Squamous Cells

1. Squamous Cells Physiology: Why is it important to Speech Pathologists? Presented by Kelly George

2. Outline • Physiology • What can go wrong • Signs/Symptoms • What these things cause • What do we as Speech Pathologists

3. Squamous Cells • Squamous refers to shape – flat except for nucleus making it bulge a little • Do not receive direct blood supply • Oxygen and nutrients travel through other cells to reach squamous layers • These cells renew frequently

4. Types of Squamous (flat) Cells • Simple – cells are flat, scale-like, in a single layer supported by and underlying basement membrane. • Where – mesothelium that lines all body cavities and covers all organs, and the endothelium that makes up the walls of the capillaries and the inner lining of blood vessels and lung air sacs • Function - protect • Membrane - permeable

5. Types (cont.) • Stratified – Flat & 2 or more layers • Where – • Non-keratinizing = wet surfaces receiving significant wear and tear • Inside mouth, esophagus, and anal canal • Keratinizing = same morphology but outer layer undergoes change to tough non-living layer of keratin • Function- protect • Membrane - permeable

7. Vocal Fold Epithelium • Stratified squamous • Yes flat, but has microridges to increase surface area • Desmosomes help adhesion in deeper layers, lesson closer to the surface to allow for exfoliation • Complete with nucleus, nucleolus, Golgi Apparatus, rough endoplasmic reticulum, lysosomes, mitochondria, and tonofiliments that provide rigidity and resilience

8. Vocal Fold: Basement Membrane • Transitional area between squamous and lamina propria • Secures the two layers together • Disease: epidermolysis • Genetic basis • Leads to incomplete formation of anchoring fibers • Fatal – skin can’t stay on body • Some cancers secrete enzymes that “eat away” at the basement membrane, taking away its natural barrier for tumor growth.

9. Basil Cell Layer

10. Vocal Fold: Lamina Propria • Ground substance • Contains fluid and insterstitial matrix • Under normal conditions, fluid is limited • Tissue injury causes accumulation of fluid from capillaries - inflammation • Fibroblasts • Cells that synthesis most extracellular material • Collagen, elastin, and ground substance • Elastic fibers • Run parallel to vocal fold edge • Can stretch to approx. 2 x natural length and return to natural shape

11. Vocal Fold: Lamina Propria (cont.) • Collagenous fibers • Also run parallel to vocal fold edge • Gives resilience • Fibronectin • Adhesive functions – made of protein • Important in wound healing • Following injury, fibronectin is deposited on damaged collagen serving as a scaffold for the tissue – lots of fibronectin in the lamina propria indicates severe injury and reparation • Not removed after healing – Found in Nodules, not in Polyps • Capillaries • Glands • Serous • Muous

12. Edema • Water retention – abnormal insterstitial fluid accumulation - can be seen in other parts of the body many times • What causes it • Injury • Hormones • Renin – chemical reaction allowing angiotensin to constrict the arterioles in the kidneys (and elsewhere) resulting in sodium retention, causing H2O retention, and increasing arteriole pressure • Norepinepherine also resulting in renal constriction • Aldosterone – transports sodium and potassium through renal tubular walls, and instead of getting rid of too much potassium, just increases fluid to balance • Birth control - progestin • Liver/kidney disturbances • Heart Failure – pulmonary edema

13. Edema – related to Voice • Increased interstitial fluid in the lamina propria and the squamous cells increases mass of the vocal folds – lowering voice • Reinke’s Edema – swelling of the superficial layer of the Lamina propria • Often caused from smoking, Laryngo-pharyngeal reflux disease, and straining to produce voice. • High Sopranos can lose entire top octave • Females may not appreciate lowering of voice if they depend on using their voice for their job. • Morning vs. Evening • Wake up – arms and face • Evening – legs and feet • Gravity pulls it down, thus voice would probably be most effected in the morning. • After Cancer treatment, edema lasting 3 months or more suggests residual cancer cells or a recurrent tumor developing.

14. Edema: What can people do? • Lie down in day time – distributes more evenly – won’t help with the voice. • Avoid tight fitting clothes • Exercise • Include diuretic foods • Anise, Celery, Onion, Parsley, Coffee or tea (unless caffeine is a concern), Eggplant, Garlic, and Peppermint. • Diuretic drugs may not be safe during pregnancy • Birth Control • Squamous cells on vocal folds same type as on cervix, thus very sensitive to birth control hormone progestin • New BC on market targeting women who experience weight gain while on the pill – Yasmin – uses different form of progestin - drospironone • Has diuretic properties • However loss of too much water and sodium may raise potassium levels • This can create severe heart concerns • Those with kidney or liver disease should not take this

15. Nodules & Polyps • Nodes – fibronectin deposits • Polyps • Primary injury in Lamina Propria • Basement membrane not usually injured • Reinke’s Edema

16. Keratinocyte Cancer: Squamous Cell Carcinoma • Happens all over the body: Along with Basal Cell Carcinoma = the most common type of skin cancer (but not most lethal = melanoma). • Underrepresented in registries, and combined with BCC in studies – little known about SCC incidence and patterns specifically. • Numbers rising about 3 – 10% each year • One source: SCC most commonly found in head and neck in Caucasians • While another source said the reverse. • In darker pigmented individuals (Africans, East Asians, South Asians) often in areas of chronic injury or cutaneous irritation • Leg ulcers, burn scars, skin infections, irritation from tight clothing • Most often in lower extremities

17. SCC in Larynx • Most tumors can be readily seen, palpated, evaluated and biopsies easily taken. • Early may appear as an nodule that won’t go away or shallow ulcer with poorly defined edges • Tumors may be exophytic or infiltrative and may extend rapidly into underlying muscle tissue causing fixation • May result in fixation – difficulty with swallowing and speech • Tumors usually respond well to radiation therapy if caught in time, especially if they are still limited to the mucosa.

18. Cellular Changes • Intracellular edema – due to protein imbalance within the cell and interstitially • Inflammatory cell infiltration • Increase of mucosal collagen • Wrinkling of basement membrane • “Disorganized” layering of the cells • Appearance of keratohyalin in the cells adjacent to the basement membrane • Dispersing of nuclear chromatic • Multiple nucleoli with abnormal shapes • Lack of cellular maturation • Presence of mitotic figures near superficial layer • www.emedicine.com – excellent source of information

19. ? • If the squamous cells on the vocal folds are non-keratinizing, then why is the laryngeal squamous cell carcinoma a keratinocyte cancer? • Keratosis = the production of keratin superficially in the epithelium and is a normal process on the skin, but not on a mucosal surface. Keratin appears dull white, think or thick, and sometimes rough and papillary. It does not rub off. (Leukoplakia) • Note the word Leukoplakia has clinically become known for non-white atypical specimens.

21. Keratosis • Keratosis without atypia is usually benign (as described in class) – can be callus like. • Hyperkeratosis – redundant term used for white horny projections from the vocal folds. Often are recurring and are considered well differentiated carcinomas. • Keratosis with atypia – dry reddend, thickend, roughend, or granular patches. Needs to be removed to be tested.

22. Other terms: • Carcinoma in situ • Malignant cells present – confined to the epithelial layers • Erythroplasia • A superficial flat lesion that is red velvet in appearance and bleeds easily. • Represents atypia on the mucosal surface • Is at least carcinoma in situ, and may be associated with invasive carcinoma • Invasion • Any pattern of malignant epithelial cells down to the basement membrane • May occur without surface abnormality • Metaplasia • The transformation of an adult cell type into another cell type – typically glandular epithelium changes to squamous epithelium. Metaplasia sometimes precedes squamous cell carcinoma.

23. Effects of Radiation Therapy • If cancer returns, radiation may not be an option because the tumor may be the result of cells that were left over from the first course of radiation, and apparently resistant to it. • Pain may be worse than that which results from surgery, and the elderly seem not to tolerate the radiation well. • If done after laryngectomy, may prevent recurrence in the stoma ( which is very bad!!!) if there is any thought of undetected metastisis. • May cause significant edema (rare), usually edema shows recurrence • May cause laryngeal chondritis and necrosis (rare) • Late sequelae may involve telangiectasis, subcuntaeous fibrosis, or an immobile laryinx

24. Genetics on the Squamous cells (in Nucleus) • Genetic studies show that sporadic SCC’s have allelic loss on several chromosomes, most of the sites for mutations are unknown. • Environmental factors can initiate the mutations • Tumor suppressor gene, TP53, mutated from UV rays with substitutions of nucleic acids • Thymine-thymine for Cytosine-Cytosine in the DNA – If this doesn’t kill the cell itself • In Sporadic cases, the mutation must be present at more than site • Proteins in the membrane of the squamous cells have been found to have tumor suppressing properties – if cell doesn’t produce these proteins more susceptible to tumor • Environmental irritants • Smoking/tobacco & alcohol • Asbestos • Heavy metals • Chronic Irritation – GERD & LPRD • Cessation of Smoking found to decrease chances for Lung Cancer, but not Laryngeal Squamous Cell Carcinoma

25. HPV • Human Papilloma virus may be found in 15%-50% of Squamous cell carcinomas depending on where in the body. • HPV is present in 90% of cervical cancers. • Beginning in the 1980’s, HPV was starting to be found in oral squamous cell carcinomas. • HPV stops normal cell growth regulatory processes to support the growth/survival of the virus. • Also targets TP53, which would self destruct mutated cell. • Leads to immortal cells

26. Epstein-Barr Virus • Main virus to cause Mono-Nucleosis • A few studies have shown EB viral DNA in squamous cell carcinoma cells. • Further investigation is being conducted

27. As SLPs. • We see patient much more often than the doctors – may be the first to hear a complaint. We need to be able to know if it is a concern. • When dealing with the medical community, we should be able to know language or at least be able to know where to find the info. • Patients may ask us what the doctor meant. • The voice is delicate, and the cells are very similar to many throughout the body. Voice may be effected before symptoms elsewhere.

28. Works Cited abcNews. (2002, November 20). The Skinny on Yasmin. Retrieved April 4, 2003, from http://printerfriendly.abcnews.com BC Cancer Agency. (n.d.) Head & Neck – Squamous Cell Carcinoma of the Larynx. Retrieved April 5, 2003, from www.bccancer.bc.ca/HPI/CancerManagementGuidelines Biology Primer. (n.d.). A Journey to the Bottom of the World. Retrieved April 4, 2003, from http://users.capu.net/~kwelch/pp/biology/primer.html Family Practice Notebook (n.d.). Edema, Fluid Overload. Retrieved April 5, 2003, from http://www.fpnotebook.com/REN15.htm

29. Works Cited (cont.) Gilbert, S. (n.d.). iVillage nutritionist. Bloating: Foods to Fight Water Retention. Retrieved April 4, 2003, from http://www.parentsplace.com/expert/nutritionist Guyton, A.C., M.D. (1981). Textbook of Medical Physiology. Philadelphia: W.B. Saunders Co. Hoffmann, D.L..,B.Sc. (n.d.) A Bachelor’s Degree in Herbal Sciences. Water Retention – Edema. Retrieved April 5, 2003, from http://www.healthy.net Myers, E.N., M.D., & Suen, J.Y., M.D. (1996). Cancer of the Head and Neck (3rd ed). Philadelphia: W.B. Saunders Co. N.A. (n.d.). Epithelium. Retrieved April 4, 2003, from http://lifesci.rutgers.edu/~babiarz/epithe.htm Sober, A.J., M.D., & Haluska, F.G. M.D., PhD. (2001). Atlas of Clinical Oncology Skin Cancer. Hamilton: B.C. Decker Inc.

30. The Voice Disorders Centerat the Massacheucetts Eye and Ear Infirmary, (n.d.). Reinke’s Edema. Retrieved April 7, 2003, from http://www.voicedisordercenter.meei.harvard.edu/disorders/reinkes.html Titze, I.R. (Ed). (1993). Vocal Fold Physiology, Frontiers in Basic Science. San Diego: Singular Vaughan, C.W., M.D. (2002, May 7). Emedicine, Instant Access to the Minds of Medicine. Pathology: Squamous Cell Carcinoma. Retrieved April 5, 2003, from www.emedicine.com Wang, C.C., M.D. (1990). Radiation Therapy for Head and Neck Neoplasms: Indications, Techniques, and Results. Chicago: Year Book Medical Publishers, Inc.