Low risk of solid tumors in persons with Down syndrome

PurposeThe aim of this study was to investigate cancer incidence in a large cohort of persons with Down syndrome.MethodsDown syndrome was identified from the Danish Cytogenetic Register. Cancer occurrence was identified by linkage to the Danish Cancer Registry. Standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) were calculated based on observed and expected numbers from rates for all Danish residents. The cohort consisted of 3,530 persons with Down syndrome contributing 89,570 person-years at risk.ResultsAcute leukemia risk was highest from 1–4 years of age and remained elevated until age 30. The overall risk of solid tumors was decreased (SIR 0.45; 95% CI 0.34–0.59), especially in persons 50 years or older (SIR 0.27; 95% CI 0.16–0.43). We found a significantly lower risk of lung cancer (SIR 0.10; 95% CI 0.00–0.56), breast cancer (SIR 0.16; 95% CI 0.03–0.47), and cervical cancer (SIR 0.0; 95% CI 0.00–0.77). Testicular cancer was the only solid tumor with an increased SIR (2.9; 95% CI 1.6–4.8).ConclusionsThe risk of all major groups of solid tumors was decreased, except testicular cancer. Altered screening strategies should be considered for persons with Down syndrome. This unusual pattern of cancer occurrence may help understanding carcinogenesis in the general population.Genet Med 18 11, 1151–1157.     

Mucinous carcinoma of the colon in a 16-year-old Turkish boy with Bloom syndrome: cytogenetic, histopathologic, TP53 gene and protein expression studies.

A 17-year-old Turkish boy with Bloom syndrome (BS) developed mucinous carcinoma of the transverse colon. He was followed from 2 to 17 years of age. Increased sister chromatid exchanges (SCE) were observed, and he was diagnosed with BS at the age of 7. Sun-sensitive skin lesions were examined by skin biopsy, and histopathological studies of these lesions were done. During the follow-up period, an intraabdominal mass at the transverse colon was found, and mucinous carcinoma of colon was diagnosed at the age of 16. We examined TP53 protein expression from paraffin-embedded colon tissue of the patient with an immunohistochemical method. Polymerase chain reaction products of exons 4-9 of the TP53 gene were examined by SSCP. No evidence of overexpression of TP53 protein or mutations of the TP53 gene was observed. The patient in this report is the first case with a mucinous carcinoma of colon diagnosed at an early age in the Bloom Syndrome Registry. Based on our results, carcinoma of the colon in BS patient may occur earlier than 35 years of age and the TP53 gene may not be directly related to carcinoma in Bloom syndrome.     

Gastric cancer in individuals with Li-Fraumeni syndrome

PurposeLi-Fraumeni syndrome is a rare hereditary cancer syndrome associated with germline mutations in the TP53 gene. Although sarcomas, brain tumors, leukemias, breast and adrenal cortical carcinomas are typically recognized as Li-Fraumeni syndrome-associated tumors, the occurrence of gastrointestinal neoplasms has not been fully evaluated. In this analysis, we investigated the frequency and characteristics of gastric cancer in Li-Fraumeni syndrome.MethodsPedigrees and medical records of 62 TP53 mutation-positive families were retrospectively reviewed from the Dana-Farber/National Cancer Institute Li-Fraumeni syndrome registry. We identified subjects with gastric cancer documented either by pathology report or death certificate and performed pathology review of the available specimens.ResultsAmong 62 TP53 mutation-positive families, there were 429 cancer-affected individuals. Gastric cancer was the diagnosis in the lineages of 21 (4.9%) subjects from 14 families (22.6%). The mean and median ages at gastric cancer diagnosis were 43 and 36 years, respectively (range: 24–74 years), significantly younger compared with the median age at diagnosis in the general population based on Surveillance Epidemiology and End Results data (71 years). Five (8.1%) families reported two or more cases of gastric cancer, and six (9.7%) families had cases of both colorectal and gastric cancers. No association was seen between phenotype and type/location of the TP53 mutations. Pathology review of the available tumors revealed both intestinal and diffuse histologies.ConclusionsEarly-onset gastric cancer seems to be a component of Li-Fraumeni syndrome, suggesting the need for early and regular endoscopic screening in individuals with germline TP53 mutations, particularly among those with a family history of gastric cancer.     

Solid variant of papillary thyroid carcinoma: An analysis of 28 cases with current literature

IntroductionSolid variant papillary thyroid cancer (SVPTC) is a rare variant of papillary thyroid carcinoma (PTC) and its prognostic value is still unclear. Therefore, we re-evaluate the histopathological and clinicopathological features of 28 patients with SVPTC in the light of current literature.Material-methodsOf the 1308 cases were previously diagnosed with PTC and 28 (2,1%) of them which had been diagnosed with SVPTC were re-evaluated retrospectively.ResultsOf the 28 patients with SVPTC, 85.7% were female, mean age was 45.18 years and mean tumor diameter was 2.96 cm. Microscopically; tumors had a solid growth pattern amounting to at least 50.0% of the tumor volume. In all cases the tumor cells had characteristic nuclear features of conventional PTC. 11 patients had multifocal tumors, extrathyroidal extension was present in 4 patients and vascular invasion was observed in 7 cases. Regional lymph node metastases were noted in 2 (7.1%) cases at the time of diagnosis. One patient died because of locally advanced disease. Another patient is alive with lung metastases after 48 months from the initial surgery. There was no evidence of local recurrence in other patient.ConclusionsSVPTC is a rare variant of PTC that should be considered in the differential diagnosis of tumors which show a solid/trabecular growth pattern in the thyroid. It has poor prognostic features such as widespread angioinvasion, extrathyroidal extention, lymph node metastasis, and distant organ metastasis. Multicenter studies involving large number of cases are needed to reveal the prognostic significance of SVPTC, with standardized diagnostic criteria.     

Considerations for radiotherapy in Bloom Syndrome: A case series

Bloom Syndrome (BS) is a genetic DNA repair disorder, caused by mutations in the BLM gene. The clinical phenotype includes growth retardation, immunodeficiency and a strong predisposition to different types of malignancies. Treatment of malignancies in BS patients with radiotherapy or chemotherapy is believed to be associated with increased toxicity, but clinical and laboratory data are lacking. We collected clinical data of two Dutch BS patients with solid tumors. Both were treated with radiotherapy before the diagnosis BS was made and tolerated this treatment well. In addition, we collected fibroblasts from BS patients to perform in vitro clonogenic survival assays to determine radiosensitivity. BS fibroblasts showed less radiosensitivity than the severely radiosensitive Artemis fibroblasts. Moreover, studies of double strand break kinetics by counting 53BP1 foci after irradiation showed similar patterns compared to healthy controls. In combination, the clinical cases and laboratory experiments are valuable information in the discussion whether radiotherapy is absolutely contraindicated in BS, which is the Case in other DNA repair syndromes like Ataxia Telangiectasia and Artemis.     

Prognostic and clinicopathological significance of SR-B1 in solid tumors: A meta-analysis

BackgroundThe expression of cell surface receptors is abnormal in malignant tumors. The scavenger receptor class B type I (SR-B1) is an integral membrane glycoprotein receptor that facilitates the selective uptake of cholesterol by malignant cells. Accumulated studies investigated the prognostic role of SR-B1 in many solid tumors, such as breast cancer, lung cancer and so on. However, the conclusions remain undefined. Therefore, we conducted this meta-analysis to obtain more accurate evaluation of prognostic significance of SR-B1 in solid tumors.Materials and methodsWe searched PubMed, Embase, Web of science and Cochrane library for eligible studies published before November 2018. The included studies investigated the association between the SR-B1 level and clinicopathological features including survival outcomes in solid tumors. Hazard ratios (HRs) with 95% confidence intervals (CIs) were adopted to assess the survival outcomes and odds ratio (ORs) with 95% confidence intervals (CIs) were pooled to evaluated the clinicopathological features.ResultsA total of 10 studies involving 2585 patients were included in this meta-analysis. The results showed that low SR-B1 level was significantly correlated with earlier tumor grade (pooled OR = 2.09, 95%CI = 1.28–3.43, P = 0.001), less nodal involvement (pooled OR = 2.07, 95%CI = 1.43–3.0, P < 0.001), less distant metastasis (OR = 19.8, 95%CI = 2.58–151.65, P = 0.004), smaller tumor size (OR = 2.34, 95%CI = 1.53–3.57, P < 0.001), earlier TNM stage (OR = 3.77, 95%CI = 1.67–8.48, P = 0.001), lower recurrence (HR = 1.98, 95%CI = 1.57–2.49, P = 0.000), and better OS (HR = 1.99, 95%CI = 1.70–2.31, P = 0.000).ConclusionThe low expression of SR-B1 was significantly associated with better clinicopathological status and longer survival in patients with solid tumors. SR-B1 might act as a promising prognostic biomarker for solid tumors.     

Clinical outcomes of a genomic screening program for actionable genetic conditions

PurposeThree genetic conditions—hereditary breast and ovarian cancer syndrome, Lynch syndrome, and familial hypercholesterolemia—have tier 1 evidence for interventions that reduce morbidity and mortality, prompting proposals to screen unselected populations for these conditions. We examined the impact of genomic screening on risk management and early detection in an unselected population.MethodsObservational study of electronic health records (EHR) among individuals in whom a pathogenic/likely pathogenic variant in a tier 1 gene was discovered through Geisinger’s MyCode project. EHR of all eligible participants was evaluated for a prior genetic diagnosis and, among participants without such a diagnosis, relevant personal/family history, postdisclosure clinical diagnoses, and postdisclosure risk management.ResultsEighty-seven percent of participants (305/351) did not have a prior genetic diagnosis of their tier 1 result. Of these, 65% had EHR evidence of relevant personal and/or family history of disease. Of 255 individuals eligible to have risk management, 70% (n = 179) had a recommended risk management procedure after results disclosure. Thirteen percent of participants (41/305) received a relevant clinical diagnosis after results disclosure.ConclusionGenomic screening programs can identify previously unrecognized individuals at increased risk of cancer and heart disease and facilitate risk management and early cancer detection.     

Cancer risks by gene,age, and gender in 6350 carriers of pathogenic mismatch repair variants: findings from the Prospective Lynch Syndrome Database

PurposePathogenic variants affecting MLH1, MSH2, MSH6, and PMS2 cause Lynch syndrome and result in different but imprecisely known cancer risks. This study aimed to provide age and organ-specific cancer risks according to gene and gender and to determine survival after cancer.MethodsWe conducted an international, multicenter prospective observational study using independent test and validation cohorts of carriers of class 4 or class 5 variants. After validation the cohorts were merged providing 6350 participants and 51,646 follow-up years.ResultsThere were 1808 prospectively observed cancers. Pathogenic MLH1 and MSH2 variants caused high penetrance dominant cancer syndromes sharing similar colorectal, endometrial, and ovarian cancer risks, but older MSH2 carriers had higher risk of cancers of the upper urinary tract, upper gastrointestinal tract, brain, and particularly prostate. Pathogenic MSH6 variants caused a sex-limited trait with high endometrial cancer risk but only modestly increased colorectal cancer risk in both genders. We did not demonstrate a significantly increased cancer risk in carriers of pathogenic PMS2 variants. Ten-year crude survival was over 80% following colon, endometrial, or ovarian cancer.ConclusionManagement guidelines for Lynch syndrome may require revision in light of these different gene and gender-specific risks and the good prognosis for the most commonly associated cancers.     

Analysis of clinicopathological features and prognosis of 1315 cases in colorectal cancer located at different anatomical subsites

PurposeCompare and analyze the clinicopathological features and prognosis of 1315 patients with colorectal cancer located at different anatomical subsites.MethodsA retrospective study was conducted to analyze the clinicopathological features and prognosis from 1315 patients with colorectal cancer who underwent surgery in the department of gastrointestinal surgery at the Second Affiliated Hospital of Dalian Medical University from January 2013 to January 2019. Among them, 287 patients were divided into the right-sided colon cancer (RCC) group; 329 patients were included into the left-sided colon cancer (LCC) group and the remaining 699 patients were assigned to the rectal cancer (RC) group. Clinicopathological features such as gender, age, pathological differentiation, neurovascular invasion, TNM stage, related tumor markers, maximum tumor diameter (MTD), median survival time and overall survival rate were extracted and analyzed.ResultsPatients in the RCC group had the oldest age of onset, highest positive rate of serum CA199 and greatest number of poorly differentiated adenocarcinomas among the three groups and significant statistical differences were found. The RC group had the highest positive rate of vascular invasion (42.9%) and the greatest number of patients in stage I and IV (19% and 3.9%, respectively). Besides, the number of patients with stage T1-T2 adenocarcinoma in RC group was also the highest among the three groups. There were no significant differences in gender, perineural invasion as well as serum levels of CEA, CA724 and CA242. The median survival time of RCC, LCC and RC were 72, 70 and 73 months, respectively, with significant inter-group differences (P = 0.049).ConclusionThe age of onset of right-sided colon cancer is the oldest on average and poorly differentiated tumors accounted for the highest proportion. Besides, average maximum tumor diameter is the largest in right-sided colon cancer. In terms of median survival time, LCC is worse than RCC and RC. Colorectal cancer at different anatomical subsites has different epidemiological, clinicopathological features and prognosis. Fully understanding the clinicopathological features of colorectal cancer at different anatomical subsites is of certain guiding significance for the clinical diagnosis and treatment of colorectal cancer, and is conducive to individualized treatment and accurate treatment.     

Worldwide prevalence of Lynch syndrome in patients with colorectal cancer: Systematic review and meta-analysis

PurposeLynch syndrome (LS) is the most common hereditary colorectal cancer (CRC) syndrome, with an estimated prevalence of 2% to 3% of CRC. A prevalence study is needed to provide accurate estimates of the true prevalence of LS.MethodsMEDLINE (Ovid), Embase, and Web of Science were searched. Prevalence was calculated by random effects meta-analysis models. I² score was used to assess heterogeneity across studies. Meta-regression was performed for between-study variance.ResultsA total of 51 studies were included in this review. The overall pooled yield of LS screening was 2.2% based on all methods of detection. Studies performing germline tests on all participants with CRC reported higher prevalence (5.1%) as opposed to studies only performing germline tests on participants with tumors with mismatch repair deficiency (1.6%) or microsatellite instability (1.1%). Selected cohorts of CRC had a higher prevalence of germline LS diagnoses.ConclusionLS prevalence across multiple ethnic, geographic, and clinical populations is remarkably similar. Universal germline testing of patients presenting with cancer identifies that most CRCs are attributed to LS. Young patients presenting with CRC and those who fulfill criteria for a familial risk provide the highest returns for LS identification. Our study supports the universal germline CRC screening for LS.     

Risk of cancer in heterozygous relatives of patients with Fanconi anemia

PurposeFanconi anemia (FA) is a cancer-prone inherited bone marrow failure syndrome caused by biallelic pathogenic variants in one of >22 genes in the FA/BRCA DNA repair pathway. A major concern is whether the risk of cancer is increased in individuals with a single pathogenic FA gene variant.MethodsWe evaluated the risk of cancer in the relatives of patients with FA in the National Cancer Institute Inherited Bone Marrow Failure Syndrome cohort. We genotyped all available relatives and determined the rates, types of cancer and the age of patients at cancer diagnosis. We calculated the observed-to-expected (O/E) cancer ratios using data from the Surveillance, Epidemiology, and End Results Program adjusted for age, sex, and birth cohort.ResultsThe risk of cancer was not increased among all FA relatives and FA heterozygotes (O/E ratios of 0.78 and 0.79, respectively). In particular, the risk of cancer was not increased among FANCA or FANCC heterozygotes (O/E ratios of 0.92 and 0.71, respectively). Relatives did not have typical FA cancers, and age at cancer diagnosis was not younger than expected.ConclusionUnderstanding the risk of cancer in individuals with single pathogenic FA variants is critical for counseling and management. We did not find increased risk of cancer in these individuals. These findings do not extend to the known cancer predisposition autosomal dominant FA genes, namely BRCA1, BRCA2, PALB2, BRIP1, and RAD51C.     

The cost of molecular-guided therapy in oncology: a prospective cost study alongside the MOSCATO trial

AimThere is increasing use of molecular technologies to guide cancer treatments, but few cost data are available. Our objective was to assess the costs of molecular-guided therapy for patients with advanced solid tumors alongside the Molecular Screening for Cancer Treatment and Optimization (MOSCATO) trial.Materials and methodsThe study population consisted of 529 patients. The molecular diagnosis included seven steps from tumor biopsy to the multidisciplinary molecular tumor board. The cost of a complete molecular diagnosis was assessed by micro-costing. Direct costs incurred from enrollment until progression were assessed from the French National Health Insurance perspective.ResultsThe patients’ mean age was 54 years (range: 3–82) and the mean follow-up period was 145 days (range: 1–707 days). A complete molecular diagnosis cost €2,396. There were 220 patients with an actionable target (42%), among whom 105 (20%) actually received a targeted therapy. The cost of molecular-guided therapy per patient was €31,269. The main cost drivers were anticancer drugs (54%) and hospitalizations (35%).ConclusionThis prospective cost analysis showed that molecular diagnosis accounts for only 6% of the cost of molecular-guided therapy per patient. The costs of drugs and hospitalizations are the main cost drivers.Genet Med advance online publication 01 December 2016     

Triple negative breast cancer: adjuvant chemotherapy effect on survival

PurposeThe purpose of this study was to evaluate the overall survival of patients with triple negative breast cancer and the impact of different adjuvant chemotherapy regimens on survival.Material/MethodsThe study group consisted of 99 breast cancer patients with immunohistochemically confirmed triple negative breast cancer. The impact of various factors as well as the impact of different chemotherapy regimens on survival was evaluated.ResultsThe overall survival of breast cancer patients was 97.0% (95% CI 90.9–99.0), 84.9% (95% CI 76.1–90.6) and 66.5% (95% CI 55.5–75.3) 10, 30 and 60 months after diagnosis, respectively. Univariate analysis demonstrated that the following were significant risk factors for breast cancer patients survival: patient's age, stage of disease, tumour size, lymph node status, type of surgery and chemotherapy. Better survival was related to younger patients’ age, smaller tumour size, lower stage of disease, no lymph nodes involvement. Survival rates were higher among patients who received adjuvant chemotherapy and underwent quadrantectomy. In the multivariate statistical analysis the significant independent prognostic variables influencing survival were lymph node status and adjuvant chemotherapy. Survival rates of the patients, who received adjuvant anthracycline containing chemotherapy were higher, than those in non-anthracycline containing treatment group, but the difference was not statistically significant.ConclusionPatients who had lymph node status N2–3 and those who did not receive adjuvant chemotherapy showed worse prognosis and survival than other patients. The impact of chemotherapy type (anthracycline containing or non-anthracycline containing) on patients survival was not statistically significant.     

Ethnic differences in patients’ preferences for prostate cancer investigation: a vignette-based survey in primary care

BackgroundMinority ethnic groups in the UK have worse outcomes for some cancer types compared with the white majority. Black males have worse staging at diagnosis of prostate cancer and often present as emergencies, suggesting possible delays in the diagnostic pathway. Delay may arise from lower awareness of cancer symptoms, reluctance to report symptoms, reduced desire for investigation, or a combination of these. Reduced desire for investigation was examined in this studyAimTo investigate whether black males in the UK would choose to be tested for prostate cancer compared with the white majority.MethodThe vignettes described possible prostate cancer symptoms (equating to risk levels of 2%, 5%, and 10%), investigative procedures, and possible outcomes. Participants indicated whether they would choose investigation in these scenarios. Analysis used logistic regression, with preference for investigation as the outcome variable and ethnicity as the main explanatory variable.ResultsIn total, 449 (81%) of 555 participants opted for investigation, regardless of risk levels; of these, the acceptance rate was 94% (251 out of 267) among white males and 70% (198 out of 285) among black males. In multivariable analyses, preference for investigation was lower in black males, even after controlling for relevant confounding factors including specific risk level (odds ratio 0.13; 95% confidence interval = 0.07 to 0.25; P<0.001).ConclusionBlack males are less likely to opt for investigation at any risk level of prostate cancer compared with white males. This may explain some of their late-stage presentation at diagnosis and subsequent poorer outcomes.     

Bloom syndrome does not always present with sun-sensitive facial erythema

Bloom syndrome is an autosomal recessive condition characterized by severe pre- and postnatal growth deficiency, immunodeficiency, an increased risk for malignancies, craniofacial dysmorphisms, and “typical” erythematous sun-sensitive skin lesions of the face. This facial rash has a butterfly-shaped distribution around the nose and is usually observed for the first time during the early years of life. Though reported as being a main feature of Bloom syndrome, there seems to be phenotypic variability regarding this facial skin rash among patients. It has been previously reported that in some individuals with Bloom syndrome these sun-sensitive lesions are less prominent or even absent. In this report we describe a 36 year old woman with short stature, microcephaly, several dysmorphisms, congenital hypothyroidism and premature ovarian failure. She was diagnosed with nasopharyngeal carcinoma at 36 years of age, only a few months after her consultation at the department of Clinical Genetics. Whole Exome Sequencing demonstrated that she had Bloom syndrome caused by a compound heterozygous mutation in BLM (c.2207_2212delinsTAGATTC; p.(Tyr736Leufs*5) and c.3681del; p.(Lys1227Asnfs*52)). She did not have facial sun-sensitive erythematous rash during childhood nor adulthood. We conclude that Bloom syndrome does not always present with erythematous sun-sensitive skin lesions of the face. We would like to underline that phenotypic variation regarding this “hallmark” feature of Bloom syndrome exists. Being aware of this might prevent a delay in diagnosing this rare short-stature syndrome and, subsequently, its potential clinical implications.     

Cancer in the oldest old

Our previous work revealed that 88% of centenarians delay or escape the age-related lethal diseases cardiac disease, stroke and diabetes. In the cases of those having a history of cancer we have observed anecdotes of centenarians presenting with large primary tumors that would have otherwise been expected to have metastasized and to have been lethal. However, these tumors were removed without consequence. To better understand the relationship between cancer and exceptional longevity, we quantified age of cancer diagnoses, life-time clinically evident cancer prevalence, tobacco use and family histories through medical record review and interviews. One thousand one hundred and forty-three subjects were studied revealing 20% (N=152) of female and 22% (N=80) of male centenarians with a history of non-skin cancer. The most common cancers were prostate (11.7% of males), breast (8.2% of females), and colon (5.7%). The average age of diagnosis was 80.5 years compared to 63.2 years in the general population according to National Cancer Institute SEER data. Similar delays were noted when age of onset was examined according to specific type of cancer. In conclusion, the age of diagnosis of cancer is relatively delayed in those who live to 100 years. Some cancers are very rare among these individuals suggesting that there are certain cancers that may be incompatible with survival to extreme old age.     

Early age of onset and broad cancer spectrum persist in MSH6- and PMS2-associated Lynch syndrome

PurposeThis study aimed to characterize MSH6/PMS2-associated mismatch repair–deficient (MMR-D)/microsatellite instability-high (MSI-H) tumors, given revised guidelines suggesting more modest phenotypes.MethodsPatients who consented to Institutional Review Board–approved protocols of tumor/germline sequencing or Lynch syndrome registry at a single institution from February 2005 to January 2021 with germline, heterozygous MSH6/PMS2 pathogenic/likely pathogenic variants were identified. Clinical data were abstracted and correlated with MMR/microsatellite instability status using nonparametric tests.ResultsWe identified 243 patients (133 sequencing, 110 registry) with germline MSH6/PMS2 pathogenic/likely pathogenic variants; 186 (77%) had >1 cancer. Of 261 pooled tumors, colorectal cancer (CRC) and endometrial cancer (EC) comprised 55% and 43% of cancers in MSH6 and PMS2, respectively; 192 tumors underwent molecular assessments and 122 (64%) were MMR-D/MSI-H (77 in MSH6, 45 in PMS2). MMR-D/MSI-H cancers included CRC (n = 56), EC (n = 35), small bowel cancer (n = 6), ovarian cancer (n = 6), urothelial cancer (n = 5), pancreas/biliary cancer (n = 4), gastric/esophageal cancer (n = 3), nonmelanoma skin tumors (n = 3), prostate cancer (n = 2), breast cancer (n = 1), and central nervous system/brain cancer (n = 1). Among MMR-D/MSI-H CRC and EC, median age of diagnosis was 51.5 (range = 27-80) and 55 (range = 39-74) years, respectively; 9 of 56 (16%) MMR-D/MSI-H CRCs were diagnosed at age <35 years.ConclusionMSH6/PMS2 heterozygotes remain at risk for a broad spectrum of cancers, with 16% of MMR-D/MSI-H CRCs presenting before upper threshold of initiation of colonoscopy per guidelines.     

Patients with colorectal cancer associated with Lynch syndrome and MLH1 promoter hypermethylation have similar prognoses

PurposeMismatch repair–deficient (dMMR) colorectal cancer (CRC) is caused by Lynch syndrome (LS) in 3% and sporadic inactivation of MLH1 by hypermethylation (MLH1-hm) in 12% of cases. It is not clear whether outcomes between LS-associated and MLH1-hm CRC differ. The objective of this study was to explore differences in clinical factors and outcomes in these two groups.MethodsPatients with dMMR CRC identified by immunohistochemistry staining and treated at a single institution from 1998 to 2012 were included. MLH1-hm was established with BRAF mutational analysis or hypermethylation testing. Patients’ charts were accessed for information on pathology, germ-line MMR mutation testing, and clinical course.ResultsA total of 143 patients had CRC associated with LS (37 patients, 26%) or MLH1-hm (106 patients, 74%). Patients with LS were younger, more often male, presented more often with stage III disease, and had more metachronous disease than patients with MLH1-hm tumors. There was no difference in cancer-specific survival (CSS) between the groups; overall survival was longer in patients with LS, but this difference was minimal after adjusting for age and stage at diagnosis.ConclusionCSS did not differ in LS-associated CRC compared with MLH1-hm CRC, suggesting that they carry a similar prognosis.Genet Med 18 9, 863–868.     

Muir Torre syndrome: a case report

Muir Torre Syndrome (MTS) is a rare syndrome complex of association of multiple sebaceous skin tumors with visceral malignancies. Till date a total of 205 cases have been reported in the world literature and to the best of our knowledge this is the first case report from the Indian subcontinent. Multiple, synchronous and metachronous, tiny sebaceous lesions is a hallmark of MTS along with multiple primary carcinomas at different sites, the commonest being gastro-intestinal tract cancers. The visceral cancers occur at a relatively young age. They are low-grade, non-aggressive and have a good prognosis. Awareness of this rare entity is essential. A case report of a 55-year-old male presenting with multiple sebaceous skin tumors, colonic cancer and positive family history in younger brother is presented.