2014, 2015a; Amit et al., 2015b; Ellington et al., 2012; Feinstein et al., 2011; Ferrell et al., 2019; Hong et al., 2015; Mahmood et al., 2011; Nam et al., 2016; Oliver et al., 2019; Otsuka et al., 2016; Patel et al., 2015; Suzuki et al., 2015; Terhaard et al., 2004). For disease-specific survival, five articles with sufficient data were included (Amit et al., 2014, 2015a; Amit et al., 2015b; Biron et al., 2015).
In numerous types of cancer, the primary tumor site can show a correlation with disease behavior and survival outcomes. In salivary gland tumors (SGTs) this association remains controversial. This study assessed the association between primary sites of SGTs and prognosis. Studies from five databases were assessed and a meta-analysis was performed using studies that presented 95 % confidence interval (95 % CI), hazard ratio (HR) and survival analysis. Gathered information from 46,361 patients showed that site had a prognostic impact on SGTs. Tumors involving minor salivary glands showed worse overall survival (HR = 1.60; 95 % CI = 1.17–2.19; p = 0.003), disease-specific survival (HR=1.63; 95 % CI = 1.12−2.37; p = 0.01), and cause-specific survival (HR=2.10; 95 % CI = 1.72−2.55; p = 0.00001). Tumors from major salivary glands showed better recurrence-free survival (HR=2.31; 95 % CI = 1.77−3.02; p = 0.00001), and locoregional control of disease (HR=2.66; 95 % CI = 1.20−5.91; p = 0.02). Our results showed that the primary site of SGTs has an impact on patient prognosis.
Expression of EpCAM in adenoid cystic carcinoma
2018, Pathology
Citation Excerpt :
We showed that tumour location tends to affect ACC patients' progression-free survival by multivariate analysis. Lin et al. compared the ACCs of salivary and non-salivary origin, and they also found that sinonasal, lacrimal, and tracheobronchial ACCs had significantly worse outcomes than ACCs of the major salivary glands.40 The different patients' outcomes between salivary and non-salivary sites of tumour may come from difficulties of diagnosis and complete resection as well as different tumour biologies, but further studies are required to clear these differences according to tumour location.
The mutational landscape of adenoid cystic carcinoma (ACC) is currently being revealed, but further studies are needed to identify biomarkers as therapeutic targets or prognostic factors of ACC. In this study, we investigated the expression of epithelial cell adhesion molecule (EpCAM) in ACCs. We retrospectively collected 83 cases of surgically resected ACCs. Using tissue microarray, we conducted immunohistochemical staining using the anti-EpCAM antibody. EpCAM expression was analysed by intensity score and the total immunostaining score. The positivity was 97.6% (81/83 cases), regardless of the intensity score. A higher histological grade (p = 0.006) and specific tumour location (non-salivary gland origin, p = 0.02) showed a correlation with higher EpCAM intensity. Higher EpCAM expression by total immunostaining score was associated with histological grade (p = 0.004), distant metastasis (p = 0.004) and poorer prognosis (overall survival p = 0.015 and progression-free survival p = 0.033). We suggest EpCAM as a candidate prognostic marker and a putative therapeutic target in ACC. Also, ACCs arising from salivary gland and non-salivary gland sites, respectively, might display different pathophysiologies in which EpCAM could play a role.
Diagnosis and Management of Malignant Salivary Gland Tumors of the Parotid Gland
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Immunoprofile of c-MET/PI3K signaling in human salivary gland tumors
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The aim of this study was to analyze the expression pattern of proteins in the HGF/c-MET/PI3K signaling pathway in salivary gland tumors (SGTs) and to correlate the findings with the proliferative index and clinical parameters.
We assembled tissue microarrays (TMAs) of 108 cases of SGTs, including 69 cases of pleomorphic adenoma (PA), 24 cases of adenoid cystic carcinoma (AdCC), and 15 cases of mucoepidermoid carcinoma (MEC). An immunohistochemical analysis of hepatocyte growth factor (HGF), MET phosphorylation (p-MET), protein kinase B (AKT) phosphorylation (p-AKT), and Ki-67 proteins was performed.
Benign and malignant SGTs presented similar scores of HGF-positive cells (P = .36), whereas, malignant SGTs exhibited higher levels of p-MET (P = .001) and p-AKT (P = .001) than benign SGTs. No correlation of HGF, p-MET, or p-AKT expression was observed with clinical parameters. PA had a lower proliferative index than either AdCC (P = .001) or MEC (P = .001).
The salivary gland carcinomas exhibited increased activation of the HGF pathway, as evidenced by the phosphorylation of the MET receptor, and increased activation of the PI3K pathway, as indicated by p-AKT. These data suggest that the HGF/c-MET/PI3K signaling pathway is active in SGTs, especially in malignant neoplasms.
Focused review of investigation, management and outcomes of salivary gland disease in specialty-specific journals
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For certain salivary gland tumours, the site of origin affects the prognosis. Acinic cell carcinomas located in the sinonasal, lacrimal, and tracheobronchial regions have a worse outcome because they occur in anatomically confined areas and complete excision is difficult.61 Radiotherapy reduces recurrence, but increasing age, grade and stage, invaded margins, nodal disease, and tumours that express Ki-67, carry a poorer prognosis.61,62
We review papers on diseases of the salivary glands published in journals relating to the head and neck, which are commonly read by members of our specialty. Most of the papers focus on the investigation and treatment of diseases of the parotid gland, which reflects the relative prevalence of parotid lesions among salivary gland diseases. Minimally invasive surgery is increasingly of interest. There is a lack of clinical trials that address the many controversies concerning salivary gland surgery, and much of the evidence for treatment is based on small case series and expert opinion, partly because of the relative rarity of salivary disease and the disparate groups that treat it. This problem could be addressed if regional and national oral and maxillofacial surgery (OMFS) units, and possibly other specialties, could collaborate more closely and combine data.

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Clinical PaperHead and Neck OncologyClinicopathological features of salivary and non-salivary adenoid cystic carcinomas

Abstract

Section snippets

Patients and clinical characteristics

Clinicopathological features

Discussion

Competing interests

Funding

Ethical approval

Hum Pathol

Int J Radiat Oncol Biol Phys

Ann Oncol

Mod Pathol

Mod Pathol

Am J Otolaryngol

J Oral Maxillofac Surg

Gynecol Oncol

Outcomes in patients with adenoid cystic carcinoma of the lacrimal gland

Ophthal Plast Reconstr Surg

Reduced E-cadherin expression correlates with unfavorable prognosis in adenoid cystic carcinoma of salivary glands of the oral cavity

Am J Clin Pathol

Adenoid cystic carcinoma of salivary and lacrimal gland origin: localization, classification, clinical pathological correlation, treatment results and long-term follow-up control in 84 patients

Anticancer Res

Long-term survival after resection of primary adenoid cystic and squamous cell carcinoma of the trachea and carina

Ann Thorac Surg

Clinical Paper
Head and Neck Oncology
Clinicopathological features of salivary and non-salivary adenoid cystic carcinomas