1. CUTANEOUS MELANOMA OF THE HEAD AND NECK: THE ROLE OF NECK DISSECTION JAMES M. ROTH, M.D. PAUL FRIEDLANDER, M.D.

2. 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

3. 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

4. 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

5. ABCD ASSYMETRY- UNEVEN GROWTH RATE BORDER- IRREGULAR (THE STRONGEST PREDICTOR OF MALIGNANCY) COLOR- VARIETIONS AND SHADING DIAMETER- INCREASES IN SIZE OR A DIAMETER >6MM

6. 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

7. HISTORY XERODERMA PIGMENTOSA –AUTOSOMAL RECESSIVE –MULTIPLE SKIN CANCERS BEFORE AGE 10 –NUCLEOTIDE EXCISION REPAIR FAMILIAL MELANOMA/ DYSPLASTIC NEVUS SYNDROME –p16 GENE ON CHROMOSOME 9p21

8. PATHOLOGICAL SUBTYPES LENTIGO MALIGNA MELANOMA SUPERFICIAL SPREADING MELANOMA NODULAR MELANOMA ACRAL LENTIGINOUS MELANOMA DESMOPLASTIC MELANOMA

9. LENTIGO MALIGNA MELANOMA 5-10% OF ALL MELANOMA PROLONGED RADIAL GROWTH PHASE INVASION OF THE PAPILLARY DERMIS ULCERATION VERY SIGNIFICANT IN PROGNOSIS

10. SUPERFICIAL SPREADING MOST COMMON SUBTYPE (75%) INITIAL RADIAL GROWTH PHASE VERTICAL GROWTH HERALDED BY ULCERATION AND BLEEDING CELLS HAVE A UNIFORM APPEARANCE

11. NODULAR MELANOMA 10-15% NO RADIAL GROWTH PHASE VERTICAL GROWTH FROM THE ONSET

12. ACRAL LENTIGINOUS PALMS AND SOLES MOST COMMON MELANOMA IN AFRICAN AMERICANS

13. DESMOPLASTIC MELANOMA SPINDLE CELLS AMONG A FIBROUS STROMA “SCHOOLS OF FISH” OFTEN NOT PIGMENTED PROPENSITY TO SPREAD PERINEURALLY

14. STAGING SYSTEMS CLARK LEVEL BRESLOW THICKNESS AJCC TNM CLASSIFICATION MODIFICATIONS OF THE AJCC

15. 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

16. CLARK LEVEL LEVEL IV –INVASION INTO THE RETICULAR DERMIS LEVEL V –INVASION THROUGH THE RETICULAR DERMIS INTO THE SUBCUTANEOUS TISSUE

17. 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

18. 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

19. 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

20. 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

21. 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

22. 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

23. 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

24. 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

25. 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

26. 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

27. REGIONAL LYMPHATICS POSTERIOR NECK/ SCALP HAD NO INVOLVEMENT OF THE PAROTID GLAND, LOW INVOLVEMENT OF LEVEL 1, AND INCREASED INVOLVEMENT OF LEVEL 5

28. 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

29. 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

30. 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

31. 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

32. 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

33. 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

34. 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

35. 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?

36. 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

37. 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

38. 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

39. 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

40. 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

41. 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 4.0MM 1.5-3.99MM SHOWED A STATISTICALLY SIGNIFICANT INCREASE IN SURVIVAL RATE.76-1.49MM SHOWED IMPROVEMENT THAT WAS NOT STATISTICALLY SIGNIFICANT

42. 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

43. 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

44. 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

45. 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

46. 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

47. 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

48. SURGICAL MORBIDITY SUPERFICIAL PAROTIDECTOMIES RISK INJURY TO THE FACIAL NERVE AND GUSTATORY SWEATING POSTOPERATIVE HEMATOMA CHYLOUS FISTULA SKIN FLAP NECROSIS COSMETIC AND FUNCTIONAL DEFECT

49. 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

50. 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

51. 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

52. SENTINEL NODE BIOPSY TECHNICHALLY A DEMANDING PROCEDURE THAT REQUIRES MORE DATA TO SUPPORT ITS USE IN THE HEAD AND NECK

53. 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

54. 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

55. 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

56. 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

57. CONCLUSIONS NODE (-) NECKS –LACK OF RANDOMIZED PROSPECTIVE DATA –ROLE OF SENTINEL NODE BIOPSY AND RADIATION THERAPY HOLD PROMISE BUT NEED FURTHER INVESTIGATION –PET SCAN?

58. CONCLUSIONS WEAR YOUR SUNSCREEN!!!

59. 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

60. 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.

61. 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