malignant skin lesions and management

1. MALIGNANT
SKIN LESIONS

2. Skin
• Largest organ of the body
• Weight - 16% TBW
• Surf. Area - 2sq.m
• Thickness - 0.5-1mm in palms and sole, 0.05-0.09mm on eyelid
• Layers
1. Epidermis(5% of skin)
2. Dermis
3. Subcutaneous Layer
• Blood supply : Cutaneous branches which are direct branches of segmental
arteries, perforate the underlying muscle and directly to deeper tissues

4. Epidermis
• Stratified sq. epithelium
• Different layers:
1. Stratum corneum (Superficial)
2. Stratum lucidum
3. Stratum granulosum
4. Stratum spinosum
5. Stratum basale (deepest and contains melanocytes)

5. Dermis
Thickness - 0.6-3mm
2 layers :
1. Papillary
2. reticular
Skin appendages
Blood vessels
Nerve endings
Cells: Mast cells and Histiocytes

6. Function of Skin
• Barrier
• Regulates temperature and water homeostasis
• Excretory Function
• Endocrine and Metabolic functions
• Sensory

7. 1. Acanthosis
It implies increased thickness of the Malpighian layer
2. Hyperkeratosis
Hyperkeratosis is thickening of the stratum corneum
3. Mole/Naevi
When these melanocytes layer in the epidermis they form a simple mole.
Melanocytes that aggregate in the dermis or at the dermoepidermal junction
are called naevus cells.

8. Congenital Disorders associated with Skin Malignancies
1. Neurofibromatosis
Chromosome 17 :
Arises from Schwann cells
AD – 70%
Sporadic – 30%
NF1 (Von Recklinghausen Disease) :
• more than equal to 5 café-au-lait spots
• Subcutaneous fibromatosis
• Armpit and groin freckling
• Lisch nodules

9. 2. Naevoid Basal Cell Carcinoma (GORLIN SYNDROME)
Abnormal TSG on Chr9q22-31 coding the patched protein
AD
Clinical Features:
Multiple BCC
Over-developed supra orbital ridges
Broad nasal roots
Hypertelorism
Bifid ribs
Scoliosis
Palmar pits
Molar odontogenic cysts

10. 3. Xeroderma Pigmentosa
AR
Chr9q - patched gene- Aberrant Nucleotide Excision Repair
More than 2000 times high risk of developing skin cancer
90% mortality by age of 20yrs due to metastasis

11. 4. Gardner Syndrome
AD
Associated with FAP Syndrome
Chr5
Dermatological Findings : Multiple Epidermoid Cysts and Lipomata

12. 5. Ferguson Smith Syndrome
AD
Chr9q
Multiple self healing BCC

13. PRE-MALIGNANT LESION
1. Leukoplakia and erythroplakia
2. Actinic/Solar Keratosis
3. Radiation Keratosis
4. Bowens disease
5. Erythroplasia of Queyrat
6. Pagets disease
7. Atypical (Dysplastic) Naevus
8. Giant Congenital Pigmented Naevus (GPCN) (Giant Hairy Naevus)

14. 1. LEUCOPLAKIA
Incidence: Occurs in 40 – 70yrs of age with male dominance
Histopathology
Gross feature: White hyperkeratotic patch in the mucosa
Histology : hyperkeratosis over a thickened acanthotic but orderly
mucosal epithelium
Etiology : Smoking, Syphilis, Sepsis (infection by HPV-16), Sharp edge of the
tooth(Ill fitting dentures), Spirits, Spices (6S)

15. ERYTHROPLAKIA
• Erythroplakia is analogous to the term leukoplakia which describes white patches.
• When a lesion contains both red and white areas, the term "speckled leukoplakia"
or "eyrthro-leukoplakia" is used.
• 200 times more malignant potential than leukoplakia
• Complete excision of the lesion is sometimes advised depending on the
histopathology found in the biopsy.

16. 2. ACTINIC/SOLAR/SENILE KERATOSIS
Etiology : Sun exposure (U.V) and hydrocarbons contact
Incidence : Past middle life, M>F
Prognosis : SCC may develop (20% cases)
Etiology
• Occupation = outdoor works
• Race = fair skinned, blue eyes
Can lead to BCC
When a actinic keratosis has a surface with a
height greater than its diameter, it is termed as
Keratin/Cutaneous Horn out of which 10% will
have an underlying SCC.

17. Gross feature: Multiple lesions on the face and the backs of hands
Hyperkeratotic patch in the mucosa.
Wax and Wane between macular and papular
Lesions are less than 1 cm in diameter; are tan brown, red or skin
colored; and have a rough, sandpaper like consistency.
Histology : hyperkeratosis over a thickened acanthotic but orderly mucosa
epithelium. Intact BM
Prevention : recreational exposure, sunscreen & protective clothing

18. 3. RADIATION KERATOSIS
Etiology : Exposure to ionizing radiation
Early: erythema, which goes onto desquamation and pigmentation
Late: atrophy, irregular hyperpigmentation and telangectasia and hair
loss.
SCC may eventually develop

19. 4. BOWEN DISEASE
• Squamous intra-epidermoid neoplasia/SCIS
• Etiology : Involve predominantly skin unexposed to the sun (i.e., protected)
• Role of HPV 16
• Incidence : Involves the genital region of both men and women above the age of 35
• Prognosis : May transform into SCC
• Gross feature : Solitary, thickened, gray-white, opaque plaque with shallow ulceration
and crusting or it can be slightly scaling, slightly crusted, eczematous
appearing patch.
• Histology : the epidermis shows proliferation with numerous mitoses, some atypical.

20. 5. Erythroplasia of Queyrat
Bowen’s disease of the penis
Etiology : Role of HPV 16
Incidence : Men, usually above age of 25yrs
Prognosis : Has a potential to develop into invasive carcinoma (SCC)
Gross feature : Appears on the glans penis and prepuce as single or
multiple shiny red, velvety plaques.
It may at times produce a discharge and become painful.

21. Management
• Curettage
• Electrodessication
• Cryotherapy
• Protection : 5 fluorouracil cream and Imiquimod Cream
• Dermabrasion
• CO2 laser vaporization
• Photodynamic therapy (for Bowen Disease)
• Surgical Excision with 4mm margin
• Mohs’ Micrographic Surgery – for large or recurrent lesions

22. 7. EXTRA-MAMMARY PAGET’S DISEASE
• Also known as Intraepidermal Adenocarcinoma
• It is a form of intraepidermal adenocarcinoma, which may occur in the
genital, perianal regions or in cutaneous sites rich in apocrine glands
such as the axilla
• Approximately 25% cases are associated with in situ or invasive
carcinomas
• The early skin changes are subtle and may present as an eczematous
lesion or intertrigo
• Treatment : Surgery

23. 7. ATYPICAL (DYSPLASTIC) NAEVUS
• To be atypical naevi, lesions must have three of the following features:
1. Variegated pigmentation
2. Ill-defined Borders
3. Undulating surfaces
4. Measure >5mm
• Histology : Irregular proliferation of melanocytes at the basal layer of epidermis
• Can be sporadic or familial (FAMMM Syndrome)
• FAMMM – Familial atypical multiple mole-melanoma
• Possession of more than 5 confers a relative risk of melanoma six times greater
than usual

24. 8. GIANT CONGENITAL PIGMENTED NAEVUS (GPCN)
(GIANT HAIRY NAEVUS)
• It is a hamartoma of naevo-melanocytes that has a tendency to dermatological
distribution
• Naevus cells are distributed variably from the epidermis throughout all layers of
epidermis
• Precursor of melanoma
• Presentation :
• 15% Of MM present at birth
• 62% by puberty
• 99% by 45 years of age

25. SKIN MALIGNANCIES
1. Basal cell carcinoma (BCC)
2. Squamous Cell Carcinoma (SCC)
3. Malignant melanoma

26. A. BASAL CELL CARCINOMA
• Slow growing, locally invasive, malignant tumor of pleuripotential epithelial
cells arising from basal epidermis and hair follicles
• Synonyms: basal cell epithelioma, basalioma, rodent ulcer
• BCC have no apparent precursor lesions
• Only the outer layer that actively divide

27. • Age 40-80yrs
• Race= less in dark skinned
• Outdoor exposure
• High altitudes, equator
• Majority in the face : Line connecting the corners of the mouth to the
bottom of the ears
EPIDEMIOLOGY

28. ETIOLOGY AND PATHOGENESIS
• Sunlight – Strongest predisposing factor
• Genetics: chromosome 9q22.3 (PTCH)
• Ionizing radiation: 10 Gy
• Carcinogens: tar, oils and arsenic
• Chronic skin damage: scars of trauma and vaccination
• Other factors : immunosuppression

29. 1. Localised
• Nodular
• Nodulocystic
• Cystic
• Pigmented
• Naevoid
2. Generalised
• Superficial
i. Multifocal
ii. Superficial spreading
• Infiltrative
i. Morphoeic
ii. Ice pick
iii. Cicatrizing
TYPES OF BCC

30. SUPERFICIAL BCC
• Synonyms: multicentric, pagetoid, eczematoid
• Superficial, multiple
• Pink or brown scaly plaque
• >10cm

31. A. NODULAR / NODULOCYSTIC BCC
• Most common type
• Appears as a pearly semi-translucent papule or nodule that has a depressed
centre, telangiectasia, and rolled waxy border
• Crusting and ulceration frequently occur
• The most common location is on the face, particularly the nose

32. B. CYSTIC BCC
• Soft translucent papule
• Marked telangiectasia
• Eyelids

33. C. PIGEMENTED BCC
• Blacks, Hispanics, Native Americans
• Papular or nodular
• Slate-blue to black
• DD :
1. Melanocytic nevus
2. Blue nevus
3. Malignant melanoma

34. D. INFILTRATIVE/MORPHEAFORM BCC
• Also known as Cicatricial BCC
• Appears as an atrophic, whitish, scar-like eroded or crusted plaque
• Synthesize type 4 collagenase, hence spread rapidly
• Ill defined edge
• Yellow and white waxy plaques
• Enlarging scar
• Nose, forehead
• Clinically aggressive

35. E. ULCERATED BCC
• Synonyms: Ulcus rodens, rodent ulcer
• Large, destructive
• Ragged border
• Nasolabial fold, medial canthus and ear lobules
• Crusts and granulation tissues

36. DIFFERENTIAL DIAGNOSIS
Depends on the type
1. For nodular BCC
• Sebaceous hyperplasia
• fibrous papule of the nose
• nonpigmented nevus
• squamous cell carcinoma
Dermatitis, psoriasis, and Bowen’s disease (SCC in situ) appear similar to
superficial BCC.

37. • Seborrheic keratosis, pigmented nevus, and, most important, malignant melanoma
must be ruled out in the case of pigmented BCC.
• For crusted non-healing scar-like lesions, the differential diagnosis is mainly
between BCC and SCC.
• A skin biopsy, either shave, punch, or excision, should be accomplished to confirm
the diagnosis of BCC.
• The tumor is composed of a thickened epidermis with invasive buds and lobules of
basaloid cells.

38. HISTOPATHOLOGY

39. COURSE AND PROGNOSIS
• Low risk BCC
• Usually 95% cure rate
• High risk BCC
• Large >2cm
• Ear, nose and eye (Where direct invasion give access to cranium)
• Recurrent tumours
• Tumours in presence of immunosuppression
• Micro-nodular or infiltrating histological subtypes

40. TREATMENT
• Curettage and electrodesiccation – Most common
• Excision
• Mohs’ Micrographic surgery
• Radiation therapy
• Cryosurgery
• Topical chemotherapy with 5FU or Imiquimod Cream

44. B. SQUAMOUS CELL CARCINOMA
• Squamous cell carcinoma is a malignant neoplasm of keratinocyte and
its appendages that are locally invasive and has the potential to
metastasize (2% cases).
• It arises from the stratum basalis of the epidermis and expresses CK1
and CK10

45. EPIDEMIOLOGY
30-60/100000
2nd most common skin cancer
SCC:BCC=1:4
Age >40 years
M>F
Occupation= outdoor workers, fairer skin > dark skin
Genetics = xeroderma pigmentosa

46. CAUSES
• Irradiation: UV, PUVA, Heat
• Chronic degenerative and inflammatory process
• Chemical carcinogens: petroleum, tobacco
• Oncogenic Viruses: HPV
• Genetic disorders: Xeroderma pigmentosum
• Immunosuppression
• Personal habits: alcohol and tobacco

47. CLINICAL FINDINGS
• Indistinct clinical picture
• Hard exophytic, inflamed nodule or papule
• Ulcerated and necrotic - more destructive
• Metastases
Unfavorable signs:
1. rapid growth
2. Induration
3. bleeding

49. DIFFERENTIAL DIAGNOSIS
1. Keratoacanthoma
2. Hypertrophic actinic keratosis
3. Wart
4. BCC
5. Lichen Simplex Chronicus
6. Pyoderma Gangrenosum
Any lesion that is crusted or ulcerated should be suspected of being
squamous cell carcinoma, and biopsy must be done.

50. KERATOACANTHOMA
• Rapidly growing, nodular tumors
• Symmetry around a central, keratin filled crater
• M:F = 2:1
• Face and Limbs
• Chronically sun damaged
• 50-70yrs
• white skin
• Caused by HPV

51. Histopathology

52. • SCC can be graded according to BRODER’S GRADING which describes the
proportion of de-differentiated cells in the tumour.
• Stains positive for CK1 and CK10
• The histopathology report on an SCC should include
1. Pathological pattern (e.g. adenoid)
2. Cellular morphology (e.g. spindle)
3. Broders’ grade
4. Depth of invasion
5. Perineural or vascular invasion
6. Deep and peripheral margin clearance

53. PROGNOSIS
A. Independent prognostic variables :
1. Depth : Deeper the lesion, the worse the prognosis
SCC <2mm depth - No metastasis
SCC >6mm depth – 15% of SCC will have metastasised
2. Surface size >2cm
3. Histological Grade
4. Microscopic invasion of lympho-vascular spaces or nerve tissue
B. Dependant prognostic variables :
1. Site : SCC on lips and ears
2. Aetiology
3. Immunosuppression

54. TREATMENT
1. Surgical Excision
2. Margins of clearance
• <2cm size : 4mm clearance
• >2cm size : 1cm clearance
3. 95% of local recurrence and regional metastasis occur within 5 years

55. MARJOLIN’S ULCER
• Squamous cell carcinoma which develops in a chronic scar such as a
long standing ulcer or osteomyelitis sinus.
• Slow growth – relatively avascular
• Painless
• Absence of secondary deposits in regional lymph nodes

56. C. CUTANEOUS MALIGNANT MELANOMA
• Arises from melanocytes
• Site : Skin, mucosa, retina, leptomeninges
• Incidence : less than 5% of skin malignancies
• 75% skin- malignancy related death
• Young adults (30-40yrs)

57. PATHOPHYSIOLOGY
• Cumulative UV exposure leads to later onset disease – Lentigo MM
• Flash fry exposure leads to rapidly acquired other variants of MM
• Can be genetically acquired - Early age of onset
• Only 10-20% form in pre-existing naevi
• 80-90% arise in normal skin

58. RISK OF MM
• Past history of MM or first degree relatives with MM
• >30 sun acquired naevi or history of significant sun burn at age <16
• Fair skin, red hairs
• Equator
• Immunosuppression (20-30 times increased risk)
• Most likely naevi to form MM are :
• Atypical Naevi
• Atypical junctional lentiginous naevi (usually facial)
• GPCN

59. Types of Malignant Melanoma
1. Superficial spreading melanoma (SSM)
2. Nodular Melanoma (NM)
3. Lentigo Malignant Melanoma (LMM)
4. Acral Lentigious Melanoma (ALM)
5. Miscellaneous :
1. Amelanotic Melanoma – Flesh coloured, Mets from unknown primary
skin lesion or in GI obstruction or
intussusception
2. Desmoplastic Melanoma – Head And Neck, perineural infiltration

60. 1. SUPERFICIAL SPREADING MELANOMA
• Most common type (70%)
• Usually arises over a pre-existing naevus
• Usually slow growth over several years followed by fast growth before presentation
• Nodularity heralds vertical growth
• MM under finger nail are usually SSM with classical feature of Hutchinson’s sign :
1. Progressive nail fold pigmentation
2. Triangular pigmented macule
3. Nail dystrophy

61. 2. NODULAR MELANOMA
• 15% of MM
• Short onset
• More aggressive than SSM
• Usually arises over a normal skin
• M>F
• Blue/black papules
• 1-2cm in diameter
• No horizontal growth

62. 3. LENTIGO MALIGNANT MELANOMA
• Earlier known as ‘Hutchinson’s melanotic freckle’
• Elderly
• Slow growing
• Variegated brown macule
• Face, neck, hands
• F>M
• Least metastatic out of all MM

63. 4. ACRAL LENTIGIOUS MELANOMA
• Sole and palm
• Rare in white skin individual
• Flat, irregular macule
• 25% cases are amelanotic

68. TREATMENT
1. Local Treatment : Surgery
Lentigo maligna (Melanoma in situ) should be completely excised
2. Regional LN : Proportional to Breslow thickness
No role of SLNB in MM (Done only as investigation with Breslow
thickness >1mm)
Margins in Surgery
In situ melanoma 5mm
Melanoma <1mm deep 1cm
Melanoma >2mm deep 2cm only

69. 3. Adjuvant therapy : Targeted therapy in stage IV
• Dorafenib or Vemurafenib (Blocks BRAF action)
• Trametinib – Acts on MAPK pathway & blocks cellular growth
• Iplimumab and Nivolimumab – Selective immune check point inhibitor
When mutation locks BRAF protein to “on” , it affects MAPK signalling pathway,
promoting malignant transformation and progression to metastasis in 50% of MM
with BRAF V600 mutation

70. PROGNOSIS
• Breslow thickness in the absence of LN status – Most imp factor
• Higher the mitotic index, poorer is the prognosis
• Once regional Nodes are Clinically Involved, 70-85% pt will have occult distant
metastasis

71. Miscellaneous Skin Malignancies
1. KAPOSI SARCOMA
Malignant proliferative tumors of vascular endothelium
Associated with HIV and After Transplantation
HHV-8
Clinical Features : Brown, indurated, plaque-like, skin lesion, nodular
which latter ulcerates
Treatment : Radiotherapy

72. 2. ANGIOSARCOMA (MALIGNANT ANGIOENDOTHELIOMA)
Arises from vascular endothelial cells
The Lymphangiosarcoma variant arises from lymphatic endothelium

73. 3. MERKEL CELL TUMOR
• Merkel cells – dermal mechano-receptors
• Aggressive malignant tumor
• Elderly
• F:M = 4:1
• Treatment : WLE with 25-30mm margin followed by RT

74. THANK YOU