Pleomorphic adenoma overview

# Overview
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.

# Historical Perspective
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.

# Classification
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.

# Pathophysiology
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.

# Causes
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.

# Differentiating pleomorphic adenoma from Other Diseases

# Epidemiology and Demographics
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.

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

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

# Natural History, Complications, and Prognosis
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.

# Diagnosis

## Diagnostic Study of Choice
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.

## History and Symptoms
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.

## Physical Examination
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.

## Laboratory Findings
There are no laboratory findings associated with pleomorphic adenoma.

## Electrocardiogram
There are no ECG findings associated with pleomorphic adenoma.

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

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

## CT scan
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
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

## Other Imaging Findings
FDG-PET scan is the other available imaging modality for pleomorphic adenoma.

## Other Diagnostic Studies
The other diagnostic studies available for pleomorphic adenoma are FNA and core biopsy.

# Treatment

## Medical Therapy
There is no medical treatment available for pleomorphic adenoma.

## Interventions

## Surgery
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.

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

## Secondary Prevention
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.