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Controversies in Melanoma

Controversies in Melanoma. Prof Ravi Kant , Dr Ajay Yadav, Dr Vivek Gupta, Dr Vishal Gupta, Ms Tanmya Stuti Ravi. Controversies in Melanoma. Biology Detection-Computer, USG, RT-PCR Staging- AJCC 2000 +Prognosis SLN Biopsy + ELND Surgical margins Adjuvant treatment + Vaccines Summary.

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Controversies in Melanoma

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  1. ControversiesinMelanoma Prof Ravi Kant,Dr Ajay Yadav, Dr Vivek Gupta, Dr Vishal Gupta, Ms Tanmya Stuti Ravi

  2. Controversies in Melanoma • Biology • Detection-Computer, USG, RT-PCR • Staging- AJCC 2000 +Prognosis • SLN Biopsy + ELND • Surgical margins • Adjuvant treatment + Vaccines • Summary

  3. Biology of melanoma development and progression

  4. Biology of melanoma • Melanocytes → • Nevus → • Dysplastic nevus → • Radial growth phase → • Vertical growth phase → • Metastases.

  5. Melanoma & Nevi • Class I = Precursor • Class II = Intermediate • Class III = VGP tumorigenic VGP = vertical growth phase

  6. Cell cycle regulation in melanoma

  7. Expression of defined molecules in melanoma cell

  8. Express adhesions receptors, Integrins, Adherine, and cellular adhesions molecules

  9. melanoma cells express N-adherine instead of E-adherine. • E-adherine allows melanocytes to adhere to keratinocytes, while melanoma cells can not adhere to keratinocytes

  10. B- catenin pathway

  11. Biology- what is new? • PTENpathway = phosphatase and tensin deleted on chromosome 10 → • IGF-1 → Akt / PKB (Oncogene)+PtdIns(3,4)P2→ P13 kinase →growth factor + adhesion receptor (integrin)

  12. Biology – what is new? • Ras pathway→Grb2/Sos →ras →Raf →MEK 1,2 →MAPK 1.2 →TCF/SRF/Elk-1 →Proliferation • As apoptosis is blocked by depriving • Bad & Caspase-9 from p13 kinase • Apoptosis turned into growth

  13. Naevi

  14. Nevus • Proliferative lesion of melanocytes • Scattered along basal layer • Acquired - mostly • congenital

  15. Naevi : types • Lentigo Flat • Junctional • Compound – slightly elevated • Intradermal – papillomatous

  16. Naevi: Lentigo simplex-1 • Pigmented macule, <5mm, jet black color • In infants & children • Melanocytic proliferation along basal layer

  17. Naevi: Lentigo simplex-2 • Abundant melanocytes along basal layer • Associated with Peutz-Jegher syndrome • P-J syndrome = hamartomatous polypes in GIT +naevi in oral & buccal mucosa

  18. Naevi: Junctional • Next stage after lentigo • Macular lesions, < 7mm • Less deeply pigmented than lentigo • Homogenous brown black areas • Melanocytic proliferation along basal layer • Highest malignant potential

  19. Naevi: Compound • Next stage of maturation of junctional naevi • In children & adolescent • Pale brown & papular • Junctional + dermal component

  20. Naevi: Intradermal • Last stage in maturation • Mostly after 30 years of age • Flesh colored papule with little pigment • Melanocytes confined to dermis only

  21. Blue naevi • Benign melanocytic naevi • Slate blue color • Two types : common & cellular

  22. Common Blue naevi Mostly in scalp & dorsum of hand, feet • Dermal collection of spindle melanocytes • F > M , max. in 4th decade

  23. Blue naevi: Cellular type • Uncommon • F > M • > 50% in sacrococcygeal area& buttock • < 1% under go malignancy • Rx : simple excision

  24. Nevus • Common • Atypical • Congenital • Spitz • Familial

  25. Malignant Melanoma • Arises from transformed melanocytes of epidermis • Accounts for almost all deaths from skin cancer • 4 fold increase in incidence in Australia

  26. Melanoma : Risk Factors-1 • Congenital naevi >5% BSA, 1000X • Previous melanoma • Family history • 5 naevi > 5mm (Common nevi) • 50 naevi > 2mm (Common nevi)

  27. Melanoma : Risk Factors-2 • Dysplastic nevi, Atypical= 2X for single; 12X for >10 • Family history Atypical =37-148X • Dysplatic naevi syndrome

  28. Melanoma : Risk factors-3 • White race, • Red hair, • Blond hair, • Blue eyes • Poor tanning ability, • Sunburns during childhood • Albinism

  29. Melanoma : Risk factors-4 • Freckles • Equatorial latitude • Xeroderma pigmentosa • Psoralen sunscreen • Tanning salons • Junctional naevi

  30. Melanoma : Risk factors-5 • Spitz Nevi= benign except when • >10 y age • +ulceration • >1cm • Involve subcut fat • Mitotic activity >6/mm2

  31. Melanoma : Risk factors-6 • Familial syndromes • B-K nevus syndromes • Atypical nevus • CDKN2A mutation • CDK4 mutation

  32. DD • Pigmented Basal cell CA • Seborrheic keratitis • Solar lentigines • Atypical nevi

  33. MM: Clinical features • Lentigo maligna : Hutchinson's freckle (7-15%) • Superficial spreading : most common (60-70%) • Nodular : 12-25% • Acral lentiginous • Amelanotic

  34. 1. Superficial spreading Melanoma • Most common type 70% • Occur any where on skin except hands & feet • Usually > 5 mm , flat • Variegated color pattern • Irregular edge with areas of regression • Long radial growth phase

  35. 2. Nodular Melanoma • Most malignant • Younger age group • Any part of the body • raised and always palpable with sharp irregular border • Blue, black or gray color • Lack of radial growth phase

  36. 2. Nodular Melanoma • Second most common 15-30 % • Rapid onset • ♂>♀

  37. 3. Lentigo maligna Melanoma • Hutchinsons melanotic freckle • Least common type 5% • Most commonly on face of elderly • Begins as irregularly pigmented ,flat, brown macule • quite large at the time of diagnosis late invasive growth phase • Good prognosis

  38. 4. Acral lentiginous • Uncommon 1-3% • Palm, sole, heel & subungual • More common in dark skin persons • Subungual –common in big toe or thumb • Poor prognosis , 29%@20Y • 70% ulcerate, 74% >1.5 mm

  39. 4. Acral lentiginous-risk factor • >50 y age • >3mm width, variegated border • Extension of pigment in to nail bed/ nail fold • Dark complexioned patient

  40. 5. Amelanotic Melanoma • Desmoplastic, 1.7% • H&N • Pink, reveal some pigment on close inspection; Stain+ with S-100 • Worse prognosis • Often present with regional lymph nodes metastases

  41. 5. Amelanotic Melanoma • Locally aggressive • Known for local recurrences • Stain ► S-100

  42. MM : spread • Local extension • Blood stream : lung, liver, brain, skin • Lymphatic : • embolisation, permeation • satellite nodule • in-transit nodule

  43. Controversies in Melanoma • Biology • Detection-Computer, USG, RT-PCR • Staging- AJCC 2000 +Prognosis • SLN Biopsy + ELND • Surgical margins • Adjuvant treatment + Vaccines • Summary

  44. MM : Diagnosis • Signs of transformation of mole in to MM • Major • Change in size, shape, color • Minor • Inflammation, itching • Crusting or bleeding • > 5mm diameter

  45. MM: Diagnosis • A : Asymmetry • B : irregular border • C : color variegation • D : diameter > 5 mm • E : enlargement or evolution

  46. Detection- Vision • A = asymmetry • B = border irregularity • C = color variegation • D =diameter > 6mm • E = elevation, enlargement, evolutionary changes • F= any funny change

  47. Detection- Vision • Change in size • Change in shape • Change in Color • Inflammation • Crusting / bleeding • Sensory change • > 7mm in size enlargement

  48. Detection- Digital Vision • Epiluminescence microscopy • Dermatoscopy • Surface microscopy • Incident light microscopy • Can see the dermis, epidermo-dermal junction

  49. Melanin pigment network Black dots Globules Streaks Radial streaming Blue-white milky veils Pseudopods Pseudo network Structure less area Melanin reticulum Epidermo-dermal junction Multiple brown dots Epiluminescence microscopy-ominous signs

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