Pleomorphic adenoma

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

Pleomorphic adenoma also known as (“Benign mixed tumor of the salivary glands“) is a benign neoplastic tumor of the salivary glands. It is the most common type of salivary gland tumor and the most common tumor of the parotid gland. In 1874, pleomorphic adenoma was first described by Minssen in a monograph named Ahlbom’s. Later Mark and Dahlenfors in 1986 and Bullerdiek et al. in 1987 found some clonal chromosome abnormalities related to pleomorphic adenoma, with a majority of aberrations involving 8q12. Pleomorphic adenoma can be classified on the basis of the histological appearance into 4 subgroups. Subgroup 1 is the classical pleomorphic adenoma with a stroma content of 30-50%, subgroup 2 has a stroma content of 80%, subgroup 3 has a poor stroma content of 20-30%, subgroup 4 has also a poor stroma content (6%). Pleomorphic adenoma shows chromosomal transposition mainly involving PLAG1 and HMGA2. Pleomorphic adenoma’s are usually firm, mobile, well demarcated and encapsulated on gross apperance. On microscopy it is characterized by both epithelial elements and stromal matrix which can be either hyaline, myxoid or cartilaginous. The incidence of pleomorphic adenoma is approximately 2-3.5 cases per 100,000 population. Females are predominantly affected by Pleomorphic adenoma than males. The various risk factors for the development of pleomorphic adenoma are prior irradiation to head and neck, working in rubber, asbestos industries. The most common presentation is a painless, slow growing and single palpable mass. Pleomorphic adenoma is usually asymptomatic but some people present with dysphagia, hoarseness, difficulty with chewing. MRI is the imaging modality of choice for pleomorphic adenoma. Total parotidectomy is the mainstay of treatment for pleomorphic adenoma. The complications of parotidectomy include haematoma or haemorrhage, facial nerve palsy, frey’s syndrome. The prognosis of pleomorphic adenoma is excellent after complete surgical excision.

Pleomorphic adenoma was first described by Minssen in 1874 in a monograph named Ahlbom’s. Later Mark and Dahlenfors in 1986 and Bullerdiek et al. in 1987 found some clonal chromosome abnormalities that are related to pleomorphic adenoma.

Pleomorphic adenoma can be classified into 4 subgroups on the basis of histology appearance and stromal content. Subgroup 1, subgroup 2, subgroup 3, subgroup 4.

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 stomal matrix. The stromal matrix can be of hyaline, cartilaginous, or myxoid. The epithelial components can be arranged into clumps, sheets or interlacing strands. On immunohistology these tumors are positive for S-100, GFAP, keratin, actin, myosin.

There are no well established causes for pleomorphic adenoma. However some clonal chromosomal abnormalities with aberrations involving 8q12 and 12q15 have been described. Simian virus(SV40) is thought to play a role either in the cause or progression of the tumor.

The annual incidence of pleomorphic adenoma is approximately 2-3.5 cases per 100,000 population. It accounts for 45-75% of all salivary gland neoplasms. Females are more commonly affected than males.

The major risk factors for pleomorphic adenoma are prior head and neck irradiation, working in rubber and asbestos industries.

There are no screening modalities available for early detection of pleomorphic adenoma.

Pleomorphic adenoma is usually asymptomatic though some people present with a palpable nodular mass which is slow growing and painless. The complications that arise from surgery include rupture of the capsule of the tumor, incomplete resection of the tumor, haematoma or haemorrhage, facial nerve palsy, trismus, wound infection, frey’s syndrome, parotid fistula and hypoesthesia of the greater auricular nerve. The prognosis of pleomorphic adenoma is generally excellent after complete resection of the tumor. Although a small proportion i.e 2-7% of cases can go to malignant transformation.

MRI is the study of choice for pleomorphic adenoma. On T1-weighted images they show homogeneous intensity, on T2 they show marked hyperintensity reflecting myxochondroid stroma and hypointensity fibrous capsule of the tumor. On Gd-T1 imaging it shows heterogeneous enhancement.

The majority of patients with pleomorphic adenoma are asymptomatic. Patients usually present with a history of swelling, which is gradual in onset and painless in nature. When pleomorphic adenoma arises from the parotid gland people present with dysphagia, dyspnea, difficulty in chewing, hoarseness, and dry mouth. If it occurs in lacrimal gland patients complain of proptosis, diplopia, fullness in the temporal upper eyelid and even visual impairment.

Patients with pleomorphic adenoma are usually normal in general and they have normal physical examination except a visible swelling or para-pharyngeal mass which is palpable if the tumor arises from the deep lobe of the parotid.

There are no laboratory findings associated with pleomorphic adenoma.

There are no ECG findings associated with pleomorphic adenoma.

There are no x-ray findings associated with pleomorphic adenoma.

There are no echocardiography findings associated with pleomorphic adenoma. On ultrasonography they are hypoechoic, well defined and lobulated tumors with posterior acoustic enhancement.

CT findings associated with pleomorphic adenoma include homogeneous attenuation and prominent enhancement if the tumor is small and heterogeneous enhancement and foci of necrosis, haemorrhage and even delayed enhancement if the tumor is large

MRI is the imaging modality of choice for pleomorphic adenoma. The findings on T1-weighted images are homogeneous intensity while on T2 it shows marked hyperintensity which reflects abundant myxochondroid stroma. On Gd-T1 it shows heterogeneous enhancement

FDG-PET scan is the other available imaging modality for pleomorphic adenoma.

The other diagnostic studies available for pleomorphic adenoma are FNA and core biopsy.

There is no medical treatment available for pleomorphic adenoma.

Surgery is the mainstay of treatment for pleomorphic adenoma. There are two procedures superficial parotidectomy and total parotidectomy, the latter of which is the most commonly performed one due to its low incidence on recurrence of the tumor. The complications after surgery include facial nerve palsy, frey’s syndrome, trismus, haematoma or haemorrhage and wound infection. Recurrence do occur in pleomorphic adenoma sometimes.

There are no established measures for the primary prevention of pleomorphic adenoma.

Effective measures for the secondary prevention of pleomorphic adenoma include timely radiologic imaging, blood tests, avoiding working at risk environments like rubber and asbestos industries, minimizing head and neck irradiation as much as possible.

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

Pleomorphic adenoma was first described by Minssen in 1874 in a monograph named Ahlbom’s. Later Mark and Dahlenfors in 1986 and Bullerdiek et al. in 1987 found some clonal chromosome abnormalities that are related to pleomorphic adenoma.

• In 1874, Minssen was the first to describe in detail about pleomorphic adenoma in monograph named Ahlbom’s.^[1]
• Later in 1986, Mark and Dahlenfors found some clonal chromosome abnormalities related to pleomorphic adenoma, with a majority of them involving 8q12.^[2]
• In 1987 Bullerdiek et al found another subset of tumors characterized by changes affecting 12q13-q15.^[3]

There is no much evidence on the landmark events in the development of treatment strategies.

There is no much evidence of pleomorphic adenoma on the impact on cultural history.

There aren’t any famous cases on pleomorphic adenoma.

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

Pleomorphic adenoma can be classified into 4 subgroups on the basis of histology appearance and stromal content into 4 groups. Subgroup 1, subgroup 2, subgroup 3, subgroup 4. It can also be classified based upon the component that predominates into 3 types, cellular, stroma rich, and mixed type.

• Pleomorphic adenoma can be classified based on the stromal content of the tumor into the following subgroups.^[1]
  • Subgroup 1 is the classical pleomorphic adenoma with a stroma content of 30-50%
  • subgroup 2 has a stroma content of 80%
  • subgroup 3 has a poor stroma content of 20-30% or less and an epithelial differentiation similar to subgroup 1
  • subgroup 4 has also a poor stroma content (6%) with a relatively monomorphic epithelial structure.
• Depending upon which component predominates pleomorphic adenoma can also be classified into:^[2]
  • Cellular(either epithelial or myoepithelial cell rich)
  • Stroma-rich
  • Mixed type or classic

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

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.

• The exact pathogenesis of pleomorphic adenoma is not completely understood.

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

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

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

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:
  • Epithelomucoid
  • Myxoid
  • Cartilaginous
  • Hyaline.
• 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.

  

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

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

There are no well established causes for pleomorphic adenoma. However some clonal chromosomal abnormalities with aberrations involving 8q12 and 12q15 have been described. Simian virus(SV40) is thought to play a role either in the onset or progression of the tumor.

• There are no established causes for the development of pleomorphic adenoma.
• However some clonal chromosomal abnormalities with aberrations involving 8q12 and 12q15 have been described.^[1]
• Oncogenic simian virus(SV40) may play a role in the onset or progression of pleomorphic adenoma.^[2]

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

[Disease name] must be differentiated from other diseases that cause [clinical feature 1], [clinical feature 2], and [clinical feature 3], such as [differential dx1], [differential dx2], and [differential dx3].

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As [disease name] manifests in a variety of clinical forms, differentiation must be established in accordance with the particular subtype. [Subtype name 1] must be differentiated from other diseases that cause [clinical feature 1], such as [differential dx1] and [differential dx2]. In contrast, [subtype name 2] must be differentiated from other diseases that cause [clinical feature 2], such as [differential dx3] and [differential dx4].

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Diseases	Clinical manifestations						Para-clinical findings							Gold standard	Additional findings
	Symptoms			Physical examination
							Lab Findings			Imaging			Histopathology
	Symptom 1	Symptom 2	Symptom 3	Physical exam 1	Physical exam 2	Physical exam 3	Lab 1	Lab 2	Lab 3	Imaging 1	Imaging 2	Imaging 3
Differential Diagnosis 1
Differential Diagnosis 2
Differential Diagnosis 3
Diseases	Symptom 1	Symptom 2	Symptom 3	Physical exam 1	Physical exam 2	Physical exam 3	Lab 1	Lab 2	Lab 3	Imaging 1	Imaging 2	Imaging 3	Histopathology	Gold standard	Additional findings
Differential Diagnosis 4
Differential Diagnosis 5
Differential Diagnosis 6

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

The annual incidence of pleomorphic adenoma is approximately 2-3.5 cases per 100,000 population. It accounts for 45-75% of all salivary gland neoplasms. Females are more commonly affected than males.

• The annual incidence of pleomorphic adenoma is approximately 2-3.5 cases per 100,000 population.^[1]
• It accounts for 45-75% of all salivary gland neoplasms.
• Pleomorphic adenoma distribution among the salivary glands is as follows^[2]:
  • Parotid gland: 84%
  • Submandibular gland: 8%
  • Minor salivary glands: 6.5%

• People of all age groups may develop pleomorphic adenoma.^[1]
• The incidence of pleomorphic adenoma increases with age; the average age at diagnosis is 43-46 years.

• There is no racial predilection to pleomorphic adenoma.

• Females are predominantly affected by pleomorphic adenoma than males. The female to male ratio is approximately (2:1)^[1]

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

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There are no established risk factors for [disease name].

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The most potent risk factor in the development of [disease name] is [risk factor 1]. Other risk factors include [risk factor 2], [risk factor 3], and [risk factor 4].

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Common risk factors in the development of [disease name] include [risk factor 1], [risk factor 2], [risk factor 3], and [risk factor 4].

• Common risk factors in the development of [disease name] may be occupational, environmental, genetic, and viral.
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Maneesha Nandimandalam, M.B.B.S.[2]

Pleomorphic adenoma is usually asymptomatic though some people present with a palpable nodular mass which is slow growing and painless. The complications that arise from surgery include rupture of the capsule of the tumor, incomplete resection of the tumor, haematoma or haemorrhage, facial nerve palsy, trismus, wound infection, frey’s syndrome, parotid fistula and hypoesthesia of the greater auricular nerve. The prognosis of pleomorphic adenoma is generally excellent after complete resection of the tumor. Although a small proportion i.e 2-7% of cases can go to malignant transformation.

• Pleomorphic adenoma usually presents as an asymptomatic disease.^[1]
• If symptomatic it presents as a slow growing, painless and a palpable single nodular mass.
• If left untreated a small proportion of patients with peomorphic adenoma may progress to malignant transformation.

• Rupture of the capsule of the parotid tumor.
• Incomplete resection of the tumor.
• Facial nerve transection especially after superficial parotidectomy.

• Haemorrhage or haematoma
• Infection at the site
• Trismus
• Parotid fistula
• Frey’s syndrome^[3]
• Hypoesthesia of the greater auricular nerve.^[4]

Apart from the above mentioned other complications include facial disfigurement and multiple recurrences.

• Prognosis is generally excellent for most of the patients after surgical resection.
• Depending on the extent of the tumor at the time of diagnosis, the prognosis may vary sometimes.
• Recurrence can be a problem if the tumor arises from the parotid gland.^[5][6]
• 2-7% of cases can go into malignant transformation if left untreated.^[7]

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