SKIN CANCER - internal.nfp.com · Stage IIIa – T1-4a, N1a or N2a. MELANOMA TNM/STAGING Stage I – low risk for metastases and melanoma mortality Stage II – intermediate risk

SKIN CANCER• Most common cancer diagnosis – 40% of all cancers

OBJECTIVES

� Review common and uncommon cancers of the skin. Special emphasis on melanoma and dysplastic nevus

� Review pathology/TNM/staging, which is critical in underwriting

� Review survival/mortality studies, although some are limited

2011 NFP SCHOOL OF EXCELLENCEINTERNAL USE ONLY. Not for public distribution.

GENERAL POINTS

� Careful reading of pathology report� Grade & stage – critical for solid tumors� Margins of resection, mitoses, necrosis, vascular

invasion� Beware of under-staging. Clin. vs. path.

Is treatment optimal?


� Is treatment optimal?� Clinical, laboratory, pathology evidence of recurrence� If pathology report is inadequate or unavailable, try

doctor records

PRIMARY TYPES

•80%(800,000/yr)Basal Cell

Carcinoma

•16%Squamous Cell


•16%Squamous Cell

Carcinoma

•4%Malignant Melanoma (Largely related to sun exposure)

SKIN CANCER

� Non-melanoma – most common cancer world-wide, incidence increasing

� Biggest risk factors – SUN, genetics, tobacco use in that order

� Recent increase in those < 40, esp. basal cell cancer in young females


young females� Christenson. JAMA 2005; 294:681-690

BASAL CELL CARCINOMA

� “Low metastatic potential” (met. rate <0.1%)� Mortality rate – 0.05% (deep invasion >10 cm.). Rarely fatal. Cure

highly probable. Face, head� Basosquamous cell carcinoma – greater risk. Treat as squamous cell

cancer. � Tx – Moh’s surgery, radiation, cryosurgery, topical (5FU), electrosurgery

-90 % cure


-90 % cure� Second BCC common (40% in 5 yrs)

SQUAMOUS CELL CARCINOMA

� Most remain localized & curable� Precursor – actinic, solar, senile keratosis

� Lifetime SCC risk: 6-10% if multiple lesions

� Seborrheic keratosis – not a precursor

� Assoc. w/ sun, smoking, tx w/ PUVA or immune


� Assoc. w/ sun, smoking, tx w/ PUVA or immune suppression

� If one SCC – high chance of 2nd SCC (or BCC or melanoma) within 5 yrs

SQUAMOUS CELL CARCINOMA

� Bowen’s Disease – SCC in situ� Up to 2 cm tumors- few recur or metast.� Recurrence rate – 8-16% - depends on size, depth, facial

areas, differentiation, tx� Mets w/ SCC – 1-5% (85% of those in LN). > risk if face,

scalp, ears, scars, burns, if d/t radiation/immune


scalp, ears, scars, burns, if d/t radiation/immune suppression, older men

TMN FOR SCC OF SKIN

� Tis – Carcinoma in situ (non-invasive)� T1 - < 2 cm diam. < 2 high risk features� T2 - >2 cm or any T w/ > 2 high risks� T3 & T4 – (much deeper invasion) – maxilla, mandible,

orbit, etc.


SCC HIGH RISK FEATURES

� Depth > 2 mm or Clark level IV or perineural invasion� Location – ear or hair-bearing lip� Poorly differentiated or undifferentiated (does not look like

normal skin)


SKIN SCC STAGE

Stage 0 Stage I Stage II Stage Stage


Stage 0 – Tis

N0 M0

Stage I – T1

N0 M0

Stage II – T2

N0 M0

Stage III - T3 N0 M0

Stage III T1 N1 M0

SCC TREATMENT

•97% cureMoh’s micrographic

surgery

•92% cureOther surgery


Other tx less effective: radiation, cryotherapy, 5FU

•77% cureSurgery for recurrence

Need close follow-up after treatment

SCC MORTALITY

� Overall mortality – 1% (1000/yr)� Pos lymph nodes – 25-35% 5 yr. survival & < 20% 10 yr.

survival� Distant mets - < 10% 5 yr. survival� 5 year cure rate > 90%


MALIGNANT MELANOMA

� 75% of T1 melanomas are T1a w/ 95% five yr survival & 93% ten yr survival

� Thickness proportional to how long it has been there & to risk

� Thickness & ulceration: best predictors of survivalMore common if freckles, moles (esp. atypical), non-


� More common if freckles, moles (esp. atypical), non-melanoma skin ca and sporadic sun exposure

MALIGNANT MELANOMA

� 50% of melanoma - no preexisting lesion� 10% - familial

� If family history, 8-12 fold increased incidence

� If family history, need exam Q 6 months� 2/3 secondary to sunlight (UVA & UVB)


� 2/3 secondary to sunlight (UVA & UVB)� -Intense sunburn in childhood 4- 5 x

� Sporadic sun exposure (cf. SCC, when sun more constant exposure)

MALIGNANT MELANOMA

� Life time risk 1 in 37 or 50 (1/600 in 1965)� Rare until age 10� Recent increases ages 10-20 & up� Mortality ratio stable or mild increase except men > 65 (up

150%)


� With early dx, overall survival 90%

ABCDE –MELANOMA DX

� A – asymmetry� B – border irregularity� C – color variegation� D – diameter >6 mm. (pencil

eraser)� E – evolving (change, itching,

Rigel. CA 2010;60:301-316


� E – evolving (change, itching, bleeding)

MELANOMA TYPES

� Superficial spreading – radial growth- 70%� Nodular –vertical invasion- 15-30%� Acral – dark skin, soles, palms, nails- 5%� Lentigo –elderly, in situ for years- 5%

� Abbasi. JAMA 2004;292:2771-2776


MALIGNANT MELANOMA

� Early radial (horizontal) growth, thin & confined to epidermis� In situ or microinvasion almost all curable

� But risk of another melanoma

� Vertical growth phase into dermis – metastatic potential


MELANOMA – PATH REPORT

� In situ or invasive� Breslow thickness & Clark level� Ulceration + or –� Mitoses – many or very few� Growth - radial or vertical

Regression


� Regression� Margins of resection� Satellites or vascular invasion

MM – 10 YEAR SURVIVAL

� Extremity <0.76 mm, women <60: 99%� Extremity <0.76 mm, men < 60: 98%� Axis <0.76 mm, women < 60: 97%� Axis < 0.76mm, men < 60: 94%� Extremity < 0.76 mm, women >60: 98%

Extremity < 0.76 mm, men >60: 96%


� Extremity < 0.76 mm, men >60: 96%

� * Axis: trunk, head, neck, volar, subungual

MM – 10 YEAR SURVIVAL

� Axis <0.76 mm, women >60: 92%� Axis <0.76 mm, men > 60: 84%� Extremity 0.76-1.69mm, women <60: 96%� Extremity 0.76-1.69mm, men <60: 93%� Axis 0.76-1.69mm, women <60: 86%

Axis 0.76-1.69mm, men <60: 75%


� Axis 0.76-1.69mm, men <60: 75%� Extremity 0.76-1.69mm, women >60: 90%� Extremity 0.76-1.69mm, men > 60: 81%

MM-10 YEAR SURVIVAL

� Axis 0.76-1.69mm, women >60: 67%� Axis 0.76-1.69mm, men >60: 50%� Extremity 1.7-3.6mm, women <60: 89%� Extremity 1.7-3.6mm, men <60: 80%

Axis 1.7-3.6mm, women <60: 65%


� Axis 1.7-3.6mm, women <60: 65%� Axis 1.7-3.6mm, men<60: 48%� Extremity 1.7-3.6mm, women >60: 73%� Extremity 1.7-3.6mm, men >60: 57%

� Ann Int Med 1996;125:369

MELANOMA2002 AJCC STAGING

� Tis – melanoma in situ � T1a- < or = 1.0 mm. w/o ulceration, level II,III� T1b -< or =1.0 mm. w/ ulceration or level IV, V� T2a – 1.01-2.0 mm. w/o ulceration


� T2a – 1.01-2.0 mm. w/o ulceration� T2b – 1.01-2.0 mm. w/ ulceration� T3a – 2.01-4.0 mm. w/o ulceration� T3b – 2.01-4/0 mm. w/ ulceration

� H/O Melanoma, risk of 2nd is 10-25 x.

� Recent study: 8% risk of 2nd melanoma w/in 2 yrs.

TNM & STAGING

� Stage 0 – Tis (jn situ)� Stage IA – T1a (N0 M0 for all I & II)� Stage IB – T1b or T2a� Stage IIA – T2b or T3a� Stage IIB – T3b or T4a


� Stage IIB – T3b or T4a� Stage II C – T4b� Stage IIIa – T1-4a, N1a or N2a

MELANOMA TNM/STAGING

� Stage I – low risk for metastases and melanoma mortality� Stage II – intermediate risk for metastases & melanoma

mortality� Balch. CA 2004; 54:131-149


MM – STAGE/ 5 YR SURVIVAL

� IA (T1a nonulcerated) - 95%� IB (T1b ulcerated) – 91%� IB (T2a nonulcerated) – 89%� IIA (T3a nonulcerated) – 79%� IIA (T2b ulcerated) – 77%


� IIA (T2b ulcerated) – 77%� IIB (T4a nonulcerated) – 67%� IIB (T3b ulcerated) – 63%

� Balch. CA 2004; 54:131-149

MM - STAGE/10 YR SURVIVAL

� IA (T1a nonulcerated) – 93%� IB (T1b ulcerated) – 82%� IB (T2a nonulcerated) – 80%� IIA (T2b ulcerated) – 68%� IIA (T3a nonulcerated) – 68%


� IIA (T3a nonulcerated) – 68%� IIB (T3b ulcerated) – 53%� IIB (T4a nonulcerated) – 55%

MM STAGE/ MORTALITY RATIO

� Stage IA – Slightly > 100% MR� Stage IB – 250% MR� Stage IIA – 400% MR� Stage IIB – 600% MR� Stage IIC – 900% MR


� Stage IIC – 900% MR� Stage IIIA – 1200% MR

� REMEMBER LONG MORTALITY TAIL IN - long risk for underwriting

HISTORY OF MELANOMA

� 100 fold increase risk if previous melanoma in patient� 200 fold increase risk if 2 family members with melanoma� 1200 fold increase risk if both personal and family history of

melanoma� Naeyaert. NEJM 2003;349:2233-2240


T1 & T2 MELANOMAS

� T1a - < 1.0 mm, no ulceration, only level II and level III (Clark)

� T1b - < 1.0 mm but level IV or V or ulceration regardless of level

� Clark level important only –thin melanoma� Ulceration raises lesion to next stage (IB is either T1b or


� Ulceration raises lesion to next stage (IB is either T1b or T2a)

� Stage I & II – no evidence of mets

MALIGNANT MELANOMA

� Path stage (pT) – more information than clinical stage (cT)� Caution: amelanotic melanoma (colorless) – usually

nodular; often overlooked� Melanoma in situ. No invasion, 100% survival, but still risk

of additional melanomas


MELANOMA TREATMENT

� Complete excision w/ adequate margins of surrounding tissue for cure (all directions)

� AVOID shave biopsies. Need subq for depth. May transect melanoma

� Sentinel node bx in melanomas 1.2mm to 3.5 mm. (T2-3) –survival higher cf no bx


survival higher cf no bx� Morton. NEJM 2006;355:1307-1317

� If sentinel node +, then complete node dissection w/ adjuvant tx for hope of cure

MELANOMA METS

� If + lymph node on bx, then have better survival than only clinical dx (by 20-29%)

� Satellite mets in skin by primary MM has equally poor prognosis as + lymph nodes (N2 & stage III)Stage III ten yr survival – 9-63%


� Stage III ten yr survival – 9-63%

MALIGNANT MELANOMA

� Ulceration, bleeding, regression, satellites, high mitotic rate: all worse prognosis.

� Pos. lymph nodes worst prognosis� Dermoscopy (surface microscopy) now allows

differentiation of benign and malignant pigmented lesionsP.S. – can also have melanoma in eye or GI tract (increase


� P.S. – can also have melanoma in eye or GI tract (increase risk if dysplastic nevus)

MELANOMA - FUTURE

� Identification of gene alterations will be basis of future classification of melanoma & provide rationale for drug treatment & effective targeted therapy

� Advance/Laboratory, Feb. 2011, p. 26

� For other new techniques being investigated –

-Rigel CA 2010; 60:301-316


� -Rigel CA 2010; 60:301-316

DYSPLASTIC NEVI� AKA atypical mole, BK mole, Clark’s nevi� Path & clin. between nevus and melanoma� No consensus on formal definition� Precursor or marker for melanoma� Appears at puberty. Prevalent < 30-40 y/o

Often 50 - >100 nevi on body


� Often 50 - >100 nevi on body� Autosomal dominant inheritance but not always family

history

DYSPLASTIC NEVUS

� Occurs in 2-18% of white adults (20% of all have at least one atypical mole)

� Median age 33� Occurs in 17-59% of melanoma patients� Most common on trunk, esp back


� Dysplastic nevus syndrome: >100 moles, with one > 8mm and one atypical mole

� May evolve from nevus or de novo

DYSPLASTIC NEVUS

� Relationship of familial melanoma & dysplastic nevus is FAMMM – familial atypical multiple mole- melanoma syndrome. AKA dysplastic mole syn.

� >15 x relative risk of melanoma if multiple� Intense f/u q 6-12 months w/ photos

Also increased incidence others cancers


� Also increased incidence others cancers� Naeyaert. NEJM 2003;349:2233-2240

KINDREDS & DYSPLASTIC NEVUS SYNDROME

� A: sporadic atyp mole – 1 in family � B familial atyp mole – 2 or more in family� C sporadic atyp mole & melanoma – 1 in family w/ both

conditions� D1 familial atyp mole & melanoma – 2 or more w/ atyp

mole; 1 in family w/ both


mole; 1 in family w/ both� D2 – familial atyp mole & MM – 2 or more with both atyp

mole & MM

DYSPLASTIC NEVUS TREATMENT

� Most do not evolve into melanoma� Most are therefore not excised unless changes occur� Stress again need for close follow-up, including photos, for

both dysplastic nevus and melanoma patients


LESS COMMON SKIN TUMORS

� Keratoacanthoma – looks like SCC but rapid growth. Most regress to scar. A few may be or become malignant w/ mets

� Sebaceous carcinoma. Malignant, 10 to 30 % mortality in 5 years. Face & head, esp. eyelids. Assoc. w/ 2nd cancer


LESS COMMON SKIN TUMORS

� Merkel cell carcinoma. Rare, aggressive, esp. older males or immunocompromised. Tend to recur or metastasize. Rapid growth, esp. face. Assoc. w/ 2nd cancers.

� Dermatofibrosarcoma protruberans. Locally invasive, similar to basal cell ca.


similar to basal cell ca.

CUTANEOUS LYMPHOMA

� 90% T cell lymphoma. � Majority are mycosis fungoides

� Next, anaplastic large T cell lymphoma

� 10% B cell lymphoma� 20-25% are stage IA, w/ good survival


� 20-25% are stage IA, w/ good survival� 2% of all lymphomas are cutaneous

CUTANEOUS LYMPHOMA

� Diagnosis by biopsy only� No consensus: dx of mycosis fungoides� For all – immunophenotyping to diagnose abnormal

lymphocyte clones� Can ultimately involve lymph nodes, blood and visceral

organs


organs� More aggressive leukemic variant - Sezary

TNM – CUTANEOUS LYMPHOMAS

� T0 – suspicious lesions� T1 – limited lesions < 10% skin surface� T2 – generalized lesions, > 10% skin� T3 – skin tumors


TNM STAGE MYCOSIS FUNGOIDES

� Stage IA – T1 N0 (<10%): 20-25% have� Stage IB – T2 N0 (>10%): 30-40% have� Stage IIA – T1-2, N1


SURVIVAL –MYCOSIS FUNGOIDES

� Stage IA – studies show excellent prognosis and long-term survival

� Stage IB & IIA – 20% die of MF. Median overall survival > 11 years.

� Higher stages (IIB, III and up) – very short survival


PRIMARY CUTANEOUS ANAPLASTC LARGE T CELL

� 8-18% of primary cutaneous lymphomas� Radiation therapy for most� Some regress spontaneously� Some studies – good survival


SUMMARY

Many common skin tumors have excellent survival if adequate treatment

Melanoma may have excellent survival if diagnosed early and if treated adequately


Rarer skin tumors require caution

T1, esp. T1a, and Stage I cancers have the best prognoses, best UW risks

All skin tumors require close follow-up

Thank you for the privilege ofpresenting this topic

Jack Swanson, M. D.

Documents

SKIN CANCER - internal.nfp.com · Stage IIIa – T1-4a, N1a or N2a. MELANOMA TNM/STAGING Stage I – low risk for metastases and melanoma mortality Stage II – intermediate risk