LWBK1006-14 LWW-Govindan-Review November 24, 2011 11:28
Chapter 14•Genetic Counseling 157highly penetrant cancer predisposition syndrome that results from muta-
tions in the E-cadherin gene (CDH1). This syndrome is associated with
a 70% cumulative lifetime risk for diffuse gastric cancer, an adenocarci-
noma that causes thickening of the gastric wall (linitis plastica) without a
distinct mass. There is also a 40% lifetime risk for lobular breast cancer.
The youngest reported case of gastric cancer is 14 years with a median
age at diagnosis of 38 years. Intensified surveillance with upper endoscopy
and breast mammography with MRI is recommended. Prophylactic gas-
trectomy may also be considered given the limitation in detecting diffuse
lesions. Precancerous lesions have been detected in a small series of “pro-
phylactic” gastrectomy specimens.
It is a challenge for healthcare providers to stay well informed of
their own medical discipline, let alone to maintain a working knowl-
edge of the advances for other specialties and rare syndromes. Work-
ing collaboratively with a clinical geneticist and genetic counselor may
help to facilitate the identification of families with hereditary cancer.
Although these syndromes may be considered “rare,” they often go unrec-
ognized and the opportunity for positive medical intervention for a fam-
ily is lost. The first step in the identification of hereditary cancer begins
with a thorough collection and evaluation of the family cancer history.
Detailed reviews of many hereditary cancer syndromes can be found at
http://www.genetests.orgAnswer 14.7. The answer is C.
Most hereditary cancer syndromes identified to date are characterized by
their highly penetrant, autosomal-dominant (AD) inheritance. As such,
the features of hereditary cancer are the same as other highly penetrant
AD diseases. The characteristics include young age of onset, multiple pri-
mary cancers in one individual, multiple affected family members in at
least two generations, diverse cancer types that are part of a known cancer
syndrome, and specific pathology known to be associated with a given
syndrome. A family’s ethnic and religious background is important to con-
sider. As with any genetic disease, the frequency of cancer predisposition
gene mutations may vary among ethnic groups. Knowing a family’s ethnic
background may provide a helpful clue in deciding to pursue a given diag-
nosis over another. In the family presented, the Ashkenazi Jewish ancestry
was not a feature or clue to their diagnosis. AlthoughBRCA1andBRCA2
gene mutations occur more commonly among Jewish families, E-cadherin
gene mutations do not. In contrast, the pathology of the breast and gastric
cancers proved invaluable in the syndrome identification of this family.
The HDGC syndrome is associated with lobular breast cancer and diffuse
gastric cancer. Consider whether the family had reported only a history
of breast and gastric cancer with no specific pathology details. The differ-
ential diagnoses would have expanded to include BRCA1 and BRCA2
cancer syndromes and HNPCC syndrome. Knowing the histopatho-
logic features allowed for a direct diagnosis to be made in this fam-
ily. The use of tumor pathology to identify hereditary disease is quickly
evolving.