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
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? Clinical, laboratory, pathology evidence of recurrence If pathology report is inadequate or unavailable, try doctor records
PRIMARY TYPES Basal Cell Carcinoma 80%(800,000/yr) SquamousCell Carcinoma 16% Malignant Melanoma (Largely related to sun exposure) 4%
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 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 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 suppression If one SCC high chance of 2 nd 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 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 Tis T1 T2 III - T3 III T1 N0 M0 N0 M0 N0 M0 N0 M0 N1 M0
SCC TREATMENT Moh s micrographic surgery Other surgery 97% cure 92% cure Other tx less effective: radiation, cryotherapy, 5FU Surgery for recurrence 77% cure 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 survival More common if freckles, moles (esp. atypical), nonmelanoma 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) -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, bleeding) Rigel. CA 2010;60:301-316
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 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% * 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% 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, 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
MELANOMA 2002 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 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 2 nd is 10-25 x. Recent study: 8% risk of 2 nd 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 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% 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% 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 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 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 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%
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 lesions 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
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 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 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 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/ 2 nd 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/ 2 nd cancers. Dermatofibrosarcoma protruberans. Locally invasive, 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 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 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 of presenting this topic Jack Swanson, M. D.