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Skin and soft tissue > Malignant Melanoma > Flashcards

Malignant Melanoma Flashcards

1
Q

What is melanoma

A

Malingnacy derived from melanocytes or neural crest cells

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2
Q

Where are melanocytes located

A
  • epidermis
  • hair follicles
  • uveal tract
  • retina
  • inner ear (striae vascularis)
  • leptomeninges
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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
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4
Q

What are predisposing conditions to melnaoma

A
  • FAMM
  • XP
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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
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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
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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

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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

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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
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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
  • Other pigmented lesion
    • PIgmented BCC
    • Pigmented AK
    • Dermatofibroma
    • SK
  • Vascular lesion (sclerosing hemangioma)
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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
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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
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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
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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
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15
Q

How is the breslow thickness measured

A

from s. granulosum to inferior aspect of tumor

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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

  1. 01 -2mm => 1-2cm
  2. 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
Q

What are principles of treatment for melanoma on a finger/toe?

A
  • 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
Q

How do you manage LN basin in context of melanoma

A

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
Q

What is the role of SLNBx in melanoma management

A
  • 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
Q

WHat is the MSLT1 and 2

A

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
Q

Descibe principles of management for inguinal LAD and H&N

A
  • 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
Q

What are indiciations for SLNBx in melanoma

A
  • 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
Q

What aadjuvant treatments option are recommended

A
  • 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
Q

What is the rate of recurrence of melanoma and how do recurrences appears

A
  • 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
Q

Where does melanoma metastasize to

A
  • LN, skin subcut
  • Lung
  • Liver
  • Brain
  • Bone
  • GI
34
Q

What is the treatment for metastatic melanoma

A

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
Q

What is the recommended f/u for pt diagnosed w melanoma

A
  • 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

Skin and soft tissue (13 decks)

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