Melanoma

MelanomaMelanoma

Alan L. CowanAlan L. Cowan

Anna M. PouAnna M. Pou

MelanomaMelanoma

Almost 30% of all melanomas arise Almost 30% of all melanomas arise in the head and neckin the head and neck

Widespread use of sunscreen has not Widespread use of sunscreen has not lowered the incidence.lowered the incidence.

Incidence is increasing almost 5% Incidence is increasing almost 5% per yearper year

Approximately 47,000 new cases in Approximately 47,000 new cases in 20012001

Predisposing FactorsPredisposing Factors Sun ExposureSun Exposure

Age, frequency, severity of exposure may play a Age, frequency, severity of exposure may play a rolerole

Sunscreen use may not be protectiveSunscreen use may not be protective Familial Melanoma / DNSFamilial Melanoma / DNS

Family members have almost 50% chance of Family members have almost 50% chance of developing melanomadeveloping melanoma

Lesions may be multiple and in sun shielded Lesions may be multiple and in sun shielded areasareas

Xeroderma PigmentosaXeroderma Pigmentosa Predisposes to several types of skin cancerPredisposes to several types of skin cancer Skin malignancies often appear by age 10Skin malignancies often appear by age 10

SunlightSunlight

UVB UVB (280-320nm)(280-320nm) Causes direct DNA damageCauses direct DNA damage Originally thought to be primary factorOriginally thought to be primary factor Blocked by current sunscreensBlocked by current sunscreens

UVA UVA (320-400nm)(320-400nm) Causes indirect DNA damage via free Causes indirect DNA damage via free

radicalsradicals Some now consider as more important than Some now consider as more important than

UVBUVB Sunscreen has little UVA protectionSunscreen has little UVA protection

Types of MelanomaTypes of Melanoma

Superficial SpreadingSuperficial Spreading Most commonMost common Cells atypical but uniform in appearanceCells atypical but uniform in appearance

NodularNodular Early invasion due to vertical growthEarly invasion due to vertical growth

Acral LentiginousAcral Lentiginous Appears on palms and solesAppears on palms and soles Histology shows heavily pigmented Histology shows heavily pigmented

dendritic processes in the basal layer dendritic processes in the basal layer

Types of MelanomaTypes of Melanoma DesmoplasticDesmoplastic

May lack pigmentMay lack pigment Peri-neural invasion is classicPeri-neural invasion is classic Histologic exam may show “school of fish” appearanceHistologic exam may show “school of fish” appearance

Lentigo Maligna MelanomaLentigo Maligna Melanoma May remain in-situ for decadesMay remain in-situ for decades Can spread along hair folliclesCan spread along hair follicles

MucosalMucosal Often lack melaninOften lack melanin Conventional staging system does not applyConventional staging system does not apply Site of lesion corresponds to prognosisSite of lesion corresponds to prognosis

Nasal cavity best prognosis, 31% at 5-yrsNasal cavity best prognosis, 31% at 5-yrs Paranasal sinuses worst prognosis, 0% at 5-yrsParanasal sinuses worst prognosis, 0% at 5-yrs

DiagnosisDiagnosis

HistoryHistory Family HistoryFamily History Sun exposureSun exposure Bleeding, painBleeding, pain

PhysicalPhysical ABCDABCD

HistologyHistology H&EH&E S-100, HMB-45S-100, HMB-45

BiopsyBiopsy ExcisionalExcisional

Recommended for small lesionsRecommended for small lesions Margins of 2mmMargins of 2mm

IncisionalIncisional For larger lesionsFor larger lesions Does not alter draining lymphaticsDoes not alter draining lymphatics

PunchPunch Same as incisionalSame as incisional

ShaveShave ContraindicatedContraindicated

NeedleNeedle ContraindicatedContraindicated

Clark stagingClark staging

Based upon histologic level of invasionBased upon histologic level of invasion Level I – Level I – Epidermis only (in situ)Epidermis only (in situ) Level II – Level II – Invades the papillary dermis, but Invades the papillary dermis, but

not to the papillary-reticular interfacenot to the papillary-reticular interface Level III – Level III – Invades to the papillary-reticular Invades to the papillary-reticular

interface, but not into the reticular dermisinterface, but not into the reticular dermis Level IV – Level IV – Into the reticular dermisInto the reticular dermis Level V – Level V – Into subcutaneous tissueInto subcutaneous tissue

Breslow stagingBreslow staging

Based upon absolute depth of Based upon absolute depth of invasioninvasion

Stage I – < 0.75 mmStage I – < 0.75 mm Stage II – 0.76 – 1.5 mmStage II – 0.76 – 1.5 mm Stage III – 1.51 – 4.0 mmStage III – 1.51 – 4.0 mm Stage IV - > 4.0 mmStage IV - > 4.0 mm

AJCC stagingAJCC staging

AJCC stagingAJCC staging

AJCC stagingAJCC staging

Prognosis by AJCC stagePrognosis by AJCC stage Stage IStage I

< 0.75 – 96 %< 0.75 – 96 % 0.75 – 1.5 – 87 %0.75 – 1.5 – 87 %

Stage II Stage II 1.5 – 2.49 – 75 %1.5 – 2.49 – 75 % 2.5 – 3.99 – 66 %2.5 – 3.99 – 66 % > 4.0 – 47 %> 4.0 – 47 %

Stage IIIStage III One node 45 %One node 45 % Two nodes < 20 %Two nodes < 20 %

Stage IVStage IV 8 – 10 %8 – 10 %

Percentages are five year survival except stage IV lesions Percentages are five year survival except stage IV lesions which represent one year survivalwhich represent one year survival

Treatment - Stage ITreatment - Stage I

LabsLabs LDHLDH

RadiologyRadiology CXRCXR

ExcisionExcision 1 cm margins1 cm margins

Adjunctive TherapyAdjunctive Therapy NoneNone

Treatment - Stage IITreatment - Stage II LabsLabs

LDHLDH RadiologyRadiology

CXRCXR Possible CT for metastasisPossible CT for metastasis Possible LymphoscintigraphyPossible Lymphoscintigraphy

ExcisionExcision 2 cm margins2 cm margins

Adjunctive TherapyAdjunctive Therapy Possible elective neck dissectionPossible elective neck dissection Possible sentinel lymph node biopsyPossible sentinel lymph node biopsy Possible elective radiationPossible elective radiation

Treatment - Stage IIITreatment - Stage III LabsLabs

LDHLDH Possible LFT’sPossible LFT’s

RadiologyRadiology CXRCXR CT neckCT neck Possible CT abdomen, MRI brainPossible CT abdomen, MRI brain

ExcisionExcision 2 cm margins2 cm margins Remove in-transit lymphatic basinsRemove in-transit lymphatic basins Neck dissection directed by siteNeck dissection directed by site

Posterolateral vs. Lateral vs. SupraomohyoidPosterolateral vs. Lateral vs. Supraomohyoid Adjunctive TherapyAdjunctive Therapy

Probable radiotherapyProbable radiotherapy Possible chemotherapyPossible chemotherapy

Treatment - Stage IVTreatment - Stage IV LabsLabs

CBC, LFT’s, LDHCBC, LFT’s, LDH RadiologyRadiology

CT Chest, Abdomen, PelvisCT Chest, Abdomen, Pelvis MRI brainMRI brain

ExcisionExcision 2 cm margins2 cm margins Remove in-transit lymphatic basinsRemove in-transit lymphatic basins Neck dissection directed by siteNeck dissection directed by site

Posterolateral vs. Lateral vs. SupraomohyoidPosterolateral vs. Lateral vs. Supraomohyoid Adjunctive TherapyAdjunctive Therapy

Radiation therapyRadiation therapy Consider chemotherapy as part of a clinical trialConsider chemotherapy as part of a clinical trial

Neck DissectionNeck Dissection

Neck DissectionNeck Dissection

Posterolateral NDPosterolateral ND Lesions in occipital and posterior scalp Lesions in occipital and posterior scalp

areasareas Lateral NDLateral ND

Lesions on temple, forehead, anterior Lesions on temple, forehead, anterior scalpscalp

SupraomohyoidSupraomohyoid Lesions of anterior faceLesions of anterior face

Follow-upFollow-up

Sentinel Lymph Node Sentinel Lymph Node BiopsyBiopsy

Used to determine nodal status in Used to determine nodal status in low-risk tumorslow-risk tumors

Allows for limited surgical morbidity.Allows for limited surgical morbidity. Has prognostic value for patient Has prognostic value for patient

outcomeoutcome

Sentinel Lymph Node Sentinel Lymph Node BiopsyBiopsy

ProcedureProcedure Preoperative lymph basin mapping using Preoperative lymph basin mapping using

lymphscintigraphy with Tc99lymphscintigraphy with Tc99 Preoperative injection of radiotracer allows Preoperative injection of radiotracer allows

for intraoperative gamma counter for intraoperative gamma counter localizationlocalization

Intraoperative injection of iosulfan blue Intraoperative injection of iosulfan blue allows for visual detection of involved nodes.allows for visual detection of involved nodes.

Allows for detection of sentinel nodes in 88-Allows for detection of sentinel nodes in 88-99% of patients depending on the study 99% of patients depending on the study cited.cited.

Sentinel Lymph Node Sentinel Lymph Node BiopsyBiopsy

Incidence of positive SLNB ~12%Incidence of positive SLNB ~12% False negative rate < 2%False negative rate < 2% Three year survival rates for negative vs. Three year survival rates for negative vs.

positive SLNB were 96.8% and 69.9%, positive SLNB were 96.8% and 69.9%, respectively respectively

Multivariate analysis has shown that positive Multivariate analysis has shown that positive SLNB predicts survival more accurately than SLNB predicts survival more accurately than depthdepth

Elective neck dissection has not been found to Elective neck dissection has not been found to change outcome if SLNB is negativechange outcome if SLNB is negative

Positive SLNB patients may be candidates for Positive SLNB patients may be candidates for radiation therapyradiation therapy

Sentinel Lymph Node Sentinel Lymph Node BiopsyBiopsy

Recurrence following negative SLNB is Recurrence following negative SLNB is most commonly in the assesed most commonly in the assesed lymphatics.lymphatics.

Gershenwald found that 80% of his Gershenwald found that 80% of his regional recurrences actually had regional recurrences actually had melanoma in the biopsied gland, but melanoma in the biopsied gland, but were missed on analysiswere missed on analysis

Use of S-100 or HMB-45 increases the Use of S-100 or HMB-45 increases the diagnostic value and may lower the false diagnostic value and may lower the false negative rate.negative rate.

RadiationRadiation

Indications include stage III or IV Indications include stage III or IV lesionslesions

Patients with positive SLNB should be Patients with positive SLNB should be consideredconsidered

Decreases local recurrence rates to Decreases local recurrence rates to 85-88%85-88%

Does not affect overall survivalDoes not affect overall survival May be contraindicated for lesions May be contraindicated for lesions

near the eye or for midline lesionsnear the eye or for midline lesions

ChemotherapyChemotherapy

Numerous therapy modalities existNumerous therapy modalities exist No significant benefit has been No significant benefit has been

found for any therapy to datefound for any therapy to date Administration of chemotherapy Administration of chemotherapy

should be done as part of an ongoing should be done as part of an ongoing clinical trial.clinical trial.

BibliographyBibliography Lentsch, Eric; Myers, Jeffrey. “Melanoma of the Head and Lentsch, Eric; Myers, Jeffrey. “Melanoma of the Head and

Neck: Current Concepts in Diagnosis and Management.” Neck: Current Concepts in Diagnosis and Management.” The Laryngoscope The Laryngoscope July 2001, 111:1209–1222.July 2001, 111:1209–1222.

Haywood, Rachel; Wardman, Peter; Sanders, Roy; Linge, Haywood, Rachel; Wardman, Peter; Sanders, Roy; Linge, Claire. “Sunscreens Inadequately Protect Against Claire. “Sunscreens Inadequately Protect Against Ultraviolet-A-Induced Free Radicals in Skin: Implications Ultraviolet-A-Induced Free Radicals in Skin: Implications for Skin Aging and Melanoma?” for Skin Aging and Melanoma?” The Journal of The Journal of Investigative DermatologyInvestigative Dermatology. 121:862-868, 2003.. 121:862-868, 2003.

Greene, Mark; et al. “High Risk of Malignant Melanoma in Greene, Mark; et al. “High Risk of Malignant Melanoma in Melanoma-Prone Families with Dysplastic Nevi.” Melanoma-Prone Families with Dysplastic Nevi.” Annals of Annals of Internal MedicineInternal Medicine. 102: 458-465, 1985.. 102: 458-465, 1985.

Gershenwald, Jeffrey; et al. “Multi-Institutional Melanoma Gershenwald, Jeffrey; et al. “Multi-Institutional Melanoma Lymphatic Mapping Experience: The Prognostic Value of Lymphatic Mapping Experience: The Prognostic Value of Sentinel Lymph Node Status in 612 Stage I or II Melanoma Sentinel Lymph Node Status in 612 Stage I or II Melanoma Patients.” Patients.” Journal of Clinical OncologyJournal of Clinical Oncology. 17 (3), 199:pp . 17 (3), 199:pp 976-83.976-83.

BibliographyBibliography Gershenwald, Jeffrey; et al. “Patterns of Recurrence Following a Gershenwald, Jeffrey; et al. “Patterns of Recurrence Following a

Negative Sentinel Lymph Node Biopsy in 243 Patients With Stage Negative Sentinel Lymph Node Biopsy in 243 Patients With Stage I or II Melanoma.” I or II Melanoma.” Journal of Clinical OncologyJournal of Clinical Oncology. 16 (6), 1998: pp . 16 (6), 1998: pp 2253-60.2253-60.

Ang, K.; et al. “Postoperative Radiotherapy for Cutaneous Ang, K.; et al. “Postoperative Radiotherapy for Cutaneous Melanoma of the Head and Neck Region.” Melanoma of the Head and Neck Region.” International Journal International Journal of Radiation Oncologyof Radiation Oncology. 30 (4) 1994: pp 795-98.. 30 (4) 1994: pp 795-98.

Braud, Filippo; et al. “Malignant Melanoma.” Braud, Filippo; et al. “Malignant Melanoma.” Critical Reviews in Critical Reviews in Oncology/HematologyOncology/Hematology. 47 (2003) 35-63.. 47 (2003) 35-63.

Alex, James C. “The Application of Sentinel Node Alex, James C. “The Application of Sentinel Node Radiolocalization to Solid Tumors of the Head and Neck: A 10-Radiolocalization to Solid Tumors of the Head and Neck: A 10-Year Experience.” Year Experience.” The LaryngoscopeThe Laryngoscope. 2004 Jan;114(1):2-19.. 2004 Jan;114(1):2-19.

Fauci, Anthony S.; et al. “Melanoma and Other Skin Cancers”. Fauci, Anthony S.; et al. “Melanoma and Other Skin Cancers”. Harrison’s Principles of Internal MedicineHarrison’s Principles of Internal Medicine. Chapter 88 McGraw-. Chapter 88 McGraw-Hill, San Francisco, California. 1998.Hill, San Francisco, California. 1998.

Bailey, Byron. “Melanoma of the Head and Neck”. Bailey, Byron. “Melanoma of the Head and Neck”. Head and Head and Neck Surgery – OtolaryngologyNeck Surgery – Otolaryngology. J.B. Lippincott Company, . J.B. Lippincott Company, Philadelphia, PA. 1993 pp1082-1090. Philadelphia, PA. 1993 pp1082-1090.