Fisher - Moles and Cancers Flashcards
1
Q
This 56 yo light-skinned woman complains of these persistent, firm bumps on the cheeks
They have been present for months without change
They are asymptomatic
She has tried scrubbing them and even squeezing them without benefit
WHAT IS THE BEST DX?
A
- Milia: small epidermoid cysts
- Common on cheeks, eyelids, forehead, genitals
- Occur at any age, including infants
- Often seen in sun-damaged skin
- May resolve spontaneously or be easily removed with blade or needle
- Relatively white, and filled with keratinaceous debris
2
Q
Your 35 yo physician partner requests removal of this nodule on her calf
It seemed to start as a bug bite, but has persisted for months
It is asymptomatic, but she always cuts it when shaving
It has not grown
HOW WOULD YOU MANAGE THIS LESION?
A
Reassure her that it is benign and tell her to quit shaving it
3
Q
What is this? Does it require treatment?
A
- Dermatofibroma: common, benign fibrotic tumors
- Frequently on extremities; red, brown, but NOT pigmented
- History of trauma (esp. bites) common, although etiology not well understood
- Horizontal compression (pinching) of the lesion can lead to dimpling -> DIMPLE SIGN (attached very deep to the dermis)
- If stable and asymptomatic, require no treatment
- If lesion is unusual, growing or irregular, consider further evaluation -> do get biopsied if there is ever a question (better to err on the side of biopsy rather than miss something malignant)
4
Q
What is this?
A
- Seborrheic keratosis: very superficial lesion
- Waxy, and somewhat keratotic
- Different shades of brown, so can get biopsied to rule out a melanocytic lesion
1. Can also get inflamed and become symptomatic - Can feel rough, keratotic to the touch, and don’t extend beyond the epidermis
5
Q
Seborrheic keratosis is a lesion located on which of layer of the skin?
A
Epidermis
6
Q
Are seborrheic keratosis benign, malignant, or pre-malignant?
A
Benign
7
Q
What is up with this dude?
A
- Numerous seborrheic keratoses
- Similar to the christmas tree appearance of pityriasis rosea (along the skin lines)
- Developing all of these in the course of a month, like this guy did, is unusual, and can be a sign of cancer
1. Acute onset of multiple seborrheic keratosis is a sign of cancer -> paraneoplastic from colon cancer, classically
8
Q
What is the sign of Leser-Trélat?
A
- Sudden eruption of multiple SKs can be marker for underlying cancer
- Associated cancers include adenocarcinoma of colon (classic one), breast, stomach, lung
- However, many adults have many SKs and this is thought to be rare sign
9
Q
What is this?
A
- Seborrheic keratosis: stuck-on appearing, and looks like it could be plucked off
- Keratotic, rough appearance
10
Q
What do you see here?
A
- Seborrheic keratoses: can look like a melanoma
- Biopsy, if you are concerned (better to be too cautious)
11
Q
What is this? What should you do next?
A
- Seborrheic keratosis
- This could have been easily sampled to rule out a melanoma (based on the color) -> bubbly appearance can be a helpful clue that this is SK
- Dermatoscopy: magnifier (typically x10), a non-polarised light source, a transparent plate and a liquid medium between the instrument and the skin, and allows inspection of skin lesions unobstructed by skin surface reflections
12
Q
What is the epi of SK?
A
- Usually do not appear until after age 30 (lesions of adults)
- Likely an autosomal dominant (AD) inheritance
- Males may be affected slightly more often and extensively than females
13
Q
What will the patient tell you about in their history to clue you in to an SK?
A
- Patients are often concerned about “moles” that have developed over months to years
- Lesions are usually asymptomatic unless in an area where friction causes irritation and tenderness
- Rarely, seborrheic keratoses may be pruritic
14
Q
What do SKs look like on PE?
A
- May be small, light tan and macular early on, but usually become larger, darker and raised over time
- Classic description: round or oval, skin colored to brown or black, slightly raised, “stuck on” papules and plaques on the face, trunk, and upper extremities
15
Q
What about these?
A
- Cherry angiomas: raised, bright red, fixed
- Benign, acquired vascular neoplasms
- Common on trunk in people > 40
16
Q
What is this?
A
- Keloid: suggestive of a shaving distribution
- Result from exuberant fibrous repair of tissue following a cutaneous injury, extending beyond the original site
- Usually follows injury to skin, but may also arise spontaneously
17
Q
What do you see here? Who gets these?
A
- Keloid: kind of ambiguous whether this is a case of a keloid, or hypertrophic scarring, but it does seem to have broken the boundaries of the injury line
- Most common in 30s, but can vary widely
- Equally affects men and women
- Genetic predisposition: African-American most frequent
18
Q
What is this? How are these managed?
A
- Keloid: central chest is a classic location (from thoracotomy scarring: incision into pleural space)
- No treatment for keloids is perfect
- Options include: intralesional corticosteroid injections (painful)
1. Surgical excision—high rates of recurrence; may come back even bigger! Can inject them with steroids after excision, or compress them
2. Cryotherapy (also painful; liquid nitrogen, but tend to come back)
3. Combined cryotherapy and intralesional triamcinolone (possibly more painful) - PREVENTION IS KEY! Avoid piercings and tattoos, along with other injuries to skin
19
Q
What is this? What will the pt history look like?
A
-
Keloid: may be pruritic or painful, but often asymptomatic
1. Can get parasthesias if small nerves are involved - Often the cosmetic appearance is the chief complaint
20
Q
What is an epidermal (epidermoid) cyst?
A
- Mobile dermal nodule, usually w/central punctum
1. Filled with keratinaceous debris, oils - If traumatized or rupture, can get very inflamed and abscessed
1. Keratin is something skin makes that is meant to be on the outside -> body considers it foreign material (e.g., ingrown toenail or hair)
2. If expressed, liberate rancid smelling, cheesy material - Commonly referred to as a sebaceous cyst -> not filled with sebum, but rather keratin
- If it has a central punctum (hole), and is not on the scalp, then it is most likely an epidermoid cyst
21
Q
How epidermal cysts managed?
A
- Many probably remain quiescent for years without treatment
-
Surgical removal of entire lesion has best “cure” rate
1. If you only partially remove them, they may come back - If inflamed, may need incision and drainage acutely
22
Q
What is this?
A
- 2nd most common cutaneous cyst
- Smooth, firm, dome-shaped 0.5 to 5 cm, keratin-containing, nodule to tumor, with a predilection for the scalp (90%) -> if you cut into it, it may not drain as much bc solid keratin debris inside
- Often familial with an autosomal dominant inheritance
- Much more common on scalp than in other locations
23
Q
How are nevi and SK different?
A
- Nevi do not make keratin, and have melanin in them (pigment network that SK do not have)
24
Q
What are the progenitors of BCC, SCC, and melanoma?
A
- BCC: germinative keratinocytes associated w/hair follicles (resemble dark blue basal layer)
- SCC: epidermal keratinocytes (resembles spinous layer)
- Melanoma: melanocytes
25
Where do melanocytes come from?
- _Neural crest-derived cells_, so melanoma and nevi can occur anywhere these cells migrate
- The dermal-epidermal junction just happens to be the most common site (also eye, medulla, inner ear)
- Sometimes we don’t see a primary melanoma in the skin (could be a different type of melanoma that metastasized)
26
What is this?
Melanoma
27
Which factor(s) contribute the most to patient prognosis from this lesion?
- Ulceration and _depth of dermal involvement_
- Depth of melanoma is probably the single most important prognostic feature
28
What is the relationship b/t nevi and melanoma?
- _Both are comprised by melanocytes_, and can share some mutations (e.g., BRAF)
- High numbers of nevi (esp. \>50) can increase risk of melanoma (more melanocytes in skin)
- Melanoma can develop from pre-existing nevi:
1. ~20% develop from nevi
2. _~80% develop de novo_
- Nevi can sometimes appear clinically (and histo) unusual and mimic melanoma, but are NOT pre-skin cancers (NOT pre-melanomas; BENIGN)
29
What are the types of nevi?
- Acquired melanocytic nevi:
1. Junctional (epidermis)
2. Compound (epi + dermis)
3. Intradermal (just dermis)
a. More flat if just in epidermis vs. more _raised if in the dermis_
- _Halo nevi_: common nevi the body regresses (doesn’t necessarily mean it was bad; more likely in patients with vitilligo)
- Congenital nevi
- Atypical (“dysplastic”) nevi
- Most nevi are acquired in the _first 30 years of life_ (unusual after that)
- _Remember_: these are *benign* neoplasms of melanocytes
30
What are these?
- _Junctional nevi_: nests of melanocytes are present within the dermis only
31
What is a melanoma?
- Malignant neoplasm comprised of melanocytes
- Not all melanocytic nevi are pre-melanomas -\> the great majority are NOT
- However, melanoma can develop in a pre-existing benign nevus (20%), or it can develop de novo
32
What is this?
- _Compound nevus_: nests of melanocytes are present within the epidermis and the dermis
33
What do you see here?
- _Intradermal nevus_: nests of melanocytes are present within the dermis only
34
What kind of nevus is this?
Acquired compound melanocytic nevus
35
What are these?
- Common acquired melanocytic nevi
- _Nevus_: classic definition is “any congenital lesion of the skin; a birthmark”
- _Melanocytic nevus_ refers to a benign (either congenital or acquired), localized proliferation of melanocytes within the epidermis and/or dermis
36
What is the difference between nevi and freckles?
- Nevi tend to swim alone
- Freckles are very symmetric and come up on sun-exposed surfaces (in groups; fade)
37
What is a junctional acquired melanocytic nevi?
- 2 to 3 mm in diameter
- Deeply pigmented and macular
- Arising at the dermal-epidermal junction above the basement membrane zone
38
What is a compound acquired melanocytic nevi?
- 3 to 4 mm
- Slightly raised, and moderately pigmented
- Melanocytes found both intra-epidermally and dermally
39
What is a dermal acquired melanocytic nevus?
- Larger and dome-shaped
- Cells exclusively in the dermis
40
Where does this lesion most likely originate?
Intradermally (bc it is raised)
41
What are halo nevi?
- Common acquired nevus with a surrounding zone of depigmentation -\> halo around them because the body is eliminating them (_immune response_)
- Epidemiology - _first three decades_, equal in males and females, more common in patients with vitilligo, familial tendency
- Highlights the relationship between melanocytic neoplasia and host immunity
- More common in children
42
What are these? What do they mean?
- _Halo nevi_: immune response
- When someone develops multiple halos around all of their nevi, they may have melanoma somewhere else -\> _do full body skin check_
1. Chances very low if a 10-y/o, but if 35-y/o, watch out!
43
What are congenital nevi?
- _Classified according to size_: small 20 cm
1. These are adult measurements (need to be adjusted when looking at a neonate)
- _Clinical features_: pigmentation varying from brown to black, grossly irregular surface, _hypertrichosis_ (abnormal amt. of hair growth)
- Large/giant congenital nevi: **5% risk of melanoma in first 5 years of life if nevus \> 5cm in size** (large); usually arises in dermis
1. Otherwise, like any other nevi
- Can be rough and corrugated on the surface
44
What is this?
Congenital nevus: involved spine; lots of satellite lesions (can cause seizures, in some cases)
45
What are atypical nevi?
- Controversial, but common acquired nevi that simply **appear unusual clinically**
- First described as _dysplastic nevus syndrome_ (BK mole syndrome), a *RARE* inherited syndrome
1. Pt, immediate family member may have 100's of irregular moles with hx/o melanoma
2. INC risk of melanoma in this very specific setting only
3. _CDNK2 (p16INK4A)_ tumor suppressor gene (mut only in 10% of non-familial melanoma)
- Atypical nevi are _NOT precursors to melanoma_, and do not transform into melanoma at a greater rate than any other acquired nevus
1. **One dysplastic nevus does not increase a patient’s risk of melanoma**
2. Pts with great numbers of atypical nevi probably have INC risk of melanoma, esp. if they have a family history of melanoma
46
What do you see here?
- Pt with multiple **atypical nevi**: irregular borders, variegated pigment and asymmetry of the nevi
- Matters because they look funny clinically, and can break the ABCDE rules
- _Get biopsied and excised a lot_
47
What do you think this is?
- **Dysplastic nevus**: with a fried egg appearance
- This is going to get biopsied and called a dysplastic lesion, but their _risk of melanoma is no higher than any other patient_
- Fall squarely in the nevi category (not melanoma)
48
Who gets melanomas?
- Highest risk in _Caucasian men \>50 y/o_
- Most common type of cancer in ppl 25-29 (and 2nd most common in 15-29)
- 1 American dies every hour from melanoma: pretty common
- RISING INCIDENCE
49
Who catches/finds melanomas most often?
Spouses and primary care docs
50
What is this?
Melanoma: asymmetric, streaky borders; jet black, with white streak
51
How does melanoma progress?
- Not as clearly a step-wise process as SCC, from pre-malignant to malignant lesions (e.g., melanocytic nevi do not all develop into melanoma)
- But, melanoma in situ when just in the epidermis, and not able to metastasize until it breaks through the BM
52
How are nevi and melanoma distinct histologically?
- **Nevi**: small, symmetric, and well-circumscribed
1. Nests organized and discrete, w/uniform size and shape
2. Melanocytes ‘mature’ with descent into the dermis (decrease in size), and _no melanocytes above basal layer_
- **Melanoma**: lg, asymmetric, & poorly circumscribed
1. Nests are confluent, with irregular spacing, irregular sizes and shapes
2. Melanocytes do NOT ‘mature’ with descent, and are located above the basal layer
53
What growth phase is this melanoma in?
- **Radial growth phase**: unorganized melanocytes, INC in # and _above basal layer (pagetoid spread)_
1. None have ‘invaded’ into the dermis, so this is an in situ lesion
2. Until melanoma is in the dermis, it can't metastasize -\> early detection & tx imperative
- Much more _haphazard_ than the nested nevi that have grouped melanocytes
54
What growth phase is this melanoma in?
- **Vertical growth phase**: invaded into the dermis, and can metastasize via lymphatics and blood vessels
- More risky than radial growth because this can lead to metastasis
- _Deeper it goes, the worse the prognosis_
55
What is the etiology of melanoma?
- MULTIFACTORIAL:
1. Genetic predisposition (eg. CDNK2; BRAF is in about 15% of melanomas on sun-damaged skin )
2. Environment (eg. UV)
3. Underlying immune status
56
What are the risk factors for melanoma?
- Large # of common nevi (esp. \>50)
- Giant congenital nevi (5% risk first 5 years)
- Atypical nevi, mostly if multiple and familial
- History of blistering sunburns
- Family History of Melanoma
- Light complexion, tanning bed use
- Underlying immune dysfunction
57
What are the ABC's of melanoma screening?
A - Asymmetry
B - Borders: irregular, scalloped
C - Color: mottled, variegated, not uniform
D - Diameter: \>6mm
E - Elevation (or evolution, i.e., changing)
- “Changing mole"
- "Ugly duckling sign:” when one lesion stands out among all the others
58
What is this? How can you tell?
- **Melanoma**
- Asymmetric
- Notched, irregular Border
- Color not uniform
- Diameter \>6mm
- Elevated
59
What is this?
- **Melanoma**: pigmented lesion w/irregular border
- "Ugly duckling”
- History of recent color change (in this case)
60
What is this? Why?
- **Melanoma**: notched border, asymmetrical, slight elevation
61
What do you see here?
- **Melanoma**: asymmetrical, irregular border
- Diameter \>6mm and elevated
62
What are the 5 subtypes of melanoma?
- _Acral lentiginous_: hands and feet (higher incidence in skin of color)
- _Lentigo Maligna Melanoma_: arises on sun-exposed surface of the face (brown, large patch)
- _Nodular_
- _Superficial spreading_: largely in radial growth phase (not nodular)
- _Amelonotic_: don’t have pigment, and can look very bland -\> can be easily missed
63
What is this? How is this lesion defined?
- **Acral lentiginous melanoma**: defined by anatomic location on palmar, plantar and subungual skin
- The most common type of malignant melanoma in pts with darker skin
- Acral = hands and feet
- Lentiginous = ‘like lentigo" -\> histo pattern that contains melanocytes growing like they do in a lentigo (a proliferation of solitary melanocytes that ‘line up’ along the basal layer)
64
What is this?
Acral lentiginous melanoma
65
What are these?
Acral lentiginous melanomas
66
What is this?
- **Lentigo melanoma**: older pts on sun-exposed skin; synonym for _melanoma in situ_
- Slow growing, still in radial phase (bc melanoma in situ)
- Irregularly shaped, with different shades of brown
- _NO capability of metastasizing_ if you catch it in this phase
67
What is going on here?
- _Nodule on the background of a lentigo maligna_
- Heralds the progression of the in situ lesion to an invasive one
68
What is this?
Nodular melanoma associated with a lentigo maligna
69
What is this?
Nodular melanoma
70
What is a nodular melanoma?
- Usually on sun exposed skin
- 15% of malignant melanoma; 2x M \> F
- Most have _focal, short-lived radial growth phase_ (starts in the epidermis because this is where melanocytes come from)
- Because the lesion is already in the dermis (it is in ‘vertical’ growth phase), the lesion is capable of metastasizing -\> **very quickly invade**
71
What is this?
- **Superficial spreading melanoma**: asymmetrical
- Irregular borders
- Wide variation in color
- Diameter \>6mm
- Elevated
- Red, white, and blue
- Growing outwards as it’s growing down
72
What do you see here?
Superficial spreading melanoma
73
What is this?
Seborrheic keratosis: note the indulating, cerebriform shape
74
Are these the same? Different? What are they?
- Left: seborrheic keratosis
- Right: melanoma
75
What is this? Should you biopsy it?
- **Seborrheic keratosis**: deep furrows and kind of cerebriform
- Better _biopsy this, just in case_
76
What happened here?
- **Seborrheic keratosis**: much more likely because it just fell off when going to biopsy it
77
What is this?
Seborrheic keratosis
78
What are these two lesions?
- Left: melanoma in situ
- Right: seborrheic keratosis
79
What is this?
Melanoma in situ
80
What is this?
**Melanoma in situ** (many of these lesions really could be either melanoma or SK, and need to be biopsied)
81
What is this?
- **Melanoma in situ**
- All of these lesions really could be either melanoma or SK, and need to be biopsied
82
What is this?
Melanoma
83
What is this?
Melanoma
84
What is this?
Melanoma
85
Are these the same? Different? What are they?
- Left: pigmented BCC
- Right: melanoma
- Dr. Fisher said even he couldn't really tell which is which -\> do a BIOPSY in these cases to ID
86
What is this?
Acral lentiginous melanoma
87
What is going on here?
- **Melanoma of the iris**
- Nevi can develop in the iris too -\> remember, neural crest cells in many parts of the body (see attached)
88
What is this?
Mucosal melanoma: vulvar
89
Do melanomas metastasize?
- YES -\> often _via lymphatics_, but not exclusively
- #1 organ site for metastasis: **SKIN**
- Single most important prognostic factor: _lymph node involvement_ (do sentinel node biopsy)
- Most important histological prognostic factors:
1. _Breslow thickness_ and ulceration
90
What is Breslow's thickness?
- Distance of involvement from the stratum granulosum (top) of the overlying epidermis to the deepest tumor cell (bottom)
1. Most important histo prognostic factor
- _HUGE differences in survival_ (see attached)
91
What is this?
Metastatic melanoma
92
How is melanoma treated?
- **Catch it early and CUT IT OUT**
- _Metastatic melanoma treatment_: until 2011, no definitive proof that any labwork, imaging study, or intervention increased overall survival
1. IFNa, combination chemotherapy, XRT, vaccine therapy
2. Systemic disease once it metastasizes
93
What % of melanomas have BRAF mutations?
50%
94
What is Vemurafenib?
- Small molecule inhibitor of BRAF approved for _unresectable or metastatic (stage 4) melanoma_
- Provides survival benefit (although modest):
1. Initial response impressive but melanoma adapts; _duration of response only 6 mos_
2. New trials focused on combo tx, esp. with Ipilimumab (inhibits CTLA-4)
- Pt's melanoma must be tested prior to therapy, and must harbor an activating mutation in **BRAF V600E** to be eligible for the drug
- Around _50% (or greater) patients_ with melanoma will harbor BRAF V600E mutations
95
What is Ipilimumab?
- _Anti-CTLA4 antibody_
- Normally, CTLA4 acts as an inhibitory signal to prevent T cell activation, but w/Ipilimumab, T cells activated, and induce a generalized inflammatory response to fight malignancy
- Much _more sustained duration of response_ (even years); can be combined with Vemurafenib
96
What is Nivolumab?
- Usually **first-line** therapy
- _More robust response than with Ipilimumab_
- Being used in mono and combo therapy
97
How do you select a sunscreen?
- Remember: all melanoma is NOT caused by sun exposure
98
What factors contribute to the development of skin cancer?
- Multifactorial:
1. Genetics
2. Environment: HIGH EXPOSURE to envo insults
3. Immune system response
99
Why is there so much potential for early detection of skin cancer?
- It is VISIBLE; non-invasive screening
- BCC and SCC are the two most common cancers, but neither is reportable
100
What is this? How do you know?
- **BCC**
- Telangiectasia is a helpful clue
- Red in the middle (ulcer)
- Pearly color
101
What is the most common mutation in sporadic tumors of the type attached here?
- **PTCH**: tumor suppressor gene -\> regulator of basal epidermal cell proliferation
- Common mutation in sporadic BCCs
- BCC is the most common invasive neoplasm in the US
102
Which of the following places the patient at greatest risk for metastasis from the lesion shown?
## Footnote
1. p53 mutation in the tumor
2. Location on the ear
3. The patient is immunocompetent
4. The tumor is HPV mediated
- Location on the ear
1. Ear and lips are high-risk locations for SCC metastasis -\> _good vascular supply with a very thin dermis_
- This is a **squamous cell carcinoma** (most have a p53 mutation, but this is not specific to SCC) -\> look like cells from the spinous layer
- Immunocompromised patient would have a greater risk of metastasis
103
How common are BCC and SCC?
- Two most common skin cancers in the US
- 1 in 5 lifetime risk
- Incidence rising among young females
104
What are the risk factors for BCC?
- UV exposure
- Fair complexion
- Hx/o sunburns (especially blistering)
- Family history of BCC
- Immunosuppression: incidence increased by immunosuppression (10x), but not to same degree as SCC
1. If immunosuppressed, SCC more common
105
What is this?
- **BCC**
- Can be very small, nodular, and pearly (much less disfiguring to catch it early)
106
What is this?
- **BCC**, nodular type
- Basophilic (blue) nodules emanating from the surface of the epidermis
- _How to distinguish this from melanoma_: note the peripheral **palisade** of tumor cells and **clefting** from adjacent stroma in the attached image
107
What do you see here?
- **BCC**: nodule of basophilic, pleomorphic cells with _hyperchromatic nuclei_
- Note the peripheral **palisade** of tumor cells and **clefting** from adjacent stroma
1. Peculiar cleft where the stroma (CT of the dermis) tends to separate from the tumor
108
What are the histo and clinical features of BCC?
- _Histo_: epidermal-stromal clefting in the middle panel and the peripheral palisade of cells (attached)
- _Clinical features_: pearly papules, topped with prominent, dilated subepidermal blood vessels (telangiectasia)
109
What is the histopathology of BCC?
- Basophilic, **hyperchromatic cells** that form nodules, often extending from surface epidermis
- Cells at the periphery of the aggregations form a **palisade** (cells line up like a picket fence)
- Tumor nodules are set in a mucinous stroma, with retraction (**clefting**, or ‘retraction artifact’)
1. Stroma is the CT surrounding the dermis, and is blue-ish (from mucin) and cellular -\> it appears different than normal dermis
2. Retraction from the adjacent stroma is an _artifact induced by processing of tissue_ to create H&E stained sections (slides) -\> stroma is not firmly attached, and during processing, it is easy for the tumor to retract from that stroma
110
What are the subtypes of BCC?
- _Nodular_
- _Superficial_: more amenable to superficial tx, like topical immunotherapy (imiquimod), topical chemo (5FU), and superficial destruction (eg cryotherapy)
- _Pigmented_
- _Morpheaform_ (sclerotic): looks like scleroderma (more like a scar)
- Histo subtypes we’re not expected to recognize: micronodular, cystic, infiltrative
111
Are these the same? Different? What are they?
- Both **BCC**
- _Superficial type on the left_: multifocal growth originating from the epidermis (lives much higher)
- _Nodular type on the right_: downward growth into the dermis
112
What is this?
- Classic **BCC (nodular)**: well-circumscribed nodule with pearly rolled border and central erosion
- Note telangiectasias as well
- Not all of these are ulcerated
113
What do you see here?
- **Superficial BCC** with prominent telangiectasias (superficial, dilated vessels)
114
What is this?
Nodular BCC
115
What is this?
**Superficial BCC**
## Footnote
- Can be confused with things like eczema sometimes because they are flatter
- Clearly an abnormal area with a _pearly surface_ in this example
116
What do you see here?
_Superficial BCC_: note how subtle these can be
117
What is this?
- **BCC, pigmented**
- Still has translucent qualities
- Can sometimes be confused for melanoma
118
What is this?
Pigmented BCC
119
What do you see here?
- **Morpheaform BCC**
- These can actually be very aggressive (wrapping around nerves, for example)
1. Once they invade nerves, they have a conduit to go wherever they want (and can cause neuropathies)
- Tends not to metastasize, but still very much a malignancy -\> will grow through cartilage, bone, brain, etc.
120
What is basal cell nevus syndrome?
- Aka, **Gorlin Syndrome**: auto dom, rare, mutation of **PTCH1** tumor suppressor gene
- BCCs at _early age_ (around 23-y/o); only 20% BCC presents before age 50, and rare prior to age 35
1. Devo basal cells at an alarming rate, and are disfigured as a result
- MSK defects and lots of jaw cysts
- _INC risk of other neoplasms_: medulloblastoma, fibrosarcoma
121
Does BCC metastasize?
Exceedingly rare: 0.0028% to 0.55% of cases
122
How is BCC treated?
- **Excision** (main option)
- Electrodessication and curretage
- Cryosurgery
- Radiation
- Topical treatment for superficial BCC: Imiquimod (which was originally approved for warts), 5-FU
- Vismodegib for _advanced BCC_: small molecule inhibitor -\> competitive antagonist of SMO
1. Metastatic disease, recurrent disease (post-sx), non-surgical candidates
2. AEs: can't taste food (lose weight), terrible muscle cramps, etc.
3. Numerous o/solid tumors, sarcomas have HH pathway signaling abnormalities, and clinical trials of vismodegib are underway in various stages for noncutaneous malignancies
123
If BCC rarely metastasizes, why is tx so important?
- Lack of metastasis does not mean that treatment is not required: **local destruction can be severe** (see attached image)
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What is Mohs surgery?
- Instead of cutting out skin cancer and sending to pathologist to see if margins clear, dermatologist acts as surgeon and pathologist, constantly checking the margins and using different technique (_horizontal sections_, instead of vertical)
- Able to target where margin is positive during sx, excising only that part (**skin-sparing technique** important if near structural things)
125
What is this?
- **Squamous cell carcinoma**: keratotic surface
- Doesn’t look like a BCC: not as characteristic -\> no classic description like BCC
126
How does SCC develop?
- Cutaneous squamous cell carcinoma from sun-exposed sites often follows **stepwise progression**:
1. Non-full thickness atypia -\> full-thickness atypia -\> invasive carcinoma
2. Actinic keratosis -\> squamous cell carcinoma in situ -\> Invasive SCC
- *Can metastasize*: very commonly goes to lymph nodes and lung
- Likes to invade nerves
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What is SCC? Different expressions?
- 2nd most common skin CA
- **Progression**, like cervical CA:
1. _Minimal atypia_ (actinic keratosis)
2. _Full thickness_ epidermal atypia confined above the basement membrane (SCC in situ)
a. Bowen’s Disease: patch that looks like eczema
b. Erythroplasia of Queyrat: plaque on glans penis à erythroplasia of Queyrat
3. _Invasive_ (SCC)
a. Well differentiated: better prognosis
b. Moderately differentiated
c. Poorly differentiated
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What is this?
Normal skin histo
129
What do you see here?
- **Actinic keratosis** morphology
- Cytologic atypia (dysplasia) in the lower portions of the epidermis (_cells are large and abnormal_)
- Stratum corneum is thickened with retention of nuclei (**parakeratosis**), and loss of underlying granular cell layer -\> scale seen in actinic keratosis
- Lesions may progress to full-thickness atypia, resulting in squamous cell carcinoma in-situ
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What is this? What are its clinical features?
- **Actinic keratosis**: b4 overt epidermal malignancy, series of _progressively dysplastic changes_ -\> name because dysplasia due to chronic sun exposure and results in hyperkeratosis
- **Clinical features**: flat, not firm (if it feels very thick, could be an invasive SCC bc these invade dermis and lift the skin up)
1. Common in _fair-skinned_ individuals, and predilection for sun-exposed site
2. \<1 cm in diameter, tan-brown, red, or skin colored, & rough, sand paper-like consistency
- Many regress or remain stable, however, enough become malignant w/evolution to SCC in situ and invasive SCC to _warrant treatment_
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What is going on here? How might you treat it?
- **Actinic keratoses**: thin non-indurated lesions -\> lack of induration (hardness) a clue to superficial nature of lesions
- _AK -\> SCC risk_: 1 in 1000 within 1 yr
- Can do cryotherapy to some of them
- Use _peel treatments for patients like this_; can also use Imiquimod or 5-FU
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What is this?
- Photodistributed lesions of AK -\> pre-skin cancers
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What is this?
AK with crust to it -\> warning sign
134
What are these?
Actinic keratoses
135
What are these? What next?
- **Actinic keratoses**: more, thicker lesions -\> might need to biopsy some of these
136
What do you see here?
- **Actinic keratoses**: can become thicker on hands because people rub at them
137
What is this?
**Actinic keratosis**: would be very concerned about this one because it is ulcerated and thick
138
What is this?
_SCC in situ_: note the full-thickness of the atypia (can also look for keratin pearls)
139
What is the morphology of SCC?
- Hyperchromatic, pleomorphic nuclei, disorganized growth, mitoses, invasion through the basal layer
- Cells are **pink and keratinizing**, like the stratum spinosum
- When atypical keratinocytes break through BM zone, squamous cell carcinoma becomes invasive
- While morphology of SCC may vary, they all share the features of keratinization
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What are some things that increase the likelihood of metastasis of SCC?
- Risk of metastasis related to **size** of tumor, **depth** of invasion into dermis, anatomic **site**, and host immune status:
1. Larger than 2cm clinically, greater the risk
2. Greater than 4mm in depth (subcutaneous extension), greater the risk
3. Higher risk on lips and ears
- Tumors that arise in context of actinic keratoses may be less clinically aggressive than those arising in burn scars, ulcers, and in non-sun-exposed sites
- _Remember_: SCC is common, arising on sun-exposed skin in older people
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What is this?
- **SCC, invasive**: note the islands of squamous epithelial cells extending into the dermis
- Squamous cells make small nodules of keratin, often called **keratin pearls**
- Much more pink that BCC (not blue)
- The carcinoma is trying to make keratin
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What is happening here?
- **Progression of AK to SCC in situ to SCC across one patient’s temple**
- Raised lesions should make you SUSPICIOUS
- USMLE books sometimes note that BCC is more common on the upper face, while SCC is more common on the lower face -\> this is not particularly helpful in daily practice, but perhaps it is relevant for board preparation
143
What is this?
**SCC** that looks like BCC: sometimes they break the rules
144
What is the etiology of SCC?
- No specific SCC oncogene or tumor suppressor gene has been identified
1. Increased p53 mutations only (but these are not specific as these mutations are common in many types of cancer)
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What are the risk factors for SCC?
- _MAY BE TESTED ON THESE_
- **UV**
- **HPV** (especially types 16, 18, 31, 35)
- Chronic inflammation (e.g., osteomyelitis with draining sinus tract, and some chronic inflammatory dermatoses)
1. Chronic erosive mucosal lichen planus
- Certain scars (eg. burn): fertile soil for devo of carcinoma because injury to the skin (i.e., ulcers) and chronic inflammation
- Chemical exposure, especially arsenic
- Radiation exposure
- Leukoplakia
- **Immunosuppression**
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How often does SCC metastasize? Where to?
- _Overall \<5%_ metastasis rate, but different risk in different settings:
1. Closer to 0.5-1%: actinic-induced non-mucosal skin
2. _Higher in other clinical scenerios_:
a. Actinic-induced on **lip** 2-16%
b. **Marjolin’s ulcers** 10-30% (aggressive, ulcerating SCC in area of previously traumatized, chronically inflamed, or scarred skin, e.g., burn)
c. Vulvar, perineal, penile **HPV-induced** 30%
d. Leukoplakia
- Mets to **lymph nodes and lung**
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What is this?
- **SCC**: longstanding, ulcerated plaque on the right forehead
148
What is this? How do you know?
**SCC**: bc it doesn't look like BCC
149
What is this?
- **HPV-associated, peri-ungual SCC**: rare, but can happen (transformation of wart to SCC)
150
What do you see here?
SCC in situ on lower lip
151
What is this?
**SCC** on lower lip: looks large and deep = high risk bc invasive
152
What is this?
SCC on tongue (could be from leukoplakia)
153
What do you see here?
- **Bowen’s Disease**: SCC in situ that looks like eczema
154
What is this?
- **Erythroplasia of Queyrat**: SCC in situ on the penis
- Long-standing, not acute (so less worried about STI)
155
What is this?
Radiation-induced SCC: this case was a dentist
156
What do you see here?
- **SCC** arising in a plaque of leukoplakia, probably secondary to tobacco use
157
What is this?
- Lobular tumor with focal ulceration: **SCC**
- Can grow quickly, ulcerate, and involve local lymph node base
158
What do you see here?
- **Keratoacanthoma**: neoplasm of keratinocytes
- Related to SCC, possibly a subtype
- Rapidly _grows over 2-6 weeks_
- PAINFUL
- _May involute spontaneously_: probably because immune system regresses it
- Fast-growing, dome-shaped, and keratotic
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What is this?
- **Marjolin's ulcer**: ulcerated invasive SCC arising on a background of chronic inflammation, scarring, radiation, trauma
- These are risk factors for SCC development, as mentioned before
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How is SCC treated?
- Depends on degree of progression:
1. _Actinic Keratosis_: topical therapy, cryotherapy
2. _SCC in situ_: topical therapy, intralesional, excision
3. _Invasive SCC_: excision
- **Excision is still the gold standard**
