Head and Neck Pathology

, Volume 14, Issue 1, pp 230–238 | Cite as

Acantholytic Squamous Cell Carcinoma and Salivary Duct Carcinoma Ex-pleomorphic Adenoma of the Submandibular Gland: A Report of Two Extremely Rare Cases with an Immunohistochemical Analysis

  • Kimihide KusafukaEmail author
  • Takuya Kawasaki
  • Tetsuro Onitsuka
  • Noriko Hamaguchi
  • Kotaro Morita
  • Takashi Mukaigawa
  • Yukio Nishiya
  • Tomoyuki Kamijo
  • Yoshiyuki Iida
  • Takashi Nakajima
  • Takashi Sugino
Case Report


Carcinoma ex pleomorphic adenoma (CXPA) is a malignant tumor of the salivary gland that arises from pleomorphic adenoma (PA). Squamous cell carcinoma (SCC) is extremely rare in the salivary glands. We report two cases of acantholytic SCC (ASCC) ex PA. Case 1 involved a 72-year-old female, and case 2 involved a 67-year-old male. Histologically, both cases involved PA, and salivary duct carcinoma (SDC) components, which were positive for androgen receptor (AR) and gross cystic disease fluid protein (GCDFP)-15 but negative for HER2, were seen in the intracapsular regions. The invasive components consisted of ASCC, which were positive for cytokeratin 5/6 and p63 but negative for AR and GCDFP-15. The SDC and ASCC components were positive for the epidermal growth factor receptor. In both cases, the cytoplasmic localization or decreased expression of E-cadherin was observed in the ASCC. In the early phase, CXPA might emerge as SDC, and it might change into SCC as it invades beyond the capsule due to changes in microenvironment. Also, the aberrant expression of E-cadherin is related to acantholysis in SCC.


Acantholysis Squamous cell carcinoma Salivary duct carcinoma Carcinoma ex pleomorphic adenoma E-cadherin 



Carcinoma ex pleomorphic adenoma


Pleomorphic adenoma


Salivary duct carcinoma


Androgen receptor


Gross cystic disease fluid protein-15


Human epidermal growth factor receptor 2


Squamous cell carcinoma


Acantholytic squamous cell carcinoma


Elastica van Gieson




Epidermal growth factor receptor




Prostate specific antigen


α-smooth muscle actin


Epithelial–mesenchymal transition




Alpha-methylacyl-CoA racemase


Cytoplasmic positivity


Myoepithelial cells


Ductal cells



The authors thank Mr. Isamu Hayashi, Mr. Kiyoshi Tone, Ms. Sachiyo Ono, Mr. Koji Muramatsu, Mr. Masato Abe, Mr. Hiroshi Tashiro, Mr. Masatake Honda, Ms. Chiho Tashiro, Ms. Shiori Masujima, Mr. Hiroyuki Shiiya, Mr. Shogo Fujii, Ms. Yoko Kosaka, and Ms. Miho Naka (the staff at the Pathology Division, Shizuoka Cancer Center, Shizuoka, Japan) for their excellent technical assistance. We are also grateful to Ms. Minako Ishii, (the secretary of the Pathology Division, Shizuoka Cancer Center, Shizuoka, Japan) for her valuable help during the preparation of this manuscript.

Author Contributions

KK designed and drafted the manuscript, and KK, TNa and TS made the histopathological diagnosis. TO, NH, KM, TM, TNi, TK, and YI belong to Division of Head and Neck Surgery, Shizuoka Cancer Center, Shizuoka, Japan.


The authors declare that they received no funding support for this study.

Compliance with Ethical Standards

Conflict of interest

The authors declare no conflict of interest in association with this study.

Ethics Approval and Consent to Participate

This study was approved by the institutional review board of Shizuoka Cancer Center (No. 19–49). All subjects signed informed consent forms to participate.

Consent for Publication

Written informed consent for publication of their clinical details and/or clinical images was obtained from the patient. A copy of the consent form is available for review by the Editor of this journal.


  1. 1.
    Gnepp DR. Malignant mixed tumours of the salivary glands: a review. Pathol Annu. 1993;28:279–328.PubMedGoogle Scholar
  2. 2.
    Nagao T, Licitra L, Loening T, et al. Salivary duct carcinoma. In: El-Nagger AK, Chan JKC, Grandis JR et al, editors. WHO classification of head and neck tumours. Lyon: IARC; 2017. pp. 173–5.Google Scholar
  3. 3.
    Lim CM, Hobson C, Kim S, et al. Clinical outcome of patients with carcinoma ex pleomorphic adenoma of the parotid gland: a comparative study from a single tertiary center. Head Neck. 2015;37:543–7.CrossRefGoogle Scholar
  4. 4.
    Udager AM, Chiosea SI. Salivary duct carcinoma: an update on morphologic mimics and diagnostic use of androgen receptor immunohistochemistry. Head Neck Pathol. 2017;11:288–94.CrossRefGoogle Scholar
  5. 5.
    Rosa JC, Fonseca I, Felix A, et al. Immunohistochemical study of c-cerbB-2 expression in carcinoma ex-pleomorphic adenoma. Histopathology. 1996;28:247–52.CrossRefGoogle Scholar
  6. 6.
    Taxy JB. Squamous cell carcinoma in a major salivary gland: a review of the diagnostic considerations. Arch Pathol Lab Med. 2001;125:740–5.PubMedGoogle Scholar
  7. 7.
    Weedon D. Strutton G, Rubin A. Adenoid squamous cell carcinoma. Weedon’s skin pathology, 3th edn. London: Churchill Livingstone; Elsevier; 2010. p. 694–695.Google Scholar
  8. 8.
    Cassarino DS, Derienzo DP, Barr RJ. Cutaneous squamous cell carcinoma (adenoacanthoma): a comprehensive clinicopathologic classification. Part one. J Cutan Pathol. 2006; 33: 191–206.PubMedGoogle Scholar
  9. 9.
    Garcia C, Crowson AN. A catholytic squamous cell carcinoma: is it really a more-aggressive tumor? Dermatol Surg. 2011;37:353–6.CrossRefGoogle Scholar
  10. 10.
    Lewis JE, Olsen KD, Sebo TJ. Carcinoma ex pleomorphic adenoma: pathologic analysis of 73 cases. Hum Pathol. 2001;32:596–604.CrossRefGoogle Scholar
  11. 11.
    Nakamori K. Ohuchi T, Hasegawa T, et al. Carcinoma ex pleomorphic adenoma of the buccal region is composed of salivary duct carcinoma and squamous cell carcinoma components. Int J Oral Maxillofac Surg. 2009;38:1116–8.CrossRefGoogle Scholar
  12. 12.
    Iino M, Yamada H, Ishikawa H, et al. Carcinoma ex pleomorphic adenoma of the submandibular gland: report of a case with an unusual malignant component of clear cell squamous cell carcinoma. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2008;106:e30–4.CrossRefGoogle Scholar
  13. 13.
    Garth RJ. Squamous liver metastases from a carcinoma arising within a pleomorphic adenoma of the parotid gland. J Laryngol Otol. 1990;104:152–3.CrossRefGoogle Scholar
  14. 14.
    Magaki SD, Bhuta S, Abemayer E, et al. Carcinoma ex-pleomorphic adenoma of the parotid gland consisting of high-grade salivary duct carcinoma and keratinizing squamous cell carcinoma. Oral Surg Oral Med Oral Pathol Oral Radiol. 2015;120:e169–73.CrossRefGoogle Scholar
  15. 15.
    Enokida T, Fujii S, Kuno H, et al. Combined salivary duct carcinoma and squamous cell carcinoma suspected of carcinoma ex pleomorphic adenoma. Pathol Int. 2016;66:460–5.CrossRefGoogle Scholar
  16. 16.
    Skalova A, Starek I, Vanecek T, et al. Expression of HER-2/neu gene and protein in salivary duct carcinomas of parotid gland as revealed by fluorescence in situ hybridization and immunohistochemistry. Histopathology. 2003;42:348–56.CrossRefGoogle Scholar
  17. 17.
    Takase S, Kano S, Taka Y, et al. Biomarker immunoprofile in salivary duct carcinomas; clinicopathological and prognostic implications with evaluation of the revised classification. Oncotarget. 2017;8:59023–35.CrossRefGoogle Scholar
  18. 18.
    Kusafuka K, Ebihara M, Ishiki H, et al. Primary adenoid squamous cell carcinoma of the oral cavity. Pathol Int. 2006;56:78–83.CrossRefGoogle Scholar
  19. 19.
    Kusafuka K, Onitsuka T, Miki T, et al. Squamous cell carcinoma with rhabdoid features of the gingiva: a case report with unusual histology. Med Mol Morphol. 2014;47:240–5.CrossRefGoogle Scholar
  20. 20.
    Griffin JR, Wriston CC, Peters MS, et al. Decreased expression of intercellular adhesion molecules in acantholytic squamous cell carcinoma compared with invasive well-differentiated squamous cell carcinoma of the skin. Am J Clin Pathol. 2013;139:442–7.CrossRefGoogle Scholar
  21. 21.
    Bayer-Garner IB, Smoller BR. The expression of syndecan-1 is preferentially reduced compared with that of E-cadherin in acantholytic squamous cell carcinoma. J Cutan Pathol. 2001;28:83–9.CrossRefGoogle Scholar
  22. 22.
    Lakhani SR, Rakha E, Simpson PT. Invasive lobular carcinoma. Lakhani SR, Ellis IO, Schnitt SJ, Tan PH, van de Vijver M, editors. World Health Organization Classification of Tumours of the Breast. Lyon: IARC; 2012. 40–42.Google Scholar
  23. 23.
    Kusafuka K, Kawasaki T, Maeda M, et al. Salivary duct carcinoma with rhabdoid features: a salivary counterpart of pleomorphic lobular carcinoma of the breast. Histopathology. 2017;70:164–73.CrossRefGoogle Scholar
  24. 24.
    Gu X, Jiang R, Fowler MR. Acantholytic squamous cell carcinoma in upper aerodigestive tract: Histopathology, Immunohistochemical profile and epithelial mesenchymal transition phenotype change. Head Neck Pathol. 2012;6:438–44.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Kimihide Kusafuka
    • 1
    Email author
  • Takuya Kawasaki
    • 1
  • Tetsuro Onitsuka
    • 2
  • Noriko Hamaguchi
    • 2
  • Kotaro Morita
    • 2
  • Takashi Mukaigawa
    • 2
  • Yukio Nishiya
    • 2
  • Tomoyuki Kamijo
    • 2
  • Yoshiyuki Iida
    • 2
  • Takashi Nakajima
    • 1
  • Takashi Sugino
    • 1
  1. 1.Pathology DivisionShizuoka Cancer CenterShizuokaJapan
  2. 2.Division of Head and Neck SurgeryShizuoka Cancer CenterShizuokaJapan

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