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Acinic cell Carcinoma with high-grade Squamoglandular and Chondrosarcomatous Transformation Mimicking ‘Carcinosarcoma ex-pleomorphic Adenoma’: A Wrinkle in the Proposed Nomenclature Revision for Sarcomatoid Salivary Gland Neoplasms

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Abstract

While acinic cell carcinoma (AciCC) can undergo high-grade transformation (HGT) to high-grade adenocarcinoma or poorly differentiated carcinoma, other morphologies such as spindle cell/sarcomatoid carcinoma are rare and not well-characterized. We herein report a novel case of AciCC with squamoglandular and chondrosarcomatous HGT mimicking a so-called ‘carcinosarcoma ex-pleomorphic adenoma’. The patient is an 81-year-old male with a two-month history of neck swelling and referred otalgia who presented with a left parapharyngeal space mass extending into retropharyngeal space and pterygoid muscles. On resection, the tumor showed considerable morphologic diversity with high-grade serous and mucous acinar components as well as cribriform to solid apocrine-like components with comedonecrosis and squamous differentiation, all of which were embedded in a chondromyxoid background ranging from paucicellular and bland to a high-grade chondrosarcoma/pleomorphic sarcoma-like appearance. Only a minor conventional AciCC component was noted. Immunostains were negative for AR and only focally positive for GCDFP-15 arguing against a true apocrine phenotype, while PLAG1 and HMGA2 were negative arguing against an antecedent pleomorphic adenoma. On the other hand, SOX-10, DOG-1 and PAS after diastase highlighted serous acinar differentiation, and mucicarmine, and NKX3.1 highlighted mucous acinar differentiation. NR4A3 immunohistochemical staining and NR4A3 fluorescence in situ hybridization were positive in the carcinomatous and sarcomatoid components while sequencing analysis of both components revealed identical alterations involving TP53, PIK3CB, ARID1A, and STK11. This unique case warrants caution in designating all salivary sarcomatoid carcinomas with heterologous elements as part of the ‘carcinoma ex-pleomorphic adenoma’ family.

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References

  1. Stevens TM, Agaimy A, Faquin WC, Simpson RHW, Hellquist H, Hsieh M, Kiss K Acinic cell carcinoma. In: WHO Classification of Tumours Editorial Board. Head and neck tumours. Lyon (France): International Agency for Research on Cancer; 2022.(WHO classification of tumours series, 5th ed.; vol. 9). https://publications.iarc.fr

  2. Roy S, Dhingra KK, Gupta P, Khurana N, Gupta B, Meher R Acinic cell carcinoma with extensive neuroendocrine differentiation: a diagnostic challenge. Head Neck Pathol 2009 Jun. 3(2): p. 163–168. https://doi.org/10.1007/s12105-009-0114-5

  3. Shah AA, Seethala RR Squamoglandular variant of Acinic Cell Carcinoma: a Case Report of a novel variant. Head Neck Pathol 2022 Sep. 16(3): p. 870–875. https://doi.org/10.1007/s12105-021-01399-1

  4. Romanish MG, Seethala RR (2023) Sep True Oncocytic Acinic Cell Carcinoma: A Case Image. Head Neck Pathol. 17(3): pp. 883–885. https://doi.org/10.1007/s12105-023-01578-2

  5. Chiosea SI, Griffith C, Assaad A, Seethala RR The profile of acinic cell carcinoma after recognition of mammary analog secretory carcinoma. Am J Surg Pathol 2012 Mar 36(3): p. 343–350. https://doi.org/10.1097/PAS.0b013e318242a5b0

  6. Thompson LD, Aslam MN, Stall JN, Udager AM, Chiosea S, McHugh JB Clinicopathologic and immunophenotypic characterization of 25 cases of Acinic Cell Carcinoma with High-Grade Transformation. Head Neck Pathol 2016 Jun 10(2): p. 152–160. https://doi.org/10.1007/s12105-015-0645-x

  7. Skalova A, Sima R, Vanecek T, Muller S, Korabecna M, Nemcova J, Elmberger G, Leivo I, Passador-Santos F, Walter J, Rousarova M, Jedlickova K, Curik R, Geierova M, Michal M Acinic cell carcinoma with high-grade transformation: a report of 9 cases with immunohistochemical study and analysis of TP53 and HER-2/neu genes. Am J Surg Pathol 2009 Aug. 33(8): p. 1137–1145. https://doi.org/10.1097/PAS.0b013e3181a38e1c

  8. Xu B, Saliba M, Ho A, Viswanathan K, Alzumaili B, Dogan S, Ghossein R, Katabi N Head and Neck Acinic Cell Carcinoma: a New Grading System proposal and diagnostic utility of NR4A3 immunohistochemistry. Am J Surg Pathol 2022 Jul 1. 46(7): p. 933–941. https://doi.org/10.1097/PAS.0000000000001867

  9. Ferreiro JA, Kochar AS Parotid acinic cell carcinoma with undifferentiated spindle cell transformation. J Laryngol Otol 1994 Oct 108(10): p. 902–904. https://doi.org/10.1017/s0022215100128464

  10. Stanley RJ, Weiland LH, Olsen KD, Pearson BW Dedifferentiated acinic cell (acinous) carcinoma of the parotid gland. Otolaryngol Head Neck Surg 1988 Feb. 98(2): p. 155–161. https://doi.org/10.1177/019459988809800210

  11. Seethala RR, Hunt JL, Baloch ZW, Livolsi VA, Leon Barnes E Adenoid cystic carcinoma with high-grade transformation: a report of 11 cases and a review of the literature. Am J Surg Pathol 2007 Nov 31(11): p. 1683–1694. https://doi.org/10.1097/PAS.0b013e3180dc928c

  12. Pelkey TJ, Mills SE Histologic transformation of polymorphous low-grade adenocarcinoma of salivary gland. Am J Clin Pathol 1999 Jun 111(6): p. 785–791. https://doi.org/10.1093/ajcp/111.6.785

  13. Chintakuntlawar AV, Shon W, Erickson-Johnson M, Bilodeau E, Jenkins SM, Davidson JA, Keeney MG, Rivera M, Price DL, Moore EJ, Olsen KD, Kasperbauer JL, Foote RL, Price KA, Garcia JJ (2016 May) High-grade transformation of acinic cell carcinoma: an inadequately treated entity? Oral surg oral Med oral pathol oral Radiol. 121(5):542–549. https://doi.org/10.1016/j.oooo.2016.01.011

  14. Piana S, Cavazza A, Pedroni C, Scotti R, Serra L, Gardini G (2002 Sep) Dedifferentiated acinic cell carcinoma of the parotid gland with myoepithelial features. Arch Pathol Lab Med 126(9):1104–1105. https://doi.org/10.5858/2002-126-1104-daccot

  15. Yue LE, Samankan S, Liu X, Sharif KF, Everest S, Singh T, Dhorajiya P, Baik FM, Khorsandi A, Stevens TM, Brandwein-Weber M, Urken ML Ten patients with high-grade transformation of acinic cell carcinomas: expression profiling of beta-catenin and cyclin D1 is useful. Pathol Res Pract 2020 Feb 216(2): p. 152767. https://doi.org/10.1016/j.prp.2019.152767

  16. Dardick I, George D, Jeans MT, Wittkuhn JF, Skimming L, Rippstein P, van Nostrand AW Ultrastructural morphology and cellular differentiation in acinic cell carcinoma. Oral Surg Oral Med Oral Pathol 1987 Mar 63(3): p. 325–334. https://doi.org/10.1016/0030-4220(87)90199-x

  17. Udager AM, Chiosea SI Salivary Duct Carcinoma: an update on morphologic mimics and diagnostic use of androgen receptor immunohistochemistry. Head Neck Pathol 2017 Sep. 11(3): p. 288–294. https://doi.org/10.1007/s12105-017-0798-x

  18. Chenevert J, Duvvuri U, Chiosea S, Dacic S, Cieply K, Kim J, Shiwarski D, Seethala RR DOG1: a novel marker of salivary acinar and intercalated duct differentiation. Mod Pathol 2012 Jul 25(7): p. 919–929. https://doi.org/10.1038/modpathol.2012.57

  19. Katabi N, Gomez D, Klimstra DS, Carlson DL, Lee N, Ghossein R Prognostic factors of recurrence in salivary carcinoma ex pleomorphic adenoma, with emphasis on the carcinoma histologic subtype: a clinicopathologic study of 43 cases. Hum Pathol 2010 Jul 41(7): p. 927–934. https://doi.org/10.1016/j.humpath.2009.12.011

  20. Miliauskas JR, Orell SR (2000) Oct Acinic cell carcinoma arising in pleomorphic adenoma of parotid gland. Cytopathology. 11(5): pp. 356-9. https://doi.org/10.1046/j.1365-2303.2000.00275.x

  21. Cohn ML, Elliott DD, El-Naggar AK Metastatic acinic cell carcinoma in a neurofibroma mistaken for carcinosarcoma. Head Neck 2005 Jan 27(1): p. 76–80. https://doi.org/10.1002/hed.20133

  22. Haller F, Skalova A, Ihrler S, Markl B, Bieg M, Moskalev EA, Erber R, Blank S, Winkelmann C, Hebele S, Baneckova M, Wiemann S, Muller S, Zenk J, Eils R, Iro H, Hartmann A, Agaimy A Nuclear NR4A3 immunostaining is a specific and sensitive novel marker for Acinic Cell Carcinoma of the salivary glands. Am J Surg Pathol 2019 Sep 43(9): p. 1264–1272. https://doi.org/10.1097/PAS.0000000000001279

  23. Andreasen S, Varma S, Barasch N, Thompson LDR, Miettinen M, Rooper L, Stelow EB, Agander TK, Seethala RR, Chiosea SI, Homøe P, Wessel I, Larsen SR, Erentaite D, Bishop JA, Ulhøi BP, Kiss K, Melchior LC, Pollack JR, West RB The HTN3-MSANTD3 Fusion Gene defines a subset of Acinic Cell Carcinoma of the salivary gland. Am J Surg Pathol 2019 Apr 43(4): p. 489–496. https://doi.org/10.1097/pas.0000000000001200

  24. Grunewald I, Vollbrecht C, Meinrath J, Meyer MF, Heukamp LC, Drebber U, Quaas A, Beutner D, Huttenbrink KB, Wardelmann E, Hartmann W, Buttner R, Odenthal M, Stenner M (2015 Jul) Targeted next generation sequencing of parotid gland cancer uncovers genetic heterogeneity. Oncotarget 20(20):18224–18237. https://doi.org/10.18632/oncotarget.4015

  25. Dogan S, Xu B, Rana S, Chen H, Ghossein RA, Berger MF, Ho AL, Katabi N Loss of CDKN2A/B is a molecular marker of high-grade histology and is Associated with aggressive behavior in Acinic Cell Carcinoma. Mod Pathol 2023 Jul 36(7): p. 100150. https://doi.org/10.1016/j.modpat.2023.100150

  26. Ross JS, Gay LM, Wang K, Vergilio JA, Suh J, Ramkissoon S, Somerset H, Johnson JM, Russell J, Ali S, Schrock AB, Fabrizio D, Frampton G, Miller V, Stephens PJ, Elvin JA, Bowles DW (2017 Oct) Comprehensive genomic profiles of metastatic and relapsed salivary gland carcinomas are associated with tumor type and reveal new routes to targeted therapies. Ann Oncol 1(10):2539–2546. https://doi.org/10.1093/annonc/mdx399

  27. Johnson D, Perez M, Baksh F (2000) Acinic cell carcinoma and dedifferentiated acinic cell carcinoma of the parotid gland. Mod Pathol 13:139A

    Google Scholar 

  28. Sherr CJ The INK4a/ARF network in tumour suppression. Nat Rev Mol Cell Biol 2001 Oct 2(10): p. 731–737. https://doi.org/10.1038/35096061

  29. Nichols AC, Chan-Seng-Yue M, Yoo J, Agrawal SK, Starmans MH, Waggott D, Harding NJ, Dowthwaite SA, Palma DA, Fung K, Wehrli B, Macneil SD, Lambin P, Winquist E, Koropatnick J, Mymryk JS, Boutros PC, Barrett JW (2013) A case report and genetic characterization of a massive acinic cell carcinoma of the parotid with delayed distant metastases. Case Rep Oncol Med. 2013: p. 270362. https://doi.org/10.1155/2013/270362

  30. Wang K, McDermott JD, Schrock AB, Elvin JA, Gay L, Karam SD, Raben D, Somerset H, Ali SM, Ross JS, Bowles DW (2017 Apr) Comprehensive genomic profiling of salivary mucoepidermoid carcinomas reveals frequent BAP1, PIK3CA, and other actionable genomic alterations. Ann Oncol 1(4):748–753. https://doi.org/10.1093/annonc/mdw689

  31. Ku BM, Jung HA, Sun JM, Ko YH, Jeong HS, Son YI, Baek CH, Park K, Ahn MJ (2014 Oct) High-throughput profiling identifies clinically actionable mutations in salivary duct carcinoma. J Transl Med 25:299. https://doi.org/10.1186/s12967-014-0299-6

  32. Nakaguro M, Tada Y, Faquin WC, Sadow PM, Wirth LJ, Nagao T Salivary duct carcinoma: updates in histology, cytology, molecular biology, and treatment. Cancer Cytopathol 2020 Oct 128(10): p. 693–703. https://doi.org/10.1002/cncy.22288

  33. Bou Zerdan M, Kumar PA, Zaccarini D, Ross J, Huang R, Sivapiragasam A (2023) Molecular targets in salivary gland cancers: a comprehensive genomic analysis of 118 Mucoepidermoid Carcinoma Tumors. Biomedicines. 10(2). https://doi.org/10.3390/biomedicines11020519

  34. Na K, Hernandez-Prera JC, Lim JY, Woo HY, Yoon SO Characterization of novel genetic alterations in salivary gland secretory carcinoma. Mod Pathol 2020 Apr 33(4): p. 541–550. https://doi.org/10.1038/s41379-019-0427-1

  35. Khalele B, Laforga JB, Kajo K, Kajová Macháleková K (2022) Adenosquamous Carcinomas and Mucinous Adenocarcinoma of the minor salivary glands: immunohistochemical and molecular insights. J Mol Pathol 3(4):273–285

    Article  CAS  Google Scholar 

  36. Tang S, Xue Y, Qin Z, Fang Z, Sun Y, Yuan C, Pan Y, Zhao Y, Tong X, Zhang J, Huang H, Chen Y, Hu L, Huang D, Wang R, Zou W, Li Y, Thomas RK, Ventura A, Wong KK, Chen H, Chen L, Ji H (2023 Apr) Counteracting lineage-specific transcription factor network finely tunes lung adeno-to-squamous transdifferentiation through remodeling tumor immune microenvironment. Natl Sci Rev 10(4):nwad028. https://doi.org/10.1093/nsr/nwad028

  37. Sebastiao APM, Pareja F, Kumar R, Brown DN, Silveira C, da Silva EM, Lee JY, Del A, Katabi N, Chiosea S, Weigelt B, Reis-Filho JS, Seethala RR Genomic analysis of recurrences and high-grade forms of polymorphous adenocarcinoma. Histopathology 2019 Aug 75(2): p. 193–201. https://doi.org/10.1111/his.13854

  38. Wang Y, Sun J, Sun B, Zhang C, Tian Z, Wang L, Li J (2024) The genetic and immune features of salivary gland secretory carcinoma with high-grade transformation. Oral Dis. https://doi.org/10.1111/odi.14876

    Article  PubMed  Google Scholar 

  39. Kobayashi K, Saito Y, Kage H, Fukuoka O, Yamamura K, Mukai T, Oda K, Yamasoba T CDK12 alterations and ARID1A mutations are predictors of poor prognosis and therapeutic targets in high-grade salivary gland carcinoma: analysis of the National genomic profiling database. Jpn J Clin Oncol 2023 Aug 30. 53(9): p. 798–807. https://doi.org/10.1093/jjco/hyad066

  40. Belli C, Repetto M, Anand S, Porta C, Subbiah V, Curigliano G The emerging role of PI3K inhibitors for solid tumour treatment and beyond. Br J Cancer 2023 Jun 128(12): p. 2150–2162. https://doi.org/10.1038/s41416-023-02221-1

  41. Ihrler S, Katabi N Carcinosarcoma of the salivary glands. In: WHO Classification of Tumours Editorial Board. Head and neck tumours. Lyon (France): International Agency for Research on Cancer; 2022.(WHO classification of tumours series, 5th ed.; vol. 9). https://publications.iarc.fr

  42. Ihrler S, Stiefel D, Jurmeister P, Sandison A, Chaston N, Laco J, Zidar N, Brcic L, Stoehr R, Agaimy A Salivary carcinosarcoma: insight into multistep pathogenesis indicates uniform origin as sarcomatoid variant of carcinoma ex pleomorphic adenoma with frequent heterologous elements. Histopathology 2023 Mar 82(4): p. 576–586. https://doi.org/10.1111/his.14840

  43. Virchow R Die krankhaften geschwulste. Vol. 2. 1864, Berlin: Verlag von August Hirschwald

  44. Skalova A, Hyrcza MD, Proceedings of the North American Society of Head and Neck Pathology Companion Meeting, Orleans N LA, March 12, 2023: Classification of Salivary Gland Tumors: Remaining Controversial Issues? Head Neck Pathol. 2023 Jun. 17(2): pp. 285–291. https://doi.org/10.1007/s12105-023-01541-1

  45. Dutta A, Arun P, Arun I Adenoid cystic Carcinoma with Transformation to High Grade Carcinomatous and Sarcomatoid Components: a rare case report with review of literature. Head Neck Pathol 2020 Dec 14(4): p. 1094–1104. https://doi.org/10.1007/s12105-019-01120-3

  46. Panarelli JF, Zoumalan CI, Mukkamala K, Maher EA, Iacob C, Della Rocca DA Dedifferentiated adenoid cystic carcinoma of the lacrimal gland. Ophthalmic Plast Reconstr Surg 2011 Sep-Oct 27(5): p. e119–e121. https://doi.org/10.1097/IOP.0b013e318201cb90

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  1. Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA

    Rayan Rammal, Bethany Batson, Simion I. Chiosea & Raja R. Seethala

  2. Department of Otolaryngology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA

    Matthew E. Spector

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Contributions

Conceptualization: R.R., R.R.S.; Methodology: R.R., B.B., S.I.C., R.R.S.; Molecular analysis and investigation: S.I.C., R.R.S.; Writing – original draft preparation: R.R., B.B.; Writing – review and editing: S.I.C., R.R.S.; Funding acquisition: N/A; Supervision: R.R.S.

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Rammal, R., Batson, B., Spector, M.E. et al. Acinic cell Carcinoma with high-grade Squamoglandular and Chondrosarcomatous Transformation Mimicking ‘Carcinosarcoma ex-pleomorphic Adenoma’: A Wrinkle in the Proposed Nomenclature Revision for Sarcomatoid Salivary Gland Neoplasms. Head and Neck Pathol 18, 44 (2024). https://doi.org/10.1007/s12105-024-01650-5

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