Disclosure Disease Claudia F.E. Kirsch MD Professor of Neuroradiology & Otolaryngology Consultant Primal Division Chief Neuroimaging Service Line Northwell Health Zucker Hofstra School of Medicine at Northwell Pictures - Informa North Shore University Hospital-LIJ RTOG Foundation 3504 Clinicatrials.gov NCT#TBD Funding Research Advisory Committee Northwell Health

9/29/18

Acknowledgments Salivation

Major functions

Dr. Shatzkes

When it goes wrong – how to work it up? Salivation

SSALIVA Patient presents to ENT Difficulty salivating A How do you work this up? What imaging study ? L I In order to answer this Need to understand V Salivary glands - A Salivation Salivation

S cience , Start-embryology, Stones Major functions Buffer – bicarbonate phosphate proteins A natomy Maintance oral cavity microbes L ump- mass r/o tumor I nfx, inflammatory, immunosup. V iew salivary tissue - imaging A lgorithm w/u salivary pathology

Salivation Salivation

Major functions Major functions Buffer – bicarbonate phosphate proteins Buffer – bicarbonate phosphate proteins Maintance oral cavity microbes Maintance oral cavity microbes

Bolus formation – mucins + water Bolus formation – mucins + water Taste– gustin + water Taste– gustin + water Digestion – Digestion – amylase + protease+ lipase amylase + protease+ lipase

Salivary embryology - Parotid Salivary embryology

Parotid appears 4th week as S tart to form Ectodermal furrow Epithelial buds are located near Labial commissures primitive mouth Buds grow posteriorly to otic placodes branching into solid cords w/ round ends near

Buds may penetrate lymph nodes Salivary embryology Salivary embryology

Epithelial pouch oral cavity - 6th – 8th week S tart to form Intergrowth adj ectomesenchyme Submandibular Parotid originates near corner It’s connective tissue from neural crest Stomodaeum 6th week IU Parenchyme -> secretion from Parotid Submandibular - floor of mouth Proliferating oral 6th week IU Ectodermal – parotid & Sublingual – lateral to SMG minor salivary gl. 8th week IU Transvaginal US – transverse Endodermal – Submandibular Fetal salivary glands 15.3 wk fetus Minor glands develop 12th wk IU Sublingual gl. Incl von Ebner gland

Odeh M. et al. Normal fetal salivary glands 14-16 weeks gestation as observed by transvaginal Ultrasound, US Obst Gyen 2010; 35:395-397

Similar anlage to breast Start –Embryology

S imilarities to breast tissue

Emmerson E, Knox SM. Salivary gland stem cells: A review of development, Coordination of epithelial branching and salivary gland lumen formation by Wnt and FGF signals. regeneration and cancer. Genesis. 2018 May;56(5): PMID: 29663717 Citation data: Developmental biology, ISSN: 1095-564X, Vol: 358, Issue: 1, Page: 156-67 Publication Year: 2011

Salivary Science Similar anlage to breast Secrete 1200-1500 ml/day

imilarities to breast tissue S Increased risk of parotid Science saliva Tumors in patients Enzymes With breast CA Amylase .5% solid Genetic linkage Maltase Lingual lipase 99.5% water BRAC1/BRAC2 Lysozymes Carbonic anhydrase Kallikrein Peroxidase Amylase Lactoferrin

20% Parotid

65-70% submandibular

Emmerson E, Knox SM. Salivary gland stem cells: A review of development, Plus - regeneration and cancer. Genesis. 2018 May;56(5): PMID: 29663717 Proteins, blood group antigens, amino acids Modern Pathology ISSN 1530-0285 (online) hormones, uric acids, water soluble vitamens Salivary proteomics Salivary Science & Stones

Stones Statherins Saliva Acinar cells Parotid & SMG .5% solid Early tumor detection Prevent precipitation Crystallization 99.5% water P53 – inactivation p53 gene mutation Ca+ phosphate leads to tumor In ductal fluid Elevated salivary defensin-1in oral SCC & serum levels SCC related antigen

Salivary Proteome Knowledge Base pH – saliva ceases saturated w/ Ca & phosphate – “critical pH” Usually 5.5 High Salivary Ca+ & Phos – Remineralization Low Ca+, Phosph - Dimineralization http://hspp.dent.ucla.edu/cgi-bin/spkbcgi-bin/main.cgi Salivary Diagnostics D. Wong 1st Edition Oral Histology & Embryology ,, Orban’s 12th Ed

Stones -

Anatomy Major Glands Parotid Submandibular Sublingual

Minor Glands Labial, Buccal, Palatine Glossopalatine, Lingual Blandin & Nuhn, Von Ebner’s Carmalt’s SECRETION- Serous, Mucous, Mixed

Anatomy Anatomy – Minor Salivary Glands

natomy natomy A A Labial & Buccal – & cheek Major Glands Glossopalatine – isthmus glossopalatine fold Parotid Submandibular Palatine glands – lamina propria posterolateral Sublingual hard , submucosa & uvula Minor Glands Labial, Buccal, Palatine Glossopalatine, Lingual Key Spaces & places Blandin & Nuhn, Von Ebner’s Carmalt’s

SECRETION- Serous, Mucous, Mixed Anatomy – Minor Salivary Glands Lumps – Tumors, Pseudomass, Cysts

WHO classification salivary tumors- NEW 2017 Immunohistochemistry (IHC) Lingual Fluorescence in situ hybridization Anterior Apex Tongue– New Variants Glands of Blandin & Nuhn Mammary analogue secretory carcinoma - MASC Posterior Lingual mucous – Sclerosing Polycystic Adenosis lat/post vallete papilla Posterior lingual serous - Von Ebner’s btw tongue muscles below vallete p. Polymorphous (previously Polymorphous Low grade adenocarcinoma PGLA)

Lumps – Tumors, Pseudomass, Cysts Pleiomorphic Adenoma

• Cystic • Solid 1. Lymphoepithelial cysts of HIV Single 2. 1st branchial cleft cyst 1. 3. Abscess 2. Mucoepidermoid 3. Adenoid cystic tumor 4. Schwannoma 5. Ped: Multiple, Bilateral 1. Hemangioma 1. Warthin 2. Lymphangioma 2. Lymphoma 3. Rhabomyosarcoma 3. Met 4. LN 5. Sjögren’s, Sarcoid

Pleiomorphic Adenoma Mucoepidermoid Ca

Always has capsule MUST be well define! • Infiltrative!! Superficial VS deep lobe!! Adenoid cystic carcinoma

• Infiltrative!!

0.77 • PNS!

Scans 1.5 T vs 3 T 1.5 Tesla

60 year old male liked sunshine - can’t move left side of his face

Biopsy in front of left ear 1.5 T 3.0 T skin cancer

61 y/o M slowly enlarging Biopsy inv basaloid left sided neck mass, init Rx SCCA w/ PNI w/ Abx

1.5 Tesla MRI 1.5 vs 3 Tesla!

1.5 T MRI - unremarkable 3.0 T MRI - linear 1.5 T MRI 1.5 T MRI - normal enhancement along nerve branches 3 Tesla MRI 1.5 vs 3 T images

• 3T MRI demonstrating PNS

• Patient underwent surgery

Pathology showed tumor “hitchhiking” on nerve perineural invasion!

Another Case Another Case

53 y/o patient Scan 1.5 T - read as normal 3 Tesla

PNS on 3 T! Immunosuppression/ Inflammatory

Perineural invasion in squamous cell carcinoma detected by high- field 3.0-T MRI, a case series.

S. McClurg, MD, P. Bockenstedt, B. Welling, MD, PhD, C.Kirsch, MD

Combined Otolaryngology Spring Meetings (COSM ) April 18- 22, 2012 - - pub in submission

HIV lymphoepithelial cysts Stones - Infection Stones - Infection Viewing the Gland – CT Viewing the Gland – MRI

CT – what CT its good for

When to use

MRI Sialography

Viewing the Gland – MRI Viewing Salivary Glands

Imaging Modalities

US

Nuclear Medicine

Plain films

Algorithm- Good rules of thumb Algorithm Imaging Findings

Salivary Rules of thumb Mass Diff dx Not Painful Painful Systemic Smaller gland – more serious -tumor Tumor ** Stone Sick Swelling Sick- viral , Sarcoid - CT Lymph Node Skin thickening SMG/SLG Parotid bacteria, TB, Sjogrens Cyst Enlarged nodes BMT –Pleiomorph Ad BMT –Most SMG – CT candida, fungal Gran. PAG, IgG4 Facial palsy Benign most common common R/O – stone Cat-scratch fever Sialography -MRI R/o tumor 2nd Most common Mucoepidermoidm 1st - Mumps Adenoid cystic 80 % rule Malig most common Malig most common - PNS Multiple FNA- 80% Parotids Single FISH New WHO BMT 80% Benign Mixed Tumor smoker warrents 2017 High T2 Muc ret cyst, look Warthins -tail (Pleiomorphic Adenoma) 1st bran clef., Skin/derm Ca- LNs sialocele, Lymphoma – PNS!! Immunosu. Lym epith cysts TUMOR- MRI r/o PNS Rare disorders Multiple Masses – Kimura dz – eosinophils, lymphoid prolif – Asian pts Warthins Nucs +uptake tech pertechnate Amyloid, toxoplasmosis, actinomycosis Warthin’s or LN US – superficial gland- tumor incr. vascular. Hematogenous mets (thyroid, renal, scalp)

**Some tumors gnawing dull pain, or perineural involvement Summary Review Back to our patient Key Take Home Points

S cience , Start-embryology, Stones A natomy L ump- mass r/o tumor I nfx, inflammatory, immunosup. V iew salivary tissue - imaging A lgorithm w/u salivary pathology

Radiographic images – Dx!

Thank-you – Welcome any ?