Melanoma Flashcards
What is melanoma?
Melanoma is a malignant melanocytic neoplasm characterized by an initial radial growth phase (lateral spread within the epidermis), followed by a nodular vertical growth phase (invasion into the dermis).
What are the histopathologic features of melanoma?
- Atypical melanocytes
- Pagetoid spread
- Nests of melanocytes
- Increased mitotic activity
- Invasion into the dermis
What are key histopathologic markers used to confirm melanoma?
- S-100
- HMB-45
- Melan-A
What are the major risk factors for melanoma?
- UV light exposure
- Fair skin
- History of nevi
- Family history
- Xeroderma Pigmentosum (defective nucleotide excision repair leading to UV sensitivity and DNA damage accumulation)
What are the clinical features of melanoma?
- Asymmetry.
- Border irregularity.
- Color variability.
- Diameter >6 mm.
- Evolution over time.
What is the ABCDE rule for melanoma detection?
- A: Asymmetry
- B: Border irregularity
- C: Color variation
- D: Diameter >6 mm
- E: Evolution or Elevation
What is the ‘ugly duckling’ sign?
A lesion that appears different from surrounding nevi (larger, darker, asymmetric, or rapidly changing) may be suspicious for melanoma.
How is melanoma diagnosed?
Clinical examination with dermoscopy, followed by excisional biopsy (1-3 mm margin) for histopathological evaluation.
What are the four major types of melanoma?
- Superficial Spreading Melanoma (Most common, long radial growth phase, good prognosis, macule/thin plaque).
- Nodular Melanoma (Second most common, vertical growth phase, poor prognosis, pigmented nodule).
- Lentigo Maligna Melanoma (Third most common, elderly, sun-damaged skin, slow progression, tan/brown macules).
- Acral Lentiginous Melanoma (Palmar, plantar, subungual, no sun association, more common in African-Americans and Asians).
What is acral lentiginous melanoma, and why is it unique?
It occurs on palms, soles, subungual areas, is not sun-associated, and is more common in African-Americans and Asians.
How does nodular melanoma differ from other types?
It has an aggressive vertical growth phase, is the second most common subtype, appears as a darkly pigmented nodule, and has a poor prognosis.
What is the most significant prognostic factor for melanoma?
Breslow depth (tumor depth measured in millimeters)
Other prognostic factors for melanoma besides Breslow depth:
- Ulceration
- Sentinel lymph node involvement
- Lymphovascular invasion
- Mitotic rate
What is the significance of Breslow depth?
Breslow depth (measured in mm) correlates with prognosis, risk of metastasis, and guides surgical excision margins.
How is melanoma managed based on Breslow depth?
- In situ: 0.5 cm margin.
- <1 mm: 1 cm margin.
- >1 mm: 1-2 cm margin.
- >0.8 mm: Consider sentinel lymph node biopsy.
What is the prognosis of melanoma based on Breslow depth?
Thin tumors (<1 mm) have an excellent prognosis, while thick tumors (>4 mm) have a high risk of metastasis and poor survival.
When is sentinel lymph node biopsy indicated?
Recommended for tumors >0.8 mm depth or ulcerated lesions, as it helps assess regional lymph node metastasis.
What are treatment options for metastatic melanoma?
- Surgical resection (if limited disease).
- Immunotherapy (Checkpoint inhibitors: PD-1 inhibitors [Nivolumab, Pembrolizumab], CTLA-4 inhibitor [Ipilimumab]).
- Targeted therapy (BRAF/MEK inhibitors for BRAF-mutated melanoma).
What are PD-1 inhibitors, and how do they work?
Nivolumab and Pembrolizumab are immune checkpoint inhibitors that block PD-1, restoring T-cell anti-tumor activity.
What are common adverse effects of PD-1 inhibitors?
Fatigue, rash, pruritus, immune-related adverse events (colitis, pneumonitis, endocrinopathies like thyroiditis, hypophysitis, adrenal insufficiency).
What is CTLA-4 inhibition, and how does it help treat melanoma?
Ipilimumab blocks CTLA-4, enhancing T-cell activation against tumor cells.
What are the adverse effects of CTLA-4 inhibitors?
Severe immune-related toxicities (colitis, hepatitis, endocrinopathies, skin reactions).
What is the role of targeted therapy in melanoma?
BRAF V600E mutation-positive melanomas benefit from BRAF inhibitors (Vemurafenib, Dabrafenib) and MEK inhibitors (Trametinib, Cobimetinib).
What are melanocytic nevi?
Melanocytic nevi are benign proliferations of melanocytes, commonly associated with UV light exposure and fair skin.
What are the types of melanocytic nevi?
- Junctional Nevus: Dark, macular lesion from the basal epidermis, common in children.
- Compound Nevus: Darkly pigmented papule from the basal epidermis/upper dermis interface.
- Intradermal Nevus: Skin-colored to tan papules from the dermis, common in adults.
- Atypical (Dysplastic) Nevus: Still benign but has some high-risk features associated with melanoma risk.
What is the most common location for junctional nevi?
Junctional nevi are most commonly found on the palms, soles, and genital areas due to melanocyte proliferation at the epidermal-dermal junction.
What are the clinical features of melanocytic nevi?
Nevi generally appear as <6 mm, round/oval, with a regular border, even hyperpigmentation, and a homogenous surface.
What are the key features of Atypical (Dysplastic) Nevus that should be taken into consideration?
Can progress to melanoma.
What are the distinguishing features of dysplastic nevi?
Dysplastic nevi have asymmetry, irregular borders, color variegation, and a larger diameter (>6 mm), resembling melanoma but remaining benign.
What is the significance of multiple dysplastic nevi?
Patients with multiple dysplastic nevi are at increased risk for familial atypical mole-melanoma syndrome, which predisposes to melanoma.
How are melanocytic nevi diagnosed?
Diagnosis is clinical, but biopsy may be performed if there is any uncertainty or atypical features.
What is the management of melanocytic nevi?
Observation for benign nevi. Excisional biopsy is recommended for lesions with concerning features or changes over time.
What are the risk factors for melanocytic nevi development?
UV light exposure, fair skin, and genetic predisposition are key risk factors for developing nevi.
What is the difference between congenital and acquired nevi?
Congenital nevi are present at birth and have a small risk of melanoma transformation, while acquired nevi develop later and are typically benign.
What is the halo nevus phenomenon?
A halo nevus is a melanocytic nevus surrounded by a depigmented ring, due to an autoimmune response against melanocytes.
When should a nevus be biopsied?
A nevus should be biopsied if it demonstrates rapid growth, ulceration, color changes, asymmetry, or irregular borders, which raises concern for melanoma.
What is the management of congenital giant nevi?
Congenital giant nevi (>20 cm) carry an increased risk of melanoma and may require surgical excision or close monitoring.
