Atypical and worrisome histological features in pleomorphic adenoma: challenging and potentially significant diagnostic pitfall
Status Publisher Jazyk angličtina Země Německo Médium print-electronic
Typ dokumentu časopisecké články
PubMed
39827206
DOI
10.1007/s00428-024-04015-z
PII: 10.1007/s00428-024-04015-z
Knihovny.cz E-zdroje
- Klíčová slova
- Atypical, Mimic of malignancy, Pitfall, Pleomorphic adenoma, Salivary gland neoplasms,
- Publikační typ
- časopisecké články MeSH
Pleomorphic adenoma (PA), the most prevalent salivary gland tumor, exhibits a diverse histological spectrum characterized by epithelial, myoepithelial, and mesenchymal patterns, and secretory products. However, a subset of PAs presents microscopic features suggestive of malignancy, leading to challenging and potentially significant diagnostic pitfalls. A comprehensive retrospective analysis was conducted on the Salivary Gland Tumor Registry, compiled by the authors. A total of 104 cases diagnosed between 1960 and 2023 were retrieved. Clinical findings, pathological features, and molecular genetic results were analyzed. In the study of 104 PA cases, 23 (22.1%) presented features suggestive of pseudoinvasion, with satellite nodules being the most common (43.5%) along with capsular penetration, irregular growth, pseudopodia, lipomatous changes, and vascular permeation. Features of pseudomalignant cytomorphology were found in 97 cases (93.3%), characterized by increased cellularity, cellular atypia, heightened proliferative activity, oncocytic metaplasia, and necrosis. Additionally, 30 cases (28.8%) displayed features resembling other defined malignant salivary gland tumors, particularly myoepithelial carcinoma, adenoid cystic carcinoma, and polymorphous adenocarcinoma. Despite PA's generally straightforward diagnosis, cases with these features may be mistakenly interpreted as malignant tumors. The shared morphocytological features underscore the complexity of an accurate diagnosis, emphasizing the need for meticulous examination and a comprehensive assessment, incorporating morphological, molecular, and immunohistochemical analyses to differentiate between benign and malignant salivary gland tumors, in selected cases.
Biopticka Laboratory Ltd Pilsen Czech Republic
Department of Pathology Faculty of Medicine in Pilsen Charles University Pilsen Czech Republic
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Pérez-de-Oliveira ME, da Leonel ACLS, de Castro JFL et al (2019) Histopathological findings of intraoral pleomorphic adenomas: a retrospective study of a case series. Int J Surg Pathol 27:729–735. https://doi.org/10.1177/1066896919854181 PubMed DOI
WHO Classification of Tumours Editorial Board (2022) Head and neck tumours. WHO classification of tumours, 5th ed., vol. 9. International Agency for Research on Cancer, Lyon. https://publications.iarc.fr/
Triantafyllou A, Thompson LDR, Devaney KO et al (2015) Functional histology of salivary gland pleomorphic adenoma: an appraisal. Head Neck Pathol 9:387–404. https://doi.org/10.1007/s12105-014-0581-1 PubMed DOI
Reddy V, Wadhwan V, Aggarwal P et al (2015) A benign salivary gland tumor of minor salivary gland mimicking an epithelial malignancy. Contemp Clin Dent 6:247–249. https://doi.org/10.4103/0976-237X.156058 PubMed DOI PMC
Hernandez-Prera JC, Skálová A, Franchi A et al (2021) Pleomorphic adenoma: the great mimicker of malignancy. Histopathology 79:279–290. https://doi.org/10.1111/his.14322 PubMed DOI
Ryan RE, DeSanto LW, Weiland LH et al (1978) Cellular mixed tumors of the salivary glands. Arch Otolaryngol 104:451–453. https://doi.org/10.1001/archotol.1978.00790080033008 PubMed DOI
Ethunandan M, Witton R, Hoffman G et al (2006) Atypical features in pleomorphic adenoma–a clinicopathologic study and implications for management. Int J Oral Maxillofac Surg 35:608–612. https://doi.org/10.1016/j.ijom.2006.02.009 PubMed DOI
Auclair PL, Ellis GL (1996) Atypical features in salivary gland mixed tumors: their relationship to malignant transformation. Mod Pathol 9:652–657 PubMed
Xu B, Mneimneh W, Torrence DE et al (2019) Misinterpreted myoepithelial carcinoma of salivary gland: a challenging and potentially significant pitfall. Am J Surg Pathol 43:601–609. https://doi.org/10.1097/PAS.0000000000001218 PubMed DOI PMC
Altemani A, Martins MT, Freitas L et al (2005) Carcinoma ex pleomorphic adenoma (CXPA): immunoprofile of the cells involved in carcinomatous progression. Histopathology 46:635–641. https://doi.org/10.1111/j.1365-2559.2005.02157.x PubMed DOI
de Lima-Souza RA, Scarini JF, Lavareze L et al (2023) Discovery proteomics reveals potential protein signature associated with malignant phenotype acquisition in pleomorphic adenoma. Oral Dis 29:1017–1027. https://doi.org/10.1111/odi.14102 PubMed DOI
Zhu X, Zhang J, Chen X, Feng X (2012) Comparison of Ki-67, cyclin E, and p63 in benign and malignant human pleomorphic adenoma. Oral Surg Oral Med Oral Pathol Oral Radiol 113:667–672. https://doi.org/10.1016/j.oooo.2012.01.013 PubMed DOI
Šteiner P, Andreasen S, Grossmann P et al (2018) Prognostic significance of 1p36 locus deletion in adenoid cystic carcinoma of the salivary glands. Virchows Arch 473:471–480. https://doi.org/10.1007/s00428-018-2349-6 PubMed DOI
Michal M, Agaimy A, Contreras AL et al (2018) Dysplastic lipoma: a distinctive atypical lipomatous neoplasm with anisocytosis, focal nuclear atypia, p53 overexpression, and a lack of MDM2 gene amplification by FISH; a report of 66 cases demonstrating occasional multifocality and a rare association Wi. Am J Surg Pathol 42:1530–1540. https://doi.org/10.1097/PAS.0000000000001129 PubMed DOI
Skálová A, Agaimy A, Stanowska O et al (2020) Molecular profiling of salivary oncocytic mucoepidermoid carcinomas helps to resolve differential diagnostic dilemma with low-grade oncocytic lesions. Am J Surg Pathol 44:1612–1622. https://doi.org/10.1097/PAS.0000000000001590 PubMed DOI
Skálová A, Agaimy A, Vanecek T et al (2021) Molecular profiling of clear cell myoepithelial carcinoma of salivary glands with EWSR1 rearrangement identifies frequent PLAG1 Gene fusions but no EWSR1 fusion transcripts. Am J Surg Pathol 45:1–13. https://doi.org/10.1097/PAS.0000000000001591 PubMed DOI
Skálová A, Weinreb I, Hyrcza M et al (2015) Clear cell myoepithelial carcinoma of salivary glands showing EWSR1 rearrangement. Am J Surg Pathol 39:338–348. https://doi.org/10.1097/PAS.0000000000000364 PubMed DOI
Zbären P, Stauffer E (2007) Pleomorphic adenoma of the parotid gland: histopathologic analysis of the capsular characteristics of 218 tumors. Head Neck 29:751–757. https://doi.org/10.1002/hed.20569 PubMed DOI
Orita Y, Hamaya K, Miki K et al (2010) Satellite tumors surrounding primary pleomorphic adenomas of the parotid gland. Eur Arch Otorhinolaryngol 267:801–806. https://doi.org/10.1007/s00405-009-1149-7 PubMed DOI
Grasso M, Fusconi M, Cialente F et al (2021) Rupture of the pleomorphic adenoma of the parotid gland: what to know before, during and after surgery. J Clin Med 10:5368. https://doi.org/10.3390/jcm10225368 PubMed DOI PMC
Irani S, Dehghan A, Kalvandi Z (2023) Correlation of clinical and histopathological features of salivary pleomorphic adenoma. J Dent (Shiraz, Iran) 24:404–409. https://doi.org/10.30476/dentjods.2022.96307.1933 DOI
Stennert E, Guntinas-Lichius O, Klussmann JP, Arnold G (2001) Histopathology of pleomorphic adenoma in the parotid gland: a prospective unselected series of 100 cases. Laryngoscope 111:2195–2200. https://doi.org/10.1097/00005537-200112000-00024 PubMed DOI
Altini M, Coleman H, Kienle F (1997) Intra-vascular tumour in pleomorphic adenomas–a report of four cases. Histopathology 31:55–59. https://doi.org/10.1046/j.1365-2559.1997.5790821.x PubMed DOI
Coleman H, Altini M (1999) Intravascular tumour in intra-oral pleomorphic adenomas: a diagnostic and therapeutic dilemma. Histopathology 35:439–444. https://doi.org/10.1046/j.1365-2559.1999.035005439.x PubMed DOI
Skalova A, Altemani A, Di Palma S et al (2012) Pleomorphic adenoma of the salivary glands with intravascular tumor deposits. Am J Surg Pathol 36:1674–1682. https://doi.org/10.1097/PAS.0b013e3182690afe PubMed DOI
Alves FA, Perez DEC, Almeida OP et al (2002) Pleomorphic adenoma of the submandibular gland: clinicopathological and immunohistochemical features of 60 cases in Brazil. Arch Otolaryngol Head Neck Surg 128:1400–1403. https://doi.org/10.1001/archotol.128.12.1400 PubMed DOI
Mariano FV, Costa AF, Gondak RO et al (2015) Cellular proliferation index between carcinoma ex-pleomorphic adenoma and pleomorphic adenoma. Braz Dent J 26:416–421. https://doi.org/10.1590/0103-6440201300369 PubMed DOI
Díaz KP, Gondak R, Martins LL et al (2019) Fatty acid synthase and Ki-67 immunoexpression can be useful for the identification of malignant component in carcinoma ex-pleomorphic adenoma. J Oral Pathol Med 48:232–238. https://doi.org/10.1111/jop.12820 PubMed DOI
de Lopes MLDS, Barroso KMA, Henriques ÁCG et al (2017) Pleomorphic adenomas of the salivary glands: retrospective multicentric study of 130 cases with emphasis on histopathological features. Eur Arch Oto-Rhino-Laryngology 274:543–551. https://doi.org/10.1007/s00405-016-4253-5 DOI
Alwaheeb S, Rambaldini G, Boerner S et al (2006) Worrisome histologic alterations following fine-needle aspiration of the parathyroid. J Clin Pathol 59:1094–1096. https://doi.org/10.1136/jcp.2005.029017 PubMed DOI PMC
Takeda Y (1999) An immunohistochemical study of bizarre neoplastic cells in pleomorphic adenoma: its cytological nature and proliferative activity. Pathol Int 49:993–999. https://doi.org/10.1046/j.1440-1827.1999.00968.x PubMed DOI
Ito FA, Jorge J, Vargas PA, Lopes MA (2009) Histopathological findings of pleomorphic adenomas of the salivary glands. Med Oral Patol Oral Cir Bucal 14:E57-61 PubMed
Ferrara G, Di Vizio D, Megna AS, Insabato L (2002) Warthin’s tumor: metaplastic changes after fine needle aspiration biopsy. Acta Cytol 46:442–444 PubMed
Di Palma S, Simpson RH, Skálová A, Michal M (1999) Metaplastic (infarcted) Warthin’s tumour of the parotid gland: a possible consequence of fine needle aspiration biopsy. Histopathology 35:432–438. https://doi.org/10.1046/j.1365-2559.1999.035005432.x PubMed DOI
Allen CM, Damm D, Neville B et al (1994) Necrosis in benign salivary gland neoplasms. Oral Surg, Oral Med Oral Pathol 78:455–461. https://doi.org/10.1016/0030-4220(94)90038-8 PubMed DOI
Di Palma S, Skálová A, Vanìèek T et al (2005) Non-invasive (intracapsular) carcinoma ex pleomorphic adenoma: recognition of focal carcinoma by HER-2/neu and MIB1 immunohistochemistry. Histopathology 46:144–152. https://doi.org/10.1111/j.1365-2559.2005.02058.x PubMed DOI
Di Palma S (2013) Carcinoma ex pleomorphic adenoma, with particular emphasis on early lesions. Head Neck Pathol 7(Suppl 1):S68-76. https://doi.org/10.1007/s12105-013-0454-z PubMed DOI
Skálová A, Michal M, Ryška A et al (1999) Oncocytic myoepithelioma and pleomorphic adenoma of the salivary glands. Virchows Arch 434:537–546. https://doi.org/10.1007/s004280050381 PubMed DOI
Di Palma S, Lambros MBK, Savage K et al (2006) Oncocytic change in pleomorphic adenoma: molecular evidence in support of an origin in neoplastic cells. J Clin Pathol 60:492–499. https://doi.org/10.1136/jcp.2005.031369 PubMed DOI PMC
Mariano FV, Vidaurre E, Bologna-Molina R et al (2011) Histopathological and immunohistochemical analysis of oncocytic pleomorphic adenoma. Indian J Pathol Microbiol 54:193. https://doi.org/10.4103/0377-4929.77403 PubMed DOI
Baněčková M, Uro-Coste E, Ptáková N et al (2020) What is hiding behind S100 protein and SOX10 positive oncocytomas? Oncocytic pleomorphic adenoma and myoepithelioma with novel gene fusions in a subset of cases. Hum Pathol 103:52–62. https://doi.org/10.1016/j.humpath.2020.07.009 PubMed DOI
Lavareze L, Scarini JF, de Lima-Souza RA et al (2023) Clinicopathological and survival profile of patients with salivary gland myoepithelial carcinoma: a systematic review. J Oral Pathol Med 52:101–108. https://doi.org/10.1111/jop.13395 PubMed DOI
Xu B, Katabi N (2021) Myoepithelial carcinoma. Surg Pathol Clin 14:67–73. https://doi.org/10.1016/j.path.2020.09.008 PubMed DOI PMC
Nagao T, Sato E, Inoue R et al (2012) Immunohistochemical analysis of salivary gland tumors: application for surgical pathology practice. Acta Histochem Cytochem 45:269–282. https://doi.org/10.1267/ahc.12019 PubMed DOI PMC
Skálová A, Vanecek T, Simpson RHW et al (2013) CRTC1-MAML2 and CRTC3-MAML2 fusions were not detected in metaplastic Warthin tumor and metaplastic pleomorphic adenoma of salivary glands. Am J Surg Pathol 37:1743–1750. https://doi.org/10.1097/PAS.0000000000000065 PubMed DOI
Pérez-de-Oliveira ME, Wagner VP, Araújo ALD et al (2020) Prognostic value of CRTC1-MAML2 translocation in salivary mucoepidermoid carcinoma: systematic review and meta-analysis. J Oral Pathol Med 49:386–394. https://doi.org/10.1111/jop.12970 PubMed DOI
da Cruz Perez DE, de Abreu AF, Nobuko Nishimoto I et al (2006) Prognostic factors in head and neck adenoid cystic carcinoma. Oral Oncol 42:139–146. https://doi.org/10.1016/j.oraloncology.2005.06.024 PubMed DOI
Skálová A, Hyrcza MD, Vaneček T et al (2022) Fusion-positive salivary gland carcinomas. Genes Chromosomes Cancer 61:228–243. https://doi.org/10.1002/gcc.23020 PubMed DOI
Seethala RR, Barnes EL, Hunt JL (2007) Epithelial-myoepithelial carcinoma: a review of the clinicopathologic spectrum and immunophenotypic characteristics in 61 tumors of the salivary glands and upper aerodigestive tract. Am J Surg Pathol 31:44–57. https://doi.org/10.1097/01.pas.0000213314.74423.d8 PubMed DOI
Seethala RR (2013) Oncocytic and apocrine epithelial myoepithelial carcinoma: novel variants of a challenging tumor. Head Neck Pathol 7(Suppl 1):S77-84. https://doi.org/10.1007/s12105-013-0461-0 PubMed DOI
Okuyama K, Michi Y, Kashima Y et al (2021) Epithelial-myoepithelial carcinoma of the minor salivary glands: case series with comprehensive review. Diagnostics 11:2124. https://doi.org/10.3390/diagnostics11112124 PubMed DOI PMC
El Hallani S, Udager AM, Bell D et al (2018) Epithelial-myoepithelial carcinoma: frequent morphologic and molecular evidence of preexisting pleomorphic adenoma, common HRAS mutations in PLAG1-intact and HMGA2-intact cases, and occasional TP53, FBXW7, and SMARCB1 alterations in high-grade cases. Am J Surg Pathol 42:18–27. https://doi.org/10.1097/PAS.0000000000000933 PubMed DOI PMC
Urano M, Nakaguro M, Yamamoto Y et al (2019) Diagnostic significance of HRAS mutations in epithelial-myoepithelial carcinomas exhibiting a broad histopathologic spectrum. Am J Surg Pathol 43:984–994. https://doi.org/10.1097/PAS.0000000000001258 PubMed DOI
Rupp NJ, Brada M, Skálová A et al (2020) New insights into tumor heterogeneity: a case of solid-oncocytic epithelial-myoepithelial carcinoma of the parotid gland harboring a HRAS and heterogeneous terminating ARID1A mutation. Head Neck Pathol 14:554–558. https://doi.org/10.1007/s12105-019-01055-9 PubMed DOI
Vander Poorten V, Triantafyllou A, Skálová A et al (2018) Polymorphous adenocarcinoma of the salivary glands: reappraisal and update. Eur Arch Otorhinolaryngol 275:1681–1695. https://doi.org/10.1007/s00405-018-4985-5 PubMed DOI
Hernandez-Prera JC (2019) Historical evolution of the polymorphous adenocarcinoma. Head Neck Pathol 13:415–422. https://doi.org/10.1007/s12105-018-0964-9 PubMed DOI
Rooper L, Sharma R, Bishop JA (2015) Polymorphous low grade adenocarcinoma has a consistent p63+/p40- immunophenotype that helps distinguish it from adenoid cystic carcinoma and cellular pleomorphic adenoma. Head Neck Pathol 9:79–84. https://doi.org/10.1007/s12105-014-0554-4 PubMed DOI
Xu B, Barbieri AL, Bishop JA et al (2020) Histologic classification and molecular signature of polymorphous adenocarcinoma (PAC) and cribriform adenocarcinoma of salivary gland (CASG): an international interobserver study. Am J Surg Pathol 44:545–552. https://doi.org/10.1097/PAS.0000000000001431 PubMed DOI PMC
Weinreb I, Zhang L, Tirunagari LMS et al (2014) Novel PRKD gene rearrangements and variant fusions in cribriform adenocarcinoma of salivary gland origin. Genes Chromosomes Cancer 53:845–856. https://doi.org/10.1002/gcc.22195 PubMed DOI
Andreasen S, Melchior LC, Kiss K et al (2018) The PRKD1 E710D hotspot mutation is highly specific in separating polymorphous adenocarcinoma of the palate from adenoid cystic carcinoma and pleomorphic adenoma on FNA. Cancer Cytopathol 126:275–281. https://doi.org/10.1002/cncy.21959 PubMed DOI