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Basic Salivary Gland Pathology
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Basic Salivary Gland PathologyJennifer L. Hunt, MD, MEd
Aubrey J. Hough Jr, MD, Endowed Professor of PathologyChair of Pathology and Laboratory MedicineUniversity of Arkansas for Medical Sciences
Agenda
• Common benign lesions• Warthins tumor
• Pleomorphic adenoma
• Basal cell adenoma
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• Myoepithelioma
• Common Malignancies• Mucoepidermoid carcinoma variants
• Adenoid cystic carcinoma
• Carcinoma ex pleomorphic adenoma
• Salivary duct carcinoma
Salivary Glands Background
• Major salivary glands• Parotid
• Submandibular gland
• Sublingual gland
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• Minor salivary glands• Throughout respiratory tract
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4Parotid Gland Submandibular Gland
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Warthin Tumor
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Warthin Tumor
• Incidence• Related to smoking
• Can be bilateral
• Parotid, minor salivary glands, rests
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• Clinical• Mass lesion, benign
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Warthin Tumor
• Gross• Cystic lesion
• Fluid resembles motor oil
• Histology
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• Oncocytic epithelium
• Papillary growth
• Lymphoid stroma• Germinal centers
8Warthin tumor
9Warthin tumor
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Pleomorphic Adenoma
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Pleomorphic Adenoma
• Incidence• Most common benign tumor
• Clinical• Mass lesion
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• Surgical treatment with margins
Pleomorphic Adenoma
• Gross• Bosselated
• Chondroid
• Histology: Mixed
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• Stromal: chondroid, hyalinized, myxoid
• Epithelial cells: ducts and tubules
• Myoepithelial cells
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13Pleomorphic adenoma
14Pleomorphic adenoma
15Pleomorphic adenoma
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Pleomorphic Adenoma
• IHC• Myoepithelial markers positive (GFAP)
• Ki-67: low proliferative rate (<5%)
• Prognosis
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• Local recurrence: 5-10%
• Malignant degeneration: 5%-25%• “Carcimoma ex pleomorphic adenoma”
Recurrent Pleomorphic adenoma
18Recurrent Pleomorphic adenoma
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Pleomorphic Adenoma
• Differential diagnosis• Basal cell adenoma
• Unique morphology
• Myoepithelioma N h d id t b l
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• No chondroid, no tubules
Basal Cell Adenoma
• Histology: Solid, trabecular, tubular• Two cell types
• Small, dark nuclei with pallisading
• Larger, lighter nuclei, islands and cords
Distinct basement membrane
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• Distinct basement membrane
• No chondromyxoid stroma
• Immunohistochemistry• Epithelial and myoepithelial cells
• Positive for respective markers
• GFAP negative
21Basal cell adenoma
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22Basal cell adenoma
Basal Cell Adenoma
• Histology• Membranous type (Dermal Analogue tumor)
• Similar to dermal cylindroma (“turban tumor”)
• Epithelial islands
• Peripheral small basophilic palisading cells
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• Peripheral small basophilic palisading cells
• Central large cells, squamoid whorls
• Extracellular hyaline material
Basal cell adenoma
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Myoepithelioma
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Myoepithelioma
• Incidence• Probably under-recognized
• Clinical• Mass lesion
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Myoepithelioma
• Histology: Pure myoepithelial cells• No ducts/tubules
• No chondroid matrix
• Hyalinized and myxoid matrix
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• Myoepithelial cells• Spindle, epithelioid, clear, mixed
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28Myoepithelioma, clear cells
29Myoepithelioma, S100
Myoepithelioma
• IHC• Positive for myoepithelial markers
• Variable cytokeratin staining
• Negative for CEA
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Myoepithelial Cells
• Morphologically diverse
• Variable immunohistochemical stains
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Myoepithelial Markers
Usually positive Positive or negative Usually negative
AE1-3 SMA EMA
Vimentin SMMH CEA
S100 CK14 CK7
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Calponin Cam5.2 B72.3
P63 CK5/6 Desmin
CK903 Maspin HHF-35
CD10 GFAP
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Myoepithelioma
• Differential diagnosis• Myoepithelial carcinoma
• Invasive
• Pleomorphism, mitoses, atypia
Clear cell h alini ing carcinoma
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• Clear cell hyalinizing carcinoma• CEA positive
Agenda
• Common benign lesions• Warthins tumor
• Pleomorphic adenoma
• Basal cell adenoma
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• Myoepithelioma
• Common Malignancies• Mucoepidermoid carcinoma variants
• Adenoid cystic carcinoma
• Carcinoma ex pleomorphic adenoma
• Salivary duct carcinoma
Mucoepidermoid Carcinoma
• Incidence• Most common malignant salivary gland tumor
(children and adults)
• Major and minor salivary glands
P k i id 5th t 6th d d
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• Peak incidence 5th to 6th decades
• Clinical• Mass lesion
• Surgical treatment with margins
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Histology
• Mucus cells and cysts
• Epidermoid cells
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• Intermediate cells
38Mucus cells and Cysts
Mucus cells and Cysts
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E
40Cell types
I M
E
Tumor Grading
• Tumor specific grading• Defined features
• General gradingR bl t l
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• Resemblance to normal• Nuclear features
• Grade by definition
Salivary Gland Tumors
Tumor specific General grading Grading by Definition
Mucoepidermoid Oncocytic i
Salivary Duct i
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carcinoma carcinoma
Adenoid cystic carcinoma
Adenocarcinoma, NOS
Polymorphous low-grade
No Grading
Acinic cell carcinoma
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Mucoepidermoid Translocation
• t(11;19)(q21;p13)
• MECT1-MAML2• MECT1: also known as CRTC1, TORC1,
WAMTP1
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• cAMP response element binding protein (CREB) regulated transcriptional coactivator
• MAML2: Notch coactivator
• Translocation activates Notch target genes independent of Notch ligands
MECT-MAML2 Translocation
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Courtesy of Dr. Sanja DacicUniversity of Pittsburgh
Adenoid Cystic Carcinoma
• Incidence• Relatively common
• Any salivary gland location
• Clinical
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• Mass lesion
• Nerve palsies
• Surgical treatment with margins
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Adenoid Cystic Carcinoma
• Histology• Tubular, cribriform, solid patterns
• Solid has worse behavior
• Perineural invasion
N l i ll d k d l t d
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• Nuclei small, dark, and angulated
47Adenoid cystic carcinoma, cribriform
48Adenoid cystic carcinoma, tubular
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49Adenoid cystic carcinoma, solid
50Adenoid cystic carcinoma
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Adenoid Cystic Carcinoma, perineural invasion
Adenoid Cystic Carcinoma
• IHC• CKIT and bcl-2 positive
• Epithelial cells: cytokeratins
• Myoepithelial cells: p63, SMA, CK5/6
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High Grade Transformation
• Clinical• Tumor progression with aggressive disease
• May have clinical history of adenoid cystic carcinoma
Hi t l
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• Histology• Low grade areas and high grade areas
• Epithelial predominance
• Necrosis
• Vascular invasion
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High Grade Transformation
40%
60%45% 45%
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0%
20%
Alive & Well Recurrence Death from disease
10%
Seethala RR, AJSP 3(11):1683, 2007
Adenoid cystic carcinoma with high grade transformation
57Adenoid cystic carcinoma with high grade transformation
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Solid adenoid cystic carcinoma
Adenoid cystic carcinoma high grade transformation
High Grade Transformation
• Immunohistochemistry• Loss of myoepithelial component
• SMA, p63, calponin negative
• All cells stain with cytokeratin
Strong p53 staining
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• Strong p53 staining
• High proliferative rate (Ki-67)
AE1-3
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p63
Ki-67
p53
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Adenoid Cystic Translocation
• t(6;9) (q22-23; p23-24)
• MYB-NFIB• MYB
• Transcription factor with an important role in cell proliferation, apoptosis, and differentiation
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• Highly expressed in immature proliferating cells, and down-regulated as cells become more differentiated
• NFIB: nuclear factor 1B
• Deregulation mechanism is not completely understood
Translocation in ACC
60%
80%
100%
Translocation
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0%
20%
40%
Adenoid cystic Other salivary tumors
Translocation
No translocation
Abnormal
West R, Am J Surg Pathol 2011;35:92–99
Carcinoma ex Pleomorphic Adenoma
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Carcinoma ex Pleomorphic Adenoma
• Incidence: Relatively rare
• Etiology: Arises from PA
• Clinical• Long standing mass with recent rapid
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g g penlargement
• History of PA • Resected incompletely
• Recurrent
Carcinoma ex Pleomorphic Adenoma
• Histology• Residual pleomorphic adenoma
• Carcinoma component• Specific salivary carcinoma (any type)
Ad i NOS
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• Adenocarcinoma, NOS
• IHC• Specific to type of carcinoma
69Carcinoma ex pleomorphic adenoma
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70Carcinoma ex pleomorphic adenoma
Salivary Duct Carcinoma
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Salivary Duct Carcinoma
• Incidence: Rare
• Clinical• Aggressive clinical course
• Metastases at presentation
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• Surgical treatment
• Chemotherapy & radiation
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Salivary Duct Adenocarcinoma
• Histology• Resembles breast carcinoma
• Cribriform, micropapillary, solid
• Comedo-type necrosis
• Micro and macro calcifications
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• Micro and macro calcifications
• Stromal and perineural invasion
74Salivary duct carcinoma
75Salivary duct carcinoma
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76Salivary duct carcinoma
Salivary Duct Carcinoma
• IHC• Androgen receptor positive
• HER2/neu positive
• PSA occasionally positive
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• ER/PR usually negative
78SDC, HER2/NEU SDC, Androgen
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Summary
• Common benign lesions• Warthins tumor
• Pleomorphic adenoma
• Basal cell adenoma
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• Myoepithelioma
• Common Malignancies• Mucoepidermoid carcinoma variants
• Adenoid cystic carcinoma
• Carcinoma ex pleomorphic adenoma
• Salivary duct carcinoma
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