Hereditary Syndromes Manifesting as Endometrial Carcinoma: How Can Pathological Features Aid Risk Assessment?

Table 2

Amsterdam I and II criteria as well as the Revised Bethesda Guidelines for diagnosis of Lynch syndrome. The Revised Bethesda Guidelines was developed with the intention of identifying individuals who should undergo investigation for Lynch syndrome by evaluation of MSI analysis and/or immunohistochemistry (IHC) testing of their tumors. (Adapted from [43]).

Amsterdam I criteria
(i) Three or more relatives with histologically verified colorectal cancer, one of which is a first-degree relative of the other two. Familial adenomatous polyposis should be excluded.
(ii) Two or more generations with colorectal cancer.
(iii) One or more colorectal cancer cases diagnosed before the age of 50 years.
Amsterdam II criteria
(i) Three or more relatives with histologically verified Lynch syndrome-associated cancer (colorectal cancer, cancer of the endometrium, small bowel, ureter, or renal pelvis), one of which is a first-degree relative of the other two. Familial adenomatous polyposis should be excluded.
(ii) Cancer involving at least two generations.
(iii) One or more cancer cases diagnosed before the age of 50 years.
Revised Bethesda Guidelines
(i) Colorectal carcinoma diagnosed at younger than 50 years.
(ii) Presence of synchronous or metachronous colorectal carcinoma or other Lynch Syndrome-associated tumors^#.
(iii) Colorectal carcinoma with MSI-high pathologic-associated features (Crohn-like lymphocytic reaction, mucinous/signet cell differentiation, or medullary growth pattern) diagnosed in an individual younger than 60 years old.
(iv) Patient with colorectal carcinoma and colorectal carcinoma or Lynch syndrome-associated tumor diagnosed in at least 1 first-degree relative younger than 50 years old.
(v) Patient with colorectal carcinoma and colorectal carcinoma or Lynch syndrome-associated tumor^# at any age in two first-degree or second-degree relatives.

Lynch syndrome-associated tumors include tumor of the colorectum, endometrium, stomach, ovary, pancreas, ureter, renal pelvis, biliary tract, brain, and small bowel.
Caveat: Muir Torre syndrome is considered a subset of Lynch syndrome with patients also having sebaceous neoplasms and/or keratoacanthomas.