S3.02 Histological Grade Must Be Recorded (Where Relevant). CS3.02A

S3.02 Histological grade must be recorded (where relevant).

CS3.02a Specific grading systems have not been developed for all salivary gland neoplasms. In many instances, specific tumours characteristically demonstrate either high or low grade behaviour (e.g. salivary duct carcinoma compared with polymorphous low grade adenocarcinoma)16 (See Table 1 below). , Alternatively a histologic subtype of a specific tumour may be associated with high-grade behaviour (e.g. solid type adenoid cystic carcinoma) and in these instances the histological description and diagnosis will be sufficient to indicate behaviour.20 If there are histological features indicating low or high-grade behaviour that is not typical for the tumour, these can be indicated in the report.20

In the case of mucoepidermoid carcinoma, specific grading systems have been developed (WHO classification of tumours3) (Appendix 5).

Table 1: Prognostic factors in salivary adenocarcinoma

Salivary adenocarcinomas Low High grade grade

Polymorphous low grade + adenocarcinoma

Acinic cell carcinoma + +

Basal cell adenocarcinoma +

Cribriform adenocarcinoma +

Mammary analogue secretory + + carcinoma

Myoepithelial carcinoma + +

Cystadenocarcinoma +

Epithelial-Myoepithelial carcinoma +

Mucoepidermoid carcinoma + +

Adenoid cystic carcinoma + +

Adenocarcinoma, not otherwise + + specified

Squamous cell carcinoma + +

Carcinoma ex-pleomorphic adenoma +

Salivary duct carcinoma +

Oncocytic carcinoma +

Undifferentiated carcinoma +

Reprinted from Speight PM and Barrett AW (2009). Prognostic factors in malignant tumours of the salivary glands. British Journal of Oral and Maxillofacial Surgery 47:587-593 with permission from Elsevier. CS3.02b Mucoepidermoid carcinoma

Grading of mucoepidermoid carcinoma previously involved making an assessment of the number of mucous cells in the neoplasm. An increased number of mucous cells and higher volume of mucus production are associated with less aggressive neoplasms that are less likely to metastasise. Neoplasms that are predominantly epidermoid in nature are deemed higher risk for metastasis.16

The development of more objective grading systems for mucoepidermoid carcinoma have been contentious, but the use of such systems may remove some subjectivity from the assessment. The modified AFIP grading system for example, scores specific histopathological features and can be used to provide an objective grading of neoplasms3 (refer to Appendix 5). If a specific grading system is applied, it should be specified in the report.

Generally, mucoepidermoid carcinoma arising within the submandibular gland generally has a poorer prognosis.2 Mucoepidermoid carcinoma with MECT1-MAML2 translocation is reported to have a better prognosis than those tumours without the translocation (see CS4.02b).21

CS3.02c Acinic cell carcinoma

Histological grading systems for acinic cell carcinoma are inconsistent. Factors such as increased mitoses, necrosis, neural invasion, pleomorphism and stromal hyalinisation have been associated with increased neoplasm aggressiveness. The cell proliferation marker Ki-67 has been suggested to indicate a neoplasms behaviour with increased aggressiveness in neoplasms with >5% of cells staining.3

The location of acinic cell carcinomas is important, with submandibular gland tumours demonstrating more aggressive behaviour than parotid tumours.3 Furthermore, acinic cell carcinomas arising in minor salivary glands are less aggressive than those that arise in major glands.3

CS3.02d Mammary analogue secretory carcinoma

Mammary analogue secretory carcinoma (MASC) is a recently described tumour that has features similar to acinic cell carcinoma.22 These neoplasms have variable growth patterns including solid areas, papillary cystic and microcystic spaces which contain PAS positive material.22-23 They are characterised by the ETV6-MTRK3 translocation.22-25

It has been suggested that although slightly more aggressive than acinic cell carcinoma, the clinical outcome is similar.24

CS3.02e Adenoid cystic carcinoma

Various histological patterns are associated with adenoid cystic carcinomas. Tubular and cribriform patterns are considered to be less aggressive compared to solid forms.3,26 It has been suggested that neoplasms that have more than 30% solid component should be considered as high-grade neoplasms.20

CS3.02f Carcinoma ex pleomorphic adenoma

Non-invasive carcinoma ex pleomorphic adenoma generally behave in a similar fashion to benign pleomorphic adenoma and are associated with a good prognosis.3 Invasive carcinoma ex pleomorphic adenomas are considered aggressive neoplasms. Minimally invasive carcinoma (<1.5mm of invasion) are considered low-grade variants.3,20

CS3.02g Polymorphous low-grade adenocarcinoma

Although these neoplasms are classified as low-grade according to their name, up to a third recur locally or metastasise to regional lymph nodes.16 Some studies have demonstrated a link between lymph node metastases and papillary cystic growth pattern.27

Cribriform adenocarcinoma of the tongue is a subtype of polymorphous low-grade adenocarcinoma and is associated with increased lymph node metastases.28

CS3.02h Salivary duct carcinoma

Salivary duct carcinoma, although uncommon, is a high-grade aggressive adenocarcinoma with poor prognosis3 Histologically the neoplasm has features similar to intraductal and infiltrating mammary duct carcinoma. The ductal component is demonstrates a cribriform growth pattern of epithelioid cells whilst the infiltrating component may have solid or papillary areas with psammoma bodies.3 Cytologically the neoplastic cells have pleomorphic nuclei with prominent nucleoli; prominent mitotic activity is also observed.3 Spindle cell or sarcomatoid variants have also been described.3

CS3.02i Minor salivary gland tumours

Malignant neoplasms arising in minor salivary glands are classified using the same staging principle as for other primary mucosal malignancies and include predictive factors associated with the specific histological type.3

Appendix 5 Examples of grading of mucoepidermoid carcinoma

World Health Organisation3

Histopathologic feature Point value

Cystic component <25% 2

Neural invasion 2

Necrosis 3

4 or more mitoses/ 10 hpf 3

Anaplasia 4

Tumour grade Point score

Low (Grade 1) 0-4

Intermediate (Grade 2) 5-6

High (Grade 3) 7 or more

Brandwein48 Characteristic features Defining features

Grade I Prominent goblet cell component, Lack of grade III defining cyst formation intermediate cells features, lack of aggressive may be prominent circumscribed invasion pattern growth pattern

Grade II Intermediate cells predominate Aggressive invasion pattern, over mucinous cells mostly solid lack of grade III defining tumour squamous cells may be features seen

Grade III Squamous cells predominate Necrosis perineural spread intermediate and mucinous cells vascular invasion bony invasion must also be present mostly solid >4 mitoses/10HPF high-grade nuclear pleomorphism

Feature Points Intracystic component <25% 2 Tumour front invades in small nests and islands 2 Pronounced nuclear atypia 2 Lymphatic and or vascular invasion 3 Bony invasion 3 >4 mitoses/10HPF 3 Perineural spread 3 Necrosis 3

Grade I : 0 points Grade II : 2-3 points Grade III : >4 points

© Lippincott Williams & Wilkins. Brandwein MS, Ivanov K, Wallace DI, Hille JJ, Wang B, Fahmy A, Bodian C, Urken ML, Gnepp DR, Huvos A, Lumerman H and Mills SE (2001). Mucoepidermoid carcinoma: a clinicopathologic study of 80 patients with special reference to histological grading. Am J Surg Pathol 25:835-845. Reproduced with permission.