116: Melanoma Flashcards
1
Q
What is the most common type of melanoma and where does it typically occur?
A
The most common type of melanoma is cutaneous melanoma, which typically occurs on the skin, particularly in intermittently sun-exposed areas such as the lower extremities of women and the upper back of men.
2
Q
What are the key characteristics of Nodular Melanoma (NM)?
A
Key characteristics of Nodular Melanoma (NM) include:
- Second most common subtype (15% to 30% of all melanomas)
- Most commonly found on the trunk
- Remarkable for rapid evolution, often arising over several weeks to months
- Lacks an apparent radial growth phase
- Uniformly dark blue-black or bluish-red raised lesion, with 5% being amelanotic
- Early lesions often lack asymmetry, have regular borders, and are a uniform color
- High mutation rate in the BRAF gene (up to 56% of melanomas)
3
Q
What is the median age for a melanoma diagnosis and how does incidence vary with age?
A
The median age for a melanoma diagnosis is 63 years, with 15% of cases occurring in individuals younger than 45 years. The incidence of melanoma rises with age, peaking between 55 and 74 years.
4
Q
What are the historical perspectives on the evidence of melanoma?
A
Historical perspectives on melanoma include:
- Earliest physical evidence found in Pre-Colombian mummies from Chancay and Chingas in Peru (2400 years old).
- The first documented operation for melanoma was performed by Scottish surgeon John Hunter in 1787.
5
Q
What is the significance of the ABCD criteria in melanoma diagnosis?
A
The ABCD criteria are used to assess the clinical appearance of melanoma, focusing on:
- Asymmetry: One half of the mole does not match the other.
- Border: Irregular, scalloped, or poorly defined edges.
- Color: The color is not uniform and may include shades of brown, black, blue, gray, red, or white.
- Diameter: The mole is larger than 6mm (about the size of a pencil eraser).
These criteria help in identifying potential melanomas, particularly Superficial Spreading Melanoma (SSM), which is the most common type.
6
Q
A patient with a pigmented lesion on the trunk is diagnosed with nodular melanoma. What is a key clinical feature of this melanoma subtype?
A
A key clinical feature of nodular melanoma is its rapid evolution, often arising over several weeks to months, and it commonly begins de novo.
7
Q
What is the typical demographic for LMM (Lentigo Maligna Melanoma) and its common characteristics?
A
- Typically occurs in the seventh to eighth decades of life.
- Commonly found on chronically sun-exposed areas such as the face, cheeks, and nose.
- Initially presents as a flat, slowly enlarging brown macule with irregular shapes and shades of brown and tan.
- Associated with higher rates of extensive subclinical lateral growth and higher recurrence rates.
- Least common association with nevi, at 3% of cases.
- Higher rate of association with desmoplastic melanoma and c-KIT aberrations (28% vs. 6% for BRAF).
8
Q
What are the key characteristics and mutations associated with Acral Lentiginous Melanoma (ALM)?
A
- Accounts for 2-8% of melanomas in whites and is the most common form in darker-pigmented individuals.
- Median age of onset is 65 years.
- Most common site is the sole of the palm or subungual areas.
- Typically presents as brown to black lesions with irregular borders, often misdiagnosed as plantar warts or hematomas.
- Not associated with sun exposure.
- Most frequent targetable mutation is the BRAF mutation (21%), followed by c-KIT mutation (13%).
9
Q
What are the clinical features and mutation patterns of Mucosal Melanoma?
A
- Represents 1.3% of melanomas occurring on mucosal surfaces (head, neck, genital, anorectal).
- Often presents with delayed detection and deeply pigmented irregular lesions, sometimes with signs of bleeding.
- Initially has a radial growth phase with macular pigmentation.
- More frequent in women, especially vulvar and vaginal melanomas (50% of mucosal melanomas).
- Common mutations include NF1 and RAS alterations, with higher BRAF mutations (26%) in vulvovaginal origins.
10
Q
What distinguishes Desmoplastic Melanoma (DM) from other melanoma types?
A
- Typically occurs in the 6th or 7th decade of life.
- Characterized by a firm, sclerotic, or indurated quality, with about half being amelanotic.
- Often arises in association with the Lentigo Maligna (LM) histologic subtype.
- Associated with higher local recurrence but lower nodal metastatic rates.
- High mutation burden likely induced by UV radiation; BRAF or NRAS mutations are not found.
11
Q
What are the histological features of Nevoid Melanoma?
A
- Represents a heterogeneous group of rare lesions.
- Resembles benign nevi by their symmetry and apparent maturation with descent in the dermis.
- Histologically characterized by marked hyperchromasia of the nuclei, presence of mitoses, and expansive growth of dermal cells.
- Clinically corresponds to a tan papule or nodule, often >1 cm in diameter, typically in young adults.
12
Q
What are the characteristics of Spitzoid Melanoma?
A
- Clinically and histologically resembles a Spitz nevus.
- Typically larger with asymmetry and irregular coloration.
13
Q
A 65-year-old patient presents with a pigmented lesion on the sole of their foot. The lesion is brown to black with irregular borders. What is the most likely diagnosis, and what mutation is most frequently associated with this condition?
A
The most likely diagnosis is Acral Lentiginous Melanoma (ALM). The most frequent mutation associated with this condition is the BRAF mutation, followed by c-KIT mutations.
14
Q
A 70-year-old patient presents with a slowly enlarging, freckle-like macule on their cheek with irregular borders. What subtype of melanoma is most likely, and what sun exposure pattern is associated with it?
A
The most likely subtype is Lentigo Maligna Melanoma (LMM), which is associated with cumulative sun exposure.
15
Q
A patient presents with a pigmented lesion on the nail with pigmentation extending to the proximal nail fold. What is this clinical sign called, and what subtype of melanoma does it suggest?
A
This clinical sign is called Hutchinson’s sign, and it suggests subungual melanoma, a variant of Acral Lentiginous Melanoma (ALM).
16
Q
What are the key features that favor the diagnosis of a Spitzoid melanoma over a benign Spitz nevus?
A
- Large size (greater than 1 cm in greatest dimension)
- Thick invasive component (>2 mm Breslow thickness)
- Numerous mitoses, especially atypical forms
- Cytologically atypical cells
- Very rapid growth in size or satellitosis
17
Q
What are the two most important risk factors for melanoma?
A
- Sun exposure
- Genetics
18
Q
How does intermittent sun exposure during childhood and adolescence affect melanoma risk?
A
- Intermittent exposure hypothesis suggests that periodic, intense sun exposure is more important in melanoma causation than long, continued exposure.
- Sunburn history (blistering and peeling burns) serves as a surrogate measure of intermittent sun exposure.
- 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.
19
Q
What are some non-cutaneous findings associated with melanoma?
A
- Choroidea
- Mucosa of the ear, nose, and throat (ENT) region, intestine, or urinary tract
- Unknown primary may develop from nodal nevi (precursor: nevus cells that escaped from melanocytic nevi of the skin)
20
Q
What is the significance of melanoma-associated vitiligo in patients?
A
- Melanoma-associated vitiligo is an autoimmune disease against melanocytes, occurring in up to 4% of patients.
- It is associated with a better prognosis and is frequent in patients treated with immune checkpoint blockers, correlating with a better treatment response.
21
Q
A patient with a history of melanoma-associated vitiligo is undergoing treatment. Is this condition associated with a better or worse prognosis?
A
Melanoma-associated vitiligo is associated with a better prognosis and is frequent in patients treated with immune checkpoint blockers.
22
Q
A patient with a pigmented lesion has a history of melanoma-associated retinopathy. What are the common symptoms of this condition?
A
Common symptoms of melanoma-associated retinopathy include vision problems and the presence of antiretinal antibodies.
23
Q
What factors are associated with an increased risk of melanoma due to UV radiation exposure?
A
Factors include:
- Longer duration of bed use
- Younger age at first exposure
- Higher frequency of use
- Indoor tanning leading to accelerated skin aging and ocular melanoma
- UVB directly damages DNA
- UVA contributes to the production of ROS (reactive oxygen species)
24
Q
What is the lifetime risk of developing melanoma for individuals with large congenital nevi?
A
The lifetime risk of developing melanoma for individuals with large congenital nevi is between 2% to 10%. Additionally, those with large congenital nevi located on the posterior axis or in conjunction with multiple satellite lesions have an increased risk of developing neurocutaneous melanosis and melanoma in the CNS.
25
How does family history influence the risk of melanoma?
Family history influences melanoma risk as follows:
- **Familial melanoma** accounts for approximately **5-12%** of all patients.
- Having **one first-degree relative** with melanoma **doubles** the risk.
- Having **three or more first-degree relatives** increases the risk **35 to 70-fold**.
- Shared risk factors include skin phenotype, multiple nevi, and excessive sun exposure.
26
What are the implications of CDKN2A mutations in melanoma risk?
CDKN2A mutations have significant implications for melanoma risk:
- Germline mutations account for approximately **40%** of hereditary melanoma cases.
- The melanoma risk for CDKN2A mutation carriers is:
- **76%** in the United States
- **91%** in Australia
- **58%** in the UK (lower levels of UV exposure)
- There is also a **higher risk of pancreatic cancer (15%)** associated with these mutations.
27
What is the significance of early detection in melanoma diagnosis?
Early detection is crucial in melanoma diagnosis because:
- The risk of metastases increases with the **infiltration depth** of the primary melanoma.
- The two most common early characteristics noticed by patients are:
1. **Change in color** of the lesion
2. **Increase in size** or appearance of a new lesion.
28
A patient with Fitzpatrick skin phototype I-II and a history of blistering sunburns in childhood presents with a changing pigmented lesion. What are the two most important risk factors for melanoma in this case?
The two most important risk factors are UV exposure and genetics.
29
A patient with a pigmented lesion has a family history of melanoma in three first-degree relatives. How does this affect their risk of developing melanoma?
Having three or more first-degree relatives with melanoma increases the risk 35- to 70-fold.
30
A patient with a pigmented lesion has Fitzpatrick skin phototype V. How does this skin type affect their risk of developing melanoma?
Fitzpatrick skin phototype V is less frequently associated with melanoma compared to phototypes I-II, which have a 2-3 fold increased risk.
31
A patient with a pigmented lesion has a history of using tanning beds frequently. How does this behavior affect their melanoma risk?
Frequent use of tanning beds is associated with a significantly elevated risk of melanoma due to intermittent UV radiation exposure.
32
A patient with a pigmented lesion has a history of large congenital nevi. What is their lifetime risk of developing melanoma?
The lifetime risk of developing melanoma in patients with large congenital nevi is 2-10%.
33
A patient with a pigmented lesion has a history of intermittent sun exposure during childhood. How does this exposure pattern affect their melanoma risk?
Intermittent sun exposure during childhood is a major risk factor for melanoma and more important than long, continued, heavy sun exposure.
34
A patient with a pigmented lesion has a history of familial atypical multiple mole-melanoma syndrome. What genetic mutations are commonly associated with this condition?
Inherited mutations in CDKN2A, CDK4, POT1, and TERT are commonly associated with familial atypical multiple mole-melanoma syndrome.
35
A patient with a pigmented lesion has a history of melanoma and presents with a new lesion. What is the most common early characteristic noticed by patients?
The most common early characteristics noticed by patients are a change in color and an increase in size of the lesion.
36
What does the ABCDE rule stand for in the evaluation of pigmented lesions?
A stands for **asymmetry** (one half is not identical to the other half), B for **border** (irregular, notched, scalloped, ragged, or poorly defined borders), C for **color** (varying shades from one area to another), D for **diameter** (greater than 5 mm), and E for **evolution** (changes in the lesion over time).
37
What is the significance of the Ugly Duckling sign in dermatology?
The **Ugly Duckling sign** refers to a pigmented lesion that is different from other pigmented lesions on a particular individual, indicating it should be approached with a high index of suspicion for melanoma.
38
What are the major architectural features of melanoma?
The major architectural features of melanoma include:
1. **Asymmetry**
2. **Poor circumscription** (cells at the edge tend to be small, single, and scattered rather than nested)
3. **Large size** (>5 to 6 mm).
39
What is the role of digital dermoscopy in melanoma diagnosis?
**Digital dermoscopy** or digital epiluminescent microscopy allows for computerized retrieval and examination of digital dermoscopic images, improving the early diagnosis of melanoma.
40
What is the importance of excisional biopsy in melanoma management?
**Excisional biopsy** should be performed after incisional biopsy of melanoma with ≥50% of the lesion remaining to ensure accurate assessment and staging. A wider margin should be taken after complete excision for histologic evaluation of the whole lesion.
41
What immunohistochemical markers are significant in melanoma diagnosis?
Key immunohistochemical markers in melanoma include:
- **S100** and **Sox10** (expressed in almost all melanomas)
- **HMB-45** (high specificity for melanoma cells)
- **MART-1**
- **Melan-A** (more sensitive than HMB-45 and more specific than S100).
42
What laboratory tests are relevant in monitoring melanoma progression?
Relevant laboratory tests for monitoring melanoma progression include:
- Increased levels of **LDH** detected in serum.
43
What are key immunohistochemical markers in melanoma?
Key immunohistochemical markers in melanoma include: S100 and Sox10 (expressed in almost all melanomas), HMB-45 (high specificity for melanoma cells), MART-1, and Melan-A (more sensitive than HMB-45 and more specific than S100).
44
What laboratory tests are relevant in monitoring melanoma progression?
Relevant laboratory tests for monitoring melanoma progression include: Increased levels of LDH detected in serum, S100B in serum (more specific than LDH but lacks sensitivity), and blood investigations mainly used to monitor clinical course, especially in patients with distant metastatic disease.
45
What diagnostic acronym should be used to evaluate a pigmented lesion?
The ABCDE acronym should be used: A - Asymmetry, B - Border irregularity, C - Color variation, D - Diameter >5 mm, E - Evolution over time.
46
What architectural feature of melanoma is described by nests of melanocytes in the lower epidermis and dermis that vary in size and shape?
This describes poor circumscription, where cells at the edge of the lesion tend to be small, single, and scattered rather than nested.
47
What is the most sensitive noninvasive method to detect nodal metastases in melanoma?
Skin and lymph node ultrasonography is the most sensitive noninvasive method to detect nodal metastases.
48
What is the significance of Sentinel Lymph Node Biopsy (SLNB) in melanoma?
SLNB is a powerful staging and prognostic tool that detects occult micrometastases in regional lymph nodes and is the best baseline staging test for detecting occult nodal metastasis.
49
What are the initial presentation statistics for melanoma?
- 85%: localized disease
- 10%: regional metastases
- 5%: distant metastases
50
What is the 5- to 10-year survival rate for patients with localized thin primary melanoma less than 1 mm in Breslow depth?
The 5- to 10-year survival rate for patients with localized thin primary melanoma <1 mm in Breslow depth is more than 90%.
51
What is the recommended imaging for high-risk melanoma patients?
CT, MRI, or PET scans are indicated only in high-risk and known metastatic melanoma patients.
52
What is the significance of a positive SLNB result?
A positive SLNB result is a powerful predictor of survival and indicates the presence of occult micrometastases in regional lymph nodes.
53
What is the significance of Breslow thickness in melanoma prognosis?
Breslow thickness is the single most important prognostic factor for survival and clinical management in localized stage I and II cutaneous melanoma. Survival decreases with increasing Breslow thickness.
54
How does ulceration correlate with melanoma prognosis?
Ulceration correlates with tumor thickness and is an independent prognostic factor for localized melanoma. The presence of ulceration in the primary melanoma confers a higher risk of developing advanced disease and is associated with a worse prognosis.
55
What is the role of mitotic rate in melanoma prognosis?
In clinically localized melanoma, a mitotic rate of 1/mm² or greater is described as the second most powerful predictor of survival, after tumor thickness.
56
What are the clinical implications of angiolymphatic invasion in melanoma?
Angiolymphatic invasion involves the invasion of tumor cells into the microvasculature and significantly increases the risk of relapse, lymph node involvement, distant metastases, and death.
57
What is the significance of tumor-infiltrating lymphocytes (TILs) in melanoma?
Tumor-infiltrating lymphocytes (TILs) represent the host antitumor immune response. TILs in the vertical growth phase are less frequent, indicating different biological behaviors of the tumor.
58
What is the most powerful prognostic factor for survival in melanoma?
The status of the regional lymph nodes is the most powerful prognostic factor for survival in melanoma.
59
What does ulceration of the primary lesion indicate in regional stage III melanoma?
Ulceration of the primary lesion indicates a worse prognosis in regional stage III melanoma.
60
What is the prognosis associated with elevated serum LDH levels in metastatic melanoma?
Elevated serum LDH levels are associated with a worse prognosis, regardless of the site of metastatic disease.
61
What is the prognosis for patients with satellite metastases in melanoma?
Satellite metastases, both clinical and microscopic, portend the worst prognosis for regional metastases, with a 5-year survival rate of less than 50%.
62
What are the two most important risk factors for melanoma?
The two most important risk factors for melanoma are UV exposure and genetics.
63
What type of sun exposure is most important for melanoma causation?
Intermittent sun exposure is the most important type of sun exposure for melanoma causation.
64
What represents the best baseline staging test for detection of occult nodal metastasis?
Sentinel lymph node biopsy (SLNB) is the best baseline staging test for detection of occult nodal metastasis.
65
How is Breslow thickness measured?
Breslow thickness is measured from the top of the granular layer of the epidermis to the greatest depth of tumor invasion, in millimeters.
66
Which immunostain is more sensitive than HMB-45 and more specific than S100?
Melan A is more sensitive than HMB-45 and more specific than S100.
67
What is the ABCDE checklist used for in melanoma assessment?
The ABCDE checklist is used to evaluate moles and skin lesions for signs of melanoma: A - Asymmetry, B - Border, C - Color, D - Diameter, E - Evolution.
68
What are some dermoscopic features of melanoma?
- Atypical pigment network
- Negative network
- Atypical dots or globules
- Irregular streaks
- Regression structures
- Blue-white veil
- Shiny white lines
- Atypical blotch
- Polymorphous vessels
69
What are the differential diagnoses for melanoma?
| Condition | Description |
|-----------|-------------|
| Atypical nevi | ABCD criteria help to differentiate |
| Seborrheic keratosis | No pigment seen in dermoscopy |
| Basal cell carcinoma | Especially if pigmented: more black than brown, prominent vascularity |
| Hemangioma | Can be difficult to distinguish from amelanotic melanoma |
| Pyogenic granuloma | Especially difficult to distinguish from amelanotic melanoma |
| Solar lentigo | Pigmented actinic keratosis, flat seborrheic keratosis: can mimic lentigo maligna melanoma |
| Plantar wart | Might be hard to distinguish from acral melanoma.
70
What do the ABCD criteria help to differentiate?
Nevi
## Footnote
ABCD criteria are used to evaluate moles for signs of melanoma.
71
What is seen in dermoscopy for seborrheic keratosis?
No pigment seen in dermoscopy.
72
What are the characteristics of pigmented basal cell carcinoma?
More black than brown, prominent vascularity.
73
What can hemangioma be difficult to distinguish from?
Amelanotic melanoma.
74
What is especially difficult to distinguish from amelanotic melanoma?
Pyogenic granuloma.
75
What can mimic lentigo maligna melanoma?
Pigmented actinic keratosis, flat seborrheic keratosis.
76
What might be hard to distinguish from acral melanoma?
Plantar wart.
77
What is especially difficult to distinguish from acral or subungual hematoma?
Hematoma.
78
What should you look for in longitudinal melanonychia?
Hutchinson sign.
79
What are the clinical and pathological staging groupings for cutaneous melanoma?
Clinical Stage 0: Tis N0 M0; IA: T1a N0 M0; IB: T1b N0 M0; IIA: T2a N0 M0; IIB: T2b N0 M0; IIC: T2c N0 M0; IIIA: T1-2 N1a M0; IIIB: T1-2 N1b M0; IIIC: T3-4 N1c M0; IV: Any T Any N M1.
80
What role does the CDKN2A gene play in melanoma development?
The CDKN2A gene is a tumor suppressor gene that accounts for approximately 40% of hereditary melanoma cases. Its mutations lead to loss of cell cycle control and impaired apoptosis.
81
What is the standard therapy for primary cutaneous melanoma?
The standard therapy for primary cutaneous melanoma is wide local excision (WLE).
82
How is the risk of satellite metastasis related to primary melanoma?
The risk of satellite metastasis is directly related to the thickness of the primary melanoma.
83
What is the role of elective lymph node dissection (ELND) in the treatment of microscopic nodal disease?
There is no role for ELND today, especially with the development and availability of sentinel lymph node dissection (SLND).
84
What is the significance of the SLND procedure?
The SLND procedure is a powerful staging tool that identifies micro-metastatic nodal disease.
85
What percentage of patients may have evidence of non-SLN metastases after a positive SLND?
After a positive SLND, up to 15% to 20% of patients have evidence of non-SLN metastases found during complete lymph node dissection (CLND).
86
What is the current standard of therapy for macroscopic nodal disease in melanoma?
The current standard of therapy for macroscopic (stage IIIB or IIIC) melanoma is complete lymph node dissection (CLND) of the involved regional basin.
87
What is the purpose of adjuvant treatment in melanoma management?
Adjuvant treatment is for patients with surgically resected disease who are at high risk for relapse, such as those with thick primary melanomas or nodal disease.
88
What role do interferon-α cytokines play in the immune response?
Interferon-α cytokines are released by cells in response to pathogens and lead to protection of neighboring cells from virus infection and have antineoplastic activity.
89
What surgical considerations should be taken into account for melanoma excision at special sites?
Melanoma excision at special sites such as the soles requires separate surgical and functional considerations due to the unique anatomy and potential impact on mobility. Wide local excision (WLE) is the standard therapy.
90
What is the standard therapy for a patient with stage IIIB melanoma and macroscopic nodal disease?
The standard therapy for macroscopic nodal disease in stage IIIB melanoma is complete lymph node dissection (CLND) of the involved regional basin.
91
What is the role of sentinel lymph node dissection (SLND) in melanoma?
SLND is a staging tool that identifies micro-metastatic nodal disease, helping to guide further treatment.
92
What are the two different dosage regimens for the treatment mentioned, and what are their phases?
High-dose regimen: Induction phase: 20 MU/m² BSA IV 5 days a week for 4 weeks. Maintenance phase: 10 MU/m² BSA SQ 3x a week for 48 weeks. Low-dose regimen: 3 MU/m² BSA SQ 3x a week for 1.5 years.
93
What are the main side effects associated with the treatment mentioned?
The main side effects associated with the treatment include: Flulike symptoms, Depression, Hepatotoxicity, Myelosuppression, Vitiligo.
94
What is the mechanism of action of CTLA-4 (CD152) in immune checkpoint blockers?
CTLA-4 (CD152) is an immune checkpoint molecule that is expressed on the surface of activated T cells. It leads to their deactivation by binding to CD80 or CD86 on the surface of antigen-presenting cells, thereby downregulating an immune response after activation and preventing autoimmunity.
95
What are the three main risk factors for relapse after radiotherapy following CLND in stage III melanoma patients?
The three main risk factors for relapse are: 1. ≥ 3 lymph node metastases 2. Lymph nodes with extracapsular spread 3. Lymph nodes >3 cm in diameter.
96
What are the therapeutic options for managing larger in-transit or satellite metastases?
For larger metastases, the therapeutic options include: Intralesional injections with the oncolytic virus talimogene laherparepvec (T-VEC), Electrochemotherapy (ECT).
97
What is the reported effectiveness of intralesional interleukin-2 for small and superficial metastases?
Intralesional interleukin-2 is reported to be a very effective approach, especially for small and superficial metastases, with a response rate of more than 50%.
98
What are the two dosage regimens for Interferon-α in adjuvant treatment?
1. High-dose: Induction phase (20 MU/m² BSA IV 5 days a week for 4 weeks) and Maintenance phase (10 MU/m² BSA SQ 3x a week for 48 weeks). 2. Low-dose: 3 MU/m² BSA SQ 3x a week for 1.5 years.
99
What are the three main risk factors for relapse in stage III melanoma patients that may warrant adjuvant radiotherapy?
1. ≥ 3 lymph node metastases. 2. Lymph nodes with extracapsular spread. 3. Lymph nodes >3 cm in diameter.
100
What are two alternative therapeutic options for a patient with in-transit metastases who is not a candidate for surgery?
1. Intralesional injections with the oncolytic virus talimogene laherparepvec (T-VEC). 2. Electrochemotherapy (ECT).
101
What are the main toxicities associated with high-dose interferon-α treatment?
Toxicities include flu-like symptoms, depression, hepatotoxicity, myelosuppression, and vitiligo.
102
What is Talimogene Laherparepvec (T-VEC) and what are its main side effects?
Talimogene Laherparepvec (T-VEC) is a transgenic herpes virus 1 (type 1) that selectively replicates in tumors and produces granulocyte macrophage colony-stimulating factor (GM-CSF) to enhance local and distant immune responses. The main side effects include fatigue and fever.
103
What is Electrochemotherapy (ECT) and what are its requirements?
Electrochemotherapy (ECT) is an effective treatment option for patients with in-transit metastases, combining local or systemic chemotherapy (usually bleomycin or cisplatin) with intralesionally applied electrical pulses. It requires general or local anesthesia with sedation and is typically performed in an operating room.
104
What is the purpose of Isolated Limb Perfusion (ILP) and what are its exclusion criteria?
Isolated Limb Perfusion (ILP) is used for loco-regional disease control limited to an extremity, involving the perfusion of an isolated extremity under hyperthermic conditions with cytotoxic agents like Melphalan. Exclusion criteria generally include elderly age and serious medical comorbidities.
105
What are the treatment options for unresectable metastatic disease and their impact on patient survival?
Treatment options for unresectable metastatic disease can substantially improve patient survival from a median of 6 to 9 months to 2 years, with a chance to achieve long-term tumor control.
106
What is the role of surgery and radiotherapy in the treatment of isolated visceral metastases?
Surgical excision of isolated visceral metastases can be considered and may be performed, often serving a palliative purpose.
107
What is the mechanism of action of talimogene laherparepvec (T-VEC)?
T-VEC is a transgenic herpes virus type 1 that selectively replicates in the tumor and produces granulocyte macrophage colony-stimulating factor (GM-CSF) to augment local and potentially distant immune responses.
108
What are the main side effects of electrochemotherapy (ECT)?
ECT is generally well-tolerated but requires general or local anesthesia with sedation. It may cause local pain and swelling.
109
What is the primary goal of isolated limb perfusion (ILP) in melanoma treatment?
The primary goal of ILP is loco-regional disease control limited to an extremity, not overall survival.
110
What are the exclusion criteria for isolated limb perfusion (ILP)?
Elderly age and serious medical comorbidities are generally considered exclusion criteria for ILP.
111
What are the benefits of surgical excision of skin/subcutis or distant lymph node metastases in melanoma treatment?
Surgical excision may result in improved loco-regional control and decreased morbidity.
112
What is the role of radiotherapy in the treatment of brain metastases in melanoma?
Radiotherapy is preferably used to treat brain metastases, especially using stereotactic radiation for limited brain disease.
113
What are the two stimulating signals required for T-cell activation in immunotherapy?
1. T-cell receptor (TCR) recognition of antigens associated with MHC antigen-presenting molecules. 2. Binding of a costimulatory molecule like CD28, CD27, GITR, OX40, or ICOS.
114
What is the significance of Ipilimumab in melanoma treatment?
Ipilimumab is a monoclonal blocking antibody against CTLA-4 that stops inhibition of T-cell response and was the first drug to show significant benefit for overall survival (OS) in patients with stage IV melanoma.
115
How do Nivolumab and Pembrolizumab function in melanoma treatment?
Nivolumab and Pembrolizumab are PD-1 blocking antibodies that play a critical role in tumor escape by downregulating tumor-associated T cells through the PD-1/PD-L1 pathway.
116
What is the process involved in Adoptive T-Cell Therapy for melanoma?
Autologous in vitro expanded tumor-infiltrating lymphocytes (TILs) from melanoma metastases are expanded under GMP conditions and reinfused into the patient after lymphablative chemotherapy followed by high-dose interleukin-2 treatment.
117
What was the significance of high-dose interleukin-2 in melanoma treatment?
High-dose bolus IL-2 was the only FDA-approved immunologic treatment for metastatic melanoma recognized to produce rare but durable complete responses.
118
What is the most common mutation found in melanomas of sun-exposed skin?
The BRAF V600 mutation is the most common in melanomas of sun-exposed skin and can be detected in about 50% of melanomas.
119
What was Sorafenib's role in melanoma treatment?
Sorafenib was the first BRAF inhibitor used, which is an unspecific RAF inhibitor that inhibits B-raf and C-raf, demonstrating little activity with unresectable stage III or stage IV melanoma.
120
What is the role of adoptive T-cell therapy in melanoma treatment?
Adoptive T-cell therapy involves autologous in vitro expanded tumor-infiltrating lymphocytes (TILs) reinfused into the patient after lymphodepleting chemotherapy and high-dose interleukin-2 treatment.
121
What are the two signals required for T-cell activation in immunotherapy?
1. T-cell receptor (TCR) recognition of antigens associated with MHC molecules. 2. Binding of a costimulatory molecule like CD28, CD27, GITR, OX40, or ICOS.
122
What is the mechanism of action of ipilimumab in melanoma treatment?
Ipilimumab is a monoclonal antibody that blocks CTLA-4, stopping the inhibition of T-cell response and enhancing immune activity against melanoma.
123
What is the mechanism of action of nivolumab and pembrolizumab in melanoma treatment?
Nivolumab and pembrolizumab are PD-1 blocking antibodies that prevent the PD-1/PD-L1 pathway from downregulating tumor-associated T cells, enhancing immune response.
124
What are the indications for palliative radiation in melanoma?
Palliative radiation is indicated for spinal cord compression and painful bone metastases.
125
What is the role of stereotactic radiation in melanoma treatment?
Stereotactic radiation is used to treat limited brain metastases in melanoma patients.
126
What is the survival benefit of high-dose interleukin-2 (IL-2) in metastatic melanoma?
High-dose IL-2 was the only FDA-approved immunologic treatment for metastatic melanoma that produced rare but durable complete responses.
127
What is the benefit of surgical excision of isolated visceral metastases in melanoma?
Surgical excision of isolated visceral metastases can improve loco-regional control, decrease morbidity, and may be palliative.
128
What are the benefits and limitations of using BRAF inhibitors like Vemurafenib and Dabrafenib in melanoma treatment?
Benefits: Prolongs survival with a median PFS of 7 to 8 months and median OS of 16 to 18 months. Faster response, particularly beneficial for patients with high tumor load. Limitations: Most patients develop later resistance to the treatment.
129
What is the standard of care for patients with BRAF mutant melanoma?
The standard of care for patients with BRAF mutant melanoma is a combination treatment with a BRAF inhibitor and a MEK inhibitor, in addition to immunotherapeutic options.
130
What are the common side effects associated with BRAF inhibitor treatment?
Common side effects of BRAF inhibitor treatment include: Fatigue, Nausea, Diarrhea, Arthralgia, Skin side effects such as exanthemas, hyperkeratosis, verrucous lesions, and secondary malignancies (e.g., cutaneous squamous cell carcinoma and melanoma).
131
What is the role of Imatinib in the treatment of melanoma?
Imatinib is a tyrosine kinase inhibitor that has demonstrated significant responses in patients with metastatic melanoma harboring activating mutations in c-KIT.
132
What is the only FDA-approved chemotherapy for metastatic melanoma and what are its response rates?
The only FDA-approved chemotherapy for metastatic melanoma is Dacarbazine (DTIC). Response rates are generally in the.
133
What is the only FDA-approved chemotherapy for metastatic melanoma and what are its response rates?
The only FDA-approved chemotherapy for metastatic melanoma is Dacarbazine (DTIC). Response rates are generally in the 10% range, with a median response duration of 4 to 6 months.
134
What are the primary prevention strategies for melanoma?
Primary prevention strategies for melanoma should focus on:
- Safe sun exposure, including limited UV exposure and sunburn prevention.
- Early detection through regular skin examinations, awareness of skin changes, and knowledge of early signs of melanoma.
135
What is the role of temozolomide (TMZ) in melanoma treatment?
Temozolomide (TMZ) is an alkylating agent with the same active metabolite as dacarbazine (DTIC) but is orally administered.
136
What is the benefit of combining BRAF and MEK inhibitors in melanoma treatment?
Combining BRAF and MEK inhibitors leads to higher response rates (up to 70%), a median progression-free survival (PFS) of 10-11 months, and a median overall survival (OS) of about 2 years.
137
What is the most common mutation in melanomas of sun-exposed skin, and how is it targeted?
The BRAF V600 mutation is the most common and is targeted using selective BRAF inhibitors like vemurafenib and dabrafenib.
138
What are the common side effects of BRAF inhibitors?
Common side effects include fatigue, nausea, diarrhea, arthralgia, and skin side effects such as exanthemas, hyperkeratosis, verrucous lesions, and secondary malignancies.
139
What is the mechanism of action of c-KIT inhibitors in melanoma?
C-KIT inhibitors like imatinib target activating mutations or amplification of the tyrosine kinase receptor KIT, which is common in acral and mucosal melanomas.
140
What is the recommended follow-up interval for melanoma patients after treatment, and how does it vary by stage?
The follow-up interval for melanoma patients ranges from every 3 to 6 months for the first 1 to 3 years, and then annually thereafter. This schedule primarily depends on the stage of the disease.
141
What surgical treatment is recommended for Stage I melanoma?
For Stage I melanoma, the recommended surgical treatment is wide local excision, with specific criteria based on tumor size:
1. Tumors ≤ 1 mm (0.1 cm) - Wide local excision
2. Tumors > 1 mm (1 cm) - Wide local excision
3. Tumors > 2 mm (2 cm) - Wide local excision
142
What systemic treatments are considered for Stage IV melanoma?
For Stage IV melanoma, the following systemic treatments are considered:
- Immune checkpoint blockers (e.g., ipilimumab, nivolumab, pembrolizumab)
- PD-1 antibody monotherapy
- Targeted therapy (e.g., BRAF/MEK inhibition, KIT inhibition for KIT mutation)
143
What is the primary focus of primary prevention in melanoma?
Primary prevention focuses on safe sun exposure, including limited UV exposure and sunburn prevention, especially during childhood and adolescence.
144
What is the recommended follow-up interval for melanoma patients?
Follow-up intervals range from every 3 to 6 months for 1 to 3 years and annually thereafter, depending on the stage of the disease.
