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1 Basic Salivary Gland Pathology 1 Basic Salivary Gland Pathology Jennifer L. Hunt, MD, MEd Aubrey J. Hough Jr, MD, Endowed Professor of Pathology Chair of Pathology and Laboratory Medicine University of Arkansas for Medical Sciences [email protected] Agenda Common benign lesions Warthins tumor Pleomorphic adenoma Basal cell adenoma 2 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 3 Minor salivary glands Throughout respiratory tract

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Page 1: Basic Salivary Gland Pathology - c.ymcdn.com · Basic Salivary Gland Pathology 1 ... • Histology • Low grade areas and high grade areas • Epithelial predominance • Necrosis

1

Basic Salivary Gland Pathology

1

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

[email protected]

Agenda

• Common benign lesions• Warthins tumor

• Pleomorphic adenoma

• Basal cell adenoma

2

• 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

3

• Minor salivary glands• Throughout respiratory tract

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4Parotid Gland Submandibular Gland

4

Warthin Tumor

5

Warthin Tumor

• Incidence• Related to smoking

• Can be bilateral

• Parotid, minor salivary glands, rests

6

• Clinical• Mass lesion, benign

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Warthin Tumor

• Gross• Cystic lesion

• Fluid resembles motor oil

• Histology

7

• Oncocytic epithelium

• Papillary growth

• Lymphoid stroma• Germinal centers

8Warthin tumor

9Warthin tumor

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Pleomorphic Adenoma

10

Pleomorphic Adenoma

• Incidence• Most common benign tumor

• Clinical• Mass lesion

11

• Surgical treatment with margins

Pleomorphic Adenoma

• Gross• Bosselated

• Chondroid

• Histology: Mixed

12

• 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

16

• 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

19

• 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

20

• 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

23

• Peripheral small basophilic palisading cells

• Central large cells, squamoid whorls

• Extracellular hyaline material

Basal cell adenoma

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Myoepithelioma

25

Myoepithelioma

• Incidence• Probably under-recognized

• Clinical• Mass lesion

26

Myoepithelioma

• Histology: Pure myoepithelial cells• No ducts/tubules

• No chondroid matrix

• Hyalinized and myxoid matrix

27

• 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

30

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Myoepithelial Cells

• Morphologically diverse

• Variable immunohistochemical stains

31

32

Myoepithelial Markers

Usually positive Positive or negative Usually negative

AE1-3 SMA EMA

Vimentin SMMH CEA

S100 CK14 CK7

33

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

34

• Clear cell hyalinizing carcinoma• CEA positive

Agenda

• Common benign lesions• Warthins tumor

• Pleomorphic adenoma

• Basal cell adenoma

35

• 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

36

• Peak incidence 5th to 6th decades

• Clinical• Mass lesion

• Surgical treatment with margins

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Histology

• Mucus cells and cysts

• Epidermoid cells

37

• 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

41

• Resemblance to normal• Nuclear features

• Grade by definition

Salivary Gland Tumors

Tumor specific General grading Grading by Definition

Mucoepidermoid Oncocytic i

Salivary Duct i

42

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

43

• cAMP response element binding protein (CREB) regulated transcriptional coactivator

• MAML2: Notch coactivator

• Translocation activates Notch target genes independent of Notch ligands

MECT-MAML2 Translocation

44

Courtesy of Dr. Sanja DacicUniversity of Pittsburgh

Adenoid Cystic Carcinoma

• Incidence• Relatively common

• Any salivary gland location

• Clinical

45

• 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

46

• 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

53

High Grade Transformation

• Clinical• Tumor progression with aggressive disease

• May have clinical history of adenoid cystic carcinoma

Hi t l

54

• Histology• Low grade areas and high grade areas

• Epithelial predominance

• Necrosis

• Vascular invasion

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High Grade Transformation

40%

60%45% 45%

55

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

59

• 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

64

• 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

65

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

66

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Carcinoma ex Pleomorphic Adenoma

• Incidence: Relatively rare

• Etiology: Arises from PA

• Clinical• Long standing mass with recent rapid

67

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

68

• Adenocarcinoma, NOS

• IHC• Specific to type of carcinoma

69Carcinoma ex pleomorphic adenoma

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70Carcinoma ex pleomorphic adenoma

Salivary Duct Carcinoma

71

Salivary Duct Carcinoma

• Incidence: Rare

• Clinical• Aggressive clinical course

• Metastases at presentation

72

• 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

73

• 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

77

• ER/PR usually negative

78SDC, HER2/NEU SDC, Androgen

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Summary

• Common benign lesions• Warthins tumor

• Pleomorphic adenoma

• Basal cell adenoma

79

• Myoepithelioma

• Common Malignancies• Mucoepidermoid carcinoma variants

• Adenoid cystic carcinoma

• Carcinoma ex pleomorphic adenoma

• Salivary duct carcinoma