Malignant Melanoma Flashcards
What is melanoma
Malingnacy derived from melanocytes or neural crest cells
Where are melanocytes located
- epidermis
- hair follicles
- uveal tract
- retina
- inner ear (striae vascularis)
- leptomeninges
What are risk factors for melanoma
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
What are predisposing conditions to melnaoma
- FAMM
- XP
What are diangostic criteria for FAMM
- >100 melanocytic nevi
- >1 nevi greater than 8mm
- >1 nevi with atypical features
- absent at birth but increase in size since puberty
What are precursors for malignant melanoma and pathology
- 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
What are the clinico-histologic subtypes /classify melanoma
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
What are the histologic characteristics of the most common subtypes?
- Superficial Spreading
- NOdular
- Lentigo MM
- Acral
- 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
What are prognostic indicators for melanoma
(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
What is you differential Dx of a pigmented lesion
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)
How do you identify high risk lesion for melanoma
- Asymmetry
- Border irregularity
- Color varigation
- Diamter >6mm
- Elevated surface or evolving
- Ugly duckling
Describe your history and physical for pt presenting w chief complaint of changing mole
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
When and what type of biopsy is indicated?
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
What investigations will you require for workup of melanoma diagnosis
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
How is the breslow thickness measured
from s. granulosum to inferior aspect of tumor
What is the important factor predicting recurrence?
Breslows thickness
What is the important factor predicting survival?
presence of LN metastasis
If present, # of LNs is most imortant prognosticator
What is the 5yr survival of melanoma patients according to breslows thickness?
Breslows thickness => % 5yr survival
- <0.75mm => 90-100%
- 0.76 - 1 mm =>75 %
- 1.5 - 4 mm=> 45%
- > 4mm => <45%
What are clark’s levels
I- confined to epidermis
2- Papillary dermis
3- P-R junction
4- Reticular dermis
5- subcut
How is melanoma staged
According to TNM
- Clinical staging
- Physical exam, biopsy/Excision (WLE), imaging
- Pathologic staging
- uses all of the above + Bx of LN +/- organs
Define micrometastasis, macrometastasis, microsatellite, satellites metastases, intransit metastases
- 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
How is melanoma treated?
1- Primary treatment = WLE, deep fascia left intact
2- Management of LN basin
3- Adjuvant therapy
What are the surgical margins for WLE of melanoma?
Based on breslows thickness
MIS => 0.5cm
<1 mm => 1 cm
- 01 -2mm => 1-2cm
- 01 - 4mm => 2cm
>4.01 mm => 2cm
What are principles of treatment for melanoma on an ear?
- 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
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
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
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
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
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
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
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
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
Where does melanoma metastasize to
- LN, skin subcut
- Lung
- Liver
- Brain
- Bone
- GI
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
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
