Cutaneous Malignancies, Sarcomas, Carcinoma of Unknown Primary
Joanne Jeter, MD
Lee Cranmer, MD, PhD, FACP
Targeted therapies often used in malignant melanoma accompany agent-specific toxicities. Match the agent with its unique toxicity profile:
Vemurafenib ____ Dabrafenib ____ Trametinib _____
A. Iritis/uveitis
B. QT prolongation
C. Cardiomyopathy
D. Cut SCC
E. Retinal detachments
View Answer
Targeted therapies often used in malignant melanoma accompany agent-specific toxicities. Match the agent with its unique toxicity profile:
Vemurafenib A, B, and D Dabrafenib A, C, and D Trametinib C and E.
A. Iritis/uveitis
B. QT prolongation
C. Cardiomyopathy
D. Cut SCC
E. Retinal detachments
Suggested Readings:
Abraham J, Gulley JL. The Bethesda Handbook of Clinical Oncology. 5th ed. Wolters Kluwer; 2018.
DeVita VT, Rosenberg SA, Lawrence SL. DeVita, Hellman, and Rosenberg’s Cancer: Principles & Practice of Oncology. 11th ed. Wolters Kluwer; 2018.
What is the characteristic pattern of extraocular spread of uveal melanoma?
View Answer
Liver is the most common site of metastatic disease for uveal melanoma, and liver metastases are present in 89% of patients with metastatic disease.
Other common sites of metastasis are lung (29% of patients with metastasis), bone (17%), skin/subcutaneous tissue (11%), and lymph nodes (11%).
Suggested Readings:
Diener-West M, Reynolds SM, Agugliaro DJ, et al. Development of metastatic disease after enrollment in the COMS trials for treatment of choroidal melanoma: Collaborative Ocular Melanoma Study Group Report No. 26. Arch Ophthalmol. 2005;123(12):1639-1643.
Abraham J, Gulley JL. The Bethesda Handbook of Clinical Oncology. 5th ed. Wolters Kluwer; 2018.
DeVita VT, Rosenberg SA, Lawrence SL. DeVita, Hellman, and Rosenberg’s Cancer: Principles & Practice of Oncology. 11th ed. Wolters Kluwer; 2018.
In addition to cutaneous melanoma, germline mutations in the CDKN2A gene are associated with what other malignancies?
View Answer
CDKN2A mutations are also associated with increased incidence of pancreatic cancer and astrocytoma, and genetic testing should be considered for individuals with two or more of these cancers in their personal or family histories.
Suggested Readings:
Goldstein AM, Fraser MC, Struewing JP, et al. Increased risk of pancreatic cancer in melanoma-prone kindreds with p16INK4 mutations. N Engl J Med. 1995;333(15):970-974.
Kaufman DK, Kimmel DW, Parisi JE, et al. A familial syndrome with cutaneous malignant melanoma and cerebral astrocytoma. Neurology. 1993;43(9):1728-1731.
Abraham J, Gulley JL. The Bethesda Handbook of Clinical Oncology. 5th ed. Wolters Kluwer; 2018.
DeVita VT, Rosenberg SA, Lawrence SL. DeVita, Hellman, and Rosenberg’s Cancer: Principles & Practice of Oncology. 11th ed. Wolters Kluwer; 2018.
Germline mutation in what gene should be suspected in a family with cases of ocular melanoma, cutaneous melanoma, mesothelioma, and basal cell carcinoma?
View Answer
Inherited BAP1 mutations have been associated with increased incidence of ocular melanoma, mesothelioma, basal cell carcinomas, and cutaneous melanomas, including skin lesions suggestive of this syndrome termed MBAITs (melanocytic BAP1-mutated atypical intradermal tumors). Mutations in this gene may be associated with clear cell carcinoma of the kidney and other cancers as well.
Suggested Readings:
Walpole S, Pritchard AL, Cebulla CM, et al. Comprehensive study of the clinical phenotype of germline BAP1 variant-carrying families worldwide. J Natl Cancer Inst. 2018;110(12):1328-1341.
Abraham J, Gulley JL. The Bethesda Handbook of Clinical Oncology. 5th ed. Wolters Kluwer; 2018.
DeVita VT, Rosenberg SA, Lawrence SL. DeVita, Hellman, and Rosenberg’s Cancer: Principles & Practice of Oncology. 11th ed. Wolters Kluwer; 2018.
What differences are seen in somatic testing of mucosal melanomas as compared to cutaneous melanomas?
View Answer
Mucosal melanomas have an increased incidence of KIT mutations, targetable by inhibitors, and decreased incidence of BRAF mutations, as compared to cutaneous melanomas.
Suggested Readings:
Curtin JA, Busam K, Pinkel D, Bastian BC. Somatic activation of KIT in distinct subtypes of melanoma. J Clin Oncol. 2006;24(26):4340-4346.
Abraham J, Gulley JL. The Bethesda Handbook of Clinical Oncology. 5th ed. Wolters Kluwer; 2018.
DeVita VT, Rosenberg SA, Lawrence SL. DeVita, Hellman, and Rosenberg’s Cancer: Principles & Practice of Oncology. 11th ed. Wolters Kluwer; 2018.
What is the rationale for including an MEK inhibitor in combination with a BRAF inhibitor for treatment of advanced melanoma?
View Answer
The combination of BRAF and MEK inhibitors has been shown to increase response rates and survival in melanoma patients with BRAF-mutated tumors. In addition, the combination therapy has a decreased incidence of second primary cutaneous malignancies associated with single-agent BRAF inhibitors.
Suggested Readings:
Flaherty KT, Infante JR, Daud A, et al. Combined BRAF and MEK inhibition in melanoma with BRAF V600 mutations. N Engl J Med. 2012;367(18):1694-1703.
Abraham J, Gulley JL. The Bethesda Handbook of Clinical Oncology. 5th ed. Wolters Kluwer; 2018.
DeVita VT, Rosenberg SA, Lawrence SL. DeVita, Hellman, and Rosenberg’s Cancer: Principles & Practice of Oncology. 11th ed. Wolters Kluwer; 2018.
For what subgroup of melanoma patients might therapy be considered with talimogene laherparepvec?
View Answer
Talimogene laherparepvec, or T-Vec, is an attenuated oncolytic herpes simplex virus that contains the granulocyte-macrophage colony-stimulating factor gene. It is given intralesionally for patients who have unresectable melanoma metastases primarily involving the skin, soft tissue, and nodes that are accessible for subcutaneous injection.
Suggested Readings:
Andtbacka RH, Kaufman HL, Collichio F, et al. Talimogene laherparepvec improves durable response rate in patients with advanced melanoma. J Clin Oncol. 2015;33(25):2780-2788.
Abraham J, Gulley JL. The Bethesda Handbook of Clinical Oncology. 5th ed. Wolters Kluwer; 2018.
DeVita VT, Rosenberg SA, Lawrence SL. DeVita, Hellman, and Rosenberg’s Cancer: Principles & Practice of Oncology. 11th ed. Wolters Kluwer; 2018.
Aside from basal cell carcinomas, often first diagnosed before the age of 30 years, what other clinical characteristics may be found in basal cell nevus syndrome (Gorlin syndrome)?
View Answer
Major criteria for Gorlin Syndrome Odontogenic keratocyst of the jaw, palmar/plantar pitting, lamellar calcifications of the falx cerebri in the brain, medulloblastoma.
Minor criteria for Gorlin Syndrome Macrocephaly, skeletal malformations, rib abnormalities, cardiac or ovarian fibromas, cleft lip/palate, ocular abnormalities, lymphomesenteric cysts.
For a clinical diagnosis, two major criteria or one major and two minor criteria are required.
Suggested Readings:
Bree AF, Shah MR; BCNS Colloquium Group. Consensus statement from the first international colloquium on basal cell nevus syndrome (BCNS). Am J Med Genet A. 2011;155A(9):2091-2097.
Abraham J, Gulley JL. The Bethesda Handbook of Clinical Oncology. 5th ed. Wolters Kluwer; 2018.
DeVita VT, Rosenberg SA, Lawrence SL. DeVita, Hellman, and Rosenberg’s Cancer: Principles & Practice of Oncology. 11th ed. Wolters Kluwer; 2018.
What are the primary causes implicated in Merkel cell carcinoma?
View Answer
Merkel cell polyomavirus can be found in 79% of Merkel cell carcinomas.
UVB mutation signatures have been found in Merkel cell carcinoma as well, and epidemiologic data implicate UV radiation as a cause. Immunosuppression may also increase the risk of Merkel cell carcinoma.
Suggested Readings:
Santos-Juanes J, Fernández-Vega I, Fuentes N, et al. Merkel cell carcinoma and Merkel cell polyomavirus: a systematic review and meta-analysis. Br J Dermatol. 2015;173(1):42-49.
Abraham J, Gulley JL. The Bethesda Handbook of Clinical Oncology. 5th ed. Wolters Kluwer; 2018.
DeVita VT, Rosenberg SA, Lawrence SL. DeVita, Hellman, and Rosenberg’s Cancer: Principles & Practice of Oncology. 11th ed. Wolters Kluwer; 2018.
What immune checkpoint inhibitors are FDA approved for treatment of advanced, unresectable, cutaneous squamous cell carcinoma?
View Answer
Cemiplimab (PD1 inhibitor) and pembrolizumab (PDL-1 inhibitor) are FDA approved for treatment of advanced cutaneous squamous cell carcinoma in October 2018.
Use immunotherapy agents with caution in patients with history of solid organ transplantation, autoimmune conditions, or prior HSCT given the risk of organ rejection, autoimmune exacerbation, or graft-versus-host disease, respectively.
Suggested Readings:
Abraham J, Gulley JL. The Bethesda Handbook of Clinical Oncology. 5th ed. Wolters Kluwer; 2018.
DeVita VT, Rosenberg SA, Lawrence SL. DeVita, Hellman, and Rosenberg’s Cancer: Principles & Practice of Oncology. 11th ed. Wolters Kluwer; 2018.
What pathway is inhibited by drugs such as vismodegib and sonidegib in the treatment of advanced, unresectable basal cell carcinomas?
View Answer
Vismodegib and sonidegib work on the hedgehog pathway by inhibiting the signaling activity of smoothened homologue (SMO). Nearly all basal cell carcinomas have alterations in this pathway.
Toxicity profile is similar between these two agents, and most commonly patients experience muscle spasms, dysgeusia, and alopecia.
Suggested Readings:
Sekulic A, Migden MR, Oro AE, et al. Efficacy and safety of vismodegib in advanced basal-cell carcinoma. N Engl J Med. 2012;366(23):2171-2179.
Abraham J, Gulley JL. The Bethesda Handbook of Clinical Oncology. 5th ed. Wolters Kluwer; 2018.
DeVita VT, Rosenberg SA, Lawrence SL. DeVita, Hellman, and Rosenberg’s Cancer: Principles & Practice of Oncology. 11th ed. Wolters Kluwer; 2018.
Between basal cell carcinoma and cutaneous squamous cell carcinoma, which disease imposes the greater risk for developing metastatic spread?
View Answer
Metastatic disease in cutaneous squamous cell is more common, ranging from 0.1% to 9.9% in different series.
Basal cell carcinomas metastasize very rarely, with incidence of metastatic disease ranging between 0.0028% and 0.55% of tumors.
Suggested Readings:
Snow SN, Sahl W, Lo JS, et al. Metastatic basal cell carcinoma. Report of five cases. Cancer. 1994;73:328-335.
Weinberg AS, Ogle CA, Shim EK. Metastatic cutaneous squamous cell carcinoma: an update. Dermatol Surg. 2007;33(8):885-899.
Abraham J, Gulley JL. The Bethesda Handbook of Clinical Oncology. 5th ed. Wolters Kluwer; 2018.
DeVita VT, Rosenberg SA, Lawrence SL. DeVita, Hellman, and Rosenberg’s Cancer: Principles & Practice of Oncology. 11th ed. Wolters Kluwer; 2018.
What are the most common cutaneous malignancies associated with solid organ transplant recipients?
View Answer
Although basal cell carcinomas are more common in the general population, in transplant patients, cutaneous squamous cell carcinomas are the most common, occurring in up to 8% of transplant recipients.
The incidence of melanoma and Merkel cell carcinomas is also increased in the transplant population relative to the general population.
Suggested Readings:
Garrett GL, Blanc PD, Boscardin J, et al. Incidence of and risk factors for skin cancer in organ transplant recipients in the United States [published correction appears in JAMA Dermatol. 2017;153(3):357]. JAMA Dermatol. 2017;153(3):296-303.
Abraham J, Gulley JL. The Bethesda Handbook of Clinical Oncology. 5th ed. Wolters Kluwer; 2018.
DeVita VT, Rosenberg SA, Lawrence SL. DeVita, Hellman, and Rosenberg’s Cancer: Principles & Practice of Oncology. 11th ed. Wolters Kluwer; 2018.
What oral medication is associated with a decreased risk of nonmelanoma skin cancers in a randomized, placebo-controlled clinical trial?
View Answer
Nicotinamide (vitamin B2) 500 mg bid for 12 months resulted in a 23% reduction of nonmelanoma skin cancers compared to placebo controls. Statistically significant reductions were seen in incidence of squamous cell carcinomas (30%) and actinic keratosis (11%). Basal cell carcinomas were reduced by 20% but had only borderline statistical significance.
Suggested Readings:
Chen AC, Martin AJ, Choy B, et al. A phase 3 randomized trial of nicotinamide for skin-cancer chemoprevention. N Engl J Med. 2015;373(17):1618-1626.
Abraham J, Gulley JL. The Bethesda Handbook of Clinical Oncology. 5th ed. Wolters Kluwer; 2018.
DeVita VT, Rosenberg SA, Lawrence SL. DeVita, Hellman, and Rosenberg’s Cancer: Principles & Practice of Oncology. 11th ed. Wolters Kluwer; 2018.
A. t(2;13)
B. t(11;22)
C. t(X;18)
D. CDK4
E. MDM2
F. KIT mutation
G. PDGFRA mutation
H. t(21;22)
I. t(1;13)
J. RANK
K. NF1 deletion
|
View Answer
A. t(2;13)
B. t(11;22)
C. t(X;18)
D. CDK4
E. MDM2
F. KIT mutation
G. PDGFRA mutation
H. t(21;22)
I. t(1;13)
J. RANK
K. NF1 deletion
| ||||||||||||||||||||||||
Related posts:
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
