Head and Neck Melanoma Overview Diagnosis and Evaluation Staging Treatment
Head and Neck Overview In 2010, estimated 68,130 new cases and 8,700 died of disease in the U.S. (under estimate as many are unreported) Incidence is increasing in men more rapidly than any other malignancy, and in women, second to lung cancer. Median age at diagnosis is 59 and ranks second to adult leukemia in loss of years of life per death.
Overview Since 1950 increase of > 600% in annual incidence and 165% increase in annual mortality Seventh most common cancer in women and fifth most common in men. Head and neck melanoma accounts for 30% of all cases, due to sun exposure and melanocyte density.
Overview: Etiology Ultraviolet exposure Positive family history Prior Melanoma carries a 10x greater risk of second primary Multiple atypical moles or dysplastic nevi Fair skin (although any ethnic group and non-exposed skin can develop melanoma)
Overview: Outcomes 80% present with localized disease 15% present with regional disease 5% present with distant disease Localized disease, <1.0mm thick, 90% 5 yr survival Nodal disease reduces survival by half Distant disease, survival less than 10%
Lentigo Maligna Atypical proliferation of melanocytes Precursor to melanoma? Typically sun exposed cheek of the elderly Although non-invasive, 20% exhibit features of lentigo maligna melanoma
Lentigo Maligna Melanoma 5-10% of melanomas but 50% of head and neck melanomas are lentigo maligna melanoma. Hallmark is invasion into papillary dermis Radial growth phase is prolonged.
Superficial Spreading Melanoma Most common melanoma variant Radial growth phase followed by a vertical growth phase Homogeneous neoplastic cells are distributed in all layers of the epidermis
Desmoplastic Melanoma Least common melanoma variant Often atypical appearance, may be nonpigmented, often occur in the head and neck Local recurrence, distant mets, perineural invasion and decreased survival
Melanoma History Fair skin Early or severe sunburns Ultraviolet light exposure Family history Prior skin cancer Prior radiation exposure Immunosuppression
Melanoma Physical Exam “ABCD” Assymetry Border irregularities Color variegation Diameter > 6mm Woods lamp black light highlights borders Palpation of cervical nodes and parotid glands
Melanoma: Biopsy Excisional biopsy with 1-3 mm margin preferred. (avoid wider margin to permit subsequent SLNB) Orient the biopsy with ultimate excision in mind Full thickness incisional or punch of thickest part of lesion acceptable Shave biopsy may compromise assessment of Breslow thickness but is acceptable if index of suspicion is low
Clark Levels: I: in-situ, epidermis II: papillary dermis III: to reticular derm IV: into reticular V: into subcu. Tissue Breslow Thickness: Stage I: <0.75mm Stage II: 0.76-1.50 StageIII: 1.51-4.0 StageIV: >4.0mm
Melanoma Workup Lentigo maligna melanoma and thin lesions (no ulceration or spread to reticular dermis), stage 0 or stage 1A do not require additional testing Early stage melanoma: LDH and CXR More advanced stage: CT, MRI, PET/CT
Melanoma: Treatment of the Primary Lesion Surgical excision with margin (frozen sections not reliable) Moh’s micrographic excision by experienced dermatologists and dermatopathologists, with rapid immunohistochemical stains
Melanoma Treatment: Radiation Therapy Melanoma historically deemed “radio- resistant” Currently used as primary treatment for unresectable disease or medically unfit for surgery Adjuvant for adverse features of primary, regional disease and mets.
Melanoma: Risk of Occult Regional Disease Tumor thickness: 0.75 - 1.5mm, 5% risk Tumor thickness: 1.50 – 4.0mm, 20% risk Tumor thickness: >4.0mm, 35% risk Overall 15-20% of clinically Stage I and Stage II lesions have occult Stage III disease and are at risk for recurrence
Melanoma: Sentinel Node Biopsy Introduced by Morton, et al, 1992 “Identification of a positive sentinel lymph node has emerged as the most important prognostic factor for recurrence and survival in cutaneous melanoma.” SLNB can be augmented by injection of iso-sulfan blue dye
Melanoma and Sentinel Node Biopsy Allows detection of occult regional mets, promotes accurate staging and decision making for adjuvant therapies Spares unnecessary elective neck dissection for 80% of patients with intermediate-thickness who do not have regional mets Indicated for 0.8-4.0mm thick or ulcerated lesions of any thickness. Due to high rate of presumed regional mets in those >4.0mm, no added benefit to SLNB
Melanoma: SLNB False negative rate up to 10% Limit false negatives: remove all blue nodes, suspicious nodes and those with >10% of ex-vivo radioactive count of the most radioactive sentinel node.
Melanoma: Neck Dissection Indications Clinically N+ disease Positive sentinel lymph node No role for elective node dissection (N0 or SLNB negative) “The staging of intermediate thickness (1.2- 3.5mm) primary melanomas according to the results of sentinel node biopsy provides important prognostic information and identifies patients with nodal mets. whose survival can be prolonged by immediate lymphadenectomy.” Morton, NEJM 355:1307, 2006
Melanoma: Neck Dissection for Intermediate Thickness Lesions Multicenter Selective Lymphadenectomy Trial (MSLT-1), Morton, NEJM 2006 1339 patients with 1.2-3.5mm melanomas Randomized to wide excision with observation and possible delayed neck dissection vs wide excision with SLNB and immediated neck dissection for SLNB +. Delayed TLND had 52.4% 5 yr. survival Immediate TLND had 72.3% 5 yr. survival SLNB negative had 90.2% 5 yr. survival
Neck Dissection for Stage III Melanoma Include involved lymph nodes and nodes at greatest risk according to drainage patterns For microscopic disease: functional neck dissection preserving SCM, XI, and IJV For macroscopic disease: sacrifice of non- lymphatic structures should be based on clinical invasion
Adjuvant Systemic Therapy for Advanced Melanoma
Systemic Therapy for Advanced Melanoma High-dose interferon (IFN@-2b) is ( the only adjuvant treatment approved by the FDA to minimize recurrence and mets in stage IIB to III melanoma (Moore et al, Head and Neck Cancer, 2008) Combinations of interferon with melanoma vaccines, other biologic response modifiers such as interleukin-2, gene therapy and chemo. such as dacarbazine, cisplatin and vinblastine are the subject of clinical trials.
Melanoma of the Head and Neck: References NCCN Guidelines Version 3.2012 Head and Neck Cancer An Evidence-Based Team Approach, Moore et al, ch.9, Carcinoma of the Skin of the Head, Face, and Neck, 152-179, 2008 Melanoma of the Head and Neck, Conley, 1990 Role of Neck Dissection in Melanoma (presentation), Bradford, Update in Head and Neck Cancer (course), April 27-29,2012, Harvard Medical School.