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Management of skin
malignancy
Dr Anil Gupta
AIIMS, New Delhi
Introduction
• Skin is the largest organ of the body
• The layers of the epidermis from
superficial to deep are
- Stratum corneum
- Stratum lucidum
- Stratum granulosum
- Stratum spinosum
- Stratum basale
• The dermis incorporates the adnexal
structures (hair follicles, sebaceous
glands, and sweat glands) and is made
up of collagen, elastic tissue, and
reticular fibers
• The subcutis is made up of adipose
tissue.
Skin Malignancy
• Skin cancers are broadly divided into melanoma and nonmelanoma
skin cancers (NMSC)
• NMSC includes 82 types with variable prognosis
• As per WHO classification (We’ll discuss)
- Keratinocytic/epidermal tumors- cSCC and BCC
- Melanocytic tumors
- Appendageal tumors
- Tumors of hematopoietic and lymphoid origin
- Soft tissue and neural tumors- Dermatofibrosarcoma Protuberans
Basal Cell Carcinoma (BCC)
• Is the most common type of skin cancer
• It arises from the basal keratinocytes of the epidermis (according to
some authors, the tumor originates from the hair follicle epithelium)
• The most common presentation is a pink, pearly papule or plaque on
sun exposed skin
• Risk factors - fair complexion, chronic sun exposure, and IR
• Patients > 40 years of age are more prone to BCC, although incidence
is increasing in younger patients
• It is a slow-growing skin cancer with an extremely low metastatic
potential
• it does not develop on precursor lesions such as actinic keratosis, but
it may arise on nevus sebaceous
• It does not metastasize through blood vessels or lymphatics in the
great majority of cases.
• It progresses slowly in the absence of treatment and causes an
irregular outgrowth toward adjacent tissue.
• Direct invasion of the tumor may be detected on fasciae, periosteum,
perichondrium, and nerve sheaths.
• In neglected cases it may even penetrate bone
• MC site- face, particularly the nose
• Patient may relay a history of a bump or blemish that never heals
completely or bleeds easily
Nodular Type Superficial Type Morphoeic (Sclerosing)
Type
Pigmented Type Basosquamous Type
AJCC STAGING
Treatment algorithm for BCC
Topical Treatments
• Photodynamic therapy (PDT), 5-FU, and imiquimod can be used in the
management of premalignant lesions and superficial BCC.
• The data regarding use of PDT for superficial BCC and SCC in situ
are relatively limited, though some treatment protocols have resulted in
promising cure rates
• Imiquimod and 5-FU have been more recently approved by the FDA for
the treatment of superficial BCC on the trunk and extremities.
• Cure rates- 50% to 90% depending on type of tumor, frequency of
application, and duration of treatment course
• Not approved other subtype or site
Electrodesiccation and Curettage (ED&C)
• Most effective for the destruction of well-defined, superficial skin
cancers
Excision
Mohs Micrographic Surgery
• Is a specialized technique of excision and margin examination that
provides the highest cure rates and maximum conservation of
normal tissue
• The cure rates associated with Mohs surgery for the treatment of
BCC and SCC are well established and approach 99%
• The technique is particularly well suited for high-risk tumors
• Ensures both that 100% of the surgical margin is histologically
examined and that only the malignant tissue – with a minimal
margin of normal tissue – is removed
Radiotherapy
• The likelihood of cure is similar after surgery or RT for early-stage
BCCs and SCCs
• Selection of one modality over another is based on other parameters
such as function, cosmesis, age of the patient, convenience, cost,
availability of appropriate RT equipment, and the wishes of the
patient
• Patients with advanced cancers are often best treated with surgery
and adjuvant RT if the cancer is resectable and the functional and
cosmetic outcomes are acceptable to the patient
• Postoperative RT is added after surgery if pathologic examination of
the surgical specimen reveals findings indicative of a high risk for
local recurrence, such as close or positive margins and/or invasion of
nerve, cartilage, or bone
RT Techniques
• External beam techniques
• Interstitial implant
• Combination with external beam techniques
Dose Per Fraction
As high as 20 Gy
Reason???
Squamous Cell Carcinoma (SCC)
• It is the second most common skin cancer
• Presents as slowly enlarging, irregular reddish patches
• Approximately 5% of cases develop an invasive component and of
these up to 30% have metastatic potential
• Manifests predominantly in lighter skin and is most common in
adulthood, with the highest incidence in patients older than 60 years
• The etiology is possibly multifactorial including particularly solar
radiation, arsenic exposure, and HPV infection
• It may involve any area of the body but most frequently occurs on
sun-exposed areas such as the face, neck, arms, and lower legs
• The incidence of cSCC and other carcinomas of the skin varies
globally, but is thought to be increasing overall since the 1960s at a
rate of 3–8% per year from the epidermal keratinocytes of the skin
and mucous membranes
Difference between BCC and cSCC
BCC
• occurs more frequently around the
central portion of the face
• Appearance- keratotic
papules/plaques
• has a low incidence of lymphatic
spread
• rarely produce metastases
• Histology- basaloid epithelium
typically forms a palisade
cSCC
• more often on the ears,
preauricular and temporal area,
scalp, and skin of the neck
• Rodent ulcer
• estimated to be at least 10% to 15%
• may develop distant metastases
• nests of squamous epithelial cells
with keratinisation (keratin pearls
)
Treatment algorithm for cSCC
Primary Cutaneous Malignant
Melanoma
• Is the third most common type of skin cancer
• It is the leading cause of death due to skin cancer
• Can arise in many organs, the most common form, cutaneous
melanoma, arises from the melanocytes Site- 91.2% of melanomas
are cutaneous, 5.3% are ocular, 1.3% are mucosal, and 2.2% other
• Often presents as an irregularly bordered, pigmented macule with
numerous shades of colors, ranging from tan to brown to jet-black,
but they can also be evenly colored.
• Should be considered a systemic disease and remains a serious life-
threatening entity
• The most common sites in males are on the back and in the head and
neck regions. In women, the most common sites are in the lower
extremities, commonly below the knee
• Several immunostains that can be used on frozen sections have been
studied extensively, including MART-1, S-100, MEL-5, Melan-A (A-
103), and HMB-45
• The classic appearance of primary cutaneous melanoma is
summarized as ABCD for
- asymmetry
- border irregularity
- color variation
- diameter >6 mm
Amelanotic Melanoma Amelanotic Melanoma
Superficial spreading
Melanoma
Superficial Melanoma
Superficial spreading
Melanoma with
satellite nodules
Acral lentiginous
Melanoma
Lentigo MelanomaNodular Melanoma
Types of Primary Cutaneous Malignant Melanoma
The classic appearance of primary cutaneous melanoma
is summarized
by the mnemonic ABCD for asymmetry, border irregularity,
color variation, and diameter >6 mm
Workup
• Biopsy-full-thickness biopsy of the entire lesion, with a narrow (1 to 2
mm) margin of grossly normal skin sentinel node biopsy
• Metastatic workup- chest radiography, and CT or MRI scanning,
positron emission tomography (PET)
• Serum LDH
Breslow depth
• A standardized method to measure melanoma depth.
• It requires an optical micrometer fitted to the ocular position of a
standard microscope
• The most important prognostic factor for localized melanomas is
tumor thickness
• ≤1.0 mm (melanoma in situ and thin invasive tumors)
• 1.01–2.0 mm
• 2.01–4.0 mm
• ≥4.0 mm
Clark level
• Refers to penetration of the
melanoma through the layers of the
skin.
• Level I: Melanoma cells confined to the
(melanoma in situ)
• Level II: penetrates the basement membrane
the papillary dermis
• Level III: fills the papillary dermis and
on the reticular dermis
• Level IV: invades the reticular dermis
• Level V: into the subcutaneous fat
is less reproducible among pathologists and
not reflect prognosis as accurately as tumor
thickness
Tumor-infiltrating Lymphocytes (TILs)
Lymphocytes that infiltrate and disrupt tumor nests and/or directly
oppose tumor cells-
• Absent TIL infiltrate
• Non brisk TIL infiltrate
• Brisk TIL infiltrate
 TIL infiltration in primary cutaneous melanoma is a favourable
prognostic factor
Neurotropism
• Presence of melanoma cells abutting nerve sheaths
• Usually circumferentially- perineural invasion
• Within nerves - intraneural invasion
• Tumor itself may form neuroid structures- neural
transformation
 Associated with an increased local recurrence rate
An Electronic Prediction Tool Based on the Melanoma
http://www.lifemath.net/cancer/melanoma/nodal/index.php
Treatment of Melanoma
• Surgical excision of the primary tumor is the standard treatment for
invasive melanoma
• Sentinel lymph node biopsy should be considered in cases of invasive
melanoma with a Breslow thickness greater than 1.0 mm
• Moh's surgery is generally considered inappropriate for definitive
treatment of a invasive melanoma
• SLNB If positive for nodal disease, a complete nodal basin excision
would ordinarily be performed
Adequate margins
• The key prognostic factor for predicting the metastatic potential of a
given primary tumor is its Breslow thickness
• Likewise, the key prognostic factor for predicting overall survival in a
given patient is sentinel lymph node status
• Other key prognostic factors identified by stratified analyses included
ulceration, lesion site, and patient age
• Paradox- There is a greater risk of lymph node metastasis in young
patients at the time of SNBx especially for patients younger than age
35 years, but the melanoma-associated mortality risk increases with
age for all thickness ranges
Radiotherapy in Malignant Melanoma
• Postoperative adjuvant radiation may be delivered with 2- to 3-cm
margins around the resected lesion if margins are inadequate, or
following resection of a locally recurrent lesion
• Neurotropic melanomas of the head and neck have a propensity to
recur at the skull base by tracking along cranial nerves, and
postoperative adjuvant radiation including the resection bed and the
cranial nerve pathway should be considered for this variant
• Large unresectable primary lesions should be considered for
palliative radiation therapy
• Patients with positive SNBx or palpable regional nodal metastases
(stage III disease) are treated with therapeutic inguinal, axillary, or
cervical lymph node dissections
• Several large retrospective studies have identified lymph node
extracapsular extension, large lymph nodes (≥3 cm in diameter), four
or more involved lymph nodes, or recurrent disease after previous
lymph node dissection as adverse risk factors that increase the risk
for nodal basin recurrence following therapeutic nodal dissection to
30% to 50%
METASTATIC MELANOMA (STAGE IV)
RT- brain metastases, vertebral mets
Abscopal effect
Dermatofibrosarcoma Protuberans (DFSP)
• Most common type of cutaneous sarcoma
• DFSP is a dermal neoplasm that almost always extends into the
subcutis
• Is a locally aggressive cutaneous tumor with low to intermediate
grade malignant potential
• The tumor is composed of fairly uniform spindled cells with
elongated nuclei
• Presents as a slow-growing, solitary or multiple, polypoid
nodular lesion that ranges in size from 0.5 cm to 10 cm
• It has predilection for the trunk and proximal extremities of
young and middle-aged adults, with slight male predominance
• Local recurrence is common and the risk of metastases is rare
(<0.5% of cases, usually to the lungs)
• Usually, metastatic disease is preceded by multiple local recurrences
and appears to be associated with fibrosarcomatous transformation
• Is characterized by a reciprocal translocation, t(17;22)(q22;q13)
(COL1A1 and PDGFB genes)
• IHC: The tumor cells are strongly positive for CD34
and negative for factor XIIIa, S-100 protein, and CD117 .
CD99 is also positive in some cases
• Cause is unknown
• A wide surgical excision with adequate margins or Mohs technique
are used
• Minimal margin of at least 3 cm of surrounding skin, including the
underlying fascia, without elective lymph node dissection
• Radiation therapy may be recommended for patients with
positive/inadequate margins or in recurrence
• The complete radiation therapy dose ranges from 50-70 Gy
• Imatinib mesylate is indicated for the treatment of adult patients
with unresectable, recurrent, and/or metastatic DFSP
• The recommended oral dose is 800 mg/d
Conclusion
• Basal cell ca (BCC), cutaneous squamous cell ca(cSCC) and
dermatofibrisarcoma protuberans (DFSP) has good prognosis as
compared to cutaneous malignant melanoma (cMM)
• BCC has lower lymphatic spread and distant metastases as compared
to cCC
• Surgery with adequate resection margin is the mainstay of cSCC,
BCC, cMM and DFSP
• Radiotherapy is alternative treatment which is used in adjuvant
setting in cSCC, BCC, cMM and DFSP with high risk features.
• It can used as upfront treatment in unresectable cSCC, BCC, cMM
and DFSP
THANK YOU

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Management of skin malignancy

  • 1. Management of skin malignancy Dr Anil Gupta AIIMS, New Delhi
  • 2. Introduction • Skin is the largest organ of the body • The layers of the epidermis from superficial to deep are - Stratum corneum - Stratum lucidum - Stratum granulosum - Stratum spinosum - Stratum basale • The dermis incorporates the adnexal structures (hair follicles, sebaceous glands, and sweat glands) and is made up of collagen, elastic tissue, and reticular fibers • The subcutis is made up of adipose tissue.
  • 3. Skin Malignancy • Skin cancers are broadly divided into melanoma and nonmelanoma skin cancers (NMSC) • NMSC includes 82 types with variable prognosis • As per WHO classification (We’ll discuss) - Keratinocytic/epidermal tumors- cSCC and BCC - Melanocytic tumors - Appendageal tumors - Tumors of hematopoietic and lymphoid origin - Soft tissue and neural tumors- Dermatofibrosarcoma Protuberans
  • 4. Basal Cell Carcinoma (BCC) • Is the most common type of skin cancer • It arises from the basal keratinocytes of the epidermis (according to some authors, the tumor originates from the hair follicle epithelium) • The most common presentation is a pink, pearly papule or plaque on sun exposed skin • Risk factors - fair complexion, chronic sun exposure, and IR • Patients > 40 years of age are more prone to BCC, although incidence is increasing in younger patients
  • 5. • It is a slow-growing skin cancer with an extremely low metastatic potential • it does not develop on precursor lesions such as actinic keratosis, but it may arise on nevus sebaceous • It does not metastasize through blood vessels or lymphatics in the great majority of cases. • It progresses slowly in the absence of treatment and causes an irregular outgrowth toward adjacent tissue. • Direct invasion of the tumor may be detected on fasciae, periosteum, perichondrium, and nerve sheaths. • In neglected cases it may even penetrate bone
  • 6. • MC site- face, particularly the nose • Patient may relay a history of a bump or blemish that never heals completely or bleeds easily Nodular Type Superficial Type Morphoeic (Sclerosing) Type Pigmented Type Basosquamous Type
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  • 10. Topical Treatments • Photodynamic therapy (PDT), 5-FU, and imiquimod can be used in the management of premalignant lesions and superficial BCC. • The data regarding use of PDT for superficial BCC and SCC in situ are relatively limited, though some treatment protocols have resulted in promising cure rates • Imiquimod and 5-FU have been more recently approved by the FDA for the treatment of superficial BCC on the trunk and extremities. • Cure rates- 50% to 90% depending on type of tumor, frequency of application, and duration of treatment course • Not approved other subtype or site
  • 11. Electrodesiccation and Curettage (ED&C) • Most effective for the destruction of well-defined, superficial skin cancers
  • 13. Mohs Micrographic Surgery • Is a specialized technique of excision and margin examination that provides the highest cure rates and maximum conservation of normal tissue • The cure rates associated with Mohs surgery for the treatment of BCC and SCC are well established and approach 99% • The technique is particularly well suited for high-risk tumors • Ensures both that 100% of the surgical margin is histologically examined and that only the malignant tissue – with a minimal margin of normal tissue – is removed
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  • 16. Radiotherapy • The likelihood of cure is similar after surgery or RT for early-stage BCCs and SCCs • Selection of one modality over another is based on other parameters such as function, cosmesis, age of the patient, convenience, cost, availability of appropriate RT equipment, and the wishes of the patient • Patients with advanced cancers are often best treated with surgery and adjuvant RT if the cancer is resectable and the functional and cosmetic outcomes are acceptable to the patient • Postoperative RT is added after surgery if pathologic examination of the surgical specimen reveals findings indicative of a high risk for local recurrence, such as close or positive margins and/or invasion of nerve, cartilage, or bone
  • 17. RT Techniques • External beam techniques • Interstitial implant • Combination with external beam techniques
  • 18. Dose Per Fraction As high as 20 Gy Reason???
  • 19. Squamous Cell Carcinoma (SCC) • It is the second most common skin cancer • Presents as slowly enlarging, irregular reddish patches • Approximately 5% of cases develop an invasive component and of these up to 30% have metastatic potential • Manifests predominantly in lighter skin and is most common in adulthood, with the highest incidence in patients older than 60 years
  • 20. • The etiology is possibly multifactorial including particularly solar radiation, arsenic exposure, and HPV infection • It may involve any area of the body but most frequently occurs on sun-exposed areas such as the face, neck, arms, and lower legs • The incidence of cSCC and other carcinomas of the skin varies globally, but is thought to be increasing overall since the 1960s at a rate of 3–8% per year from the epidermal keratinocytes of the skin and mucous membranes
  • 21. Difference between BCC and cSCC BCC • occurs more frequently around the central portion of the face • Appearance- keratotic papules/plaques • has a low incidence of lymphatic spread • rarely produce metastases • Histology- basaloid epithelium typically forms a palisade cSCC • more often on the ears, preauricular and temporal area, scalp, and skin of the neck • Rodent ulcer • estimated to be at least 10% to 15% • may develop distant metastases • nests of squamous epithelial cells with keratinisation (keratin pearls )
  • 23. Primary Cutaneous Malignant Melanoma • Is the third most common type of skin cancer • It is the leading cause of death due to skin cancer • Can arise in many organs, the most common form, cutaneous melanoma, arises from the melanocytes Site- 91.2% of melanomas are cutaneous, 5.3% are ocular, 1.3% are mucosal, and 2.2% other • Often presents as an irregularly bordered, pigmented macule with numerous shades of colors, ranging from tan to brown to jet-black, but they can also be evenly colored. • Should be considered a systemic disease and remains a serious life- threatening entity
  • 24. • The most common sites in males are on the back and in the head and neck regions. In women, the most common sites are in the lower extremities, commonly below the knee • Several immunostains that can be used on frozen sections have been studied extensively, including MART-1, S-100, MEL-5, Melan-A (A- 103), and HMB-45 • The classic appearance of primary cutaneous melanoma is summarized as ABCD for - asymmetry - border irregularity - color variation - diameter >6 mm
  • 25. Amelanotic Melanoma Amelanotic Melanoma Superficial spreading Melanoma Superficial Melanoma Superficial spreading Melanoma with satellite nodules Acral lentiginous Melanoma Lentigo MelanomaNodular Melanoma Types of Primary Cutaneous Malignant Melanoma The classic appearance of primary cutaneous melanoma is summarized by the mnemonic ABCD for asymmetry, border irregularity, color variation, and diameter >6 mm
  • 26. Workup • Biopsy-full-thickness biopsy of the entire lesion, with a narrow (1 to 2 mm) margin of grossly normal skin sentinel node biopsy • Metastatic workup- chest radiography, and CT or MRI scanning, positron emission tomography (PET) • Serum LDH
  • 27. Breslow depth • A standardized method to measure melanoma depth. • It requires an optical micrometer fitted to the ocular position of a standard microscope • The most important prognostic factor for localized melanomas is tumor thickness • ≤1.0 mm (melanoma in situ and thin invasive tumors) • 1.01–2.0 mm • 2.01–4.0 mm • ≥4.0 mm
  • 28. Clark level • Refers to penetration of the melanoma through the layers of the skin. • Level I: Melanoma cells confined to the (melanoma in situ) • Level II: penetrates the basement membrane the papillary dermis • Level III: fills the papillary dermis and on the reticular dermis • Level IV: invades the reticular dermis • Level V: into the subcutaneous fat is less reproducible among pathologists and not reflect prognosis as accurately as tumor thickness
  • 29. Tumor-infiltrating Lymphocytes (TILs) Lymphocytes that infiltrate and disrupt tumor nests and/or directly oppose tumor cells- • Absent TIL infiltrate • Non brisk TIL infiltrate • Brisk TIL infiltrate  TIL infiltration in primary cutaneous melanoma is a favourable prognostic factor
  • 30. Neurotropism • Presence of melanoma cells abutting nerve sheaths • Usually circumferentially- perineural invasion • Within nerves - intraneural invasion • Tumor itself may form neuroid structures- neural transformation  Associated with an increased local recurrence rate
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  • 34. An Electronic Prediction Tool Based on the Melanoma http://www.lifemath.net/cancer/melanoma/nodal/index.php
  • 35. Treatment of Melanoma • Surgical excision of the primary tumor is the standard treatment for invasive melanoma • Sentinel lymph node biopsy should be considered in cases of invasive melanoma with a Breslow thickness greater than 1.0 mm • Moh's surgery is generally considered inappropriate for definitive treatment of a invasive melanoma • SLNB If positive for nodal disease, a complete nodal basin excision would ordinarily be performed
  • 37. • The key prognostic factor for predicting the metastatic potential of a given primary tumor is its Breslow thickness • Likewise, the key prognostic factor for predicting overall survival in a given patient is sentinel lymph node status • Other key prognostic factors identified by stratified analyses included ulceration, lesion site, and patient age • Paradox- There is a greater risk of lymph node metastasis in young patients at the time of SNBx especially for patients younger than age 35 years, but the melanoma-associated mortality risk increases with age for all thickness ranges
  • 38. Radiotherapy in Malignant Melanoma • Postoperative adjuvant radiation may be delivered with 2- to 3-cm margins around the resected lesion if margins are inadequate, or following resection of a locally recurrent lesion • Neurotropic melanomas of the head and neck have a propensity to recur at the skull base by tracking along cranial nerves, and postoperative adjuvant radiation including the resection bed and the cranial nerve pathway should be considered for this variant • Large unresectable primary lesions should be considered for palliative radiation therapy
  • 39. • Patients with positive SNBx or palpable regional nodal metastases (stage III disease) are treated with therapeutic inguinal, axillary, or cervical lymph node dissections • Several large retrospective studies have identified lymph node extracapsular extension, large lymph nodes (≥3 cm in diameter), four or more involved lymph nodes, or recurrent disease after previous lymph node dissection as adverse risk factors that increase the risk for nodal basin recurrence following therapeutic nodal dissection to 30% to 50%
  • 40. METASTATIC MELANOMA (STAGE IV) RT- brain metastases, vertebral mets Abscopal effect
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  • 42. Dermatofibrosarcoma Protuberans (DFSP) • Most common type of cutaneous sarcoma • DFSP is a dermal neoplasm that almost always extends into the subcutis • Is a locally aggressive cutaneous tumor with low to intermediate grade malignant potential • The tumor is composed of fairly uniform spindled cells with elongated nuclei • Presents as a slow-growing, solitary or multiple, polypoid nodular lesion that ranges in size from 0.5 cm to 10 cm • It has predilection for the trunk and proximal extremities of young and middle-aged adults, with slight male predominance
  • 43. • Local recurrence is common and the risk of metastases is rare (<0.5% of cases, usually to the lungs) • Usually, metastatic disease is preceded by multiple local recurrences and appears to be associated with fibrosarcomatous transformation • Is characterized by a reciprocal translocation, t(17;22)(q22;q13) (COL1A1 and PDGFB genes) • IHC: The tumor cells are strongly positive for CD34 and negative for factor XIIIa, S-100 protein, and CD117 . CD99 is also positive in some cases • Cause is unknown
  • 44. • A wide surgical excision with adequate margins or Mohs technique are used • Minimal margin of at least 3 cm of surrounding skin, including the underlying fascia, without elective lymph node dissection • Radiation therapy may be recommended for patients with positive/inadequate margins or in recurrence • The complete radiation therapy dose ranges from 50-70 Gy • Imatinib mesylate is indicated for the treatment of adult patients with unresectable, recurrent, and/or metastatic DFSP • The recommended oral dose is 800 mg/d
  • 45. Conclusion • Basal cell ca (BCC), cutaneous squamous cell ca(cSCC) and dermatofibrisarcoma protuberans (DFSP) has good prognosis as compared to cutaneous malignant melanoma (cMM) • BCC has lower lymphatic spread and distant metastases as compared to cCC • Surgery with adequate resection margin is the mainstay of cSCC, BCC, cMM and DFSP • Radiotherapy is alternative treatment which is used in adjuvant setting in cSCC, BCC, cMM and DFSP with high risk features. • It can used as upfront treatment in unresectable cSCC, BCC, cMM and DFSP