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Salivary glands Flashcards

1
Q

What are the salivary gland tumours with a myoepithelial cell component?

A
  1. Benign: myoepithelioma, pleomorphic adenoma, basaloid adenoma
  2. Malignant: epithelial-myoepithelial carcinoma, adenoid cystic carcinoma, polymorphous adenocarcinoma, basaloid carcinoma
  3. Congenital: sialoblastoma, salivary gland anlage tumour
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2
Q

What normal structure is epithelial-myoepithelial carcinoma said to be recapitulating/mimicking?

A

The intercalated duct

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3
Q

What are the various morphologic types of myoepithelial cells in salivary gland, and what tumours can they be seen in?

A
  1. Stellate/myxoid (PA)
  2. Spindled/myoid (PA, myoepithelioma)
  3. Hyaline/plasmacytoid (PA, myoepithelioma)
  4. Clear cells (many tumours - around ducts, epithelial-myoepithelial ca)
  5. Lipoid cells (PA with lipometaplasia)
  6. Oncocytic (epi-myoepi ca of oncocytic type, PA, oncocytic myoepithelioma)
  7. Osteoblastic (PA)
  8. Squamous (PA)
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4
Q

What is a possible significance of the presence of myoepithelial cells in a salivary gland tumour?

A

Better prognosis/less aggressive - may have anti-invasive properties e.g. inhibit angiogenesis, etc

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5
Q

What are some salivary gland tumours that can occur in heterotopic salivary gland tissue?

A
  1. PA
  2. MEC
  3. Adenoid cystic

*Problem - ddx is metatastic tumour to a lymph node vs primary in heterotopic tissue

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6
Q

What are some changes seen in aging in salivary glands?

A

Increased oncocytes, fatty infiltration

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7
Q

What are the patterns of oncocytes seen in salivary gland?

A

Occasional cells

Nodular hyperplasia (nodules, unencapsulated)

Oncocytosis (diffuse)

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8
Q

Oncocytes can be seen in which salivary gland tumours?

A

Warthin’s

Basal cell adenoma

PA

Myoepithelioma

Polymorphous

MEC

Acinic cell

Pure oncocytoma

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9
Q

What are the reactive changes that can occur in salivary gland?

A
  1. Metaplasia (squamous, mucous, necrotizing sialometaplasia)
  2. Hyperplasia (esp in minor glands - sialadenosis - endocrine/nutritional abnormalities)
  3. Atrophy (common -> obstruction of excretory duct + inflammation)
  4. Regeneration (embryonic, atypical but lobular architecture preserved)
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10
Q

What are the biphasic (epithelial and myoepithelial components) tumours of salivary gland?

A
  1. PA
  2. Adenoid cystic
  3. Basal cell adenoma
  4. Epithelial-myoepithelial carcinoma
  5. Polymorphous
  6. Basal cell carcinoma
  7. Embryonic tumours
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11
Q

What salivary gland tumour morphologically corresponds to the acinus?

A

Acinic cell carcinoma

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12
Q

What salivary gland tumour(s) morphologically correspond to the intercalated duct?

A

PA

Adenoid cystic

Monomorphic adenoma

Epithelial-myoepithelial carcinoma

Polymorphous

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13
Q

What salivary gland tumour(s) morphologically correspond to the striated duct?

A

Warthin’s tumour

Oncocytoma

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14
Q

What salivary gland tumours morphologically correspond to the excretory ducts?

A

MEC

Ductal adenocarcinoma

Epidermoid carcinoma

Papilloma

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15
Q

What are the similarities and differences between a mucocoele and a ranula?

A

Mucocoele: various sites, pseudocyst with denuded epithelial lining, granulation tissue

Ranula: similar but is from sublingual gland so only floor of mouth (can be plunging/cervical/extra-oral)

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16
Q

What is the pathogenesis of the lymphoepithelial cyst in salivary gland?

A

Cystic dilatation and squamous metaplasia of intranodal salivary gland inclusions

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17
Q

What are the histologic features of a lymphoepithelial cyst in salivary gland?

A

Cyst lined by flattened to stratified squamous epithelium surrounded by lymphoid stroma

Occasional - glandular epithelium

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18
Q

In what clinical situation are lymphoepithelial cysts of salivary gland more common?

A

HIV - “cystic lymphoid hyperplasia”

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19
Q

What are the histologic features of sclerosing polycystic adenosis of the parotid gland?

A

Mass-forming, mixture of sclerotic and cystic stroma with entrapped glands and inflammation

Apocrine metaplasia

Complex ductal hyperplasia (like UDH in breast)

Intraductal necrosis

Atypia

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20
Q

What is the differential diagnosis of a neck cyst?

A

Lymphoepithelial cyst

Thyroglossal duct cyst

Branchial cleft cyst

Ranula

Dermoid cyst

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21
Q

What are the histologic features of necrotizing sialometaplasia?

A

Early: infarction of seromucinous glands, extravasation of luminal contents, acute and chronic inflammation

Few days: squamous metaplastic cells in necrotic acini -> mitoses, atypia, can be mixed with residual non-infarcted mucous cells (ddx: MEC) -> stays lobular

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22
Q

What is the diagnosis?

A

Necrotizing sialometaplasia

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23
Q

What is the usual clinical setting for necrotizing sialometaplasia?

A

Prior surgery

Trauma

(Vascular compromise -> necrosis, inflammation, regeneration with squamous metaplastic cells)

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24
Q

What are the histologic features of radiation-related change in salivary gland?

A

Retained lobular architecture

Similar to necrotizing sialometaplasia

Radiation like atypia (smudged cells)

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25
What is a mass-forming form of chronic sialadenitis?
Chronic sclerosing sialadenitis/Kuttner tumour
26
What are the histologic features of a Kuttner tumour?
Preserved lobular architecture Periductal fibrosis Periductal lymphoplasmacytic infiltrate Progressive atrophy Reactive lymphoid follicles IgG4-related (Can get MALToma)
27
What is the differential diagnosis of chronic inflammation in salivary gland?
1. Chronic sialadenitis (obstruction, stone, etc) 2. Kuttner tumour 3. Sjogren syndrome
28
What are the histologic features of enlarged salivary glands in Sjogren syndrome?
Benign lymphoepithelial lesion/lymphoepithelial sialadenitis/Mikulicz disease (increased risk of MALToma)
29
What are the diagnostic criteria for Sjogren syndrome in salivary gland?
At least 4 lobules with at least 2 foci of lymphocytes per 4mm2 (focus = cluster of 50 or more lymphocytes)
30
What clinical situations can result in sialadenitis?
Viral (EBV, coxsackie, etc) Bacterial (staph aureus, etc) Rheumatoid arthritis (chronic sial) Dehydration Malnutrition Immunosuppression Sialolithiasis (Granulomatous - TB, fungi, sarcoid, duct obstruction)
31
What are the causes of granulomatous sialadenitis?
Infection (TB, fungi) Sarcoidosis Duct obstruction
32
What is the main differential diagnosis of benign lymphoepithelial lesion?
Malignant lymphoepithelial carcinoma (EBV assoc, undiff ca with lymphoid stroma) MALT lymphoma
33
What is the characteristc pattern of metastasis in adenoid cystic carcinoma
Late met to lung (can be years)
34
Where do primary salivary gland tumours usually met to?
Local lymph nodes
35
What tumours can met to salivary glands?
SCC, melanoma, Merkel cell - beware met to intraparotid lymph node!
36
List the benign epithelial tumours of the salivary gland
1. PA 2. Myoepithelioma 3. Basal cell adenoma 4. Warthin tumour 5. Oncocytoma 6. Lymphadenoma 7. Cystadenoma 8. Sialadenoma papilliferum 9. Ductal papillomas 10. Sebaceous adenoma 11. Canalicular adenoma (and other ductal adenomas)
37
What are the genes possibly translocated in PAs?
PLAG1 and HMGA2 (by FISH)
38
What are the indications to perform FISH testing in PAs?
1. To establish diagnosis of PA in histologically difficult tumours 2. To establish PA as basis for carcinoma ex PA (which has better prognosis compared to other ca)
39
What are the histologic features of myoepithelioma?
Monophasic Myoepithelial cells with variable appearance (oncocytic, clear cell, spindled, stellate/myxoid, epithelioid, plasmacytoid) Can have reticular or microcystic appearance
40
What is the immunoprofile of myoepithelioma?
S100+, CK7+, calponin +, GFAP+ \*pitfall - plasmacytoid variant may be negative for myoepithelial markers
41
What is the differential diagnosis of myoepithelioma?
Depends on morphology: Clear cell - metastatic RCC Myoepithelial carcinoma - invasive Spindle cell - schwannoma, nodular fasciitis, synovial sarcoma..
42
What syndrome MAY be associated with basal cell adenoma of the parotid gland?
Brooke-Spiegler syndrome: multiple familial trichoepitheliomas
43
What are the histologic features of basal cell adenoma?
cellular monotonous nests of basaloid cells may have squamoid features
44
What are the subtypes of basal cell adenoma?
1. Trabecular: interlacing narrow bands of cells, may have ductal lumens, loose fibrous stroma 2. Solid: nests with surrounding dense collagenous stroma, palisading, squamous whorls/eddies 3. Tubular: lumens lined by cuboidal ductal cells (like canalicular adenoma) 4. Membranous: prominent hyaline material or basal lamina surrounding nests of cells
45
What are the histologic features of Warthin's tumour/papillary cystadenoma lymphomatosum?
Thin capsule Bilayered epithelium (columnar and basaloid oncocytic cells) Cystic Epithelium forms papillae Surrounding lymphoid stroma +/- follicles Cyst contents - cellular debris, corpora amylacea, calcs +/- Squamous metaplasia
46
What is the differential diagnosis of bilateral salivary gland lesions/lumps?
1. Acute parotitis 2. Chronic sialadenitis 3. Lymphoma 4. Warthin's tumour (can be bilateral or multifocal) 5. Sjogren's 6. Lymphoepithelial cysts in HIV patients 7. Acinic cell carcinoma I.e. Non-neoplastic (infection - viral or bacterial, obstruction, AI) or neoplastic (Warthins, lymphoma)
47
What is the differential diagnosis of Warthin's tumour?
Oncocytoma - usually more solid, no lymphoid Papillary oncocytic cystadenoma - no lymphoid Lymphoepithelial cyst - no oncocytes Lymphadenoma - no oncocytes Parotid duct cyst - no lymphoid
48
What are the two components of pleomorphic adenoma?
Epithelial (ductal structures with myoepithelial cells of variable appearance, squamous, bland) Mesenchymal (myxoid, hyaline, cartilagenous, osseous)
49
What are the other variants of pleomorphic adenoma (apart from usual)?
1. Cellular (predominant epithelial component \>80%) 2. Myxoid (myxochondromatous element predominates)
50
What is the differential diagnosis of pleomorphic adenoma?
Ca ex PA (look for malignant tumour - of any kind) Polymorphous - esp in minor gland, PNI, infiltrative, single file, tubular
51
How does a pleomorphic adenoma present in the superficial lobe and in the deep lobe?
Superficial - palpable mass Deep - oral retrotonsillary mass or mass in parapharyngeal space
52
What are the clinical features associated with malignant PA?
Older Male Multiple recurrences In deep lobe
53
What clinical risk factors are associated with Warthin's tumour?
Male Smoking Older
54
What are the histologic features of sebaceous lymphadenoma?
Epithelial component (basaloid with palisading and central sebaceous) Lymphoid background FB type reaction +/- squamous metplasia
55
What is the diagnosis?
Sebaceous lymphadenoma
56
List the malignant salivary gland tumours
1. MEC 2. Adenoid cystic carcinoma 3. Acinic cell carcinoma 4. Secretory carcinoma 5. Polymorphous adenocarcinoma 6. Salivary duct carcinoma 7. Epithelial-myoepithelial carcinoma 8. Myoepithelial carcinoma 9. Clear cell carcinoma 10. Basal cell adenocarcinoma 11. Intraductal carcinoma 12. Sebaceous adenocarcinoma 13. Carcinosarcoma 14. Lymphoepithelial carcinoma 15. Adenocarcinoma NOS 16. SCC 17. Poorly differentiated carcinoma 18. Oncocytic carcinoma 19. Sialoblastoma
57
What is the diagnosis?
Cystadenoma
58
What are the histologic features of cystadenoma of salivary gland?
Cystic (single or multiple) Intraluminal papillary proliferation lined by columnar/cuboidal epithelium Luminal contents - eosinophilic fluid, epithelial/inflamm cells +/- rare glands +/- squamous metplasia +/- oncocytic metaplasia
59
What is the differential diagnosis of salivary gland cystadenoma?
Warthin - bilayered oncocytic, lymphoid stroma Congenital polycystic disease - developmental malformation of ductal system, multicystic, luminal spheroliths, apocrine-like lining, infants/kids Duct ectasia w/ focal epi prolif secondary to obstruction - acinar atrophy, chronic inflammation, fibrosis Intraductal papilloma - always unicystic, dilated salivary gland duct, more papillary fronds that are more complex Low-grade papillary cystadenocarcinoma - invasive (exclude LG MEC)
60
What is the diagnosis?
Sialadenoma papilliferum
61
What is the diagnosis?
Ductal papilloma
62
What is the diagnosis?
Canalicular adenoma
63
What is the differential diagnosis of a "blue" (basaloid) salivary gland tumour?
Adenoid cystic Basal cell adenoma/adenoca Cellular PA Polymorphous adenoca
64
What is the differential diagnosis of a "pink" (oncocytic) salivary gland tumour?
Acinic cell ca MEC Oncocytoma/oncocytic ca myoepithelioma/myoep ca low-grade intraductal ca PA salivary duct ca clear cell carcinoma
65
What is the differential diagnosis of a clear cell neoplasm in salivary gland tumours?
clear cell ca acinic cell ca MEC oncocytoma/ca epi-myoepi ca myoepithelioma/myoep ca mets (RCC)
66
What biomarker is important in salivary duct carcinoma?
HER2 amplification in 30%, predicts sensitivity to trastuzumab (herceptin)
67
Describe the grading system for MEC
AFIP ## Footnote Cystic \<20% - 2 Neural invasion - 2 Necrosis - 3 \>4/10HPF mites - 3 Anaplasia - 4 0-4 = LG, 5-6 = IG, \>7 = HG
68
Describe the ETV6-NTRK3 rearranged tumours
Secretory carcinoma (of SG and breast) Infantile fibrosarcoma Congenital mesoblastic nephroma (targeted tx: larotrectinib)
69
What benign salivary gland tumour can have isolated vascular invasion?
PA
70
What benign salivary gland tumour can metastasize?
PA
71
What is the most common bilateral salivary gland malignancy?
Acinic cell carcinoma
72
What are the histologic features of acinic cell carcinoma?
Acinar cells with blue appearance due to granules Also has ductal cells, clear cells Various architecture: solid, microcystic, hobnail, papillary-cystic (macrocystic with papillae), follicular (looks like thyroid) TALP (tumour-associated lymphoid proliferation) +/- stromal hyalinisation/fibrosis +/- poorly diff/dediff component
73
What is the immunoprofile/stains of acinic cell carcinoma?
DOG1 (luminal) and SOX10 + (not specific) PAS+ D-resistant granules - luminal accentuation (most helpful)
74
What proportion of acinic cell carcinomas undergo high grade transformation?
15% Undiff, small or large cell appearance, anaplastic Comedonecrosis
75
What is the differential diagnosis of a high grade NE tumour in salivary gland?
1. Primary (e.g. primary NEC, high grade transformation of other salivary tumour e.g. acinic cell) 2. Metastatic Merkel cell carcinoma (or other met NEC)
76
What is the molecular alteration in secretory carcinoma?
ETV6-NTRK3 fusion (with infantile fibrosarcoma and congenital mesoblastic nephroma)
77
Apart from salivary gland, where else can secretory carcinoma can be seen?
Breast Skin GU Thyroid
78
What are the features of high grade transformation in secretory carcinoma?
Pleomorphism Necrosis Mitoses
79
What are the histologic features of secretory carcinoma?
1. Lobulated growth pattern with fibrous septae 2. Variable architecture: microcystic/solid, papillary-cystic, tubular, follicular 3. Distinctive luminal secretion 4. Small/uniform nuclei 5. Eosinophilic granular to vacuolated cytoplasm +/- high grade transformation
80
What is the differential diagnosis of secretory carcinoma?
1. \*\*Acinic cell carcinoma (has PAS+ granules, unlike secretory) 2. MEC (epidermoid areas but has oncocytic and clear cell types, MAML2) 3. Polymorphous adenocarcinoma (minor glands, variable architecture, S100+)
81
What is the immunoprofile of secretory carcinoma?
S100+ diffuse Mammaglobin+ Negative for PAS-D
82
What is the most common malignancy of the submandibular gland?
Adenoid cystic carcinoma
83
What are the 3 main histologic growth patterns of adenoid cystic carcinoma?
1. Cribriform (classic) 2. Tubular 3. Solid - most have a mix
84
Describe the histologic features of adenoid cystic carcinoma?
1. Cribriform, tubular, solid 2. Cribriform spaces contain BM-like material 3. Angulated, hyperchromatic nuclei 4. Hyalinised/collagenous stroma 5. PNI common 6. Biphasic (myoep component)
85
What is the molecular alteration in adenoid cystic carcinoma?
MYB- or MYBL1-NFIB fusion
86
What chromosomal alteration in adenoid cystic carcinoma is associated with a poorer prognosis?
Loss of 1p and/or 6q (often solid tumours)
87
What is the immunoprofile of adenoid cystic carcinoma?
p63+ in myoep component CD117+ (not specific)
88
What is the differential diagnosis of adenoid cystic carcinoma?
1. Polymorphous (minor glands, PNI common) 2. Basaloid SCC (look for in situ) 3. Epithelial-myoepithelial carcinoma (not cribriform, biphasic, outer cell is prominent with clear cytoplasm)
89
Where does polymorphous adenocarcinoma usually occur?
Palate (60%) Other minor glands (buccal, base of tongue, upper lip, etc)
90
What are the histologic features of polymorphous adenocarcinoma?
1. Cytologic uniformity (bland, small, mitoses/necrosis usually only in HG transformation, can have oncocytic/clear/squamous/mucous cells) 2. Histologic diversity (lobular, trabecular, microcystic, cribriform, papillary-cystic, solid, mucinous or collagenous stroma) 3. Infiltrative growth pattern (PNI common)
91
What is an emerging variant of polymorphous adenocarcinoma, possibly a separate entity?
Cribriform adenocarcinoma of tongue
92
What benign entity/ies can MEC mimic?
1. Mucocoele (beware LG MEC!) 2. Sialometaplasia (reactive squamous met, no cystic areas, no intermediate cells) 3. PA 4. Sclerosing polycystic adenosis 5. Warthin's (oncocytic variant with lymphoid component) 6. Sclerosing sialadenitis (sclerosing variant)
93
What is the molecular alteration in MEC?
CTRC1-MAML2 fusion
94
What special stains can be of use in MEC?
Mucicarmine - identify mucous cells
95
What are the histologic features of MEC?
1. 3 populations of cells (mucous, epidermoid, intermediate-type) 2. Cystic/papillary cystic with lumina filled with mucin 3. Extravasated mucin 4. Sclerosing variant (sclerotic stroma) 5. Oncocytic variant 6. Clear cell
96
What are the histologic features of epi-myoep carcinoma?
1. Multinodular 2. Tubules with biphasic/bilayered inner ductal cells and outer clear myoep cells 3. +/- solid 4. +/- necrosis 5. PNI common 6. Vascular invasion rare
97
What is the differential diagnosis of epithelial-myoep carcinoma?
1. PA (mesenchymal element) 2. Myoepithelial carcinoma (no ducts) 3. Adenoid cystic (more angulated, hyperchromatic nuclei, more infiltrative) 4. Polymorphous (minor glands, bland, infiltrative/single-file, myoep component not prominent)
98
What the usual demographic for salivary duct carcinoma?
Older men
99
What molecular alteration is sometimes seen in salivary duct carcinoma?
HER2 amplification (like breast)
100
What does salivary duct carcinoma resemble?
IDC of breast/DCIS with comedonecrosis
101
What is lymphoepithelial carcinoma of salivary gland associated with?
EBV infection (like NPC)

Head & Neck Pathology (6 decks)

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