Clinicopathological and Demographic Pattern of Salivary Gland Neoplasms
Introduction
Salivary gland neoplasm comprises 1-2% of all the neoplastic disease in the head-neck region. Nearly all salivary neoplasms present as slowly growing masses which have often been present for several years. Unfortunately pain is not a reliable indication of Malignancy1. Benign neoplasm (pleomorphic aderoma) is a most common tumour of major salivary gland and 90% occurs in the parotid glands and 50% occurs in the submandibular gland. Nearly all arises from the superfacial lobe of the parotid gland, warthin’s tumour arises from the tail of the parotid gland just anterior to the lobe of the ear. On palpation, the tumour is usually smooth or bosselated, superfacial, rounded, mobile and lobulated. The tumour is highly implantable & recurrence rate after primary surgery (without enucleation) is about 5%. If simple enucleation is performed, the recurrence rate is between 20 & 30%2.
Parotid neoplasms are rare in the pediatric population. Benign tumours make up 80% of parotidmasses. Among all the benign tumour (pleomorphic adenoma) is common and it is a mixed tumour in children3. Benign neoplasm (pleomorphic aderoma) is the most common salivary gland tumor and accounts for approximately 60% of all salivary gland neoplasms. The mean age at presentation is 46 years. There is a slight female predominance. Approximately 80% of benign neoplasm arises from the parotid gland, 10% the submandibular gland and 10% from the minor salivary gland of the oral cavity, nasal cavity, paranasal sinuses and upper aerodigestive tract4. The average age of salivary gland tumor patients was 41 years for the benign cases and 45 years for the malignant ones. The male: female ratio was 0.99:1 in benign cases and 1.34:1 in the malignant ones5. Salivary gland tumors are uncommon, corresponding to approximately 3% to 10% of all neoplasms of the head-neck region. Incidence rate of malignant salivary gland tumors 0.5 to 1.2 cases per 100000 in habitants per year. Patients with benign & malignant tumors presented with a mean age of 47.7 years & 48.8 years respectively6. The first classification of salivary gland tumors developed by the World Health Organization (WHO) in 1972, the classification was revised in 1992 and recategorised several of the salivary gland tumors. Between 74% and 80% of major salivary gland tumors are benign of which pleomorphic adenoma is the commonest one and the most frequently affected gland is the parotid. In two different studies of intra-oral minor salivary gland tumors in Brazil between 62% and 65% were benign and 34% to 38% malignant. The majority of patients with benign salivary gland tumors are aged between 40 & 59 years7. The etiopathogenesis of minor salivary gland tumors remain unclear. It is not correlated with the smoking but exposure to ionizing radiation is the only confirmed risk factor for MSGTs and has a high recurrence rate (5-30%) when surgical removal is incomplete and the possibility of malignant transformation may be taken is to consideration8. The demographic (Age, sex, site) distribution of salivary gland neoplasms are seen in the Department of oral surgery at Mulago Hospital, Uganda between 1988 and 2000 comprised 7.8% of which 77 (54.23%) cases were benign and 65 (45.77%) cases were malignant. The mean age for the benign lesion was 42 years and for the malignant lesion was 51 years. Both males and females are affected equally9. The annual incidence rate in the world varies between slightly less than 2 and less than 0.05 per 100000. Recently in the USA during 1974-1999, a significant increase in the incidence rate of salivary gland cancer has been reported. This cancer accounted for 6.3% in 1974 to1976 compared to 8.1% of all head-neck cancers in 1998-1999. The sensitivity of FNAC was 90.9% and specificity was 100% (percent). Surgery of recurrent benign neoplasm most commonly (pleomorphic adenoma) presents an increased risk of facial nerve injury and a considerable re-recurrence rate. Salivary gland neoplasms represent the most complex and diverse group of tumors encountered by the head-neck oncologist. Proper management of these tumors require an accurate diagnosis by the pathologist, correct interpretation by the surgeon & knowledge of the surgical anatomy of salivary glands with a clear understanding of the factors leading to recurrence and complications.
The preoperative diagnosis of MSGTs is based on the clinical history,thorough physical examination and supported by complementary techniques(Investigations) such as magnetic resonance imaging (MRI), computed tomography (CT) alone or combined with sialography and fine needle aspiration biopsy (FNAB). The diagnosis must be confirmed postoperatively by histopathological examination. Fine needle aspiration has a high sensitivity and specificity with the accuracy rate ranging from 87% to 96% . Open biopsy is not usually recommended due to high risk of seedling. The accuracy of frozen section diagnosis is quite controversial. Fine needle aspiration (FNA) biopsy is a safe & alternative to open biopsy of major gland. This technique claims a high accuracy and specificity. FNAC is a afe procedure & almost free of complication and helpful in the preoperative diagnosis and planning of treatment. Histological evaluation revealed 65 malignant tumors and 163 benign lesions (150 neoplasms and 13 non-neoplastic lesions). The cytological findings were non-diagnostic in 13 (5.7%).Between January 1990 and December 1998, 410 parotid glands were resected at the Department of Otorhinolaryngology–Head and Neck Surgery at the University of Berne, Inselpital (Berne, Switzerland). Included in the study were 228 cases with preoperative FNAC. In a retrospective study the results of FNAC were analyzed and compared with the corresponding histopathological diagnosis, true-negative in 146 (64%), true-positive in 39 (17%), false-negative in 22 (9.8%) and false-positive in 8 (4.5%) cases in detecting malignant tumors. Nineteen of 39 (49%) malignant tumors (true-positive) and 123 of 146 (84%) benign lesions (true-negative) were classified accurately. The accuracy, sensitivity, and specificity were 86%, 64%, and 95% respectively.Fine-needle aspiration cytology is a valuable adjunct to preoperative assessment of parotid masses. Preoperative recognition of malignant tumors may help prepare both the surgeon and patient for an appropriate surgical procedure.14
Histopathological examination after operative treatment is the most accurate way to determine the pathology. Though available diagnostic tools give some clue regarding exact type of lesion, it is very difficult to determine the type of pathology without histopathological confirmation. The importance of benign neoplasm most commonly (pleomorphic adenoma) lies in the significant risk of malignant transformation compared with other benign salivary gland neoplasm.so proper diagnosis & appropriate treatment of benign neoplasm is mandatory.
Rationale
Salivary gland neoplasm is a rare form of neoplastic diseases present in our country and the whole world. Though most of them are slow growing and benign in nature.Some times they present as malignant in nature, some of them are more aggressive and fatal. Some benign neoplasms appear recurrently after operation and some may be transformed into malignancy after a long period of time. This type of neoplasm may have association with some definite demographic factors such as age, sex, geographic area, professions and socioeconomic status. Better understanding of these demographic factors may reveal the risk factors, early doagnosis and prognosis of salivary gland neoplasms. Although there are many studies on the demographic factors associated with salivary gland neoplasm outside but in our country there are very few studies. So the aim of my study is i) to determine the associated demographic factors of salivary gland neoplasms ii) .clinical presentation of various type of salivary gland neoplasms and their pathology.
Hypothesis
Benign neoplasms are more common salivary gland neoplasms, occurring commonly in the Parotid gland with female predominance.
Objectives
General objectives: To see the Clinicopathological and Demographic pattern of salivary gland neoplasms.
Specific objectives:
i) To evaluate the type of salivary gland neoplasms.
ii) To evaluate the site of frequency of salivary gland neoplasms.
iii) To see the demographic pattern of salivary gland neoplasms.
Review of Literature
Historical Background:
The salivary glands are the site of origin of a wide variety of neoplasms. The histopathology of this tumour is said to be the most complex and diverse of any organ of the body. Salivary gland neoplasms are also relatively uncommon with an estimated annual incidence in the United States of America 2.2 to 2.5 cases per 100000 people. They constitute only about 2% of all head –neck neoplasms. Nearly 80% of these tumours occur in the parotid glands, 15% in the submandibular glands and the remaining 5% in the sublingual and minor salivary glands in the upper aero-digestive tract. Benign neoplasms make up about 80% of parotid tumours, 50% of submandibular tumours and less than 40% of sublingual and minor salivary gland neoplasms.11
Benign neoplasms(e.g Pleomorphic adenoma) are the most common of all salivary gland neoplasms. It comprises about 70% of all parotid tumours, 50% 0f all submandibular tumours, 40% of all minor salivary gland tumours but only 6% of sublingual tumours. The most common site is the parotid( 85%) followed by the submandibular(10%) then minor salivary glands ( e.g palate, upper lip and buccal mucosa )are most commonly affected. More common in the 4th to 6th decade of life and uncommon in children. More common in female and female to male ratio 3-4: 1.In the parotid 90% occurs in the superfacial lobe.The typical clinical presentation of a benign salivary gland neoplasms are a slow-growing, painless mass.The second most common tumour is warthin’s tumour, more common in the tail of the parotid gland.In benign neoplasms facial nerve paralysis almost never occur, even with extremely large tumours.11
Surgery of recurrent pleomorphic adenoma presents increased risk of facial nerve injury and a considerable re-recurrence rate. Multifocal recurrence were observed in 73% cases and carcinoma in pleomorphic adenoma in 9% cases.Permanent partial facial nerve injury after surgery was 23% in patients with initial enucleation and 14% patients with superfacial parotidectomy.12
14 years retrospective clinico-statistical analysis of 237 salivary gland neoplasms in Lagos, Nigeria were undertaken with a view to providing further insights into the presentation of this disease in Africans. These neoplasms constituted 10 % of all head-neck neoplasms and were most frequently situated at the parotid gland( 32.1%), the palate (24.9%) and the submandibular gland (19.4%).Whereas mucoepidermoid carcinoma more common in parotid and more in females( 53.3%) than in males (11.8%).Male presenting with pleomorphic adenoma were relatively younger than their female counterparts.This is especially true for palatal pleomorphic adenoma.The recurrence rate of benign tumours were 4.8% .15
A 21 years review of cases seen at University College Hospital , Ibadan. All cases of benign and malignant salivary gland neoplasms histologically diagnosed between 1975 and 1995 in the Oral Pathology Department and Cancer Resistry of the University College Hospital , Ibadan were reviewed .Salivary gland neoplasms accounted for 3.5% of head-neck neoplasms, the majorit ( 46.5%) occuring in the parotid ,followed by the submandibular (18.1%) and palatal glands (10.7%).The ratio of benign to malignant neoplasms were 1.1 to 1. Mucoepidermoid carcinoma and adenoid cystic carcinoma were the most common malignant neoplasms.16
Neoplasms of the Salivary Glands:A Descriptive Retrospective Study of 142 Cases-Mulago Hospital, Uganda from January 1988 to December 2000.Of all neoplasms seen in the Department , salivary gland tumours comprised 7.8% of which 77 ( 54.23%) were benign and 65 ( 45.77% ) were malignant. Pleomorphic adenoma was the most prevalent over all.The mean age for the benign lesions were 26.74 +_16.0 and for the malignant lesions were 42.49 +_ 19.15. 75% of the pleomorphic adenomas are present in the parotid gland as compared to 39.8% in the palate.9
Minor salivary gland tumours : A clinicopathological study of 18 cases-Representing 10-15 % of all salivary neoplasms ,among the 18 cases 12 were female (66.7%) and 6 were male (33.3%). The great majority ( 94.4%) were benign tumours ,more common in the hard palate ,followed by the soft palate and the upper lip. The histopathological diagnosis was pleomorphic adenoma (55.3%) and warthin’s tumour (5.6%) .In complete surgical removal showed (5-30% ) recurrence and over all benign neoplasms relapse was 6% , versus 65% of all malignant lesions.Tumours of the salivary glands can appear at any age, the maximum incidence is in the fourth decade of life for benign tumour and the fifth decade for malignant tumours.More common in female than male. 8
Salivary Gland In Tanzania:
A Cross-sectional retrospective study was done over a period of twenty years from 1982 to 2001.Data regarding demographic, clinical and histologic information was analysed.Among the salivary gland tumours, 54% was benign and 46% was malignant, which occurred in 80 males and 53 females.Peak age was between 20 and 49 years.Among the benign tumours, pleomorphic adenoma was 83.9% , followed by adenoma 9.9%. The parotid gland was the commonest site of occurrence followed by the palate.The patient usually present with a painless slow-growing swelling .7
Patients with benign and malignant tumours presented with a mean age of 47.7 years and 48.8 years, respectively .The frequency of benign tumours were 80% and malignant tumours 20%. Tumours were localized in the parotid gland 71%, in the submandibular gland 24% and in the minor salivary gland 5% .The most common benign tumours were pleomorphic adenoma in 84% and warthin’s tumour in 13%.Among malignant tumours ,mucoepidermoid carcinoma was the most common in 52% ,adenoid cystic carcinoma was in 20%.6
Tumors of the salivary glands are uncommon and represent 2-4% of head and neck neoplasms. They may be broadly categorized into benign neoplasms, tumorlike conditions, and malignant neoplasms. The glands are divided into major and minor salivary gland categories. The major salivary glands are the parotid, the submandibular, and the sublingual glands. The minor glands are dispersed throughout the upper aerodigestive submucosa (ie, palate, lip, pharynx, nasopharynx, larynx, parapharyngeal space).
Most (70%) salivary gland tumors (SGTs) originate in the parotid gland. The remaining tumors arise in the submandibular gland (8%) and minor salivary glands (22%). Although 75% of parotid gland tumors are benign, slightly more than 50% of tumors of the submandibular gland and 80% of minor SGTs are found to be malignant. Pleomorphic adenomas (benign mixed tumors) are the most common benign SGTs, comprising 85% of all salivary gland neoplasms.17
Development of Salivary Glands18
A) Parotid gland: Gland proper,duct and alveoli: From Ectoderm Capsule and stroma –From Mesenchyme
B)Submandibular and Sublingual glands: Glandular part,duct and alveoli-From Endoderm.
Capsule and Stroma –From Mesenchyme.
Anatomy of the Salivary Gland19
The Parotid Gland:
Surgical Anatomy: The parotid gland lies in a recess bounded by the ramus of the mandible, the base of the skull and the mastoid process.It lies on the carotid sheath and the XIth and XIIth cranial nerves and extends forward over the masseter muscle.The gland is enclosed in a sheath of dense deep cervical fascia.Its upper pole extends just below the zygoma
Figure-1:Anatomical location of major salivary gland
and its lower pole into the neck.
Several important structures run through the parotid gland.
These include:1)branches of the facial nerve 1)the terminal branch of the external carotid artery that divides into the maxillary and the superfacial temporal artery 3)the retromandibular vein 4)intraparotid lymphnodes.The gland is arbitrarily divided into deep and superfacial lobes,separated by the into the tributaries of external jugular vein.Lymphatic drainage:Lymph drains into superfacial and deep groups of parotid lymph nodes.The efferent vessels from these nodes terminate into jugulo-digastric group of deep cervical nodes.
Nerve Supply:
i) Parasympathetic supply &
ii) ii) Sympathetic supply
Figure-2: Blood supply of the salivary gland.
The Submandibular Gland
Surgical Anatomy: The submandibular glands are paired salivary glands that lie below the mandible on either side.They consist of a larger superficial and a smaller deep lobe that arecontinuous around the posterior border of the mylohyoid muscle.Important anatomical relations include the anterior facial vein running over the surface of thegland and the facial artery.The deep part of the gland lies on the hyoglossus muscle closely related to the lingual nerve and inferior to the hypoglossal nerve.The gland is surrounded by a well-defined capsule that is derived from the deep cervical fascia which splits to enclose it.The gland is drained by a single submandibular duct that emerges from its deep surface and runs in the space between the hyoglossus and mylohyoid muscles.It drains into the anterior floor of the mouth at the sublingual papilla.There are several lymph nodes immediately adjacent and sometimes within the superfacial part of the gland .Important anatomical relationships of the submandibular glands:
1) Lingual nerve
2) Hypoglossal nerve
3) Anterior facial vein
4) Facial artery
5) Marginal mandibular branch of the facial nerve.
Blood Supply:
Branches of facial and lingual arteries; the veins correspond to the arteries and drain into internal jugular vein
Lymphatic drainage: Drains into submandibular lymph nodes and thence into the jugulo-digastric lymph nodes.
NERVE SUPPLY:
i) Parasympathetic supply &
ii) Sympathetic supply.
The Sublingual Gland:
Surgical Anatomy: The sublingual glands are a paired set of minor salivary glands lying in the anterior part of the floor of the mouth between the mucous membrane ,the mylohyoid muscle and the body of the mandible close to the mental symphysis.Each gland has numerous excretory ducts that open either directly into the oral cavity or indirectly via ducts that drain into the submandibular duct .
Blood Supply:
Sublingual and submental arteries with their corresponding veins.
LYMPHATIC DRAINAGE: The lymphatics drain into the submental and submandibular nodes.
Nerve supply: Same as that of submandibular gland.
Minor Salivary Glands:
Surgical Anatomy: The mucosa of the oral cavity conains approximately 450 minor salivary glands.They are distributed in the mucosa of the lips,cheeks,palate,floor of the mouth and retromolar area.These minor salivary glands also appear in the other areas of the upper aerodigestive tract including the oropharynx,larynx and trachea as well as the sinuses.They have a histological structure similar to that of mucous-secreting major salivary glands.Overall,they contribute to 10% of the total salivary volume.
Histological Structures of Salivary Gland: 20
The structural framework of the three major salivary glands are similar.They are only minor differences in details of histology and cytology.Each gland consists of numerous lobules which are held together by fibro-areolar stroma in which vessels and nerves ramify.The lobule is composed in succession of secretory end pieces, intercalated ducts, straited ducts collecting ducts.
Figure-3:Histological structures of salivary gland
The secretory end-piece may be tubulo-alveolar and is lined by simple columnar epithelium consisting of three types of cells: serous, mucous and seromucous.The serous cell contains numerous, small, membrane –bound electron-dense, eosinophilic cytoplasmic granules.The granules of mucous cells are large ill-defined, electron-lucent and poorly eosinophilic.The seromucous cells contain an admixture of small electron-dense and large electron-lucent granules.
The secretory end-piece which is lined by one type of epithelium is called the homocrine glands; when it possesses more than one type of cells, it is termed heterocrine A layer of contractile myo-epithelial cells intervene between the basement membrane and the lining epithelial cells of the end-piece and the ensuing ducts.In the parotid gland the secretory end-piece is lined by seromucous cells.In the submandibular and sublingual glands, the lining epithelium consists of mucous and seromucous cells.
The seromucous cells form demilunes which are crescentic in shape and are sandwiched between the basement membrane and columnar mucous cells.The intercalated ducts convey the secreted material from the end-piece to the straited ducts.Such ducts are lined by simple cubical or flattened epithelium and modify the saliva by the addition of water and electrolytes.The straited ducts are characterised by basal striations caused by the arrangements of elongated mitochondria with infoldings of basal plasma membrane between them.The straited ducts help resorption of sodium ions from the saliva and transport of potassium ions, kallikrein and lysozyme to the saliva.In addition ,IgA secreted by the plasma cells is conveyed by the duct.
Physiology of the Salivary Gland21
Salivation:
Formation of Saliva: Saliva is a secretion of the three main pairs of salivary glands and the numerous small buccal glands.Salivation is reflexly activated.
Afferent Impulses: Arise from stimulation of the lingual mucosa via the 5th cranial nerve.They also arise from stimulation by irritants acting on the sensory vagal endings in the stomach and from stimulation of the nerves of special sensation such as the sight ,taste or smell of food.
Efferent Impulses: Are conveyed by fibres of the autonomic nervous system.The salivary glands are supplied by:1)The parasympathetic nervous system-From the superior salivary nucleus,secretomotor fibres run in the chorda tympani branch of the7th nerve and finally join the lingual nerve branch of the 5th cranial nerve;thence they pass through the submandibular ganglion to supply thesubmandibular and sublingual glands.From the inferior salivary nucleus secretomotor fibres run to the otic ganglion,from which the postganglionic fibres pass to the parotid gland via the auriculotemporal nerve.2)The sympathetic nervous system.
Amount and rate of secretion:
Vary enormously in different individuals but average about 1.5 litres in 24 hours Parasympathetic stimulation causes profuse secretion of a watery saliva low in organic content.Sympathetic stimulation causes release of small amounts of saliva rich in organic material.
Composition of saliva:
Salivs has certain bactericidal and coagulating properties.Theaverage pH is about 68.It consists of:
i)Water-99.42%
ii)Salts 0.22%.The salts are mainly those of calcium phosphate and carbonate.
iii)Organic content 0.22%. Mucin is secreted by the buccal ,sublingual and submandibular glands, the parotid being serous.
iv)Enzymes-0.14%.These include ptyalin,which initiates the first stage of digestion by catalysing the hydrolysis starches, in several stages, to maltase
v)Immunoglobulins.
Aetiology: 22, 23, 24, 25
Radiation induces salivary gland neoplasms.This study was established in after second World War.An increased incidence of second primary tumours has also been documented in patients with thyroid cancer treated by radioiodine (I131).A small set of genes has been identified that plays a role in development of common benign and malignant neoplasms,e.g in pleomorphic adenoma ,the gene PLAG1 is activated by chromosomal translocations at 8q12.Salivary malignancy rises with increasing smoking and alcohol consumption. The difference in registration varies between geographical areas.Diet and nutritional habits also mportant,polyunsaturated fatty acids exert beneficial effect. Occupation,worker involved with livestock feed processing,crops contaminated by aflatoxins have increased risk of salivary gland malignancy.EBV,HPV,Herpesvirus and CMV may play a role in development of salivary malignancy.
Risk Factors
The etiologic factor for the general salivary glands neoplasms isn’t well defined, but some research’s statements suggest associations with:
• Radiation: radiotherapy in low dosages has been implied in the pleomorphic adenoma pathogenesis, squamous cell carcinoma and mucoepidermoid carcinoma after 15 to 20 years of exposure. The greater evidence of such association is in the increased incidence of these tumors in survivors from areas exposed to atomic bomb
• Smoking: in spite it’s not bound to the development of salivary glands carcinoma, smoking has been associated to the WARTHIN’s tumor.
• Epstein-Barr’s Virus: except for the undifferentiated carcinoma, the viral etiologic role was not present in the salivary glands neoplasms.
• Genetic Factors: P53 (tumor suppressing gene) and MDM2 (oncogene) were identified in high percentage in the pleomorphic ex-adenoma carcinomas; high levels of (VEGF) endothelial growth factor would be bound to a larger tumor size, vascular invasion, recurrence,metastasis and aggressivity. Allelic loss or translocations 12q13-15 are associated with the pleomorphic adenoma.
Diet and the Risk of Salivary Gland Cancer:
Vitamin A deficiency is to be associated with a significant increase in salivary gland tumors in rats and beta-carotene supplementation, but not retinol supplementation, to decrease the yield of dimethylbenzanthracene
(DMBA)-induced salivary gland tumors. These findings suggest that investigation of the relation between salivary gland cancer and diet, particularly antioxidant vitamins, is warranted.24
Radiation exposure: Radiation treatment to the head and neck area for other medical reasons increases yourrisk of salivary gland cancer.Workplace exposure to certain radioactive substances may also increase the risk of salivary gland cancer.
Family history:Very rarely, members of some families seem to have a higher than usual risk ofdeveloping salivary gland cancers.
Other possible risk factors
Certain workplace exposures: Some studies have suggested that working with certain metals (nickel alloy dust) orminerals (silica dust) may increase the risk for salivary gland cancer, but these links arenot certain. The rarity of these cancers makes this a difficult area to study.
Tobacco and alcohol use:
Tobacco and alcohol can increase the risk for several cancers of the head and neck area,but they have not been strongly linked to salivary gland cancers in most studies.
Diet
Some studies have found that a diet low in vegetables and high in animal fat may increase the risk of salivary gland cancer, but more research is needed to confirm this possible link.
Cell phones:
One recent study suggested an increased risk of parotid gland tumors among heavy cellphone users. In this study, most of the tumors seen were benign (not cancer). Otherstudies looking at this issue have not found such a link. Research in this area is still inprogress. If there is any excess risk, it could be decreased by using corded or cordlessearpieces that move the device away from the user’s head and decrease the amount ofradiation that reaches the body.25
Epidemiology and distribution: 22, 26
Salivary gland tumours are relatively uncommon.Fewer than 3% of all neoplasms arise in the salivary glands.Most tumour types are a slight female preponderance.All age groups are affected from birth to old age but pleomorphic adenoma is more common in the 4th decade of life.Majority of benign tumours develop in the parotid gland then submandibular and sublingual glands.22 These correspond to approximately 1% of the head and neck tumors, with an approximate incidence of 1.5 cases/100.00 (1). Despite the incidences vary according to the literature, 67.7% to 84% of the neoplasms start in the parotid, 10% to 23% in the submandibular gland and the other cases in the sublingual gland and in the minor salivary glands . 95% of the cases occur in adults and are rare in children. About 75% of the neoplasms are benign and the pleomorphic adenoma is the most common histological type. The smaller the gland, the greater the probability for the neoplasm to be malignant. 25% of the parotid tumors are malignant, while in the submandibular gland this number goes up to 43% and hits 82% in the minor salivary glands. In the parotids, the most common histological subtype is the pleomorphic adenoma (53.3%), followed by the Warthin’s tumor (28.3%) and by the mucoepidermoid carcinoma (9%). In the other glands the pleomorphic adenoma is also the most common (36% in the submandibular and 43% in the sublingual and minor glands),
followed by the cystic adenoid carcinoma (25% in the submandibular and 34% in the sublingual and minor glands) and by the mucoepidermoid carcinoma (12% in the submandibular and 11% in the sublingual and minor glands).26
Brief Description Of Some Common Salivary Gland Neoplasms: 27
As a rough guide the site and nature of salivary gland tumours may be summarized by the following three statements.1)90% of salivary tumours involve the parotid 2)90% of parotid tumours are benign 3)90% of minor salivary gland tumours are malignant.
Pleomorphic Adenoma:
A benign epithelial tumour with mucopolysaccharide stroma.It has a pseudocapsule which is incomplete such that protuberances of tumour extend beyound the apparent capsule.They must be excised with as large a margin as is possible to reduce the high recurrence rate.Most occur in the parotid gland.The longer the tumour is in place the higher thechance of malignant change.The mean age at presentation is 46 years but may occur at any time of life.Slight female predominance(1.4:1).80% occurs in parotid gland,11% occurs in submandibular and sublingual glands;9% occurs in minor salivary glands(most common in palate,next in lips and the cheeks).Clinically present as a slow-growing painless mass with bosselated surface and bluish area ,palatal adenoma become ulcerated by friction or trauma.Treatment is by surgical excision of the gland.In cases where the tumour has ruptured during removal or there is suspected tumour remnant radiation may be given in order to reduce recurrence.Recurrence after formal parotidectomy is a difficult situation to deal with as the facial nerve is at great risk in revision surgery.
Adenolymphoma (Warthin’s Tumour):
Benign .Almost exclusively seen in middle-aged and elderly men.Nearly always occurs in the tail of the parotid.It is susceptable to inflammation associated with upper respiratory tract infection.The history may include one of pain and fluctuating swelling.14% of all salivary gland neoplasms and is the second most common tumour.Peak age 7th decade,sex distribution is more equal,uncommon in black people,10% bilateral and compressible.Treatment is by surgical excision.Unlike pleomorphic adenoma recurrence is unusual.
Oncocytoma (Oxyphil adenoma):
Oncocytomas are rare tumours.They are predominantly tumours of those over middle age,women are more common than men.Slow-growing,rarely bilateral and malignant change may occur.Benign tumour and excision is cura
Mucoepidermoid Carcinoma:
Most common major salivary gland malignances accounting for one-third of cases.Among all more common in parotid gland,often presenting as a painless mass and some aggressive cancer presenting with pain, swelling and facial palsy.In high-grade cancers,lymph node metastases occur in nearly three-quarters of patients at presentation.Most common in children,low-grade tumour tend to cystic and high-grade tumour tend to be solid,30% lymph node metastases and distant metastases occur in lungs,bone and brain.Treatment of low-grade tumour wide local resection and high-grade tumour radical resection with radiotherapy.
Adenoid Cystic Carcinoma:
Commonest along the perineural sheath and bony canals.Usually present with severe pain and facial nerve palsy.Distant metastases occur late.Treatment is by radical excision salivary gland malignancy.More common in minor salivary glands,submandibular and sublingual glands but rare in parotid gland.More common in female.40% occurs in the oral cavity of which 50% in the hard palate.It grows slowly spreading and radiotherapy.
Adenocarcinoma:
Account for about 3% of parotid neoplasms and about 11% 0f neoplasms of the minor glands.Most cases present as a painless lump.The commonest indication of malignancy is fixation to surrounding tissues.Facial palsy in about 5% of cases.One in five have involvement regional nodes at presentation.Recurrence is usually local but distant metastases do occur.Initial treatment is radical local excision followed by radiotherap
Carcinoma Ex Pleomorphic Adenoma:
10% of all malignant salivary cancer and tend to arise in the major glands.It is very rare to occur within a pre-existing pleomorphic adenoma(3%) but risk of malignancy increase upto 10%.Malignant transformation most commonly occur in men over 40 years with history of previous operation.Poor prognosis,usually 40% five years survival rate.
Acinic Cell Tumour:
Very slow growing malignant tumour.Usually seen in the parotid gland.Distant metastases or local recurrence can appear many years after control of the primary site.Regional lymph nodes are rarely involved at presentation.Treatment is by wide excision of the gland.Usually the main branches of the facial nerve can be preserved in cases involving the parotid.Adjunctive radiotherapy should be considered.
Histopathology Of Common Benign Tumours:23
Pleomorphic adenoma: Capsule-complete or incomplete.Stroma-Myxoid stroma is the most characteristic features,it forms major part of the tumour.Mucoid in nature,extremely fragile .Pseudo-cartilage,true bone with fatty marrow spaces may be found.Variable amount of elastic tissue can be found.The Cells-Derived from intercalated duct and myoepithelial cells which differentiated into epithelial and connective tissue structures.Squamous metaplasia with keratinization is common.
Warthin’s Tumour
Characteristic eosinophilic,glandular epithelial component and a stroma of lymphocytes which may form follicle and cysts.Aspiration shows brownish fluid.
Fig: Parotid gland swelling
Clinical Presentation of Salivary Gland Neoplasms: 22
HISTORY: Most parotid and submandibular gland tumours develop in an insidious fashion, grow slowly over a long period of time. A very small number of cases produce discomfort by obstructing salivary flow. Pain is extremely uncommon and if present, usually heralds malignant changes. Facial weakness or palsy is virtually never seen unless malignant change has supervened.The patient with a parotid tumour present with a firm mass behind the angle of the mandible i.e in the retromandibular region, in front of the tragus or in the cheek. Deep lobe parotid tumours and minor oropharyngeal glands tumour displace the tonsils & palate medially and are often impalpable from outside.Tumours arising from the submandibular gland present as a swelling in the submandibular triangle which is localised more accurately by bimanual palpation of the floor of the mouth.
Benign tumours in the minor salivary glands of the oral and pharyngeal mucosa present as a firm submucosal swellings.Ulcer is rarely seen, if seen without trauma suspicion for malignancy.Recurrent tumours are usually multiple tissuses in the area are scarred and difficult to palpate accurately.
History Of Pastillness : Nothing contributary in case of benign tumours but in case of malignant tumours Ionizing radiation may plays a role.
Geographical Area: Nothing Contributary Detected.
Family History: Nothing contributary.
Physical Examination
General Examination:
a) To assess functional status of the salivary gland.
b) Search for metastasis: Examination of the cervical lymph nodes, lungs, liver, brain & bone.
Local Examination
Site, size, shape and surface of the swelling. Routine inspection and palpation of the salivary glands should be carried out to locate the swelling viz. parotid, submandibular, sublingual and other minor salivary gland region. A small swelling is clinically isolated may not be immediately obvious .If need careful palpation. It also requires feeling opposite site.
Temperature and Tenderness:
Overlying skin is usually normal. When inflammatory condition occurs, the colour of the skin is changed.
Tenderness – indicates malignant and inflammatory changes occur.
Consistancy and Fixity: Variable in consistancy usually firm to cystic ,if hard indicates malignant changes. It is usually freely mobile but if fixed to the underlying structures & overlying skin indicates malignancy.
Dysphagia: Tumours arising from the deep lobe and oro-pharyngeal minor salivary gland may produce dysphagia.
Lymph nodes: Usually not palpable if palpable indicates malignancy( usually)
Examination of the ears: For pain, narrowing of the EAC &TM joint intact or not and displacement of the ear lobule.
Examination of the oral cavity & oropharynx : For any swelling and sign of inflammation around the duct orifice.
ASSESSMENT: Proper History taking,Clinical Examination and Imaging-
USG: The advantages of ultrasonography of salivary gland tumours are frequently extolled by radiologist.There is little doubt that it can be useful to confirm a clinical suspicion.It can detect whether the tumour is solid or cystic and or any calcification present or not.
CT/MRI: MRI gives better soft tissue evaluation than CT and is the preferred imaging modality.Occasionally, CT scanning will show calcifications in a salivary gland tumour and this strongly suggests that it is a pleomorphic adenoma. MRI has proven to be equally sensitive in the detection of salivary neoplasms but it can differentiate salivary tissue from extra salivary tissues.
PET: It has a little value jn the assessment of salivary gland tumours.
CYTOLOGY (FNAC): It is safe, cheap, easily available,less chance of complication, less painful and quickly done;no chance of seedling and gives valuable information about Warthin’s tumour, tuberculosis, benign or HIV-associated lymphoepithelial lesions.It can easily miss a small area of malignant change in a pleomorphic adenoma.It is possible to differentiate malignant from benign salivary gland tumours with 80%-90% accuracy. IMMUNOCYTOCHEMISTRY: It improves the accuracy of diagnosis.
HISTOPATHOLOGY: It is a definitive test and done in every patient after operation.
FIGURE-5: FNAC slide of Pleomorphic Adenoma
FIGURE-6: FNAC slide of Mucoepidermoid Carcinoma
FIGURE-7:Histopathological slide of Pleomorphic Adenoma.
FIGURE-8: Histopathological slide of Warthin’s Tumour.(shows glandular epithelium in papillary cystic arrangement with intervening lymphoid tissue).
FIGURE-9: Histopathological slide of Mucoepidermoid Carcinoma.
FIGURE-10: Histopathological slide of Adenoid Cystic Carcinoma.
Personal series
Methodology:
Type of Study: Cross sectional study.
Place of Study: Dhaka Medical College & Hospital,Dhaka
Bangabandhu Sheikh Mujib Medical University
Sir SalimullahMedical College & Mitford Hospital,
SHAHID SHAWARDI MEDICAL COLLEGE &
HOSPITAL, DHAKA.
Period of study: July 2009- 30 June 2010
Study population : Patient who are referred or came individually into the OPD and admitted into the hospital & fulfill the inclusion criteria of this study.
Sample size : The patients who fulfill the inclusion criteria & admitted into the hospital are taken and sample size is detected by using the following formula.
N = (Z2 ´ p ´ q)/d2, where
Z = Standard normal deviate = 1.96
p = Prevalence (assumed) of the disease
q = (1-p), and
d = Desired accuracy or degree of allowable error (here 10% of p)
Assuming a 90% prevalence of benign salivary gland neoplasms & allowable error 10% of the prevalence. We get the required number of cases by calculating, n = 1.962 ´ 0.9 ´ (1-0.9) / (0.05)2 = 138 subject’s. To make a valid comparison between groups, maximum number of sample will be taken as per as possible.
Sampling technique: Purposive sampling. Proposed study will be carried out in the ENT & Head-Neck surgery department of the major Hospital and Health Institute of the Dhaka City, where appropriate facilities are available. Purposefully we chose the four major institution, e.g. Dhaka Medical College & Hospital (DMCH) Dhaka, Bangabandhu Sheikh Mujib Medical University (BSMMU), Shahid Shawardi Medical College & Hospital and Sir Salimullah Medical College & Mitford Hospital, Dhaka. All the patient with FNAC and Histopathologically proved salivary gland neoplasms in the hospital will be included in this study.
5.7 Inclusion criteria:
Patient presenting with salivary gland swelling in the Dept. of ENT and Head-Neck surgery, Dhaka Medical College & Hospital (DMCH), Bangabandhu Sheikh Mujib Medical University (BSMMU), Shahid Shawardi Medical College Hospital and Sir Salimullah Medical College & Mitford Hospital, Dhaka.
Exclusion criteria:
1. Patients with other than salivary gland swelling .
2. Patients with non-neoplastic salivary gland swelling.
3. Patient with traumatic or iatrogenic swelling.
Data collection method: After taking informed consent of the subject the data will be collected by the investigator through a structured questionnaire and thorough clinical examination with certain investigations and cyto/histopathological support.
Questionnaire : A structured questionnaire will be administered to collect the relevant information from the selected patient.
Reports: Radiological, Cytological & Histopathological.
Method of Study:
1)History: A thorough history was taken from each and every study subjects about detail demographic profiles and clinical symptoms also history of pastillness, family history, medical history, drug history etc. were recorded in every study subjects.
2) Physical Examination: Thorough general physical examination was done in every study subjects.
3) Examination of the ENT region: Each and every case was examined meticulously. Site, size, shape, surface, margin, tenderness, consistancy, mobility and overlying skin condition are noted in every cases of salivary gland swelling.
4) Bimanual palpation has done in every cases of submandibular salivary gland swelling.
5) Examination of the oral cavity, oropharynx, ear, nose and paranasal sinuses have done in every case.
6) Systemic Examination:All the systems are examined in each and every cases.
7) Investigations: Complete blood count, RBS, ECG and other necessary investigations are done in almost every case.
8) Radiological assessment done in selected cases.
9) In all 138 cases of my study series (which were already proved as neoplastic lesion) histopathology of resected surgical specimen were done, report was collected and was compared with preoperative FNAC report.
Data Collection:
Above data were recorded in data collection sheet for each patients of salivary gland neoplasms. After compiling the results,they had been arranged and presented in various tables and figures. On the basis of these result, the significance of this study was tested statistically by using the chi-square test X2 & ‘Z’ test, X and ‘Z’ values were compared with corresponding probability value. The interpretation of probability value is as following as- a) When P> O.O5, the test is not significant. b) When P value is in between o.o5-o.o1, the test is significant. When P value is less than o.o1 , the test is highly significant ( Makijan 1997 ).
Observation and Results
One hundred and thirty eight patients presented with salivary gland swellings were selected from ENT Department of DMCH , BSMMU ,SSMCH & SSMCH, DHAKA, during the period of July 2009 to 30 June 2010 . All cases were evaluated thorough history taking ,clinical examination and some important relevant investigations such as FNAC and Histopathological examination were done in all cases.The patients of both sexes and different age groups were included .
Table I:Age Distribution (n=138)
| Age Group (Years ) | No. of Patients | Percentage ( % ) | |
| 0 – 10 | 6 | 4.34 % | |
| 11 -20 | 12 | 8.69 % | |
| 21 – 30 | 30 | 21.73 % | |
| 31 – 40 | 16 | 11.59 % | |
| 41 – 50 | 45 | 32.60 % | |
| 51 -60 | 28 | 20.28 % | |
| 61 – 70 | 1 | 0.72% |
On statistical analysis the above table shows the mean age of salivary gland neoplasms were 43.92 years ,of which benign neoplasms were 41 years and malignant neoplasm was 51.25 years. In case of female in benign neoplasm mean age was 30.55 years and in male was 45.90 years.
Benign neoplasms were more common in female and more common age group was 41-50 years ( 4th & 5th decades ) .Mean age was 41 years in benign neoplasm. Malignant neoplasms were more common in male and more common age group was 51-60 years ( 5th & 6th decades ) .Mean age was 51.25 years. Statistical analysis shows there is a significant association between age and sex of the patient of salivary gland neoplasms .
TABLE-II: Sex Distribution in Benign and Malignant Neoplasms (n=138)
| Types of neoplasms | Male | Female | M:F | Male |
(%)Female
(%)Benign43651: 1.539.81%60.18%Malignant22082.75: 173.33%26.66%
The above table shows 43 ( 39.81 %) cases male and 65 (60.18%) cases female in case of benign neoplasms but 22 (73.33%) cases male and 8 ( 26.66%) cases female in case of malignant neoplasms and representing male : female ratio 1:1.5 in case of benign neoplasms and 2.75:1 in case of malignant neoplasms .
TABLE-III: Distribution of Patients by Educational Status ( n = 138 )
| Educational Status | No. of Patients | Percentage ( % ) |
| Illiterate | 45 | 32.60 % |
| Primary Education | 38 | 27.53 % |
| Secondary Education | 27 | 19.56 % |
| Higher Secondary Education | 20 | 14.49 % |
| Graduation or Above | 8 | 5.79 % |
| Total | 138 | 100 % |
The above table shows 45 ( 32.60%) cases had no formal education ,38 ( 27.53%) cases had up to primary level ,27 ( 19.56%) cases had upto secondary level ,17 ( 14.49%) cases had upto higher secondary level and 8 ( 5.79%) cases had graduation degree or above .
TABLE –IV: Occupational Distibution ( n = 138 )
| Name of Occupation | No of Patients | Percentage ( % ) |
| Housewife | 40 | 28.98 % |
| Farmer | 32 | 23.18 % |
| Businessman | 27 | 19.56 % |
| Others | 39 | 28.26 % |
The above table shows 40 ( 28.98%) cases were housewife ,32 ( 23.18 %) cases were farmer , 27 ( 19.56%) cases were businessman and 39 ( 28.26%) cases were others group .So, there is no statistically significant difference between different occupation groups .
TABLE-V: Socio-economic status ( n = 138 )
| Type of classes | No of Patients | Percentage ( % ) |
| Lower Class | 75 | 54.34 % |
| Middle Class | 45 | 32.60 % |
| Higher Class | 18 | 13.04 % |
The above table shows total number of patient 138 of which 75 ( 54.34%) cases found lower class family, 45 ( 32.60 %) cases found middle class family and 18 ( 13.04%) cases found higher class family .Lower class family found more , it may be due to less treatment cost in the Govt. hospital .
Table-VI:Distribution of rural and urban population (n =138)
| Area of Distribution | No. of patients | Percentage(%) |
| Rural area | 76 | 55.07% |
| Urban area | 62 | 44.92% |
In this study the above table shows total number of patient 138 of which 76 (55.07%) cases were presented from rural area and 62 (44.92%) cases presented from urban area.So there is no statistically significant difference between rural and urban population. TABLE-VII: Distribution & Frequency of Benign Salivary Gland Neoplasms According to Site ( n = 108)
| Site | No of Patients | Percentage ( %) | Frequency |
| Parotid Glands | 84 | 77.77 % | Most Common |
| Submandibular Glands | 14 | 12.96 % | Uncommon |
| Sublingual Glands | 01 | 0.92 % | Very Rare |
| Minor Glands | 09 | 8.33 % | Rare |
The above table shows benign salivary gland neoplasms are more common in parotid gland among all the salivary gland neoplasms.It was 84 ( 77.77%) cases among the 108 cases .
TABLE-VIII:Distribution of Malignant Salivary Gland Neoplasms ( n = 30 )
| Site | No of Patients |
| Parotid Glands | 18 (60%) |
| Submandibular Glands | 09 (30%) |
| Sublingual Glands | 0 (0%) |
| Minor Glands | 03 (10%) |
The above table shows malignant salivary gland neoplasms are more common in the parotid gland among all the salivary gland neoplasms and it was 18 ( 60%) cases among 30 cases
TABLE-IX: Distributin of Different Types of Benign Salivary Glands Neoplasms ( n = 108 )
| Types of Neoplasms | No. of Patients | Percentage ( % ) |
| Pleomorphic Adenoma | 95 | 87.96 % |
| Warthin’s Tumour | 06 | 5.55 % |
| Oncocytoma | 02 | 1.85 % |
| Others | 05 | 4.62 % |
The above table shows pleomorphic adenoma is more common among all types of benign salivary gland neoplasms both major & minor glands and pleomorphic adenoma was 95 ( 87.96%) cases .
TABLE-X : Distribution of Malignant Salivary Gland Neoplasms According to Types (n=30)
| Types of Tumours | No of Patients | Percentage ( % ) |
| Mucoepidermoid Carcinoma | 13 | 43.33 % |
| Adenoid Cystic Carcinoma | 07 | 23.33 % |
| Squamous Cell Carcinoma | 03 | 10 % |
| Adeno-carcinoma | 02 | 6.66 % |
| Lymphoma | 02 | 6.66 % |
| 0thers | 03 | 10 % |
The above table shows mucoepidermoid carcinoma is more common among all types of malignancy occurring both major & minor salivary gland and parotid is the commonest site & it is 13 ( 43.33%) cases .
TABLE-XI: Presenting Symptoms of Salivary Gland Neoplasms ( n = 138 )
| Symptoms | No. of Patients | Percentage ( % ) |
| Swelling in the Salivary Gland Region | 138 | 100 % |
| Painless Swelling | 115 | 83.33 % |
| Painful Swelling | 23 | 16.66 % |
| Facial Palsy | 12 |