Prognostic Categories of Salivary Tumors
The histologic classification of salivary tumors is difficult in a significant proportion of tumors. The main reasons are that they are rare compared with tumors of other organs, and they comprise an unusual large spectrum of benign ( n = 11) and malignant ( n = 20) tumor entities. Moreover, most entities show a heterogenous and overlapping spectrum of cytologic and structural differentiation. As in other organs, tumorous lesions of salivary glands comprise four prognostically relevant categories: metaplastic lesions, benign tumors, and low-grade and high-grade cancer ( Table 6.1 ). While the diagnosis of metaplastic lesions and of high-grade cancer is mostly straightforward, the distinction between benign tumors and low-grade cancer is more frequently difficult than in other organ systems.
| Reactive/Metaplasia | Benign Tumor | Low-Grade Carcinoma (G1) | High-Grade Carcinoma (G3) |
|---|---|---|---|
| No (or low-grade) cellular atypia | No (or low-grade) cellular atypia | Low-grade (or no) cellular atypia | Usually high-grade cellular atypia |
| Not infiltrative | Not infiltrative (or pseudo-infiltrative) | Mostly, not always, infiltrative | Usually clearly infiltrative |
| Mucinous or squamous metaplasia | Pleomorphic adenoma | Acinic cell carcinoma | Salivary duct carcinoma |
| Rarely misdiagnosis as tumor | Rarely recurrence or malignant transformation | Frequently local recurrence, rarely metastases | Frequent recurrences and metastases |
An important reason for the difficulty is the multitude of low-grade malignant entities, which often comprise no or only a minor degree of cellular atypia, no increase of proliferation, and/or absence of clear invasion (e.g., acinic cell carcinoma, mucoepidermoid carcinoma, polymorphous adeno carcinoma, clear cell carcinoma). On the other hand, benign tumors may exhibit some degree of cellular atypia and may show pseudo-infiltration, mimicking malignancy.
Therefore in difficult situations, the primary aim of the pathologist should not be to enforce a distinction between the categories: benign vs low-grade malignant. Rather, the pathologist should concentrate on the exact identification of the tumor entity on the basis of cellular, structural, immunohistological, and, with increasing relevance, molecular criteria. The primary identification of the tumor entity establishes its status (benign vs low-grade malignant). Clinicians should appreciate that histologic classification (and hence establishment of status: benign versus low grade malignant) in many cases is not easy, particularly in incisional biopsies, cytology, and frozen sections.
Diagnostic and Therapeutic Impact of Genetic Alterations
Characteristic genetic alterations have been identified in about half of malignant salivary tumor entities. Unexpectedly for epithelial malignancies, translocations proved to be the most frequent genetic alterations, similar to hematologic and soft tissue tumors ( Table 6.2 ). These genetic aberrations manifest in 40% to over 90% of a given tumor entity (in case of translocations often with different partners) and are rather specific for different tumor entities. Therefore, in a difficult differential diagnosis, a positive mutation analysis may be an extremely helpful additional diagnostic criterion to establish the suspected tumor entity (and in consequence status: benign vs low-grade malignant). Apart from initial therapeutic studies in Her2neu- or androgen receptor-positive tumors, the main focus of testing for genetic aberrations is to enhance diagnostic accuracy.
