Salivary gland neoplasms

Introduction:

Tumors involving major / minor salivary glands could either be from epithelial or mesenchymal tissues. Larger the size of salivary gland, more are the chances of tumor being benign. Nearly 80% of parotid, 60% of submandibular and 25% of minor salivary glands are benign. it should be pointed out that the incidence of malignacy in minor salivary glands are rather higher.

The pointers towards the diagnosis of salivary gland malignant lesions include:

1. Rapid growth

2. Restricted mobility

3. Skin fixity

4. Pain

5. Involvement of facial nerve

Classification of tumors of salivary glands:

Salivary gland tumors could be classified into:

Benign tumors:

Epithelial

1. Pleomorphic adenoma 2. Warthin tumor 3. Oncocytoma 4. Other adenomas

Mesenchymal:

1. Hemangioma 2. Lymphangioma 3. Lipoma 4. Neurofibroma

Malignant tumors:

Epithelial

1. Mucoepidermoid carcinoma - Low grade / High grade 2. Adenoid cystic carcinoma (cylindroma) 3. Acinic cell carcinoma 4. Adenocarcinoma 5. Malignant mixed tumor 6. Squamous cell carcinoma 7. Undifferentiated carcinoma

Mesenchymal:

1. Lymphoma 2. Sarcoma

Pleomorphic adenoma:

This is the most common salivary gland tumor. This is also known as the mixed tumor because of its dural origin from epithelial and myoepithelial elements.

Etiology:

Is unknown. The incidence of this tumor has shown an increase in the last two decades. One study suggests that oncogenic simian virus (SV40) may play a role in the onset / progression of pleomorphic adenoma.

Epidemiology:

This is the most common benign salivary gland neoplasm. It constitues nearly 75% of all salivary gland tumors. This tumor occurs in individuals of all ages. It is however most common in the 3-6th decades. The incidence of pleomorphic adenoma is slightly more in females than in males (2:1). This tumor predominantly affects the superficial lobe of the parotid gland. Distribution among various salivary glands are as follows:

Parotid gland - 84%

Submandibular gland - 8%

Minor salivary glands - 6.5%

Pathophysiology:

Microscopy show a highly varied appearance and hence the term pleomorphic is used to describe this condition. It is characterized by mixed proliferation of polygonal epithelial and spindle shaped myoepithelial cells in a variable stroma matrix of myxoid, mucoid, cartilaginous or hyaline origin.

Epithelial elements are usually polygonal, spindle or stellate shaped cells that are arranged to form duct like structures, sheets, clumps or interlacing strands.

The tumor lacks true capsule and is surrounded by a fibrous pseudo capsule of variable thickness. The tumor extends through normal glandular parenchyma in the form of finger like pseudopodia. These microscopic extensions account for the high risk of recurrence in cases treated with simple enucleation or surgical resections performed with inadequate surgical margins.

Clinical features:

Pleomorphic adenoma usually presents as a solitary mobile slow growing, painless mass. This mass could be present for many years without causing significant issues other than the size.

Signs and symptoms usually depend on size, location and potential to undergo malignant transformation. In parotid gland signs of facial nerve weakness occur when the tumor is large or if it undergoes malignant transformation. Pleomorphic adenoma in the deep lobe of parotid gland could present as an oral retro tonsillar mass / parapharyngeal mass. Rapid enlargement of tumor mass should arouse the suspicion of malignant transformation.

Diagnosis:

Imaging helps in localization of the lesion and histopathological studies confirms it. FNAC can be resorted to for tissue diagnosis.

Management:

Enucleation procedures have been abandoned due to high recurrance rates. Currently either superficial parotidectomy / total parotidectomy has been performed in these patients.

Warthin's tumor (Adenolymphoma):

This is a fairly common tumor. It makes up about a third of parotid tumors. It is commonly seen in parotid gland.

Features:

Age of the patient - In men it peaks at the 7th decade and in females it peaks at the 6th decade.

Smoking history - Retrograde flow of substances in tobacco smoke into the salivary gland ducts could cause this problem.

Lack of symptoms

Delay in presentation

This condition could be bilateral in nearly 10% of patients.

Histopathology is confirmatory. Classic features include presence of oncocytic epithelial cells in a lymphoid stroma.

This tumor can be managed by surgical resection.

Oncocytoma:

This tumor arises from acidophilic cells called oncocytes. These are epithelial cells with abundant granular, eosinophilic cytoplasm. They have a centrally placed pyknotic nucleus and are crammed with numerous mitochondria of various sizes. They constitute about 1% of all salivary gland tumors. This condition is mostly seen in the elderly. These lesions are cystic in nature and does not grow more than 5 cm. It affects parotid gland commonly.

WHO classification recognizes three oncocytic entities: Oncocytosis, Oncocytoma and Oncocytic carcinoma. Among these entities oncocytoma is the commonest.

This lesion is a well circumscribed mass, composed of layers of oncocytes. Pathogenesis is obscure, but mitochondrial functional defects are believed to mediate the progressive degeneration of salivary epithelial cells. Oncocytic cells are believed to be metaplastic cells formed in response to adverse changes, with normal cells losing their original specialization.Ageing causes exhaustion of mitochondrial enzymes and a compensatory hyperplasia of mitochondria results. This is responsible for oncocytic change. Viral infections with EB virus, herpes virus have also been implicated.

Superficial parotidectomy is used to manage this condition.

Hemangioma:

This is the most common benign tumor of parotid in children. These lesions are commonly found in females. These are vascular abnormalities characterised by increased proliferation and renewal of endothealial cells. These lesions are classified as cavernous, capillary and mixed hemangiomas.

This is the most common benign tumor of parotid in children. Most of these lesions are discovered at birth. They grow rapidly during the neonatal period and then involutes spontaneously. Cutaneous hemangioma may be associated in nearly half of these patients.

These lesions are soft and painless. They increase in size when the child cries or strains. Overlying skin may show bluish discoloration.

Lesions that fail to undergo spontaneous resolution should be managed by excision. Pre op embolisation can be considered in large lesions.

Lymphangiomas:

These lesions are less common than that of hemangioma. Lymphangiomas involve parotid and submandibular salivary glands. These lesions don't regress spontaneously.

This is a benign lesion comprising of multiple lymphatic spaces. These are benign lymphatic malformations frequently observed in pediatric age group and exceedingly rare in older individuals. These lesions should be considered as benign developmental abnormalities of lymphoid system.

Ultrasonogram typically would show multicystic, hypoechoic lesion with thin walls. CT scan will reveal a homogeneous cystic lesion with surrounding smooth, thin wall.

These cysts could present for a long duration to time without any symptoms. Complications like infection, bleeding into the cyst, effects caused by compression of facial nerve.

Malignant tumors:

Mucoepidermoid carcinoma:

This is the most common malignant neoplasm involving major salivary glands. They account for nearly 15% of all cases (including benign and malignant). This lesion arises from pluripotent reserve cells of excretory ducts that are capable of differentiating into squamous, columnar and mucous cells.

This lesion most frequently occurs in the parotid gland. This term was first coined by Stewart in 1945 to define salivary gland tumors characterized by a mixed pattern of two main cell types (epidermoid and mucous producing cells). However a third cell type, also known as intermediate cells which is neither mucoid nor fully epidermoid may also be present frequently. High grade tumors are known to be composed of squamous cell lines. Low grade tumors have predominant mucous cells.

These tumors are known to invade nerves. If parotid gland is affected then facial nerve can also be involved.

High grade tumors can be managed by total parotidectomy while low grade ones can be managed by conservative procedures like superfical parotidectomy.

Adenoid cystic carcinoma:

This is also known as cylindroma. This is a slow growing tumor, but invades into the tissue planes and muscles. These lesions invades perineural spaces, with propensity for local recurrence and distant metastasis later.

These lesions can arise fromy any salivary gland, but nearly half of these lesions arise from minor salivary glands. Women are more commonly affected than men.

Clinically these lesions could well be deceptive because of its small size and slow growth. Histologically these lesions could manifest three patterns: (tubular, cribriform and solid pattern). Among these patterns it is the solid variety that is associated with increased local recurrence, high metastatic rate and thereby higher mortality.

Treatment is surgical followed by irradiation.

Acinic cell carcinoma:

This is a rare tumor arising from salivary glands accounting for about 2-5% of primary neoplasms of the parotid gland. This tumor is formed by acinic cells with very little stroma. In well differentiated tumors the neoplasia has an innocuous appearance, because of the simiarity between normal parotid tissue and the neoplam. Hence these tumors become difficult to diagnose.

These lesions almost exclusively occur in parotid gland with a female to male ratio of 3:2. Usually these lesions present as well defined solitary nodule.

Patterns of growth incude:

Solid

Microcystic

Papillary - cystic

Follicular

A combination of two or three patterns may also be found.

Total excision with adequate surgical margins is the treatment of choice.

Adenocarcinoma:

This is a highly aggressive locally infiltrating tumor, often involving the minor salivary glands. Usually these tumors present with distant metastasis.

Commonly involved gland happens to be the sublingual salivary gland. Tumors involving the sublingual glands are commonly malignant.

Total excision with adequate margins is the treatment of choice.

Malignant mixed tumor involving salivary glands:

There are two varieties of these tumors:

1. Carcinoma arising from pre-existing benign mixed tumor

2. Tumor arising de novo

Tumor arising de novo has a very short history as this type is virulent. Rapid growth associated with pain in a benign tumor should always arouse suspicion of malignant transformation.

Treatment is by radical surgery.

Squamous cell carcinoma:

This rapidly growing tumor infiltrates, causes pain and ulcerates through the skin. It can metastasize to the neck nodes. Treatment is by radical excision. If nodal metastasis is present it should be combined with neck dissection.

Frequency of primary squamous cell carcinoma involving major salivary glands ranges between 1-4%. Previous exposure to radiation therapy increases the risk of this tumor formation.

Average age of these affected patients happens to be more than 60.

Undifferentiated carcinoma:

This is a rare and very aggressive tumor. It has a tendency to spread locally, rapidly and causes pain. The lesion gets fixed to the skin which later ulcerates. It can cause facial nerve paralysis, and cervical nodal metastasis. Treatment is by wide excision, radical neck and post operative radiation.

Lymphoma:

This rare tumor usually associated with systemic disease. It may also occacionally be a primary tumor. Treatment is by using chemotherapy.