International Journal of Oral & Maxillofacial Pathology. 2013;4(2):07-11 ISSN 2231 – 2250

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Original Research

Different Histolopathologic Features of Pleomorphic Adenoma in Salivary Glands

Mahmood Jahangir Nezhad, Saedeh Atarbashi Moghadam, Sepideh Mokhtari, ShirinTaravati


Back ground: Pleomorphic adenoma is the most common salivary gland tumor. It is composed of varying proportions of epithelial and myoepithelial cells that are arranged in a great variety of

morphological patterns. Therefore, it has a diverse histological presentation that may cause diagnostic problems with other salivary gland tumors. Purpose of Study: The objective of this
study was to assess the different histopathological features of pleomorphic adenoma in salivary
glands. Materials and Methods: Fifty specimens of pleomorphic adenoma were analyzed. All the cases were primary neoplasms and excisional biopsies. The tumors were classified as stroma- rich, cell-rich and classic (balanced amount of epithelial and stromal component).The mesenchymal component was divided into myxoid, chondroid, hyaline, fatty and calcified tissue. The parenchymal component was analyzed according to presence of spindle, plasmacytoid, basaloid, squamous, cubic, mucous and oncocytoid cells. The architectural pattern was divided in to ductal, solid and trabecular. Presence of capsule was also analyzed. Results: The most common pattern was cell-rich (38%). Myxoid (78%) and Hyalinized (56%) stroma were the most frequent mesenchymal tissues. Spindle shaped (92%) and plasmacytoid (86%) cells were also the most common cell types. Ductal (72%) and solid (66%) structures were the most frequent patterns. All specimens had capsule. There was no evidence of cellular atypia or necrosis in all cases. Conclusion: The knowledge about various microscopic patterns of pleomorphic adenoma is essential and helps to have a proper diagnosis and better treatment.

Key words: Complex and Mixed Neoplasms; Histopathology; Mixed Tumor; Myoepithelial Tumor; Pleomorphic adenoma; Salivary Gland Tumors;

Mahmood Jahangir Nezhad, Saedeh Atarbashi Moghadam, Sepideh Mokhtari, ShirinTaravati. Different Histolopathologic Features of Pleomorphic Adenoma in Salivary Glands. International Journal of Oral & Maxillofacial Pathology; 2013:4(2):07-11. ©International Journal of Oral and Maxillofacial Pathology. Published by Publishing Division, Celesta Software Private Limited. All Rights Reserved.

Received on: 12/02/2013 Accepted on: 24/07/2013


Pleomorphic adenoma (PA) is a benign neoplasm with remarkable degree of
morphological diversity. It is the most common tumor of salivary glands and mainly affects the parotid.1 Clinically PA presents as a slow growing firm mass, which is
usually encapsulated. It is more frequent in adults aged 30 to 50 years, with a slight predominance among females.2 These tumors are composed of epithelial and
myoepithelial cells. Epithelial cells typically form ductal structures. The stroma demonstrates varying degrees of myxomatous, hyaline, cartilaginous and
osseous differentiation.3 Recurrence rate is
20 - 45% after the simple procedure of tumor enucleation.4 The purpose of this study was to evaluate the various microscopic features of PA and determine the diversity of
histopathological features in this tumor.

Materials and methods

Fifty specimens of PA were collected from the archives of pathology department of
Ahvas University of Medical Sciences. All
the cases were excisional biopsies and primary tumors. Clinical data were recorded. Histopathological features were assessed by using hematoxylin and eosin (H & E) stained sections.
An average of four slides was analyzed for per patient. The tumors were classified as stroma-rich (myxoid), cell-rich (cellular) and classic (balanced amount of epithelial and stromal components) as described by Seifert
et al.3 The stromal changes were analyzed according to the presence of myxoid,
hyaline, chondroid, fatty and osseous tissue.
The parenchymal component was analyzed according to presence of spindle, plasmacytoid, basaloid, squamous, cubic, mucous and oncocytoid cells. The architectural pattern was divided to ductal, solid and trabecular. Presence of capsule was analyzed. The sections were observed with Olympus CX21 light microscope. SPSS (Statistical Package for Social Science) software (Version 16) was used to analyze the data.

©2013 International Journal of Oral and Maxillofacial Pathology. Published by Publishing Division, Celesta Software Private Limited. All Rights Reserved

8 Mahmood Jahangir Nezhad, et al. ISSN 2231 - 2250


The majority of cases were located in the parotid (68%). The male to female ratio was
1:1 (25 persons in each group). The mean age was 39 years ranging from 19 to 75
years and the peak of incidence was in the
fourth and sixth decades. Tumors were classified as cell-rich, classic and stroma- rich (Table 1).
Spindle cells were the most common cell type, being present in 92% of studied

Table 4: Stroma subtypes in pleomorphic adenoma


Pleomorphic adenomas are the most common neoplasms of salivary glands.
These benign tumors are composed of
epithelial and myoepithelial cells with various


neoplasms. Plasmacytoid and Cubic cells
morphological patterns and subtypes.
were present in more than 80% of cases representing the next most frequent cell types. Squamous and basaloid cells were found in few cases. There was no evidence of mucous or oncocytic metaplasia in the specimens (Table 2).
In one case, keratin pearl formation was evident (Fig 1). Concerning the morphological patterns of parenchymal
component, duct formation (72%) was the
capsule varies in presence and thickness,
and many tumors show finger-like processes projecting into the capsule. Naeim et al has divided the PAs,according to their cellularity, into 3 groups as hypocellular, moderately cellular and hypercellular (similar to Seifert
definition).6 Here, cell-rich subtype was the most common pattern followed by classic
and stroma-rich architecture; however, the
results were close to each other. Stroma-rich pattern has been the most common subtype


most frequent pattern (Table 3). Myxoid
in few other studies.
Bullerdiek et al states
change (78%) was the most common stromal change (Fig 2). In addition, Hyalinized stroma was most frequent in cell- rich PAs (Fig 3). Chondroid change and fatty stroma (Fig 4 & 5) were less common (Table
4). All specimens had capsule. There was no evidence of calcified material, atypical cells or necrosis in all cases.


pattern Number Percent

that the majority of classic tumors have 8q12
rearrangement whereas myxoid PAs demonstrate normal karyotype. 12q13-15 rearrangement is also more common in cellular PAs.7
Harney et al research revealed that PAs of the superficial lobe of parotid had more stromal component than tumors of the deep lobe. They also found no significant difference in predominant cell types between


Stroma-rich 15 30

tumors of superficial and deep lobes. In

Cellular 19 38

Classic 16 32

Total 50 100

Table 1: Histological classification of pleomorphic adenoma in 50 cases

our study, spindle and plasmacytoid cells
were the most frequent cell types that was in accordance with other studies.3,4 Ellis et al suggests that these cells appear to be in
transition from one form to the other form.3

Interestingly, recent studies show that plasmacytoid cells in PA originate from

Cell type

Plasmac ytoid


e Cubic

Basal oid

Squam ous

luminal cells rather than myoepithelial cells.10 Here, similar to other studies, cubic

Numb 43

46 40 2 7

cells were the third most common cell type.

er (86%) (92%) (80%) (4%) (14%) Table 2: Cellular types present in the parenchymal component of pleomorphic adenoma

Squamous cells were in the fourth grade. Extensive squamous metaplasia and keratin pearl formation could be mistaken for malignant tumors such as mucoepidermoid carcinoma and squamous cell carcinoma. In


pattern of epithelial


Duct Solid Trabecular

addition, pleomorphic adenoma and polymorphous low-grade adenocarcinoma are frequently mistaken with each other.11

Tumors number 36 (72%)

33 (66%)

28 (56%)

In our specimens, no mucous and oncocytic cells were found. Triantafyllou et al suggest

Table 3: Morphology of epithelial

components of pleomorphic adenoma
that mucous cells in PA reflect an abnormal line of differentiation.12 This abnormality is an increased synthesis of luminal cells or

ISSN 2231 – 2250 Different Histolopathologic Features of Pleomorphic Adenoma in... 9

retention of glycoproteins.10 Development of oncocytes is most associated with acini and striated duct cells.13 Oncocytoid variant of PA has also been reported in the literature.14
In this study, ductal and solid structures were the most frequent patterns followed by trabecular architecture.However, in Ito et al study the trabecular and ductal patterns
were the most common features.3

Figure 1: The photomicrograph of pleomorphic adenoma shows various histopathological patterns like keratin pearl formation (a, x200), ductal structures with in the myxoid stroma (b, x400), hyalinization (c,x200), chondroidareas (d,x200) and fatty changes in the stroma(e,x40).

The present investigation demonstrates the predominance of myxoid and hyalinized stroma which is similar to Ito et al results.3
Some studies show that prominent zones of hyalinization are related to the aggressive behavior or malignant transformation of the tumor in future. This feature has also been
found in long standing neoplasms.15 We found no evidence of atypical cells or
necrotic areas in our specimens. Atypical
cells could be found in benign pleomorphic adenomas.3,16 Ohtake et al observed cellular atypia in fifty one percent of their analyzed
cases.17 Ethunandan et al also reported atypical histological features in some cases of benign pleomorphic adenoma.18 Atypical cells are frequently associated with previous
manipulation of tumor by biopsy or fine needle aspiration.16
Here, sebaceous cells were found in 4% of cases.Cutaneous adnexal differentiation could be present in PA and may present diagnostic pitfalls. This variation must not be
misinterpreted as carcinoma.19

10 Mahmood Jahangir Nezhad, et al. ISSN 2231 - 2250

Many histological and immunohistochemical studies have been done to predict the recurrence rate of PA.4,20-23 Some
histopathological features are related to the recurrence of tumor after conservative surgery.4 Soares et al confirm that MUC-1 is
related to the recurrence of PA. They also mention that this protein is associated with malignant transformation of tumor.23 In
Stenert et al investigation, myxoid subtype was predominant in recurrent tumors.4
However, this relation was not found in other studies.20 Kazanceva et al suggest that recurrent PAs are frequently hypocellular. They also state that the amount of chondro-
myxoid stroma increases with the duration of neoplasm.24
The relation between histopathological features in PA and the presence of capsule has also been investigated. Most recurrences of PAs are multi-nodular.21
Stenert et al state that many stroma-rich tumors and some of other type PAs show a focal absence of the capsule. They conclude that conservative surgery, especially in tumors of stroma-rich type, is a major risk
factor of recurrence.4


The numerous phenotypic features of pleomorphic adenoma may challenge the
pathologists. As many PAs may resemble some malignant salivary gland tumors which
can lead to misdiagnosis and unnecessarily lead to aggressive therapy. Therefore,
histopathological variations in PA should be
well-known and this is essential for correct diagnosis and better treatment.


We would like to acknowledge all the staff members for their support and guidance.

Author Affiliations

1.Dr.Mahmood Jahangir Nezhad, Associate Professor, Department of Periodontics, Faculty of Dentistry, Jundishapur University of Medical Sciences, Ahvaz, Iran, 2.Dr.Saedeh Atarbashi Moghadam, Assistant Professor, 3.Dr.Sepideh Mokhtari, Assistant Professor, Department of Oral and Maxillofacial Pathology, Dental School of Shahid Beheshti University of Medical Sciences, Tehran, Iran, 4.Dr.Shirin Taravati, Resident of Pediatric Dentistry, Faculty of Dentistry, Babol University of Medical Sciences, Babol, Iran.


1. Gordon-Nunez MA, Godoy GP, Soares
RC, Souza LB, Freitas RA, Queiroz LM. Immunohistochemical expression of
PCNA, P53 and bcl-2 in pleomorphic
adenomas. Int J Morphol 2008;26:567-
2. Felix A, Rosa JC, Fonseca L, Cidadao A, Soares J. Laminin and collagen IV in pleomorphic adenoma and carcinoma
ex-pleomorphic adenoma: An
immunohistochemical study. Hum Pathol
3. Ito FA, Jorge J, Vargas PA, Lopes MA.
Histopathological findings of pleomorphic adenomas of the salivary gland. Med Oral Pathol Oral Cir Buccal
4. Stennert E, Guntinas-Lichius O, Klussmann JP, Arnold G. Histopathology of pleomorphic adenoma in the parotid
gland: a prospective unselected series
of 100 cases. Laryngoscope
5. Goulart MC, Freitas-Faria P, Goulart
GR, et al. Pleomorphic adenoma with extensive squamous metaplasia and keratin cyst formations in minor salivary gland: a case report. J Appl Oral Sci
6. Naeim F, Forsberg MI, Waisman J, Coulson WF. Mixed tumors of the salivary glands: growth pattern and
recurrence. Arch Pathol Lab Med
7. Bullerdiek J, Wobst G, Meyer-Bolte K, Chilla R, Haubrich J, Thode B. Cytogenetic subtyping of 220 salivary gland pleomorphic adenomas: correlation to occurrence, histological subtype, and in vitro cellular behavior. Cancer Genet Cytogenet 1993;65(1):27-
8. Harney MS, Murphy C, Hone S, Toner M, Timon CV. A histological comparison of deep and superficial lobe pleomorphic adenomas of the parotid gland. Head Neck 2003;25:649-53.
9. Fliss DM, Rival R, Gullane P, Mock D, Freeman JL. Pleomorphic adenoma: a preliminary histopathological comparison between tumors occurring in the deep and superficial lobes of the parotid gland. Ear Nose Throat J 1992;71:254-
10. Ogawa Y, Kishino M, Atsumi Y, et al.
Plasmacytoid cells in salivary-gland pleomorphic adenomas: evidence of luminal cell differentiation. Virchows
Arch 2003;443:625-34.
11. Abu El-Naaj I, Leiser Y, Wolff A, Peled M. Polymorphous low-grade adenocarcinoma: case series and review of surgical management. J Oral Maxillofac Surg 2011;69:1967-72.

ISSN 2231 – 2250 Different Histolopathologic Features of Pleomorphic Adenoma in... 11

12. Triantafyllou A. Acinar phenotypes in salivary gland pleomorphic adenoma: usual differentiation or disordered functional activity? Pathol Res Pract
13. Chang A, Harawi SJ. Oncocytes, oncocytosis, and oncocytic tumors.
Pathol Annu 1992;27:263-304.
14. Mariano FV, Vidaurre EC, Bologna- Molina RE, Carlos-Bregni R, Paes de Almeida O. Histopathological and
immunohistochemical analysis of
oncocytic pleomorphic adenoma. Indian
J Pathol Microbiol 2011;54:193-5.
15. Auclair PL, Ellis GL. Atypical features in salivary gland mixed tumors: their relationship to malignant transformation. Mod Pathol 1996;9:652-7.
16. Takeda Y. An immunohistochemical study of bizarre neoplastic cells in pleomorphic adenoma: its cytological nature and proliferative activity. Pathol Int 1999;49:993-9.
17. Ohtake S, Cheng J, Ida H, Suzuki M, Ohshiro K, Zhang W. Precancerous foci in pleomorphic adenoma of the salivary gland: recognition of focal carcinoma and atypical tumor cells by P53 immunohistochemistry. J Oral Pathol Med 2002;31:590-7.
18. Ethunandan M, Witton R, Hoffman G, Spedding A. Brennan PA. Atypical features in pleomorphic adenoma—a clinic-pathologic study and implications for management. Int Oral Maxillofac Surg 2006;35:608-12.
19. Schmidt LA, Olsen SH, McHugh JB.
Cutaneous adnexal differentiation and stromal metaplasia in palate pleomorphic adenomas: a potential diagnostic pitfall that may be mistaken for malignancy. Am J Surg Pathol
20. Soares AB, Altemani A, de Araújo VC.
Study of histopathological, morphological and immunohistochemical features of recurrent pleomorphic adenoma: an attempt to predict recurrence of pleomorphic adenoma. J Oral Pathol Med 2011;40:352-8.
21. Stennert E, Wittekindt C, Klussmann JP, Arnold G, Guntinas-Lichius O. Recurrent pleomorphic adenoma of the parotid gland: a prospective histopathological and immunohistochemical study. Laryngoscope 2004;114:158-63.
22. Henrikson G, Westrin KM, Carlsoo B, Silfversward C. Recurrent primary pleomorphic adenoma of salivary gland
origin: intrasurgical rupture,
histopathological features, and pseudopodia. Cancer 1998;82:617-20.
23. Soares AB, Demasi AP, Altemani A, de Araújo VC. Increased mucin 1 expression in recurrence and malignant
transformation of salivary gland
pleomorphic adenoma. Histopathology
24. Kazanceva A, Groma V, Smane L, Korneva E, Teibe U. Proliferative potential in benign mixed salivary gland
tumors and its value in primary and
recurrent neoplasms. Stomatologica
Baltic Dental and Maxillofacial Journal

Corresponding Author

Dr.Saedeh Atarbashi Moghadam, Assistant Professor,

Dept. of Oral and Maxillofacial Pathology, Dental School of Shahid Beheshti University

of Medical Sciences,

Velenjak Street, Tehran, Iran. Tel.: +98-912-2385589


Source of Support: Nil, Conflict of Interest: None Declared.