HNPCC | pacs

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Hereditary non-polyposis colorectal cancer (HNPCC), also known as Lynch syndrome, is an autosomal dominant condition which predisposes to a host of malignancies, including colorectal carcinoma. It is considered the most frequent form of hereditary colorectal cancer. Diagnosis requires evaluation using clinical criteria (see: Amsterdam criteria for HNPCC).

Epidemiology

Lynch syndrome is the most common cancer syndrome, affecting 1 in 400 persons . Typically HNPCC patients present in their forties and fifties with colorectal cancer , or with one of the associated malignancies. It is 5 times more common than familial adenomatous polyposis syndromes (FAP) . It is the most common hereditary cause of endometrial cancer .

Pathology

HNPCC is due to mutations in DNA mismatch repair (MMR) genes , resulting most frequently in colorectal carcinoma (10-82% lifetime risk ) as well as extracolonic malignancies, including :

genitourinary tract malignancies
- endometrial carcinoma: 15-60% lifetime risk , most often endometrioid type
- ovarian tumor: 4-12% lifetime risk
- prostate cancer: 30% lifetime risk
- urothelial tract cancer: 1-7% lifetime risk
small bowel cancer: ~5% lifetime risk
- duodenum 45%
- jejunum 29%
- ileum 12%
- not specified 14%
gastric cancer: 6-13% lifetime risk
hepatobiliary tract malignancies: 1-4% lifetime risk
pancreatic malignancies: 1-6% lifetime risk
CNS tumors: most often glioblastoma

There is a described association with breast malignancy, although the relationship is inconsistent . The MMR genes most commonly affected are MLH1, MSH2 (these two 70-85% of cases, MSH6, and PMS2 or EPCAM, an upstream gene in MSH2 expression .

Variants

Muir-Torre syndrome: HNPCC-variant with sebaceous tumors and keratoacanthocytomas

Radiographic features

Radiographic features are related to the underlying conditions:

colorectal carcinoma (CRC): more frequently right sided (70% proximal to the splenic flexure) . Despite the name, colorectal cancers arise from adenomatous polyps. Diffuse polyposis is characteristically absent.
small bowel adenocarcinoma: most commonly duodenal
endometrial carcinoma
ovarian tumors
urinary tract malignancies

Treatment and prognosis

The high risk of colorectal carcinoma warrants screening of the colon every 1 to 2 years starting from 25-40 years of age and may require colectomy. With close surveillance and resection of any adenomas which develop, the risk of CRC can be reduced by 60% .

Due to a high number of extracolonic tumors, various screening programs have been instituted. Examples include transvaginal ultrasound screening of the uterus and ovaries (in post-menopausal women , at the clinician's discretion) and serum CA-125 . One follow up regimen recommends annual transvaginal ultrasound and endometrial biopsy , although screening should be individualized .

History and etymology

Lynch syndrome was first described by Aldred Scott Warthin (1866-1931) , an American pathologist, from University of Michigan in Ann Arbor, Michigan, in 1913, after research into a family with several members with cancers. In the mid 1960s, Henry T Lynch (1928-fl.2019), an American oncologist, published further detailed painstaking work on the same family studied by Warthin, shedding further light on these apparently hereditary cancers . The condition was later renamed after Lynch who doggedly pursued the then heterodoxy that cancer could be hereditary.