Abstract
Objectives:
To describe the CT and MR imaging characteristics of primary carcinoma ex pleomorphic adenoma (Ca-ex-PA) in major salivary glands and present more information for recognizing this malignancy.
Methods:
212 patients with primary Ca-ex-PA in major salivary glands (169 in the parotid gland, 36 in the submandibular gland, 7 in the sublingual gland) underwent CT and MR imaging (plain and contrast-enhanced scans) prior to surgical management and histopathological examination. The CT and MR imaging findings of this condition were retrospectively reviewed and correlated with their pathological types: non-invasive carcinoma (Type I, 37 cases), minimally invasive carcinoma (Type II, 18 cases), and widely invasive carcinoma (TypeIII, 157 cases). The binary logistic regression analysis was used to analyze the independent influencing factors of morphology and boundary for differentiating between Type I/II and Type III of Ca-ex-PA, and the sensitivity, specificity and positive predictive value were calculated. Differences in apparent diffusion coefficient (ADC) values between Type I/II and Type III of Ca-ex-PA were calculated by independent sample t-tests.
Results:
On CT and MR imaging, there were 190/212 cases (89.6%) identified as lobular, 203/212 cases (95.8%) with enhancement, and 173/212 cases (81.6%) with inhomogeneous after contrast administration.Calcification within the mass was shown in 76 of 192 cases (39.6%) on plain CT examination. Of 55 neoplasms with Type I and II, 38 (69.1%) were presented as round or oval and 42 (76.4%) as well-defined margins. Of 157 neoplasms with Type III, 103 (65.6%) were presented as irregular form and 110 (70.1%) as uneven margins or with partial uneven margins.The sensitivity, specificity and positive predictive value for distinguishing Type I/II and Type III tumors according to the morphology and boundary were 78.34%, 63.64% and 86.01%, respectively. The mean ADC value of Ca-ex-PA (22 cases) in major salivary glands was about 0.93 × 10−3 mm2 s−1, and there was no significant difference in mean ADC value between Type I/II and Type III of this neoplasm. Cervical lymph node metastasis and distance metastasis were found in 67 patients (31.6%, Type III) and 32 patients (15.1%, Type I in 1; Type II in 1; and Type III in 30), respectively.
Conclusions:
Most Ca-ex-PA is characterized by an irregular, lobular, and inhomogeneous enhanced neoplasm with uneven margin or partial uneven margin on CT and MR imaging, which is frequently corresponding with Type III. And a round or oval mass with well-defined margin usually correlates with Type I and II. Morphology and boundary are important basis for distinguishing Type I/II and Type III tumors. Calcification within the neoplasm shown on CT may be regarded as a specific sign for indicating this malignancy. Low ADC value is an important manifestation of this neoplasm.Ca-ex-PA with Type III is more likely to have cervical lymph node metastasis and distant metastasis.
Keywords: Carcinoma ex pleomorphic adenoma, Major salivary gland, CT, MR imaging, Pathological type
Introduction
According to the classification of WHO salivary gland tumors published in 2017, malignant pleomorphic adenomas are usually classified as three main subtypes: carcinoma ex pleomorphic adenoma (Ca-ex-PA), carcinosarcoma (also known as “true malignant mixed tumor”), and metastasizing pleomorphic adenoma.1 Most of the malignant mixed tumors are Ca-ex-PA, the latter two types are very rare. Ca-ex-PA is a malignant tumor originating from the epithelial components of primary or recurrent pleomorphic adenoma (PA). Histology has both benign and malignant components, and there may be various histological subtypes of cancer. Ca-ex-PA of the salivary gland is a rare malignant tumor. The malignancy was reported to represent approximately 3–5% of all salivary gland neoplasms and 5–15% of salivary gland malignancies.2–6
Fine needle aspiration cytology is an invasive method for pre-operative diagnosis of parotid tumors, and the results of fine-needle aspiration cytology sometimes have some errors. Sometimes, it is impossible to obtain enough samples because of the small sample size or the deep location of the tumor. This error, especially for Ca-ex-PA, can lead to missed diagnosis and misdiagnosis. Some authors concluded that the diagnostic accuracy of fine-needle aspiration cytology for Ca-ex-PA was less than 50%.7–9 Bartels et al10 confirmed that imaging examination was more valuable than fine-needle aspiration cytology in the diagnosis of salivary gland tumors.
The role of CT and MR imaging in the diagnosis of salivary gland tumors has been widely described. However, at present, the researches on the CT and MR imaging characteristics of Ca-ex-PA are mostly based on small samples.2,11,12 To improve the comprehensive evaluation, a supplement for the CT and MR imaging findings of salivary gland Ca-ex-PA on the basis of large samples is required. This study tries to describe the CT and MR imaging features of Ca-ex-PA in major salivary glands and the comparative analysis between the CT/MR imaging findings and pathological types, so as to present more information for recognizing this malignancy.
Methods and materials
Patients
This retrospective study was approved by the Institutional Review Board of Shanghai Ninth People’s Hospital. The study cases were selected according to the following criteria: (1) primary Ca-ex-PA; (2) patients underwent either conventional plain and contrast-enhanced CT or/and MR scan before clinical management; (3) CT and MR images could be acquired and interpreted. From January 2004 to December 2017, 212 subjects with Ca-ex-PA of major salivary glands confirmed by operation and pathology were enrolled in the study. Of the 212 subjects, 174 cases were only scanned by CT, 20 cases were scanned only by MR imaging, and 18 cases were scanned by both CT and MR imaging at the same time. The general information of the 212 subjects was shown in Table 1.
Table 1.
General information of 212 subjects with major primary salivary gland carcinoma ex PA
| Location of carcinoma ex PA | No. of cases (%) | No. of male | No. of female | Male/ Female | Mean age (range) (years) | Metastatic lymph nodes of neck (%) | Distance metastases (%) |
|---|---|---|---|---|---|---|---|
| Parotid gland | 169 (79.7%) | 113 | 56 | 2.02/1 | 57.6 (20–94) | 49 (29%) | 21 (12.4%) |
| Submandibular gland | 36 (17.0%) | 26 | 10 | 2.6/1 | 56.3 (26–82) | 13 (36.1%) | 8 (22.2%) |
| Sublingual gland | 7 (3.3%) | 5 | 2 | 2.5/1 | 52.9 (45–73) | 5 (71.4%) | 3 (42.9%) |
| Total | 212 | 144 | 68 | 2.12/1 | 57.2 (20–94) | 67 (31.6%) | 32 (15.1%)a |
PA, pleomorphic adenoma.
32cases with distance metastases included lung metastases in 25 cases, rib in 2 cases, brain in 1 case, spine in 1 case, liver in 1 case, lung with spine in 1 case, as well as lung with liver with 1 case.
Image acquisition
CT examination
CT examinations were performed on 64-row helical CT system (Philips Brilliance, Philips Medical Systems, Best, the Netherlands) and 16-section GE LightSpeed® (General Electric Medical Systems, Milwaukee, WI). The scanning parameters were 120–140 kV/200–300 mAs (Philips Brilliance), and 120 kV/250 mAs (GE LightSpeed General Electric Medical Systems,Milwaukee, WI). Enhanced CT was obtained after intravenous injection of iopamidol (Iopamiro 320, Bracco, Milan, Italy) or iopromide (Ultravist 300, Schering, Germany) with a dose of 1.5 ml kg−1 body weight.
MR imaging examination
MR imaging examinations were performed on a 1.5 T GE Signa Twin- Speed system (General Electric Medical Systems) and 3.0 T scanner (Philips Ingenia 3.0 T; Amsterdam, the Netherlands). Axial plain MR images were obtained using T1WI turbo spin echo (TSE) [repetition time (TR)/echo time (TE) = 561–600 ms/11–18 ms) and T2WI TSE (TR/TE = 3278–4700 ms/85 ms, thickness/gap = 4 mm/0.4 mm, field of view (FOV) = 240 × 240 mm, and matrix = 320–368 × 240–264). Coronal MR images were acquired using T2 weighted fast spin-echo sequence (TR/TE = 3191–3200/90-100 ms, thickness/gap = 3–5 mm/0.3–1 mm, FOV = 180×180 mm, matrix = 276–320×160–215). DW-MR imaging examination was done by using echoplanar single-shot spin-echo sequence (TR/TE = 2200–3000/68-70 ms, thickness/gap = 4.5–5.0 mm/0.5 mm, FOV = 240×240 mm, matrix = 192–256×192], with b values of 0, 1000 s/mm2. The apparent diffusion coefficient (ADC) maps were automatically generated. Contrast enhanced MR imaging was obtained after intravenous injection of gadopentetate dimeglumine (Magnevist; Schering, Berlin, Germany) with a dosage of 0.1 mmol/kg body weight. Axial and coronal contrast-enhanced T1 weighted spin-echo sequence with or without fat suppression were scanned after the intravenous injection of gadolinium contrast medium
Image analysis
Two experienced radiologists independently interpreted the CT and MR images of all patients and reached an agreement after consultation with each other on the inconsistent results. The observed items on CT and MR images include location, size (maximum diameter on axial or reconstructed coronal images), shape (irregular, round or oval, lobulated), margin (even, uneven, partial even and uneven), the internal structure (homogeneous or heterogeneous attenuation/signal intensity; calcification), cervical lymph node metastasis and distant metastasis. The region of interest was placed on the ADC map with a calculation of the ADC value of the tumor. Non-enhancement was defined as the density or signal intensity of the tumor was lower than or close to the adjacent muscle after intravenous injection of contrast medium, and enhancement was greater than the adjacent muscle. Homogeneous or heterogeneous masses were recorded after intravenous injection of contrast medium.
According to the classification of WHO salivary gland tumors published in 2017,1 Ca-ex-PA was divided into three pathological types: non-invasive carcinoma (intracapsular, Type I), minimally invasive carcinoma (＜1.5 mm penetration of the malignant components into extracapsular tissue, Type II), and widely invasive carcinoma (>1.5 mm of invasion from the tumor capsule into the adjacent tissue, Type III).
SPSS 20.0 software (IBM Corp, Armonk, NY) was used for statistical analysis.The binary Logistic regression analysis was used to analyze the independent influencing factors of morphology and boundary for differentiating between Type I/II and Type III of Ca-ex-PA, and the sensitivity, specificity and positive predictive value were calculated. The receiver operating characteristic curve was depicted and the area under the curve (AUC) was used to evaluate the diagnostic efficiency of the logistic regression model. Differences in ADC values between Type I/II and Type III of primary Ca-ex-PA were calculated by independent sample t-tests. The difference was considered statistically significant when p < 0.05.
Results
According to the results of operation and pathology, 37 cases (17.5%) were diagnosed as Type I (32 cases in the parotid gland, 5 cases in the submandibular gland, Figure 1); 18 cases (8.5%) were diagnosed as Type II (16 cases in the parotid gland, 2 cases in the submandibular gland, Figures 2 and 3); 157 cases (74.0%) were diagnosed as Type III (122 cases in the parotid gland, 28 cases in the submandibular gland, 7 cases in the sublingual gland, Figures 4–7).
Figure 1.
Ca-ex-PA (non-invasive carcinoma) sited in the left parotid gland (62-year-old male). Axial CT image (soft tissue window, (a) )shows a round mass with even margin in the left parotid gland. Coronal contrast-enhanced CT image (soft tissue window, (b)) shows the mass with heterogeneous enhancement. Ca-ex-PA, carcinoma ex pleomorphic adenoma.
Figure 2.
Ca-ex-PA (minimally invasive carcinoma) sited in the left parotid gland (65-year-old male). Axial CT image (soft tissue window, (a) )shows an irregular, lobular mass with even margin and scattered calcification (white arrow) in the left parotid gland. Coronal contrast-enhanced CT image (soft tissue window, (b)) shows the mass with heterogeneous enhancement. Ca-ex-PA, carcinoma ex pleomorphic adenoma.
Figure 3.
Ca-ex-PA (minimally invasive carcinoma) sited in the left submandibular gland (29-year-old male). Axial plain T1 weighted image (a) and Coronal plain T2 weighted image (b) show a mass with round shape and even margin in the left submandibular gland with a low signal capsule (white arrow). Coronal contrast-enhanced T1 weighted image (c) shows the mass with heterogeneous enhancement. Ca-ex-PA, carcinoma ex pleomorphic adenoma.
Figure 4.
Ca-ex-PA (widely invasive carcinoma) sited in the left parotid gland (63-year-old male). Axial CT image (soft tissue window, (a)) shows an irregular, lobular mass with partial even and uneven margins and spotted calcification (white arrow) in the left parotid gland. Coronal contrast-enhanced CT (soft tissue window, (b)) shows the mass with heterogeneous enhancement and metastatic lymph nodes of the neck (white arrow). Photomicrograph (c) shows there are abundant collagen fibers with vitreous degeneration (white arrow) in the tumor, and calcification (black arrow) appears in the collagen fibers with vitreous degeneration (hematoxylin-eosin stained, magnification 100 × 100). Ca-ex-PA, carcinoma ex pleomorphic adenoma.
Figure 5.
Ca-ex-PA (widely invasive carcinoma) sited in the left submandibular gland (28-year-old male). Axial plain CT image (soft tissue window, (a)) shows an irregular mass with partial even and uneven margins (white arrow) in the left submandibular gland. Axial contrast-enhanced CT (soft tissue window, (b)) shows the mass with heterogeneous enhancement with metastatic lymph nodes of the neck and submandibular area (white arrow). Coronal contrast-enhanced CT (soft tissue window, (c)) shows multiple metastatic lymph nodes in the left neck (white arrow). Ca-ex-PA, carcinoma ex pleomorphic adenoma.
Figure 6.
Ca-ex-PA (widely invasive carcinoma) sited in the right parotid gland (68-year-old male). Axial plain T1 weighted image (a) and T2 weighted image (b) show an irregular mass with partial even and uneven margin in the right parotid gland. Axial contrast-enhanced T1 weighted image (c) shows the mass with heterogeneous enhancement. Coronal contrast-enhanced T1 weighted image (d) shows ipsilateral metastatic lymph nodes of the neck (white arrow). DWI (e) shows the mass with uneven high signal intensity. (f) ADC value of the ROI (circle) is 0.963 × 10−3 mm2 s−1 (b = 1000 s mm−2). ADC, apparent diffusion coefficient; Ca-ex-PA, carcinoma ex pleomorphic adenoma; ROI, region of interest.
Figure 7.
Ca-ex-PA (widely invasive carcinoma) sited in the right sublingual gland (51-year-old male). Axial plain T1 weighted image (a) and T2 weighted image (b) show a mass with round shape and even margin in the right sublingual gland with a low signal capsule (white arrow). Axial contrast-enhanced T1 weighted image (c) shows the mass with heterogeneous enhancement. Coronal contrast-enhanced T1 weighted image (d) shows metastatic lymph nodes of the neck (white arrow). (e) ADC value of the ROI (circle) is 0.614 × 10−3 mm2 s−1 (b = 1000 s mm−2). ADC, apparent diffusion coefficient; Ca-ex-PA, carcinoma ex pleomorphic adenoma; ROI, region of interest.
The routine CT and MR imaging findings of 212 subjects with primary Ca-ex-PA in major salivary glands are listed in Tables 2 and 3. The correlated analysis between CT and MR imaging features and pathological types of 212 subjects with primary Ca-ex-PA in major salivary glands is listed in Table 4. The ADC values of 22 subjects with primary Ca-ex-PA in major salivary glands are listed in Table 5.
Table 2.
CT and MR imaging findings of 212 subjects with primary salivary gland carcinoma ex PA
| Location | Parotid gland | Submandibular gland | Sublingual gland | Total |
|---|---|---|---|---|
| No. of salivary sides | 169 | 36 | 7 | 212 |
| Mean maximum diameter of the maximum mass (mm (range) | 37.5 (10–120) | 34.7 (12–121) | 35 (18–91) | 36.6 (10–121) |
| Irregular | 100 | 17 | 3 | 120 (56.6%) |
| Round or oval | 69 | 19 | 4 | 92 (43.4%) |
| Lobular | 155 | 30 | 5 | 190 (89.6%) |
| Homogeneous | 29 | 9 | 1 | 39 (18.4%) |
| Heterogeneous | 140 | 27 | 6 | 173 (81.6%) |
| Calcification | 57/152 | 15/34 | 4/6 | 76/192a (39.6%) |
| Enhancement | 163 | 33 | 7 | 203 (95.8%) |
| Non-enhancement | 6 | 3 | 0 | 9 (4.2%) |
| Even margin | 71 | 12 | 6 | 89 (42.0%) |
| Uneven margin | 21 | 9 | 1 | 31 (14.6%) |
| Partial even and uneven margins | 77 | 15 | 0 | 92 (43.4%) |
PA, pleomorphic adenoma.
192 subjects were examined with CT scan, in which the calcification within the mass could be clearly identified.
Table 3.
Involvement of adjacent structures by 212 salivary gland carcinoma ex PA
| Location | Parotid gland | Submandibular gland | Sublingual gland | Total |
|---|---|---|---|---|
| No. of salivary sides | 169 | 36 | 7 | 212 |
| Maxilla | 1 | 0 | 0 | 1 |
| Mandible | 7 | 2 | 0 | 9 |
| Palatine bone | 0 | 0 | 0 | 0 |
| Masseter muscle | 13 | 1 | 0 | 14 |
| Medial pterygoid muscle | 21 | 1 | 0 | 22 |
| Lateral pterygoid muscle | 10 | 0 | 0 | 10 |
| Nasal cavity | 0 | 0 | 0 | 0 |
| Carotid sheath | 16 | 0 | 0 | 16 |
| Central skull base | 2 | 0 | 0 | 2 |
| Cavernous sinus | 0 | 0 | 0 | 0 |
| Orbit | 0 | 0 | 0 | 0 |
| Ethmoid sinus | 0 | 0 | 0 | 0 |
| Tongue | 0 | 1 | 7 | 8 |
| Submandibular gland | 2 | - | 0 | 2 |
| Sublingual gland | 0 | 1 | - | 1 |
| Parapharyngeal space | 19 | 0 | 0 | 19 |
| Sternocleidomastoid muscle | 7 | 0 | 0 | 7 |
PA, pleomorphic adenoma.
Table 4.
CT and MR imaging findings correlated with the pathological types of carcinoma ex PA in 212 subjects
| Pathological type | Intracapsular carcinoma (Type I) | Minimally invasive carcinoma (Type II) | Widely invasive carcinoma (Type III) | Total |
|---|---|---|---|---|
| No. of patients | 37 | 18 | 157 | 212 |
| Location (Parotid/Submandibular/Sublingual) | 32/5/0 | 16/2/0 | 121/29/7 | 169/36/7 |
| Mean maximum diameter of mass (mm) (range) | 34.7 (15–76) | 24.8 (10–55) | 38.9 (10–121) | 36.6 (10–121) |
| Irregular | 10 (27.0%) | 7 (38.9%) | 103 (65.6%) | 120 (56.6%) |
| Round or oval | 27 (73.0%) | 11 (61.1%) | 54 (34.4%) | 92 (43.4%) |
| Lobular | 30 (81.1%) | 15 (83.3%) | 145 (92.4%) | 190 (89.6%) |
| Homogeneous | 9 (24.3%) | 4 (22.2%) | 26 (16.6%) | 39 (18.4%) |
| Heterogeneous | 28 (75.7%) | 14 (77.8%) | 131 (83.4%) | 173 (81.6%) |
| Calcification | 6/32a (18.8%) | 4/15a (26.7%) | 66/145* (45.5%) | 76/192a (39.6%) |
| Enhancement | 34 (91.9%) | 17 (94.4%) | 152 (96.9%) | 203 (95.8%) |
| Non-enhancement | 3 (8.1%) | 1 (5.6%) | 5 (3.1%) | 9 (4.2%) |
| Even margin | 28 (75.7%) | 14 (77.8%) | 47 (29.4%) | 89 (41.4%) |
| Uneven margin | 3 (8.1%) | 0 (0%) | 28 (18.1%) | 31 (14.6%) |
| Partial even and uneven margins | 6 (16.2%) | 4 (22.2%) | 82 (52.5%) | 92 (43.4%) |
| Metastatic lymph nodes of neck | 0 (0%) | 0 (0%) | 67 (48%) | 67 (31.6%) |
| Distance metastases | 1 (2.7%) | 1 (5.6%) | 30 (20.0%) | 32 (15.1%) |
PA, pleomorphic adenoma.
192 subjects were examined with CT scan, in which the calcification within the mass could be clearly identified.
Table 5.
The ADC value of 22 subjects with primary salivary gland carcinoma ex PA
| Pathological type | Number of cases | Mean ADC value (1 × 10–3 mm 2/s) (range) | p-value |
|---|---|---|---|
| Type I and II | 5 | 1.0 (0.8–1.1) | 0.455 |
| Type III | 17 | 0.91 (0.6–1.5) | |
| Total | 22 | 0.93 (0.6–1.5) |
PA, pleomorphic adenoma.
In addition, the two independent influencing factors of morphology and boundary for differentiating between Type I/II and Type III of Ca-ex-PA was analyzed (sensitivity = 78.34%, specificity = 63.64%, positive predictive value = 86.01%, AUC = 0.749)(Figure 8).
Figure 8.
ROC curve of the morphology and boundary for differentiating between type I/II and type III of Ca-ex-PA. Ca-ex-PA, carcinoma ex pleomorphic adenoma; ROC, receiver operating characteristic.
Among the 169 cases in the parotid gland, 49 cases (29%) were confirmed by operation and pathology to have cervical lymph node metastasis, including 41 with extraglandular lymph node metastasis, 3 with intraparotid lymph node metastasis, and 5 with both extraglandular and intraparotid lymph node metastasis. The rate of extraglandular lymph node metastasis was 93.9% (46/49). Among the 43 cases in the submandibular gland and sublingual gland, 18 cases (41.9%, 18/43) had cervical lymph node metastasis confirmed by operation and pathology, and 11 cases (25.6%, 11/43) had distant metastasis.
Discussion
Ca-ex-PA is a malignant tumor originating from the epithelial components of primary or recurrent pleomorphic adenoma. Andreasen et al13 and M.H. Valstar et al14 concluded that about 1.8–6.2% of the pleomorphic adenoma in the salivary gland was transformed into Ca-ex-PA. According to a study in the United States, the incidence of Ca-ex-PA had increased in the past decade (0.24–0.63 per 1,000,000 from 2005 to 2015).4
In this study, we reported the CT and MR imaging features of 212 cases of Ca-ex-PA in major salivary glands in Chinese population, which was the largest sample size, specifically reported the imaging features of this rare tumor. Most patients were identified to be male, the male/female ratio was 2.12:1, and the average age was 57.2 years, which was consistent with the previous study.3,4,15,16
Invasiveness is an important factor affecting the prognosis of Ca-ex-PA.3,16–18 The prognosis of patients with noninvasive carcinoma and minimally invasive carcinoma is significantly better than that of patients with widely invasive carcinoma. Hu et al showed that the overall survival of non-invasive Ca-ex-PA was 100% at 5 years, and the overall survival of minimally invasive Ca-ex-PA was 98% at 5 years; however, the overall survival of widely invasive Ca-ex-PA was 59% at 5 years3. Therefore, studying the CT and MR imaging findings of different pathological types of Ca-ex-PA and summarizing the imaging features is of great significance for guiding clinical treatment and evaluating the prognosis of patients. According to our observation, the CT and MR imaging characteristics of primary Ca-ex-PA in major salivary glands vary depending on different pathological types of the neoplasm.
Widely invasive carcinoma (Type III) is the most common pathological type of Ca-ex-PA.3 Of 212 patients with primary Ca-ex-PA in major salivary glands, 157 (74.1%) were Type III in this study. Most of them appear as an irregular, lobulated, heterogeneous enhanced mass with uneven or partial uneven margins on CT and MR imaging. Non-invasive carcinoma (Type I) and minimally carcinoma (Type II) are mostly round or oval, with well-defined heterogeneous enhanced masses. And all the three types of tumors can be characterized by lobulation, calcification, and heterogeneous enhancement. The morphology and boundary are important imaging characteristics for the differentiation between Type III and Type I/II tumors. In this study, the sensitivity was 78.34%, specificity was 63.64% and positive predictive value was 86.01%.
However, it is difficult to distinguish Ca-ex-PA of Type I/II from benign parotid gland tumors based on morphological characteristics, because both tumors may appear as regular masses with well-defined margins in the major salivary gland. Recently, the application of DW-MR imaging plays a significant role in the differential diagnosis between benign and malignant salivary glands.19–23 Pleomorphic adenoma showed a low cellular area with high ADC value, and salivary carcinomas showed a high cellular area with low ADC value. At the same parameters of DW-MR imaging,20 our previous data showed that the mean ADC value of PA (50 cases) was about 1.43 ± 0.26 × 10−3 mm2 s−1. Many previous studies reported that the mean ADC values of benign lesions in salivary glands (between 1.49 and 2.1 × 10−3 mm² s−1) were significantly higher than malignant lesions (between 1.0 and 1.2 × 10−3 mm² s−1), and ADC values of Warthin’s tumor (between 0.96 and 1.16 × 10−3 mm² s−1) didn't have significant difference with malignant lesions.24–28 In this study, the mean ADC value of Ca-ex-PA (22 cases) in major salivary glands was about 0.93 × 10–3 mm2 s, which was significantly lower than other benign salivary gland tumors except Warthin’s tumor. However, among the different pathological types of Ca-ex-PA, we find there was no significant difference in mean ADC value between Type I/II and Type III of this neoplasm.
On the other hand, this study seems to notice a situation that the calcification within the salivary neoplasm may be an important sign for indicating the salivary Ca-ex-PA, although the incidencpe of calcification within the Ca-ex-PA is less than 50%. Some studies proposed that calcification was an important finding of Ca-ex-PA.2,29,30 Pathologically, the calcification in Ca-ex-PA is mainly distributed in vitreous collagen fibers (Figure 4c). We speculate that the following two reasons may lead to calcification in Ca-ex-PA: one is that the slow growth of this disease can result in calcium deposition; the other is that the vitreous collagen fibers are very abundant in the Ca-ex-PA. Rauso et al31 reported a case of ossification Ca-ex-PA in the accessory parotid gland and pointed out that the extensive ossification area was distributed in the rich collagen fibers, which was consistent with our viewpoints.
In addition, we also noticed that the CT and MR imaging characteristics of primary Ca-ex-PA in major salivary glands vary depending on different sites.
Parotid gland Ca-ex-PA
Ca-ex-PA mainly occurs in the parotid gland.4 The data of this study shows that about 4/5 of the neoplasms occured in the parotid gland, which mostly were widely invasive carcinoma, appeared as an irregular, lobulated, enhanced heterogeneous mass with uneven or partial uneven margins on conventional CT and MR imaging. Most cervical lymph node metastases are extraglandular lymph node metastases, while intraglandular lymph node metastases are uncommon (only eight cases). Distant metastases usually occur in the lungs, but also in the ribs, brain, spine, and liver. In addition, we find that the infiltration into the surrounding adjacent structures is more common of Ca-ex-PA in the parotid gland, including the internal and external pterygium, parapharyngeal space, carotid sheath, masseter, sternocleidomastoid, and mandible, which had important implications for our clinical diagnosis and management. Raine et al11 also suggested that the involvement of adjacent deep structure was an important imaging basis for salivary gland malignant tumors.
Submandibular gland and sublingual gland Ca-ex-PA
The Ca-ex-PA located in the submandibular gland and sublingual gland is infrequently reported in the previous investigations. Our observations reveal that the Ca-ex-PA in the submandibular gland and sublingual gland has the following characteristics: (1) most of the Ca-ex-PA are widely invasive carcinomas, accounting for 83.7% (36/43). (2) On CT and MR imaging, most of them are lobulated and heterogeneous enhanced masses, which may be round/oval or regular. (3) The Ca-ex-PA in the submandibular gland is mostly with uneven or partial uneven margin, while the Ca-ex-PA in the sublingual gland is mostly well-defined. (4) The Ca-ex-PA in the submandibular gland and sublingual gland seems to have a higher incidence of calcification (44.2%). (5) The sublingual gland Ca-ex-PA mostly infiltrates the adjacent tongue tissues, but the submandibular gland Ca-ex-PA uncommonly infiltrates the surrounding structures. (6) The incidence of cervical lymph node metastasis and distant metastasis is higher than those of parotid Ca-ex-PA, especially sublingual gland Ca-ex-PA.
Differential diagnosis
The differential diagnosis depends on the pathological type of Ca-ex-PA. According to our experiences and knowledge, it is difficult to distinguish Type I /II of Ca-ex-PA from benign tumors of salivary glands, because of lack of characteristics. But the application of DWI images provides important information, and the ADC value of Ca-ex-PA is lower than that of benign tumors. For Type III of Ca-ex-PA, although there are similarities with other salivary gland malignant tumors. The findings such as irregularity, heterogeneity, invasion and ill-defined borders are well-known indicators of malignancy. These findings are specific to all malignancies, not just Ca-ex-PA. But calcification is a rare sign in other malignant tumors. Calcification within the neoplasm may be regarded as a specific sign for indicating Ca-ex-PA. And the clinical course of disease is also of great significance. Patients with Ca-ex-PA are older. Previous researches addressed that the mean age of Ca-ex-PA were 55.1–61 years old,17,21,32 Our study showed that the average was 57.2 years old. The longer the untreated period after the diagnosis of PA, the higher the likelihood of the the incidence of Ca-ex-PA.21
Conclusions
Most Ca-ex-PA occurs in the parotid gland is characterized by an irregular, lobular, and inhomogeneous enhanced neoplasm with uneven margin or partial uneven margin on CT and MR imaging, which is frequently corresponding with Type III. And, a round or oval mass with well-defined margin usually correlates with Type I and Type II. Morphology and boundary are important basis for distinguishing Type I/II and Type III tumors. Calcification within the neoplasm shown on CT may be regarded as a specific sign for indicating this malignancy. Low ADC value is an important manifestation of this neoplasm. Ca-ex-PA in the submandibular glands and sublingual glands is more likely to have cervical lymph node metastasis and distant metastasis.
Footnotes
Acknowledgments: We thank Dr. Qiang Yu (Department of Radiology, Ninth People’s Hospital, School of Medicine, Shanghai Jiao Tong University) for conducting this project. We thank Siyi Li (Department of Oral and Maxillofacial Head and Neck Oncology, Ninth People’s Hospital, School of Medicine, Shanghai Jiao Tong University) and Jingjing Sun (Department of Pathology, Ninth People’s Hospital, School of Medicine, Shanghai Jiao Tong University) for conducting the pathology.
Funding: This study was supported by the“Clinical +Plan” Project of the Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine (JYLJ201918)
The authors Ling Zhu and Pingzhong Wang contributed equally to the work.
Contributor Information
Can Wang, Email: 374056440@qq.com.
Qiang Yu, Email: yuqiang6155@163.com.
Siyi Li, Email: dr.lisiyi@hotmail.com.
Jingjing Sun, Email: 421214938@qq.com.
Ling Zhu, Email: puxuke12@126.com.
Pingzhong Wang, Email: kcb027@163.com.
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