Basic Salivary Gland Pathology Basic Salivary Gland Pathology 1 Basic Salivary Gland Pathology Jennifer

  • View
    2

  • Download
    0

Embed Size (px)

Text of Basic Salivary Gland Pathology Basic Salivary Gland Pathology 1 Basic Salivary Gland Pathology...

  • 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

    jhunt2@uams.edu

    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

  • 2

    4 Parotid 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

  • 3

    Warthin Tumor

    • Gross • Cystic lesion • Fluid resembles motor oil

    • Histology

    7

    • Oncocytic epithelium • Papillary growth • Lymphoid stroma

    • Germinal centers

    8 Warthin tumor

    9 Warthin tumor

  • 4

    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

  • 5

    13 Pleomorphic adenoma

    14 Pleomorphic adenoma

    15 Pleomorphic adenoma

  • 6

    Pleomorphic Adenoma

    • IHC • Myoepithelial markers positive (GFAP) • Ki-67: low proliferative rate (

  • 7

    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

  • 8

    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

  • 9

    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

  • 10

    28 Myoepithelioma, clear cells

    29 Myoepithelioma, S100

    Myoepithelioma

    • IHC • Positive for myoepithelial markers • Variable cytokeratin staining • Negative for CEA

    30

  • 11

    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

  • 12

    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

  • 13

    Histology

    • Mucus cells and cysts

    • Epidermoid cells

    37

    • Intermediate cells

    38Mucus cells and Cysts

    Mucus cells and Cysts

  • 14

    E

    40Cell types

    I M

    E

    Tumor Grading • Tumor specific grading

    • Defined features

    • General grading R 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

  • 15

    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 Dacic University of Pittsburgh

    Adenoid Cystic Carcinoma

    • Incidence • Relatively common • Any salivary gland location

    • Clinical

    45

    • Mass lesion • Nerve palsies • Surgical treatment with margins

  • 16

    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

  • 17

    49Adenoid cystic carcinoma, solid

    50Adenoid cystic carcinoma

  • 18

    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

  • 19

    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

  • 20

    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

  • 21

    p63

    Ki-67

    p53

  • 22

    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

  • 23

    Carcinoma ex Pleomorphic Adenoma

    • Incidence: Relatively rare • Etiology: Arises from PA • Clinical

    • Long standing mass with recent rapid

    67

    g g p enlargement

    • History of PA • Resected incompletely • Recurrent

    Carcinoma ex Pleomorphic Adenoma

    • Histology • Residual pleomorphic adenoma • Carcinoma component

    • Specific salivary carcinoma (any type) Ad i NOS