Salivary gland hybrid tumour revisited: could they represent high-grade transformation in a low-grade neoplasm?

Abstract

Salivary gland hybrid tumour, first described in 1996, is a very rare neoplasm for which exact morphological criteria have not been universally agreed upon. In contrast, the concept of high-grade transformation (HGT) in salivary neoplasms has been widely accepted during the last decade, and the number of reported cases is rapidly increasing. A review of the literature revealed 38 cases of hybrid tumour reported in 22 publications. During approximately the same time period, well over 100 cases of HGT in salivary neoplasms have been reported. There are important histological similarities between hybrid tumours and salivary tumours with HGT. In the latter, containing one tumour component of low-grade malignancy and the other of high grade, the two tumour components are not entirely separated and appear to originate in the same area. Virtually, all cases reported as hybrid tumour had no clear lines of demarcation between the two tumour types. We are inclined to suggest that most of the 38 cases of hybrid tumours described in the literature would today better be called tumour with HGT rather than hybrid tumour. The relative proportion of the two components may vary, and the high-grade component is sometimes very small, which emphasises the importance of very generous sampling of the surgical specimen. The molecular genetic mechanisms responsible for HGT, including what used to be called hybrid tumour, remain largely unknown. Abnormalities of a few genes (including p53, C-MYC, cyclin D1, HER-2/neu) have been documented. As insufficient data exist on gene abnormalities in these lesions, conclusions as to whether or not they have a common origin and which mechanisms are involved in transformation cannot be drawn. Due to the small number of cases reported, many of which lack follow-up details; indicators of prognosis of hybrid tumours are not available, but their behaviour seems to be similar to that of tumours with HGT, i.e. an accelerated aggressive course. HGT of salivary gland neoplasms greatly influences macroscopic and microscopic evaluation of the specimen but also, given the high incidence of metastases and morbidity, carries significant treatment implications.

An Unusual Hybrid Salivary Gland Tumor: Molecular Analysis Informs the Potential Pathogenesis of This Rare Neoplasm

“…Genetic analyses of the tumor components that may provide useful information regarding tumorigenesis are even more limited [4, 9]. When encountering such cases, several important differential diagnoses arise regarding the potential relationship and pathogenesis of the tumor components, including hybrid tumor, collision tumor, and malignant transformation or high-grade transformation [2, 4, 10]. A hybrid salivary gland tumor has been defined as the coexistence of two distinct salivary gland tumor entities originating within the same topographical area.…”

“…A hybrid salivary gland tumor has been defined as the coexistence of two distinct salivary gland tumor entities originating within the same topographical area. In contrast, a collision tumor refers to a meeting of two malignant neoplasms that arise at independent topographical sites but subsequently grow into and invade each other; this terminology has most frequently been used to describe tumors of distinct histogenesis (i.e., carcinoma and lymphoma) [4, 11]. Malignant transformation is the process whereby a benign neoplasm undergoes biologic transformation to a malignant neoplasm, most commonly manifested as carcinoma ex pleomorphic adenoma in the salivary glands.…”

High‐grade transformation/dedifferentiation of an adenoid cystic carcinoma of the minor salivary gland to myoepithelial carcinoma

“…A gradual transitional area between the high-and low-grade components suggested HGT/dedifferentiation from lowgrade ACC to myoepithelial carcinoma, rather than a hybrid tumor, although the exact definition of a hybrid tumor is considered controversial. 8 Although approximately 40 cases of ACC with HGT/ dedifferentiation have been described since the first case report by Cheuk et al in 1999, 9 only five cases of ACC with myoepithelial dedifferentiation, including our case, have been described in the English literature ( Table 2). The present case is the second example of ACC with HGT/ dedifferentiation to myoepithelial carcinoma, and is the first example to occur in a salivary gland of the epipharynx ( Table 2).…”

“…The low‐grade component was conventional, cribriform‐type ACC and the high‐grade component demonstrated sarcomatoid features, with positive immunostaining for calponin, α‐SMA, p63 which were consistent with myoepithelial carcinoma. A gradual transitional area between the high‐ and low‐grade components suggested HGT/dedifferentiation from low‐grade ACC to myoepithelial carcinoma, rather than a hybrid tumor, although the exact definition of a hybrid tumor is considered controversial …”

Importance of High Grade Transformation and Translocations in Salivary Gland Neoplasms

“…Several findings indicated that very likely the mechanism had been a highgrade transformation rather than two different tumours occurring at the same place (still to be separated from so-called collision tumours). During the same period of time (1996-2016) more than a hundred cases of HGT in salivary gland neoplasms had been reported [2]. In another study, we investigated the clinical consequences of HGT in salivary adenoid cystic carcinoma.…”