KRAS codon 12 mutations characterize a subset of de novo proliferating "metaplastic" Warthin tumors.
Cystadenolymphoma
KRAS mutations
Metaplastic Warthin tumor
Mucoepidermoid carcinoma
Salivary glands
Warthin tumor
Journal
Virchows Archiv : an international journal of pathology
ISSN: 1432-2307
Titre abrégé: Virchows Arch
Pays: Germany
ID NLM: 9423843
Informations de publication
Date de publication:
May 2023
May 2023
Historique:
received:
10
11
2022
accepted:
26
01
2023
revised:
16
01
2023
medline:
5
5
2023
pubmed:
9
2
2023
entrez:
8
2
2023
Statut:
ppublish
Résumé
Warthin tumor (WT; synonym: cystadenolymphoma) represents one of the most frequent salivary gland tumors with a frequency equaling or even outnumbering that of pleomorphic adenomas in some series. Histologically, the tumor displays tall columnar oncocytic cells, arranged into two cell-thick layers lining variably cystic glands within an organoid lymphoid stroma. Tumors with exuberant squamous metaplasia in response to FNA-induced or other types of tissue injury/infarction have been referred to as "metaplastic WTs." However, the same terminology was used for tumors with variable mucinous cell and solid or stratified epidermoid proliferations (occasionally mimicking mucoepidermoid carcinoma), although the "metaplasia concept" has never been proven for the latter. We herein investigated 22 WTs showing prominent mucoepidermoid-like or solid oncocytoma-like proliferations without prior FNA or histological evidence of infarction/ trauma using the TruSight Tumor 15 gene panel and KRAS pyrosequencing. As a control, we tested 11 conventional WTs. No statistically significant differences were observed between the two subcohorts regarding patient's age and tumor size. Six of 22 (27%) proliferating/ metaplastic WTs revealed oncogenic KRAS mutations clustering at codon 12 (exon 2), while all conventional tumors lacked these mutations. Our findings are in line with a neoplastic nature of the epidermoid/ mucoepidermoid proliferations in non-injured "metaplastic" Warthin tumors. We propose the descriptive term "de novo proliferating Warthin tumor" for this variant to distinguish it from infarcted/inflamed genuine metaplastic Warthin tumor.
Identifiants
pubmed: 36752878
doi: 10.1007/s00428-023-03504-x
pii: 10.1007/s00428-023-03504-x
pmc: PMC10156774
doi:
Substances chimiques
Proto-Oncogene Proteins p21(ras)
EC 3.6.5.2
KRAS protein, human
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
839-848Informations de copyright
© 2023. The Author(s).
Références
Simpson RHW, Di Palma S, Faquin WC, Pasricha S (2022) Warthin tumour. In: WHO Classification of Tumours Editorial Board. Head and neck tumours. Lyon (France): International Agency for Research on Cancer. (WHO classification of tumours series, 5th ed, (vol. 9). https://publications.iarc.fr/
Eveson JW, Cawson RA (1986) Warthin’s tumor (cystadenolymphoma) of salivary glands. A clinicopathologic investigation of 278 cases. Oral Surg Oral Med Oral Pathol 61:256–262
doi: 10.1016/0030-4220(86)90371-3
pubmed: 3458128
Seifert G, Bull HG, Donath K (1980) Histologic subclassification of the cystadenolymphoma of the parotid gland. Analysis of 275 cases. Virchows Arch A Pathol Anat Histol 388:13–38
doi: 10.1007/BF00430674
pubmed: 7467121
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
doi: 10.1046/j.1365-2559.1999.035005432.x
pubmed: 10583558
Maisch S, Mueller SK, Traxdorf M, Weyerer V, Stoehr R, Iro H, Hartmann A, Agaimy A (2020) Sinonasal papillomas: a single centre experience on 137 cases with emphasis on malignant transformation and EGFR/KRAS status in “carcinoma ex papilloma.” Ann Diagn Pathol 46:151504
doi: 10.1016/j.anndiagpath.2020.151504
pubmed: 32203683
Psychogios G, Vlastos I, Thölken R, Zenk J (2020) Warthin’s tumour seems to be the most common benign neoplasm of the parotid gland in Germany. Eur Arch Otorhinolaryngol 277:2081–2084
doi: 10.1007/s00405-020-05894-z
pubmed: 32189070
Mantsopoulos K, Iro H (2020) Pleomorphic adenoma compared with cystadenolymphoma of the parotid gland: which is more common? Br J Oral Maxillofac Surg 58:361–363
doi: 10.1016/j.bjoms.2019.12.014
pubmed: 31980273
Lawal AO, Adisa AO, Kolude B et al (2013) A review of 413 salivary gland tumours in the head and neck region. J Clin Exp Dent 5(e218–22):9
Chapnik JS (1983) The controversy of Warthin’s tumor. Laryngoscope 93:695–716
doi: 10.1288/00005537-198306000-00002
pubmed: 6304434
Arida M, Barnes EL, Hunt JL (2005) Molecular assessment of allelic loss in Warthin tumors. Mod Pathol 18:964–968
doi: 10.1038/modpathol.3800379
pubmed: 15861216
Honda K, Kashima K, Daa T, Yokoyama S, Nakayama I (2000) Clonal analysis of the epithelial component of Warthin’s tumor. Hum Pathol 31:1377–1380
doi: 10.1016/S0046-8177(00)80007-6
pubmed: 11112212
Zaccarini DJ, Khurana KK (2020) incidence of non-salivary gland neoplasms in patients with Warthin tumor: a study of 73 cases. Head Neck Pathol 14:412–418
doi: 10.1007/s12105-019-01049-7
pubmed: 31228167
Lewis PD, Baxter P, Paul Griffiths A, Parry JM, Skibinski DO (2000) Detection of damage to the mitochondrial genome in the oncocytic cells of Warthin’s tumour. J Pathol 191:274–281
doi: 10.1002/1096-9896(2000)9999:9999<::AID-PATH634>3.0.CO;2-U
pubmed: 10878549
Mandic R, Agaimy A, Pinto-Quintero D, Roth K, Teymoortash A, Schwarzbach H, Stoehr CG, Rodepeter FR, Stuck BA, Bette M (2020) Aberrant expression of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in Warthin tumors. Cancers (Basel) 12:1112
doi: 10.3390/cancers12051112
pubmed: 32365590
Bullerdiek J, Haubrich J, Meyer K, Bartnitzke S (1988) Translocation t(11;19)(q21;p13.1) as the sole chromosome abnormality in a cystadenolymphoma (Warthin’s tumor) of the parotid gland. Cancer Genet Cytogenet 35:129–132
doi: 10.1016/0165-4608(88)90131-8
pubmed: 3180001
Mark J, Dahlenfors R, Stenman G, Nordquist A (1990) Chromosomal patterns in Warthin’s tumor. A second type of human benign salivary gland neoplasm. Cancer Genet Cytogenet 46:35–39
doi: 10.1016/0165-4608(90)90006-V
pubmed: 2331681
Nordkvist A, Mark J, Dahlenfors R, Bende M, Stenman G (1994) Cytogenetic observations in 13 cystadenolymphomas (Warthin‘s tumors). Cancer Genet Cytogenet 76:129–135
doi: 10.1016/0165-4608(94)90463-4
pubmed: 7923062
Wemmert S, Willnecker V, Sauter B, Schuh S, Brunner C, Bohle RM, Urbschat S, Schick B (2014) Genomic alterations in Warthin tumors of the parotid gland. Oncol Rep 31:1899–1904
doi: 10.3892/or.2014.3028
pubmed: 24549898
Skálová A, Vanecek T, Simpson RH, Vazmitsel MA, Majewska H, Mukensnabl P, Hauer L, Andrle P, Hosticka L, Grossmann P, Michal M (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
doi: 10.1097/PAS.0000000000000065
pubmed: 24121173
Bieńkowski M, Kunc M, Iliszko M, Kuźniacka A, Studniarek M, Biernat W (2020) MAML2 rearrangement as a useful diagnostic marker discriminating between Warthin tumour and Warthin-like mucoepidermoid carcinoma. Virchows Arch 477:393–400
doi: 10.1007/s00428-020-02798-5
pubmed: 32222825
pmcid: 7443186
Rotellini M, Paglierani M, Pepi M, Franchi A (2012) MAML2 rearrangement in Warthin’s tumour: a fluorescent in situ hybridisation study of metaplastic variants. J Oral Pathol Med 41:615–620
doi: 10.1111/j.1600-0714.2012.01159.x
pubmed: 22582766
Ishibashi K, Ito Y, Masaki A, Fujii K, Beppu S, Sakakibara T, Takino H, Takase H, Ijichi K, Shimozato K, Inagaki H (2015) Warthin-like mucoepidermoid carcinoma: a combined study of fluorescence in situ hybridization and whole-slide imaging. Am J Surg Pathol 39:1479–1487
doi: 10.1097/PAS.0000000000000507
pubmed: 26457352
Seifert G (1997) Carcinoma in pre-existing Warthin tumors (cystadenolymphoma) of the parotid gland. Classification, pathogenesis and differential diagnosis. Pathologe 18:359–367
doi: 10.1007/s002920050227
pubmed: 9432671
Skálová A, Michal M, Nathanský Z (1994) Epidermoid carcinoma arising in Warthin’s tumour: a case study. J Oral Pathol Med 23:330–333
doi: 10.1111/j.1600-0714.1994.tb00070.x
pubmed: 7965888
Mantsopoulos K, Psychogios G, Agaimy A, Künzel J, Zenk J, Iro H, Bohr C (2015) Inflamed benign tumors of the parotid gland: diagnostic pitfalls from a potentially misleading entity. Head Neck 37:23–29
doi: 10.1002/hed.23541
pubmed: 24488708
Kerk SA, Papagiannakopoulos T, Shah YM, Lyssiotis CA (2021) Metabolic networks in mutant KRAS-driven tumours: tissue specificities and the microenvironment. Nat Rev Cancer 21:510–525
doi: 10.1038/s41568-021-00375-9
pubmed: 34244683
Alqaidy D, Moran CA (2021) Primary Warthin’s-like adenocarcinoma of the lung: a clinicopathological, immunohistochemical, and molecular analysis of three cases. Pathol Res Pract 227:153648
doi: 10.1016/j.prp.2021.153648
pubmed: 34656914
Tong K, Zhu W, Fu H, Cao F, Wang S, Zhou W, Liu C, Chen D, Fan S, Hu Z (2020) Frequent KRAS mutations in oncocytic papillary renal neoplasm with inverted nuclei. Histopathology 76:1070–1083
doi: 10.1111/his.14084
pubmed: 31997427
Sudduth CL, McGuire AM, Smits PJ, Konczyk DJ, Al-Ibraheemi A, Fishman SJ, Greene AK (2020) Arteriovenous malformation phenotype resembling congenital hemangioma contains KRAS mutations. Clin Genet 98:595–597
doi: 10.1111/cge.13833
pubmed: 32799314
pmcid: 7955771
Baumhoer D, Kovac M, Sperveslage J, Ameline B, Strobl AC, Krause A, Trautmann M, Wardelmann E, Nathrath M, Höller S, Hardes J, Gosheger G, Krieg AH, Vieth V, Tirabosco R, Amary F, Flanagan AM, Hartmann W (2019) Activating mutations in the MAP-kinase pathway define non-ossifying fibroma of bone. J Pathol 248:116–122
doi: 10.1002/path.5216
pubmed: 30549028
Turek D, Haefliger S, Ameline B, Alborelli I, Calgua B, Hartmann W, Harder D, Flanagan AM, Amary F, Baumhoer D (2022) Brown tumors belong to the spectrum of KRAS -driven neoplasms. Am J Surg Pathol 46:1577–1582
doi: 10.1097/PAS.0000000000001963
pubmed: 36040039
pmcid: 9561227
Stenman G (2013) Fusion oncogenes in salivary gland tumors: molecular and clinical consequences. Head Neck Pathol 7(Suppl 1):S12–S19
doi: 10.1007/s12105-013-0462-z
pubmed: 23821214
Nakaguro M, Urano M, Ogawa I, Hirai H, Yamamoto Y, Yamaguchi H, Tanigawa M, Matsubayashi J, Hirano H, Shibahara J, Tada Y, Tsuzuki T, Okada Y, Sato Y, Ikeda K, Sukeda A, Honda Y, Mikami Y, Nagao T (2020) Histopathological evaluation of minor salivary gland papillary-cystic tumours: focus on genetic alterations in sialadenoma papilliferum and intraductal papillary mucinous neoplasm. Histopathology 76:411–422
doi: 10.1111/his.13990
pubmed: 31505033
Agaimy A, Mueller SK, Bumm K, Iro H, Moskalev EA, Hartmann A, Stoehr R, Haller F (2018) Intraductal papillary mucinous neoplasms of minor salivary glands with AKT1 p.Glu17Lys mutation. Am J Surg Pathol. 42:1076–1082
doi: 10.1097/PAS.0000000000001080
pubmed: 29738361
Bishop JA, Gagan J, Baumhoer D, McLean-Holden AL, Oliai BR, Couce M, Thompson LDR (2020) Sclerosing polycystic “adenosis” of salivary glands: a neoplasm characterized by PI3K pathway alterations more correctly named sclerosing polycystic adenoma. Head Neck Pathol 14:630–636
doi: 10.1007/s12105-019-01088-0
pubmed: 31605313
Skálová A, Baněčková M, Laco J, Di Palma S, Agaimy A, Ptáková N, Costes-Martineau V, Petersson BF, van den Hout MFCM, de Rezende G, Klubíčková N, Koblížek M, Koshyk O, Vaneček T, Leivo I (2022) Sclerosing polycystic adenoma of salivary glands: a novel neoplasm characterized by PI3K-AKT pathway alterations-new insights into a challenging entity. Am J Surg Pathol. 46:268–280
doi: 10.1097/PAS.0000000000001807
pubmed: 34510113
Hernandez-Prera JC, Saeed-Vafa D, Heidarian A, Gewandter K, Otto K, Wenig BM (2022) Sclerosing polycystic adenoma: conclusive clinical and molecular evidence of its neoplastic nature. Head Neck Pathol 16:416–426
doi: 10.1007/s12105-021-01374-w
pubmed: 34410594
Rooper LM, Agaimy A, Assaad A, Bal M, Eugene H, Gagan J, Nonogaki H, Palsgrove DN, Shah A, Stelow E, Stoehr R, Thompson LDR, Weinreb I, Bishop JA (2022) Recurrent IDH2 mutations in salivary gland striated duct adenoma define an expanded histologic spectrum distinct from canalicular adenoma. Am J Surg Pathol. Online ahead of print. https://doi.org/10.1097/PAS.0000000000002004
McLean AC, Rooper LM, Gagan J, Thompson LDR, Bishop JA (2022) A subset of salivary intercalated duct lesions harbors recurrent CTNNB1 and HRAS mutations: a molecular link to basal cell adenoma and epithelial-myoepithelial carcinoma? Head Neck Pathol. https://doi.org/10.1007/s12105-022-01513-x
doi: 10.1007/s12105-022-01513-x
pubmed: 36480093
Novoplansky O, Jagadeeshan S, Regev O, Menashe I, Elkabets M (2022) Worldwide prevalence and clinical characteristics of RAS mutations in head and neck cancer: a systematic review and meta-analysis. Front Oncol 12:838911
doi: 10.3389/fonc.2022.838911
pubmed: 35600380
pmcid: 9121358
Sau P, Graham JH, Helwig EB (1995) Proliferating epithelial cysts. Clinicopathological analysis of 96 cases. J Cutan Pathol. 22:394–406
doi: 10.1111/j.1600-0560.1995.tb00754.x
pubmed: 8594071