A Dissertation on CYTOLOGIC SPECTRUM OF SALIVARY GLAND LESIONS WITH HISTOPATHOLOGICAL CORRELATION Dissertation submitted to THE TAMILNADU Dr.M.G.R MEDICAL UNIVERSITY CHENNAI-600032 In Partial fulfillment of the regulations Required for the award of M.D.Degree in PATHOLOGY (BRANCH III) DEPARTMENT OF PATHOLOGY COIMBATORE MEDICAL COLLEGE MAY 2020 UNIVERSITY REGISTRATION NO: 201713251
123
Embed
A Dissertation on CYTOLOGIC SPECTRUM OF SALIVARY …
This document is posted to help you gain knowledge. Please leave a comment to let me know what you think about it! Share it to your friends and learn new things together.
Transcript
A Dissertation on
CYTOLOGIC SPECTRUM OF SALIVARY GLAND LESIONS
WITH HISTOPATHOLOGICAL CORRELATION
Dissertation submitted to
THE TAMILNADU Dr.M.G.R MEDICAL UNIVERSITY
CHENNAI-600032
In Partial fulfillment of the regulations
Required for the award of
M.D.Degree in PATHOLOGY (BRANCH III)
DEPARTMENT OF PATHOLOGY
COIMBATORE MEDICAL COLLEGE
MAY 2020
UNIVERSITY REGISTRATION NO: 201713251
DECLARATION
I solemnly declare that the dissertation titled “CYTOLOGIC
SPECTRUM OF SALIVARY GLAND LESIONS WITH
HISTOPATHOLOGICAL CORRELATION” was done by me at
Coimbatore Medical College, during the period 2018 -2019 under the
guidance and supervision of Prof.A.DHANALAKSHMI, MD., to be
submitted to The Tamilnadu Dr.M.G.R.Medical University towards the
partial fulfilment of requirements for the award of MD DEGREE in
PATHOLOGY BRANCH –III.
Place : Coimbatore
Date :22.10.2019 Dr.T.ANITHA,
Post Graduate Student, Department of Pathology,
Coimbatore Medical College.
CERTIFICATE I
This to certify that the dissertation entitled “CYTOLOGIC
SPECTRUM OF SALIVARY GLAND LESIONS WITH
HISTOPATHOLOGICAL CORRELATION” is a record of bonafide
work done by Dr. T.ANITHA, Post Graduate Student in the Department of
Pathology, Coimbatore Medical College and Hospital, Coimbatore under the
guidance and supervision of Dr.M.KAVITHA, M.D., Senior Assistant
Professor, Department of Pathology, Coimbatore Medical College and
Hospital, Coimbatore in partial fulfillment of the regulations of The
Tamilnadu Dr.M.G.R Medical University, Chennai towards the award of
degree of M.D.PATHOLOGY.
Guide
Dr. M.KAVITHA, M.D., Dr. A.DHANALAKSHMI, M.D.,
Senior Assistant Professor, Professor & Head, Department of Pathology, Department of Pathology, Coimbatore Medical College, Coimbatore Medical College, Coimbatore. Coimbatore.
Dr. B.ASOKAN, M.S, M.Ch.,
Dean, Coimbatore Medical College,
Coimbatore.
CERTIFICATE –II
This is to certify that this dissertation work titled “CYTOLOGIC
SPECTRUM OF SALIVARY GLAND LESIONS WITH
HISTOPATHOLOGICAL CORRELATION” of the candidate
Dr.T.ANITHA with registration number 201713251 for the award of
M.D degree in the branch of PATHOLOGY. I personally verified the
urkund.com website for the purpose of plagiarism check I found that the
uploaded thesis file contains from introduction to conclusion pages and
result shows 7 (Seven) percentage of plagiarism in the dissertation.
Guide and Supervisor sign with seal
ACKNOWLEDGEMENT
To begin with I thank the almighty God for bestowing his blessing
on me in this dissertation a successful one.
I wish to thank the dean Dr ASHOKAN, MS., Mch., Coimbatore
Medical College and Hospital, for permitting me to conduct the study.
It’s a great pleasure to express my humble gratitude to the most
respectable teacher Dr .A. Dhanalakshmi MD., Professor and Head of
the Department, Department of Pathology, Coimbatore Medical College,
Coimbatore for her guidance and support.
I express my gratitude and sincere thanks to my guide
Dr.M.Kavitha M.D., Department of Pathology, Coimbatore Medical
College, Coimbatore.
I thank all Assistant Professors and Tutors of Department of
Pathology, Coimbatore Medical College for their opinion and
encouragement.
I thank my parents, my children Srinidhi and Harshan, my friend
Dr.Swathi for their extensive support.
CONTENTS
TABLE OF CONTENTS
S.NO TITLE PAGE.NO
1 INTRODUCTION 1
2 AIM AND OBJECTIVES 4
3 REVIEW OF LITERATURE 5
4 MATERIALS AND METHODS 46
5 OBSERVATION AND RESULTS 49
6 DISCUSSION 71
7 SUMMARY 79
8 CONCLUSION 80
BIBLIOGRAPHY
ANNEXURES
MASTERCHART
LIST OF TABLES S.NO TITLE PAGE.NO
1 Age wise distribution of lesions of salivary gland 49
2 Gender wise distribution of lesions of salivary gland 51
3 Distribution of cases based on clinical diagnosis 52
4 Distribution of cases based on duration of lesion 53
5 Distribution of cases based on size of lesion 55
6 Distribution of cases based on consistency 56
7 Distribution of cases based on location of lesion 57
8 Distribution of neoplastic tumors according to histopathological diagnosis and location 58
9 Distribution of cases based on cellularity 59
10 Cytological diagnosis of salivary gland lesions 60
11 Cytological categorization of lesions 62
12 Histopathological diagnosis of lesion 63
13 Histopathological categorization of lesion 65
14 Cytohistopatholgical correlation 66
15 Diagnostic accuracy in benign neoplastic lesions of salivary gland 67
16 Diagnostic accuracy in malignant neoplastic lesions of salivary gland 68
17 Comparison of consistency –Benign Vs Malignant 69
18 Comparison of site of lesion-Benign Vs Malignant 70
19 Comparison of cellularity – Benign Vs Malignant 70
LIST OF CHARTS
S.NO CHART PAGENO
1 Distribution of cases based on age
groups
50
2 Gender wise distribution of cases 51
3 Distribution of cases based on clinical
diagnosis
52
4 Distribution of case based on duration
of lesions
54
5 Distribution of cases based on size of
lesion
55
6 Distribution of cases based on
consistency
56
7 Distribution of cases based on location
of lesion
57
8 Distribution of cases based on
cellularity
59
9 Distribution of cases based on
Cytologic diagnosis
61
10 Distribution of cases based on
histopathological diagnosis
64
ABBREVIATION
FNAC - Fine needle aspiration cytology
PA – Pleomorphic adenoma
WT – Warthin’s tumor
MEC – Mucoepidermoid Carcinoma
CH SA – Chronic sialadenitis
SD CA – Salivary duct carcinoma
H &E – Hematoxylin and Eosin
MGG – May GrunwaldGiemsa
HPE –Histopathology Examination
WHO - World Health Organisation
INTRODUCTION
1
INTRODUCTION
Salivary glands are exocrine organs that secrete saliva widely
distributed throughout the mouth and oropharynx. There are three pairs of
salivary glands-parotid, submandibular and sublingual glands15.
Minor salivary glands are about 800-100 located throughout the oral
cavity in the buccal, labial lingual mucosa ,the soft palate ,lateral parts of
hard palate and the floor of mouth.
Salivary gland lesions form 2-5 percent of all Head and neck
neoplasms4,6,8. Age incidence varies widely, extending from children to
adults over 80 years of age. These glands are usually not subjected to
incisional or core needle biopsy, because of the possible risk of fistula
formation and tumor seedling18.
Cysts and associated lesions with cystic changes are commonly
encountered in Head and neck region. Pathology of these lesions are
diverse and includes developmental, inflammatory, benign and malignant
tumors which can be primary or metastatic.
FNAC is a useful method for evaluating salivary gland lesions. It is
of particular relevance in the head and neck area because of easy
accessibility of the target site6 minimally invasive procedure, excellent
patient compliance and thereby help to avoid surgery in non-neoplastic,
inflammatory conditions.
2
It is a preferred method due to its low cost, rapid turnaround time,
minimum morbidity. It has a high sensitivity and specificity for
diagnosing neoplastic and non-neoplastic lesions
It is useful to categorize the lesions into inflammatory, reactive,
benign and malignant lesions and thereby useful for appropriate
therapeutic management6,8,10. However, the heterogenecity of many
salivary gland tumors along with overlap of cytomorphological features
presents as a challenging work to conclude with precise diagnosis in some
instances.
The purpose of FNAC is not only to provide a definite specific
diagnosis. But it is also used in conjunction with clinical and radiological
findings to provide the best possible initial assessment from which
management can be planned1,10.
Till date, ultrasonography is acting as bridge between surgery and
pathology.17 Pre-operative assessment of parotid swelling by cytology and
ultrasonography is especially significant in our country where
tuberculosis and metastatic squamous cell carcinoma invading
perisalivary lymph nodes mimic parotid swelling.
Major salivary gland neoplasms usually present with non-specific
clinical symptoms ,requiring high degree of suspicion. FNAC offers an
invaluable and accurate initial diagnostic tool for the management of
these patients even in the era of the Immunohistochemistry.
3
The present study aims to correlate cytomorphological features of
salivary gland lesions in FNAC and the corresponding histopathology in
suspicious malignant cases.
Keeping histopathological diagnosis as gold standard sensitivity,
specificity and diagnostic accuracy of FNAC was calculated. An adequate
and representative sampling is essential for proper cytological evaluation
to reduce the errors in diagnosis.
The diagnostic pitfalls in FNAC were evaluated along with
practical suggestions to improve the diagnostic accuracy especially while
dealing with mucinous lesions. Other varied reasons for diagnostic errors
may be due to uncertainty of the site and tissues aspirated , minimal
material and lack of architectural pattern in the smears as compared to
histological sections.
Relevant clinical data, radiological findings, along with
cooperation between the clinician and cytopathologist10,13 are important
in order to use FNAC to its best advantage.
Thus the present study offers to examine the sensitivity, specificity
and diagnostic accuracy of FNAC of salivary gland lesions with
histopathological correlation and to identify the discrepancies
contributing to pitfalls in diagnosis.
AIM & OBJECTIVES
4
AIMS AND OBJECTIVES
AIM:
To analyse the diagnostic accuracy, sensitivity and specificity of FNAC
in various salivary gland lesions and correlate with the histopathological
findings.
OBJECTIVES:
1. To analyse the clinical, Histological and cytological features of
salivary gland lesions.
2. To correlate the cytological features of salivary gland lesions with
Histological diagnosis.
3. To analyse the reasons for diagnostic pitfalls in cases that have
cytohistological discrepancy.
REVIEW OF LITERATURE
5
REVIEW OF LITERATURE
Over the past three decades, in the work up of salivary gland lesion
fine needle aspiration has been well recognized as the first diagnostic tool.
It is widely accepted as a simple, safe, cost effective a technique in the
evaluation of salivary gland lesions and thereby helps to plan for further
management.
FNAC has an important relevance in head and neck area because of
easy accessibility of the target site, patient compliance, minimally
invasive and thereby helps to avoid surgery in inflammatory lesions and
non-neoplastic lesions.6
The use of aspiration cytology was first reported by Kun in 18479.
The procedure was reintroduced by Martin & Ellis in evaluation of head
and neck lesions in 19305,9. It was further promoted especially in salivary
gland lesions in 1950 and 1960 by Enroth et al9.
Salivary gland tumors constitute about 3-10% of head and neck
tumors4,8,9. When performed and analysed by experienced hands, FNAC
has the advantage of giving valuable diagnostic data in a relatively short
period of time.
6
ANATOMY
Salivary glands are compound tubuloacinar exocrine glands found
in oral cavity that secrete complex fluid called saliva.
There are three pairs of salivary glands involving parotid,
submandibular and sublingual region15.
1.Types of salivary gland based on size:
Major salivary gland
Collection of secretory cells aggregated into large bilaterally paired
extra oral glands with extended duct system through which the gland
secretions reach the mouth. Parotid gland, Submandibular and sublingual.
Minor salivary gland
Collection of secretory cells scattered throughout the mucosa and
submucosa of the oral cavity with short ducts opening directly onto
mucosal surface - serous glands of van ebner.
Anterior lingual glands
Lingual , buccal, labial palatal glands
Glossopalatine and retromolar glands
2 Based on the type of secretory cells
Serous-parotid
Mixed{seromucous}-submandibular
Mucous - minor salivary glands
7
Parotid is the largest salivary gland that constitutes about 60-65%
of total saliva.15 The superficial portion of gland is located subcutaneously
in front of the external ear and the deeper portion lies behind the ramus of
mandible associated with facial nerve.
Stenson’s duct runs forward across masseter muscle, turns inwards
at the anterior border of masseter and opens at just opposite second
maxillary molar crown.19,24
Submandibular gland weighs around 10-15 gm and constitutes for
about 2-30% of total saliva.24 It is located at posterior portion of floor of
mouth, medial aspect of mandible and wrapping around the posterior
border of mylohyoid.
Wharton’s duct opens into the mouth beneath the tongue lateral to
lingual frenulum19.
Sublingual gland constitutes about 2.5% of total saliva. It is located at
anterior part of floor of the mouth, just between mucosa and mylohyoid
muscle. Bartholin’s duct opens with submandibular duct at sublingual
caruncle
.
8
EMBRYOLOGY
Development of salivary gland19
Stage I - Bud formation
Stage II - Formation and growth of epithelial Chord
Stage III - Initiation of branching in parts of epithelial chord
Stage IV - Branching of epithelial chord and Lobule formation
Stage V - Canalization
Stage VI - Cytodifferentiation
Parotid develops around 4 -6 week, submandibular around 6th week
of intrauterine life19.Sublingual and minor salivary gland develops around
8th week of intrauterine life.
9
Secretory component of gland continues to grow postnatally.
Ductal, connective tissue and vascular component decreases upto two
years of age.
HISTOLOGY OF SALIVARY GLAND
Comprises of a series of secretory end piece- acini connected to the
oral cavity by – ductal system
SEROUS CELLS
It is present in demilune formation at the blind ends of mucous
secretory tubules. It is pyramidal in shape, with a spherical nuclei situated
at the basal third of the cell20.
Apical cytoplasm is filled with secretory granules, while basal
cytoplasm contains rough endoplasmic reticulum converging towards the
golgi complex. It also contains cytoskeleton components.
The lumen of serous end piece has small extensions in the form of
intercellular canaliculi.
MUCOUS CELLS:
It forms the secretory cell type of sublingual and most of the minor
salivary glands. It has a tubular or round configuration, larger than serous
cells with a flattened nucleus placed at the base20.Apical cytoplasm is
filled with mucous secretory droplets.
10
Myoepithelial cells-basket cells
These are contractile cells located around the terminal secretory
units, they are stellate like with a flattened nucleus, scant perinuclear
cytoplasm and long branching process which surrounds the secretory
duct cells.
DUCTS
Intercalated ducts:
These are small ducts into which secretory end piece empties24.It is
lined by a single layer of low cuboidal cells and myoepithelial bodies.
Function:
Contributes to the salivary secretion- lysozymes & lactoferrin
11
Undergo proliferation and differentiation to replace damaged or
dying cells in the striated ducts.
Striated ducts:
These are larger duct into which intercalated ducts empty. It is
lined by columnar epithelium15
Function:
Change the salivary secretion-isotonic to hypotonic
Sodium reabsorption &potassium excretion
Terminal excretory ducts:
Main duct leading from the gland to the oral cavity15,24.They are
lined by pseudostratified with columnar cells admixed with small basal
cells and goblet cells.
Function:
Alter the electrolyte concentration of saliva
In the present study the parotid gland was the most frequently
involved followed by submandibular gland and submental gland5,8,9,24.
FNAC has been used for the diagnosis of salivary gland lesions for more
than three decades and was found to be beneficial not only in the diagnosis
of salivary gland lesions , but also in differentiating neoplastic and non-
neoplastic lesions5,6,8.
12
Though the most accurate method of diagnosis is histopathology
yet the role of Fine needle aspiration cytology for the diagnosis of salivary
gland lesions is significant12.
The most common source of diagnostic error is inadequate
sampling because FNAC derives sample only from a small area11.Keeping
into consideration the significance of clinical features in forming the idea
about diagnosis, the role of FNAC in diagnosis of lesion and its accuracy
with histopathology is determined.
Combined with clinical and radiological findings, it can provide a
preliminary assessment on which management decision is based17.
Ultrasound guidance along with immediate assessment of the material by
cytopathologist improves the accuracy of FNAC.
Additionally the degree of differentiation of neoplastic cells can be
determined, which aid in the selection of surgical intervention.9
Categorizing the malignant lesion as low grade or high grade can
determine the extent of surgery example the preservation of facial nerve
and the indication for neck dissection in the case of malignant tumors of
parotid gland .
Assessment of FNAC of suspected salivary gland lesions should
follow step by step approach10. The first aim is to decide whether the
lesion is of salivary gland origin29.The next step is to identify the cells and
13
their morphology to classify them as non-neoplastic and neoplastic
categories.
The majority of salivary gland lesions occur in the superficial lobe
and less often in the deep lobe of parotid gland .Cytopathologist
performing FNAC should be familiar of the basic anatomy of salivary
gland.
A critical aspect of salivary gland FNAC is adequate sampling and
appropriate sample preparation. In FNAC, the adequate cellularity of
target lesion is important for an accurate interpretation5.Specific criteria
for adequacy of salivary gland is yet to be defined.
Many factors including the aspiration technique {manual versus
ultrasound guided}, nature of the lesion {solid versus cystic}sample
collection and preservation method, preparation technique artifacts,
calibre of needle and presence of obscuring blood or other material can
influence the adequacy of salivary gland aspirate.
Advances in technology like ultrasound, sialography, immune
markers are available to aid in the diagnosis, the accelerated use of FNAC
has reduced the expenditure.
The risk of malignancy prior to FNAC varies depending upon its
size and location. 20-25% in the parotid gland,40-50% in the
submandibular gland 80% in the sublingual and minor salivary glands.
14
Kim et al 2018 found a diagnostic accuracy of FNAC to be 92% in
differentiating malignant from benign salivary gland tumors.
Fakhry et al 2012 evaluated the sensitivity and specificity of FNAC
to be 80% and 89.5% respectively.
WHO classification of the Tumors of Head and Neck.25
BENIGN TUMORS
Pleomorphic adenoma
Myoepithelioma
Monomorphic adenoma
Warthin’s tumor
Oncocytoma,
Basal cell and canalicular adenoma
Lymphadenoma
Cystadenoma
Sialadenoma papilleferum
Ductal papilloma
Sebaceous adenoma
NEOPLASTIC LESIONS
Adenoid cystic carcinoma
Mucoepidermoid carcinoma
Acinic cell carcinoma
Polymorphous low-grade adenocarcinoma
15
Epithelial- myoepithelial carcinoma
Carcinoma ex-pleomorphic adenoma
Salivary duct carcinoma
Clear cell carcinoma
Basal cell adenocarcinoma
Intraductal carcinoma
Adenocarcinoma,NOS
Salivary duct carcinoma
Secretory carcinoma
Sebaceous adenocarcinoma
Carcinosarcoma
Poorly differentiated carcinoma
Undifferentiated carcinoma
Large cell neuroendocrine carcinoma
Small cell neuroendocrine carcinoma
Lymphoepithelial carcinoma
Squamous cell carcinoma
Oncocytic carcinoma
Sialoblastoma
Uncertain malignant potential
NON NEOPLASTIC EPITHELIAL LESIONS
Sclerosing polycystic adenosis
16
Nodular oncocytic hyperplasia
Lymphoepithelial sialadenitis
Intercalated duct hyperplasia
BENIGN SOFT TISSUE LESIONS
Hemangioma
Lipoma/sialolipoma
Nodular fasciitis
HAEMOTOLYMPHOID TUMORS
Extranodal marginal zone lymphoma of mucosa associated
lymphoid tissue (MALT LYMPHOMA)
TNM Classification of carcinoma of the major salivary glands25
T - Primary tumor
Tx - Primary tumor cannot be assessed
To - No evidence of primary tumor
T1- Tumor <2 cm in greater dimension, without extra parenchymal
extension.
T2- Tumor >2 cm but <4cm in greater dimension, without extra
parenchymal extension.
T3 – Tumor > 4cm and/or with extra parenchymal extension
T4a- Tumor invades skin, mandible,ear canal or facial nerve.
T4b- Tumor invades base of skull or Pterygoid plates or encases
carotid artery
17
N - Regional lymph nodes – cervical node
Nx – Regional lymph nodes cannot be assessed
N0 – No regional lymph node metastasis
N1 – Metastasis in a single ipsilateral lymph node < 3cm in greater
dimension
N1 – Metastasis in a single ipsilateral lymph node <3cm in greater
dimension.
N2a – Metastasis in a single ipsilateral lymph node,>3cm but < 6cm
in greater dimension.
N2b – Metastasis in multiple ipsilateral lymph nodes, all <6 cm in
greater dimension.
N2c – Metastasis in bilateral or contralateral lymph nodes, all<6 cm
in greater dimension.
N3 – Metastasis in a lymph node >6cm in greater dimension
M - Distant metastasis
M0 – No distant metastasis
M1 – Distant metastasis
STAGE GROUPING
Stage I - T1 N0 M0
Stage II - T2 N0 M0
Stage III - T3 N0 M0
- T1-3 N1 M0
18
Stage IVA - T1-3 N2 M0
- T4a N0-2 M0
Stage IVB - T4b AnyN M0
- AnyT N3 M0
Stage IVC - AnyT AnyN M1
This classification applies to carcinomas of major salivary glands
parotid, submandibular and sublingual glands.
Carcinomas arising in minor salivary glands (mucin secreting
glands in the lining membrane of the upper aerodigestive tract) are not
included in the classification25.
Foschini et al 2008 stated that a non-diagnostic aspirate is one that
for qualitative and quantitative reasons provides insufficient diagnostic
material to provide an informative interpretation.
In the present study,45 cases of major salivary gland lesions were
included irrespective of age and sex.Of the 45cases studied, age range of
15 to 70 years with mean age of 48 years and had male preponderance.
Non –neoplastic lesions constitute 26% and Neoplastic lesions constitute
72% of all the cases9.
Among benign neoplasms, pleomorphic adenoma was more
frequent5. Cytologic smear shows ductal epithelial cells and myoepithelial
cells in varying proportion, extracellular matrix and chondromyxoid
stroma.
19
Among malignant neoplasm, mucoepidermoid carcinoma was
reported in 7 cases5,8. Cytologic smear includes predominantly