Salivary gland WHO 2017

1. Updates and new entities in salivary
gland tumours -WHO
classification(2017)
Presenter: G Santhipriya
Moderator: Dr Arathi CA
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2. Contents
• WHO classification old and new
• New entities
–Morphology
–Diagnosis
• Summary
• References
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3. WHO 2005 WHO 2017
Malignant epithelial tumours
• Acinic cell carcinoma
• Mucoepidermoid
carcinoma
• Adenoid cystic carcinoma
• Polymorphous low-grade
adenocarcinoma
• Epithelial-myoepithelial
carcinoma
• Clear cell carcinoma, not
otherwise specified
• Basal cell adenocarcinoma
• Sebaceous carcinoma
Malignant tumours
• Acinic cell carcinoma
• Mucoepidermoid
carcinoma
• Adenoid cystic carcinoma
• Polymorphous
adenocarcinoma
• Epithelial- myoepithelial
carcinoma
• Clear cell carcinoma
• Basal cell adenocarcinoma
• Sebaceous adenocarcinoma
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4. WHO 2005 WHO 2017
Malignant epithelial tumours
• Sebaceous
lymphadenocarcinoma
• Cystadenocarcinoma
• Low-grade cribriform
cystadenocarcinoma
• Mucinous
adenocarcinoma
• Oncocytic carcinoma
• Salivary duct carcinoma
• Adenocarcinoma, not
otherwise specified
• Myoepithelial carcinoma
Malignant tumours
• lntraductal carcinoma
• Secretory carcinoma
• Oncocytic carcinoma
Uncertain malignant
potential
• Salivary duct carcinoma
• Adenocarcinoma, NOS
• Myoepithelial carcinoma
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5. WHO 2005 WHO 2017
Malignant epithelial tumours
• Carcinoma ex
pleomorphic adenoma
• Carcinosarcoma
• Metastasizing
pleomorphic adenoma
• Squamous cell carcinoma
• Small cell carcinoma
• Large cell carcinoma
• Lymphoepithelial
carcinoma
• Sialoblastoma
Malignant tumours
• Carcinoma ex pleomorphic
adenoma
• Carcinosarcoma
• Squamous cell carcinoma
• Poorly differentiated
carcinoma
– Undifferentiated carcinoma
– Large cell neuroendocrine
carcinoma
– Small cell neuroendocrine
carcinoma
• Lymphoepithelial carcinoma
• Sialoblastoma12/9/2019 5PESIMSR SEMINAR

6. WHO 2005 WHO 2017
Benign epithelial tumours
• Pleomorphic adenoma
• Myoepithelioma
• Basal cell adenoma
• Warthin tumour
• Oncocytoma
• Canalicular adenoma
• Sebaceous adenoma
• Lymphadenoma
– Sebaceous
– Non-sebaceous
• Ductal papillomas
– Inverted ductal papilloma
– Intraductal papilloma
– Sialadenoma papilliferum
• Cystadenoma
Benign tumours
• Pleomorphic adenoma
• Myoepithelioma
• Basal cell adenoma
• Warthin tumour
• Oncocytoma
• Canalicular adenoma and
other ductal adenomas
• Sebaceous adenoma
• Lymphadenoma
• Sialadenoma papilliferum
• Ductal papillomas
– Inverted ductal papilloma
– Intraductal papilloma
• Cystadenoma12/9/2019 6PESIMSR SEMINAR

7. WHO 2005 WHO 2017
 Soft tissue tumours
• Haemangioma
 Haematolymphoid tumours
• Hodgkin lymphoma
• Diffuse large B-cell lymphoma
• Extranodal marginal zone B-
cell lymphoma
 Secondary tumours
 Non-neoplastic epithelial
lesions
• Sclerosing polycystic adenosis
• Nodular oncocytic hyperplasia
• Lymphoepithelial sialadenitis
• lntercalated duct hyperplasia
 Benign soft tissue lesions
• Haemangioma
• Lipoma/sialolipoma
• Nodular fasciitis
 Haematolymphoid tumours
• Extranodal marginal zone
lymphoma of mucosa-
associated lymphoid
tissue(MALT lymphoma)12/9/2019 7PESIMSR SEMINAR

8. Polymorphous adenocarcinoma (PAC)
• Syn. Low-grade polymorphous
adenocarcinoma (PLGA); terminal duct
carcinoma; lobular carcinoma
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9. Polymorphous adenocarcinoma (PAC)
• PAC is the second most common intraoral
malignant salivary gland tumour
• Palate
• Painless mass of variable duration
• Bleeding, telangiectasia, and ulceration of the
overlying mucosa
• Bone invasion- may be seen
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10. Typically present as firm, circumscribed,
unencapsulated, yellowish-tan lobulated nodules of
variable size
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11. Polymorphous adenocarcinoma (PAC)
Submucosal
unencapsulated
Cytological uniformity
Histological diversity
Infiltrating growth pattern
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12. Polymorphous adenocarcinoma (PAC)
Cribriform variant Pale, optically clear and vesicular nuclei
Similar to PTC
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13. Immunoreactivity PAC
• CK 7 100%+
• P63 100%+
• P40 –
• Galectin 3 expresion
• BCL2 overexpressed
• Mammaglobin is positive
in 67- 100%
• S100 97 %+
• KIT (CD117) 60% +
• CEA 54%+
• GFAP 15%+
• MSA 13%+
• EMA 12%+
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14. Genetics and prognosis- PAC
• HRAS mutations
• Alterations of the PRKD gene family
– Rearrangements of PRKD1, PRKD2, and PRKD3
– Activating mutation of PRKD1
• Good prognosis
• High grade transformation- unfavourable
prognosis
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15. Adenocarcinoma, NOS
• Spectrum of epithelial carcinomas
– Ductal
– Glandular
• Structures (with or without cystic formation)
• Exclude
– salivary duct carcinoma,
– high-grade mucoepidermoid carcinoma,
– polymorphous adenocarcinoma and
– metastatic adenocarcinoma
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16. Adenocarcinoma, NOS
• parotid gland > minor glands > hard palate,
>buccal mucosa, and lips
• Asymptomatic solitary
• Firm or cystic masses
• Ulcerated
• Erode bony structures
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17. Adenocarcinoma, NOS
• Gross:
– partly circumscribed,
– irregular and infiltrative appearance.
– tan or yellow,
– with or without areas of necrosis and haemorrhage.
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18. Adenocarcinoma, NOS
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19. Adenocarcinoma, NOS
• Subtypes
– Mucinous adenocarcinoma with variable cystic
formation (cystadenocarcinoma)
– Intestinal-type adenocarcinoma – CK 20 and CK
2+
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20. Adenocarcinoma, NOS
Intestinal typed adenoca- ductal neoplastic stuctures lined
by tall columnar neoplastic cells
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21. Adenocarcinoma, NOS
• Immunohistochemistry
• Aggressive clinical course
• Prognosis
– tumour location,
– tumour grade, and clinical stage
– High-grade
Acinic cell carcioma CK18, DOG1 +
Myoepithelial calponin, SMA, CK5/6, p63
Intestinal type CK 20 and CK 2+
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22. Secretory carcinoma
• Low grade
• Morphological resemblance -mammary
secretory carcinoma
• ETV6-NTRK3 gene fusion
• Mammary analogue secretory carcinoma
• Parotid gland
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23. Secretory carcinoma
• Painless
• Slow growing mass
• Gross
– Poorly defined and rubbery
– Cut section- light tan
– Cyst formation and yellowish white fluid
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24. Secretory carcinoma
• Circumscribed or (often) infiltrative
• lobulated growth pattern with fibrous septa
• Microcystic/ solid, tubular, follicular, and
papillary- cystic structures with distinctive
luminal secretion
• Occasional perineural invasion
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25. Secretory carcinoma
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26. Secretory carcinoma
• t(12;15) (p13;q25) chromosomal
rearrangement resulting in the fusion of the
ETV6 and NTRK3 genes
• Atypical fusion transcripts (4-14 or 5-14
junctions) ETV6-RET fusion
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27. Secretory carcinoma
• IHC
• S100, mammaglobin positive
• DOG 1 negative
• Adverse prognostic factors
– High clinical stage
– High grade transformation
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28. Poorly differentiated carcinoma
• Primary carcinomas - large and small cell types
with or without neuroendocrine differentiation
• Exclusion
• Painless mass
• Older age
• Parotid gland
• Facial nerve paralysis
• Poorly defined firm white mass
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29. Poorly differentiated carcinoma
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30. Poorly differentiated carcinoma
• Both SmCCs and LCNECs
– High grade
– organoid cellular growth
– minimal differentiation,
– high mitotic rates,
– frequent presence of coagulative necrosis.
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31. Poorly differentiated carcinoma
• SmCNECs Vs LCNEC
– scant cytoplasm,
– Smaller cell size (< 2-3 times the diameter of a
normal lymphocyte),
– angulated moulded nuclei with inconspicuous
nucleoli,
– smudgy basophilic material
– surrounding intratumoural blood vessels.
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32. Poorly differentiated carcinoma
• Synaptophysin+
• chromogranin +
• SmCC can show
– perinuclear dot-like positivity for pancytokeratins
and CK20,
– similar to the expression pattern seen in cutaneous
Merkel cell carcinoma
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33. Poorly differentiated carcinoma
• The small-cell variant
– small round blue cell tumours (e.g. desmoplastic
small round cell tumour and other Ewing family
tumours),
– salid adenoid cystic carcinoma
– metastatic neuroblastoma,
– lymphomas, and melanoma.
• TP53, NOTCH1, PTEN, and CDKN2A
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34. Intraductal carcinoma
• Intracystic or
intraductal
proliferations of
neoplastic epithelial
cells
• Syn- cribriform
cystadenocarcinoma
• Mostly parotid gland
• Excellent prognosis
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35. Intraductal carcinoma
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36. Intraductal carcinoma
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37. Intraductal carcinoma
• Tumor cells are monomorphic and ovoid
and evenly spaced with round nuclei
and scant eosinophilic cytoplasm.
• Oncocytic and apocrine change and
intermediate grade cytonuclear features are
uncommon.
• Exclude cystadenocarcinoma
• Excellent prognosis
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38. Ductal papillomas
• Luminal ductal epithelial proliferations that
occur at various sites within the salivary duct
system.
• Subclassified
– Intraductal papilloma
– Inverted ductal papilloma.
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39. Intraductal papilloma- terminal-ED
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40. Inverted ductal papilloma
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41. Ductal papillomas
• Differential diagnosis
– Mucoepidermoid carcinoma
• Intraductal papilloma lacks the
multicystic,multinodular, and infiltrative
growth pattern of mucoepidermoid
carcinoma
• Surgery- complete excision
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42. Sclerosing polycystic adenosis (SPA)
• Synonymum: sclerosing polycystic adenoma
o Benign neoplasm
o Fibrocystic changes and sclerosing adenosis of
the breast
o HUMARA ASSAY ( Human androgen receptor
assay)
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43. Circumscribed lesion, embedded in
parotid gland
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44. Well circumscribed, with multiple
variably sized cystic ducts
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45. Ducts lined by flattened to cuboidal
epithelium with apocrine and foamy
change
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46. • Both benign and malignant conditions
• sclerosing sialadenitis, polycystic dysgenetic disease,
PA, LG cystadenocarcinoma, AciCCa,
mucoepidermoid carcinoma
• management is surgical with conservative subtotal
parotidectomy
• prolonged surveillance
• High risk of recurrences
• very low risk of carcinomatous transformation
Sclerosing polycystic adenosis (SPA)
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47. Nodular oncocytic hyperplasia (NOH)
• Multiple non-neoplastic nodular proliferations
• abundant granular eosinophilic (oncocytes)
and/or clear cytoplasm (clear cells)
• In one or both parotid glands
• Etiology
– Unknown
– HPV infection (HPV 53)
– Mitochondrial DNA mutations
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48. NOH - Gross
• Scattered
• well-circumscribed
• brown or mahogany to
whitish-tan nodules
• 0.2 to 2.5 cm
• Oncocytoma arising within
NOH- well circumscribed and
partially encapsulated
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49. Nodular oncocytic hyperplasia (NOH)
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50. Lymphoepithelial sialadenitis
• Benign lesion -acinar atrophy, ductal
hyperplasia, and epimyoepithelial islands in
lymphoid stroma.
• Predominantly females
• Fourth to seventh decade of life
• Etiology
– an autoimmune lesion
– Sjógren syndrome
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51. Lymphoepithelial sialadenitis
CK
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52. lntercalated duct hyperplasia
• Salivary ductal proliferation resembling
intercalated ducts
• Reactive or hyperplastic process
• A precursor role
• Incidental
• Basal cell adenoma or epithelial-myoepithelia
carsinoma
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53. • Nodular -small ductules of attenuated
myoepithelial and cuboidal ductal cells
• lf well circumscribed, it must be distinguished
from the striated form of ductal adenoma
• Benign hyperplastic lesion
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54. Summary
• Polymorphous adenocarcinoma
• lntraductal carcinoma
• Secretory carcinoma
• Adenocarcinoma, NOS
• Poorly differentiated carcinoma
– Undifferentiated carcinoma
– Large cell neuroendocrine
carcinoma
– Small cell neuroendocrine
carcinoma
• Sialadenoma papilliferum
• Ductal papillomas
– Inverted ductal papilloma
– Intraductal papilloma
• Non-neoplastic epithelial lesions
– Sclerosing polycystic
adenosis
– Nodular oncocytic
hyperplasia
– Lymphoepithelial
sialadenitis
– lntercalated duct hyperplasia
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55. References
• Barnes L, Eveson JW, Reichart P, Sidransky D. World
Health Organization classifications tumours. Pathology and
genetics of head and neck tumours. Lyon: IARC. 2005.
• El-Naggar AK, editor. WHO classification of head and neck
tumours. International Agency for Research on Cancer;
2017.
• Jonathan B In.Goldblum JR, Lamps LW, McKenney JK,
Myers JL. Rosai and Ackerman's Surgical Pathology.
Elsevier Health Sciences; 2017:235-58
• Zhu S, Schuerch C, Hunt J. Review and updates of
immunohistochemistry in selected salivary gland and head
and neck tumors. Archives of Pathology and Laboratory
Medicine. 2015;139(1):55-66.
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56. • Thanks you!!
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