Premalignant and Malignant Neoplasms

Question 1

AKs:
1. Grading system, describe
2. Dermoscopic features
3. Histopath key features
4. Talk through use, dose, SE, expectations, outcomes:
- Efudix
- Imiquimod
5. Ways to optimise efudix use
6. PDT refresher

Answer 1

1. Olsen. Grade I - III
2. Erythema, increased prominence follicular units. Keratotic plugs with ‘seeds of the strawberry’ appearance
3. Epi: hyperkeratosis, parakeratosis. Alternating ortho and parakeratosis ‘flag sign’.
   Partial thickness atypical keratinocytes w nuclear pleomorphism, disordered maturation. Lower portion of epidermis
4. See drug cards
5. Pretreat with retinoid, acid. Efudix wraps.

Question 2

SCCIS
1. Dermoscopic features
2. Histopath features
3. Treatment ladder

Answer 2

1. Erythema, glomerular vessels, scale and keratosis
   Pigmented: linearly arranged brown or grey dots. Grey circles
2. Parakeratosis. Acanthosis.
   Full thickness epidermal atypia with dyskeratosis, nuclear polymorphism, apoptosis, mitoses
3. Depends on site, risk, comorbidities, pt pref.
   5FU, aldara
   C+C
   Cryosurgery
   Curettage alone
   PDT
   Ablative laser
   JAAD Review - C+C and cryo + curettage had lower recurrence rates than topicals + PDT

Question 3

SCC
1. Percent of cSCC that progress to advanced SCC
2. BWH staging
3. AJCC8 staging
4. Risk factors for invasive SCC
5. What is the DANGER framework to identify high risk primary cutaneous lesions?
6. Dermoscopic features
7. Histopath features

Answer 3

1. ~5% (AJD). BJD 2-5% metastatic potential
2. BWH: based on risk factors
   – Tumour diameter >2cm
   – PNI >0.1mm
   – Poorly differentiated
   – Tumour invasion beyond subcutaneous fat
   T1 = 0 risk factor
   T2a = 1 risk factor
   T2b = 2-3 risk factor
   T3 = >/= 4 RF or bone invasion
3. AJCC8. TMN. T based on tumour size
   T1= <2cm diameter
   T2 = 2-4cm
   T3= >4cm OR bone invasion OR PNI OR invasion beyond s/c fat or >6mm
4. > 2mm (Cancer council says >4mm) thick, >2cm diameter. High risk Location: ears, lips, mucosae. Arising within scar (burn, irradiation). Poor differentiation. Immunosuppressed. Recurrent lesion. PNI/LVI.
5. Depth (>4mm), Drugs (immsupp)
   Anatomical site (ears, lips)
   Nerve involvement (histo >0.1mm, or named nerve)
   Grade (poor diff)
   Extent (>2cm dimension)
   Residual (<1mm margin)
6. Linear irregular vessels. Hairpin vessels in milky halo. Dotted vessels
7. Downward proliferation lobules, aggregations of glassy eosinophilic keratinocytes. Pleomorphism, mitoses. Apoptotic cells. Keratin pearls

Question 4

KA
1. Variants

Answer 4

1. Solitary - CMGS
   >Classic SCC variant
   >Mucosal
   > Giant
   > Subungual, erodes bone
   Multiple - CMGF
   > Centrifugum marginatum
   > Muir Torre assoc
   > Gryzbowski (eruptive, itchy, ectropion)
   > Ferguson Smith (AD, onset childhood)

Question 5

BCC
1. Differentiate low vs high risk BCC
2. BJD guideline excision margins
Recurrence rate with incomplete excision
3. Subtypes
4. Dermoscopic features
5. Histopath
6. Hedghog inhibitors refresher

Answer 5

1.
Low risk: <2cm, well defined. Primary. Nodular or superficial
High risk: >2cm, poorly defined. Recurrence. Infiltrative, basosquamous. Immunosuppressed
2. Low risk - 4mm margin. High risk - 5mm margin. Close margin <1mm.
Incomplete excision, recurrence at least 25% over 5 years
3. Nodular, superficial, infiltrative (includes morphoeaform, sclerosing, micronodular)
4. Arborising telangiectasia; fosi of microulceration; blue grey ovoid nests; blue grey dots and globules; leaf like structures; spoke wheel pigmentation
5. Aggregates basaloid keratinocytes, fibromyxoid stroma. Connection to epidermis. Peripheral palisading. Tumour stromal cleft.
– Cystic/nodulocystic: have pools of mucin
– Micronodular: small tumour islands

Question 6

Gorlin’s
1. Inheritance, gene
2. Diagnostic criteria
3. Other cutaneous features
4. Tumour associations
5. MDT workup and involvement

Answer 6

1. AD. PTCH1 (50-70%), PTCH2, SUFU
2. BC PROM, MC FLOOR
3. Milia, epidermoid cysts, multiple naevi, facies (coarse face, frontal bossing, broad nasal bridge)
4. Medulloblastoma (<3yo. 20x higher risk if SUFU)
   – Meningioma
   – Ovarian fibromas, 13-60%
   – Cardiac fibromas
5. OMFS (PTCH1 2 yearly from 8yo OPG/MRI, prn from 22yo. Yearly from first OKC)
   – Neuro 4/12ly MRI B if SUFU or no genetics. PTCH1 - only if Sx
   – Cardiology: fibromas
   – Gynae: ovarian fibromas
   – Ophthal: baseline

Question 7

AI in skin cancer Dx
Legal and ethical considerations

Answer 7

• Liability
  ○ False positives, negatives.
  ○ Who is liable for AI errors
  
  • Medical negligence
    ○ Inappropriately / inadequately consenting pts for use of AI, limitations of AI. Breach of duty of care
  • Not suitable for all populations - eg SOTR
  • Difficult sites, lower diagnostic accuracy - hair bearing, acral
  • Software developers and suppliers have a duty of care
  • Privacy
    Data being transferred without pt permission

Question 8

Melanoma
1. Modifiable RF
2. Non modifiable RF

Answer 8

1. UVR exposure: burns, tanning, AKs, early life UV exposure
   PMHx: immunosuppression, transplantation
   Vit D
   herbicides
2. Age, sex, race. Phenotype (hair colour, eeye colour)
   Genotype (CDKN2A, MITF also RCC, MC1R red hair blue eyes, BRCA2 per Ingrid)
   PMHx: PHx or FHx melanoma, CLL, HSCT, genodermatosis

Question 9

NMSC
1. Modifiable risk factors
2. Non modifiable risk factors

Answer 9

1. UV exposure, sunburns, indoor tanning, occupational UV exposure
   Med history: immunosuppression, transplantation, serum vit D, chronic inflammation (eg ulcer)
   Other: smoking, EtOH, ionising radiatino
2. Sex (male). Phenotype (red blonde hair, fair skin, light eye colour)
   Genotype (MC1R red hair blue eyes, TP53)
   Med hx: CLL,, HSCT, genodermatosis

Question 10

Skin cancer risk in immunosuppressed
1. Highest risk organs
2. Highest risk immunosuppression
3. Wait time for transplantation after skin malignancy
> Melanoma at diff stages
> cSCC at diff stages/risk

Answer 10

1. Multivisceral (heart lung) > thoracic organ > pancreas and renal > renal > liver
2. CNI > thiopurines (AZA) > IMDH inhibitors (MMF) > mTOR
3. MIS - no wait
   1a melanoma <1mm - 2y
   1b/2a melanoma - 2-5 y
   2b/c - 5y
   cSCC
   Low risk - no delay
   High risk, no PNI - 2y
   High risk, PNI or RF - 2-3y
   High risk, local nodal involvement - 5y

Question 11

Immuno and targeted therapy
1. Types of immunotherapy
2. ICI. - types of reactions. Timing of them.
3. ICI - grading reactions
4. TVEC vs BVEC
5. Non cutaneous AEs of PD1
6. Preferred Rx for melanoma
7. what are advantages of neoadjuvant therapy?
8. BRAF. AEs

Answer 11

1. ICI
   PD1: pembrolizumab, nivolumab, cemiplimab
   CTLA4: ipilimumab
2. – Maculopapular (eczematous and lichenoid). 3-6/52
   – Psoriasiform. 5-12/52
   – Pruritus. 3-10/52
   – Vitiligo. Much more common in melanoma. Positive predictor tumour response. Late onset - months after starting
   – Immunobullous. 2-27 months
   – SCAR
3. 4 grades (except psoriasiform)
   1=macules and papules <10% BSA
   2 = 10-30%
   3= >30%
   4= any life threatening
4. TVEC = talimogene laherparepvec. Live HSV containing GMCSF. CI: pregnancy, immunosuppressed. Intralesional, for intransit mets.
   BVEC = beremagene geperpavec.
   Dead virus. Topical. EB.
5. Gastritis; thyroiditis; endocrinopathies; colitis; hepatitis; pneumonitis; hypophysitis (inflamed pituitary)
6. PD1 first line, considered standard of care.
7. assess treatment response, tumour shrinkage and higher surgical clearance, greater immunological effect due to presence of macroscopic tumour
8. General: fever, fatigue, GI upset, arthralgias, LFT dernagement, heart failure, HTN, renal toxicity. Neurologic disorders
   – Cutaneous: BRAF alone. AK, SCC, KA. Eruptive melanocytic naevi. KP like eruption
   Granulomatous reactions (JAAD review).

Question 12

Melanoma 1 of 3
1. Risks of partial biopsy
2. Look at questions in table on melanoma page
3. Clinical and dermoscopic features subungual melanoma (past exam Q)
4. When to consider testing for CDKN2A and genetic counselling
5. Types of melanoma

Answer 12

1. Misdiagnosis; inaccurate microstaging
2. Clinical findings: wider proximally, Hutchinson’s sign, pigment on paronychia or hyponychium. Erythronychia. Nail dystrophy, fissuring or nail plate destruction
   Dermoscopic features: multiple bands of irregular colour, width and spacing with disruption of parallelism. Hyponychial pigment will have acral melanoma features - parallel ridge pattern, irregular fibrillary pattern, irregular and diffuse pigment with multiple colours. Micro Hutchinson’s sign (can onlly be seen by dermoscopy). Less common signs - atypical vessels, blood spots
3. Consider in: strong FHx (3 or more first or second degree relatives), and other predictive features eg - multiple primary melanoma, early age onset, pancreatic cancer
4. SSM, nodular, lentigo maligna, ALM
   Spitzoid, desmoplastic, malignant blue naevus. Mucosa.

Question 13

Melanoma 2 of 3
6. Cutaneous melanoma dermoscopy
7. Where is BT measured from?
8. Melanocytic IHC markers?
9. What is the AJCC8 T staging?
10. histopath buzz words

Answer 13

6. Atypical network, focal streaks, atypical dots and globules, negative pigment network. White shiny structures. Grey dots/granulas. Blue white veil. Vascular structures
7. BT measured in mm from top of granular layer
8. S100, HMB45, MART1, Melan A
9. Tis = MIS
   T1 <1mm
   1a <0.8mm and no ulceration
   1b <0.8mm + ulceration oR 0.8-1mm
   T2 >1-2mm
   T3 >2-4mm
   T4 >4mm
   All T divided into A and B, a without ulceration, b with ulceration
10. Asymmetric, poorly circumscribed. Nests of melanocytes
    Pagetoid spread. No maturation of melanocytes. Pleomorphism. Mitotic figures. Necrotic melanocytes.

Question 14

Melanoma 3 of 3
11. Excision margins
12. When to consider slnbx
13. Follow up intervals
14. ABCDEF algorithm for nail unit melanoma
15. Dermoscopy lentigo maligna

Answer 14

11. pT1 - <1.0mm: WLE 1cm margin
    pT2 - 1.01mm - 2.00mm: WLE 1-2cm
    pT3 - 2.01 - 4.00mm: WLE 1-2cm
    pT4 - >4.0mm: WLE 2cm
12. Consider when >1mm thick or >0.75mm thick and other high risk pathological features
    – Provides staging of LN basin. Presents high yield, low volume tissue sample for histopath assessment
    13 .
    Stage 1 (T1) = annual 10 yrs
    Stage IIa (T2b, 3a) = 6/12 2yrs, annually 8yrs
    Stage IIb, IIc (T3b, 4a, 4b) = 3-4/12 2 yrs, 6/12 yr 3, annual 5 yrs
    Stage IIIa-c (T and nodes) = same
13. Age 50s-70s. Band brown - black >3mm or 40%+
    Change size
    Digit. Thumb > hallux. Dominant hand
    Extension to periungual - Hutchinson
    FHx melanoma, DN
14. Annular granular pigment; asymmetric follicular openings; rhomboidal structures; follicular destruction
    Circle within a circle