3/7 SCC, BCC, Melanoma Flashcards
Actinic Keratosis
What type of skin cancer is it?
What are some features of it? (What causes it? Who is most at risk?)
What is the gross apperanace of it?
What is the histological features of it?
How do you treat it?
- pre-malignant squamous cell lesion of the skin induced by UV light; common in fair-skinned people or immunosuppressed people with lots of sun exposure
GROSS
- *- scalely red, rough plaque** on UV-exposed areas (forehead, temples, nose, cheeks, dorsum of hands)
- *tender* - good clue
- can be very thick, giving the appearance of a “cutaneous horn”
Histology:
- proliferation of epidermis, with overlying thickening and retention of nuclei in the stratum corneum; CONFINED to epidermis
- cells at the base of the epidermis show disorganization and atypia
Treatment:
- Liquid N2
- Topical treatments (5FU, imiquimod, PDT)
Squamous Cell Carcinoma in situ
What type of skin cancer is it?
What are some features of it? (What causes it? Who is most at risk?)
What is the gross apperanace of it?
What is the histological features of it?
How do you treat it?
“Squamous Cell Carcinoma In Situ (SCCis)
Bowen’s Disease”
- *- early form of SCC**
- commonly found on UV-exposed areas (ie legs)
Gross appearance: - well defined pink, brown scaly plaques
Histology: full thickness epidermal keratinocyte atypia that extends into the granular layer, but have not yet invaded into the dermis
Treatment:
- EDC
- Topical treatments (5FU, imiquimod, PDT)
- Standard excision (higher-risk lesions)
- MOH (high-risk lesions, those that occur in high risk locations – eyelid, lipis, ears, genitals)
Squamous Cell carcinoma
What type of skin cancer is it?
What are some features of it? (What causes it? Who is most at risk?)
What is the gross apperanace of it?
What is the histological features of it?
How do you treat it?
- arise from unregulated growth of keratinocytes in the epidermis
- commonly due to UV-related damage (ie TP53 is mutated in >90% of SCC patients)
Gross:
- solitary, enlarging nodule with a red indurated base and a central scale or ulceration; often found in sun exposed areas; often painful/tender
histology:
- Atypical keratinocytes that extends into the dermis; can have peri-neural invasion
- cells have eosinophilic cytoplasm
- presence of KERATIN PEARLS in the dermis
Treatment:
Treatment:
- EDC (low risk lesions)
- Standard excision (higher-risk lesions)
- MOH (high-risk lesions, those that occur in high risk locations – eyelid, lipis, ears, genitals)
- XRT - large aggressive tumors or patients who are not good surgical candidates
What is the difference between squamous cell carcinoma and basal cell carcinoma?
Bonus: What are the clinical subtypes of each?
- *Squamous Cell Carcinoma** – uncontrolled proliferation of keratinocytes
- Actinic keratosis
- Squamous cell carcinoma in situ (aka Bowens Disease)
- *Basal Cell Carcinoma** – uncontrolled proliferation of follicular related basal cell layer keratinocytes (hair follicle) – MOST common type
- Superficial
- Nodular
- Morpheaform
- Infiltrative
- Micronodular
- Pinkus Tumor
What type of skin cancer this patient have?
What are some features of it? (What causes it? Who is most at risk?)
What is the gross apperanace of it?
What is the histological features of it?
How do you treat this?
Actinic Keratosis (Squamous Cell Carcinoma)
- pre-malignant lesion of the skin induced by UV light; common in fair-skinned people or immunosuppressed people with lots of sun exposure
GROSS
- scalely red, rough plaque on UV-exposed areas (forehead, temples, nose, cheeks, dorsum of hands)
- *tender* - good clue
- can be very thick, giving the appearance of a “cutaneous horn”
Histology:
- proliferation of epidermis, with overlying thickening and retention of nuclei in the stratum corneum; CONFINED to epidermis
- cells at the base of the epidermis show disorganization and atypia
Treatment:
- Liquid N2
- Topical treatments (5FU, imiquimod, PDT)
What does this patient have?
What are some features of it? (What causes it? Who is most at risk?)
What is the gross apperanace of it?
What is the histological features of it?
How do you treat this?
“Squamous Cell Carcinoma In Situ (SCCis)
Bowen’s Disease”
- early form of SCC
- commonly found on UV-exposed areas (ie legs)
Gross appearance: - well defined pink, brown scaly plaques
Histology: full thickness epidermal keratinocyte atypia that extends into the granular layer, but have not yet invaded into the dermis
Treatment:
- EDC
- Topical treatments (5FU, imiquimod, PDT)
- Standard excision (higher-risk lesions)
- MOH (high-risk lesions, those that occur in high risk locations – eyelid, lipis, ears, genitals)
What does this patient have?
What are some features of it? (What causes it? Who is most at risk?)
What is the gross apperanace of it?
What is the histological features of it?
How do you treat this?
Squamous Cell Carcinoma
- arise from unregulated growth of keratinocytes in the epidermis
- commonly due to UV-related damage (ie TP53 is mutated in >90% of SCC patients)
Gross:
- solitary, enlarging nodule with a red indurated base and a central scale or ulceration; often found in sun exposed areas; often painful/tender
histology:
- Atypical keratinocytes that extends into the dermis and sometimes beyond; can have peri-neural invasion
- cells have eosinophilic cytoplasm
- presence of KERATIN PEARLS in the dermis
Treatment:
- EDC (low risk lesions)
- Standard excision (higher-risk lesions)
- MOH (high-risk lesions, those that occur in high risk locations – eyelid, lipis, ears, genitals)
- XRT - large aggressive tumors or patients who are not good surgical candidates
What is the difference between well differentiated and poorly differentiated squamous cell carcinoma?
Well differentiated - resemble normal keratinocytes and often have evidence of keratinization
Poorly differentiated - irregular cell size, bizarre nuclei, mitoses and little to no keratinization.
What are some features of squamous cell carcinoma that increases its risk of malignancy (9)
- Location
- Size >20mm,10mm,6mm
- Recurrent
- Immunosuppressed patient
- Prior XRT
- Peri-neural involvement **impt**
- Neurologic symptoms
- Rapid Growth
- Breslow depth > 2mm (measure from granular layer to deepest layer)
What is this?
What are some features of it?
How would you treat it?
Keratoacanthoma
- subtype of squamous cell carcinoma
- low grade, more indolent but is treated the same as SCC (EDC, standard excision, MOH, or XRT) )
- undergoes rapid growth followed by involution
- may be viral related
What does this person have?
What are some risks associated with a poor prognosis of this partciular disease? (8)
Basal cell carcinoma - arises from pluripotent stem cells from teh basal cells of the epidermis or hair follicle
High Risk features depend on:
- Location
- Size >20mm,10mm,6mm
- Ill defined
- Recurrent
- Immunosuppressed patient
- Prior XRT
- Peri-neural involvement
- Subtypes
What is the metz potential of basal cell carcinoma?
low.
(it has low mortality but the morbidity is high)
What is basal cell carcinoma?
How common is it?
Where is it normally found?
What is the general prognosis of it?
How do you treat it?
- arises from basal cells of the epidermis or hair follicles
- commonly found in in UV-exposed locations, but can present elsewhere
- low mortality, but significant morbidity (low metz risk)
- *Treatment**:
- EDC (nodular + superficial)
- Standard excision (good for all types)
- MOH (sclerosing, those that occur in high risk locations)
- XRT - large, aggressive tumors, or patients who are not good surgical candidates
What subtype of Basal carcinoma is this?
Superficial
Gross: BCC forms an erythematous thin plaque with focal scaling and crusting with a fine peraly, thread-like border.
Histology: basophilic tumor buds originating in the epidermis
What subtype of Basal carcinoma is this?
Nodular
Gross: COMMON & CLASSIC; pearly papule/plaque that can ulcerate; rarely metz.
Histology: large tumor nests (round clusters of basophilic cells) with peripheral palisading in the dermis. Retraction artifact.
What subtype of Basal carcinoma is this?
Micronodular
Gross: clinically indistinguishable from nodular (pearly papule/plaque)
Histology: tumor nests are smaller compared to nodular
What subtype of Basal carcinoma is this?
Infiltrating
Gross: translucent, pearly quality with superficial blood vessels. affects H&N
histology: vertically oriented cords of basaloid cells. bad because its deeper than it really looks
What subtype of Basal carcinoma is this?
Morpheaform/Sclerosing
Gross: scar-like appearance
Histology: small islands and strands of infiltrating basaloid cells surrounded by sclerotic stroma
What is liquid nitrogen used to treat?
superficial stuff only!
Actinic Keratosis (AK)
Squamous Cell Carcinoma In Situ (SCCis)
Superficial basal cell carcinoma (SBCC)
How would you treat Actinic Keratosis?
- Liquid N2
- Topical treatments (5FU, imiquimod, PDT)
How would you treat squamous cell carcinoma - IN SITU if it was “low-risk”? What if it’s “high risk”?
- EDC
- Topical treatments (5FU, imiquimod, PDT)
- Standard excision (higher-risk lesions)
- MOH (high-risk lesions, those that occur in high risk locations – eyelid, lipis, ears, genitals)
How do you treat Squamous cell carcinoma that is considered “low risk”? What if it was considered “high risk”?
- EDC (low-risk lesions)
- Standard excision (higher-risk lesions)
- MOH (high-risk lesions that occur in high risk locations – head, neck, hands/feet, genitals)
- XRT - large, aggressive tumors, or patients who are not good surgical candidates
How would you treat basal cell carcinoma if it was considered low risk? high risk?
- EDC (nodular + superficial)
- Standard excision (good for all types)
- MOH (sclerosing, those that occur in high risk locations)
- XRT - large, aggressive tumors, or patients who are not good surgical candidates
What are the benefits of using radiation therapy for removing skin cancers?
disadvantages? (3)
Benefits of no cutting, good cosmetic outcomes on highly contoured areas
- Many treatments
- Atrophy, scarring, dyspigmentation
- Can only treat each area one time
What has the highest cure rate for removing skin cancers?
MOH’s micrographic surgery.
What are 2 oral therapies that are used to treat skin cancrs?
- *Cetuximab**
- chimeric (mouse/human) antibody
- EGFR inhibitor
- *Vismodigeb**
- Competitively inhibits “smoothened” in the hedgehog signaling pathway
- Response rates are relatively low <50% and duration only ~7months
- For advanced or metastatic BCC
What are some mainstay topical therapies used to treat skin cancers?
5-fluorouracil (5FU) or Imiquimod (Aldara) – most common!
What is melanoma?
How does this contrast to squamous cell carcinoma and Basal cell carcinoma in terms of the cells affected and the histological features of each?
melanoma
- melanocytes
- hx: abundant pigmentation
squamous cell carcinoma
- keratinocytes
- hx: keratin pearls +/- perineural invasion
basal cell carcinoma
- follicular-related basal layer keratinocytes
- hx: nests with **pallisading** dermis or infiltrating with sclerosis
What is the metz potential of melanoma? basal cell carcinoma? squamous cell carcinoma?
Melanoma - significant risk of metz
squamous cell carcinoma - locally invasive, but may sparead to LN and will rarely metz
basal cell carcinoma - locally invasive, but almost never metz
What is a tumor marker of melanoma?
S100
How does melanoma form?
a malignant change within a nest of nevus cells or it may arise de novo from epidermal melanocytes
Most common causes of Melanoma?
basal cell carcinoma?
squamous cell carcinoma?
(according to first-aid)
melanoma: UV
Squamous: UV, immunosuppression, arsenic exposure
basal: UV, fair skinned
What is the prognosis: 5 year survival rate of melanoma?
- melanoma only (detected early) = 98%
- melanoma + LN = 62%
- melanoma + distant organs = 15%
What are some of the risk factors of melanoma?
- fair-skinned
- UV exposure
- CDKN2A (9p21 mutation)
- Nevi
- immunosuppression
What areas of the body does melanoma affect? BCC? SCC?
(first-aid)
BCC: sun-exposed areas
SCC: face, lower lip, ears, hands
Melanoma: women:legs Men: trunk, sun exposed areas
How does a CDKN2A (9p21) mutation cause melanoma?
What other gene is commonly found to be mutated in melanoma?
- *CDKN2A (9p21) -** codes for p16 and p14ARF, both prevent cell cycle progression
- mutation in p16 -> progression through S phase without repair of mutations
- mutation in p14ARF -> loss of ability to prevent p53 destruction -> no p53 -> tumor growth
BRAF activating mutation - allows for cell cycle progression
What subtype of melanoma is this?
Where does it affect?
Who does it affect?
Lentigo Maligna (LM)
- Large, flat, freckle-like lesion confined to epidermis, ill defined borders.
- occurs on sun-exposed skin
- Elderly
FYI: growth progresses very slowly and when there is a bumpy surface, then it is considered to be a LMM (lentigo maligna melanoma) - discussed in a different FC
What subtype of melanoma is this?
Where does it affect?
Who does it affect?
Melanoma in Situ (MIS)
- confined to epidermis, well-defined borders
- occurs on both sun or non-exposed skin
very early stage of melanoma
What subtype of melanoma is this?
Where does it affect?
Who does it affect?
Superficial Spreading Melanoma (SSM)
- MOST COMMON in both adults + children; affects 30-50yo
- 1/3 arise in pre-existing nevus
- Men: trunk
- Women: legs
prolonged radial growth phase followed by a vertical growth phase.
What subtype of melanoma is this?
Where does it affect?
Who does it affect?
Nodular Melanoma (NM)
- Second most common, but is the most aggressive form according to wiki
- can arise from nevi or de novo, but it has a rapid growth, especially vertically
- Trunk, H&N
- affects 60 yo
What subtype of melanoma is this?
Where does it affect?
Who does it affect?
(not the nodule, but the stuff surrounding it)
Lentigo Maligna Melanoma (LMM)
- progressed from Lentigo Maligna, LM, but with deeper penetration and bumpy surface
- deeper than LM and nodular melanoma
- Chronically sun-damaged skin
- 70 yo
What subtype of melanoma is this?
Where does it affect?
Who does it affect?
Acral Lentiginous Melanoma (ALM)
- Palms, soles, or nail beds
- Hutchinson Sign = extension of pigment into proximal or lateral nail fold
- Mostly in dark-skinned individuals
- Does not appear to be linked to sun exposure
- 50-60 yo
What subtype of melanoma is this?
Amelanotic
- non-pigmented cancer that does not make melanoma
- can appear similiarly to BCC
- can be dfifficult to diagnose because it can appear in a variety of colors, even the color of skin. Thus the diagnosis is often delayed, resulting in poor prognosis and high recurrence rates.
T/F Melanoma only occurs on the skin.
FALSE - it can arise novo or from nevi on the skin, but it can also occur in:
- periungual (around the nail)
- subungual (under the nail)
- ocular
- mucosal areas (genital, oral, anus, rectum)
- melanoma of unknown primary - metastatic melanoma that presents internally, but no original source from the skin is known
What is melanoma of unknown primary?
metastatic melanoma that presents internally, but no original source from the skin is known
What do these children have?
melanoma….
T/F Melanoma does not occur in children.
FALSE
children with congenital melanocytic nevi have a 465-fold increased risk of developing melanoma in childhood and adolescence
Who usually finds the melanoma?
- patient 50%
- physician 25% - finds it earlier and patient does better
- family member 17%
What are the clinical signs of melanoma?
- A Asymmetry
- B Border – uneven, crusty, or notched
- C Color – variety of colors; NOT uniform
- D Diameter ≥6 mm, pencil eraser
- E Evolving (∆ size, shape, color)
Other than ABCDE, what are other suspicious factors concerning melanomas?
- inflammation within or around nevus “ugly duckling”
- bleeding or crust in absence of trauma
How is melanoma screened for?
Skin exam by dermatologist
Dermoscopy & clinical inspection – skin surface microscopy or epiluminescence microscopy. _MOST helpful _
Total body photography - not as helpful
Computerized evaluation
Define the prognosis of melanoma in terms of:
Gender
Site
Ulceration
Breslow thickness
LN
Metz
Age
Mitosis
- **Male gender **- poorer prognosis
- Site % survival: (best) extremity lesions > head, neck, trunk, > volar or sublingual (worst)
- Ulceration – worse prognosis
- **Breslow thickness: **ncreasing thickness is bad
- Lymph nodes: macroscopic (palpable) nodal metastases with poorer prognosis
- Site of distant metastases - visceral metastases with poorer prognosis than nonvisceral (skin, nodes)
- **Age **- older age = worse prognosis
- Mitoses – > 1 = worse
What is the normal skin biopsy obtained for melanoma?
How is this different than a shave biopsy?
adequate biopsy = specimen includes the entire lesion and gets beneath the lesion (to the sub-cu fat layer) = depth of tumor correlates with risk of metz
shave biopsy = compromises pathologic diagnosis and complete assessment of Breslow thickness but is acceptable when the index of suspicion is low
What is the clinical staging of melanoma?
What is stage correlated with?
How is each stage treated?
Clinical staging - (stage is correlated with mortality rate)
stage I/II – cutaneous disease
stage III – regional metz to LN
stage IV – distant metz to LN and distant sites
Stage I/IIa – excision
Stage IIb/c – excision +/- IFN
Stage III – wide local excision + IFN alpha (or observation)
Stage IV – new and changing; accounts for ~40% of the total annual cost for melanoma treatment
What is the breslow thickness?
Why is this measure important?
thickness measured from the stratum granulosum to the deepest invasion of the specimen (used in both melanoma and SCC)
MOST IMPORTANT prognostic factor
- thickness is correlated with risk of metz and mortality)
When is a sentinal LN biopsy performed?
What would you do if it turns out to be positive?
indicated for melanomas with a Breslow depth of >1mm
If it’s positive, then a lymphadenectomy is recommended for prognostic purposes.
What is the standard of care for melanoma?
- *Surgical excision** - standard of care
- amount of margin (surrounding melanoma) to excise is based on Breslow’s depth of the initial melanoma
- sentinel LN biopsy provides info on subclinical LN status
What is Ipilumumab?
What are the pros of using Rx? Cons?
What is an alternate drug that is commonly used?
- *Ipilumumab** – mAb that inhibits CTLA-4 (normally down-regulates T cells) -> enhanced T-cell activation and proliferation
- in melanoma, it may indirectly mediate T-cell immune responses against tumors
Pros: average survival increase ~2 months
- *Cons**:
- overall response rate is 20%;
- effect can take months
- increased autoimmune events
- diarrhea (can be additive with IL-2)
USE VEMURAFENIB instead
What is Vemurafenib?
How does it work?
ADRs?
BRAF kinase inhibitor (remember that 45% of metastatic melanoma have BRAF activating mutation)
MoA: inhibitor of BRAF kinase activity -> inhibits tumor growth in cells harboring the mutation
Pros
- greater response rate of 40-50%
- effect seen in days-weeks
- 20% survival increase at 6months
Cons/ADR
- *- SCC eruptions**
- *- photosensitivity**
- *- duration of response is only 5-6 months**
How is melanoma prevented?
decrease UV exposure (sunscreen, clothing, sun avoidance, regular skin examination in high risk populations)
sunscreen (broad spectrum):
regular dermatologic surveillance, esp for patients with
- hx of melanoma
- multiple atypical moles
- family hx of melanoma ≥2 blood relatives
