Head and Neck MelanomaHead and Neck MelanomaHenry Ho, M.D.Henry Ho, M.D.

Head and Neck MelanomaHead and Neck Melanoma

OverviewOverview Diagnosis and EvaluationDiagnosis and Evaluation StagingStaging TreatmentTreatment

Head and Neck OverviewHead and Neck Overview

In 2010, estimated 68,130 new cases and In 2010, estimated 68,130 new cases and 8,700 died of disease in the U.S. (under 8,700 died of disease in the U.S. (under estimate as many are unreported)estimate as many are unreported)

Incidence is increasing in men more Incidence is increasing in men more rapidly than any other malignancy, and in rapidly than any other malignancy, and in women, second to lung cancer.women, second to lung cancer.

Median age at diagnosis is 59 and ranks Median age at diagnosis is 59 and ranks second to adult leukemia in loss of years second to adult leukemia in loss of years of life per death.of life per death.

OverviewOverview

Since 1950 increase of > 600% in Since 1950 increase of > 600% in annual incidence and 165% increase annual incidence and 165% increase in annual mortalityin annual mortality

Seventh most common cancer in Seventh most common cancer in women and fifth most common in women and fifth most common in men.men.

Head and neck melanoma accounts Head and neck melanoma accounts for 30% of all cases, due to sun for 30% of all cases, due to sun exposure and melanocyte density.exposure and melanocyte density.

Overview: EtiologyOverview: Etiology

Ultraviolet exposureUltraviolet exposure Positive family historyPositive family history Prior Melanoma carries a 10x greater risk Prior Melanoma carries a 10x greater risk

of second primaryof second primary Multiple atypical moles or dysplastic neviMultiple atypical moles or dysplastic nevi Fair skin (although any ethnic group and Fair skin (although any ethnic group and

non-exposed skin can develop non-exposed skin can develop melanoma)melanoma)

Overview: OutcomesOverview: Outcomes

80% present with localized disease80% present with localized disease 15% present with regional disease15% present with regional disease 5% present with distant disease5% present with distant disease Localized disease, <1.0mm thick, 90% Localized disease, <1.0mm thick, 90%

5 yr survival5 yr survival Nodal disease reduces survival by halfNodal disease reduces survival by half Distant disease, survival less than 10%Distant disease, survival less than 10%

Lentigo MalignaLentigo Maligna

Atypical proliferation of melanocytesAtypical proliferation of melanocytes Precursor to melanoma?Precursor to melanoma? Typically sun exposed cheek of the Typically sun exposed cheek of the

elderlyelderly Although non-invasive, 20% exhibit Although non-invasive, 20% exhibit

features of lentigo maligna features of lentigo maligna melanomamelanoma

Lentigo Maligna MelanomaLentigo Maligna Melanoma

5-10% of melanomas but 50% of 5-10% of melanomas but 50% of head and neck melanomas are head and neck melanomas are lentigo maligna melanoma.lentigo maligna melanoma.

Hallmark is invasion into papillary Hallmark is invasion into papillary dermisdermis

Radial growth phase is prolonged.Radial growth phase is prolonged.

Superficial Spreading Superficial Spreading MelanomaMelanoma

Most common melanoma variantMost common melanoma variant Radial growth phase followed by a Radial growth phase followed by a

vertical growth phasevertical growth phase Homogeneous neoplastic cells are Homogeneous neoplastic cells are

distributed in all layers of the distributed in all layers of the epidermisepidermis

Desmoplastic MelanomaDesmoplastic Melanoma

Least common melanoma variantLeast common melanoma variant Often atypical appearance, may be Often atypical appearance, may be

nonpigmented, often occur in the nonpigmented, often occur in the head and neckhead and neck

Local recurrence, distant mets, Local recurrence, distant mets, perineural invasion and decreased perineural invasion and decreased survival survival

Melanoma History Melanoma History

Fair skinFair skin Early or severe sunburnsEarly or severe sunburns Ultraviolet light exposureUltraviolet light exposure Family historyFamily history Prior skin cancerPrior skin cancer Prior radiation exposurePrior radiation exposure ImmunosuppressionImmunosuppression

Melanoma Physical ExamMelanoma Physical Exam

““ABCD”ABCD” AssymetryAssymetry Border irregularitiesBorder irregularities Color variegationColor variegation Diameter > 6mmDiameter > 6mm Woods lamp black light Woods lamp black light

highlights bordershighlights borders Palpation of cervical Palpation of cervical

nodes and parotid nodes and parotid glandsglands

Melanoma: BiopsyMelanoma: Biopsy

Excisional biopsy with 1-3 mm margin Excisional biopsy with 1-3 mm margin preferred. (avoid wider margin to permit preferred. (avoid wider margin to permit subsequent SLNB)subsequent SLNB)

Orient the biopsy with ultimate excision in Orient the biopsy with ultimate excision in mindmind

Full thickness incisional or punch of thickest Full thickness incisional or punch of thickest part of lesion acceptablepart of lesion acceptable

Shave biopsy may compromise assessment of Shave biopsy may compromise assessment of Breslow thickness but is acceptable if index of Breslow thickness but is acceptable if index of suspicion is lowsuspicion is low

Clark Levels:Clark Levels: I: in-situ, epidermisI: in-situ, epidermis II: papillary dermisII: papillary dermis III: to reticular dermIII: to reticular derm IV: into reticularIV: into reticular V: into subcu. V: into subcu.

TissueTissue Breslow Thickness:Breslow Thickness: Stage I: <0.75mmStage I: <0.75mm Stage II: 0.76-1.50Stage II: 0.76-1.50 StageIII: 1.51-4.0StageIII: 1.51-4.0 StageIV: >4.0mmStageIV: >4.0mm

Melanoma WorkupMelanoma Workup

Lentigo maligna melanoma and thin Lentigo maligna melanoma and thin lesions (no ulceration or spread to lesions (no ulceration or spread to reticular dermis), stage 0 or stage 1A reticular dermis), stage 0 or stage 1A do not require additional testingdo not require additional testing

Early stage melanoma: LDH and CXREarly stage melanoma: LDH and CXR More advanced stage: CT, MRI, More advanced stage: CT, MRI,

PET/CTPET/CT

Melanoma: Treatment of the Melanoma: Treatment of the Primary LesionPrimary Lesion

Surgical excision with margin (frozen Surgical excision with margin (frozen sections not reliable)sections not reliable)

Moh’s micrographic excision by Moh’s micrographic excision by experienced dermatologists and experienced dermatologists and dermatopathologists, with rapid dermatopathologists, with rapid immunohistochemical stainsimmunohistochemical stains

Melanoma Treatment: Melanoma Treatment: Radiation TherapyRadiation Therapy

Melanoma historically deemed Melanoma historically deemed “radio-resistant”“radio-resistant”

Currently used as primary treatment Currently used as primary treatment for unresectable disease or medically for unresectable disease or medically unfit for surgeryunfit for surgery

Adjuvant for adverse features of Adjuvant for adverse features of primary, regional disease and mets.primary, regional disease and mets.

Melanoma: Risk of Occult Melanoma: Risk of Occult Regional DiseaseRegional Disease

Tumor thickness: 0.75 - 1.5mm, 5% riskTumor thickness: 0.75 - 1.5mm, 5% risk Tumor thickness: 1.50 – 4.0mm, 20% Tumor thickness: 1.50 – 4.0mm, 20%

riskrisk Tumor thickness: >4.0mm, 35% riskTumor thickness: >4.0mm, 35% risk Overall 15-20% of clinically Stage I and Overall 15-20% of clinically Stage I and

Stage II lesions have occult Stage III Stage II lesions have occult Stage III disease and are at risk for recurrencedisease and are at risk for recurrence

Melanoma: Sentinel Node Melanoma: Sentinel Node BiopsyBiopsy

Introduced by Morton, et al, 1992Introduced by Morton, et al, 1992 ““Identification of a positive sentinel Identification of a positive sentinel

lymph node has emerged as the lymph node has emerged as the most important prognostic factor for most important prognostic factor for recurrence and survival in cutaneous recurrence and survival in cutaneous melanoma.”melanoma.”

SLNB can be augmented by injection SLNB can be augmented by injection of iso-sulfan blue dyeof iso-sulfan blue dye

Melanoma and Sentinel Node Melanoma and Sentinel Node BiopsyBiopsy

Allows detection of occult regional mets, Allows detection of occult regional mets, promotes accurate staging and decision promotes accurate staging and decision making for adjuvant therapiesmaking for adjuvant therapies

Spares unnecessary elective neck dissection Spares unnecessary elective neck dissection for 80% of patients with intermediate-for 80% of patients with intermediate-thickness who do not have regional metsthickness who do not have regional mets

Indicated for 0.8-4.0mm thick or ulcerated Indicated for 0.8-4.0mm thick or ulcerated lesions of any thickness.lesions of any thickness.

Due to high rate of presumed regional mets Due to high rate of presumed regional mets in those >4.0mm, no added benefit to SLNB in those >4.0mm, no added benefit to SLNB

Melanoma: SLNBMelanoma: SLNB

False negative rate up to 10%False negative rate up to 10% Limit false negatives: remove all blue Limit false negatives: remove all blue

nodes, suspicious nodes and those nodes, suspicious nodes and those with >10% of ex-vivo radioactive with >10% of ex-vivo radioactive count of the most radioactive count of the most radioactive sentinel node.sentinel node.

Melanoma: Neck Dissection Melanoma: Neck Dissection IndicationsIndications

Clinically N+ diseaseClinically N+ disease Positive sentinel lymph nodePositive sentinel lymph node No role for elective node dissection (N0 or No role for elective node dissection (N0 or

SLNB negative)SLNB negative) ““The staging of intermediate thickness (1.2-The staging of intermediate thickness (1.2-

3.5mm) primary melanomas according to the 3.5mm) primary melanomas according to the results of sentinel node biopsy provides results of sentinel node biopsy provides important prognostic information and important prognostic information and identifies patients with nodal mets. whose identifies patients with nodal mets. whose survival can be prolonged by immediate survival can be prolonged by immediate lymphadenectomy.” Morton, NEJM 355:1307, lymphadenectomy.” Morton, NEJM 355:1307, 20062006

Melanoma: Neck Dissection for Melanoma: Neck Dissection for Intermediate Thickness LesionsIntermediate Thickness Lesions Multicenter Selective Lymphadenectomy Multicenter Selective Lymphadenectomy

Trial (MSLT-1), Morton, NEJM 2006Trial (MSLT-1), Morton, NEJM 2006 1339 patients with 1.2-3.5mm melanomas1339 patients with 1.2-3.5mm melanomas Randomized to wide excision with Randomized to wide excision with

observation and possible delayed neck observation and possible delayed neck dissection vs wide excision with SLNB and dissection vs wide excision with SLNB and immediated neck dissection for SLNB +.immediated neck dissection for SLNB +.

Delayed TLND had 52.4% 5 yr. survivalDelayed TLND had 52.4% 5 yr. survival Immediate TLND had 72.3% 5 yr. survivalImmediate TLND had 72.3% 5 yr. survival SLNB negative had 90.2% 5 yr. survivalSLNB negative had 90.2% 5 yr. survival

Melanoma: Cutaneous Melanoma: Cutaneous Lymphatic Drainage PatternsLymphatic Drainage Patterns

Neck Dissection for Stage III Neck Dissection for Stage III MelanomaMelanoma

Include involved lymph nodes and Include involved lymph nodes and nodes at greatest risk according to nodes at greatest risk according to drainage patternsdrainage patterns

For microscopic disease: functional For microscopic disease: functional neck dissection preserving SCM, XI, neck dissection preserving SCM, XI, and IJVand IJV

For macroscopic disease: sacrifice of For macroscopic disease: sacrifice of non-lymphatic structures should be non-lymphatic structures should be based on clinical invasionbased on clinical invasion

Nodal Basins to Dissect in Nodal Basins to Dissect in TLNDTLND

Anterior scalp, temple, anterior Anterior scalp, temple, anterior auricle, pre-auricular skin, forehead: auricle, pre-auricular skin, forehead: dissect superficial parotid, SND I-IVdissect superficial parotid, SND I-IV

Midline chin, nose, cheek medial to Midline chin, nose, cheek medial to lateral canthus, anterior neck skin: lateral canthus, anterior neck skin: SND I-IV (consider bilateral drainage)SND I-IV (consider bilateral drainage)

Nodal Basins to Dissect in Nodal Basins to Dissect in TLND TLND

Posterior scalp, posterior auricle, Posterior scalp, posterior auricle, posterior neck skin: postero-lateral posterior neck skin: postero-lateral SND II-V plus post-auricular and SND II-V plus post-auricular and occipital nodesoccipital nodes

Lateral neck skin, scalp and ear that Lateral neck skin, scalp and ear that overlap plane of external auditory overlap plane of external auditory canal: SND I-V, superficial canal: SND I-V, superficial parotidectomy for scalp/earparotidectomy for scalp/ear

Neck Levels of Lymph Node Neck Levels of Lymph Node DissectionDissection

Adjuvant Systemic Therapy for Adjuvant Systemic Therapy for Advanced MelanomaAdvanced Melanoma

Systemic Therapy for Systemic Therapy for Advanced MelanomaAdvanced Melanoma

High-dose interferon (IFN@-2b) is ( the High-dose interferon (IFN@-2b) is ( the only adjuvant treatment approved by the only adjuvant treatment approved by the FDA to minimize recurrence and mets in FDA to minimize recurrence and mets in stage IIB to III melanoma (Moore et al, stage IIB to III melanoma (Moore et al, Head and Neck Cancer, 2008)Head and Neck Cancer, 2008)

Combinations of interferon with melanoma Combinations of interferon with melanoma vaccines, other biologic response modifiers vaccines, other biologic response modifiers such as interleukin-2, gene therapy and such as interleukin-2, gene therapy and chemo. such as dacarbazine, cisplatin and chemo. such as dacarbazine, cisplatin and vinblastine are the subject of clinical trials.vinblastine are the subject of clinical trials.

Melanoma of the Head and Melanoma of the Head and Neck: ReferencesNeck: References

NCCN Guidelines Version 3.2012 NCCN Guidelines Version 3.2012 Head and Neck Cancer An Evidence-Based Head and Neck Cancer An Evidence-Based

Team Approach, Moore et al, ch.9, Team Approach, Moore et al, ch.9, Carcinoma of the Skin of the Head, Face, Carcinoma of the Skin of the Head, Face, and Neck, 152-179, 2008and Neck, 152-179, 2008

Melanoma of the Head and Neck, Conley, Melanoma of the Head and Neck, Conley, 19901990

Role of Neck Dissection in Melanoma Role of Neck Dissection in Melanoma (presentation), Bradford, Update in Head (presentation), Bradford, Update in Head and Neck Cancer (course), April 27-and Neck Cancer (course), April 27-29,2012, Harvard Medical School.29,2012, Harvard Medical School.