Histological reclassification of parotid gland carcinomas: importance for clinicians

For many clinicians, a change of histological diagnosis represents a certain taboo. In our series, the primary histopathological diagnosis was changed in about a quarter of patients. We were able to find only a few other reports discussing this issue. Van der Wal et al. reassessed specimens of tumours of small salivary glands and of the parotid gland, which resulted in change of diagnosis in 29 and 11.7 % of patients, respectively. In that series, histological verification and reclassification was based exclusively on a repeat microscopic examination of the specimens. It is worth to point out that after histological revision, the diagnosis of 7 adenomas was changed to carcinoma (total in intraoral and parotid location): (2 polymorphous low-grade adenocarcinoma, 2 MEC, adenoid cystic carcinoma, epithelial–myoepithelial carcinoma, malignant myoepithelioma), and 6 cancers (2 MEC, 2 adenoid cystic carcinoma, CxPA, adenocarcinoma not otherwise specified) to adenomas and cyst [6, 7]. In the study presented by Godballe et al., in which 85 parotid gland carcinomas were reanalysed, diagnosis was changed after microscopic reassessment and immunohistochemical tests in 20 patients (23.5 %) [8]. In a large national study in Denmark, a revision of 886 cancers of the large and small salivary glands was done and diagnosis was changed in 121 of them (14 %). In 11 cases, the diagnosis was changed from carcinoma to adenoma, in 7 CxPA in situ was diagnosed, and in next 12 cases cancers appeared to be non-epithelial malignant tumours, and in 90 cases a subtype of cancer was changed. In one case, it was found that the cancer does not originate from the salivary glands [12]. Histological assessment of salivary gland neoplasms is difficult and requires specialist experience to avoid diagnostic traps, such as misdiagnosis of necrotizing sialometaplasia or squamous metaplasia within Warthin tumour as carcinoma [10, 12, 13]. Moreover, due to significant progress in the adjunct diagnostic procedures, diagnosis of parotid gland carcinomas may require immunohistochemical and molecular tests. Nowadays, many types of cancers of the salivary glands (adenoid cystic carcinoma, epithelial‐myoepithelial carcinoma, MEC, MASC, hyalinizing clear cell carcinoma, CxPA, SDC, acinic cell carcinoma) have specific molecular biomarkers, which are used to confirm the diagnosis and also have prognostic significance [14]. Interesting results were presented by Bishop et al. After microscopic and immunohistochemical re-evaluation, and after applying molecular techniques (FISH) to acinic cell carcinoma (AcCC) specimens, the diagnosis was changed to an MASC in 9/11 (82 %) of tumours in intraoral location, 2/2 in submandibular gland, and only in 3 of 16 (19 %) in parotid [15]. Another problem faced by nonspecialist pathologists is lack of awareness of newly defined salivary neoplasms such as mucinous variant of myoepithelioma and MASC, as discovered in our study. This is illustrated in our study by the relatively high number of patients, whose diagnoses were changed from primary carcinoma of a salivary gland to a secondary lesion (metastasis to the parotid gland from kidneys, breast or skin). This is similar to the findings of Godballe et al., who reported revision of primary carcinomas to metastatic ones in 6 % of patients, with the primary location of the tumour in the breast, prostate, skin and lung [8]. Metastases to the parotid gland make 5–11 % of all malignancies of this gland with the vast majority of them originating in the skin on the head (squamous cell carcinoma and malignant melanoma) [16‐18]. However, occasionally, the primary malignancy is located outside the head and neck (kidney, breast and lung), and the metastatic tumour can be its first symptoms [18, 19]. This illustrates why access to full clinical data is necessary for proper diagnosis [16‐19].

Predicting the clinical course based on histology and progression of the disease is not obvious and to a great extent is subjective. In the studies by Van der Wal et al., during further follow-up of patients after histological reclassification there were no events observed to confirm the accuracy of diagnosis change [6, 7]. A change in the diagnosis from a malignant neoplasm to a benign one, a non-neoplastic lesion or an in situ cancer (CXPA), has a psychological significance for the patient; however, the practical (economic) aspect is important as well (shortening/conclusion of follow-up). Moreover, a change in diagnosis can occasionally enable new therapeutic options such as use of monoclonal antibody treatment (Trastuzumab, Cetuximab), kinases inhibitors BRAF, MTOR, MEK, androgen receptor blockers and others [14, 20].