CUTANEOUS MELANOMA OF THE HEAD AND NECK: THE ROLE OF NECK DISSECTION

JAMES M. ROTH, M.D.

PAUL FRIEDLANDER, M.D.

CUTANEOUS MELANOMA

• IN 2001, 47,700 NEW CASES WILL BE DIAGNOSED

• INCIDENCE IS INCREASING AT 5% PER YEAR

• BY THE YEAR 2000 1 IN 75 PEOPLE WILL DEVELOP MELONAMA

• THIS INCREASE IS GREATER THAN ANY OTHER CANCER IN MEN AND SECOND ONLY TO LUNG CANCER IN WOMEN

CUTANEOUS MELANOMA• 15-30% OF MELANOMA OCCUR IN

THE HEAD AND NECK

• 10 YEAR SURVIVAL FOR STAGE 1 MELANOMA OF THE HEAD AND NECK IS 69% COMPARED TO 89% WITH MELANOMA OF THE EXTREMITY

• 50% RECCURRENCE RATE AFTER 5 YEARS FOR HEAD AND NECK COMPARED TO 50% IN 10 YEARS FOR EXTREMITY

RISK FACTORS

• SUN EXPOSURE: UV B AND TO SOME EXTENT UV A/ VISIBLE

• CONTROVERSY OVER CUMULATIVE EXPOSURE AND EARLY EXPOSURE

• PRE-EXISTING LESION: 1/3 ARISE IN CONGENITAL NEVI; 1/3 IN NEVI > 5 YEARS; 1/3 IN NEVI < 5 YEARS

• BLUE/GREEN EYES; BLOND/RED HAIR; FAIR CMPLEXION; INABILITY TO TAN

ABCD

• ASSYMETRY- UNEVEN GROWTH RATE

• BORDER- IRREGULAR (THE STRONGEST PREDICTOR OF MALIGNANCY)

• COLOR- VARIETIONS AND SHADING

• DIAMETER- INCREASES IN SIZE OR A DIAMETER >6MM

HISTORY

• MAJORITY ARE DETECTED BY THE PATIENT WITH ONLY 25% BEING DETECTED BY PHYSICIANS

• GROWTH OR COLOR CHANGE IN A PRE-EXISTING LESION

• BLEEDING, ITCHING, ULCERATION, AND PAIN- ALL OF THESE ARE USUALLY LATE SIGNS

HISTORY

• XERODERMA PIGMENTOSA– AUTOSOMAL RECESSIVE– MULTIPLE SKIN CANCERS BEFORE AGE

10– NUCLEOTIDE EXCISION REPAIR

• FAMILIAL MELANOMA/ DYSPLASTIC NEVUS SYNDROME– p16 GENE ON CHROMOSOME 9p21

PATHOLOGICAL SUBTYPES

• LENTIGO MALIGNA MELANOMA

• SUPERFICIAL SPREADING MELANOMA

• NODULAR MELANOMA

• ACRAL LENTIGINOUS MELANOMA

• DESMOPLASTIC MELANOMA

LENTIGO MALIGNA MELANOMA

• 5-10% OF ALL MELANOMA

• PROLONGED RADIAL GROWTH PHASE

• INVASION OF THE PAPILLARY DERMIS

• ULCERATION VERY SIGNIFICANT IN PROGNOSIS

SUPERFICIAL SPREADING

• MOST COMMON SUBTYPE (75%)

• INITIAL RADIAL GROWTH PHASE

• VERTICAL GROWTH HERALDED BY ULCERATION AND BLEEDING

• CELLS HAVE A UNIFORM APPEARANCE

NODULAR MELANOMA

• 10-15%

• NO RADIAL GROWTH PHASE

• VERTICAL GROWTH FROM THE ONSET

ACRAL LENTIGINOUS

• PALMS AND SOLES

• MOST COMMON MELANOMA IN AFRICAN AMERICANS

DESMOPLASTIC MELANOMA

• SPINDLE CELLS AMONG A FIBROUS STROMA “SCHOOLS OF FISH”

• OFTEN NOT PIGMENTED

• PROPENSITY TO SPREAD PERINEURALLY

STAGING SYSTEMS

• CLARK LEVEL

• BRESLOW THICKNESS

• AJCC TNM CLASSIFICATION

• MODIFICATIONS OF THE AJCC

CLARK LEVEL• LEVEL I

– ONLY INVOLVES THE EPIDERMIS

• LEVEL II– INVASION OF PAPILLARY DERMIS BUT

DOES NOT REACH THE PAPILLARY RETICULAR INTERFACE

• LEVEL III– INVASION FILLS AND EXPANDS THE

PAPILLARY DERMIS

CLARK LEVEL

• LEVEL IV– INVASION INTO THE RETICULAR

DERMIS

• LEVEL V– INVASION THROUGH THE

RETICULAR DERMIS INTO THE SUBCUTANEOUS TISSUE

BRESLOW THICKNESS

• STAGE I– 0.75MM OR LESS

• STAGE II– 0.76MM TO 1.50MM

• STAGE III– 1.51MM TO 4.0MM

• STAGE 1V– 4.0MM OR GREATER

AJCC TNM CLASSIFICATION• PRIMARY TUMOR (T)

– TX: CAN NOT BE ASSESSED

– T0: NO EVIDENCE OF PRIMARY TUMOR

– Tis: MELANOMA IN SITU CLARK LEVEL I

– T1: BRESLOW STAGE I CLARK LEVEL II

– T2: BRESLOW STAGE II CLARK LEVEL III

– T3: BRESLOW STAGE III CLARK LEVEL IV

• a- 1.5mm but no more than 3mm

• b- 3mm but no more than 4mm

– T4: BRESLOW STAGE IV CLARK LEVEL V AND/OR SATELLITE LESIONS WITHIN 2CM

• a-> 4mm or invades the subcutaneous tissue

• b- Satellite(s) within 2 cm of the primary

AJCC TNM CLASSIFICATION• REGIONAL LYMPH NODES (N)

– NX: CAN NOT BE ASSESSED

– NO: NO REGIONAL LYMPH NODES

– N1: >3CM DIAMETER IN ANY REGIONAL LYMPH NODE

– N2: >3CM AND OR IN-TRANSIT METASTASIS

• a-> 3cm in diameter

• b- in-transit metastasis

• c- both a and b

• in-transit metastasis involves skin or subcutaneous tissue >2cm from primary but not beyond the regional lymph nodes

AJCC TNM CLASSIFICATION

• DISTANT METASTASIS– MX: CAN NOT BE ASSESSED– MO: NO DISTANT METASTASIS– M1: DISTANT METASTASIS

• a: Metastasis in the skin or subcutaneous nodules beyond the regional lymph nodes

• b: visceral metastasis

AJCC TNM CLASSIFICATION

• STAGE 0: Tis, NO, MO

• STAGE I: T1/2, NO, MO

• STAGE II: T3/4, NO, MO

• STAGE III: ANY T, N1/2, MO

• STAGE IV: ANY T, ANY N, M1

M.D. ANDERSON MODIFICATIONS

• NOT USING OPTIMAL CUTOFFS OF TUMOR THICKNESS

• NO USE OF ULCERATION IN THE SYSTEM DESPITE IT BEING A POWERFUL PROGNOSTIC INDICATOR

• NUMBER OF NODES MORE IMPORTANT THAN SIZE

• SATELLITES, IN-TRANSIT METASTASIS HAVE SIMILAR OUTCOMES

M.D. ANDERSON MODIFICATIONS

• CUTOFFS FOR TUMOR THICKNESS SHOULD BE 1, 2, 4 MM- SIMPLER AND STILL SIGNIFICANT

• INCORPORATE ULCERATION SINCE THIS HAS BEEN SEEN IN MORE AGGRESSIVE LESIONS AND HAS BEEN STRONG IN PREDICTING OUTCOME

M.D. ANDERSON MODIFICATIONS

• NODAL STATUS STRONG INFLUENCE ON SURVIVAL 5YEARS SURVIVAL DATA N+ 32% AND N- 71% IN THICK TUMORS

• REGIONAL SKIN AND SUBCUTANEOUS METASTASIS A SEPARATE CATEGORY

• NUMBER OF NODES POSITIVE SHOULD REPLACE NODAL SIZE

PRIMARY LESIONS• WIDE LOCAL EXCISION

• TUMOR THICKNESS MOST SIGNIFICANT FACTOR FOR LOCAL RECURRENCE

• MARGINS RECOMMENDED FOR EXTREMITY NOT ALWAYS POSSIBLE IN THE HEAD AND NECK– <1MM 1CM MARGIN– 1-4MM 2CM MARGIN– >4 MM 2-3CM MARGIN

REGIONAL LYMPHATICS• SHAH 1991 MSK- ANALYZED 111

PATIENTS WITH MELANOMA AND METASTAIC DISEASE

• LESIONS INVOLVING THE EAR, FACE, AND ANTERIOR SCALP WERE AT HIGH RISK FOR PAROTID INVOLVEMENT

• LEVELS II THROUGH IV WERE MOST COMMONLY INVOLVED WITH LEVEL I INVOLVED 23% OF THE TIME AND LEVEL V INVOLVED 19% OF THE TIME

REGIONAL LYMPHATICS

• POSTERIOR NECK/ SCALP HAD NO INVOLVEMENT OF THE PAROTID GLAND, LOW INVOLVEMENT OF LEVEL 1 , AND INCREASED INVOLVEMENT OF LEVEL 5

REGIONAL LYMPHATICS

• LESIONS LESS THAN .76MM RARELY METASTASIZE

• LESIONS .76MM TO 4.0MM METASTASIZE 14-44% OF PATIENTS

• LESIONS >4.00 METASTASIZE 50-60% OF PATIENTS

• LESIONS <1.5MM HAD ONLY 8% METASTASIS

NODE POSITIVE NECK

• RADICAL VERSUS MODIFIED/ SELECTIVE NECK DISSECTION

• RADICAL NECK DISSECTION IS NOT ALWAYS NECESSARY AND MAY NOT PROVIDE ADDITIONAL BENEFIT

• O’BRIEN 1995 SYDNEY MELANOMA UNIT

SYDNEY MELANOMA UNIT

• 175 PATIENTS WITH 183 NECK DISSECTIONS

• 58% HAD A MODIFIED/SELECTIVE NECK DISSECTION IN THE PRESENCE OF CLINICAL NECK DISEASE

• NECK RECURRENCE OCCURRED IN 14% OF RADICAL, 0% OF MODIFIED, AND 23% OF SELECTIVE NECK DISSECTIONS

SYDNEY MELANOMA UNIT

• RADICAL NECK DISSECTIONS WERE MORE LIKELY TO HAVE MULTIPLE POSITIVE NODES AND NO ADJUVANT RADIATION THERAPY

• MODIFIED NECK DISSECTION HAD ONLY ONE NODE INVOLVEMENT

• CLINICAL METASTATIC MELANOMA (N+) CAN BE WELL CONTROLLED BY MRND

SYDNEY MELANOMA UNIT

• SELECTIVE NECK DISSECTION, WHERE ONLY SPECIFIC LEVELS WERE DISSECTED, SEEMED LESS EFFECTIVE

• BYERS 1998 M.D. ANDERSON AGREED THAT LESS THAN RADICAL SURGERY IS AN OPTION SECONDARY TO “PUSHING” CHARACTERISTIC OF THE NODES

NODE POSITIVE NECK

• STAGE III AND IV MELANOMA OF THE HEAD AND NECK SHOULD UNDERGO NECK DISSECTION AND MODIFIED RADICAL NECK DISSECTION APPEARS APPROPRIATE

• LEVELS I-IV IN ANTERIOR LESIONS

• LEVELS II-V IN POSTERIOR LESIONS

NODE NEGATIVE NECKS

• THE ROLE OF ELECTIVE NECK DISSECTION IS EVEN MORE CONTROVERSIAL

• LACK OF DATA TO SHOW ANY SIGNIFICANT SURVIVAL BENEFIT

• TUMOR < 0.75 MM, NONULCERATED ARE VERY RARE TO METASTIASIZE

NODE NEGATIVE NECKS• TUMORS > 4.0MM HAVE A HIGH

RATE OF DISTANT METASTASIS (70%) AND POTENTIAL BENEFIT FROM NECK DISSECTION IS LOW

• >4MM ELND MAY BENEFIT TO HELP STAGE THERE DISEASE AND POSSIBLY QUALIFY FOR ADJUVANT IMMUNOTHERAPY

• WHAT ABOUT TUMORS .76-3.9MM?

NODE NEGATIVE NECKS

• ELECTIVE LYMPH NODE DISSECTION (ELND)

• MAY BE OF THERAPUETIC BENEFIT

• MAY BE USEFUL IN PREDICTING PROGNOSIS AND BENEFIT OF ADJUVANT THERAPY

• STEPWISE PROGRESSION- LOCAL TO REGIONAL TO DISTANT

• HEAD AND NECK MAY NOT FOLLOW THE RULES

NODE NEGATIVE NECKS

• PROPONENTS

• PERALTA 1998 U. OF WASHINGTON

• DREPPER 1993 MULTICENTER STUDY IN GERMANY

• URIST 1984 AND BALCH 1996 INTERGROUP MELANOMA SURGICAL PROGRAM

• IMMUNOTHERAPY

PERALTA 1998 U. OF WASHINGTON

• 1.5-3.9MM LESIONS TREATED WITH AND WITHOUT ELND

• 174 TOTAL MELANOMA TREATED OF THESE 38 HAD CLINICALLY NODE NEGATIVE AND INTERMEDIATE THICKNESS AND 10 UNDERWENT ELND

• THE RATE OF DISTANT METASTASIS AND MORTALITY WERE 44% AND 35% LOWER THAN THOSE WHO DID NOT UNDERGO ELND AFTER 3 YEARS OF FOLLOW UP

• NUMBERS TO SMALL TO BE SIGNIFICANT

DREPPER 1993• 9 MEDICAL CENTERS

• 3616 WITH T2 TO T4 LESIONS (>0.76MM)

• <70 YEARS OLD

• NOT SPECIFIC FOR HEAD AND NECK MELANOMA

• ELND BENEFITTED MALE PATIENTS, NON ULCERATED LESIONS, AXIAL OR ACRAL MELANOMA, TUMORS >1.5MM TO 4.5MM

• 20% INCREASE IN 5 YEAR SURVIVAL

BALCH 1996

• 740 STAGE I AND II , 1-4MM LESIONS

• NOT CONFINED TO THE HEAD AND NECK ONLY 8 WITH HEAD AND NECK

• BENEFIT CONFINED TO PATIENT’S <60YEARS OLD, ESPECIALLY WITHOUT ULCERATION AND WITH THICKNESS OF 1-2MM (88% TO 81%)

• >60 YEARS OLD HAD WORSE SURVIVAL WITH ELND

URIST 1984• 534 PATIENTS WITH STAGE I HEAD AND

NECK MELANOMA PROSPECTIVE NON-RANDOMIZED

• SSM AND NM ELND DID NOT PROVIDE ANY BENEFIT FOR MELANOMA <0.76MM OR >4.0MM

• 1.5-3.99MM SHOWED A STATISTICALLY SIGNIFICANT INCREASE IN SURVIVAL RATE

• .76-1.49MM SHOWED IMPROVEMENT THAT WAS NOT STATISTICALLY SIGNIFICANT

IMMUNOTHERAPY

• KIRKWOOD 1996 U. OF PITTSBURGH

• MELANOMA AS A IMMUNOLOGIC DISEASE– SPONTANEOUSLY REGRESS– INFILTRATES OF B CELLS, T CELLS, AND

MACROPHAGES– VITILIGO AS A RESULT OF

ANTIMELANOCYTE ACTIVITY– SERA CONTAINS MELANOMA BINDING

ANTIBODIES

KIRKWOOD 1996 U. OF PITTSBURGH

• INTERFERON alpha- 2b

• PROLONGATION OF RELAPSE FREE SURVIVAL AND PROLONGATION OF OVERALL SURVIVAL

• BENEFIT GREATEST AMONG NODE POSITIVE PATIENTS

• NOT LIMITED TO THE HEAD AND NECK

NODE NEGATIVE NECKS

• ARGUMENTS AGAINST ELND

• KNUTSON 1972 U. OF MISSOURI

• O’BRIEN 1991 SMU

• KANE 1997 MAYO CLINIC

• SURGICAL MORBIDITY

• SENTINEL LYMPH NODE MAPPING

• RADIATION THERAPY

KNUTSON 1972 U. OF MISSOURI

• 87 PATIENTS MELANOMA OF THE HEAD AND NECK 42 UNDERWENT NECK DISSECTION

• 23 UNDERWENT ELECTIVE RADICAL NECK DISSSECTION

• 21.7% ELND HAD POSITIVE NODES

• 78.2% UNDERWENT A PROCEDURE WITH NO DEFINITIVE BENEFIT

• SMALL NUMBER OF PATIENT’S

O’BRIEN 1991 SMU

• THIS DATA WAS APART OF THE DATA USED BY URIST

• WHEN THE SMU DATA WAS PULLED FROM THIS A SURVIVAL BENEFIT WAS ORIGINALLY SEEN ON UNIVARIATE ANALYSIS

• MULTIVARIATE ANALYSIS ELIMINATED THIS BENEFIT

KANE 1997 MAYO CLINIC• GREATER PROGNOSTIC UTILITY

THAN SURVIVAL BENEFIT

• 180 STAGE 1 UNDERWENT ELND

• 8.3% HAD DISEASE ON PATHOLOGY

• T3 AND T4 LESIONS HAD 14% AND 30% POSITVE PATHOLOGIC SPECIMENS

• NO BENEFIT SEEN IN THESE THICKER LESIONS OR STAGE 1 LESIONS

• STILL RECOMMEND ELND FOR TUMORS >1.5MM

SURGICAL MORBIDITY

• SUPERFICIAL PAROTIDECTOMIES RISK INJURY TO THE FACIAL NERVE AND GUSTATORY SWEATING

• POSTOPERATIVE HEMATOMA• CHYLOUS FISTULA• SKIN FLAP NECROSIS• COSMETIC AND FUNCTIONAL DEFECT

SENTINEL NODE BIOPSY• RECENT ADVANCEMENT IN

MELANOMA THERAPY

• BASED ON THE STEPWISE PROGRESSION OF CANCER

• MOSTLY USED IN TRUNK AND EXTREMITY MELANOMA

• IS THE HEAD AND NECK PREDICTABLE?

• NEED FOR LYMPHOSCINTIGRAPHY?

• WELLS 1997 U. OF SOUTH FLORIDA

WELLS 1997 U. OF SOUTH FLORIDA

• IF PREOPERATIVE LYMPHOSCINTIGRAPHY IS NOT PERFORMED ELND AND NODE BIOPSIES MAY BE MISDIRECTED IN 50% OF CASES

• ALL NODAL BASINS AT RISK

• IN-TRANSIT NODAL AREAS

• NUMBER OF SENTINEL NODES

• LOCATION OF THE SENTINEL NODE IN RELATION TO OTHER NODES

SENTINEL NODE BIOPSY

• USE OF TWO MAPPING TECHNIQUES MAY INCREASE SENSITIVITY TO 95%

• IF PAROTID INVOLVED NEED TO PERFORM SUPERFICIAL PAROTIDECTOMY

• LESSER SURGERY GOES AGAINST SAFE PAROTID SURGERY

• NO PROSPECTIVE RANDOMIZED STUDIES

SENTINEL NODE BIOPSY

• TECHNICHALLY A DEMANDING PROCEDURE THAT REQUIRES MORE DATA TO SUPPORT ITS USE IN THE HEAD AND NECK

RADIATION THERAPY

• ORIGINALLY THOUGHT TO BE OF NO BENEFIT IN MELANOMA

• HYPERFRACTIONATION MAY PROVIDE BENEFIT

• GEARA 1996 M.D. ANDERSON 174 PATIENTS

• >1.5MM + WLE, WLE + TLND, TLND FOR RELAPSE

• 6GY FIVE TIMES OVER 2.5 WEEKS

RADIATION THERAPY• 9 OUT 174 HAD A RECURRENCE

ABOVE THE CLAVICLES

• 58 OUT OF 174 HAD DISTANT FAILURE

• 88% 5 YEAR LOCO-REGIONAL CONTROL

• 47% 5 YEAR SURVIVAL

• O’BRIEN DECREASE IN LOCAL RECURRENCE OF 12.2% IN PATIENTS WITH NODE (+) NECKS

CONCLUSIONS

• MELANOMA IS A COMPLEX AND PERPLEXING DISEASE PROCESS ESPECIALLY IN THE HEAD AND NECK

• CUTANEOUS MELANOMA OF THE HEAD AND NECK MAY BEHAVE DIFFERENTLY THAN MELANOMA OF THE EXTREMITY

CONCLUSIONS

• FOR NODE (+) NECKS- NECK DISSECTION IS APPROPRIATE AND A MODIFIED NECK DISSECTION IS OFTEN POSSIBLE

• IMMUNOTHERAPY WITH INTERFERON alpha- 2b APPEARS PROMISING FOR INDIVIDUALS WITH PATHOLOGICALLY POSITIVE NECK DISEASE

CONCLUSIONS

• NODE (-) NECKS– LACK OF RANDOMIZED PROSPECTIVE

DATA– ROLE OF SENTINEL NODE BIOPSY AND

RADIATION THERAPY HOLD PROMISE BUT NEED FURTHER INVESTIGATION

– PET SCAN?

CONCLUSIONS

•WEAR YOUR SUNSCREEN!!!

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