Pleomorphic adenoma pathophysiology

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Maneesha Nandimandalam, M.B.B.S.[2]

Overview

The exact pathogenesis of pleomorphic adenoma is not fully understood. Chromosomal abnormalities involving 8q12 and 12q15 have been described. The gross features of pleomorphic adenoma are firm, well demarcated, encapsulated, and mobile. On microscopic histopathology they are a mixture of both epithelial cells and stromal matrix. The stromal matrix can be either hyaline, cartilaginous, myxoid. The epithelial components can be arranged into clumps, sheets or interlacing strands. On immunohistology these tumors are positive for S-100, GFAP, actin, keratin.

Pathophysiology

Pathogenesis

The exact pathogenesis of pleomorphic adenoma is not completely understood.

Genetics

PLAG1 and HMGA2 chromosomal rearrangments are specific to pleomorphic adenoma.^[1]

Some clonal chromosomal abnormalities involving 8q12 and 12q15 have been noted.^[2]

Gross Pathology

Pleomorphic adenoma gross appearance Source:Department of Pathology,Calicut Medical College

The gross pathological features of Pleomorphic adenoma are as follows^[3]:

Firm
Mobile
Well demarcated
Encapsulated(mostly, but the Myxoid and Stroma rich subtype sometimes show focal absences of capsule)
Tan-white in appearance

Microscopic Pathology

Pleomorphic adenoma has a highly variable appearance on microscopy, hence the name given. On microscopic histopathological analysis, the characteristic findings of pleomorphic adenoma are:^[4]

The tumor is enclosed by a fibrous capsule of which may vary in thickness.
Stromal matrix mixed with polygonal epithelial and spindle-shaped myoepithelial cells constitutes majority of the tumor histopathology.
Depending upon the nature of the stroma adenomas can be:
Based upon which element predominates pleomorphic adenoma can be:
- Cellular(either epithelial or myoepithelial cell rich)
- Stroma-rich
- Mixed type or classic
Epithelial components are usually of polygonal,spindle, or stellate shaped cells which may be arranged into various patterns:^[5]
- Sheets
- Clumps
- Interlacing strands.
- Duct-like structures
The ducts and tubules that are present in pleomorphic adenoma consists of two cell types:^[5]
- An outer myoepithelial layer
- Inner cuboidal epithelial cell layer
This particular outer myoepithelial cell layer is the one that blends into the surrounding stroma which contains scattered or clumped myoepithelial element cells.^[5]
Areas of squamous metaplasia and epithelial pearls are also seen.
Librepath [CC BY-SA 3.0 (https://creativecommons.org/licenses/by-sa/3.0) or GFDL (http://www.gnu.org/copyleft/fdl.html)], from Wikimedia Commons

On immunohistochemical analysis, the positive stains of pleomorphic ademona include:

Positive S-100 protein^[6]
Positive GFAP mainly in myxomatous and early chondromatous differentiation.^[7]
Keratin^[8]
Actin
Myosin
BMP-6 protein overexpression.^[9]

References

↑ Mendoza, Pia R.; Jakobiec, Frederick A.; Krane, Jeffrey F. (2013). “Immunohistochemical Features of Lacrimal Gland Epithelial Tumors”. American Journal of Ophthalmology. 156 (6): 1147–1158.e1. doi:10.1016/j.ajo.2013.06.034. ISSN 0002-9394.
↑ Debnath SC, Adhyapok AK (June 2010). “Pleomorphic adenoma (benign mixed tumour) of the minor salivary glands of the upper lip”. J Maxillofac Oral Surg. 9 (2): 205–8. doi:10.1007/s12663-010-0052-5. PMC 3244097. PMID 22190789.
↑ Zhan KY, Khaja SF, Flack AB, Day TA (April 2016). “Benign Parotid Tumors”. Otolaryngol. Clin. North Am. 49 (2): 327–42. doi:10.1016/j.otc.2015.10.005. PMID 27040584.
↑ Zhan, Kevin Y.; Khaja, Sobia F.; Flack, Allen B.; Day, Terry A. (2016). “Benign Parotid Tumors”. Otolaryngologic Clinics of North America. 49 (2): 327–342. doi:10.1016/j.otc.2015.10.005. ISSN 0030-6665.
↑ ^5.0 ^5.1 ^5.2 Bokhari MR, Greene J. PMID 28613579. Missing or empty |title= (help)
↑ Furuse, Cristiane; de Sousa, Suzana O. Machado; Nunes, Fabio Daumas; de Magalhaes, Marina Helena Cury Gallottini; de Arauijo, Vera Cavalcanti (2016). “Myoepithelial Cell Markers in Salivary Gland Neoplasms”. International Journal of Surgical Pathology. 13 (1): 57–65. doi:10.1177/106689690501300108. ISSN 1066-8969.
↑ Nishimura T, Furukawa M, Kawahara E, Miwa A (December 1991). “Differential diagnosis of pleomorphic adenoma by immunohistochemical means”. J Laryngol Otol. 105 (12): 1057–60. PMID 1664847.
↑ Mori M, Tsukitani K, Ninomiya T, Okada Y (October 1987). “Various expressions of modified myoepithelial cells in salivary pleomorphic adenoma. Immunohistochemical studies”. Pathol. Res. Pract. 182 (5): 632–46. PMID 2446294.
↑ Kusafuka K, Yamaguchi A, Kayano T, Takemura T (December 1999). “Immunohistochemical localization of the bone morphogenetic protein-6 in salivary pleomorphic adenomas”. Pathol. Int. 49 (12): 1023–7. PMID 10632922.

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[MendozaJakobiec2013-1] Mendoza, Pia R.; Jakobiec, Frederick A.; Krane, Jeffrey F. (2013). “Immunohistochemical Features of Lacrimal Gland Epithelial Tumors”. American Journal of Ophthalmology. 156 (6): 1147–1158.e1. doi:10.1016/j.ajo.2013.06.034. ISSN 0002-9394.

[pmid22190789-2] Debnath SC, Adhyapok AK (June 2010). “Pleomorphic adenoma (benign mixed tumour) of the minor salivary glands of the upper lip”. J Maxillofac Oral Surg. 9 (2): 205–8. doi:10.1007/s12663-010-0052-5. PMC 3244097. PMID 22190789.

[pmid27040584-3] Zhan KY, Khaja SF, Flack AB, Day TA (April 2016). “Benign Parotid Tumors”. Otolaryngol. Clin. North Am. 49 (2): 327–42. doi:10.1016/j.otc.2015.10.005. PMID 27040584.

[ZhanKhaja2016-4] Zhan, Kevin Y.; Khaja, Sobia F.; Flack, Allen B.; Day, Terry A. (2016). “Benign Parotid Tumors”. Otolaryngologic Clinics of North America. 49 (2): 327–342. doi:10.1016/j.otc.2015.10.005. ISSN 0030-6665.

[pmid28613579-5] 5.0 ^5.1 ^5.2 Bokhari MR, Greene J. PMID 28613579. Missing or empty |title= (help)

[Furusede_Sousa2016-6] Furuse, Cristiane; de Sousa, Suzana O. Machado; Nunes, Fabio Daumas; de Magalhaes, Marina Helena Cury Gallottini; de Arauijo, Vera Cavalcanti (2016). “Myoepithelial Cell Markers in Salivary Gland Neoplasms”. International Journal of Surgical Pathology. 13 (1): 57–65. doi:10.1177/106689690501300108. ISSN 1066-8969.

[pmid1664847-7] Nishimura T, Furukawa M, Kawahara E, Miwa A (December 1991). “Differential diagnosis of pleomorphic adenoma by immunohistochemical means”. J Laryngol Otol. 105 (12): 1057–60. PMID 1664847.

[pmid2446294-8] Mori M, Tsukitani K, Ninomiya T, Okada Y (October 1987). “Various expressions of modified myoepithelial cells in salivary pleomorphic adenoma. Immunohistochemical studies”. Pathol. Res. Pract. 182 (5): 632–46. PMID 2446294.

[pmid10632922-9] Kusafuka K, Yamaguchi A, Kayano T, Takemura T (December 1999). “Immunohistochemical localization of the bone morphogenetic protein-6 in salivary pleomorphic adenomas”. Pathol. Int. 49 (12): 1023–7. PMID 10632922.

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