Basic Salivary Gland Pathology. Agenda. Salivary Glands Background. Common benign lesions. Common Malignancies. Major salivary glands

Transcription

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 1 Agenda Common benign lesions Warthins tumor Pleomorphic adenoma Basal cell adenoma Myoepithelioma Common Malignancies Mucoepidermoid carcinoma variants Adenoid cystic carcinoma Carcinoma ex pleomorphic adenoma Salivary duct carcinoma 2 Salivary Glands Background Major salivary glands Parotid Submandibular gland Sublingual gland Minor salivary glands Throughout respiratory tract 3 1

2 Parotid Gland Submandibular Gland 4 4 Warthin Tumor 5 Warthin Tumor Incidence Related to smoking Can be bilateral Parotid, minor salivary glands, rests Clinical Mass lesion, benign 6 2

3 Warthin Tumor Gross Cystic lesion Fluid resembles motor oil Histology Oncocytic epithelium Papillary growth Lymphoid stroma Germinal centers 7 Warthin tumor 8 Warthin tumor 9 3

4 Pleomorphic Adenoma 10 Pleomorphic Adenoma Incidence Most common benign tumor Clinical Mass lesion Surgical treatment with margins 11 Pleomorphic Adenoma Gross Bosselated Chondroid Histology: Mixed Stromal: chondroid, hyalinized, myxoid Epithelial cells: ducts and tubules Myoepithelial cells 12 4

5 Pleomorphic adenoma 13 Pleomorphic adenoma 14 Pleomorphic adenoma 15 5

6 Pleomorphic Adenoma IHC Myoepithelial markers positive (GFAP) Ki-67: low proliferative rate (<5%) Prognosis Local recurrence: 5-10% Malignant degeneration: 5%-25% Carcimoma ex pleomorphic adenoma 16 Recurrent Pleomorphic adenoma Recurrent Pleomorphic adenoma 18 6

7 Pleomorphic Adenoma Differential diagnosis Basal cell adenoma Unique morphology Myoepithelioma No chondroid, no tubules 19 Basal Cell Adenoma Histology: Solid, trabecular, tubular Two cell types Small, dark nuclei with pallisading Larger, lighter nuclei, islands and cords Distinct basement membrane No chondromyxoid stroma Immunohistochemistry Epithelial and myoepithelial cells Positive for respective markers GFAP negative 20 Basal cell adenoma 21 7

8 Basal cell adenoma 22 Basal Cell Adenoma Histology Membranous type (Dermal Analogue tumor) Similar to dermal cylindroma ( turban tumor ) Epithelial islands Peripheral small basophilic palisading cells Central large cells, squamoid whorls Extracellular hyaline material 23 Basal cell adenoma 8

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 Myoepithelial cells Spindle, epithelioid, clear, mixed 27 9

10 Myoepithelioma, clear cells 28 Myoepithelioma, S Myoepithelioma IHC Positive for myoepithelial markers Variable cytokeratin staining Negative for CEA 30 10

11 Myoepithelial Cells Morphologically diverse Variable immunohistochemical stains Myoepithelial Markers Usually positive Positive or negative Usually negative AE1-3 SMA EMA Vimentin SMMH CEA S100 CK14 CK7 Calponin Cam5.2 B72.3 P63 CK5/6 Desmin CK903 Maspin HHF-35 CD10 GFAP 33 11

12 Myoepithelioma Differential diagnosis Myoepithelial carcinoma Invasive Pleomorphism, mitoses, atypia Clear cell hyalinizing ing carcinoma CEA positive 34 Agenda Common benign lesions Warthins tumor Pleomorphic adenoma Basal cell adenoma Myoepithelioma Common Malignancies Mucoepidermoid carcinoma variants Adenoid cystic carcinoma Carcinoma ex pleomorphic adenoma Salivary duct carcinoma 35 Mucoepidermoid Carcinoma Incidence Most common malignant salivary gland tumor (children and adults) Major and minor salivary glands Peak incidence id 5th to 6th decadesd Clinical Mass lesion Surgical treatment with margins 36 12

13 Histology Mucus cells and cysts Epidermoid cells Intermediate cells 37 Mucus cells and Cysts 38 Mucus cells and Cysts 13

14 I M E Cell types 40 Tumor Grading Tumor specific grading Defined features General grading Resemblance to normal Nuclear features Grade by definition 41 Salivary Gland Tumors Tumor specific General grading Grading by Definition Mucoepidermoid Oncocytic carcinoma Salivary Duct carcinoma Adenoid cystic carcinoma Adenocarcinoma, NOS Polymorphous low-grade No Grading Acinic cell carcinoma 42 14

15 Mucoepidermoid Translocation t(11;19)(q21;p13) MECT1-MAML2 MECT1: also known as CRTC1, TORC1, WAMTP1 camp response element binding protein (CREB) regulated transcriptional coactivator MAML2: Notch coactivator Translocation activates Notch target genes independent of Notch ligands 43 MECT-MAML2 Translocation Courtesy of Dr. Sanja Dacic University of Pittsburgh 44 Adenoid Cystic Carcinoma Incidence Relatively common Any salivary gland location Clinical Mass lesion Nerve palsies Surgical treatment with margins 45 15

16 Adenoid Cystic Carcinoma Histology Tubular, cribriform, solid patterns Solid has worse behavior Perineural invasion Nuclei small, dark, and angulated 46 Adenoid cystic carcinoma, cribriform 47 Adenoid cystic carcinoma, tubular 48 16

17 Adenoid cystic carcinoma, solid 49 Adenoid cystic carcinoma 50 17

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 Histology Low grade areas and high grade areas Epithelial predominance Necrosis Vascular invasion 54 18

19 High Grade Transformation 60% 45% 45% 40% 20% 10% 0% Alive & Well Recurrence Death from disease Seethala RR, AJSP 3(11):1683, Adenoid cystic carcinoma with high grade transformation Adenoid cystic carcinoma with high grade transformation 57 19

20 Adenoid cystic carcinoma high grade transformation Solid adenoid cystic carcinoma High Grade Transformation Immunohistochemistry Loss of myoepithelial component SMA, p63, calponin negative All cells stain with cytokeratin Strong p53 staining High proliferative rate (Ki-67) 59 AE1-3 20

21 p63 Ki-67 p53 21

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 Highly expressed in immature proliferating cells, and down-regulated as cells become more differentiated NFIB: nuclear factor 1B Deregulation mechanism is not completely understood 64 Translocation in ACC 100% 80% 60% 40% 20% Translocation No translocation Abnormal 0% Adenoid cystic Other salivary tumors West R, Am J Surg Pathol 2011;35: Carcinoma ex Pleomorphic Adenoma 66 22

23 Carcinoma ex Pleomorphic Adenoma Incidence: Relatively rare Etiology: Arises from PA Clinical Long standing mass with recent rapid enlargement History of PA Resected incompletely Recurrent 67 Carcinoma ex Pleomorphic Adenoma Histology Residual pleomorphic adenoma Carcinoma component Specific salivary carcinoma (any type) Adenocarcinoma, NOS IHC Specific to type of carcinoma 68 Carcinoma ex pleomorphic adenoma 69 23

24 Carcinoma ex pleomorphic adenoma 70 Salivary Duct Carcinoma 71 Salivary Duct Carcinoma Incidence: Rare Clinical Aggressive clinical course Metastases at presentation Surgical treatment Chemotherapy & radiation 72 24

25 Salivary Duct Adenocarcinoma Histology Resembles breast carcinoma Cribriform, micropapillary, solid Comedo-type necrosis Micro and macro calcifications Stromal and perineural invasion 73 Salivary duct carcinoma 74 Salivary duct carcinoma 75 25

26 Salivary duct carcinoma 76 Salivary Duct Carcinoma IHC Androgen receptor positive HER2/neu positive PSA occasionally positive ER/PR usually negative 77 SDC, HER2/NEU SDC, Androgen 78 26

27 Summary Common benign lesions Warthins tumor Pleomorphic adenoma Basal cell adenoma Myoepithelioma Common Malignancies Mucoepidermoid carcinoma variants Adenoid cystic carcinoma Carcinoma ex pleomorphic adenoma Salivary duct carcinoma 79 27