Ultrasonography characteristics of cystic components in primary salivary gland tumors

doi:10.21203/rs.3.rs-2218298/v1

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Ultrasonography characteristics of cystic components in primary salivary gland tumors

https://doi.org/10.21203/rs.3.rs-2218298/v1

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Objectives The present study aimed to characterize the ultrasonography (US) features of cystic components in salivary gland tumors (SGTs).

Material and methods A total of 207 patients (218 lesions) with pathologically confirmed primary SGTs were analyzed. Preoperative US revealed the presence of cystic components in lesions. Lesion size, shape, margin, and US findings of the cystic components, including number, distribution, margin, occupying rate, and internal characteristics, were evaluated.

Results Similarities were observed between the US performance of benign SGTs (B-SGTs) and malignant SGTs (M-SGTs) with cystic components. Differences in sex and age of patients, number, distribution, and internal characteristics of cystic components were statistically significant. For SGTs with cystic components, the proportions of M-SGTs to ill-defined margins (P = 0.002), eccentric distribution (P = 0.019), and none of the internal characteristics (P = 0.019) were significantly higher than those of B-SGTs. For every one-year increase in age, the presence of B-SGTs increased by 4.9%

(95% confidence interval for the odds ratio, 1.020-1.078). The risk of ill-defined margins for the presence of M-SGTs was 10.030 times higher than that for well-defined margins (95% confidence interval for odds ratio, 3.377-29.787). Cystic component features needed to be combined with lesion indicators (border and shape) to improve diagnostic sensitivity.

Conclusions US features of the B-SGTs and M-SGTs were significantly different. Cystic component is of interest in the US-related differential diagnosis of B-SGT and M-SGT.

Clinical Relevance Cystic components are potentially valuable in the differential diagnosis of B-SGTs and M-SGTs on US.

Salivary gland tumor

Cystic component

Ultrasonography

Pleomorphic adenoma

Warthin tumor

Salivary gland tumors (SGTs) are rare, representing 2-6.5% of all head and neck neoplasms¹. The parotid gland is the most common site, followed by the submandibular gland. Benign SGTs (B-SGTs) are predominantly represented by pleomorphic adenoma (PA) and Warthin’s tumor (WT). Malignant SGTs (M-SGTs) are mainly represented by mucoepidermoid carcinomas and adenoid-cystic carcinoma². Accurate predictions of the histopathologic characteristics of tumors along with radiologic findings are useful for adequate surgical planning, especially for avoiding unnecessary surgeries and consequent complications³.

Ultrasonography (US) is readily available, cost-effective, and widely accepted by patients. US is considered a basic examination for the preoperative assessment of SGTs. US findings for the differentiation of B-SGTs and M-SGTs have been well described, primarily emphasizing the shape, margins, lymph node enlargement, and vascularity⁴. However, the sensitivity of US is low⁵.

Cystic components have been reported as common imaging features of SGTs^6,7. Magnetic resonance imaging (MRI) manifestations of cystic components in benign and malignant tumors differ⁸. No studies have compared the US manifestations of cystic components in SGTs. This study aimed to describe the US features of cystic components in SGTs and determine whether these features can be useful as indicators for differential diagnosis.

We reviewed the patients’ medical data and identified 1172 patients (1210 lesions) with histopathologically confirmed primary SGTs who had received preoperative US between January 2015 and 2018. The US images stored in the picture archiving and communication system were reviewed, and 207 patients (218 lesions) with cystic components were included in this study (Fig. 1). Patients without cystic components and those with unclear US findings were excluded.

Imaging Methods

US was performed using an Aplio 500 (Toshiba, Tokyo, Japan) and MyLab Twice (Esaote, Italy) systems. The transducers used were 14L5 and LA533. Data from the first preoperative examination were considered. Two certified radiologists with experience in head and neck imaging independently reviewed the US images. They were blinded to the pathological types. Disagreements regarding the imaging features were resolved by consensus.

Preoperative Evaluations

Clinical characteristics included sex, age, region, pathological type. Tumor size was considered to be the maximal length of the transverse section. Lesion shapes were divided into regular (round and oval) and irregular (including lobulated). The margin characteristics were classified as well-defined or ill-defined from the surrounding normal gland tissue.

Cystic components were defined as echoless on gray-scale US. Evaluated imaging findings of cystic components included number (single or multiple), distribution, margin, occupying rate, and internal characteristics.

Distribution was classified by location: eccentric, central, scattered, and entire (Fig. 2). The scattered distribution comprised two types: tumors with a few small circular anechoic areas and tumors with a sponge-like appearance, in which large and small anechoic areas are finely mixed within the solid part. The entire distribution comprised two other types: entire tumor cystic and hyperechoic separation evident inside.

The occupation rate was categorized into four grades (1–4) as follows:1, small occupying area of 1–25% of the tumor; 2, moderate (26–50%); 3, extensive (51–75%); and 4, diffuse (76–100%).

Statistical Analyses

Statistical analyses were performed using SPSS Statistics for Windows version 28.0 (IBM Corp., Armonk, NY, USA). Student’s t-test, Mann-Whitney U test, Pearson’s χ² test, and Fisher’s exact test were used to analyze the US findings of cystic components in SGTs. The Hosmer-Lemeshow test was used to assess the goodness of fit of the logistic regression model. P < 0.05 indicated statistical significance.

Thirty-one patients with M-SGTs and 176 with B-SGTs were included. Eleven patients with B-SGTs had two masses; in all cases, both masses were Warthin tumors. None of the patients with M-SGT had multiple lesions.

Clinical Characteristics

Eighteen types of SGTs underwent preoperative US. These included seven types of benign tumors and 11 types of malignant tumors (Supplementary Table 1). Oncocytoma, myoepithelioma, poorly differentiated carcinoma, and sebaceous carcinoma displayed obvious cystic components by US. The proportion of cystic components in M-SGTs (31/135, 22.9%) was slightly higher than that in benign tumors (187/1025, 18.2%), but the difference was not statistically significant (Pearson’s χ² test, P = 0.187).

Among B-SGTs, lymphadenomas had the highest frequency (1/1, 100%) of cystic components. Warthin tumors (115/187, 61.5%) accounted for the highest proportion of B-SGTs with cystic components. Among M-SGTs, acinar cell carcinoma had the highest frequency (7/14, 50%) of cystic components. Mucoepidermoid carcinomas (9/31, 29%) accounted for the highest proportion of M-SGTs with cystic components. Relevant clinical findings are described in Table 1.

Table 1

Clinical characteristics of salivary gland tumor
Variables	M-SGTs	B-SGTs	P value
n	31	176
Sex^*			0.019
Male	18	137
Female	13	39
Age (y)^*			< 0.001
Average ± SD	43.7 ± 3.5	56.0 ± 1.0
Region			0.507
Parotid gland	28	175
Submandibular gland	3	12
M-SGT, malignant salivary gland tumor; B-SGT, Benign salivary gland tumor.
^* difference was statistically significant.

The proportion of males with B-SGTs was significantly higher than those with M-SGTs. The difference between males and females was statistically significant (Pearson’s χ² test, P = 0.024). The age of onset for M-SGTs was significantly younger than that for B-SGTs (Mann-Whitney U test, P < 0.001). The vast majority of primary M-SGT and B-SGT events occurred in the parotid gland (90.3% and 93.6%, respectively). Occurrence in the submandibular glands was rare (Pearson’s χ² test, P = 0.507).

Gray-scale Us Characteristics

The gray-scale US characteristics of M-SGTs and B-SGTs are summarized in Table 2. Patients with multiple masses were evaluated. The lesion size of M-SGTs was slightly smaller than that of B-SGTs (11–51 vs. 9–73 mm; Student’s t-test, P = 0.452). Most M-SGTs and B-SGTs had multiple cystic components (61.3% and 65.2%, respectively). No significant difference was detected between M-SGTs and B-SGTs in the number of cystic components (Fisher’s exact test, P = 0.670).

Table 2

Imaging findings of cystic components
Variables		M-SGT	B-SGT		P value
n		31(100)	187 (100)
Lesion Size (mm)	28.0 ± 1.9			29.6 ± 0.8	0.452
Number					0.670
Single		12 (38.7)	65 (34.8)
Multiple		19 (61.3)	122 (65.2)
Margin^*					0.002
Well-defined		14 (45.2)	137 (73.2)
Ill-defined		17 (54.8)	50 (26.7)
Distribution^*					0.019
Eccentric		16 (51.6)	64 (34.2)
Central		7 (22.6)	21 (11.2)
Scattered		8 (25.8)	91 (48.6)
Entire		0	11 (5.9)
Occupying rate					0.786
1		19(61.3)	101 (54.0)
2		6(19.4)	35 (18.7)
3		2 (6.5)	22 (11.8)
4		4(12.9)	29 (15.5)
Internal characteristic^*					0.019
Presrnt		12 (38.7)	115 (61.5)
None		19 (61.2)	72 (38.5)
M-SGT, malignant salivary tumor; B-SGT, Benign salivary tumor;
^* difference was statistically significant.

A significant difference was noted between the cystic components of M-SGTs and B-SGTs with respect to their distribution (Fisher’s exact test, P = 0.019). The proportion of M-SGTs showing an eccentric distribution was significantly higher than that of the B-SGTs (51.6% vs. 34.2%). M-SGTs and B-SGTs differed in their cystic component margin characteristics. Most M-SGTs (54.8%) exhibited an ill-defined border, whereas most B-SGT lesions (73.2%) had well-defined margins. A significant difference was observed (Pearson’s χ² test, P = 0.002). Most M-SGT and B-SGT lesions had a low occupying rate of cystic components (61.3% and 54%, respectively), with no significant difference (Pearson χ² test, P = 0.786).

The evaluated internal characteristics included papillary structures and spongiform cysts. Most M-SGT lesions lacked these characteristics (61.2%), while the majority of B-SGT lesions (61.5%) had one of the two features (Supplementary Table 2). A significant difference was evident (Pearson’s χ² test, P = 0.019).

Multi-factor Analysis

Based on the above results, sex, age, distribution, margin, and internal characteristics were used as variables for binary logistic regression analysis. The outcome was benign or malignant. Two indicators were statistically significant: age (P < 0.001) and margin (P < 0.001). For every one-year increase in age, the presence of B-SGTs increased by 5.6% (95% confidence interval [CI] for the odds ratio [OR], 1.025–1.088). The risk of ill-defined margins for the presence of M-SGTs was 8.577 times higher than that for well-defined margins (95% CI for OR, 3.2-28.662). The Hosmer-Leme show goodness of χ² fit value was 8.217 (P = 0.413).

Efficacy Of Us Features In Diagnosis Of M-sgts

In terms of the diagnostic efficacy of cystic components, the sensitivity and specificity for diagnosing M-SGTs alone were low (Table 3). In addition, the ability of the lesion features of shape and margin in combination with cystic components to diagnose M-SGTs was assessed. When two or more of the indicators were present, the sensitivity of the diagnosis was highest (83.9%). An ill-defined margin of the lesion had the highest specificity (98.9%) for diagnosing malignancy.

Table 3

Efficacy of image features in the diagnosis of M-SGTs
Feature	Sensitivity	Specificity
Cystic components
Ill-defined margin	54.8%	73.2%
Eccentric distribution	51.6%	65.8%
No internal characteristic	61.3%	61.5%
Lesion
Ill-defined margin	64.5%	98.9%
Irregular shape	35.5%	98.4%
Two or more above features	83.9%	73.8%
M-SGT, malignant salivary tumor.

Cystic Components In Pas And Wts

The cystic components in PAs and WTs were significantly different in the US (Table 4). Compared with PA, most WT cystic components had multiple (80.9% and 31.8%, respectively), scattered distribution (73.9% and 11.4%, respectively), and internal characteristics (87.8% and 9.1%, respectively). The probability of an ill-defined margin (38.3% and 6.8%, respectively) was greater than that of PA. Moreover, the proportion of small occupying rate of cystic components (< 25%) in WTs was smaller than that in PAs (52.3%, and 75%, respectively).

Table 4

Cystic components in pleomorphic adenoma and Warthin tumor
Variables	PA	WT	P value
n	44	115
Number^*			< 0.001
Single	30 (68.2)	22 (19.1)
Multiple	14 (31.8)	93 (80.9)
Margin^*			< 0.001
Well-defined	41(93.2)	71 (61.7)
Ill-defined	3 (6.8)	44 (38.3)
Distribution^*			< 0.001
Eccentric	29 (65.9)	24 (20.9)
Central	10 (22.7)	5 (4.3)
Scattered	5 (11.4)	85 (73.9)
Entire	0	1 (0.9)
Occupying rate^*			0.021
1	33 (75)	60 (52.3)
2	5 (11.4)	26 (22.6)
3	1 (2.3)	18 (15.7)
4	5 (11.4)	11 (9.6)
Internal characteristic^*			< 0.001
Papillary structure	4 (9.1)	23 (20)
Spongiform cyst	0	78 (67.8)
None of the above characteristics	40 (90.9)	14 (12.2)
PA, Pleomorphic adenoma; WT, Warthin tumor;
^* difference was statistically significant.

Imaging modalities are frequently used to assess SGTs before surgery. The exact location, size, extent, number (single or multiple), and architectural features (cystic, solid, and margins) of the masses can be assessed. MRI is the preferred modality for patients with SGTs⁹. However, the high cost, long appointment time, contraindications to magnetic field exposure, and relatively long scan times (which may increase the likelihood of motion or necessitate the use of sedation in claustrophobic patients), hamper the use of MRI. For superficial tumors within the parotid or submandibular glands, US is the preferred initial imaging technique. Use of US can provide excellent tissue characterization, multiplanar information, and vascular pattern¹⁰. Reports on the US performance of SGTs have mainly focused on the shape, margin, echogenicity, echotexture, posterior echo, and blood flow. However, the sensitivity is low⁵, possibly because low-grade M-SGTs may exhibit US characteristics of benign tumors^11,12. Herein, we aimed to identify new features to improve the diagnostic efficiency of US.

Cystic components have been reported as common imaging features of SGTs, such as WTs⁶, basal cell adenomas⁷, cystadenoma¹³, mucoepidermoid carcinomas¹⁴, acinic cell carcinomas, and mammary analog secretory carcinoma¹⁵. The proportion of cystic components in B-SGTs can reach 79%⁸. US is a quick method to differentiate solid from cystic lesions in the superficial areas of the head and neck¹⁰. The 4th World Health Organization classification issued in 2017 defines 11 different types of benign epithelial salivary tumors and 22 carcinomas. In the present study, we retrospectively found that 18 types of epithelial SGTs underwent preoperative US between January 2015 and January 2018. Of these, 14 types of SGTs had cystic components (five B-SGTs and nine M-SGTs). Among them, WT was the most common type.

Given the prevalence of cystic components in SGTs, we summarized the US performance of cystic components of B-SGTs and M-SGTs and clarified whether they could provide effective information for the differential diagnosis of the two. We found that the proportion of cystic components differed in SGTs of different pathological types. The US features of the B-SGTs and M-SGTs were significantly different. The cystic components in M-SGTs had a higher probability of displaying ill-defined, eccentric, and no internal features than B-SGTs. Despite the low sensitivity of cystic components as the sole means of diagnosing M-SGT, these components remain potential indicators for differential diagnosis. When combined with US features of the lesion, including border and shape, the diagnostic efficiency can be significantly improved.

Most studies on the imaging findings of SGTs only determined the presence or absence of cystic components within the lesions. Studies of the imaging features of cystic components are rare. It has been reported that cystic components of PAs and WTs can be classified into various patterns on US¹⁶. More importantly, imaging manifestations of cystic components in benign and malignant tumors differ. Irregular margins of cystic components are more frequently observed in M-SGTs than in B-SGTs⁸. This is consistent with the present observation of the significantly higher proportion of ill-defined borders in M-SGTs than in B-SGTs, and the association of the presence of these borders as a risk factor for M-SGTs. However, in terms of distribution, M-SGTs appeared to have the highest proportion of eccentric distribution. The central distribution was not unique to M-SGTs, in contrast to an earlier study⁸. This may reflect the different grouping criteria used in the two studies. The present study divided the distribution into four types, while the distribution of the prior study comprised three groups.

Pathologically, multicystic and papillary growth patterns, cystic changes, necrosis, and hemorrhage in solid SGTs are responsible for the cystic components of tumors¹⁷. The imaging differences are thought to result from histological differences. We evaluated the internal characteristics and found a correlation between US and pathological findings. On US, the majority of WTs displayed papillary bulges or spongiform cysts (87.8%), which may be related to the slit-like space and papillary structures protruding into the cystic cavity of WTs on histopathology. For cystadenomas, most lesions displayed features of papillary bulges, which should also correlate with the pathological features of intraluminal papillary proliferation. Notably, marked differences were observed in the internal characteristics of benign and malignant tumors. Most M-SGT lesions showed no internal features. This may be because the cystic components of malignant tumors usually result from necrosis or hemorrhage^8,18.

Most (80–85%) parotid gland tumors are benign, and most are PAs and WTs¹⁹. These two tumors have different malignant transformation probabilities and treatment methods. Preoperative differential diagnosis is important²⁰. Cystic areas within lesions were reportedly detected in 20.8% of PAs and 45.2% of WTs²¹. Therefore, because of the predominant incidence of PA and WT in SGTs, we performed a separate analysis of the cystic components and found significant differences. The differences were statistically significant across all assessed features. Thus, cystic components can be definitive indicators for the differential diagnosis between the two.

We further compared the effectiveness of cystic component features in the diagnosis of M-SGTs, including ill-defined margins, eccentric distribution, and absence of internal characteristics. However, their sensitivity and specificity for diagnosing M-SGTs alone are not ideal. Given the important role of lesion margins and shapes in the differentiation of benign and malignant tumors⁴, we further evaluated the diagnostic efficacy of combining lesion features with cystic component features. The sensitivity significantly increased. Thus, cystic components are potentially valuable in the differential diagnosis of B-SGTs and M-SGTs on US. Comprehensive evaluations of lesions are needed for a definitive conclusion.

The present study clarified the US performance of cystic components in SGTs. The study has two limitations. First, it was a single-center, retrospective study. US features were analyzed based on storage images and were not evaluated in real-time. In real-time US, cystic components may appear as fluttering scattered hyperechoic spots, whereas on still images, they may appear as isoechoic areas that cannot be distinguished from solid components on retrospective analysis. Therefore, our study may have underestimated the proportion of SGTs with cystic degeneration. Second, there was a lack of comparison with other imaging methods such as MRI.

This study is the first-known comparison of the US performance of cystic components in SGTs. The study included the evaluation of multiple characteristics. Margin, distribution, and internal characteristics were the key characteristics. On US, cystic components are of interest in the differential diagnosis of B-SGT and M-SGT. A comprehensive evaluation of the lesion is needed to improve the sensitivity of the diagnosis.

Ethics approval The study was approved by the Institutional Review Board of Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine (date of approval: 2022-05-12, approval number: SH9H-2022-T116-1). Because this was a retrospective study, written informed consent was not required.

Conflict of interest The authors declare no competing interests.

Authors’ contributions Angang Ding: Conceptualization, Methodology, Formal analysis, Funding acquisition, Writing - Original Draft. Huan LV: Data Curation

Jinye Cao: Data Curation. Xin Wang: Conceptualization, Methodology, Funding acquisition, Writing - Review & Editing. Ping Xiong: Conceptualization, Methodology, Supervision, Funding acquisition.

Funding Research grants from the Special Project of Clinical Research in Health Industry of the Shanghai Municipal Health Commission (20214Y409) and the National Natural Science Foundation of China (81971618, 81900410) are gratefully acknowledged.

Availability of data and materials All data generated or analysed during this study are included in this published article and its supplementary information files.

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No competing interests reported.

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Ultrasonography characteristics of cystic components in primary salivary gland tumors

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Version 1

Abstract

Figures

Introduction

Material And Methods

Imaging Methods

Preoperative Evaluations

Statistical Analyses

Results

Clinical Characteristics

Gray-scale Us Characteristics

Multi-factor Analysis

Efficacy Of Us Features In Diagnosis Of M-sgts

Cystic Components In Pas And Wts

Discussion

Conclusion

Declarations

References

Additional Declarations

Supplementary Files

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