20 - 116: MELANOMA Flashcards
This melanoma subtype is most commonly arise from a slowly changing preexisting nevi. Arises commonly on intermittently sunexposed skin: the lower extremities in women and upper back in men
Superficial Spreading Melanoma
This melanoma begins de novo on the trunk with rapid evolution, 5% are amelanotic, with highest association with BRAF gene mutation.
Nodular Melanoma
This melanoma is most commonly seen in the 7 thto 8 th decades, on sun exposed face, cheeks & nose, with history of cumulative sun exposure. With a prolong radial growth phase then invades. More frequently associated with c-kit aberrations.
Lentigo Maligna Melanoma
Most common site for acral lentiginous melanoma
Sole>Palm&Subungal
Suspicion of malignancy in pigmented nail lesions include the following except.
a. Pigmentation extending to the periungual skin
b. Pigmentation is isolated on a single digit
c. Occurrence in 2 nd to 3 rd decade of life
d. Pigmentation occurring after a history of trauma after ruling out subungual hematoma
Answer: C. 4th -6th decade table 116-1 p 1986
This immunostain has high specificity for melanoma cells
a. S100 and Sox-10
b. HMB-45
c. Melan-A
d. MiTF
Answer: B. p 1994
- S100 and Sox 10 are expressed in all melanomas but also in melanocytic nevi
- HMB 45 is a monoclonal antibody with high specificity for melanoma cells
- Melan A is expressed in both benign and malignant lesions. More sensitive than HMB 45, more specific than S 100
So yung ranking: Top 1. HMB-45 2. Melan-A 3. S100
Useful marker for amelanotic melanoma since this stains the nucleus, whereas all other markers are mainly intracytoplasmic
MiTF
Correct arrangement visceral sites of melanoma metastasis
Lung > liver > brain > bone > GI
This is the single most important prognostic factor for survival and clinical management on localized stage I and II cutaneous melanoma
Breslow thickness
Stage of melanoma where the patient has microscopic nodal disease to bulky clinical nodes or in transit metastasis
III
What is the standard of therapy for primary cutaneous melanoma?
Wide local excision
Surgical margins for melanoma 1 to 2 mm thickness
1-cm – 2-cm
Stage 4 systemic treatment for melanoma
a. Immune checkpoint blocker
b. Targeted therapy
c. Low-dose interferon for high risk primary
d. A and B
e. All
d. A and B
A powerful staging tool that identifies micrometastatic nodal disease.
SLNB
In management of satellite or in-transit metastases, it is an effective and tolerable treatment option for patients with in-transit metastases but needs special technical equipment.
Electrochemotherapy
Most common subtype of melanoma
Superficial spreading melanoma
accounting for approximately 70% of all cutaneous melanomas.
subtype of melanoma most commonly associated with preexisting nevi
Superficial spreading melanoma
second most common melanoma subtype and accounts for approximately 15% to 30% of all melanomas
NODULAR MELANOMA NM
Most common site of nodular melanoma
Trunk
It is more common to begin de novo than to arise in a preexisting nevus
nodular melanoma
SSM is diagnosed most commonly on intermittently sunexposed areas, most frequently the _____ of women, and the _______ of men.
lower extremity - women
upper back - men
This type of melanoma most commonly begin de novo than to arise in a preexisting nevus
Nodular melanoma
What types of melanoma have the highest rate of mutations in the BRAF gene?
SSM, NM
is a melanoma in situ with a prolonged radial growth phase
Lentigo Maligna
LM is a melanoma in situ with a prolonged radial growth phase that eventually becomes invasive and is then called ________
LENTIGO MALIGNA MELANOMA (LMM)
Age group where LM and LMM are commonly found
7th to 8th decades
Uncommon before age 40
Most common location of LM and LMM
chronically sun-exposed face, on the **cheeks and nose **in particular; the neck, scalp, and ears in men.
sun exposure history of LM and LMM
cumulative sun exposure
are associated with significantly higher rates of extensive subclinical lateral growth, resulting in higher recurrence rates with standard recommended margins and failure to completely excise the lesion
LM and LMM
these types of melanoma have the least common association with nevi, at 3% of cases
LM and LMM
These types of melanoma have the highest rate of association with desmoplastic melanoma
LM and LMM
represents the most common form of melanoma in darker-pigmented individuals
ACRAL LENTIGINOUS MELANOMA ALM
most common site for ALM
sole, with the palm and subungual locations following
This type of melanoma is not thought to be associated with sun exposure.
ACRAL LENTIGINOUS MELANOMA (ALM)
Subungual melanoma, considered a variant of ALM, generally arises from what part of the nail?
Nail matrix, most commonly on the great toe or thumb
finding of pigmentation on the proximal nail fold
Hutchinson sign
may be noted with subungual melanoma
In acral melanoma, the most frequent targetable mutation is
BRAF Mutation
When will you consider Malignancy in Pigmented Nail Lesions?
associated with higher local recurrence but lower nodal metastatic rates than other subtypes of melanoma
DESMOPLASTIC MELANOMA (DM)
In desmoplastic melanoma, BRAF and NRAS mutations are not found; instead, other genetic alteration known to activate the MAPK signaling cascade were identified, for example, mutations in ____________ in more than 90% of cases.
neurofibromin (NF1)
most frequent location for mucosal melanoma
nasal cavity
this type of melanoma describes a heterogeneous group of rare lesions that histologically resemble benign nevi by their symmetry and apparent maturation with descent in the dermis, thus with greater potential for misdiagnosis
NEVOID MELANOMA
Clues to their histologic diagnosis include marked hyperchromasia of the nuclei of the tumor cells, the presence of mitoses, and expansive growth of the dermal cells.
subtype of melanoma that clinically and histologically resembles a Spitz nevus, but tends to be larger and have asymmetry and irregular coloration.
SPITZOID MELANOMA
Features that favor the diagnosis of a Spitzoid melanoma over a benign Spitz nevus are large size (greater than 1 cm in greatest dimension); lesions with a thick invasive component (>2 mm Breslow thickness); lesions with numerous mitoses (especially any atypical forms), many cytologically atypical cells, and lesions that have a clinically concerning course such as very rapid growth in size or satellitosis
Uveal melanomas account for about 5% of all melanomas and develop mainly where?
choroid, followed by ciliary body and iris of the eye
most common primary intraocular malignancy.
UVEAL MELANOMAS
T/f. Vitiligo in association with melanoma has a worse prognosis.
False
The development of a melanoma-associated vitiligo as an accompanying autoimmune disease against melanocytes is reported to occur in up to 4% of patients and is associated with a better prognosis.
p1989
best measures to estimate melanoma risk
Risk prediction models reveal in detail that the number of nevi, presence of freckles, history of sunburn, hair color, and skin color are the best measures to estimate melanoma risk
Most common sites of melanoma in younger men and women
Men - trunk and upper back
Women - Lower legs and trunk
most common location for melanoma in older persons
face
with the addition of the neck, scalp, and ears as well, in older men
phenotypic features associated with an increased risk of melanoma of 2- to 3-fold
Light skin pigmentation, blond or red hair, blue or green eyes, prominent freckling tendency, and tendency to sunburn with Fitzpatrick skin phototype I–II
There is an increased risk of melanoma associated with nevi, both in a quantitative (ie, number of nevi) and qualitative (ie, typical vs atypical nevi) manner.
Adults with more than _________ clinically typical-appearing nevi, children with more than _________ typical-appearing nevi, and any patient with atypical nevi are at risk.
Adults: > 100 nevi
Chihldren: > 50 nevi
large congenital nevi is defined in most studies as greater than how many cm in diameter?
> 20 cm
enumerate the ABCDE checklist of melanoma
A stands for asymmetry (one half is not identical to the other half),
B for border (irregular, notched, scalloped, ragged, or poorly defined borders as opposed to smooth and straight edges),
C for color (having varying shades from one area to another),
D for diameter (ie, greater than 5 mm), and
E for evolution (changes in the lesion over time).
dermoscopic findigs of melanoma
Immunohistochemical stains expressed by almost all melanomas but also by melanocytic nevi, and other tumor types, including cutaneous neural tumors
S100 and Sox10 proteins
monoclonal antibody with high specificity for melanoma cells
HMB-45
may be useful, especially in amelanotic melanomas, as it is a marker in the nucleus, whereas all other markers are mainly intracytoplasmic.
microphthalmiaassociated transcription factor (MiTF)
Immunohistochemically, Desmoplastic Melanomas commonly express only __________________ and lack other melanocytic markers like HMB-45, Melan-A, and MiTF.
Desmoplastic Melanoma
(+) S100 and Sox10
(-) HMB-45, Melan-A, and MiTF
- this marker for melanoma is a bit more specific than LDH but lacks sensitivity
- can be detected and monitored in clinical followup as an additional marker to detect progression of the disease
Serum S100B
Testing of the nonspecific tumor marker LDH is indicated only for patients with distant metastatic disease as it is needed for AJCC classification and prognostic evaluation
far more sensitive and accurate at detecting microscopic metastases than PET scan, CT scans, or ultrasonographic imaging combined with lymph node fine-needle aspiration
SENTINEL LYMPH NODE BIOPSY (SLNB)
Based on this risk stratification, SLNB is recommended in patients with a melanoma ≥____ mm Breslow thickness.
1 mm
The visceral sites of metastasis of melanoma from most to least common.
lungs (18%-36%),
liver (14%-20%),
brain (12%-20%),
bone (11%-17%), and
GI tract (1%-7%)
LuLiBraBoG
Melanoma metastasizes to nonvisceral sites: **distant skin/subcutaneous tissue and distant lymph nodes **in approximately half of the stage IV cases (42% to 57%) (
defined as the presence of histologically confirmed melanoma in a lymph node, visceral site, or distant skin/subcutaneous tissues without a history or evidence of a primary cutaneous, mucosal, or ocular melanom
Metastatic melanoma of unknown primary (MUP)
Approximately 60% of these involve the lymph nodes and might have developed from nodal nevi
The single most important prognostic factor for survival and clinical management in localized stage I and II cutaneous melanoma
tumor thickness
second most powerful predictor of survival, after tumor thickness
mitotic rate of 1/mm2 or greater
most powerful prognostic factor for survival in melanoma
status of the regional lymph nodes,
with regional lymph node metastasis portending a worse prognosis.
The number of lymph nodes involved (independent of tumor deposit size) is the most significant risk factor in patients with stage III melanoma
most significant prognostic factor with respect to disease-free and disease-specific survival.
SLN status
As such, consideration of SLNB to search for micro-metastatic disease has become the standard of care for most clinically node-negative patients with melanomas 1 mm and greater in thickness, and for a subset of thinner melanomas, with additional risk factors such as high mitotic rate and lymphovascular invasion, especially in younger patients.
standard of therapy for primary cutaneous melanoma
wide local excision (WLE)
For melanoma in situ, what are the margins of excision?
0.5 - 1 cm
For melanoma with <1 mm Breslow depth, what is the margin of excision.
1 cm
For melanoma with 1 - 2 mm Breslow depth, what is the margin of excision.
1 - 2 cm
For melanoma with >2 mm Breslow depth, what is the margin of excision.
2 cm
For patients with stage III disease in the USA, treatment with this anti-CTLA-4 antibody is FDA approved.
Ipilimumab
only FDA-approved chemotherapy for metastatic melanoma
dacarbazine (DTIC)
Approximately half of the lesions of this subtype arise in association with the LM histologic subtype.
DESMOPLASTIC MELANOMA
the primary metastatic site in uveal melanoma
liver
serves as a surrogate measure of intermittent intense sun exposure
Sunburn history, notably blistering and peeling burns
- In most melanoma risk prediction models, the history of sunburns is an important risk factor, not just in childhood, that is, the more sunburns in a lifetime, the higher the melanoma risk.
- One blistering sunburn in childhood more than doubles a person’s chances of developing melanoma later in life
the ABCDE Checklist does not apply to what subtype of melanoma?
nodular or desmoplastic melanoma
the most frequent mechanism of acquired therapeutic resistance
Reactivation of the MAPK pathway
thus, BRAF inhibitors have been combined with MEK inhibitors such as trametinib and cobimetinib.
