Case PresentationCase Presentation

John Francis McGuire III, MD, MBAJohn Francis McGuire III, MD, MBADepartment of Otolaryngology/Head Department of Otolaryngology/Head

and Neck Surgeryand Neck SurgeryUniversity of California, IrvineUniversity of California, Irvine

HistoryHistory

68 year old male is sent to you for 68 year old male is sent to you for evaluation of an “infection” on his ear. The evaluation of an “infection” on his ear. The lesion seems has been there for around 3-lesion seems has been there for around 3-4 weeks and has not improved on 7 days 4 weeks and has not improved on 7 days of Keflex.of Keflex.

HistoryHistory

PMHx: ESRD, HTN.PMHx: ESRD, HTN. PSHx: Kidney transplant 7 years ago, PSHx: Kidney transplant 7 years ago,

several “skin freezing” procedures by several “skin freezing” procedures by dermatology in the past, none on the ear.dermatology in the past, none on the ear.

Meds: Prograft, other meds.Meds: Prograft, other meds. Allg: NKDAAllg: NKDA PHx: Quit tobacco 7 years ago.PHx: Quit tobacco 7 years ago.

Exam:

TM clear bilaterally, TF exam WNL. The left auricle is warm to touch and erythematous. It is tender to palpation. There is no fluctuance.

Nasal mucosa WNL.

Partially edentulous, otherwise oral exam WNL.

Neck shows no adenopathy.

Mirror exam WNL.

Cranial nerves 5 and 7 are intact.

There are diffuse scaly changes over the scalp.

Differential Diagnosis of Auricluar Differential Diagnosis of Auricluar LesionsLesions

VV II TT AA MM II NN CC

Differential Diagnosis of Auricluar Differential Diagnosis of Auricluar LesionsLesions

V: hemangiomaV: hemangioma I: Otitis Externa, otomycosis, furunculosis, cellulitis, I: Otitis Externa, otomycosis, furunculosis, cellulitis,

papillomapapilloma T: Neurotic excoriation, auricular hematoma/seromaT: Neurotic excoriation, auricular hematoma/seroma A: eczema, polychondritis, WGA: eczema, polychondritis, WG M: goutM: gout I: amyloidosis, seborrheic keratosisI: amyloidosis, seborrheic keratosis N: SCC, BCC, AK, MCC, T-Cell cutaneous lymphoma, N: SCC, BCC, AK, MCC, T-Cell cutaneous lymphoma,

neurofibroma, chondroid syringoma, pilomatrix neurofibroma, chondroid syringoma, pilomatrix carcinoma, other adnexal carcinomascarcinoma, other adnexal carcinomas

C: 1C: 1stst BCC BCC

Biopsy ResultsBiopsy Results

Cutaneous SCCCutaneous SCC General Facts about SCC of skin:General Facts about SCC of skin:

2nd most common skin cancer, around 20% of cutaneous 2nd most common skin cancer, around 20% of cutaneous malignancies malignancies

Lifetime risk of SCC in the United States was estimated to be Lifetime risk of SCC in the United States was estimated to be 9% to 14% in men and 4% to 9% in woman. 9% to 14% in men and 4% to 9% in woman.

UV exposure is greatest RFUV exposure is greatest RF• fair skinned =increased risk (Fitzpatrick).fair skinned =increased risk (Fitzpatrick).• Childhood exposure (est. 80% of sundamage before 18 y/o).Childhood exposure (est. 80% of sundamage before 18 y/o).• Other factors: Thermal injury (Marjolin’s ulcer), chemical Other factors: Thermal injury (Marjolin’s ulcer), chemical

carcinogenesis, chronic radiation dermatitis, human papillomavirus carcinogenesis, chronic radiation dermatitis, human papillomavirus (types 16, 18, 30, and 33)(types 16, 18, 30, and 33)

Hereditary: xeroderma pigmentosa, oculocutaneous albinismHereditary: xeroderma pigmentosa, oculocutaneous albinism

Fitzpatrick Skin Fitzpatrick Skin TypesTypes

Mechanism of UV DamageMechanism of UV Damage UVA (320-400 nm) and UVB (280-320 nm) both UVA (320-400 nm) and UVB (280-320 nm) both

function as initiators and promoters in function as initiators and promoters in carcinogenesis as well as immunosuppressors.carcinogenesis as well as immunosuppressors. UVB causes direct DNA damage and mutations by UVB causes direct DNA damage and mutations by

promoting cyclobutane pyrimidine dimers and 6-4 promoting cyclobutane pyrimidine dimers and 6-4 photoproducts. It also decreases Langerhans cell photoproducts. It also decreases Langerhans cell activity.activity.

UVA stimulates the production of reactive oxygen UVA stimulates the production of reactive oxygen species and cellular photosensitizers.species and cellular photosensitizers.

For SCC, cumulative UV exposure leads to For SCC, cumulative UV exposure leads to increased risk (as opposed to melanoma).increased risk (as opposed to melanoma).

Progression of SCCProgression of SCC

AK >> CIS >> Invasive SCC >> AK >> CIS >> Invasive SCC >> Metastatic cutaneous SCCMetastatic cutaneous SCC

Actinic Actinic KeratosisKeratosis

AKA: Solar keratosisAKA: Solar keratosis Premalignant: appx Premalignant: appx

10% become SCC10% become SCC Assc. with Assc. with

dermatoheliosisdermatoheliosis Clinical Features: Clinical Features:

Flat to slightly raised, Flat to slightly raised, scaly patches.scaly patches.

Color from pink to red to Color from pink to red to brown, or flesh-coloredbrown, or flesh-colored

Often felt better than Often felt better than seen; scale is thick and seen; scale is thick and firmly adherentfirmly adherent

Can be painfulCan be painful

AKAK Histology: Histology:

Noninvasive proliferation Noninvasive proliferation of atypical keratinocytes of atypical keratinocytes in the basal layers of the in the basal layers of the epidermis with overlying epidermis with overlying parakeratosis.parakeratosis.

Usually accompanied by Usually accompanied by underlying elastosis. underlying elastosis.

AK: Cutaneous HornAK: Cutaneous Horn

Usually associated with Usually associated with AK, although can have AK, although can have other causes.other causes.

Histologically show Histologically show hyperkeratosis and hyperkeratosis and parakeratosis.parakeratosis.

Should be excised Should be excised because higher risk of because higher risk of progression to SCCprogression to SCC

AK: RxAK: Rx PreventionPrevention

Can resolve with sun avoidance/protectionCan resolve with sun avoidance/protection

Ablative InterventionAblative Intervention CryotherapyCryotherapy Surgical excisionSurgical excision

• important for dx as wellimportant for dx as well• All CH should be biopsiedAll CH should be biopsied

Laser resurfacing/dermabrasionLaser resurfacing/dermabrasion PDTPDT

Topical medsTopical meds 5-FU: Pyrimidine analog, painful.5-FU: Pyrimidine analog, painful. Imiquimod: Activates macrophages to induce secretion of pro-Imiquimod: Activates macrophages to induce secretion of pro-

inflammatory cytokines (IFN-alpha,TNF, IL-12) = Th1 response.inflammatory cytokines (IFN-alpha,TNF, IL-12) = Th1 response. Diclofinac: an anti-inflammatoryDiclofinac: an anti-inflammatory

CISCIS

AKA: “Bowen’s Disease”AKA: “Bowen’s Disease”

-Usually presents as a -Usually presents as a reddish patch or plaque reddish patch or plaque and may have scales. and may have scales. These often arise in These often arise in sites of old burns or sites of old burns or scars. Often mistaken scars. Often mistaken for psoriasis.for psoriasis.

CISCIS Histology: Histology:

Keratinocytes lose polarity, Keratinocytes lose polarity, have atypia and and increased have atypia and and increased mitotic rate, and involve the mitotic rate, and involve the entire epidermis, but without entire epidermis, but without invasion of the basement invasion of the basement membrane. There can be also membrane. There can be also be acanthosis and elongation be acanthosis and elongation of the rete ridges. of the rete ridges.

RX: RX: Surgical ExcisionSurgical Excision Other: cyrotherapy, 5-FU.Other: cyrotherapy, 5-FU.

Invasive SCCInvasive SCC Characteristics:Characteristics:

Reddish, scaling, opaque nodules, ulcerative, Reddish, scaling, opaque nodules, ulcerative, granular base, bleed easily...granular base, bleed easily...

Invasive SCCInvasive SCC ……by definition has invaded by definition has invaded

the basement membrane.the basement membrane.

Side Note:Side Note: Highly differentiated SCC will Highly differentiated SCC will

show singes of keratinization show singes of keratinization within orn on the surface of the within orn on the surface of the tumor, therefore firm to tumor, therefore firm to palpation.palpation.

Poorly differentiated will not Poorly differentiated will not show signs of keratinization, show signs of keratinization, and will therefore appear more and will therefore appear more fleshy, granulomatous, and are fleshy, granulomatous, and are soft to palpation.soft to palpation.

SCC: can look like SCC: can look like BCC…BCC…

These nodular lesions mimic BCC, but they lack These nodular lesions mimic BCC, but they lack opalecent borders and telangectasias… need biopsy opalecent borders and telangectasias… need biopsy and excision in any case.and excision in any case.

Surgical Rx: MarginsSurgical Rx: Margins Depends on risk factors:Depends on risk factors:

High risk:High risk:• Size of 2 cm or largerSize of 2 cm or larger• More aggressive histologic subtypesMore aggressive histologic subtypes• Invasion of the subcutaneous tissueInvasion of the subcutaneous tissue• Location in high-risk areas (i.e. embryonic fusion planes).Location in high-risk areas (i.e. embryonic fusion planes).

Margins:Margins:• Low risk margins = 4 mm, Low risk margins = 4 mm, • High risk = start with 6 mm, but need frozen control.High risk = start with 6 mm, but need frozen control.

Brodland et al [1992]Brodland et al [1992]• SCC diameter less than 2 cm > 95% complete resection, greater than 2 cm, a 0.6cm SCC diameter less than 2 cm > 95% complete resection, greater than 2 cm, a 0.6cm

margin required to achieve 95% complete resection. margin required to achieve 95% complete resection.

• Histological grade of 1, 2 or 3 had tumors invading subcutaneous fat were 18%, 56% Histological grade of 1, 2 or 3 had tumors invading subcutaneous fat were 18%, 56% and 100% of the time, respectively.and 100% of the time, respectively.

• Tumors less than 1 cm, between 1 and 2 cm, and greater than 2 cm invaded 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. subcutaneous fat 15%, 39%, and 52% of the time, respectively.

Moh’sMoh’s Moh’s:Moh’s:

Recurrence of SCC for Moh’s Recurrence of SCC for Moh’s vs. non-Moh’s excisions vs. non-Moh’s excisions (Rowe 1992): (Rowe 1992):

• skin and lip, 3.1% versus skin and lip, 3.1% versus 10.9%;10.9%;

• ear, 5.3% versus 18.7%; ear, 5.3% versus 18.7%; • locally recurrent SCC, 10% locally recurrent SCC, 10%

versus 23.3%; versus 23.3%; • SCC greater than 2cm in SCC greater than 2cm in

diameter, 25.2% versus 41.7%;diameter, 25.2% versus 41.7%;• Poorly differentiated SCC, Poorly differentiated SCC,

32.6% versus 53.6%. 32.6% versus 53.6%.

Metastatic SpreadMetastatic Spread Behavior is determined by location, size, depth and Behavior is determined by location, size, depth and

grade of histologic differentiation.grade of histologic differentiation. The central zone of the face, temple, lips, ear and scalp are at The central zone of the face, temple, lips, ear and scalp are at

significant risk for local recurrence and metastases. significant risk for local recurrence and metastases.

Spread: Spread: • Along perichondrium, periosteum, fasia, nerve, and embryonic Along perichondrium, periosteum, fasia, nerve, and embryonic

fusion planes. Loves to go to parotid…fusion planes. Loves to go to parotid… Risk Factors for Metastatic Spread (30-50%)Risk Factors for Metastatic Spread (30-50%)

• Width greater than 2 cmWidth greater than 2 cm• Depth greater than 4mmDepth greater than 4mm• RecurrenceRecurrence• Perineural invasionPerineural invasion• Poorly differentiated histologic featuresPoorly differentiated histologic features

Metastatic Spread: ParotidMetastatic Spread: Parotid

Elective parotidectomy not recommended… but…Elective parotidectomy not recommended… but… Only 20% of cases of parotid involvement are clinically apparent Only 20% of cases of parotid involvement are clinically apparent

• >> >> mustmust get imaging studies with high risk lesions. get imaging studies with high risk lesions. 20% occult parotid disease after elective parotidectomy20% occult parotid disease after elective parotidectomy

• So if neck disease, parotidectomy indicated.So if neck disease, parotidectomy indicated.

If disease >> usually superficial parotidectomy indicated.If disease >> usually superficial parotidectomy indicated. The majority of nodes are in the lateral lobe. The majority of nodes are in the lateral lobe. No increase in survival or decreased recurrance with bigger No increase in survival or decreased recurrance with bigger

resection (including nerve sacrifice). resection (including nerve sacrifice). If radical parotidectomy with nerve sacrifice, immediate If radical parotidectomy with nerve sacrifice, immediate

reanimation procedures is recommended.reanimation procedures is recommended.

Metastatic Disease: NeckMetastatic Disease: Neck Facts and Concepts:Facts and Concepts:

The incidence of clinical neck disease in the absence of clinical parotid The incidence of clinical neck disease in the absence of clinical parotid involvement is approximately 30%.involvement is approximately 30%.

• But remember that if neck disease, superficial parotidectomy should be But remember that if neck disease, superficial parotidectomy should be performed.performed.

Occult neck disease in the face of parotid metastasis is between 20-Occult neck disease in the face of parotid metastasis is between 20-44%.44%.

• Therefore, elective neck dissection is warrented if there are parotid mets.Therefore, elective neck dissection is warrented if there are parotid mets.

Metastatic cutaneous SCC goes levels I, II, and III. Metastatic cutaneous SCC goes levels I, II, and III. • Therefore, supraomohyoid neck dissection is recommended.Therefore, supraomohyoid neck dissection is recommended.

Dermal mets: Dermal mets: present in 20% of cases of metastatic SCCpresent in 20% of cases of metastatic SCC Rx: resect involved skinRx: resect involved skin

Perineural Perineural Invasion (PNI)Invasion (PNI)

PNI is seen in 5%-14% of cutaneous PNI is seen in 5%-14% of cutaneous squamous cell carcinomas of the head squamous cell carcinomas of the head and neck.and neck.

Most common in the auricular area Most common in the auricular area (25.7%), cheek and maxilla (21.4%), and (25.7%), cheek and maxilla (21.4%), and forehead (18.6%).forehead (18.6%).

Dx: Dx: Clinical deficitsClinical deficits

• ……but 60-80% of metastatic lesions involving but 60-80% of metastatic lesions involving the facial nerve present with no symptoms.the facial nerve present with no symptoms.

PathologyPathology• May demonstrate skip lesionsMay demonstrate skip lesions

Radiological:Radiological:• CT scan with bone windows >> enlargement CT scan with bone windows >> enlargement

of skull base foraminaof skull base foramina• MRI with gad and fat suppression >> MRI with gad and fat suppression >>

enhancement of major nerve trunks or nerve enhancement of major nerve trunks or nerve enlargement.enlargement.

Metastatic Disease: XRTMetastatic Disease: XRT Indications for post-operative XRT:Indications for post-operative XRT:

Large or recurrent primary lesionLarge or recurrent primary lesion Close or positive surgical marginsClose or positive surgical margins PNIPNI Multiple levels of lymphatic spreadMultiple levels of lymphatic spread Histology: poorly differentiated or spindle cell SCC. Histology: poorly differentiated or spindle cell SCC.

Vanness et al (2005): Mets to NeckVanness et al (2005): Mets to Neck Combined XRT vs. Surgery Alone:Combined XRT vs. Surgery Alone:

• Locoregional recurrence >> 20% vs. 43%Locoregional recurrence >> 20% vs. 43%• 5-year disease-free survival rate >> 73% vs. 54%5-year disease-free survival rate >> 73% vs. 54%

Taylor (1991): Mets to paroitidTaylor (1991): Mets to paroitid Parotidectomy alone was 63%Parotidectomy alone was 63% XRT alone was 46%XRT alone was 46% Combined RX: 89%. Combined RX: 89%.

Organ Transplant Recipients Organ Transplant Recipients (OTRs)(OTRs)

Facts:Facts:

35 to 70 % of organ transplant patients 35 to 70 % of organ transplant patients develop skin cancer within 20 years following develop skin cancer within 20 years following transplant surgery…transplant surgery…

Increases for different lesions:Increases for different lesions:• Squamous cell carcinoma (SCC): 65-100 foldSquamous cell carcinoma (SCC): 65-100 fold• Basal Cell Carcinoma (BCC): 10 foldBasal Cell Carcinoma (BCC): 10 fold• Melanoma: 4 foldMelanoma: 4 fold

OTRsOTRs Further… Skin cancer in OTRs tends to behave more Further… Skin cancer in OTRs tends to behave more

aggressively…aggressively…

The rate of invasive skin cancer in transplant patients can be up The rate of invasive skin cancer in transplant patients can be up to 80 times greater than in the general population.to 80 times greater than in the general population.

Skin cancers in OTRs grow rapidly and tend to be multiple and Skin cancers in OTRs grow rapidly and tend to be multiple and metastatic.metastatic.

Mortality from cutanteous SCC is over 50 times higher than in Mortality from cutanteous SCC is over 50 times higher than in the general population. the general population.

Once a transplant patient develops a single skin cancer, 50% Once a transplant patient develops a single skin cancer, 50% will develop additional skin cancer within 3.5yrs will develop additional skin cancer within 3.5yrs

OTROTR Risk factorsRisk factors

Common to the general population:Common to the general population:• history of skin cancer, history of skin cancer, • history of actinic keratoses, history of actinic keratoses, • fair skin,fair skin,• a history of chronic sun exposure and/or sun burns,a history of chronic sun exposure and/or sun burns,• older ageolder age

Specific for to transplant patients…Specific for to transplant patients…• duration and intensity of immunosuppression, duration and intensity of immunosuppression, • Heart >> kidney >> liver transplantation (related to above)Heart >> kidney >> liver transplantation (related to above)• a history of HPV infection, a history of HPV infection, • CD4 lymphocytopeniaCD4 lymphocytopenia. .

Care for the OTR patientCare for the OTR patient

Prevention = #1Prevention = #1 Some Guidelines:Some Guidelines:

SunprotectionSunprotection:: Sun avoidance Sun avoidance

• Avoid sunlight from 10am to 3pm Avoid sunlight from 10am to 3pm • SunblockSunblock• UV protective clothingUV protective clothing

Long sleeved shirts Long sleeved shirts Long pants Long pants Sunglasses with Sunglasses with UV protective coating UV protective coating

Tanning beds expressly prohibitedTanning beds expressly prohibited

Care for the OTR patientCare for the OTR patient

SunblockSunblock Recommendations: Recommendations: SPF >/= 30 with broad UVA/UVB protection. SPF >/= 30 with broad UVA/UVB protection.

Sunblock Use Sunblock Use Apply ~20 minutes prior to sun-exposure. Apply ~20 minutes prior to sun-exposure. Apply to all sun-exposed areas. Don't forget lips, ears, Apply to all sun-exposed areas. Don't forget lips, ears,

back of neck, or back of legs. back of neck, or back of legs. Apply a sufficient coat of sunscreen- most common Apply a sufficient coat of sunscreen- most common

mistake is being too stingy mistake is being too stingy Reapply every 2 hours when out in the sun- more Reapply every 2 hours when out in the sun- more

frequently if in water or sweatingfrequently if in water or sweating

Care for the Care for the OTR OTR

patientpatient

Self Self examinationexamination

Keep log of Keep log of suspicious suspicious lesionslesions

OTR Clinics: OTR Clinics: UCSF UCSF

GuidelinesGuidelines