Melanoma Flashcards
Review updated tumor staging guidelines for melanoma.
- Tx: cannot be assessed
- T0: no primary tumor
-Tis: in situ - T1: ≤ 1.0 mm
— a: ≤ 0.8 mm w/o ulceration
—b: 0.8- 1.0 mm without ulceration, ≤ 1.0 mm w/ ulceration - T2: 1.1-2.0 mm
—a: w/o ulceration
—b: w/ ulceration - T3: 2.1 - 4.0 mm
— a: w/o ulceration
— b: with ulceration
-T4: > 4 mm
—a: w/o ulceration
— b: w/ ulceration
Review general overview of lymph node staging in melanoma
-Nx: regional nodes can’t be assessed
-N0: no regional Mets
-N1: 1 node
-N2: 2 or 3 nodes
-N3: ≥ 4 nodes
Subcategories for each
-A: clinically occult node(s) w/o satellites, local recurrence, or transit Mets
-B: clinically detected node(s) “ ^”
-C: no satellites (N1), 1 clinically occult node w/ “^” (N2), 2 or more nodes clinically occult or with satellites, local recurrence, or in transit Mets in > 1 node
Review the metastasis staging for melanoma
-M0: no Mets
-M1a: Mets to skin, subQ or distant LN
—(0) normal LDH
—(1) elevated LDH
-M1b: Mets to lung
—(0) normal LDH
—(1) elevated LDH
-M1c: Mets to all other visceral sites
—(0) normal LDH
—(1) elevated LDH
-M1d: Mets to brain
—(0): normal LDH
—(1): elevated LDH
What is recommended regarding genetic expression profile outside of clinical study?
Don’t recommend genetic expression profile outside of clinic study
Still get SNLB
What are liquid biopsies being explored for in melanoma?
Prognosis, monitor treatment response, genetic tumor evolution, and acquired drug resistance
Based on circulating tumor cells, cell-free tumor DNA, microRNA
What is the significance of the presence of BRAF in melanoma prognosis?
Independent prognostic factor for progression and recurrence free survival
What predicts response and prolonged survival in patients treated with pembrolizumab or nivolumab?
Undetectable cell-free tumor DNA level at baseline or within 8 weeks of therapy
What is the effect of surgery timing after biopsy on mortality risk?
Surgery within 30 days of biopsy lowers mortality risk
What margin is recommended for Breslow thickness < 1 mm?
1 cm margins
What margins are recommended for Breslow thickness > 1 but ≤ 2 mm?
1-2 cm margins
What margins are recommended for Breslow thickness > 2 mm?
2 cm margins
What technology is used for identifying sentinel lymph nodes in melanoma surgery?
Indocyanine green based technology
What are the advantages of indocyanine green over methylene blue?
Highest tissue penetration, visualization up to 1 cm deep, lack of radiation, lower side effect protein, less false negatives
Does complete lymph node dissection after positive SLNB increase survival benefit?
No increased survival benefit compared to observation of nodal basin
Complete dissection if evident disease; may depend on subgroups of melanoma
What are melanomas derived from?
Melanocytes in the stratum basale
What are the four layers of the epidermis from deep to superficial?
- Stratum basale
- Stratum spinosum
- Stratum granulosum
- Stratum corneum
What additional layer is found in glabrous skin?
Stratum lucidum
What type of cells are found in the stratum basale?
Basal cells
What do basal cells differentiate into?
Keratinocytes
What is formed in the stratum spinosum?
Intercellular connections via desmosomes
What do keratinocytes have in the stratum granulosum?
Keratohyalin granules
In the stratum corneum, how are the cells arranged?
Compact and surrounded by a lipid layer
Where are Merkel cells located?
Stratum basale
Where are Langerhans cells found?
- Stratum spinosum
- Stratum granulosum
- Dermis
What is a congenital melanocytic nevus associated with?
Abnormalities of the vertebral column, including spina bifida
What is the recommended treatment for giant congenital melanocytic nevus?
Surgical treatment does not reduce risk. Risk of melanoma in this population is 0.7 - 2.9% vs. 0.6% in the general population. Melanoma is a generic biological risk rather than related to the nevus itself. Melanoma highest risk on trunk lesions, but can still occur in satellite lesion instead of the gain nevus itself.
What defines a giant nevus?
- 20 cm in greatest dimension in an adult or will be once child grown
- Nevus > 100 cm² in area
- Nevus that cannot be excised in one stage
What is the melanoma risk in patients with multiple congenital nevi?
> 3 nevi indicates malignant potential
What is the second most common subtype of melanoma?
Nodular melanoma
When should non-urgent surgery for melanoma in pregnancy be performed? What if the risk of waiting is unacceptable?
In the second trimester to avoid preterm contractions and spontaneous abortion.
If risk to high»_space; perform a wide local excision with local anesthetic after a preioerative lymphoscintigraphy with delayed sentinel node biopsy during general anesthesia in the second trimester or after delivery
Where are nodular melanomas commonly seen?
- Trunk
- Head
- Neck
What is a characteristic appearance of nodular melanoma?
Dark, dome-shaped with a blood blister appearance
Show a rapid vertical growth phase
What is the most common subtype of melanoma?
Superficial spreading melanoma
What characterizes superficial spreading melanoma?
Lateral spreading of malignant melanocytes in the epidermis in sun exposed skin or from pre-existing nevi
What is the typical location for lentigo maligna?
Chronically sun-exposed areas like face and neck
What is the treatment of choice for lentigo maligna? What if they are not surgical candidate?
Wide local excision (5-10 mm margins)
Can’t do Mohs b/c can’t interpret melanocyte proliferation on frozen section; must send for permanent for final margins
Second line therapy is radiation and 5% imiquimod (clearance rate of 50-93% and 24.5% recurrence); can also be used on positive or close margins after excision if re-excision not possible or would cause unacceptable morbidity.
Where is acral lentiginous melanoma seen and in what population?
Found on palms, nail bed, soles of feet
Dark-skinned patients
What is the typical prognosis for acral lentiginous melanoma?
Worse than other melanoma subtypes (5 year survival 80% vs 91% in other types)
What is a characteristic feature of subungual melanoma?
Longitudinal band > 3 mm or irregular border, extension onto periungal skin (Hutchison’s sign - extends from top of nail to nail bed and into eponychium), single finger involvement
What is the current recommendation for biopsy in subungual melanoma?
Perform a biopsy of any subungual lesion after 4 weeks without significant change
What type of melanoma is desmoplastic melanoma?
Rare subtype with aggressive local growth
What is the best method of biopsy for suspected melanoma?
Excisional biopsy
What is the standard surgical treatment for melanoma?
Wide local excision + sentinel node biopsy if < 0.75 mm + high risk factors (ulceration, male sex, head/neck location), consider for 0.8-1.0 mm, all > 1 mm need SLNB.
SLN biopsy does not increase survival - it is diagnostic
Must be sent for permanent sections for final margins. Frozen sections (aka MOHs) not an option in melanoma
What is the purpose of immunoscoring and immunoprofiling?
To evaluate preexisting antitumor immunity, identify therapeutic targets, and predict response to immunotherapy or small molecule inhibitors.
Involves microscopy and molecular testing of the primary tumor or metastatic disease.
What role does CTLA-4 play in immune response?
Downregulates immune response by transmitting inhibitory signals to T cells.
Ipilimumab is an anti-CTLA-4.
How does PD-1 affect T cell proliferation?
Inhibits T cell proliferation and survival by binding PDL-1.
Nivolumab and Pembrolizumab are anti-PD-1.
What correlation exists between PDL-1 expression in pretreatment biopsies and clinical outcomes?
Correlates with response and survival.
Important for predicting the effectiveness of immunotherapy.
List some immune-mediated adverse responses associated with immunotherapy.
- Rash
- Diarrhea
- Colitis
- Vitiligo
- Hypopituitarism
- Hypophysitis
- Adrenal insufficiency
PD-1 inhibitors are associated with fewer adverse responses.
What is the function of BRAF in cell growth?
Regulates cell growth by mitogen-activated protein kinase.
Mutation common is BRAF-V600E.
What are the side effects of BRAF inhibitors?
- Arthralgia
- Fatigue
- Diarrhea
- Cutaneous toxicity
- Keratoacanthoma
- Well-differentiated SCC
Effects can be mitigated by adding a MEK inhibitor.
What is the benefit of combining BRAF and MEK inhibitors?
Increased tumor response, decreased drug resistance, and decreased SCC due to unmasking of oncogene cancer RAS mutations in sun-damaged skin.
This combination therapy helps manage side effects and improve efficacy.
When is immunotherapy considered in melanoma
Stage III melanoma (positive nodes)
Review pathological staging of melanoma
