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129 Cards in this Set
- Front
- Back
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Order the following risk factors for melanoma in order of decreasing relative risk: - Immunosuppression - Regular use of tanning bed before age 30 - Atypical nevus syndrome with personal and family history of melanoma - Large congenital nevus - Changing mole |
- Atypical nevus syndrome with personal and family history of melanoma (RR 500) - Changing mole (RR >400) - Large congenital nevus (RR 17) - Regular use of tanning bed before age 30 (RR 8) - Immunosuppression (RR 4-8) |
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The most important risk factor for the development of melanoma in patients with melanocytic nevi is... |
...the number of melanocytic lesions on the body |
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Atypical mole syndrome is define as... |
...>100 melanocytic nevi, one or more melanocytic nevi > 8mm, AND more than one melanocytic nevi with clinical atypia |
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Solar lentigenes are also known as... |
...freckles |
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What are the four common melanoma growth patterns? |
- Superficial spreading melanoma - Nodular melanoma - Lentigo maligna melanoma - Acral lentiginous melanoma |
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What are characteristics of superficial spreading melanoma? |
- Most common - 70% of melanoma cases - More common is young adults - Posterior trunk is most common site - Irregular borders with color variegation |
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What are characteristics of nodular melanoma? |
- Rapid growth - Aggressive, shorter onset - ~10% of cases - More common in middle aged men - Trunk or head/neck - uniformly blue/black or pink/red dome-shaped nodule |
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What are characteristics of lentigo maligna melanoma? |
- Older adults - 15% of cases - Arises from pre-existing lentigo maligna - May take years to develop - Sun-exposed areas - May reach large sizes >3 cm |
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What are characteristics of acral lentiginous melanoma? |
- Palmar, plantar, and subungual skin |
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What are the key aspects of H&P for melanoma? |
- New or changing nevus - Prior personal history - Family history - ROS to evaluate for metastatic disease - Total skin exam - Lymph node exam |
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What percent of patients with melanoma will have a synchronous primary? |
2% |
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What are the signs of a mole suspicious for melanoma? |
Asymmetry
Border - irregular Color - more than one Diameter > 6mm Elevation OR Enlargement |
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What kind of biopsy is preferred to rule out melanoma? With what margins? |
Narrow excisional biopsy (2-3mm margin) via punch. Wide margins may compromise subsequent SLN biopsy. On extremity, if using scalpel incision should be parallel to lymphatics (longitudinal). |
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What is the single most valuable prognotic factor for melanoma? |
The status of the sentinel lymph node |
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What are major clinical predictors of poor prognosis for melanoma? |
Older age
Male gender Location in head, neck or trunk |
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What are major histopathological predictors of poor prognosis for melanoma? |
Tumor thickness in mm (Breslow) Depth related to skin structures (Clark) Type of melanoma (i.e. nodular) Ulceration Lymphatic or perineural invasion Presence of tumor infiltrating lymphocytes (TILs) Satellite lesions Positive lymph nodes Distant metastases |
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Define T1a melanoma |
Less than 1mm without ulceration |
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Define T1b melanoma |
Less than 1mm with ulceration |
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Define T2a melanoma |
1.01-2mm without ulceration |
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Define T2b melanoma |
1.01-2mm with ulceration |
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Define T3a melanoma |
2.01-4mm without ulceration |
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Define T3b melanoma |
2.01-4mm with ulceration |
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Define T4a melanoma |
4.01mm or greater without ulceration |
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Define T4b melanoma |
4.01mm or greater with ulceration |
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Define N1 melanoma |
1 positive lymph node |
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Define N2 melanoma |
2-3 positive lymph nodes OR regional satellites or in-transit metastases |
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Define N3 melanoma |
4 or more positive lymph nodes OR lymph node basin AND regional skin/in-transit metastases |
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Define M1a melanoma |
Distant skin metastasis, normal LDH |
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Define M1b melanoma |
Lung metastases, normal LDH |
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Define M1c melanoma |
Metastasis other than lung OR Any metastases with elevated LDH |
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Define Stage 0 melanoma |
Tis N0 M0 melanoma in situ (intraepidermal) |
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Define Stage IA melanoma |
T1a N0 M0 |
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Define Stage IB melanoma |
T1b or T2a, N0 M0 |
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Define Stage IIA melanoma |
T2b or T3a, N0 M0 |
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Define Stage IIB melanoma |
T3b or T4a, N0 M0 |
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Define Stage IIC melanoma |
T4b N0 M0 |
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Define Stage IIIA melanoma |
T1a-T4a, N1a or N2a, M0 |
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Define Stage IIIB melanoma |
T1b-T4b, N1a or N2a, M0 T1a -T4a, N1b or N2b, M0 T1a-T4a, N2c, M0 |
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Define Stage IIIC melanoma |
T1b-T4b, N1b or N2b, M0 T1b-T4b, N2c, M0 Any T, N3, M0 |
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Define Stage IV melanoma |
Any T, Any N, M1 |
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What are the recommended margins for the following thickness levels: In situ <1mm 1-2mm >2-4mm >4mm |
In situ: 0.5-1cm <1mm: 1cm 1-2mm: 2cm (can accept up to 1cm margin but may have higher local recurrence rate) >2-4mm: 2cm >4mm: 2cm |
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What did the WHO Melanoma Group (1998) trial show? |
RCT of patients with melanoma 1-2mm thick who underwent 1cm vs 3cm margins No significant difference in OS, DFS, or LR Nonsignificant increase in local recurrence with 1cm margins |
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What did the Swedish (2000) trial show? |
RCT of patients with melanomas <2mm thick that underwent 2 vs 5cm margins No difference in OS, LR, or DFS |
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What did the Intergroup Melanoma trial (2001) show? |
RCT of patients with melanomas 1-4mm thick that underwent 2 vs 4cm margins No difference in OS, LR, or DFS |
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What did the British Collaborative Trial (2004) show? |
RCT of patients with melanomas >2mm thick that underwent 1cm vs 3cm margin No difference in OS or DFS Greater locoregional recurrence in 1cm margin group **DID NOT include SLN biopsy |
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What did the Swedish/Danish (2011) trial show? |
RCT of patients with melanomas >2mm thick that underwent 2 vs 4cm margins No difference in OS, LR, or DFS |
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Describe technical aspects of Wide local excision for melanoma. |
- Excision margins marked from edge of lesion or biopsy scar - With 2cm margins, a 3:1 ratio of length to width yields long axis of 12cm which is adequate for fusiform excision - Creation of flaps extending 1cm wider in subcutaneous fat allows for less tension - Complete removal of skin and subcutaneous tissue down to but not including fascia is recommended for lesions <4mm thick - For >4mm thick, consider taking fascia - No role for frozen section |
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You do a WLE with 2cm margins for a 1.5mm thick melanoma and the final pathology shows actual margin to be 1.7cm. Do you need to do a re-excision? |
No. Adequate margins are determined clinically. No role for re-excision unless margins are involved. |
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Regarding elective vs. therapeutic lymph node dissection, what did the Intergroup Melanoma Trial (2000) show? |
RCT of patients with melanomas 1-4mm thick randomized to ELND vs nodal observation. No significant difference in 10-y survival BUT patients with non-ulcerated melanomas, melanomas 1-2mm, or extremity lesions had decreased mortality |
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Regarding elective vs. therapeutic lymph node dissection, what did the WHO trial (1998) show? |
RCT of patients with truncal melanomas >1.5mm undergoing ELND vs nodal observation Patients with occult nodal disease seen on ELND had better 5-year survival than patients who developed nodal disease under observation and required TLND. |
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Before Donald Morton described sentinel lymph node biopsy in 1977, how did surgeons decide which nodal basin to electively dissect out? |
Based on Sappey's lines (lymphatic mappings done in 19th century) |
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What is the rate of successful identification of a sentinel lymph node? |
98% |
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What is the false negative rate of the sentinel lymph node for melanoma? |
12.5% |
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What is the estimated risk of nodal recurrence in a patient with a negative sentinel lymph node biopsy? |
< 5% |
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What did the Multicenter Selective Lymphadenectomy Trial (MSLT) I show in 1994? |
- Only RCT to evaluate outcomes of SLN biopsy vs. nodal observation in 1347 patients with 1.2-3.5mm melanoma (intermediate) and 314 patients with >3.5mm melanoma (thick) - No differences in 10-year DSS, but improved 10-year DFS - SLN status was the strongest predictor of recurrence or death from melanoma. With a negative SLN, 10y survival was 85% vs. 62% with positive SLN |
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What percent of patients with intermediate thickness melanoma (1mm-3.5mm) will have metastasis to regional nodes? |
20% |
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Routine biopsy is not indicated in patients with thin (<1mm) melanoma. In which of these patients should it be most strongly considered? |
+ Ulceration Mitotic rate >/= 1/mm2 Select lesions > 0.75mm with high-risk features Younger patients Male patients |
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Should you perform SLN biopsy in a patient with a thick (>4mm) melanoma? |
Yes. Patients with a negative biopsy have improved OS compared to those with positive node (prognostic). Also potentially establishes locoregional control. |
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Describe lymphoscintigraphy. |
Should be done on same day as WLE and SLN biopsy Technetium-99 sulfur colloid injected into dermis at lesion/biopsy site to raise small wheal Injections should be done 0.5cm away from lesion to avoid disrupted lymphatics |
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What happens if you see no sentinel nodes on lymphoscintigraphy? |
Injecting too deeply into subcutaneous tissues can lead to false-negative imaging Repeat injection with experienced practicioner |
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What if more than one nodal basin lights up or nodes outside of traditional basin lights up? |
Sometimes sentinel nodes may be in multiple basins. Non-traditional sentinel nodes likely represent interval or in-transit nodes All identified sentinel nodes, including interval / in-transit nodes, should be removed |
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Describe sentinel lymph node biopsy for melanoma. |
- Inject 1-5cc vital blue dye (isosulfan blue) within margins of planned WLE right before incision - Gamma probe used to identify SLN with further dissection guided by blue lymphatics - The most radioactive node, any blue nodes, clincially suspicious nodes, nodes with radioactive count 10% or greater than the most radioactive node are resected - Send for permanent section with stains for melanoma (S-100, HMB-45). NO role for frozen section since difficult to identify micromets this way. |
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What is one rationale for completion lymph node dissection after positive SLN biopsy? |
There is an increased risk of nodal recurrence if lymphadenectomy is not performed. 15% of patients with positive SLN biopsy that are observed will develop nodal disease (Wong et al) VS 5% of patient with positive SLN biopsy develop nodal recurrence even after completion lymphadenectomy (Sunbelt Trial & MSLT I) |
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What is a second rationale for completion lymph node dissection after positive SLN biopsy? |
Aside from decreased nodal recurrence rates, completion lymph node dissection may improve overall survival (Controversial). There is currently no Level 1 evidence to confirm an OS benefit, however in MSLT I the 10 year melanoma-specific survival was improved in patients who underwent completion lymphadectomy after positive SLN biopsy compared to those who were observed and underwent delayed lymphadenectomy when they developed a clinical recurrence (~60% vs 40%) |
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What is the aim of MSLT II? |
MSLT II is underway and will randomize patients with positive SLN biopsy to immediate completion lymphadenectomy vs observation. Results may help define which patients can avoid CLND. Until then CLND is standard of care. |
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What should be the next step when you identify clinically suspicious lymph nodes in a patient with melanoma? |
Fine needle aspiration |
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What should you do when a patient presents with lymphadenopathy consistent metastatic melanoma but you can find no primary? Do these patients have worse or better survival compared to patients who have a primary? |
Therapeutic lymphadenectomy is indicated. These patients actually have IMPROVED survival compared to those with identified primary (?immune response). |
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Can you think of a difference between approach to lymphadenectomy for melanoma vs that for breast cancer? |
More important to completely clear nodes for melanoma as adjuvant therapy to decrease nodal recurrence risk is less reliable (radiation therapy, for example). |
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Describe axillary dissection for melanoma. |
- Remove level I, II, and III lymph nodes, including dissection cephalad to axillary vein. - Remove all fibrofatty tissue around vein, the thoracodorsal and medial pectoral neurovascular bundles, and the long thoracic nerve. - Removal of bulky nodes ma require division of pec major. - May need to ligate/resect ax vein if involved. **Watch for results of MSLT II** |
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Describe inguinal lymph node dissection for melanoma. |
- Femoral triangle is bounded by inguinal ligament, adductor longus, and sartorius. Floor: psoas, pectineus muscles. Roof: Fascia lata - In most cases, superficial inguinal lymph node dissection is sufficient for positive SLN biopsy. - Consider deep pelvic dissection (internal iliac, external iliac, and obturator nodes) in patients with: palpable groin nodes, radiographic involvement of pelvic nodes, >/= 3 positive superficial inguinal nodes, extracapsular extension, high lymph node ratio, positive Cloquet's node |
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What is the role of adjuvant high dose interferon? |
- No clear overall survival benefit - Improves DFS - Toxic therapy but may be used in patients who undergo lymphadenectomy for positive SLN or clinically positive nodes or patients with resected in-transit disease |
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What is the role of adjuvant radiation in melanoma for patients with positive lymph nodes on lymphadenectomy?
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- No overall survival benefit - Highest rates for locoregional control are seen in head and neck melanomas with low complication rate (lymphedema not an issue) - Lowest rates for control are in inguinal disease, with high rates of lymphedema - Consider in patients with clinically positive nodes, multiple positive nodes, extranodal extension |
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Who should get metastatic workup with imaging (PET/CT, CT, or MRI)? |
- Positive sentinel LN - Clinically suspicious (and ideally FNA positive) lymph node - In-transit skin lesions |
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Discuss management of in-transit skin lesions. |
- Should be biopsy proven via FNA/core - Get staging imaging - Completely resect if feasible - Consider BCG/IFN/IL-2 injection - Consider topical imiquimoid - Conisder RT for unresectable disease - Consider isolated limb infusion / perfusion with melphalan |
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Discuss management of nodal recurrence. |
- Get FNA/core - Staging imaging - If no previous nodal recurrence, perform lymphadenectomy. - If LN dissection was done previously, repeat excision of nodal disease if possible. - If unresectable recurrence or systemic disease present, consider radiotherapy or systemic therapy or supportive care. |
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Discuss management of distant metastatic disease. |
- Get FNA/biopsy - Check LDH level - Complete full staging imaging including Brain MRI - Resect if resectable with acceptable morbidity - Consider neoadjuvant therapy - If brain mets present, consider resection and/or RT - For unresectable disease, consider systemic therapy, clinical trial, or best supportive care |
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What would you do if a patient with a head and neck primary melanoma had a positive SLN in the parotid gland or a clinically suspicious and FNA proven parotid lymph node? |
Superficial parotidectomy AND neck dissection of relevant nodal basin |
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Discuss systemic therapy options for advanced or metastatic melanoma. |
Preferred regimens** (NCCN 2015) ** Ipilimumab (anti-CTLA-4) ** Dabrafenib (anti-Braf) + trametinib (anti-MEK1) for V600 BRAF mutations (RCT showed improved outcome over single agent vemurafenib) * Pembrolizubmab (anti-PD1) * Nivolumab * Imatinib for C-kit positive melano* Vemurafenib (anti-Braf) if + for V600 BRAF mutationma * IL-2 |
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What are the major side effects of the monoclonal antibodies used for melanoma? |
- Ipilimumab - lethal immune-related events - Vemurafenib - skin complications, joint swelling |
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What is the management of merkel cell carcinoma? |
Skin lesion with no clinical nodes --> WLE with 1-3 cm margin, SLN biopsy, adjuvant radiation therapy to the primary tumor site if >1cm, close margins, lymphovascular invasion If positive clinical nodes --> FNA or core to confirm, then get staging studies Distant mets --> tumor board, trials, supportive care |
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What do you do when preop lymphoscintigraphy identifies multiple basins with uptake? |
Perform SLN biopsy in multiple basins |
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What is the preferred reconstruction method for acral melanomas at heel or ball of foot? |
Rotational flap |
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Discuss the management of anal melanoma |
- Full staging workup to evaluate for distant mets - Local excision vs APR - Both accepted, but trend toward less aggressive surgery as there is never been a demonstrated difference in overall or disease-free survival between group - Can use APR as salvage therapy if local recurrence following local excision |
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What is the management of a patient with widespread metastatic melanoma with symptomatic small bowel metastasis? |
Resection |
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What do you do if intraparotid sentinel lymph node is positive for metastasis from head and neck melanoma? |
Superficial parotidectomy |
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What is the preferred treatment of eccrine carcinoma?
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Surgical resection alone No benefits seen for SLN biopsy or adjuvant treatments for this rare, usually slow growing neoplasm |
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A bland cell, spindle cell neoplasm with immunohistochemistry was positive for desmin and beta-catenin and negative for DOG-1, myo-D1, and S-100, is indicative of what tumor? |
Desmoid |
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What is the best treatment for chondrosarcoma of acetabulum in a young patient? |
Internal hemipelvectomy |
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Name positive and negative prognostic factors for sarcoma. |
Positive prognostic factors - Age < 40 - Liposarcoma or synovial sarcoma histology - Multiagent systemic therapy Negative factors - Bony metastases |
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What tumor type is consistent with positive staining for desmin AND vimentin? |
Sarcoma |
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What is the treatment of cutaneous angiosarcoma? |
Wide local resection with 1-2cm margins, +/- adjuvant radiation |
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40-45% of liposarcomas are of which histologic subtype? |
Atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDL) Treatment: En bloc resection |
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What is the best treatment for locally recurrent extremity sarcoma if no prior radiation was given? |
Resection + brachytherapy + adjuvant external-beam radiation |
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Discuss Li Fraumeni syndrome. |
- Autosomal dominant cancer-predisposition syndrome due to p53 mutations - Wide range of malignancies; 80% will develop cancer; >40% will develop multiple primaries - Most common in adults: breast cancer (80%) & sarcoma (30%) - Most common tumors in children: osteosarcoma (30%), adrenocortical carcinoma (27%), CNS tumors (26%), sarcoma (23%) - AVOID radiation therapy in these patients, as radiation-induced cancers are more common |
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What are the borders of the superficial groin dissection? |
Lateral border: Lateral border of the sartorius Medial border: Adductor longus Superior border: Inguinal ligament Inferior border: Apex of the femoral triangle inferiorly |
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What is the rate of complete response with limb perfusion for in transit mets in melanoma? |
Complete response: 20-40% Any response: 60% |
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What is the management of ITP? |
- Start treatment if plts < 30k or symptomatic bleeding - Steroids - Rituximab - thrombopoietin (TPO)-receptor agonists - Splenectomy (if all else fails) |
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Patients with wild type GIST (negative for KIT or PDGFRA mutations) should be tested for germline mutations in which gene? |
Succinate dehydrogenase (SDH) |
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What are two medical options in patients with GIST that are nonresponsive to imatinib 400 daily? |
Increase dose to imatinib 800 daily Switch to sunitinib If failing both treatments, try regorafenib or trial |
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Describe tumor size and mitotic rate in GIST that has benign behavior. |
Size < 2cm, Mitoses < 5/50 HPF |
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Describe tumor size and mitotic rate in GISTs of very low malignant potential. |
Size 2-10cm, Mitoses < 5 / 50 HPF |
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Describe tumor size and mitotic rate in GISTs of low to moderate malignant potential. |
Size <5cm, Mitoses >5 / 50 HPF OR Size > 10cm, Mitoses < 5 / 50 HPF |
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Describe tumor size and mitotic rate in GISTs of high malignant potential. |
Size > 5cm, Mitoses > 5 / 50 HPF |
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Which genetic profiles benefit most from imatinib? |
KIT mutations in exon 11 (90% response rate) PDGFRA mutations except for D842V In the absence of KIT or PDGFRA mutations, there is little benefit |
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Define T stages for soft tissue sarcoma. |
T1a tumor size < 5cm, superficial T1b tumor size < 5cm, deep T2a tumor size >5cm, superficial T2b tumor size > 5cm, deep Superficial = above superficial fascia Deep = any invasion of superficial fascia, or exclusively beneath superficial fascia |
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Define N and M stages for soft tissue sarcoma. |
N1 + lymph nodes M1 + metastases |
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Define G stages for soft tissue sarcoma |
G1 G2 G3 |
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What genetic syndromes are associated with sarcoma (including GIST?) |
Li Fraumeni (p53) - sarcomas (esp rhabdo and pleomorphic) FAP (APC) - desmoids Carney syndrome (SDH) - GIST and paragangliomas Hereditary retinoblastoma (RB1) - leimyosarcomas (often more than 30 years after initial retinoblastoma) |
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Which targeted therapy is the main option for palliative therapy for patients with progressive, unresectable, or metastatic non-lipogenic soft tissue sarcoma? |
Pazopanib |
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Which patients with soft tissue sarcoma who undergo resection may be observed (and not receive postoperative radiation)? |
T1a-1b tumors (Size < 5cm, superficial or deep) with final surgical margins of at least 1cm and with an intact fascial plane |
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What are pros/cons of pre- vs post-op radiation after resection for STS? |
Preop RT PRO: Target tissue, well oxygenated, minimize dose/volume, possibly higher chance of getting negative margins CON: Possibly increased acute wound complications (Canadian Sarcoma group RCT) in lower extremity tumors (though IMRT may have lower complications) Postop RT PRO: Lower early wound complications CON: Late treatment related side effects more common (due to higher dose needed and volume treated) |
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Which immunohistochemical marker is helpful in KIT negative GIST? |
DOG1 |
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What did ACOSOG Z9000 show? |
Imatinib 400mg daily x 1 year improved RFS and OS in patients with high risk GIST (compared to historical controls) after resection |
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What did ACOSOG Z9001 show? |
RCT that randomized patients with resected >3cm GIST to imatinib 400 mg daily vs placebo x 1 year --> RFS was higher in imatinib arm (98% vs 83%) |
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Should imatinib be given for 1 year or 3 years postop? |
SSGXVIII/AIO showed that postop imatinib x 3 years improved RFS and OS compared to 1 year for high risk GIST |
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Other than tumor size and mitotic rate, what factors contribute to high risk GIST? |
Non-gastric location Tumor rupture |
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Which desmoids can likely be safely observed? |
Asymptomatic Small tumor size Tumors in sites where increase in size will not substantially alter surgical outcome or cause functional limitation |
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What medical therapies exist for unresectable or advanced desmoids? |
NSAIDS - sulindac or celecoxib Hormonal agents - tamoxifen Biologic agents - low dose interferon Chemotherapy - methotrexate, vinblastine, doxorubicin RTK inhibitors - imatinib, sorafenib |
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What is a major side effect of ifosfamide? |
Nephrotoxicity |
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What cancers are p16 mutations associated with? |
Pancreatic adenocarcinoma Melanoma Lung Laryngeal / Oropharyngeal SCC Esophageal |
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How do you biopsy a subungual melanocytic lesion? |
- 3mm punch biopsy into nail - Don't use local - pain means you've gone too deep and into nail bed which you want to avoid - Clean nail bed with hydrogen peroxide - If pigment disappears - likely hematoma - If pigment persists - do deeper punch biopsy of nail bed |
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What is the management if patient with forearm melanoma has clinically positive epitrochlear node? |
Epitrochlear and axillary node dissections |
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What is the management in patient with forearm melanoma with lymphoscintigraphy showing uptake in epitrochlear region and axilla? What if just the epitrochlear is positive SLN biopsy? |
Do both epitrochlear and axillary SLN biopsy If epitrochlear SLN is positive, do epitrochlear dissection AND axillary dissection (as per Morton, though this is somewhat controversial) |
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What are the boundaries of the epitrochlear triangle? |
Medial head of triceps Short head of biceps Medial epicondyle |
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Name uses for imatinib |
- High risk GIST - Unresectable dermatofibromasarcoma protuberans - Mucosal melanoma - Acral melanoma |
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Describe treatment for DFSP |
- Wide local excision, 2 cm margins preferred - Consider delayed reconstruction until you know margins negative pathologically - If margins positive, re-resect if possible - If margins positive and not resectable, radiate - Consider Gleevec for unresectable or metastatic disease |
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What are the two main subtypes of rhabdomyosarcoma? |
Pleomorphic (treat like any other sarcoma) AND Non-pleomorphic (refer to high volume institution, involve pediatric onc) |
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What is the extent of neck dissection for melanoma? |
Depends on primary site. Lesions of the ear and of the scalp and neck at the level of the ear drain to all areas of the neck and require a superficial parotidectomy and complete (levels I–V) cervical lymphadenectomy. |
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What are characteristic imaging findings of atypical lipomatous tumor /well differentiated liposarcoma? |
- size > 10 cm - thick irregular/nodular septa - non-adipose areas - fat content < 75% If imaging consistent and no concern for structures, don't need biopsy - proceed to resection. |
