1

SALIVARY GLAND NEOPLASMS IN ZARIA, NIGERIA

A TWENTY YEAR HISTOPATHOLOGICAL ANALYSIS

DR KABIRU ABDULLAHI (EXAM NO: 008/08/003/570)

BEING A DISSERTATION SUBMITTED IN PARTIAL FULFILLMENT

OF THE REQUIREMENT FOR THE FELLOWSHIP OF THE

NATIONAL POSTGRADUATE MEDICAL COLLEGE OF NIGERIA IN

PATHOLOGY, NOVEMBER 2011

2

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DECLARATION

I hereby declare that this in an original work done by me. It has not been presented to any

college for a fellowship nor has it been submitted elsewhere for publication.

…………………………

Kabiru Abdullahi

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CERTIFICATION

We hereby certify that this dissertation: Salivary Gland Neoplasms: A Twenty Year

Histopathological Analysis in Zaria was carried out in the Department of Pathology Ahmadu

Bellow University Teaching Hospital, Zaria under our supervision.

1. Dr M. S. Shehu

Consultant Pathologist,

Department of Pathology,

Ahmadu Bello University Teaching Hospital, Zaria, Nigeria.

Signature and Date: ………………………………………………………..

2. Dr M. O. A. Samaila

Consultant Pathologist,

Department of Pathology,

Ahmadu Bello University Teaching Hospital, Zaria, Nigeria.

Signature and Date: ………………………………………………………..

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DEDICATION

This work is dedicated to Allah, the Sustainer of the Universe!

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ACKNOWLEDGEMENT

All praise is to Allah the Sustainer of the Universe! This work would not have materialized if

He had not Willed it!

I thank Him for placing me in the midst of a rich assortment of (amongst other virtues)

distinguished hard working, keen eyed pathologists as mentors in my struggle to develop the

“third eye”!

Numerous these mentors are and I will fill pages if I were to mention each! A summary will

suffice: thank you Professor A. H. Rafindadi! “…look to see…!” you always admonished us!

Special thanks to Col. (Dr.) Y. Iliyasu, who in his kind ways, “actively managed” our

progress through the rigors of the College bureaucracy. Dr. A. Mohammed’s uncanny

morphologic diagnostic acumen was most inspiring!

My supervisors…what can I say…? This work was daunting! But “the toughest tasks look

easy in the hands of genius”. May Allah reward your patient guidance: Dr. M. S. Shehu

whose critical analysis of all cases was second to none and Dr. M. O. A. Samaila whose

matronly mien and perseverance ensured we beat the odds!

Our “big brother” Dr S. A. Ahmed who has been most inspiring from the word go, I say,

“thank you sir”!

It has been an honour training with Dr Almustapha Liman by my side! “There goes the

pathologic duo” were the thoughts of others when we were seen negotiating the maze of

residency together. Your finesse and culture is most distinguishing and influential.

The other residents who I have trained with I must mention specifically, Dr G. D. Waziri, Dr

B Calvin, Dr U Bappa, Dr M Shakir (Microbiology) and Dr I Nda (Hematology) Dr M.

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Abdulazeez (Microbiology). It has been a privilege knowing you. All the other residents not

here mentioned by name are however acknowledged.

The technical and administrative staff of the Pathology Department, I thank you all for your

support. Particularly, I must mention Mallam Abdullahi, who went through the arduous task

of daring the dust and retrieving archival material.

Of course, the daunting nature of this task was made light, thanks to the prayers and kind

understanding of my family.

Kabiru Abdullahi

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TABLE OF CONTENTS

1. DECLARATION……………………………………………………………………ii

2. CERTIFICATION……………………………………………….…….……………iii

3. DEDICATION……………………………………………………….….………….iv

4. ACKNOWLEDGEMENT………………………………………………………….v

5. TABLE OF CONTENTS..…………………………………….….………………...vii

6. LIST OF TABLES……………………………………….……………….………...ix

7. LIST OF FIGURES…………………………………………………………………x

8. SUMMARY………………………………………………………………………...xi

9. CHAPTER ONE……….………………………………………………...…………..1

Introduction…………….…………………………………………………………….1

Aims and Objectives………………………………………………………………....3

Rationale of the study… …………………………………….………………..…….3

10. CHAPTER TWO…………………………………………….…………………...….4

Literature review……….……………………………………………………..…….4

Anatomy of the Salivary Glands….……………………………………………..…..4

Epidemiology of Salivary Gland Neoplasms.……………………………………… 5

Aetiology of Salivary Gland Neoplasms……..………………………………….….7

Pathogenesis of Salivary Gland Neoplasms…...……………………………………8

Classification of Salivary Gland Neoplasms….……………………………………8

World Health Organization (WHO) Histological Classification of the Salivary

Gland Salivary Gland Neoplasms .………………………………………………….9

Diagnosis of Salivary Gland Neoplasms …………………………………………..11

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Immunohistochemistry of Salivary Gland Neoplasms………………………….…12

Cytogenetics and Molecular Pathology of Salivary Gland Neoplasms …...………12

Grading of Salivary Gland Neoplasms …………………………………………....13

Staging of Salivary Gland Neoplasms …………………………………………….14

Prognosis of Salivary Gland Neoplasms ………………………………………… ..14

Recurrence and Metastases of Salivary Gland Neoplasms ….…………………….15

Review of Some Morphological Types of Salivary Gland Neoplasms …….……...16

Metastatic and Infiltrating Carcinoma to the Salivary Glands……………………..19

11. CHAPTER THREE……………………………………………..………….………..20

Materials and methods ………………………….……………….……………….....20

Exclusion criteria…………………………………………….……..…………….....21

12. CHAPTER FOUR………………………………………….……………………….22

Results……………………………………………………..…………………..........22

Epithelial Salivary Gland Neoplasms……………….………………………………22

Non Epithelial Tumour Salivary Gland Neoplasms..................................................23

Sex distribution of tumours Salivary Gland Neoplasms...........................................23

Site Distribution of Salivary Gland Neoplasms....................................................... .23

13. CHAPTER FIVE………………………………………….…….………………… 32

Discussion…………………………………………….……………………………32

14. REFERENCES……………………………………………………………….........36

15. APPENDIX I………………………………………………………………………40

LIST OF TABLES

TABLE TITLE PAGE

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1 Frequency Distribution of Salivary Gland Neoplasms 25

2 Frequency Distribution of Salivary Gland Neoplasms by Age 26

3 Frequency Distribution of Salivary Gland Neoplasms by Types 27

4 Age Distribution of Tumours Salivary Gland Neoplasms 28

5 Frequency Distribution of Salivary Gland Neoplasms by Sex 29

6 Frequency Distribution of Salivary Gland Neoplasms by Site 30

7 Frequency Distribution of Salivary Gland Neoplasm Types by Site 31

LIST OF FIGURES

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FIGURE TITLE PAGE

1 Acinic Cell Carcinoma 42

2 Adenocarcinoma, NOS 43

3 Adenoid cystic carcinoma 44

4 Polymorphous Low Grade Adenocarcinoma 45

5 Pleomorphic adenoma 46

6 Pleomorphic adenoma 47

7 Sialoblastoma 48

SUMMARY

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The aim of this study was to determine the relative frequency of neoplasms of the

salivary gland seen at the Department of Histopathology, Ahmadu Bello University

Teaching Hospital, Zaria Nigeria over a period of 20years. All histologically

diagnosed cases as salivary gland neoplasms from January 1989 to December 2008

were retrieved from the histopathology records of the Department. Formalin fixed

paraffin embedded tissues stained with routine Hematoxylin and Eosin were retrieved

from the department archives and subject to morphologic re-evaluation via light

microscopy. All the cases were analysed for age, sex, site of occurrence and histologic

diagnosis based on 2005 World Health Organisation (WHO) classification.

The study showed that salivary gland neoplasms constituted 2.1% of all neoplastic

lesions seen in the study period. The male-to-female ratio was equal and majority of

the tumours affected the age group 31-40 years. Malignant tumours accounted for

50.7% (n = 131) and benign tumours 49.2% (n = 127). Pleomorphic adenoma had the

highest frequency of 43.4% and adenoid cystic carcinoma was the second commonest

(25.9%).

CHAPTER ONE

INTRODUCTION

The salivary glands are located in the head and neck region. They are grouped into major and

minor glands depending on whether they empty their secretions directly into the oral cavity or

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via ducts. Each gland is composed of secretory units separated into lobules and

approximately one litre of saliva is produced daily from all the glands. 1

Salivary gland lesions fall into three broad spectrum of developmental, inflammatory and

neoplastic. The developmental lesions are due to embryological defects, inflammatory lesions

arise from aberrations in the immune system and the neoplastic disorders follow non lethal

genetic dysregulation of the cell cycle. The neoplastic lesions are either benign or malignant

and may occur primarily or as metastases from other sites.

Salivary gland neoplasms represent 2% to 6.5% of all neoplasms occurring in the head and

neck region.2 While, head and neck cancers rank as the fifth most common malignancy in

men, and eighth in women. 3

Salivary gland neoplasms as a group are complex and diverse and thus pose considerable

diagnostic and management challenges to the pathologist and surgeon.4- 6

Globally, there is a shift in attention to cancers as a major cause of morbidity and mortality.

Currently, an estimated 22 million people are living with cancer, while approximately,

10 million new cases are diagnosed annually and 6 million of these will die of the disease.7

The global annual incidence of all salivary gland neoplasms ranges from 0.4 to 13.5 cases

per 100,000 population with variable loco-regional incidence rates.8, 9

The overall global tumour burden accounted for by salivary gland neoplasms is very small as

documented by large multicenter studies involving 22,866 salivary gland neoplasms. 10

This study is a retrospective histopathological review of salivary gland neoplasms over a

twenty-year period (1989 – 2008) in the Department of Pathology Ahmadu Bello University

Teaching Hospital, Zaria (ABUTH).

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AIMS AND OBJECTIVES

To:

1. Evaluate the frequency of all types of salivary gland neoplasms seen in Ahmadu Bello

University Teaching Hospital Zaria from 1st January 1989 to 31st December, 2008.

2. Determine the histopathological pattern of distribution of the neoplasms by patients’

age, sex and site of presentation.

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3. Compare the findings in this study with other similar studies done locally, regionally

and globally.

RATIONALE FOR THE STUDY

This is a pioneer study in our center (ABUTH) which is located in North Central zone of

Nigeria. The hospital subserves Zaria city, the rest of Kaduna state and neighboring states of

Sokoto, Zamfara, Jigawa, Kano, Katsina, Bauchi and Niger states.

The study will ascertain the frequency of salivary gland neoplasms in our environment and

serve as a baseline for future studies.

Globally, there are limited studies on salivary gland neoplasms. This study will add to

existing knowledge and literature as well as provide the current pattern of these neoplasms in

our environment using standard diagnostic criteria.8

CHAPTER TWO

LITERATURE REVIEW

Anatomy of the Salivary Glands

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The anatomy of the parotid glands and the role of the main ducts were described in the early

17th century, while the Greeks described “para-auricular swellings,” and the associated

findings of calculi and inflammation.11

The salivary glands arise from the epithelial lining of the mouth and distinction is usually

made between the major glands located at some distance from the oral mucosa and the minor

glands which lie in the mucosa or submucosa of the oral cavity. While the major glands

empty their secretions via ducts, the minor empty directly into the oral cavity to produce

saliva. 3, 12 The function of the salivary glands is essentially production of saliva which

lubricates ingested food to assist deglutition, moistening of the buccal mucosa for speech,

provision of an aqueous solvent necessary for taste, together with being a fluid seal for

sucking and suckling. In addition, it contains digestive enzymes such as salivary amylase,

hormones and other compounds, such as a glucagon-like protein, serotonin and antimicrobial

agents (IgA, lysozyme and lactoferrin). 12

In humans, the major salivary gland comprises the paired parotids, submandibular and

sublingual glands while the minor groups include those in the tongue and elsewhere in the

oral cavity. 12 Unlike the major glands, the minor salivary glands are uncapsulated and

scattered in the oral mucosa and elsewhere in the upper aero-digestive region. They are most

numerous at the junction between the hard and soft palate. Based on their secretions, salivary

glands are grouped as seromucinous or mucinous. 8

Functionally, the basic unit of the gland is composed of an acinus and a duct while

morphologically, the glands are compound tubuloacinar, with numerous lobes composed of

lobules linked by dense connective tissue. Each lobule has a single duct, whose branches

begin as dilated secretory end pieces or acini. 8, 12 The myoepithelial cells lie between the

secretory cells and the basement membrane and are immunopositive for smooth muscle actin,

myosin, and keratin 14. 8 The duct system is composed of three distinct elements comprising

of the intercalated, the striated, and the interlobular ducts. 3

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Salivary gland tissues may also be seen in a number of ectopic sites such as the external ear,

middle ear, thyroglosssal duct, thyroid capsule, parathyroid glands, cervical lymph nodes, and

intra-mandibular. 3

Epidemiology of Salivary Gland Neoplasms

The World Health Organization (WHO) has observed that a comprehensive assessment of the

epidemiology of salivary gland neoplasms has not been documented.8, 13 These lesions are

uncommon and represent 2% to 6.5% of head and neck neoplasms with a global annual

incidence of 0.4 to 13.5 cases per 100,000 population. 5, 8

Incidence rates in the United States, United Kingdom, China and India range from 0.2 to 1.1

per 100,000 population. 14

The majority of these tumours are unilateral and single. However, exceptions may be seen in

lesions such as Warthin’s tumour, benign mixed tumour and acinic cell carcinoma.15

The major glands account for a large percentage of primary epithelial salivary gland tumours

with the parotid being implicated in 64-80% of all cases while the minor salivary glands are

the second commonest sites, accounting for 9-23% of the cases. 8

Of the neoplastic lesions, the benign variants are the commonest and account for 54%-79% of

cases while malignant tumours account for 21%-46% and 15-32% of these occur in the

parotid while 41%-45% are found in the submandibular glands.8 The sublingual glands are

rarely involved, however, when affected, 70%-90% are malignant. The majority (80%-90%)

of salivary gland tumours in the retromolar areas, the floor of the mouth and the tongue are

often malignant.8

Studies from Ibadan, Nigeria revealed an incidence rate for malignant salivary gland

neoplasms of 0.4 per 100,000 in females and 0.6 per 100,000 in males accounting for 3.5% of

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head and neck neoplasms and the parotid was the most frequent site of involvement

(46.5%).16,17

Reports from Lagos, observed that salivary gland tumours accounted for 10.0% of all head

and neck tumours and involved the parotid (32.1%), palatal (24.9%), and submandibular

(19.4%) glands. 17, 18

Reports from the Maxillo-Facial Unit of ABUTH Kaduna center and Maiduguri, both of

which are geographically close to our center reported a peak age of occurrence in the third

decade for benign tumours and sixth decade for the malignant cases. The palatal and the

parotid glands were commonest sites of occurrence of all tumour types in their series.19, 20

Studies from other African countries reported varied incidences for malignant tumours

ranging from 0.1-0.8 per 100,000 in Gambia, Algiers, Kenya, Zimbabwe and South Africa

and 1.5- 4.4 per 100,000 in the Democratic Republic of Congo and Ghana. 16

Another study in Uganda reported 34%, 33.2% and 32.8% of the tumours in the parotid,

submandibular and minor salivary glands respectively with 46.6% malignant cases and

53.4% benign ones. 21While the mean age of the patients with malignant tumours was

observed to be 9.6 years older than those with benign tumours. The pattern of salivary gland

tumours in studied black African population differed from their Western population in terms

of sites involved which were predominantly in the submandibular and minor glands, while

most lesions in the parotid were malignant and Warthin’s tumour was extremely rare.21

Interestingly, studies in children were not prominent in the African series while the series

from the West observed that benign mixed tumour was the commonest in children though,

the proportion of malignant tumours in children is higher than in adults’.16

Aetiology of Salivary Gland Neoplasms

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There is little known about the aetiology of salivary gland neoplasms. High risk populations

have not been clearly identified, except for the rare lymphoepithelioma-like carcinoma which

is commoner among Eskimos.8 However, implicated in the aetiology of salivary gland

neoplasms are viral infections (Epstein-Barr virus and human herpes virus type 8), exposure

to radiation (as occurred in survivors of the atomic bomb explosions in Hiroshima and

Nagasaki) or following therapeutic radiation to the head and neck region.8, 22 A study has

shown an association between the development of the neoplasms and exposure to

microwaves, such as prolonged usage of cell phones. 23 Also, exposure to iodine 131, used in

the treatment of thyroid diseases has been associated with a risk of developing salivary gland

tumours, as the isotope is concentrated in the glands. Other associated risk factors are

exposure to nickel compounds, asbestos, rubber and wood work, while none statistically

observed significant risk factors include family history of cancer, obesity and ingestion of

meats and vegetables. 8, 24 Cigarette smoking has been associated with higher risk for the

development of Warthin’s tumour of all the salivary gland neoplasms. 25

Pathogenesis of Salivary Gland Neoplasms

Two theories exist in attempts to explain the pathogenesis of these morphologically diverse

neoplasms. 10 The first is the multicellular theory, which asserts that neoplasms of the

salivary glands arise from adult differentiated counterpart of the salivary gland unit. Thus,

acinic tumours arise from the acinar cells, oncocytic tumours arise from the striated duct

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cells, and pleomorphic adenoma develops from the intercalated ducts and myoepithelial cells,

while squamous cell and mucoepidermoid carcinomas develop from the excretory ducts.10

The second bicellular theory posits that the basal cells of the excretory and intercalated ducts

act as stem cells. While the stem cells of the intercalated ducts give rise to acinic cell

carcinoma, adenoid cystic carcinoma, mixed tumours, oncocytic tumours and Warthin’s

tumour, those of the excretory duct give rise to squamous cell and mucoepidermoid

carcinomas.10

.

Classification of Salivary Gland Neoplasms

Comprehensive classifications of the salivary gland neoplasms have been developed because

of the wide morphological diversity of the lesions and the need to reach a precise diagnosis.

The classification of salivary gland neoplasms is essentially based on morphology. 5 Two

main systems of classification exist: - WHO and AFIP schemes.

These two schemes have undergone revisions and differ in some aspects including the

grading criteria. 5

The WHO classification scheme is reproduced below:

World Health Organisation (WHO) Histological Classification of

Neoplasms of the Salivary Glands 8

Malignant Epithelial Neoplasms

Acinic cell carcinoma

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Mucoepidermoid carcinoma

Adenoid cystic carcinoma

Polymorphous low-grade adenocarcinoma (PLGA)

Epithelial-myoepithelial carcinoma

Clear cell carcinoma, not otherwise specified *

Basal cell adenocarcinoma

Sebaceous carcinoma

Sebaceous lymphadenocarcinoma

Cystadenocarcinoma

Low-grade cribriform cystadenocarcinoma

Mucinous adenocarcinoma

Oncocytic carcinoma

Salivary duct carcinoma

Adenocarcinoma, not otherwise specified *

Myoepithelial carcinoma

Carcinoma ex pleomorphic adenoma/ Carcinosarcoma

Metastasizing pleomorphic adenoma

Squamous cell carcinoma

Small cell carcinoma

Large cell carcinoma

Lymphoepithelial carcinoma

Sialoblastoma

*the phrase: “not otherwise specified (NOS)” refers to that tumour type with no

dominant growth pattern in all fields of sections examined. It is a diagnosis of

exclusion after ruling out any other specific tumour type via morphologic criteria. 2, 8

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Benign Epithelial Neoplasms

Pleomorphic adenoma

Myoepithelioma

Basal cell adenoma

Warthin tumour

Oncocytoma

Canalicular adenoma

Sebaceous adenoma

Lymphadenoma

i. Sebaceous

ii. Non-sebaceous

Ductal papillomas

Cystadenoma

Soft Tissue Neoplasms

Haemangioma

Haematolymphoid Neoplasms

Hodgkin lymphoma

Diffuse large B-cell lymphoma

Extranodal marginal zone B-cell lymphoma

Secondary Neoplasms

Diagnosis of Salivary Gland Neoplasms:

The diagnosis of salivary gland neoplasms is based on morphological appearances following

routine paraffin embedded tissue sections and staining with haematoxylin and eosin. Other

ancillary investigative measures that can be used include:

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1. Fine needle aspiration cytology: - this can provide a rapid non-surgical diagnosis of the

lesions and serve as a screening tool to triage patients into different treatment pathways. Its

diagnostic accuracy is unquestionably related to the experience of the cytopathologist and the

type and quality of the case material. However, false negativity and positivity rates range

from 5% to 10% and 0% to 6% respectively. 2, 8 It should be noted though, that while image

guided aspiration is now in use, it has not been proven to significantly improve the cytologic

evaluation of salivary gland neoplasms.8

2. Frozen section examination: - this is a useful tool in centers where it is practiced. However,

controversy exists with respect to its accuracy because of frequent over diagnosis of

pleomorphic adenoma as mucoepidermoid carcinoma.8

3. Radiographic studies: - these include plain radiography, sialography, computed

tomography (CT), ultrasonography, CT sialography and Magnetic Resonance Imaging

(MRI). Of all these, MRI is particularly useful when inflammatory disease is to be ruled out. 8

Immunohistochemistry of Salivary Gland Neoplasms

Due to the morphologic diversity and similarity among a number of salivary gland

neoplasms, immunophenotyping as a means of improving diagnostic accuracy would seem

indispensible. However, results of immunohistochemical features of these lesions have been

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described as being “disappointingly anarchical”. 5 The use of some markers such as

cytokeratins, S100 protein, actins, calponin, epithelial membrane antigen, vimentin and

carcinoembryonic antigen, have been employed in attempts to distinguish the lesions. 5 Sadly,

the major drawback of these markers is their non-specificity.

Despite these drawbacks, the use of CD 117 and glial fibrillary acidic protein (GFAP) may

be helpful in differentiating pleomorphic adenoma, polymorphous low grade adenocarcinoma

and adenoid cystic carcinoma. Many cases of adenoid cystic carcinoma are CD 117 positive,

in contrast to polymorphous low grade adenocarcinoma which is often negative. Also,

Pleomorphic adenoma is frequently positive to GFAP in contrast to polymorphous low grade

adenocarcinoma.5

Cytogenetics and Molecular Pathology of Salivary Gland Neoplasms

Cytogenetic studies of salivary gland neoplasms should eventually be able to supplant the

subjective phenotypic evaluation in the diagnosis, biological assessment and therapeutic

stratification of patients with these tumours. The studies have shown some unique genetic

lesions involved in some of the lesions such as 3p21, 8q12 and 12q13-15 chromosomal

rearrangements and increased expression of PLAG-1 and HMG-C genes in Pleomorphic

adenoma, 11q21 and 19p13 translocations in Warthin’s tumour and mucoepidermoid

carcinoma respectively and alterations in 6q, 8q and 12q seen in adenoid cystic carcinoma

and carcinoma ex-pleomorphic adenoma. 8

In addition to these genetic aberrations, it has been observed that other molecular

perturbations also occur in some of these tumours. C-erb/Her-2/neu a member of the EGFR

signal transduction family has been shown to be over expressed in mucoepidermoid and

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salivary duct carcinomas while the proto-oncogene C-Kit has been shown to be over

expressed in adenoid cystic carcinoma, polymorphous low-grade adenocarcinoma and

monomorphic adenoma. 8, 26

Grading of Salivary Gland Neoplasms

Microscopic grading of salivary gland carcinomas has been shown to be an independent

predictor of behaviour and also plays a vital role in optimizing treatment.2 There is a positive

correlation between the grade and clinical stage of the disease. 2, 5

Squamous cell carcinoma and adenocarcinoma, not otherwise specified (NOS) are graded in

a similar manner as extra-salivary lesions. However, grading is more complex when other

salivary gland tumours are encountered. The WHO and AFIP series agree that tumour grade

is part of a spectrum of features and has no absolute significance in individual cases.

The AFIP fascicle proposes grading the tumours with respect to the diagnosis made so that

certain tumours such as acinic cell carcinoma, basal cell adenocarcinoma and polymorphous

low grade adenocarcinoma, which have low-grade biologic behaviour will have a single

grade. While a diagnosis of undifferentiated carcinoma connotes a high grade tumour.

Adenoid cystic carcinoma is graded into intermediate and high grade types based on

evaluation of predominant growth pattern as cribriform, tubular or solid. Specific grading

criteria are applied to mucoepidermoid carcinoma and this combines the presence or absence

of growth characteristics and cytomorphologic features.2

Staging of Salivary Gland Neoplasms

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Although grade is important in guiding oncologists as to the possible biological behaviour of

a neoplasm, it has been shown that the clinical stage particularly, the tumour size, is the

critical factor in determining the outcome of salivary gland cancers.2, 5 While the use of the “4

cm rule” has been advocated, the TNM system, whose parameters include tumour size, local

extension, metastasis to local and regional nodes and distant sites is widely used. 5, 8

Survival also correlates closely with the stage of the tumour and the 10 year survival rates

was 83%, 53%, 35% and 24% respectively for patients with stage I through stage IV disease.2

Prognosis of Salivary Gland Neoplasms

The prognosis of salivary gland neoplasms correlates most strongly with the clinical stage. 2, 8

the other independent predictors of behaviour include microscopic type and tumour grade. 8

Malignant neoplasms of the parotid gland with facial nerve involvement have an ominous

prognosis. A higher incidence of recurrence and metastasis is also seen in submandibular

gland when compared to similar tumours in the parotid gland. 16

Recurrence and Metastasis of Salivary Gland Neoplasms

Malignant tumours occurring in the minor salivary glands are infamous for late recurrences

and metastases and 70% of recurrences appear within 2 years of initial diagnosis.10 Adenoid

cystic carcinoma, adenocarcinoma, NOS and pleomorphic adenoma are bound to recur in the

presence of inadequate resection margins. In a reported series, the incidence of distant

metastasis for adenoid cystic carcinoma was 25%-50% and the most frequent sites were the

lung and bone. 10

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Review of Some Morphological Types of Salivary Gland

Neoplasms

Pleomorphic Adenoma

This is a benign epithelial derived tumour composed of cells that demonstrate both epithelial

and myoepithelial differentiation.2 It is the most commonly reported benign epithelial tumour

of the salivary glands. In a reported four large series, they represented 45% to 75% of all

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salivary gland tumours. 2, 10 The average age of patients with this tumour is 43years and

females are more commonly affected. However, reports from Maiduguri, Nigeria, observed a

frequency of 58.9% with a male predominance in the third decade of life20 while a study in

Uganda showed a frequency of 74%.21

Grossly pleomorphic adenoma typically presents as an encapsulated irregular round to ovoid

mass with well defined borders. The cut surfaces of the neoplastic tissue are mostly

homogenous and have translucent myxo-chondroid areas.2, 8

Microscopically the tumour is renowned for its protean histologic and cytomorphologic

diversity. The essential diagnostic feature is the presence of epithelial and mesenchyme-like

tissues. An infinite number of architectural configurations occur and vary within each tumour

and from one tumour to another. 2, 8

Warthin’s Tumour (papillary cystadenoma lymphomatosum)

This is an adenoma in which bilayered columnar and basaloid oncocytic epithelia form

multiple cysts and have numerous papillations. It occurs almost exclusively in the parotid

gland and is the second most common benign parotid tumour, accounting for 4 to 11.2% of

all salivary gland tumours. It comprised 10.5% of all benign parotid tumours seen in a report

from the Armed Forces Institute of Pathology (AFIP).2 It has a relatively low incidence in

Blacks. 2, 21

Grossly, the tumour is nearly always well circumscribed. The cut surface shows a variable

number of cysts that exude clear, mucoid or brown fluid or caseous semi-solid debris. The

intercystic areas are composed of small tan to white nodular foci.

29

Microscopically, it is characterized by cystic spaces lined by papillary proliferation of

bilayered oncocytic epithelium whose supporting stroma is composed largely of lymphoid

tissue. While the luminal epithelium is composed of tall columnar cells that often show

palisading of their ovoid nuclei. Beneath the columnar cells are smaller basaloid cells. The

epithelium forms variably sized and shaped papillae that project into the cystic spaces.

Mucoepidermoid Carcinoma

This is a malignant epithelial tumour that is composed of varying proportions of mucous,

epidermoid, intermediate, columnar and clear cells and often demonstrates prominent cystic

growth. The tumour is divided into low, intermediate and high grade types. Many series have

reported it as the most common malignant tumour. Its frequency in the major and minor

salivary glands respectively is 22% and 41%. Its peak age of occurrence is in the third to

seventh decades with a mean age of 47years and a female predilection while other reports

indicate an equal sex distribution. 2, 20, 21

Grossly, it typically lacks a capsule especially the high grade type while its cut surface is

usually firm, gray, tan-yellow or pink and lobulated. Cysts are usually seen, but vary in size

and prominence.

Microscopically, the intermediate cells outnumber the other cell types (epidermal, mucus,

columnar and clear) in most tumours. These cells are “intermediate” in size and appear

between basal cells and epidermoid cells. They are slightly larger than lymphocytes. The

mucous cells are the neoplastic cells in mucoepidermoid carcinoma and contain epithelial

mucin, regardless of morphology. They comprise less than 10% of the tumour cells.

Epidermoid cells form small solid nests or partially lined cystic spaces. Clear cells account

30

for about 10% of most mucoepidermoid carcinomas. Special stains using periodic acid Schiff

(PAS) and mucicarmine reveal the presence of glycogen and occasional mucin. Columnar

cells are less numerous than mucous cells and often line cystic spaces.

Adenoid cystic Carcinoma

This is a malignant epithelial tumour that is often slow to metastasize but persistent and

relentless in growth. It shows myoepithelial (predominantly) and ductal differentiated cells.

Characteristically, it exhibits cribriform, tubular and solid patterns of growth in varying

proportions. The cribriform pattern of the tumour forms cylindrical accumulations of basal

lamina, glycosaminoglycans and stroma.2

It accounts for 7.5% of all malignant epithelial tumours of the salivary glands and is the

second commonest. 2, 20, 21

Grossly, the tumour is usually firm with a white to gray-white cut surface. Circumscription is

deceptive because the tumour tissue has often infiltrated beyond the tumour margin.

Microscopically, based on the morphologic growth patterns, the tumour has been classified

into cribriform, tubular and solid forms. Most common is the cribriform pattern and least

common is the solid pattern. Typically, a mixture of these patterns is seen. One of the hall

marks of adenoid cystic carcinoma is peripheral nerve invasion which is usually perineural

within the nerve sheath, but tumour may also be found within the nerve. 2, 20, 21

Metastatic and infiltrating Carcinoma to the Salivary Glands

31

The major salivary glands can be involved by malignant neoplasm originating outside the

salivary glands. Metastatic tumours account for 10% of salivary gland tumours.2 The minor

intraoral salivary glands are often involved by cancer of the oral mucosa, sarcomas of the oral

soft tissues and metastasis from distant primary sites. The routes of such involvement include

the following:

1. Direct invasion: such a scenario is seen in the parotid and submandibular glands with

involvement from a primary squamous cell carcinoma and basal cell carcinoma of the

skin overlying these.2

2. Hematogenous and lymphatic spread: approximately 80% of such tumours affecting the

parotid glands via theses routes are from the head and neck region, while 20% are

from the infraclavicular primaries. A higher proportion of infraclavicular tumours

involve the submandibular glands. Majority of metastatic tumours in the parotid and

submandibular glands are carcinomas and malignant melanomas, while metastatic soft

tissue tumours are rare. Other tumours that have been reported to have metastasized to

the salivary glands include: retinoblastoma, sebaceous carcinoma, eccrine carcinoma,

Merkel’s cell carcinoma and intracranial neoplasms. A relatively common finding is a

metastatic thyroid papillary carcinoma. Tumours from the infraclavicular sites include

the lung, kidney and breast. Infrequently, tumours from the colon, stomach, uterus

and urinary bladder have been reported. 2, 8

CHAPTER THREE

MATERIALS AND METHOD

This retrospective analysis was based on all specimens obtained from salivary gland tumours

submitted to the Pathology Department of the Ahmadu Bello University Teaching Hospital

32

(ABUTH) Zaria, for histopathological examination in the period: 1st January, 1989 to 31st

December 2008 (20 years). The hospital is a referral center for the North-central region of the

country subserving neighboring states of Sokoto, Zamfara, Jigawa, Kano, Katsina, Bauchi

and Niger states.

All cases registered as salivary gland neoplastic lesions were extracted from the departmental

records comprising the bench books, reception registers, requisition cards and documented

reports. The patients’ case cards filled by the requesting clinicians, together with all the

relevant histology slides stained with routine Hematoxylin and Eosin (H & E) were retrieved.

For cases in which there was inadequate information on their cards, the surgical operation

notes or the patient charts were also consulted.

In cases of broken and missing slides, fresh sections were made from stored tissue blocks.

All the slides were reviewed with the Supervising Consultants and classified using WHO

Classification of Tumours of the Head and Neck8 as a guide for diagnostic criteria.

The age, sex and site of tumour for all patients were extracted from the accompanying case

cards.

Analysis of the collected data was carried out using Statistical Program for Social Sciences

(SPSS) Version 15.0, and data presented in frequency distribution tables and figures

(photomicrographs with legends).

Ethical clearance had been sought and obtained from the Ethics and Scientific Committee of

the ABUTH, Shika- Zaria for the study.

EXCLUSION CRITERIA

The following were excluded from the study:

33

1. Cases with grossly inadequate information (bio data, site of biopsy, etc) when such

information cannot be retrieved from other records (patients’ case notes, theatre records,

radiologic records, etc)

2. Cases in which both slides and tissue blocks were missing.

CHAPTER FOUR

34

RESULTS

A total of 44,698 surgical specimens were received and processed in the Department of

Pathology ABUTH, Zaria during the period 1st January 1989 to 31st December 2008.

Neoplastic lesions accounted for 12,337(27.6%) and of these, benign were 3,683 (8.2%)

while malignant were 8,654 (19.4%).

Two hundred and fifty eight (258) salivary gland neoplastic lesions were analyzed. They

represented 0.6% of the total specimens and 2.1% of neoplastic lesions seen in the study

period.

The overall male: female ratio was approximately 1: 1. (Table 1)

The age range for all the neoplasms was 2.5 - 91years with a mean age of 50.7years and peak

age distribution in the 3rd – 5th decades. (Table 2)

There were one hundred and twenty seven (127) benign tumours of which 121 were epithelial

in origin and comprised 46.9% while malignant tumours were one 131, representing 50.7%

and all were epithelial in origin. (Table 3)

Epithelial Salivary gland Neoplasms

The benign epithelial neoplasms comprised mainly pleomorphic adenoma 112 cases (43.4%),

basal cell adenoma-8 cases (3.1%) and one cystadenoma (0.4%). (Table 3)

The highest frequency of these epithelial tumuors 37 (14.3%) occurred in the third decade of

life. (Table 4)

Adenoid cystic carcinoma accounted for 67(25.9%) and muco-epidermoid carcinoma 47

(18.2%) cases. The least common tumours were a case each of acinic cell carcinoma

(affecting the parotid gland of a 17 year old female) and sialoblastoma (affecting the parotid

gland of a 3 year old female). These represented 0.4% each. (Table 3, 5 and 7)

35

Non Epithelial Salivary gland Neoplasms

This group comprised three lipomas and solitary cases of fibromyxoma and fibrohistiocytoma

(representing 0.4% each). (Table 3)

Sex Distribution of Salivary gland Neoplasms

A total of 131 (50.8%) salivary gland neoplasms occurred in males and127 (49.2%) in

females. Of these, 30.2% (78 cases) and 20.5% (53 cases) represented malignant variants in

males and females respectively. The commonest malignant epithelial neoplasm in both sexes

was adenoid cystic carcinoma with a frequency of 37 (14.3%) in males and 30 (11.6%) in

females, while mucoepidermoid carcinoma was the second commonest in both sexes.

Polymorphous Low Grade Adenocarcinoma (PLGA) had a frequency of 2 (0.8%) and 3

(1.2%) in males and females respectively. (Tables 1 and 5)

Out of the 53 benign lesions in males, 49 (19.0%) were epithelial and 4 (1.6%) were of soft

tissue origin. In females, 72 (27.9%) were epithelial in origin. (Table 5)

Pleomorphic adenoma was the commonest benign lesion in both sexes with a female

predominance (25.6%). (Table 5)

Site Distribution of Salivary Gland Neoplasms

One hundred and thirty nine cases (53.9%) occurred in the parotid gland and 63 cases

(24.4%) occurred in the minor salivary glands. Other sites were the submandibular gland with

37 tumours (14.3%) and the neck region with 12 cases (4.7%). (Table 6)

Pleomorphic adenoma and mucoepidermoid carcinoma were the commonest tumours in the

parotid gland. The solitary cases of sialoblastoma and acinic cell carcinoma also involved the

parotid gland. (Table 7)

36

Table 1: Frequency Distribution of Salivary gland Neoplasms by Sex

SEX Number Frequency (%)

Male 131 50.8

Female 127 49.2

Total 258 100.0

37

Table 2: Frequency Distribution of Salivary gland Neoplasms by Age

AGE (Years) Number Frequency (%)

1-10 4 1.6

11-20 25 9.7

38

21-30 58 22.4

31-40 65 25.2

41-50 53 20.5

51-60 36 14.0

61-70 8 3.1

71 + 4 1.6

Unspecified 5 1.9

Total 258 100.0

Table 3: Frequency Distribution of Salivary gland Neoplasms by Types

TUMOUR TYPE Number Frequency (%)

Benign

Epithelial Origin

39

Pleomorphic adenoma 112 43.4

Basal cell adenoma 8 3.1

Cystadenoma 1 0.4

Sub-total 121 46.9

Soft Tissue Origin

Lipoma 3 1.2

Fibromyxoma 2 0.8

Fibrohistiocytoma 1 0.4

Sub-total 6 2.4

Malignant

Epithelial Origin

Acinic cell carcinoma 1 0.4

Mucoepidermoid carcinoma 47 18.2

Adenoid cystic carcinoma 67 25.9

Polymorphous low-grade adenocarcinoma 5 1.9

Clear cell carcinoma NOS* 1 0.4

Basal cell adenocarcinoma 2 0.8

Cystadenocarcinoma 2 0.8

Adenocarcinoma, NOS* 5 1.9

Sialoblastoma 1 0.4

Sub-total 131 50.7

Grand Total 258 100.0

* Not Otherwise Specified

Table 4: Age Distribution of Salivary gland Neoplasms

Tumour Type Age Range

1-10 11-20 21-30 31-40 41-50 51-60 61-70 71+ Unsp

ecifd*

Total (%)

Benign

Epithelial Origin

40

* Unspecified

** Polymorphous Low Grade Adenocarcinoma

*** Not Otherwise Specified

Table 5: Frequency Distribution of Salivary gland Neoplasms by Sex

TUMOUR TYPE

Frequency Total (%)

Male Female

Benign

Epithelial Origin

Pleomorphic

Adenoma

1 13 37 25 21 9 1 1 4 112 (43.4)

Basal cell

Adenoma

0 0 0 4 1 2 1 0 0 8 (3.1)

Cystadenoma 0 0 0 1 0 0 0 0 1 (0.4)

Sub-total 1 13 37 30 22 11 2 1 4 121 (46.9)

Soft Tissue

Lipoma 0 0 0 1 1 1 0 0 0 3 (1.2)

Fibromyxoma 1 1 0 0 0 0 0 0 0 2 (0.8)

Fibrohistiocytoma 0 0 0 0 0 1 0 0 0 1 (0.4)

Sub-total 1 1 0 1 1 2 0 0 0 6 (2.4)

Malignant

Epithelial Origin

Acinic cell

Carcinoma

0 1 0 0 0 0 0 0 0 1 (0.4)

Mucoepidermoid

Carcinoma

1 5 10 11 9 8 3 0 0 47 (18.2)

Adenoid cystic

Carcinoma

0 5 9 18 16 12 2 4 1 67 (25.9)

PLGA* 0 0 0 1 1 2 1 0 0 5 (1.9)

Clear cell carcinoma 0 0 0 1 0 0 0 0 0 1 (0.4)

Basal cell adencarcnma 0 0 1 0 1 0 0 0 0

2 (0.8)

Cystadenocarcinoma 0 0 0 0 1 1 0 0 0 2 (0.8)

Adenocarcinoma,

NOS**

0 0 1 2 2 0 0 0 0 5 (1.9)

Sialoblastoma 1 0 0 0 0 0 0 0 0 1 (0.4)

Sub-total 2 11 21 33 30 23 6 4 1 131 (50.7)

Grand Total 4 25 58 64 53 36 8 5 5 258(100.0)

41

Pleomorphic adenoma 46 66 112 (43.4)

Basal cell adenoma 3 5 8 (3.1)

Cystadenoma 0 1 1 (0.4)

Sub-total 49 72 121 (46.9)

Soft Tissue Origin

Lipoma 2 1 3 (1.2)

Fibromyxoma 1 1 2 (0.8)

Fibrohistiocytoma 1 0 1 (0.4)

Sub-total 4 2 6 (2.4)

Malignant

Epithelial Origin Acinic cell carcinoma 0 1 1 (0.4)

Mucoepidermoid carcinoma 30 17 47 (18.2)

Adenoid cystic carcinoma 37 30 67 (25.9)

PLGA* 2 3 5 (1.9)

Clear cell carcinoma 1 0 1 (0.4)

Basal cell adenocarcinoma 2 0 2 (0.8)

Cystadenocarcinoma 2 0 2 (0.8)

Adenocarcinoma, NOS** 4 1 5 (1.9)

Sialoblastoma 0 1 1 (1.9)

Sub-total 78 53 131 (50.7)

Grand Total 131 127 258(100.0)

* Polymorphous Low Grade Adenocarcinoma

** Not Otherwise Specified

Table 6: Frequency Distribution of Salivary gland Neoplasms by Site

SITE OF TUMOUR Number Frequency (%)

42

Parotid gland 139 53.9

Submandibular gland 37 14.3

Minor salivary glands 63 24.4

Neck 12 4.7

Unspecified 7 2.7

Total 258 100.0

Table7: Frequency Distribution of Salivary gland Neoplasm Types by Site

Tumour type Site

Parotid

gland

Submandibular

gland

Minor

salivary

gland

Neck

Unspecified

Total (%)

43

* Polymorphous Low Grade Adenocarcinoma

** Not Otherwise Specified

CHAPTER FIVE

DISCUSSION

Benign

Epithelial Origin

Pleomorphic adenoma 64 20 19 9 0 112 (43.4)

Basal cell Adenoma 5 1 1 0 1 8 (3.1)

Cystadenoma 1 0 0 0 0 1 (0.4)

Sub-total 70 21 20 9 1 121 (46.9)

Soft Tissue Origin

Lipoma 0 1 0 0 2 3 (1.2)

Fibromyxoma 1 0 0 0 1 2 (0.8)

Fibrohistiocytoma 1 0 0 0 0 1 (0.4)

Sub-total 2 1 0 0 3 6 (2.4)

Malignant

Epithelial Origin

Acinic cell Carcinoma 1 0 0 0 0 1 (0.4)

Mucoepidermoid carcinoma 32 3 11 1 0 47 (18.2)

Adenoid cystic carcinoma 25 10 31 1 0 67 (25.9)

PLGA* 0 1 1 1 2 5 (1.9)

Clear cell carcinoma NOS** 0 0 0 0 1 1 (0.4)

Basal cell adenocarcinoma 2 0 0 0 0 2 (0.8)

Cystadenocarcinoma 2 0 0 0 0 2 (0.8)

Adenocarcinoma, NOS** 4 1 0 0 0 5 (1.9)

Sialoblastoma 1 0 0 0 0 1 (0.4)

Sub-total 67 15 43 3 3 131 (50.7)

Total 139 37 63 12 7 258 (100.0)

44

A total of 258 salivary gland neoplasms which occurred over a twenty year period were

analyzed. The tumours represented 2.1% of neoplasms seen in the study period. Our figure is

comparable to Ogunniyi et al’s 296 tumours (21 years) and Arotiba et al’s 237 tumours

(14years) in South Western Nigeria, thus supporting the relative rarity of these tumours in our

environment. However, Edda et al in Uganda had 268 cases within a ten year period. 18, 21, 27

The equal sex distribution of the tumours as observed in this study conforms to other studies

that showed no statistically significant difference between the sexes, although, the World

Health Organization (WHO) favours a slight female preponderance. 8, 27, 28

The youngest patient in our series was 2.5 years old and the oldest, 91 years old. This finding

is in keeping with studies by Nitin et al in India and Ma’aita et al in Jordan with an age range

of 2years to 81years. Studies from Uganda and Sudan also reported an age range of 0.5 to 80

years and 11years to 90 years respectively while a study from Enugu South Eastern Nigeria,

reports a 10year - 74 years range. 3, 21, 29, 30, 31

Our mean age of occurrence of these tumours was 50.7 years in contrast to the WHO and

Armed Forces Institute of Pathology (AFIP) reported mean age of 46 years.8 It is also higher

than the observed mean age of 48.8 years in Central Sudan, 41 years in South Eastern

Nigeria, 38.1 years in Uganda and 30.4 years in North Eastern Nigeria. 21, 31- 33

The epithelial tumour types had the highest frequency of occurrence comparable to WHO and

AFIP findings. The 49.3% benign lesions observed in this study is similar to other studies in

Nigeria and Uganda though lower than the WHO and AFIP expected estimate of 54-79%.

Likewise, our 50.8% malignant cases though comparable to studies in Africa, are higher than

the WHO and AFIP’s 21 - 46% estimate. 2, 8, 21, 32, 33

Pleomorphic adenoma was the commonest benign epithelial lesion accounting for 43.4%.

Reports from Uganda (74.8%), Kenya (78%), Ethiopia (58.5%), other parts of Nigeria

(Lagos, Ibadan and Maiduguri respectively representing 65.5%, 29.2% and 44.3%) and

WHO/AFIP also favour pleomorphic adenoma. 2, 8, 21, 32-36

45

The commonest malignant epithelial neoplasm was adenoid cystic carcinoma, with a

frequency of 26.0% and the second commonest was mucoepidermoid carcinoma with a

frequency of 18.2%. The WHO and AFIP reports and studies from Uganda (Edda et al), and

Lagos (Ladeinde et al) support this finding. While other studies by Hill et al in Kenya and

Abiose et al reported mucoepidermoid carcinoma as the commonest malignant epithelial

tumour.8, 21, 32-36

Polymorphous Low Grade Adenocarcinoma (PLGA) a relatively recent entry to the list of

malignant epithelial tumours showed a frequency of 1.9%. Its key diagnostic criteria include

architectural diversity and cytologic uniformity. The striking feature of these carcinomas is

the variety of morphologic configurations between tumours and within individual tumour.

The main microscopic patterns are: 1) lobular, 2) papillary or papillary-cystic (typically

focal), 3) cribriform areas sometimes resembling those seen in adenoid cystic carcinoma, and

4) trabecular or small, gland-like structures lined by a single layer of cuboidal cells. The cells

form concentric whorls or targetoid arrangements round blood vessels or nerves. Foci of

oncocytic, clear, squamous or mucous cells may be found. Stroma may show areas of

mucinosis or hyalinization. Despite the innocuous cytologic appearance, the neoplasm always

invades adjacent soft tissues and is uncapsulated. Neurotropism is common in PLGA.

Invasion of adjacent bone may be seen in tumours of the palate or mandible.8 Use of the term

“lobular carcinoma” to describe this tumour has been discouraged by the Armed Forces

Institute of Pathology (AFIP). This is to prevent confusing the tumour with lobular carcinoma

of the breast. However, the WHO did not discuss extensively on the terminology of this

tumour. 2, 8

Other studies on salivary gland neoplasms were generally silent on PLGA. This may be

attributable to the fact that strict diagnostic criteria were yet to be applied in its diagnosis at

the time of these earlier studies. The AFIP and WHO however report a frequency of 11% and

26% respectively. 2, 8 This tumour is easily confused with adenoid cystic carcinoma due to its

46

growth pattern, however, if attention is paid to the bland cytologic features of the tumour

cells, such a scenario will be avoided.2

The only case of sialoblastoma was seen in the parotid gland of a 2.5year old boy. This is a

rare, potentially aggressive, parotid or submandibular tumour that is usually present at birth

and recapitulates the primitive salivary anlage. Most tumours are identified at birth or shortly

thereafter; sometimes, children may be diagnosed after the age of two years. The male to

female ratio is 2:1. Sialoblastomas are composed of basaloid epithelial cells, with scanty

cytoplasm, round to oval nuclei, single or few nucleoli, and relatively fine chromatin pattern.

More mature cuboidal epithelial cells with pink cytoplasm can also be seen. These cells form

ductules, bud-like structures and solid organoid nests, and may demonstrate peripheral

palisading. The intervening stroma may appear loose and immature. Only 11 and 23 cases

have so far been reported in the AFIP and WHO series respectively.2, 8, 35

Lipoma was the commonest non-epithelial benign neoplasm representing 1.2% of all tumours

seen. This is comparable to the AFIP’s observed frequency range of 0.5-1.2% with a male

preponderance. Two of our three cases occurred in males. 2

The parotid gland was the commonest site involved by these tumours with a frequency of

53.9%. Several studies from various regions support this finding. For example, WHO’s 64-

80%, India- 66.8%, Jordan – 70.2%, Ethiopia – 43.2%, Uganda – 34% and Lagos 72.4%. The

minor salivary glands accounted for 24.4% of cases and falls within the estimated range of 9-

23%. However, Edda et al reported a higher frequency of 32.8% in the minor glands in

Uganda and a similarly higher figure of 31.9% was observed in Ibadan. 2, 3, 8, 10, 21, 27

The sublingual glands were entirely spared in conformity with the reported rarity of

involvement of this site. 2, 8

In conclusion, the study showed that salivary gland neoplasms are rare with males being

more likely to have malignant salivary gland tumours as compared to females. While benign

47

salivary tumours are especially likely in females, in agreement with WHO’s finding of a

slightly increased female preponderance. 8

However, this is a hospital based study which may underscore the true frequency of

occurrence of these tumours.

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APPENDIX I

TNM Classification of Salivary Gland Neoplasms 8

T – Primary tumour

TX -Primary tumour cannot be assessed

52

T0 -No evidence of primary tumour

T1 -Tumour 2 cm or less in greatest dimension without extraparenchymal extension

T2 -Tumour more than 2 cm but not more than 4 cm in greatest

dimension without extraparenchymal extension

T3 -Tumour more than 4 cm and/or tumour with extraparenchymal

extension

T4a -Tumour invades skin, mandible, ear canal, or facial nerve

T4b -Tumour invades base of skull, pterygoid plates, or encases carotid artery

N – Regional lymph nodes

NX -Regional lymph nodes cannot be assessed

N0 -No regional lymph node metastasis

N1 -Metastasis in a single ipsilateral lymph node, 3 cm or less in greatest dimension

N2 -Metastasis as specified in N2a, 2b, 2c below

N2a- Metastasis in a single ipsilateral lymph node, more than 3 cm but not more than 6 cm in

greatest dimension

N2b -Metastasis in multiple ipsilateral lymph nodes, none more than 6 cm in greatest

dimension

N2c -Metastasis in bilateral or contralateral lymph nodes, none more

than 6 cm in greatest dimension

N3 -Metastasis in a lymph node more than 6 cm in greatest dimension

Note: Midline nodes are considered ipsilateral nodes.

M – Distant metastasis

MX -Distant metastasis cannot be assessed

M0 -No distant metastasis

M1 -Distant metastasis

53

Stage Grouping

Stage I T1 N0 M0

Stage II T2 N0 M0

Stage III T3 N0 M0

(T1, T2, T3 N1 M0)

Stage IVA T1, T2, T3 N2 M0

T4a N0, N1, N2 M0

Stage IV B T4b Any N M0

Any T N3 M0

Stage IV C Any T Any N M1

54

Figure 1: Acinic cell carcinoma, showing glandular and solid growth patterns,

composed of acinar cells (Hematoxylin and Eosin, Magnification X100).

55

Figure 2: Adenocarcinoma, NOS showing tubular, solid cribriform and comedo

patterns of growth (Hematoxylin and Eosin, Magnification X 100)

56

Figure 3: Adenoid cystic carcinoma, showing cribriform, solid and small glandular

growth patterns, with myxohyaline material in the cores of the cribriform areas.

(Hematoxylin and Eosin, Magnification X100)

57

Figure 4: Polymorphous Low Grade Adenocarcinoma (PLGA), showing glandular,

focal cribriform and papillary growth patterns, with bland cytologic features

(Hematoxylin and Eosin, Magnification X100).

58

Figure 5: Pleomorphic adenoma, showing juxtaposing of chondroid areas and epithelial

areas, with pseudovascular growth patterns (Hematoxylin and Eosin, Magnification X

100).

59

Figure 6: Pleomorphic adenoma, showing nests, glandular and chondromyxiod to

collagenous areas (Hematoxylin and Eosin, Magnification X100).

60

Figure 7: Sialoblastoma showing sheets and tubules of primitive small round blue cells

(Hematoxylin and Eosin, Magnification X 100)