【医学英文ppt课件】-Melanoma

Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,【医学英文课件】 Melanoma,【医学英文课件】 Melanoma,1,【医学英文ppt课件】-Melanoma,2,【医学英文ppt课件】-Melanoma,3,Risk Factors,UV light,: strongest association for intermittent exposure and sunburn in adolescence and childhood,an analysis of more than 20 epidemiological studies indicates that people who begin using tanning devices before age 30 are 75% more likely to develop melanoma.,Phenotypic traits,: fair complexion, inability to tan, blue/green eyes, blonde/red hair, freckling,Familial,: 10%, multiple genes involved, ex: xeroderma pigmentosa (AR), Familial atypical multiple-mole melanoma syndrome (CDKN2),Atypical nevi,: 3 to 20 fold increase risk, ex: giant congenital nevus, greater than 100 nevi,Immunosuppression,Risk FactorsUV light: stronges,4,Classification,Superficial spreading,: is the most common of the melanomas (70%). It usually occurs in middle age, but may occur in younger people. Characterized by horizontal growth phase,Lentigo maligna (10-15%),: usually occurs in older people (6th decade) and occurs in chronically sun exposed areas, most commonly on the face. Hutchinson Freckle This type carries the best prognosis,Classification,5,Classification,Acral-lentiginous melanoma,(5%) is most frequent in blacks and Asians. The most common site is the plantar surface of the foot; may be subungual,Nodular melanoma,(15%)most often occurs in middle age and is more frequent in males. Characterized by vertical growth phase. Typically carries the worst prognosis,Classification,6,Classification,Desmoplastic: frequently mistaken for a scar; pale and fleshy,Classification,7,Growth Phases,Horizontal (radial): more indolent, stays relatively superficial,Vertical: grows deep, have increased metastatic potential; vertical growth phase melanomas may arise from radial growth phase or de novo, nodular melanoma have most vertical phase,Growth PhasesHorizontal (radia,8,Clinical Diagnosis,A: asymmetry- one half of lesion doesnt match the other,B: border irregularity-ragged, notched, fuzzy,C: color-not uniform,D: diameter- greater than 6 mm,E: enlargement/evolution,Nodular,Elevated,Firm,growing,Clinical DiagnosisA: asymmetry,9,Diagnosis,Histopathology necessary for diagnosis,Melanoma markers: S-100, Melan-A, HMB-45,Initial biopsy: excisional biopsy preferred with 1-2 mm of normal appearing skin, orient the incision along langers line of stress, or parallel to long axis of extremity,Larger lesions: punch or incisional biopsy, not as accurate because the thickest part of the lesion may not be the part sampled.,DiagnosisHistopathology necess,10,Diagnosis,Shave biopsy: can underestimate depth of invasion. Only good if lesion is not transected (i.e. deep margin is negative),DiagnosisShave biopsy: can un,11,Clarks Level,describes the level of anatomical invasion of the melanoma in the skin,Five anatomical levels, and higher levels have worsening prognostic implications,1. Melanoma confined to the epidermis,2. Invasion into the papillary dermis,3. Invasion to the junction of the papillary and reticular dermis,4. Invasion into the reticular dermis,5. Invasion into the subcutaneous fat,Clarks Level,12,Breslow Depth,Total vertical height of lesion,Used to predict prognosis and determines excisional margins,Depth and sentinel node status are most important prognostic factors,Breslow Thickness Approximate 5 year survival,In situ,4mm 50%,Breslow Depth Breslow Thicknes,13,Prognosis,Tumor thickness in millimeters,depth related to skin structures (Clark level),type of melanoma?,presence of ulceration,presence of lymphatic/perineural invasion,presence of tumor-infiltrating lymphocytes,presence of satellite lesions (including microsatellites)*,presence of regional or distant metastasis,PrognosisTumor thickness in mi,14,Treatment,Surgical excision is primary treatment,Surgical margins based on depth of invasion (Breslows),Tumor Depth,Surgical Margin,In situ,0.5cm,T1 (0.1-1.0mm),1cm,T2 (1.01-2.0mm),1-2cm,T3 (2.01-4.0mm),2cm,T4 (4mm),2cm,TreatmentTumor DepthSurgical M,15,Surgery: Sentinel Node Biopsy,Along with depth of invasion, SLN is the most important prognostic factor,Sentinel lymph node biopsy detects occult lymph node metastases in patients who are,clinically node negative,Should be done in all patients T1,Should be done in T1b (ulceration or mitoses 0/hpf) patients with melanoma 0.75-1mm deep,If the sentinel lymph node is negative there is a 96% chance that the rest of the nodes are negative,If positive, a regional lymphadenectomy is indicated, metastatic workup is indicated,Surgery: Sentinel Node BiopsyA,16,Sentinel Lymph Node Biopsy,Tc labeled Sulphur colloid injected pre-op with lymphatic mapping,Isousulfan blue injected in OR,Remove all “hot and/or blue nodes”,10% rule,Sentinel Lymph Node Biopsy,17,Lymphoscintigraphy,Important to note all possible nodal basins,May have more than 1 SLN,Lymphoscintigraphy,18,Staging,Staging,19,Staging Work-Up,Potential to metastasize to any organ: skin, subcutaneous tissue, nodes lung, liver, brain, bone,Early stage (in situ, Stage I or II) no formal workup needed unless pt has specific symptoms. Standard pre-op labs/images only,Typically preformed for stage III and IV,CT,PET,MRI brain,LDH,BRAF mutation status for unresectable Stage III or Stage IV,Staging Work-UpPotential to me,20,In Transit Melanoma,Intradermal lymphatic metastases between the melanoma and primary nodal basin,Signifies at least N2c disease,Same pathologic process are satellite lesions and microsatellitosis,Poor prognosis,Can be treated with resection, but often unresectable,In Transit Melanoma,21,Adjuvant Treatment for Resected Stage III,Immunotherapy,Ipilimumab (CTLA-4 Inhibitor) now becoming standard of care. Shown to improve overall survival in Stage IV and prolong disease free survival in stage III,Interferon has been shown to improve disease free survival in high risk stage II and Stage III. Conflicting data on improved overall survival. Recent Sunbelt Melanoma trial showed no benefit from IFN in any subgroub. Seems to work best in ulcerated primaries,Ongoing clinical trials of PD-1 and MEK inhibitors,Standard chemotherapy largely inefective in melanoma,Adjuvant Treatment for Resecte,22,Treatment for Stage IV Disease,Check BRAF status,If BRAF mutation found, can use BRAF inhibitors (vemurafenib, dabrafenib). Work quickly but drug resistance develops,MEK inhibitors can be used aline or in combination with BRAF inhibitors,PD1 inhibitors (nivolumab) most promising new development,Ipilimumab,High Dose IL-2, rarely used, administered in ICU,Resection of metastatic lesions can be considered in appropriately selected patients,Treatment for Stage IV Disease,23,Treatment of In Transit Disease,Represents at least N2c, Stage IIIb disease,Can be resected with negative margin if feasible,Isolated limb infusion/perfusion (melphalan, TNF),Immunotherapy (Ipilimumab, BRAF, PD-1, MEK inhibitors),Intralesional Therapy (Talimogene lahaperepvec T-Vec): First FDA approved oncolytic viral therapy. Improves durable response rate. 15% of patients had regression of visceral mets. Amy take several months to see an effect,Treatment of In Transit Diseas,24,Surveillance,Primary objective to identify potentially curable locoregional recurrences and second primary cancers,Stage I and II: most locoregional reoccurrences,Stage III: systemic recurrences more common,Most reoccurrences caught by PE,Stage IA recommend detailed medical history and PE every 6 to 12 months,Stage IB to III history and PE every 3 to 6 months for 3 years, every 4 to 12 mo for 2 years,Order additional studies based on symptoms,SurveillancePrimary objective,25,Case,56 year old male presents with pigmented lesion on his left forearm. Raised, 1.5cm diameter, irregular borders.,What to do?,Case56 year old male presents,26,Case,HPI: Lesion noted 1 year ago, slowly growing since then. Over last month, became raised and borders changed. No other lesions. No family history of melanoma. Long history of sun exposure as a child and adult working in the oil and gas industry.,PE: WNL except arm lesion. No clinical lymphadenopathy. No satellite lesions.,What to do next?,CaseHPI: Lesion noted 1 year a,27,Case,Biopsy (What kind?),Excisional or full thickness punch biopsy. No shave biopsy,Pathology: Melanoma 2.75mm depth with ulceration. 6 mitoses/hpf with lymphovascular invasion present. No microsatellitosis.,What is the clinical stage (TNM)?,CaseBiopsy (What kind?),28,Case,Clinical Stage T3b (2.01-4mm deep with ulceration) N0,What is the primary treatment?,CaseClinical Stage T3b (2.01-4,29,Case,Surgical Resection with 2cm margins and sentinel node biopsy,Pathology: Residual melanoma in situ at previous scar, margins negative. 2 sentinel nodes negative for metastatic disease.,Final stage Stage IIb,Is any adjuvant treatment required?,CaseSurgical Resection with 2c,30,Case,Not required. IFN is an option for high risk stage II patients but observation and close follow up is acceptable.,2 years later the patient develops increasing axillary lymophadenopathy. No new skin lesions present.,What to do next?,CaseNot required. IFN is an o,31,Case,Biopsy of node proves presence of metastatic disease.,Check BRAF status,Metastatic workup (Brain MRI, PET CT, LDH),CaseBiopsy of node proves pres,32,Case,Workup shows no evidence of disease outside of the axilla.,What to do next,CaseWorkup shows no evidence o,33,Case,Axillary dissection (levels I-III),Systemic Immunotherapy,Questions?,CaseAxillary dissection (level,34,