Lynch Syndrome and Muir-Torre Syndrome: An update and review on the genetics, epidemiology, and management of two related disorders

Le, Stephanie; Ansari, Umer; Mumtaz, Aisha; Malik, Kunal; Patel, Parth; Doyle, A. P.; Khachemoune, Amor

doi:10.5070/d32311037239

Cited by 30 publications

(17 citation statements)

References 60 publications

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“…In addition, there was no significant correlation between HPV infection and p16 expression which could predict disease outcome. 19,21,22 By linking p16 expression and HPV infection with MSI, we could not find a significant correlation which could contribute to the pathogenesis of SN. This is consistent with prior studies that failed to proof an association between p16, MSI and HPV.…”

Section: Discussionmentioning

confidence: 66%

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Microsatellite Instability in Near East Sebaceous Neoplasms: Toward Improved Prediction

Hajj

Saliba

Shaheen

et al. 2021

Applied Immunohistochemistry &Amp; Molecular Morphology

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Sebaceous neoplasms (SN) comprise a heterogeneous spectrum of tumors with different biological behaviors. In the Near-East Region (NER), microsatellite instability (MSI) in SN’s development, and its correlation with the clinicopathologic features of tumors is not well elucidated. A cohort of 225 SN patients (40 benign SNs and 185 sebaceous carcinomas) from the NER was retrospectively reviewed. Clinical variables and available follow-up information were recorded. MSI proteins (MLH1, MSH2, MSH6, and PMS2) as well as P53, P16, EMA, CD8, and PDL-1 expressions were examined by immunohistochemistry. Detection of human papilloma virus was determined by polymerase chain reaction. Microscopic features such as mitotic count and tumor-infiltrating lymphocytes were documented. A minority of SNs from benign (n=2) or malignant (n=3) tumors in the NER exhibit MSI (2.2%). MSI is exclusively found in patients with extraocular lesions (back, n=5) and presented a poor outcome. Among these, PMS2 protein was mostly lost (average=80%, n=4). SN with MSI exhibited a significant increase in p53 expression, (average=62.10%, P=0.002). There was no significant correlation between MSI status and any of the following: PD-L1, CD8, p16, and human papilloma virus infection. Microscopically, SN with MSI show significantly higher mitotic count, cystic changes and increased tumor-infiltrating lymphocytes. MSI is rarely found in NER’s SN. When detected, it is exclusively in extraocular SNs with minimal predicative microscopic features and worse outcome.

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Section: Discussionmentioning

confidence: 66%

“…20 In the NER, the incidence of MTS is described as unclear. 20,21 In addition, MTS is significantly associated with extraocular lesions. Since most of sebaceous lesions in our cohort are ocular, and based on the literature, the incidence of MTS syndrome could not be related to MSI.…”

Section: Discussionmentioning

confidence: 99%

Microsatellite Instability in Near East Sebaceous Neoplasms: Toward Improved Prediction

Hajj

Saliba

Shaheen

et al. 2021

Applied Immunohistochemistry &Amp; Molecular Morphology

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“…Generally, KA are benign keratinocyte skin tumours mostly seen in patients over 60 2 . In this young patient with two KA/cSCC, a sebaceoma, and a family history of digestive cancers, a genetic disease, such as a Muir‐Torre syndrome (MTS), was suspected 3–6 . MTS is a variant of hereditary non‐polyposis colorectal cancer or Lynch syndrome, 7 which is an autosomal dominant disorder due to DNA mismatch repair (MMR) default including deleterious germline mutation of MLSH1, MSH2, MSH6 or PMS2.…”

Section: Discussionmentioning

confidence: 98%

“…2 In this young patient with two KA/cSCC, a sebaceoma, and a family history of digestive cancers, a genetic disease, such as a Muir-Torre syndrome (MTS), was suspected. [3][4][5][6] MTS is a variant of hereditary non-polyposis colorectal cancer or Lynch syndrome, 7 which is an autosomal dominant disorder due to DNA mismatch repair (MMR) default including deleterious germline mutation of MLSH1, MSH2, MSH6 or PMS2. After identifying the mutation responsible of MTS in our patient, this genetic defect could be screened among other family members.…”

Section: Discussionmentioning

confidence: 99%

Keratoacanthoma or cutaneous squamous cell carcinoma revealing a DNA mismatch repair default (Muir‐Torre Syndrome)

Miao

Kolb

Tomasic

et al. 2021

Acad Dermatol Venereol

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Keratoacanthoma (KA) and well‐differentiated cutaneous squamous cell carcinoma (cSCC) are hardly distinguishable clinically and histologically. They both can be seen in patients with hereditary non‐polyposis colorectal cancer (HNPCC) or Lynch Syndrome, corresponding to DNA microsatellite instability. In our case, a young man had the excision of two rapidly growing skin tumours for which distinction between KA and cSCC was initially clinically and pathologically challenging. The diagnosis of well‐differentiated cSCCs was made and the patient was treated with surgery. Ten years after the first cSCC, he was diagnosed with Muir‐Torre syndrome, a variant of Lynch syndrome, with an heterozygote mutation of the MSH2 gene. This later diagnosis allowed to screen his family members for the same mutation and to adopt an appropriate follow‐up regarding the risk of digestive tumours for him and his family. Furthermore, it is important to know that, in case of non‐resectable cSCC occurring in this patient, immunotherapy using anti‐PD1 antibody would probably be effective due to the known increased immunogenicity of MMR deficient tumours.

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“…Errors in MMR result in microsatellite instability that in turn drives oncogenesis. 1 The current standard of care for the management of cutaneous neoplasms in MTS consists of active surveillance and therapy with destruction or surgical resection. Importantly, though, isotretinoin has shown efficacy in the treatment of sebaceous neoplasms associated with MTS, in addition to its well-documented effect on preventing KAs.…”

mentioning

confidence: 99%

Isotretinoin as chemoprophylaxis for cutaneous malignancies in Muir‐Torre syndrome: A novel concept

Joshi

Farr

Lewis

2022

Dermatologic Therapy

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Muir-Torre syndrome (MTS) is an autosomal dominant cancer syndrome that is a phenotypic variant of hereditary nonpolyposis colorectal carcinoma (HNPCC), or Lynch syndrome. MTS is characterized by sebaceous neoplasms and HNPCC-associated malignancies such as colorectal, endometrial, and urothelial carcinomas. The Amsterdam criteria require the presence of at least one sebaceous adenoma, sebaceous epithelioma, sebaceous carcinoma, or keratoacanthoma (KA) with sebaceous differentiation in addition to a HNPCCassociated visceral malignancy. Multiple KAs and a visceral malignancy together with a family history of MTS are also diagnostic. MTS is precipitated by pathogenic variants of DNA mismatch repair genes such

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Lynch Syndrome and Muir-Torre Syndrome: An update and review on the genetics, epidemiology, and management of two related disorders

Cited by 30 publications

References 60 publications

Microsatellite Instability in Near East Sebaceous Neoplasms: Toward Improved Prediction

Microsatellite Instability in Near East Sebaceous Neoplasms: Toward Improved Prediction

Keratoacanthoma or cutaneous squamous cell carcinoma revealing a DNA mismatch repair default (Muir‐Torre Syndrome)

Isotretinoin as chemoprophylaxis for cutaneous malignancies in Muir‐Torre syndrome: A novel concept

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