MRI PROTOCOL

The recommended multiparametric MRI protocols must include the following:

• Unenhanced T1 and T2 without fat saturation (FS). The purpose is to assess lesion borders, tumour homo/heterogeneity and signal compared to the surrounding tissues.
• DWI with 2 b-values (0; 1000 s/mm²) or 3 b-values (0; 500; 1000 s/mm²) and with calculation of an apparent diffusion coefficient (ADC in mm²/s) map. The purpose is to assess tumour cellularity. Assessment is done visually or quantitatively. Quantitative measurements require Region of Interest (ROI) positioning on solid tumour portions.
• DCE-MRI with repeat FS T1 sequence acquisitions (20-30s temporal resolution) during a total time frame of 300s. The purpose is to study perfusion characteristics. Selected ROIs placed on solid tumour portions are used to obtain Time signal Intensity Curves (TICs) as described by Yabuuchi and al. (Fig 1).
• After iv. Gadolinium-based contrast agent administration, T1 ± FS sequences are obtained. The purpose is to improve morphologic tumour assessment.
• 3D T1 FS contrast-enhanced sequences are essential to estimate intracranial, perineural, meningeal and subtle bone extension. This sequence is also used to determine the relationship of the facial nerve within the parotid tumour before surgery.

Fig 1: Time-intensity curves (TIC, white curves) according to Yabuuchi obtained by performing a dynamic contrast-enhanced MRI acquisition (DCE-MRI): Type A curve corresponds to moderate and progressive enhancement Type B curve shows a wash-out >30% at 300s and a time to peak enhancement (Tpeak)<120s. Type C curve shows a plateau enhancement pattern, i-e., a wash-out < 30% at 300s and a time to peak enhancement (Tpeak) <120s. Type D curve is a flat line without enhancement. The arterial enhancement curve is rendered in red for comparison.

CHARACTERISATION KEY POINTS

Location

Parotid tumours account for 70% of all SGTs, and 80% of parotid tumours are benign. In contrast, tumours arising in the submandibular and sublingual glands are malignant in 50% and 90% of cases, respectively.

The most common benign SGTs are pleomorphic adenomas and Warthin tumours while basal cell adenoma, myoepithelioma, oncocytoma, lipoma and intraglandular facial nerve schwannoma are rare.

The most common malignant SGTs include mucoepidermoid carcinoma and adenoid cystic carcinoma. Squamous cell carcinoma (SCC) and salivary ductal carcinoma or adenocarcinoma are infrequent. SCC and adenocarcinoma must be distinguished from metastases of tumours originating outside the head and neck area or from skin SCC.

Morphology

Before interpreting any additional sequences, morphological features of SGTs must be carefully analysed. While benign tumours tend to have a relatively high T2 signal and well-defined borders (Figs. 2 and 3), malignant tumours tend to have intermediate to low T2 signal and ill-defined margins. Extra-glandular extension, e.g., invasion of muscles or bony structures, signs of perineural spread or evidence of lymph node metastases also indicate malignancy. However, these obvious signs are rare in the context of SGTs.

Fig 2: Schematic representation of the typical morphological characteristics of the most common salivary gland tumours Warthin tumour: Well-delineated mass with low/intermediate signal on T1with occasionally hyperintense foci (haemorrhagic or proteinaceous debris); heterogeneous T2 signal (epithelial elements => intermediate signal, cystic areas => high signal, focal haemorrhagic areas => low signal); inhomogeneous contrast enhancement (CE) on fat saturated (FS) T1 depending on the amount of solid vs. cystic or haemorrhagic components. Pleomorphic adenoma: Well-delineated mass with low signal on T1 and very high T2 signal (due to myxoid components), occasionally with small intra-tumoural hypointense areas on T2 (cellular components); relatively homogenous contrast enhancement; often low signal intensity rim (fibrous capsule). Low grade mucoepidermoid carcinoma: well-delineated mass with intermediate-low T1 signal, intermediate T2 signal with occasionally high signal cystic areas, and intense heterogenous contrast enhancement. High grade mucoepidermoid carcinoma: infiltrating mass with low T1 and T2 signal and heterogenous contrast enhancement.

Fig 3: Illustration of different morphologic MRI features of SGTs.

DWI

ADC values tend to be highest in pleomorphic adenoma (1.6-2 x 10^-3 mm²/s) followed by mucoepidermoid carcinoma and other malignant tumours, which tend to have ADC values of about 1-1.4 x 10^-3 mm²/s whereas Warthin tumours typically have very low ADC values (0.7-0.9 x 10^-3 mm²/s) (Fig. 4)

Fig 4: ADC values in SGTs. Illustration of typical ADC values in SGTs: pleomorphic adenoma, mucoepidermoid carcinoma, ductal salivary carcinoma and Warthin tumour. Note that the indicated ADC values are are mean ADC values while the range of values tends to overlap!

Because of their microstructural characteristics and variable degrees of cellularity, ADC values of benign and malignant tumours tend to overlap. Therefore, DWI should always be interpreted combined with morphologic features.

Perfusion curves (TICs)

The wash-in TIC component reflects tumour neo-angiogenesis, whereas the wash-out phase depends on tumour cellularity. The higher the ratio cells to stroma, the faster the wash-out.

Fig. 1 and Fig. 5 illustrate the 4 different TIC types that are useful for SGT characterisation according to Yabuuchi and al.:

• Type A curve (progressive and moderate enhancement) seen in 95% of benign SGTs.
• Type B curve (rapid wash-in and rapid wash-out) is typical of Warthin tumours, but as many as 25% of malignant SGTs also display a type B TIC.
• Type C curve (rapid wash-in followed by a slow wash-out) occurs in 80% of malignant tumours.
• Type D curve is a flat line, i.e., no enhancement.

Fig 5: Illustration of the 4 different types of TIC curves according to Yabuuchi et al. as measured in clinical routine and their respective diagnostic significance.

Combined multiparametric evaluation as a must

As discussed above, type A, B and C TICs can be encountered both in malignant and in benign SGTs (Fig. 6).

Fig 6: Perfusion curves (TICs) alone do not allow reliable distinction between benign and malignant SGTs. They should be evaluated in combination with morphology and DWI. Upper row: histologically proven Warthin tumour presenting as a well-defined solid lesion with multiple hyperintense foci on T1, heterogeneous but mostly intermediate T2 and a TIC type B. Lower row: Pleomorphic adenoma with carcinoma ex pleomorphic adenoma presenting as a solid tumour in the deep lobe of the parotid gland (blue arrow on T1). Myxoid portions (hyperintense on T2, green arrow). Hypercellular area with an intermediate signal on T2 (asterisk) like normal parotid parenchyma. This hypercellular area had a type B TIC. In correlation with pathology, the tumour part with an intermediate T2 signal and a type B curve (blue ROI) corresponded to the malignant degenerated portion (carcinoma ex pleomorphic adenoma).

Likewise, low ADC values can be seen both in some benign (Warthin tumour) and in malignant SGTs (Fig. 7).

Fig 7: ADC values alone do not allow tumour characterisation. DWI should always be evaluated at least in combination with morphology. Upper row: Well-defined tumour in the superficial lobe of the left parotid gland with low T1 and low T2 signal. Hyperintense intralesional T1 and T2 foci (yellow arrows). Restricted diffusion with low ADC values. Lower row: tumour in the left parotid gland with ill-defined contours, low T2 and low T1 signal. Moderately high ADC value. The case in the upper row was a Warthin tumour, whilst the case in the lower row was a low-grade mucoepidermoid carcinoma.

Therefore, multiparametric MRI taking all information into account is a must in SGTs. 

TYPICAL ILLUSTRATIVE CASES

Benign tumours

Pleomorphic adenomas (Fig. 8) are often localised in the parotid gland but they can also be ectopic (Fig. 9). They have epithelial, myoepithelial and stromal-myxoid components surrounded by a thin fibrous capsule.

Typical MRI features include:

• low T1 and very high T2 signal
• a hypointense rim due to fibrous capsule and pseudopodia
• high ADC values except in cases with high cellularity or malignant transformation
• type A TIC ( Figs. 8 and 9).

Fig 8: Typical pleomorphic adenoma of the left parotid gland. The tumour shows a very high homogenous T2 signal with high ADC values and progressive enhancement (type A curve). Posteriorly, note finger-like projections corresponding to pseudopodia (green arrow on T2) extending towards the stylo-mastoid foramen. Pseudopodia are a risk for post-surgical recurrence. Note also on T2 a low signal intensity rim due to a fibrous capsule. The sagittal oblique reconstruction of the 3D T1FS contrast-enhanced sequence demonstrates the course of the facial nerve (blue arrows) and its relationship to the tumour. Note that the intra-parotid facial nerve main trunk is located posteriorly to the tumour. This information is important for surgical planification, to preserve the and for pre-operative patient information. Doppler US image performed before FNAC shows a solid, polypoid, well-defined tumour with intense posterior enhancement (arrows).

Fig 9: Ectopic pleomorphic adenoma arising from subcutaneous ectopic minor salivary glands. Well-defined lesion (arrows) next to the left submandibular compartment, located in the subcutaneous fat tissue superficial to the platysma. This lesion shows a high and homogenous T2 signal and a very high ADC value (> 2 x 10 -3mm2/sec). The Time-intensity curve (TIC) displays a progressive enhancement pattern (type A curve ). Ultrasonography-guided Fine Needle Aspiration Cytology (US- FNAC) confirmed the diagnosis. SMG = left submandibular gland.

Warthin tumours are composed of a lymphoid stroma and eosinophilic epithelial cells.

Typical MRI features include:

• intralesional hyperintense T1 foci due to proteinaceous, haemorrhagic or cholesterol debris ( Fig. 10)
• T2 heterogeneity, partially cystic
• sometimes multiple and bilateral, typically in the parotid tail ( Fig. 11)
• type B TIC of solid parts in 90% of cases and rarely type C TIC
• low ADC values (overlap with malignant tumours, see Fig. 7).

Fig 10: Typical Warthin tumour. Well-defined tumour showing a hypointense T2 signal compared to the normal gland parenchyma. Note slightly hyperintense foci on T1 (arrows). Restricted diffusivity with low ADC values, especially in the periphery (green circles). On the colour coded Area Under the Curve (AUC) map derived from DCE-MRI, there is increased peripheral perfusion (white arrows). RMV = retromandibular vein. The DCE-MRI acquisition reveals a type B TIC (>30% washout). The region of interest measurements (ROI) for the tumour were placed on the areas indicated on the AUC image by white arrows.

Fig 11: Typical bilateral Warthin tumours with cystic degeneration, internal septa and debris. Well-defined bilateral tumours situated in the superficial lobe near the parotid tail. Both tumours are mostly cystic with internal septa (dashed arrows). The solid peripheral portions (arrows) and the septa have an intermediate T2 signal and restricted diffusion. No restriction in the cystic portions. Increased perfusion in the solid tumour parts. The DCE-MRI acquisition reveals a type B TIC (>30% washout) in both tumours. Region of interest measurements (ROI) were placed on the areas indicated in blue and yellow, respectively. Characteristic US aspect of both tumours: mainly cystic with posterior enhancement and internal debris. US-FNAC suggested Warthin tumours bilaterally. Surgery performed 2 years later because of increasing size of tumours confirmed the diagnosis.

Malignant tumours

Many cases of mucoepidermoid carcinoma (Fig. 4 and Fig. 12) or of adenoid cystic carcinoma (Fig. 13) behave as low-to-intermediate-grade malignancies. The tumours often present as well-defined masses with low T1 and heterogeneous-to-intermediately high T2 signal. Their (micro)cystic components may explain moderately high ADC values, which can be misleading (Figs. 13). In rare cases, type A TICs are also present (Fig. 13) making the differential diagnosis challenging especially if US-FNAC is inconclusive.

Fig 12: Histologically proven mucoepidermoid carcinoma: 7mm large nodule in the right parotid tail (arrows) with a slightly hyperintense rim on T2 and T1, mixed hyperintense and isointense signal on T2 compared to surrounding gland parenchyma, restricted diffusion and a type B TIC. The ADC value is higher than the ADC value of Warthin tumours. On Doppler US, the tumour appears less well-defined than on MRI with a slightly enhanced posterior shadow and increased central vascularisation. US FNAC suggested mucopepidermoid carcinoma, which was confirmed after surgery.

Fig 13: Histologically proven adenoid cystic carcinoma of left submandibular gland. Tumour in the anterior region of the left submandibular gland (SMG) with low T1 and moderately high T2 signal (compared to the SMG). Note peripheral low T2 rim. The DCE-MRI shows peripheral enhancement with a TIC type A (ascending curve). No restricted diffusion. Because of absent restriction and a TIC type A, this lesion was initially diagnosed as a cellular variant of pleomorphic adenoma on MRI. However, the US aspect (well-defined cyst-like lesion with intense posterior enhancement) and US-FNAC were inconclusive as they were not typical of pleomorphic adenoma. Surgery revealed adenoid cystic carcinoma.

Salivary duct carcinomas often display the MRI characteristics of highly aggressive malignant tumours:  infiltrative masses with low T2 signal, restricted diffusion, and type C TIC (Figs. 14 and 15).

Fig 14: Surgically proven invasive ductal carcinoma of the left parotid gland. Infiltrative mass with ill-defined borders (blue arrows) and signs of extra-capsular spread (dashed arrows). Hypointense tumour signal on T2 (compared to normal gland parenchyma). Restricted diffusion. TIC type C curve (blue circle). All MRI features suggest a malignant tumour. The intraparotid facial nerve visible on an oblique reconstruction of the 3D T1 FS sequence is seen as a black line (red arrows) tangential and medial to the tumour mass (asterisk). US shows a strongly hypoechoic lesion, ill-defined and with calcifications equally suggesting a malignant tumour.

Fig 15: Surgically proven high-grade ductal carcinoma of left parotid gland. The tumour is in the superficial lobe of the gland. It shows very low T1 and T2 signal. The lesion has ill-defined borders, extending posteriorly beyond the capsule (blue arrows). Pseudo-restricted diffusivity due to T2 black-out effect (due to very low T2 signal). The DCE-MRI sequence demonstrates heterogenous enhancement and a type C TIC.

TRICKY CASES

Because of partly overlapping features between intra-parotid schwannoma, low-flow venous malformations and pleomorphic adenoma, US and US-FNAC can sometimes be used as complementary diagnostic tools (Fig. 16).

Fig 16: Facial nerve schwannoma. Well-defined mass in the superficial lobe of the right parotid gland (green arrows), showing heterogeneous T2 and hypointense T1 signal. ADC values = 1.5 x 10-3 mm2/sec. The lesion is enhancing progressively with a type A TIC. MRI suggested a possible cellular pleomorphic adenoma. The lesion did not extend into the stylomastoid foramen. Doppler US shows a poorly vascularized lesion with cyst-like parts (asterisks), a “spongy” appearance and posterior enhancement not typical of a pleomorphic adenoma. US-FNAC suggested schwannoma. Surgery confirmed schwannoma.

Rarely, inflammatory/autoimmune diseases can mimic malignant tumours, e.g., Kimura disease or IgG4-related disease (Fig. 17), where laboratory findings, biopsy and clinical evolution complement the diagnosis.

Fig 17: IgG4 related submandibular swelling. The patient was addressed for exploration of a submandibular gland (SMG) mass. The first MRI (upper row), shows an ill-defined mass in the right SMG with intermediate T2 and hypointense T1 signal (green arrows) and restriction of diffusion with low ADC values. The lesion is poorly defined. The MRI is highly suspicious of malignancy. Nevertheless, the patient was diagnosed with IgG4 related disease with SMG involvement based on laboratory and biopsy findings. Clinical evolution was favourable, and a new MRI eight months later showed a normal SMG, increasing ADC values and regression of gland enhancement (blue arrows).

In our experience, if MRI and US-FNAC results are concordant, the probability of a correct diagnosis is extremely high. However, discrepant findings on MRI and US-FNAC warrant further workup and multidisciplinary discussion to guide patient management.