LWBK1006-20 LWW-Govindan-Review December 12, 2011 19:4
274 DeVita, Hellman, and Rosenberg’s CANCER: Principles and Practice of Oncology ReviewANSWERS
Answer 20.5.1. The answer is A.
Desmoid disease is second only to colorectal cancer as a common cause
of death among patients with FAP. There is heterogeneity in the clinical
presentation of desmoid tumors from asymptomatic abdominal mass to
bowel or ureteral obstruction. Sporadic desmoid tumors also occur. Ret-
rospective studies have not confirmed the role of adjuvant radiation or
chemotherapy for desmoid tumors. For unresectable tumors, chemother-
apy, hormonal therapy, and targeted agents such as imatinib have been
reported in literature as possible palliative options.Answer 20.5.2. The answer is C.
This patient meets the Amsterdam criteria for HNPCC with at least three
affected relatives in at least two successive-generation relatives and one
first-degree relative diagnosed with colorectal cancer before age 50 years.
Unlike FAP, which is characterized by chromosomal instability caused
by mutations in the APC tumor suppressor gene, HNPCC is character-
ized by MSI caused by mutations in the DNA MMR genes. HNPCC is
the most common hereditary syndrome predisposing one to colorectal
cancers. It accounts for approximately 2% to 3% of all colorectal can-
cer cases. The lifetime risk for developing colon cancer among patients
with HNPCC approaches 80%. HNPCC is also associated with other
malignancies, including endometrial, gastric, ampullary, biliary, and uri-
nary tract cancers. This patient has Muir-Torre syndrome characterized
by multiple colon cancers and multiple cutaneous neoplasia, including
sebaceous adenomas.Answer 20.5.3. The answer is D.
HNPCC can be confirmed by the demonstration of the MSI-H phenotype
and germ line mutation in any of the DNA MMR genes, such as MLH1
on chromosome 3p, MSH2 on chromosome 2p, MSH6 on chromosome
2p, PMS1 on 2q, and PMS2 on 7q. Germ line mutations involving MSH2
and MLH1 genes account for more than 60% of the known mutations
present in patients with HNPCC. The National Comprehensive Cancer
Network guidelines recommend the use of tumor screening with MSI and
lack of expression of MMR protein expression by immunohistochem-
istry initially, followed by MMR mutation testing, although proceeding
directly to MMR mutation testing is also acceptable. A negative MMR
mutation test result does not rule out Lynch syndrome or HNPCC.Answer 20.5.4. The answer is C.
Once a germ line MMR mutation is identified in a patient, genetic coun-
seling and testing of at-risk family members are essential. The patient’s
three daughters, along with all her first-degree relatives, have a 50%
probability of being a carrier of the mutant gene. In general, for family