Milan system of reporting
salivary gland
By – Dr Prajakta R Kothurkar
Moderator – Dr M H Shariff
Anatomy
HISTOLOGY
Role of FNAC in salivary gland cytology
▪ Differentiate between
neoplastic and non-
neoplastic salivary gland
lesions
▪ Differentiate between low-
and high-grade
carcinomas
Salivary gland FNA : How effective it is?
▪ Overall sensitivity : 86-100%
▪ Overall specificity : 48-94%
▪ Accuracy based upon grade:
– Benign / low grade vs high grade malignant : 81-
100%
Salivary gland FNA : How does it impact in
management?
▪ Non neoplastic : clinical follow up
▪ Benign / low grade : limited resection
▪ Metastatic disease to parotid LNs : lymph node
resection
▪ Lymphoma: hematological treatment
▪ High grade carcinoma : radical resection / nerve
sacrifice / lymph node dissection
Salivary gland FNA is not just a
screening test .....but give a
better path towards the
treatment.
Diagnostic Dilemma
▪ Reporting confusion
– Diversity of diagnostic categories, vs.
– Descriptive reports (no categories), vs.
– Surgical pathology terminology
▪ General agreement on the need for a
defined set of diagnostic categories for
salivary gland FNA
– Clarity of communication (implicit
cancer risk)
– Exchange of data across institutions
e m fo r
n S y s t
e M i l a
Th a r y
g S a l i v
r t i n
Repo o l o g y
to p a t h
a n d C y
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WHY MILAN ?
• Sponsored by the ASC and the
IAC
• User-friendly &
internationally accepted
evidence-based system with a
useful format for clinicians
• The classification system and
ROM for the diagnostic
categories further refined
according to literature
The Benefits of a Uniform
Reporting System for Salivary
Gland Cytopathology
• Improve communication
between pathologists and
clinicians
• Improve patient care
• Facilitate cytologic-histologic
correlation
• Promote research into the
epidemiology, molecular biology,
pathology, and diagnosis
• Foster sharing of data from
different laboratories for
collaborative studies
I - Non diagnostic category
A Non-Diagnostic salivary gland aspirate is
one that for qualitative and/or quantitative
reasons provides insufficient diagnostic
material to provide an informative
interpretation
Cytologic Criteria
Rare or absent cells; less than 60 lesional cells
Cytologic Criteria
Poorly prepared slides with artifacts (e.g., air-drying,
obscuring blood, and poor staining) that preclude the
evaluation of the cellular component
Cytologic Criteria
Non-neoplastic (normal) salivary gland elements in the
setting of a clinically or radiologically defined mass
Cytologic Criteria
Non-mucinous cyst fluid without an epithelial component
should be subcategorized - “Non-Diagnostic, cystic fluid
only
Sample reports
II – Non neoplastic
▪ Relatively common
▪ Clinically mimic a neoplasm
– Due to the presence of a distinct mass
CHRO Most
ACUTE
NIC common
GRANULO
MATOUS
II – Non neoplastic
Specimens that show benign nonneoplastic changes, associated
with acute or chronic reactive responses to inflammation,
structural alterations, and infection.
Deconstructive cytology
▪ Recognize individual basic key elements /
details of architectural pattern
▪ Attempt to construct a image with these key
elements
(schematic rendition )
Acute Sialadenitis
Cytologic Criteria
• Abundant neutrophils ±
bacteria
• Histiocytes
• Necroinflammatory
debris (suppurative)
• Granulation tissue (later
stages)
Chronic Sialadenitis
Cytologic Criteria
• Hypocellular
• Small groups of ductal cells,
may be basaloid or
metaplastic
• Absent or scant acinar cells
• Chronic inflammation
(including lymphocytes and
plasma cells)
Granulomatous Sialadenitis
Cytologic Criteria
• Hypocellular (scant acinar
and ductal cells)
• Groups of epithelioid
histiocytes
• Variable amounts of acute
and chronic inflammatory cells
• ± Multinucleated giant cells
• ± Necrotic background debris
Benign lymphoepithelial lesion/
lymphoepithelial sialadenitis
Cytologic Criteria
• Cellular aspirate
• Cohesive sheets of ductal cells,
squamous metaplastic changes,
small mature lymphocytes
• Mixed population of
lymphocytes, dendritic
cells, ,tingible body
macrophages
with predominance of small
mature lymphocytes
III - Atypia of Undetermined Significance
Salivary gland FNA that lacks either qualitative
or quantitative cytomorphologic features to be
diagnosed with confidence as non-neoplastic or
neoplastic.
Cytologic criteria - AUS
1. Reactive and reparative atypia indefinite for a neoplasm
Rare atypical cells
in an inflammatory
background,
indefinite for a
neoplasm
Cytologic criteria - AUS
2. Squamous, oncocytic, or other metaplastic changes indefinite for
a neoplasm
Cytologic criteria - AUS
3. Low cellularity specimens suggestive of, but not diagnostic
of a neoplasm
Rare group of
mildly atypical
epithelial
cells with associated
“Lymphocytic tangles,”
suggestive but not
diagnostic of a
neoplasm
Cytologic criteria - AUS
4. Specimens with preparation artifacts hampering distinction
between a non-neoplastic and neoplastic process
The epithelial
cells are
suggestive of a
neoplastic
process but abundant
blood
limits the evaluation
Cytologic criteria - AUS
5. Mucinous cystic lesions with an absent or very scant
epithelial component
differential diagnosis
includes a benign
mucinous cyst; however,
low-grade
mucoepidermoid
carcinoma cannot be
excluded
Cytologic criteria - AUS
6. Salivary gland lymph nodes or lymphoid lesions that are
indefinite for a lymphoproliferative disorder
lymphoma cannot be
excluded, particularly in
the absence of flow
cytometry
SAMPLE REPORTS
IV Neoplasm
Benign SUMP
Reserved for benign Reserved for FNA
samples that are
neoplasms diagnosed diagnostic of a neoplasm; diagnosis
based on established of a
specific entity cannot be
cytologic criteria made
A} Benign
FNA specimen shows characteristic cytomorphologic
features of a specific benign epithelial or mesenchymal
neoplasm of the salivary gland
Benign
Epithelial Mesenchymal
Pleomorphic Adenoma Lipoma
Warthin Tumor Schwannoma
Oncocytoma Lymphangioma
Hemangiom
a
1) Pleomorphic adenoma
Cytologic criteria – pleomorphic adenoma
Distinctive
chondromyxoid
matrix
Cytologic criteria – pleomorphic adenoma
Myoepithelial cells
Variety of shapes
Bland nuclear features
predominant cell type
Cytologic criteria – pleomorphic adenoma
Iconic PA :Modestly cellular, readily identifiable, abundant fibrillar
matrix,,bland ductal epithelial and myoepithelial cells
2. Warthin Tumor – cytologic criteria
Tripartite appearance
with dirty
proteinaceous
background,
lymphocytes,
sheets of oncocytes
2. Warthin Tumor – cytologic criteria
Oncocytes: Abundant
-Epithelial cell nuclei: Centrally placed and round, granular
homogeneous
prominent nucleolus cytoplasm (orange on
Papanicolaou
stain) , well-defined borders
- Lymphocytes: Mixed population dominated by
small mature-appearing cells
3. Oncocytoma – cytologic criteria
• Irregular sheets , clusters - large polygonal
cells, abundant homogeneous granular
cytoplasm
• Oncocytes: Well-defined cytoplasmic borders
• Nuclei: Enlarged, round, distinct nucleolus
• Background: Clean or contains red blood
cells
• Nuclear pleomorphism and mitotic figures
absent
Mesenchymal – 1) lipoma
• Lacelike sheets, clusters of very
low nuclear-cytoplasmic (N:C)
ratio cells,optically clear cytoplasm
• Individual cells: Single large clear
vacuole occupying entire
cytoplasmic volume
• Nuclei: Small, hyperchromatic,
displaced to margin of the cell
• Background: May contain
droplets of lipid (best seen on
Romanowsky stains)
2. Schwannoma
• Scant to moderately cellular
aspirate
• Spindle-shaped cells - wispy
bipolar cytoplasmic processes
• Cells: cohesive groups, clusters
• Cytoplasm: Pale and ill-defined
• Nuclei: Small, dark, bland, and
elongate/spindled
• Nucleoli: Small or absent
• Background: Myxoid
IV. Neoplasm
Benign SUMP
Reserved for benign Reserved for FNA
samples that are
neoplasms diagnosed diagnostic of a neoplasm; diagnosis
based on established of a
cytologic criteria 1. Cellular basaloid neoplasm
specific entity cannot be
made
2. Cellular oncocytic/oncocytoid
neoplasm
3.Cellular neoplasm with clear cell
features
Salivary Gland Neoplasm of Uncertain
Malignant Potential
▪ Definitive diagnosis of a specific entity cannot be made
▪ Malignant neoplasm cannot be excluded
FNA specimens showing cytomorphologic features diagnostic of a
neoplastic process, but a malignant neoplasm cannot be excluded.
I. Cellular Basaloid Neoplasm
1) Predominant
population of cells with
scanty cytoplasm with
hyaline stroma
2) Monotonous population
of basaloid cells arranged
in cohesive groups with
scanty hyaline stroma
I. Cellular Basaloid Neoplasm
II. Cellular Oncocytic/Oncocytoid
Neoplasm
• Cellular aspirate
• Neoplastic cells: Oncocytic or oncocytoid features that cannot be
classified further
II. Cellular Oncocytic/Oncocytoid
Neoplasm
• Moderate amounts of
oncocytic granular
cytoplasm
• Round to oval nucleus
± distinct nucleolus
• lack high-grade cellular
features :
- marked nuclear atypia,
- high mitotic activity
- necrosis.
II. Cellular Oncocytic/Oncocytoid
Neoplasm
III. Cellular Neoplasm with Clear Cell
Features
- Neoplasm with clear cell to oncocytoid features showing sheets of
epithelial cells with finely vacuolated cytoplasm.
- Histologic follow-up - acinic cell carcinoma
III. Cellular Neoplasm with Clear Cell
Features
- Monotonous population of neoplastic cells arranged in cohesive
groups with finely granular
Cytoplasm
-Background: Thin mucin, clear histiocytic-type
-Differential diagnosis - mucoepidermoid carcinoma
FNA CASE
V. Suspicious for Malignancy
A salivary gland FNA is classified as SM when some,
but not all the criteria for a specific diagnosis of
malignancy are present, and yet the overall cytologic
features are suggestive of malignancy.
Cytologic category - SM
Markedly atypical cells with poor smear preparation, poor cell
preservation, fixation artifact, or obscuring inflammation and blood
Cytologic category - SM
epithelial cells
with epidermoid
features,
suggestive of
mucoepidermoid
carcinoma
Presence of limited cytologic features of a specific malignant lesion
(e.g., adenoid cystic carcinoma, mucoepidermoid carcinoma, and
acinic cell carcinoma)in an otherwise sparsely cellular aspirate
Cytologic category - SM
markedly atypical
cytologic features in a
subset of cells
admixed with features
of pleomorphic
adenoma
Presence of markedly atypical and/or suspicious cytologic features in
a subset of cells but admixed with features of a benign salivary gland
lesion
FNA CASE
VI MALIGNANT
▪ Salivary gland aspirates classified as “Malignant”
– contain a combination of cytomorphologic features
that, either alone or in combination with ancillary
studies
– When possible, an attempt should be made to provide
the grade of the neoplasm as well as the specific tumor
type
VI MALIGNANT
Acinic Cell Carcinoma
1) Cellular smears with
“monotonous” population
of epithelial cells
2) Polygonal tumor cells
with low nuclear–
cytoplasmic (N:C) ratio ,
abundant delicate
vacuolated cytoplasm with
basophilic quality
Acinic Cell Carcinoma
1) sheet of cells
with abundant delicate
cytoplasm with scattered
small coarse granules
2) three-dimensional
clusters of acinar cells
with abundant delicate
cytoplasm;
Secretory
Carcinoma
Different architectural patterns
of microcystic, tubular,
microfollicular,
And solid sheets of glandular
cells with eosinophilic colloid-
like secretory material
Epithelial-Myoepithelial
Carcinoma
Biphasic tumor
with inner cuboidal
ductal cells and
prominent outer
myoepithelial cells
Epithelial-Myoepithelial
Carcinoma
prominent
concentrically
laminated
proteinaceous
secretions
Salivary Duct Carcinoma
High-grade malignant cells with abundant cytoplasm, nuclear
pleomorphism, prominent nucleoli, and glandular features
Mucoepidermoid Carcinoma
1) Abundant mucin in background, loose sheets of bland epidermoid
and mucinous cells
2) Bland epidermoid cells - moderate amounts of dense cytoplasm well-
defined cell borders, mucus cells - abundant delicate pink mucinous
cytoplasm
Adenoid Cystic
Carcinoma
Small high N:C ratio basaloid
tumor cells surrounding acellular
matrix with: a cribriform pattern
Carcinoma ex Pleomorphic Adenoma
Defined as an epithelial or myoepithelial malignancy developing from primary or
recurrent
-Loose groups of high-grade carcinoma cells.
- Scant background metachromatic material - residual pleomorphic adenoma.
Sample report
Increasing availability of FISH markers
SAMPLE REPORT
Recent Article
Summary
REFERENCES
1) Robbins & Cotran; Pathologic Basis of Disease, South
Asia Edition.
2) van Zante , et al The Milan System for Reporting Salivary
Gland Cytopathology: Benefits and Cautions. AJSP:
Reviews & Reports. 2020 Sep 1;25(5):235-42.
3) Vallonthaiel AG, et al. Application of the Milan system for
risk stratification and its comparison with a previous
reporting system of parotid gland cytopathology in a
tertiary care centre. Acta cytologica. 2018;62(5-6):352-9.
4) Rossi ED,et al. The Milan System for Reporting Salivary
Gland Cytopathology (MSRSGC): an ASC-IAC-
sponsored system for reporting salivary gland fine-needle
aspiration. Acta Cytologica. 2018;62(3):157-65.
REFERENCES
5) Field, A., Zarka, M. and Field, P., 2016. Practical
Cytopathology. Saintt Louis: Elsevier Health Sciences.
6) Faquin, W., Rossi, E., Baloch, Z., Barkan, G., Foschini,
M., Kurtycz, D., Pusztaszeri, M. and Vielh, P., n.d. The
Milan System for Reporting Salivary Gland
Cytopathology.
7) Webinars
- The milan system of reporting salivary gland
cytopathology - Dr Faquin (PATHCAST)
- FNA Cytology of salivary gland lesions : A novel
practical pattern based approach to diagnosis – Dr Zarka
(PATHCAST)
THANK YOU