Malignant Neoplasms of the Colon
Philip H. Gordon, Santhat Nivatvongs, Lee E. Smith, Scott Thorn Barrows, Carla Gunn, Gregory Blew, David Ehlert, Craig Kiefer, Kim Martens in Neoplasms of the Colon, Rectum, and Anus, 2007
What patients with suspected HNPCC should be referred for genetic counseling and testing? Because HNPCC is not always obvious based on clinical findings, either preoperatively or during resection, the clinical management of a possible HNPCC patient is complex. A detailed family history, with sites of malignancy verified, is critical to determine whether the patient fits the Amsterdam criteria and other associated features of HNPCC. Analysis of neoplastic material would provide assistance in determining whether to test the proband’s germline DNA (i.e., a blood sample) for HNPCC mutations (after genetic counseling) and refer the first-degree relatives should a mutation be detected. In the instance of a positive family history it is ideal for testing to be conducted despite microsatellite instablility (MSI) phenotype. The clinical algorithm would be much the same as for FAP, with the exception that the multiple genes might need to be analyzed unless tests on pathogenic samples narrow the search. It is important to point out that at present, detection of a confirmed pathogenic mutation occurs in less than 50% of HNPCC families. In the absence of an identified deleterious mutation, genetic testing is inconclusive, which must be explained to the patient by an individual skilled in genetic counseling. Family members can be given general advice for colorectal carcinoma screening of first-degree relatives of patients with this malignancy.
Risk Reduction and Screening for Women’s Cancers
James M. Rippe in Lifestyle Medicine, 2019
The Amsterdam criteria are as follows:At least three relatives with Lynch/HNPCC-associated cancer. colon, endometrium, small bowel, renal pelvis, or ureter Of note, not included in this list is stomach, ovary, bladder, brain, or skin.One affected person is a first-degree relative of the other two.At least two successive generations are involved.One person was diagnosed below the age of 55.Familial adenomatous polyposis has been excluded.Tumors have been verified by a pathologist.
Colorectal cancer
Pat Price, Karol Sikora in Treatment of Cancer, 2014
HNPCC is also associated with other malignancies including endometrial, ovarian, gastric, pancreatic and renal malignancies. The Muir-Torre syndrome is a particular variant in which CRC is associated with sebaceous tumours and keratoacanthomas.30 The value of several of the proposed diagnostic criteria in identifying subjects with mutations in HNPCC-associated mismatch repair genes has been evaluated by Syngal et al.31 (Table 15.1). Of 70 families, 28 fulfilled the Amsterdam criteria, 39 the modified Amsterdam criteria, 34 the Amsterdam II criteria, and 56 at least one of the seven Bethesda Guidelines for the identification of HNPCC patients. The sensitivity and specificity of the Amsterdam criteria were 61% and 67%, respectively. The sensitivities of the modified Amsterdam and Amsterdam II criteria were 72 and 78%, respectively. Overall, the most sensitive criteria for identifying families with pathogenic mutations were the Bethesda criteria, with a sensitivity of 94% but a specificity of only 25%. Use of only the first three criteria of the Bethesda Guidelines was associated with a sensitivity of 94% and a specificity of 49%. In practice, any patients with suspected HNPCC, either from the family history or from pathological features (including loss of staining of the mismatch repair genes by immunohistochemistry), should be referred for genetic counselling and possible gene testing.
Challenges in diagnosis of polycystic ovary syndrome in adolescence
Published in Gynecological Endocrinology, 2021
Elene Asanidze, Jenaro Kristesashvili, Nino Parunashvili, Natalia Karelishvili, Nana Etsadashvili
Currently, for the diagnosis of PCOS the criteria adopted by the Rotterdam Consensus in 2003 are also used in adolescents [6]. However these criteria do not take into account the peculiarities of adolescent physiology. Different diagnostic criteria for adolescents have been proposed by some authors, but there is still no complete consensus [7,8]. Amsterdam criteria suggests that all three elements of the Rotterdam criteria should be present in adolescents for diagnosis of PCOS [9]. By ESHRE guideline 2018, in adolescents with irregular menstrual cycles and hyperandrogenism, an ovarian ultrasound is not necessary for PCOS diagnosis, because data in young women with age of <8 years after menarche is inadequate, that peak ovarian maturity has not yet been reached and that defining polycystic ovary morphology at this life stage is not currently possible [10]. There was recognition of the risk of overdiagnosis in adolescents if ultrasound criteria were included in this age group, which can also influence an adolescents’ quality of life [11]. ESHRE proposed that for adolescents who have features of PCOS but do not meet diagnostic criteria, an ‘increased risk’ could be considered and reassessment advised at or before full reproductive maturity, 8 years post menarche [10]. This was a strong consensus recommendation and not an evidence-based recommendation, because reliable data regarding longitudinal ovarian morphology was limited.
Risk of colorectal polyps and of malignancies in asymptomatic carriers of mutations in the main DNA mismatch repair genes
Published in Scandinavian Journal of Gastroenterology, 2018
Maurizio Ponz de Leon, Monica Pedroni, Annalisa Pezzi, Blerta Sulce, Luca Roncucci, Federica Domati, Giuseppina Rossi, Luca Reggiani Bonetti
Mutation carriers (Mut+) were individuals belonging to already diagnosed Lynch families in whom constitutional mutations in one of the three major DNA mismatch repair genes could be detected. All of them were asymptomatic at time of the molecular test and did not refer history of cancer. Some of them had already started colonoscopic surveillance when the disease had been diagnosed on the basis of Amsterdam criteria. Nongene carriers (Mut−) were individuals belonging to the same 74 Lynch families in whom genetic testing resulted negative for mutations. As a whole, 81 mutation carriers in 42 families were identified between 1994 and 2015, together with 113 nongene carriers in 48 families. Among Mut + subjects, 40 were carrier of MLH1 mutation (including 10 with the founder mutation), 35 MSH2 and 6 MSH6 gene variants.
Therapeutic strategies for upper tract urothelial carcinoma
Published in Expert Review of Anticancer Therapy, 2018
Yuval Freifeld, Laura-Maria Krabbe, Timothy N. Clinton, Solomon L. Woldu, Vitaly Margulis
Initial screening and consideration for further diagnostic tests should be done based on the Bathesda [100] or Amsterdam [101] criteria for HNPCC; however, these criteria offer relatively low sensitivity [102], and may prove to be cumbersome to the urologist. The EAU guidelines suggests that H-UTUC should be suspected in patients fulfilling one of the conditions described in Table 3, those patients should further undergo genetic testing aimed at MSH2, MSH6, or MLH1 mutations to establish the final diagnosis [1]. Another suggested option is sending specimens of all newly diagnosed UTUC patients for MSI testing by polymerase chain reaction (PCR) or immunohistochemistry (IHC) evaluation of MMR proteins [102]. Metcalfe et al. compared different screening options including the Amsterdam criteria, IHC, and MSI PCR, recognizing 13.9% of patients as at risk and eventually 5.2% with confirmed Lynch syndrome, all of which were recognized by a combination of Amsterdam criteria and IHC [103].
Related Knowledge Centers
- Colorectal Cancer
- Genetic Testing
- Histology
- Microsatellite Instability
- Small Intestine
- Ureter
- Endometrium
- Large Intestine
- Hereditary NONpolyposis Colorectal Cancer
- Familial Adenomatous Polyposis