Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. The Quest for Diagnosis of Minor Salivary Gland Neoplasms From Biopsy To the Editor: In the paper by Turk and Wenig, 1 the authors highlighted the diagnostic difficulties faced by pathologists when dealing with small incisional biopsies from minor salivary gland tumors, especially when the borders of the lesion are not present in the sample. The authors also stated that, in such sce- nario, it is impossible to reach a specific diagnosis or even to tell a benign from a malignant lesion. We feel obliged to disagree with the authors in some aspects, based on our own experience. We agree that among the more frequent minor salivary gland tumors, such as pleomorphic adenoma (PA), mucoepidermoid carcinoma (MEC), polymorphous low-grade adenocarci- noma (PLGA), and adenoid cystic carcinoma (ACC), the only lesion identifiable solely by its cellular com- ponents is the MEC. Nevertheless, even a small fragment of biopsy can contain precious detail on tissue architecture, which is indeed characteristic of each of those lesions, and therefore, the essence to tell them apart. 2 A minor salivary gland PA has a strong cellular component, usually rep- resented by modified myoepithelial cells (hyaline or, more frequently, plasmacy- toid), as well as duct-like structures con- taining both epithelial and myoepithelial cells within the stroma. This picture is typical of a PA. The exception to that rule is myoepithelioma, which is merely an academic classification, and therefore irrelevant from the prognostic point of view, as both lesions are benign and the treatment is also the same. The real challenge with a PA is to exclude the possibility of a malignant trans- formation, based on clinical suspicion. A carcinoma ex-PA is thankfully an extremely rare event in minor salivary glands, however, both myoepithelial and duct cells can become malignant without any clear features of malignization. 3 Tumor diagnosis then becomes imprac- tical without the borders of the lesion in the biopsy sample to check for invasion. ACC is also composed of 2 cell types, epithelial/ductal and myoepithelial; however, the tissue architecture encoun- tered in this lesion is rather typical and it goes beyond its peculiar nuclear mor- phology, as described by the authors. ACC usually presents with a cribriform pattern, with the formation of small ducts of epithelial cells among many pseudo- cystic spaces surrounded by myoepithelial cells. The small ducts stand out because of their eosinophilic epithelial cytoplasm. The solid type of ACC is the most diffi- cult to diagnose: whenever it shows a cribriform pattern the cystic spaces are then surrounded by epithelial cells. 4 PLGA is usually characterized by a single cell type, which was really well described by the authors. It is impor- tant to highlight that it is extremely difficult to detect 2 types of cells, ductal and myoepithelial, in these lesions. 5 Ducts made of a single layer of cells are only found in PLGA and canalicular adenoma, never in PA or ACC. 6 Regarding the use of immunohis- tochemistry, contrary to the authors’ opinion, we believe that it plays an important role on diagnosing minor salivary gland neoplasms, even in small incisional biopsy samples. 2 CK7 and vimentin-positive cells are present in all PLGA cells and they help to dis- tinguish between ductal and myoepi- thelial cells in PA, ACC, and basal cell adenoma. This is a crucial tool to dif- ferentiate the cribriform areas between a PLGA and an ACC. 4 They are also helpful to differentiate between PLGA and canalicular adenoma, which is another minor salivary gland tumor composed exclusively of ductal cells. 6 S-100 marks PA and PLGA, but not ACC. 7 Futhermore, p53 staining helps to distinguish between a PA and a carcinoma ex-PA. 8,9 The illustrations on the paper may also contain some errors, for instance, Figures 2E and 2F are good examples of ACC, as ductal cells with an eosi- nophilic cytoplasm can be seen among myoepithelial cells. Figure 6D shows ducts formed of a single layer of cells, therefore, not a PA, however, very similar to the image seen in Figure 2B. Immunohistochemistry would, therefore, have been rather useful to distinguish between those lesions. On the basis of a considerable lifetime experience in teaching, research- ing, and diagnosing minor salivary gland tumors, we do believe that it is possible to distinguish between them, with very few exceptions, thus setting the grounds for safe treatment planning. Vera C. de Araujo, DDS, MSc, PhD Marcelo Sperandio, DDS, MSc, PhD Ney S. Araujo, DDS, MSc, PhD Sao Leopoldo Mandic Research Center Campinas, SP, Brazil REFERENCES 1. Turk AT, Wenig BM. Pitfalls in the biopsy diagnosis of intraoral minor sali- vary gland neoplasms: diagnostic consid- erations and recommended approach. Adv Anat Pathol. 2014;21:1–11. 2. de Arau´jo VC, de Sousa SO, Carvalho YR, et al. Application of immunohisto- chemistry to the diagnosis of salivary gland tumors. Appl Immunohistochem Mol Morphol. 2000;8:195–202. 3. Altemani A, Martins MT, Freitas L, et al. Carcinoma ex pleomorphic adenoma (CXPA): immunoprofile of the cells involved in carcinomatous progression. Histopathology. 2005;46:635–641. 4. Arau´jo VC, Loducca SV, Sousa SO, et al. The cribriform features of adenoid cystic carcinoma and polymorphous low- grade adenocarcinoma: cytokeratin and integrin expression. Ann Diagn Pathol. 2001;5:330–334. 5. Araujo V, Sousa S, Jaeger M, et al. Characterization of the cellular compo- nent of polymorphous low-grade adeno- carcinoma by immunohistochemistry and electron microscopy. Oral Oncol. 1999;35:164–172. 6. Furuse C, Tucci R, Machado de Sousa SO, et al. Comparative immunoprofile of polymorphous low-grade adenocarci- noma and canalicular adenoma. Ann Diagn Pathol. 2003;7:278–280. 7. Furuse C, Sousa SO, Nunes FD, et al. Myoepithelial cell markers in salivary gland neoplasms. Int J Surg Pathol. 2005; 13:57–65. 8. Freitas LL, Arau´jo VC, Martins MT, et al. Biomarker analysis in carcinoma ex pleomorphic adenoma at an early phase of carcinomatous transformation. Int J Surg Pathol. 2005;13:337–342. 9. Soares AB, Altemani A, de Arau´jo VC. Study of histopathological, morpholog- ical and immunohistochemical features of recurrent pleomorphic adenoma: an attempt to predict recurrence of pleo- morphic adenoma. J Oral Pathol Med. 2011;40:352–358. The authors have no funding or conflicts of interest to disclose. LETTERS TO THE EDITOR Adv Anat Pathol  Volume 22, Number 4, July 2015 www.anatomicpathology.com | 279