Melanoma

Question 1

What is melanoma?

Answer 1

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).

Question 2

What are the histopathologic features of melanoma?

Answer 2

• Atypical melanocytes
• Pagetoid spread
• Nests of melanocytes
• Increased mitotic activity
• Invasion into the dermis

Question 3

What are key histopathologic markers used to confirm melanoma?

Answer 3

• S-100
• HMB-45
• Melan-A

Question 4

What are the major risk factors for melanoma?

Answer 4

1. UV light exposure
2. Fair skin
3. History of nevi
4. Family history
5. Xeroderma Pigmentosum (defective nucleotide excision repair leading to UV sensitivity and DNA damage accumulation)

Question 5

What are the clinical features of melanoma?

Answer 5

• Asymmetry.
• Border irregularity.
• Color variability.
• Diameter >6 mm.
• Evolution over time.

Question 6

What is the ABCDE rule for melanoma detection?

Answer 6

• A: Asymmetry
• B: Border irregularity
• C: Color variation
• D: Diameter >6 mm
• E: Evolution or Elevation

Question 7

What is the ‘ugly duckling’ sign?

Answer 7

A lesion that appears different from surrounding nevi (larger, darker, asymmetric, or rapidly changing) may be suspicious for melanoma.

Question 8

How is melanoma diagnosed?

Answer 8

Clinical examination with dermoscopy, followed by excisional biopsy (1-3 mm margin) for histopathological evaluation.

Question 9

What are the four major types of melanoma?

Answer 9

1. Superficial Spreading Melanoma (Most common, long radial growth phase, good prognosis, macule/thin plaque).
2. Nodular Melanoma (Second most common, vertical growth phase, poor prognosis, pigmented nodule).
3. Lentigo Maligna Melanoma (Third most common, elderly, sun-damaged skin, slow progression, tan/brown macules).
4. Acral Lentiginous Melanoma (Palmar, plantar, subungual, no sun association, more common in African-Americans and Asians).

Question 10

What is acral lentiginous melanoma, and why is it unique?

Answer 10

It occurs on palms, soles, subungual areas, is not sun-associated, and is more common in African-Americans and Asians.

Question 11

How does nodular melanoma differ from other types?

Answer 11

It has an aggressive vertical growth phase, is the second most common subtype, appears as a darkly pigmented nodule, and has a poor prognosis.

Question 12

What is the most significant prognostic factor for melanoma?

Answer 12

Breslow depth (tumor depth measured in millimeters)

Other prognostic factors for melanoma besides Breslow depth:
- Ulceration
- Sentinel lymph node involvement
- Lymphovascular invasion
- Mitotic rate

Question 13

What is the significance of Breslow depth?

Answer 13

Breslow depth (measured in mm) correlates with prognosis, risk of metastasis, and guides surgical excision margins.

Question 14

How is melanoma managed based on Breslow depth?

Answer 14

1. In situ: 0.5 cm margin.
2. <1 mm: 1 cm margin.
3. >1 mm: 1-2 cm margin.
4. >0.8 mm: Consider sentinel lymph node biopsy.

Question 15

What is the prognosis of melanoma based on Breslow depth?

Answer 15

Thin tumors (<1 mm) have an excellent prognosis, while thick tumors (>4 mm) have a high risk of metastasis and poor survival.

Question 16

When is sentinel lymph node biopsy indicated?

Answer 16

Recommended for tumors >0.8 mm depth or ulcerated lesions, as it helps assess regional lymph node metastasis.

Question 17

What are treatment options for metastatic melanoma?

Answer 17

1. Surgical resection (if limited disease).
2. Immunotherapy (Checkpoint inhibitors: PD-1 inhibitors [Nivolumab, Pembrolizumab], CTLA-4 inhibitor [Ipilimumab]).
3. Targeted therapy (BRAF/MEK inhibitors for BRAF-mutated melanoma).

Question 18

What are PD-1 inhibitors, and how do they work?

Answer 18

Nivolumab and Pembrolizumab are immune checkpoint inhibitors that block PD-1, restoring T-cell anti-tumor activity.

Question 19

What are common adverse effects of PD-1 inhibitors?

Answer 19

Fatigue, rash, pruritus, immune-related adverse events (colitis, pneumonitis, endocrinopathies like thyroiditis, hypophysitis, adrenal insufficiency).

Question 20

What is CTLA-4 inhibition, and how does it help treat melanoma?

Answer 20

Ipilimumab blocks CTLA-4, enhancing T-cell activation against tumor cells.

Question 21

What are the adverse effects of CTLA-4 inhibitors?

Answer 21

Severe immune-related toxicities (colitis, hepatitis, endocrinopathies, skin reactions).

Question 22

What is the role of targeted therapy in melanoma?

Answer 22

BRAF V600E mutation-positive melanomas benefit from BRAF inhibitors (Vemurafenib, Dabrafenib) and MEK inhibitors (Trametinib, Cobimetinib).

Question 23

What are melanocytic nevi?

Answer 23

Melanocytic nevi are benign proliferations of melanocytes, commonly associated with UV light exposure and fair skin.

Question 24

What are the types of melanocytic nevi?

Answer 24

1. Junctional Nevus: Dark, macular lesion from the basal epidermis, common in children.
2. Compound Nevus: Darkly pigmented papule from the basal epidermis/upper dermis interface.
3. Intradermal Nevus: Skin-colored to tan papules from the dermis, common in adults.
4. Atypical (Dysplastic) Nevus: Still benign but has some high-risk features associated with melanoma risk.

Question 25

What is the most common location for junctional nevi?

Answer 25

Junctional nevi are most commonly found on the **palms, soles, and genital areas** due to melanocyte proliferation at the **epidermal-dermal junction**.

Question 26

What are the clinical features of melanocytic nevi?

Answer 26

Nevi generally appear as **<6 mm, round/oval, with a regular border, even hyperpigmentation, and a homogenous surface**.

Question 27

What are the key features of Atypical (Dysplastic) Nevus that should be taken into consideration?

Answer 27

Can progress to melanoma.

Question 28

What are the distinguishing features of dysplastic nevi?

Answer 28

Dysplastic nevi have **asymmetry, irregular borders, color variegation, and a larger diameter (>6 mm)**, resembling melanoma but remaining benign.

Question 29

What is the significance of multiple dysplastic nevi?

Answer 29

Patients with multiple dysplastic nevi are at increased risk for **familial atypical mole-melanoma syndrome**, which predisposes to melanoma.

Question 30

How are melanocytic nevi diagnosed?

Answer 30

Diagnosis is **clinical**, but biopsy may be performed if there is any uncertainty or atypical features.

Question 31

What is the management of melanocytic nevi?

Answer 31

**Observation** for benign nevi. **Excisional biopsy** is recommended for lesions with concerning features or changes over time.

Question 32

What are the risk factors for melanocytic nevi development?

Answer 32

**UV light exposure**, **fair skin**, and **genetic predisposition** are key risk factors for developing nevi.

Question 33

What is the difference between congenital and acquired nevi?

Answer 33

**Congenital nevi** are present at birth and have a small risk of melanoma transformation, while **acquired nevi** develop later and are typically benign.

Question 34

What is the halo nevus phenomenon?

Answer 34

A **halo nevus** is a melanocytic nevus surrounded by a **depigmented ring**, due to an autoimmune response against melanocytes.

Question 35

When should a nevus be biopsied?

Answer 35

A nevus should be biopsied if it demonstrates **rapid growth, ulceration, color changes, asymmetry, or irregular borders**, which raises concern for melanoma.

Question 36

What is the management of congenital giant nevi?

Answer 36

Congenital **giant nevi (>20 cm)** carry an increased risk of melanoma and may require **surgical excision or close monitoring**.