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

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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. O F 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!!!

BIBLIOGRAPHY • Balch, C. et al. Efficacy of an Elective Regional Lymph Node Dissection of 1-4mm Thick Melanoma for Patients 60 Years of Age and Younger. Annals of Surgery. 1996; 224 (3): 255-266 • Buzaid, A. et al. Critical Analysis of the Current AJCC Staging System for Cutaneous Melanoma and Proposal of a New Staging System. Journal of Clinical Oncology. 1997; 15(3): 1039-51 • Breslow, A. Thickness, Cross-Sectional Area and Depth of invasion in Prognosis of Cutaneous Melanoma. Annals of Surgery. 1970; 172 (5): 902-8 • Byers, R. Treatment of the Neck in Melanoma. Otolaryngologic Clinics of North America. 1998; 31 (5): 833-39 • Drepper, H. et al. Benefit of Elective Lymph Node Dissection in Subgroups of Melanoma Patients. Cancer. 1993; 72(3): 741-49 • Jansen, L. et al. Sentinel Node Biopsy for Melanoma in the Head and Neck Region. Head and Neck. 2000:27-33 • Kane, W. et al. Treatment Outcome for 424 Primary Cases of Clinical Stage 1 Cutaneous Malignant Melanoma of the Head and Neck. Head and Neck. 1997:457-65

BIBLIOGRAPHY • Kirkwood, J. et al. Interferon Alfa-2b Adjuvant Therapy of High-Risk Resected Cutaneous Melanoma: the ECOG Trial EST 1684. Journal of Clinical Oncology. 1996; 14(1):7-17 • Knutson, C. et al. Melanoma of the Head and Neck. American Journal of Surgery. 1972; 124:543-550 • Lentsch, E. et al. Melanoma of the Head and Neck: Current Concepts in Diagnosis and Management. The Laryngoscope. 2001; 11:1209-22 • Myers, J. Value of Neck Dissection in the Treatment of Patients with Intermediate- Thickness Cutaneous Malignant Melanoma of the Head and Neck. AOHN. 1999; 125:110-115 • O’Brien, C. et al. Experience with 998 Cutaneous Melanomas of the Head and Neck over 30 Years. American Journal of Surgery. 1991; 162:310-314 • O’Brien, C. et al. Radical, Modified, and Selective Neck Dissection for Cutaneous Malignant Melanoma. Head and Neck. 1995:232-41 • O’Brien, C. et al. Adjuvant Radiotherapy Following Neck Dissection and Parotidectomy for Metastatic Malignant Melanoma. Head and Neck. 1997:589-94.

BIBLIOGRAPHY • Peralta, E. et al. Malignant Melanoma of the Head and neck: Effect of Treatment on Survival. The Laryngoscope. 1998; 108:220-223 • Shah, J. et al. Patterns of Lymph Node Metastases from Cutaneous Melanomas of the Head and Neck. American Journal of Surgery. 1991; 162: 320-23 • Shah, P. et al. Adjuvnt Immunotherapy for Patients with Melanoma: Are Patients with Melanoma of the Head and Neck Candidates for This Therapy. Head and Neck. 1997:595-603 • Stadlemann, W. et al. Cutaneous Melanoma of the Head and neck: Advances in Evolution and Treatment. Plastic and Reconstructive Surgery. 2000; 105(6): 2105-26 • Urist, M. et al. The Influence of Surgical Margins and Prognostic Factors Predicting the Risk of Local Recurrence in 3445 Patients with Primary Cutaneous Melanoma. Cancer. 1985; 55:1398-1402 • Urist, M. et al. Head and Neck Melanoma in 534 Clinical Stage 1 Patients. Annals of Surgery. 1984:769-75 • Wells, K. et al. Sentinel Lymph Node Biopsy in Melanoma of the Head and Neck. Plastic and Reconstructive Surgery. 1997; 100(3):591-94