Case Presentation

1. Case Presentation John Francis McGuire III, MD, MBA Department of Otolaryngology/Head and Neck Surgery University of California, Irvine

3. History PMHx: ESRD, HTN. PSHx: Kidney transplant 7 years ago, several �skin freezing� procedures by dermatology in the past, none on the ear. Meds: Prograft, other meds. Allg: NKDA PHx: Quit tobacco 7 years ago.

5. Differential Diagnosis of Auricluar Lesions V I T A M I N C

6. Differential Diagnosis of Auricluar Lesions V: hemangioma I: Otitis Externa, otomycosis, furunculosis, cellulitis, papilloma T: Neurotic excoriation, auricular hematoma/seroma A: eczema, polychondritis, WG M: gout I: amyloidosis, seborrheic keratosis N: SCC, BCC, AK, MCC, T-Cell cutaneous lymphoma, neurofibroma, chondroid syringoma, pilomatrix carcinoma, other adnexal carcinomas C: 1st BCC

7. Biopsy Results

8. Cutaneous SCC General Facts about SCC of skin: 2nd most common skin cancer, around 20% of cutaneous malignancies Lifetime risk of SCC in the United States was estimated to be 9% to 14% in men and 4% to 9% in woman. UV exposure is greatest RF fair skinned =increased risk (Fitzpatrick). Childhood exposure (est. 80% of sundamage before 18 y/o). Other factors: Thermal injury (Marjolin�s ulcer), chemical carcinogenesis, chronic radiation dermatitis, human papillomavirus (types 16, 18, 30, and 33) Hereditary: xeroderma pigmentosa, oculocutaneous albinism

9. Fitzpatrick Skin Types

10. Mechanism of UV Damage UVA (320-400 nm) and UVB (280-320 nm) both function as initiators and promoters in carcinogenesis as well as immunosuppressors. UVB causes direct DNA damage and mutations by promoting cyclobutane pyrimidine dimers and 6-4 photoproducts. It also decreases Langerhans cell activity. UVA stimulates the production of reactive oxygen species and cellular photosensitizers. For SCC, cumulative UV exposure leads to increased risk (as opposed to melanoma).

11. Progression of SCC AK >> CIS >> Invasive SCC >> Metastatic cutaneous SCC

12. Actinic Keratosis AKA: Solar keratosis Premalignant: appx 10% become SCC Assc. with dermatoheliosis Clinical Features: Flat to slightly raised, scaly patches. Color from pink to red to brown, or flesh-colored Often felt better than seen; scale is thick and firmly adherent Can be painful

13. AK Histology: Noninvasive proliferation of atypical keratinocytes in the basal layers of the epidermis with overlying parakeratosis. Usually accompanied by underlying elastosis.

14. AK: Cutaneous Horn Usually associated with AK, although can have other causes. Histologically show hyperkeratosis and parakeratosis. Should be excised because higher risk of progression to SCC

15. AK: Rx Prevention Can resolve with sun avoidance/protection Ablative Intervention Cryotherapy Surgical excision important for dx as well All CH should be biopsied Laser resurfacing/dermabrasion PDT Topical meds 5-FU: Pyrimidine analog, painful. Imiquimod: Activates macrophages to induce secretion of pro-inflammatory cytokines (IFN-alpha,TNF, IL-12) = Th1 response. Diclofinac: an anti-inflammatory

16. CIS AKA: �Bowen�s Disease� -Usually presents as a reddish patch or plaque and may have scales. These often arise in sites of old burns or scars. Often mistaken for psoriasis.

17. CIS Histology: Keratinocytes lose polarity, have atypia and and increased mitotic rate, and involve the entire epidermis, but without invasion of the basement membrane. There can be also be acanthosis and elongation of the rete ridges. RX: Surgical Excision Other: cyrotherapy, 5-FU.

18. Invasive SCC Characteristics: Reddish, scaling, opaque nodules, ulcerative, granular base, bleed easily...

19. Invasive SCC �by definition has invaded the basement membrane. Side Note: Highly differentiated SCC will show singes of keratinization within orn on the surface of the tumor, therefore firm to palpation. Poorly differentiated will not show signs of keratinization, and will therefore appear more fleshy, granulomatous, and are soft to palpation.

20. SCC: can look like BCC� These nodular lesions mimic BCC, but they lack opalecent borders and telangectasias� need biopsy and excision in any case.

21. Surgical Rx: Margins Depends on risk factors: High risk: Size of 2 cm or larger More aggressive histologic subtypes Invasion of the subcutaneous tissue Location in high-risk areas (i.e. embryonic fusion planes). Margins: Low risk margins = 4 mm, High risk = start with 6 mm, but need frozen control. Brodland et al [1992] SCC diameter less than 2 cm > 95% complete resection, greater than 2 cm, a 0.6cm margin required to achieve 95% complete resection. Histological grade of 1, 2 or 3 had tumors invading subcutaneous fat were 18%, 56% and 100% of the time, respectively. Tumors less than 1 cm, between 1 and 2 cm, and greater than 2 cm invaded subcutaneous fat 15%, 39%, and 52% of the time, respectively.

22. Moh�s Moh�s: Recurrence of SCC for Moh�s vs. non-Moh�s excisions (Rowe 1992): skin and lip, 3.1% versus 10.9%; ear, 5.3% versus 18.7%; locally recurrent SCC, 10% versus 23.3%; SCC greater than 2cm in diameter, 25.2% versus 41.7%; Poorly differentiated SCC, 32.6% versus 53.6%.

23. Metastatic Spread Behavior is determined by location, size, depth and grade of histologic differentiation. The central zone of the face, temple, lips, ear and scalp are at significant risk for local recurrence and metastases. Spread: Along perichondrium, periosteum, fasia, nerve, and embryonic fusion planes. Loves to go to parotid� Risk Factors for Metastatic Spread (30-50%) Width greater than 2 cm Depth greater than 4mm Recurrence Perineural invasion Poorly differentiated histologic features

24. Metastatic Spread: Parotid Elective parotidectomy not recommended� but� Only 20% of cases of parotid involvement are clinically apparent >> must get imaging studies with high risk lesions. 20% occult parotid disease after elective parotidectomy So if neck disease, parotidectomy indicated. If disease >> usually superficial parotidectomy indicated. The majority of nodes are in the lateral lobe. No increase in survival or decreased recurrance with bigger resection (including nerve sacrifice). If radical parotidectomy with nerve sacrifice, immediate reanimation procedures is recommended.

25. Metastatic Disease: Neck Facts and Concepts: The incidence of clinical neck disease in the absence of clinical parotid involvement is approximately 30%. But remember that if neck disease, superficial parotidectomy should be performed. Occult neck disease in the face of parotid metastasis is between 20-44%. Therefore, elective neck dissection is warrented if there are parotid mets. Metastatic cutaneous SCC goes levels I, II, and III. Therefore, supraomohyoid neck dissection is recommended. Dermal mets: present in 20% of cases of metastatic SCC Rx: resect involved skin

26. Perineural Invasion (PNI) PNI is seen in 5%-14% of cutaneous squamous cell carcinomas of the head and neck. Most common in the auricular area (25.7%), cheek and maxilla (21.4%), and forehead (18.6%). Dx: Clinical deficits �but 60-80% of metastatic lesions involving the facial nerve present with no symptoms. Pathology May demonstrate skip lesions Radiological: CT scan with bone windows >> enlargement of skull base foramina MRI with gad and fat suppression >> enhancement of major nerve trunks or nerve enlargement.

27. Metastatic Disease: XRT Indications for post-operative XRT: Large or recurrent primary lesion Close or positive surgical margins PNI Multiple levels of lymphatic spread Histology: poorly differentiated or spindle cell SCC. Vanness et al (2005): Mets to Neck Combined XRT vs. Surgery Alone: Locoregional recurrence >> 20% vs. 43% 5-year disease-free survival rate >> 73% vs. 54% Taylor (1991): Mets to paroitid Parotidectomy alone was 63% XRT alone was 46% Combined RX: 89%.

28. Organ Transplant Recipients (OTRs) Facts: 35 to 70 % of organ transplant patients develop skin cancer within 20 years following transplant surgery� Increases for different lesions: Squamous cell carcinoma (SCC): 65-100 fold Basal Cell Carcinoma (BCC): 10 fold Melanoma: 4 fold

29. OTRs Further� Skin cancer in OTRs tends to behave more aggressively� The rate of invasive skin cancer in transplant patients can be up to 80 times greater than in the general population. Skin cancers in OTRs grow rapidly and tend to be multiple and metastatic. Mortality from cutanteous SCC is over 50 times higher than in the general population. Once a transplant patient develops a single skin cancer, 50% will develop additional skin cancer within 3.5yrs

30. OTR Risk factors Common to the general population: history of skin cancer, history of actinic keratoses, fair skin, a history of chronic sun exposure and/or sun burns, older age Specific for to transplant patients� duration and intensity of immunosuppression, Heart >> kidney >> liver transplantation (related to above) a history of HPV infection, CD4 lymphocytopenia.

31. Care for the OTR patient Prevention = #1 Some Guidelines: Sunprotection: Sun avoidance Avoid sunlight from 10am to 3pm Sunblock UV protective clothing Long sleeved shirts Long pants Sunglasses with UV protective coating Tanning beds expressly prohibited

32. Care for the OTR patient Sunblock Recommendations: SPF >/= 30 with broad UVA/UVB protection. Sunblock Use Apply ~20 minutes prior to sun-exposure. Apply to all sun-exposed areas. Don't forget lips, ears, back of neck, or back of legs. Apply a sufficient coat of sunscreen- most common mistake is being too stingy Reapply every 2 hours when out in the sun- more frequently if in water or sweating

33. Care for the OTR patient Self examination Keep log of suspicious lesions

34. OTR Clinics: UCSF Guidelines