Malignant Melanoma Flashcards
(35 cards)
1
Q
What is melanoma
A
Malingnacy derived from melanocytes or neural crest cells
2
Q
Where are melanocytes located
A
- epidermis
- hair follicles
- uveal tract
- retina
- inner ear (striae vascularis)
- leptomeninges
3
Q
What are risk factors for melanoma
A
lifetime risk 1:75, median age dx 45-55
HOST FACTORS
- Genetics
- mutations in CDK 2Na and CDK 4
- Race
- caucasian >hispanic>blacks
- Age
- median age 57, most common ca for age 20-29
- Personal traits
- # nevi (>20), DN
- immunosuppresion
- blue/green eyes, red hair
- Personal History
- highest risk in first 2yr post Dx, 10%lifetime risk of 2nd melanoma
- Family History
- 10% pts have + FmHx
EXPOSURE
- sun exposure in childhood
- tanning beds, sun lamps
4
Q
What are predisposing conditions to melnaoma
A
- FAMM
- XP
5
Q
What are diangostic criteria for FAMM
A
- >100 melanocytic nevi
- >1 nevi greater than 8mm
- >1 nevi with atypical features
- absent at birth but increase in size since puberty
6
Q
What are precursors for malignant melanoma and pathology
A
- Dysplastic nevus
- proliferation of atypical melanocytes intra-epidermal arranged singly or nested in basal epidermis or above rete ridges
- variable or discontinuous atypia
- lifetime risk 8%, RR 2-8
- Lentigo maligna
- Non-nested proliferation of atypical melanocytes in atrophic epidermis
- 5% progression to MM
- Melanoma in situ
- intraepidermal melanocytic proliferation with fully evolved cellular atypia which is continuous
- GCMN
- >20cm, >144sq icnhes, resultign in defect that cant be closed primarily, invovling entire region
7
Q
What are the clinico-histologic subtypes /classify melanoma
A
Superficial Spreading (70%)
- arises from preexisting, trunks in M, legs in W
- raised irregular border, >6mm, varigated pink/brown/grey/blue color
Nodular (15%)
- legs, trunk
- presents as dark papule, grows quickly over months, ulcerates easily w trauma
Lentigo Maligna Melanoma (5%)
- H&N, sunexposed areas, arises in lentigo malingna w dermal invasion characterized by macular pigmentation
Acral lentiginous melanoma (2-8% in whites, 30-70% in blacks)
- arises in pals/sole/subungal
- hutchisnons ign - involved lateral or proximal nail fold
Amelanocytic melanoma
- nonpigmented flesh colored nodule mimicking bcc scc pyogenic granuloma
Desmoplastic melanoma
- firm flesh colored nodule, aggressive w PNI, LVI
Congenital melanoma
- due to metastatic mets from mom w MM - 100% fatal, ass. w neurocutaneous melanosis
Malignant Blue Nevus
Melanoma arising from GCMN
Mucosal melanoma
Verrucous melanoma
8
Q
What are the histologic characteristics of the most common subtypes?
- Superficial Spreading
- NOdular
- Lentigo MM
- Acral
A
- Superficial spreading
- Insitu component (large atypial melanocytes at DEJ with upward migration (pagetoid) or lentiginous (along adnexal structure) spread
- lateral intraepidermal extension
- loss of rete ridges, invasion of dermis
- Nodular
- extensive vertical growth into dermis with min radial extension
- dermal melanocytes have mitoses, nuclear pelomorphism, hyperchromic nuclei
- Lentigo
- in situ component
- lateral intraepidermal extension
- irregularly shaped hyperchromatic cells in spindle-shaped nests
- associated solar elastosis in dermis and atrophic epidermis due to sun damage
- Acral
- in situ component
- lateral intrapidermal extension
- melanocytes have increased melanin granules produced that fill the dendritic extensions
- acanthosis, elongated rete ridges
All positive staining s-100 HMB 45, MART1, tyrosinase
9
Q
What are prognostic indicators for melanoma
A
(indicates worse)
PATIENT FACTORS
- Gender (M)
- Age (>60)
- Location (axial >extremities)
TUMOR FACTORS *** BUDA MARS
- Breslow thickness*, Clark’s level
- Ulceration
- Diameter
- Angiolymphatic invasion
- Mitosis (>1/mm2)
- Aneuploidy DNA
- Regression
- Satellites, microscopic
OTHER
- SLN +
- LN # and clinical palpability
- LDH +
- Poor performance status
10
Q
What is you differential Dx of a pigmented lesion
A
CONGENITAL
- CMN
ACQUIRED
- Nevocellular Nevi
- Junctional, Compound, Dermal
- Spitz nevus
- Atypical nevus
- Halo nevus
- Melanocytic nevi
- Epidermal
- Ephelis
- Lentigo (simplex, solar, maligna, nevus spilus)
- Cafe au lait
- Becker nevus
- Dermal
- Blue Nevus
- Epidermal
- Other pigmented lesion
- PIgmented BCC
- Pigmented AK
- Dermatofibroma
- SK
- Vascular lesion (sclerosing hemangioma)
11
Q
How do you identify high risk lesion for melanoma
A
- Asymmetry
- Border irregularity
- Color varigation
- Diamter >6mm
- Elevated surface or evolving
- Ugly duckling
12
Q
Describe your history and physical for pt presenting w chief complaint of changing mole
A
HISTORY
- Review all RFs (FamHx, PersHx, Personal traits, Exposure, Gender, Age, Genetics, Race)
- ulceration, pruritus, change from previous or de novo
PHYSICAL
- examine ABCDE and ugle duckling
- total skin examination including nail plate and mucous membrane
- LN basin examination
13
Q
When and what type of biopsy is indicated?
A
Biopsy is indicated for any suspicious lesion
- Excisional with 1-3mm margin
- small lesion, good skin laxity allowing for 1’ clsoure
- Incisonal
- large lesion, unable to close primarily, aesthetically sensitive area
- include area w highest thickness and a segment of normal skin for invasion/satellites
- Shave biopsy Contraindicated
14
Q
What investigations will you require for workup of melanoma diagnosis
A
Laboratory
- Indicated if
- signs or symptoms of disease spread
- stage 2b (2.01mm-4mm w ulceration or >4mm)
- LDH (mets to liver + LUNG)
- ALP (mets to liver + BONE)
- AST/ALT (mets to liver)
- CBC (preop)
- BUN/Cr (pre-chemo)
Imaging
- Indicated if
- signs or symptoms of disease spread
- stage 2b (2.01mm-4mm w ulceration or >4mm)
- CXR
- CT CHest/Abdo/Pelvis
- CT head and neck
- CT/MRI brain if sxs indicate
15
Q
How is the breslow thickness measured
A
from s. granulosum to inferior aspect of tumor
16
Q
What is the important factor predicting recurrence?
A
Breslows thickness
17
Q
What is the important factor predicting survival?
A
presence of LN metastasis
If present, # of LNs is most imortant prognosticator
18
Q
What is the 5yr survival of melanoma patients according to breslows thickness?
A
Breslows thickness => % 5yr survival
- <0.75mm => 90-100%
- 0.76 - 1 mm =>75 %
- 1.5 - 4 mm=> 45%
- > 4mm => <45%
19
Q
What are clark’s levels
A
I- confined to epidermis
2- Papillary dermis
3- P-R junction
4- Reticular dermis
5- subcut
20
Q
How is melanoma staged
A
According to TNM
- Clinical staging
- Physical exam, biopsy/Excision (WLE), imaging
- Pathologic staging
- uses all of the above + Bx of LN +/- organs
21
Q
Define micrometastasis, macrometastasis, microsatellite, satellites metastases, intransit metastases
A
- Micrometastasis: + LN on pathology review
- Macrometastasis: clinically + LN
- Microsatellites; discontinuous nest of intralymphatic metastatic cells >0.05mm diameter and >0.3mm away main invasive lesion
- Satellite metastases: grossly visible cut or subcut intralymphatic mets within 2cm of primary melnaoma
- In transit metastases: grossly visible cut or subcut intralyphatic mets >2cm away from primary
22
Q
How is melanoma treated?
A
1- Primary treatment = WLE, deep fascia left intact
2- Management of LN basin
3- Adjuvant therapy
23
Q
What are the surgical margins for WLE of melanoma?
A
Based on breslows thickness
MIS => 0.5cm
<1 mm => 1 cm
- 01 -2mm => 1-2cm
- 01 - 4mm => 2cm
>4.01 mm => 2cm
24
Q
What are principles of treatment for melanoma on an ear?
A
- WLE: wedge with appropriate margins
- if wedge not done then at least perichondrium should be removed
- total auriculectomy or partial amputation if large/recurrent
- LN; if undergoing LND, should consider parotidectomy
25
What are principles of treatment for melanoma on a finger/toe?
* Distal tip, nail bed: amputation proximal to DIP jt
* Proximal finger: WLE with recommended margins based on breslows. No advantage to bone resection
* Toe: WLE involved amputation at MTP joint
26
How do you manage LN basin in context of melanoma
Palpable LN
* FNA
* if negative, open biopsy
* if positive TLND
No palpable LN
* SLNBx
* Pre-operative lymphoscintigraphy with radiocolloid intradermal injection Tc-99m sulfur colloid
* Intra-op lymphazurin blue injected for visual orientation
* INtra-op localization of Sentinel LN w hand held gamma probe
* Pathology review of entire SLN w serial sections, H&E, stains HMB-45 S100 MART1
* Completion LNB if positive SLNBx
27
What is the role of SLNBx in melanoma management
* identifies subclicical LN mets and identifies those to benefit from TLND
* prognosis (most important for survival)
* Defines those ot beenfit form adjuvant Tx
* determines eligibitlity for clinical trial
28
WHat is the MSLT1 and 2
Multicentre Selective lympadenectomy trial 1- completed
* Comparing WLE+ nodal obs OR WLE+SLNBx +/- LND if positive
* Conclusion- SLNBx prolongs 10yr DFS and melanoma specific survival for those w melanoma \>1.2mm)
MSLT2
* all patients udnergo SLNBx
* then if positive, randomized to CLND or ultrasound followup and TLND when detected by U/S
29
Descibe principles of management for inguinal LAD and H&N
* In inguinal LAD, a completion pelvic LN idssectio is completed if
* deep inguinal node is positive (Cloquet)
* \>3superficial nodes are positive
* clinically palpable nodes
* CT/PETscan shows positive LN at iliac or obturator
* In H&N, if clinically or microscopic LN+, completion parotidectomy recommended
30
What are indiciations for SLNBx in melanoma
* Offer if \>1mm thickness or 0.76-1mm with ulceration/mitoses
* Consider for 0.76-1mm without ulcertation/mitoses
* decision up to dr and patient for \<0.75mm with poor prognostic features (ulcer, LVI, mitoses)
* Consider for intransit resectable lesion
31
What aadjuvant treatments option are recommended
* Interferon alpha 2B
* for all melanoma \>1mm (stage 2b, 2c), +SLNBx, clinically +LN, intransit treated w WLE (stage 3)
* must be high dos for 1yr -\> improved 5yr DFS
* Radiation
* primary: desmoplastic melanoma w narrowm argins, recurrence, neutrophism
* Regional: post LND of clinically positive LN AND
* LDH less than 1.5x normal
* extracapsular involvement
* parotid \>1LN invovled
* cervical \>2LN involved and/or 3cm tumor in LN
* axillary \>2LN invovled and /or4cm tumor in LN
* INguinal \>3 involved and /or 4cm tumor in LN
* Metastatic: brain, symptomatic bone mets
32
What is the rate of recurrence of melanoma and how do recurrences appears
* Stage 1 = 2%
* stage 2 = 32%
Wihtin 2-3yrs usually
Recurrences:
* in scar: insitu or radial growth phase
* Tx- excise
* Satellite: sub cutaneous or dermal \<2cm from primary.
* Tx: resection w 2cm margin
* poor prognosis 20% 10yr survival
* In transit: sub cut or dermal \>2cm from primary
* Tx: IL2 or IFN injection, Isolated limb perfusion, surgery,radiotherapy, systemic Tx
* Regional LN
* Tx: CLND, Rtx if CLND already performed
Late recurrence
33
Where does melanoma metastasize to
* LN, skin subcut
* Lung
* Liver
* Brain
* Bone
* GI
34
What is the treatment for metastatic melanoma
1- Systemic Tx based on
* BRAF mutation status
* Speed of progression of disease
* presence of cancer related sxs (brain is priority
* OPTIONS: Ipilimubab (anti CTLA4), Verumafenib (anti-BRAF
2- Palliative Rtx
3- ISolated Limb perfusion- Melphalan
* S/E neutropenia, N/V, blistering, myopathy, neuropathy, art ven embolism
4- INtralesional treatment or intransit mets
35
What is the recommended f/u for pt diagnosed w melanoma
* Annual skin exam
* Educate on LN exa and skin exam
* Imaging if specific signs/symptoms
Stage 1A-2A (\<1mm to 4mm with no ulceration)
* H&P q 6mth for 5yr then annual
Stage 2B- 4 (4mm w ulceration
* H&P q 3mth for 2yr, then q 6mth for 3yr then annual
* consider CXR, CT and/or PET/CT q4-12m for recurrent disease
* consider brain MRI annually
