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GASTROENTEROLOGY 2012;xx:xxx

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Continuing Medical Education Answers: April 2012Exam 1: Enteropathy-Associated T-Cell Lymphoma Complicating an

Autoimmune Enteropathy 6

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Question 1:

Answer: c

Rationale:

Answers a, b, d, and e are not correct because the patient did not have the celiac susceptibility HLA IIgenotype. In contrast, the answer c is correct because onset of enteropathy-associated T-cell lymphoma maybe observed in autoimmune enteropathy, particularly in immunodepressive state.1

Reference1. Malamut G, Verkarre V, Callens C, et al. Enteropathy-associated T-cell lymphoma complicating an autoimmune enteropathy. Gastroenterol-

ogy 2012;141:000–000.

Question 2:

Answer: d

Rationale:

The presence of immunoglobulin (Ig)A anti-transglutaminase, severe villous atrophy, celiac susceptibilityhave already been described in autoimmune enteropathy.1 Malamut et al2 showed the possibility to findntestinal T-cell clones. Autoimmune enteropathy does not respond to a gluten-free diet.2

References1. Akram S, Murray JA, Pardi DS, et al. Adult autoimmune enteropathy: Mayo Clinic Rochester experience. Clin Gastroenterol Hepatol 2007;

5:1282–1290.2. Malamut G, Verkarre V, Callens C, et al. Enteropathy-associated T-cell lymphoma complicating an autoimmune enteropathy. Gastroenterol-

ogy 2012;141:000–000.

Question 3:

Answer: e

Rationale:

Answers a, b, c, and d allow the diagnosis of celiac disease and autoimmune enteropathy, respectively.1

Answer e lacks specificity.

Reference1. Malamut G, Verkarre V, Callens C, et al. Enteropathy-associated T-cell lymphoma complicating an autoimmune enteropathy. Gastroenterol-

ogy 2012;141:000–000.

Question 4:

Answer: c

Rationale:

Answers a, b, d, and e can be observed in both types of enteropathy-associated T-cell lymphoma.1,2

1. Malamut G, Verkarre V, Callens C, et al. Enteropathy-associated T-cell lymphoma complicating an autoimmune enteropathy. Gastroenterol-ogy 2012;141:000–000.

2. Malamut G, Afchain P, Verkarre V, et al. Presentation and long-term follow-up of refractory celiac disease: comparison of type I with type

II. Gastroenterology 2009;136:81–90. 57

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Exam 2: Frequent Detection of Pancreatic Lesions in AsymptomaticHigh-Risk Individuals

Question 1:

Answer: d

Rationale:

An individual with only 1 affected blood relative and no germline mutation or pancreatic cancer syndromemay belong to a family with sporadic pancreatic cancer. Familial pancreatic cancer (nonsyndromic) isdefined by a pair of first-degree relatives. The lifetime risk for pancreatic cancer is significantly increased,particularly when �3 first-degree relatives were affected.1 All other listed factors are known geneticsyndromes associated with increased risk of pancreatic ductal adenocarcinoma.2

References1. Klein AP, Brune KA, Petersen GM, et al. Prospective risk of pancreatic cancer in familial pancreatic cancer kindreds. Cancer Res 2004;

64:2634–2638.2. Grover S, Syngal S. Hereditary pancreatic cancer. Gastroenterology 2010;139:1076–1080.

Question 2:

Answer: c

Rationale:

This individual has a germline BRCA2 mutation and breast-ovarian cancer syndrome with 1 first-degreeand 1 second-degree relative with pancreatic cancer. Her risk for pancreatic cancer is elevated.1,2 The BRCA2tumor suppressor gene mutation is the most commonly known genetic mutation associated with familialpancreatic ductal adenocarcinoma (6%2 to 19%3), but the main causative gene (a) that accounts for themajority of familial pancreatic cancer is still unknown. CT is not recommended because of radiationexposure, particularly in this patient with a BRCA mutation (the BRCA gene is directly involved in repair ofdamaged DNA). Furthermore, CT is inferior to MRI and EUS for detection of pancreatic lesions.4 In general,

lder age is associated with increased risk for pancreatic cancer and the average risk for developingancreatic cancer is similar in familial and sporadic kindreds.5 Her chance for having a pancreatic lesion ataseline screening at age 61 is 53%.4

References1. The Breast Cancer Linkage Consortium. Cancer risks in BRCA2 mutation carriers. J Natl Cancer Inst 1999;91:1310–1316.2. Couch FJ, Johnson MR, Rabe KG, et al. The prevalence of BRCA2 mutations in familial pancreatic cancer. Cancer Epidemiol Biomarkers

Prev 2007;16:342–346.3. Hahn SA, Greenhalf B, Ellis I, et al. BRCA2 germline mutations in familial pancreatic carcinoma. J Natl Cancer Inst 2003;95:214–221.4. Canto MI, Hruban RH, Fishman EK, et al. Frequent detection of pancreatic lesions in asymptomatic high-risk individuals. Gastroenterology

2012;141:000–000.5. Klein AP, Brune KA, Petersen GM, et al. Prospective risk of pancreatic cancer in familial pancreatic cancer kindreds. Cancer Res 2004;

64:2634–2638.

Question 3:

Answer: a

Rationale:

Pancreatic cysts are the most common detected lesion in asymptomatic high-risk individuals whoundergo baseline screening. These are typically small (�1 cm) and in multiple locations, increasing inprevalence with age. Asymptomatic, incidentally found pancreatic cysts, suspected branch duct intraductalpapillary mucinous neoplasms, are also common in the general population,1 but these are far more commonin high-risk individuals,2,3

References

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2. Canto MI, Hruban RH, Fishman EK, et al. Frequent detection of pancreatic lesions in asymptomatic high-risk individuals. Gastroenterology2012141:000–000.

3. Canto MI, Goggins M, Hruban RH, et al. Screening for early pancreatic neoplasia in high-risk individuals: a prospective controlled study.Clin Gastroenterol Hepatol 2006;4:766–781.

Question 4:

Answer: b

Rationale:

Although pancreatic lesions are frequently detected in high-risk individuals, decision making regardingsurgical treatment is the most difficult part of any screening program given lack of symptoms, imperfectdiagnosis of high-grade neoplasia, uncertain natural history of detectable pancreatic precursors, andmorbidity and mortality of pancreatic surgery. MRI is better than EUS and CT for demonstrating branchduct intraductal papillary mucinous neoplasm communication1.1 To date, screening studies of high-riskindividuals have infrequently diagnosed asymptomatic prevalent and incident pancreatic ductal adenocar-cinomas, but the majority were advanced stage tumors.2,3 EUS fin-needle aspiration has a limited role forpecific diagnosis of pancreatic lesions detected by screening.1,4 There is a highly variable detection rate of

pancreatic lesions by screening imaging tests,2,5 mostly dependent on selection criteria and type of screening.owever, limited data suggest most lesions do not progress rapidly,6,7 except in certain higher risk groups,

uch as p16 (FAMMM)3 and BRCA mutation carriers.2

References1. Canto MI, Hruban RH, Fishman EK, et al. Frequent detection of pancreatic lesions in asymptomatic high-risk individuals. Gastroenterology

2012;141:000–000.2. Canto MI, Goggins M, Hruban RH, et al. Screening for early pancreatic neoplasia in high-risk individuals: a prospective controlled study.

Clin Gastroenterol Hepatol 2006;4:766–781.3. Langer P, Kann PH, Fendrich V, et al. Five years of prospective screening of high-risk individuals from families with familial pancreatic

cancer. Gut 2009;58:1410–1418.4. Poley JW, Kluijt I, Gouma DJ, et al. The yield of first-time endoscopic ultrasonography in screening individuals at a high risk of developing

pancreatic cancer. Am J Gastroenterol 2009;104:2175–2181.5. Verna EC, Hwang C, Stevens PD, et al. Pancreatic cancer screening in a prospective cohort of high-risk patients: a comprehensive strat-

egy of imaging and genetics. Clin Cancer Res 2010;16:5028–5037.6. Ludwig E, Olson SH, Bayuga S, et al. Feasibility and yield of screening in relatives from familial pancreatic cancer families. Am J Gastro-

enterol 2011;106:946–954.7. Vasen HF, Wasser M, van Mil A, et al. Magnetic resonance imaging surveillance detects early-stage pancreatic cancer in carriers of a

p16-Leiden mutationy. Gastroenterology 2011;140:850–856.

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