Melanoma is a malignant skin cancer that arises from melanocytes. It can originate in the skin, mucous membranes, or eye. Risk factors include genetic predispositions, excessive sun exposure, and the presence of atypical moles. There are several types of melanoma classified by their appearance, location, and growth pattern. Prognosis depends on the cancer stage and other factors like thickness and ulceration. Treatment involves surgical removal with biopsy and may include lymph node assessment, immunotherapy, targeted therapy, or chemotherapy for advanced cases.

2. DR.MARYAM ZAHRA
MELANOMA

3. Melanoma
 A malignant tumour arising from melanocytes
 Most commonly cutaneous in origin
 Also arise from Mucosal surfaces(e.g. oral,
conjunctival , vaginal) uveal tract & leptomeninges

4. Cont..
 Brown-black ,skin-colored to pink-red, i.e.
Amelanotic
 Melanoma ; 4% of skin cancers, 80% deaths

5. Risk Factors
 Melanoma precursors
 Congenital naevi
 Common naevi
 Atypical or dysplastic naevi
 Genetic factors
 Environmental factors

6. Genetic Factors
 Family history of cutaneous melanoma
 Lightly pigmented skin
 Tendency to burn, inability to tan
 Red hair color
 DNA repair defects (e.g. xeroderma
pigmentosum)

7. Environmental Factors
 Intense intermittent sun exposure
 Chronic sun exposure
 Residence in equatorial latitudes
 PUVA (possible)
 Tanning bed use, especially under the age of
35 years
 Iatrogenic or acquired immunosuppression

8. Genes Associated With Melanoma
 Cyclin‐dependent kinase (CDK) inhibitor 2A gene
( CDKN2A ) ,Located on chromosome 9p21
 CDK4 gene located on chromosome 12q13 ,It
encodes the kinase targeted by p16/Ink4a

9. Classification

10. Superficial Spreading Melanoma
 Most common 60 to
70 percent
 Age :40 to 60 years
 Site :Trunk of men
and the legs of
women
 Less then 5 mm in dia

11. Superficial Spreading Melanoma

12. Nodular Melanoma
 Second most common
 Sixth decade of life
 15% to 30% of all melanomas
 Frequently on the trunk, head and neck
 Rapid evolution
 Lack radial growth phase
 Blue or black

13. Nodular Melanoma

14. Nodular Melanoma

15. Lentigo Maligna Melanoma
 Sub type of melanoma in situ
 Prolonged radial growth phase
 10-15 % of CM
 Diagnosed in 7th - 8th decade
 Chronically Sun exposed areas of face
 Flat slowly enlarging freckle like macule

16. Lentigo Maligna Melanoma

17. Lentigo maligna & LMM

18. Acral Lentiginous Melanoma
 Discrete light brown or black macule with
indistinct borders
 “ dirty-like-stain”
 Sole is the prime location
 Age > 60 years
 Black > white

19. Acral Lentiginous Melanoma

20. Acral Lentiginous Melanoma

21. Subungual Acral Lentiginous
Melanoma

22. Hutchinson's Nail Sign

23. Subungual Melanoma With Ulceration
& Dystrophy

24. Melanoma In Situ
 Confined to epidermis
 Non malignant
 Cured completely by excision

25. Mucosal Melanoma

26. Anal Melanoma

27. Ocular Melanoma

28. Desmoplastic Melanoma
 Uncommon type
 Deeply invasive
 Neurotropic
 Recurrence
 Low metastatic rate
 Fibrosis

29. Regressive Melanoma
 Inflammation results in focal regression of
melanoma which is seen as an irregular focus of
hypopigmentation

30. Differential Diagnosis

31. Differential Diagnosis
 Seborrheic keratosis
Melanoma in situ,
SSM & lentigo maligna
 Solar lentigo
Lentigo maligna
 Pigmented actinic keratosis
LM

32. Differential Diagnosis
 Bcc
Nodular melanoma
 Scc
Amelanotic melanoma

33. Differential Diagnosis
 Angioma
Red nodular melanoma
 Sarcoma (AMM )

34. Differential Diagnosis
 Histiocytoma (NM)
 Dermatofibroma (NM)

35. Differential Diagnosis
 Trophic ulcers or planter warts ( ALM )
 Malignant blue naevus

36. Differential Diagnosis
 Onychomycosis (subungual melanoma)
 Paronychia or naevus
 Pyogenic granuloma

37. Diagnosing A Case Of Melanoma

38. Diagnosis
 History
 Physical examination
 Dermoscopy
 Biopsy
 Histopathology
 Immunohistochemistry
 Novel techniques

39. ABCDE Criteria
 A = Asymmetry
 B = Border irregularity
 C = Color
 D = Diameter >6 mm
 E = Evolution

40. Ugly Duckling Sign

41. Glasgow 7-Point Checklist
 Change in size
 Irregular shape
 Irregular color (major criterion)
 Diameter atleast 7 mm
 Inflammation
 Oozing/bleeding
 Change in sensation (minor criterion)

42. Dermoscopy
 Also known as Amplified surface microscopy
 Useful tool for early recognition of melanoma &
differential diagnosis of pigmented lesions of
skin

45. Difference b/w Benign vs Malignant
Pigmented Lesions

46. Histopathological Features Of
Melanoma
 Asymmetrical pigment distribution
 Inflammatory infiltrate
 Pagetoid spread of melanocytes
 Incohesive melanocytes within nests
 Sheets of melanocytes within the dermis
 Obliteration or destruction of adnexal
structures

47. Histopathological Features Of
Melanoma

48. Superficial Spreading Melanoma

49. Lentigo Maligna

50. Lentigo Maligna Melanoma

51. Nodular Melanoma
Thin epidermis
vertical
growth phase
more
Thin epidermis
Vertical growth phase

52. Acral Lentiginous Melanoma
Elongation of rete
ridges
Intraepi-
dermal
migration

53. Breslow Depth

54. Clark’s Levels Of Melanoma
Classification

55. TNM staging

56. Anatomical Stage Groupings For
Cutaneous Melanoma

58. Immunohistochemistry
 S100 protein is expressed by 99% of all
melanomas and melanocytic naevi
 HMB-45 most specific
 Melan-A (MART-1)
 MITF
 Sox-10
 Microphthalmia transcription factor

59. Novel Techniques
 Fluorescence in situ hybridization
 Comparative genomic hybridization (CGH)
 Gene expression profiling (GEP)

60. Management

61. Management
 Screening
 Counseling
 Wide local excision
 Sentinel lymph node biopsy
 Mohs micrographic surgery
 Systemic treatment of melanoma
 Immunotherapy
 Kinase inhibitors
 Chemotherapy
 Radiotherapy

62. Strategies For Early Detection
Screening
(a) High‐risk population
(b) General population
(c) Occasional screening
(d) Public health education

63. Narrow Margin Excisional Biopsy

64. Biopsy Techniques Of Melanoma

65. Recommended Clinical Margin For
Wide Local Excision Of Melanoma

66. Sentinel Lymph Node Biopsy
 Helps in detection of first node of potential
involvement
 Least invasive procedure
 A trace (Radio-colloid & vital blue dye) injected
intradermally
 Collects in SLN (primary site of metastasis)
 No after affects like lymphedema

67. SLNB Technique

68. Mohs Micrographic Surgery
 It allows precise microscopic control of the
margins by utilizing tangentially cut frozen-
section histology

70. Treatment Algorithm Of Advanced
Melanoma

71. Systemic Treatment In Melanoma
 Adjuvant systemic therapy: treatment for localized
disease after surgical resection in stage III
 Adjuvant systemic therapy: specific treatment
approaches in stage III–N2–3 disease
 Systemic therapy for metastatic disease (advanced
stage IIIB/ IIIC and stage IV disease)

72. Treatment For Localized Disease After
Surgical Resection In Stage III
 Interferon-α (IFN‐α) or Pegylated interferon
 20 MU per square BSA 4 week IV therapy 5 Ds/
week followed by 10 MU per square BSA SC
applications 3 times / week for 1 year as well as
long‐term SC therapy for 2–5 years once weekly
using Peg-INF
 S/E : Flu like symptoms, Deranged LFT’s,
Depression, mylosuppression

73. Stage III–N2–3 Disease
 Inoperable in‐transit metastases treated with
isolated limb perfusion (ILP) using melphalan or
TNF‐α
 Radiation therapy
 Electrochemotherapy

74. Stage III-N2-3 disease

75. Advanced Stage IIIB/IIIC And Stage IV
Disease
 Molecular subgroups depending upon genetic
alterations
(a) BRAF 50%
(b) NRAS 20%
(c) KIT 10%
(d) GNA11/GNAQ <1%

76. Advanced Stage IIIB/IIIC And Stage IV
Disease
 Immunotherapy
(a) anti-PD-1 (nivolumab & pembrolizumab)
(b) anti-CTLA-4 (ipilimumab)
 Kinase inhibitors
 Conventional chemotherapy

77. Immunotherapy
(a) anti-PD-1 (nivolumab & pembrolizumab)
(b) anti-CTLA-4 (ipilimumab)
(c) IL-2
MOA:
Anti-PD-1 inhibits (–ve) regulator of T cell
Anti-CTLA-4 activates T cells

78. Dose:
Ipilimumab 3mg/kg + Nivolumab 1mg/kg ( uveal
melanoma )
Ipilimumab 10mg/kg (melanoma with brain mets)
every 3weekly for 4 cycles

79. Kinase Inhibitors
 Vemurafenib & Dabrafenib (BRAF and NRAS
mutated melanoma)
 Binimetinib ,Selumetinib or Trametinib (MEK-
inhibitors)
 Imatinib ( KIT & GNAQ mutated melanoma )

80. Chemotherapy
Dacarbazine ( DTIC)
Temozolomide
Taxanes
Fotemustine

82. Follow Up Recommendations

84. Prognosis
 Good for stage I & II disease after WLE with
sentinel lymph node biopsy

85. Poor Prognostic Factors
 Thickness (Breslow index)
 Sentinel node status
 Ulceration
 Mitotic rate
 Regression
 Age (negative for older age)
 Sex (negative for males)
 Location (negative for head and neck)

86. Genetic Counseling
 A family history of invasive CM or pancreatic
cancer >3 affected members
 Multiple primary invasive CM ( >3) , including 1
early-onset tumor (at age < 45 y)
 >1 MBAIT and a family history of mesothelioma,
meningioma, &/or uveal melanoma
 >2 MBAITs