Salivary glands

The salivary glands help digest food. ENT surgeons take 'em out and want you to diagnose 'em. Cytopathology of the salivary glands is covered in the Head and neck cytopathology article.

Normal

Types of salivary glands

Types of glands:

1. Serrous - eosinophilic cytoplasmic granules, acinar arrangement - vaguely resembles the acinar morphology of the pancreas.
2. Mucinous - light eosinophilic staining.

Identifying the glands

The three main glands:

1. Parotid:
   • Serous glands - lower viscosity, acini (lobules).
   • Most tumours in this gland are benign.
2. Submandibular:
   • Serous and mucinous glands.
     • Serous ~90% of gland.
     • Mucinous ~10% of gland.
3. Sublingual:
   • Mucinous glands.

Other:

• Adipose tissue is found between the glands.
  • It increases with age.

Images:

• Salivary glands - normal (uwa.edu.au).
• Submandibular gland (ouhsc.edu) - from a Pathology Quiz.

Memory devices:

• The parotid gland vaguely resembles the pancreas.
• Submandibular = glands are mixed.

Overview

Benign tumours

Tabular form - adapted from Thompson

	Architecture	Morphology	Cell borders	Cytoplasm	Nucleus	DDx	Other	Image
Pleomorphic adenoma	var.	mixed pop.; must include: (1) myoepithelium, (2) epithelium (ductal cells), (3) chondromyxoid stroma	var.	var.	(1) plasmacytoid	adenoid cystic c.	occ. encapsulated, mixed pop. of glandular, myoepithelial and mesenchymal cells	[1]
Warthin tumour	papillary, bilayer	cuboid (basal), columnar (apical)	clearly seen	eosinophilic, abundant	unremarkable	sebaceous lymphadenoma	AKA papillary cystadenoma lymphomatosum	[2], [3]
Basal cell adenoma	var., islands surrounded by hyaline bands	basaloid	subtle	scant, hyperchromatic	granular	basal cell adenoca	-	-
Canalicular adenoma	chains of cells	cuboid or columnar	subtle	scant, hyperchromatic	granular	basal cell adenoma	exclusively oral cavity, 80% in upper lip; IHC: p63-	-
Sialoblastoma	var., islands surrounded by loose fibrous stroma	basaloid	subtle	scant, hyperch.	granular	basal cell adenoca	-	-

Malignant tumours

Tabular form - adapted from Thompson

	Architecture	Morphology	Cell borders	Cytoplasm	Nucleus	DDx	Other
Mucoepidermoid carcinoma	cystic & solid	epithelioid	distinct	fuffy, clear, abundant	nuclei sm.	?	IHC: p63+
Acinic cell adenocarcinoma (AcCC)	acinar (islands)	epithelioid	clear	granular, generous	stippled, +/-occ. nucleoli	?	?
Adenoid cystic carcinoma (AdCC)	pseudocysts, cribriform, solid, hyaline stroma	epithelioid	subtle	scant, hyperchromatic	small "carrot-shaped"	?	?
Salivary duct carcinoma	glandular, cribriform	columnar	subtle/clear	hyperchromatic	columnar	metastatic breast ca	similar to ductal breast carcinoma
Polymorphous low-grade adenocarcinoma	variable, often small nests, may be targetoid	epithelioid	indistinct	eosinophilic	ovoid & small with small nucleoli	?	minor salivary gland tumour, often in palate, cytologically monotonous; IHC: S100+, CK+, vim.+, GFAP+/-, BCL2+/-

DDx

Palate:

• Polymorphous low-grade adenocarcinoma.
• Adenoid cystic carcinoma.
• Pleomorphic adenoma.

Parotid (benign):

• Pleomorphic adenoma.
• Warthin tumour.

IHC overview

General:

• Usually has limited value.

Specifics:

• Luminal markers: CK7, CK19, CAM5.2 (LMWK).
• Basal markers: p63, HMWK, CK14.
• Myoepithelial markers: calponin, actin.
• Uncommitted: S-100.

Notes:

• p63 and S-100 are sometimes call myoepithelial.

Benign

General DDx:

• Inflammation.
• Neoplasm.
• Ductal obstrution.

Chronic Sialadenitis

General

Etiology:

• Infection.
• Autoimmune (e.g. Sjögren syndrome, systemic lupus erythematosus).
• Other.

Microscopic

Features:

• Fibrosis.
• Non-neoplastic mononuclear inflammatory infiltrate.

Image:

• Chronic sialadenitis (WC).

Mucocele

General

• Benign.

Microscopic

Features:

• Ball of mucous.

Pleomorphic adenoma

• Abbreviated PA.

General

Features:

• Very common - approx. 60% of parotid gland tumours.
• May transform into a malignant tumour.
  • Other benign salivary gland tumours do not do this.
• Only benign childhood salivary gland tumour of significance.

Weinreb's dictums

1. Most common salivary tumour in all age groups.
2. Seen in all sites (unlike other benign tumours).
3. Recurrence and malignancy risk (unlike other benign salivary gland tumours).
4. Any part of a tumour that looks like PA makes it a PA.

Gross

• May be cartilaginous appearing.

Microscopic

Features:

• Proliferation of myoepithelium and epithelium (ductal cells) in mesenchymal stroma.
  • Cells in ducts = epithelial.
  • Cells not in ducts = myoepithelial.
• Mesenchymal stroma - important feature.
  • May be any of following: myxoid, mucochondroid, hyalinized, osseous, fatty.
    • Chondroid = specific for PA; can diagnose PA without an epithelial (ductal) component if chondroid is present.
    • Myxoid = not specific for PA.

Notes:

• Mesenchymal stroma not required for diagnosis -- if >5% ducts.
  • No chondroid stroma and <5% ductal cells = myoepithelioma.
• Complete excision is often elusive; stating "completely excised" on a surgical pathology report is unwise.
• Look for, i.e. rule-out, poorly differentiated carcinoma: carcinoma ex pleomorphic adenoma.

Memory device: MEC = myoepithelium, epithelium, chondromyxoid stroma.

IHC

• S-100 +ve, SMA +ve, GFAP +ve.

Basal cell adenoma

General

• ~2% of salivary gland tumours.
• May be multifocal.
• Usu. parotid gland, occasionally submandibular gland.
• Female:male = ~2:1.
• May be seen in association with dermal cylindromas in the context of a genetic mutation.
• Malignant transformation - rarely.

Microscopic

Features:

• Basophilic cells.
• Usu. nests; may be bilayered tubules or trabeculae.

Notes:

• No chondromyxoid stroma.
  • Chondromyxoid stroma present -> pleomorphic adenoma.
• Neoplastic cells embeded in stroma ("stromal invasion") = basal cell adenocarcinoma.
  • Basal cell adenocarcinoma may be cytologically indistinguishable from basal cell adenoma, i.e. "bad" architecture makes it a basal cell adenocarcinoma.

IHC

• Luminal stains +ve: CK7 +ve, CAM5.2 +ve.

Canalicular adenoma

General

• Exclusively oral cavity.
  • 80% of lesions on upper lip.

Microscopic

Features:

• Channels - "beading of cell".
• Mucoid/hemorrhagic stroma.

DDx:

• Basal cell adenoma.

IHC

• p63 -ve.
  • Basal cell adenoma p63 +ve.

Papillary cystadeoma lymphomatosum

• AKA Warthin tumour.

General

Epidemiology:

• May be multicentric ~ 15% of the time.
• May be bilateral ~10% of the time.
• Classically: male > female -- changing with more women smokers.
• Smokers.
• Old - usu. 60s, very rarely < 40 years old.

Notes:

• No malignant transformation.
• Not in submandibular gland.
• Not in sublingual gland.
• Not in children.

Gross

• Motor-oil like fluid.
• Cystic component larger in larger lesions.
  • Small lesions may be solid.

Microscopy

Features:

• Papillae (nipple-shaped structures) with a two rows of pink (eosinophilic) epithelial cells (with cuboidal basal cells and columnar luminal cells) -- key feature.
• Fibrous capsule - pink & homogenous on H&E stain.
• Cystic space filled with debris in situ (not necrosis).
• Lymphoid stroma.

Notes:

• +/-Squamous differentiation.
• +/-Goblet cell differentiation.

DDx:

• Lymphoepithelial cyst.
  • Cyst within a lymph node.

Images:

• Warthin tumour - high mag. (WC).
• Warthin tumour - intermed. mag. (WC).

Sebaceous adenoma

Microscopic

Features:

• Benign counterpart of sebaceous carcinoma.

Oncocytoma

General

• No risk of malignant transformation.
• ~1% of all salivary gland tumours.
• Typical age: 60s-80s.
• Associated with radiation exposure.
• Major salivary glands - usu. parotid gland.

Gross

• Golden brown appearance.

Microscopic

Features:

• Like oncocytomas elsewhere.
  • Eosinophilic cytoplasm (on H&E stain).
    • Due to increased number of mitochrondria.
  • Fine capillaries.

Notes:

• May have clear cell change.
• Multiple small incidental lesions = oncocytosis - not oncocytoma.

IHC

• p63 +ve focally in nucleus.

Malignant

Approach:

• Differentiate -- luminal vs. myoepithelial vs. basal.

Mucoepidermoid carcinoma

General

• Most common malignant neoplasm of salivary gland.

Microscopic

Features:

• Abundant fluffy cytoplasm - with large mucin vacuoles - key feature.
• Nucleus distorted by mucin vacuole.
• Architecture:
  • Cystic - low grade.
  • Solid - high grade.

Notes:

• Mucin vacuoles may be rare; in a superficial glance -- it may mimic squamous cell carcinoma.

Images:

• Mucoepidermoid carcinoma 2 (WC).
• Mucoepidermoid carcinoma 3 (WC).
• Mucoepidermoid carcinoma (ouhsc.edu).

Acinic cell adenocarcinoma

• Abbreviated AcCC.

General

• Malignant neoplasm of salivary gland arising from acinic cells.
• The relative prevalence of the neoplasm in the various salivary gland reflects the abundance of acinic cells: parotid gland (~80%) > minor salivary glands (~17%) > submandibular glands (~3%).
• Affects wide age range -- including children.

Gross

• Tan or reddish.

Microscopic

Features:

• Sheets of cells.
• Abundant cytoplasm.
• Stippled chromatin.
• +/-Peri-tumoural lymphocytes.

Notes:

• Adipose tissue -- present in the salivary glands -- is absent in AcCC.

Memory device:

• AcCC - lots of "C"s - chromatin stipled, cytoplasm generous.

Images:

• AcCC (surgicalpathologyatlas.com).
• AcCC (brown.edu).
• AcCC (aciniccell.org) - image collection.

Subtypes

• Oncocytic variant.
• Clear cell variant.
• Papillary cystic variant.

Stains/IHC

• PAS +ve.
• PAS-D +ve.

Adenoid cystic carcinoma

General

• Common malignant neoplasm of salivary gland.
• AKA cylindroma.
  • Should not be confused with dermal cylindroma (a benign skin tumour).

Microscopic

Features:

• Cribriform architecture.
• Scant cytoplasm.
• Carrot-shaped nucleus.
• Hyaline stroma.

Images: Adenoid cystic carcinoma - Mod. Pathol.

Memory device:

• AdCC - mostly DNA (scant cytoplasm), distinct nucleus (carrot-shaped).

IHC

Features:

• CD117 +ve.
• Cyclin D1 +ve.

Salivary duct carcinoma

Needs work.

• Malignant counterpart of salivary duct adenoma.

Polymorphous low-grade adenocarcinoma

• Abbreviated PLGA.

General

• Almost exclusively in the oral cavity.
  • Classically found in the palate -- 60% of PLGAs in palate.
• Tumour of the minor salivary glands.
• Always a low-grade tumour - by definition.
• Female:male ~= 2:1.
• Older people ~50-70 years old.

Microscopy

Features:

• Cytologically monotonous (uniform) with variable architecture - key feature.
  • Architecture: often small nests, may be targetoid.
• Nucleus: ovoid & small with small nucleoli.
• Indistinct cell borders.
• Eosinophilic cytoplasm.

DDx:

• Adenoid cystic carcinoma.
• Pleomorphic adenoma.

Images:

• PLGA - very low mag. (WC).
• PLGA - high mag. (WC).

IHC

• S100 +ve, CK +ve, vimentin +ve.
• GFAP +ve/-ve.
• BCL2 +ve/-ve.
• Generally negative for myoepithelial markers (calponin, actin) - useful if negative.

Carcinoma ex pleomorphic adenoma

• Abbreviated Ca ex PA.

General

Definition:

• Malignant transformation of a pleomorphic adenoma.

Diagnosis (either 1 or 2):

1. History of a pleomorphic adenoma at the same site.
2. Features of a pleomorphic adenoma and a carcinoma.

Epidemiology:

• Rare.

Microscopy

Features:

• Cells with cytologic features of malignancy.
• Architecture (any of the following):
  • Glands.
  • Nests.
  • Single cells (may be subtle).

Architectural patterns:

• Ductal carcinoma NOS (arising from ductal cells) - most common pattern for Ca ex PA.
• Myoepithelial cacinoma NOS (arising from myoepithelial cells).
• "Named carcinoma":
  • Salivary duct carcinoma - second most common pattern for Ca ex PA.
  • Mucoepidermoid carcinoma.
  • Adenoid cystic carcinoma.

Note:

• Often adenocarcinoma-like.
• Myoepithelial cells may be clear cells. (???)

Subclassification

1. Non-invasive AKA intracapsular AKA in situ.
2. Minimally invasive <1.5 mm beyond the capsule.
3. Widely invasive >=1.5 mm beyond the capsule.

Sebaceous carcinoma

• Arises from sebaceous glands
• Sebaceous glands are serous glands and clear on H&E.

See also

• Head and neck pathology.
• Thyroid gland.
• Breast.
• Head and neck cytopathology.