PTEN hamartoma tumour syndrome: case report based on data from the Iranian hereditary colorectal cancer registry and literature review.

BACKGROUND: PTEN hamartoma tumour syndrome (PHTS) is a rare hereditary disorder caused by germline pathogenic mutations in the PTEN gene. This study presents a case of PHTS referred for genetic evaluation due to multiple polyps in the rectosigmoid area, and provides a literature review of PHTS case reports published between March 2010 and March 2022. CASE PRESENTATION: A 39-year-old Iranian female with a family history of gastric cancer in a first-degree relative presented with minimal bright red blood per rectum and resistant dyspepsia. Colonoscopy revealed the presence of over 20 polyps in the rectosigmoid area, while the rest of the colon appeared normal. Further upper endoscopy showed multiple small polyps in the stomach and duodenum, leading to a referral for genetic evaluation of hereditary colorectal polyposis. Whole-exome sequencing led to a PHTS diagnosis, even though the patient displayed no clinical or skin symptoms of the condition. Further screenings identified early-stage breast cancer and benign thyroid nodules through mammography and thyroid ultrasound. METHOD AND RESULTS OF LITERATURE REVIEW: A search of PubMed using the search terms "Hamartoma syndrome, Multiple" [Mesh] AND "case report" OR "case series" yielded 43 case reports, predominantly in women with a median age of 39 years. The literature suggests that patients with PHTS often have a family history of breast, thyroid and endometrial neoplasms along with pathogenic variants in the PTEN/MMAC1 gene. Gastrointestinal polyps are one of the most common signs reported in the literature, and the presence of acral keratosis, trichilemmomas and mucocutaneous papillomas are pathognomonic characteristics of PHTS. CONCLUSION: When a patient presents with more than 20 rectosigmoid polyps, PHTS should be considered. In such cases, it is recommended to conduct further investigations to identify other potential manifestations and the phenotype of PHTS. Women with PHTS should undergo annual mammography and magnetic resonance testing for breast cancer screening from the age of 30, in addition to annual transvaginal ultrasounds and blind suction endometrial biopsies.

Geospatial epidemiology of hospitalized patients with a positive influenza assay: A nationwide study in Iran, 2016-2018.

INTRODUCTION: Seasonal influenza is a significant public health challenge worldwide. This study aimed to investigate the epidemiological characteristics and spatial patterns of severe hospitalized influenza cases confirmed by polymerase chain reaction (PCR) in Iran. METHODS: Data were obtained from Iran's Ministry of Health and Medical Education and included all hospitalized lab-confirmed influenza cases from January 1, 2016, to December 30, 2018 (n = 9146). The Getis-Ord Gi* and Local Moran's I statistics were used to explore the hotspot areas and spatial cluster/outlier patterns of influenza. We also built a multivariable logistic regression model to identify covariates associated with patients' mortality. RESULTS: Cumulative incidence and mortality rate were estimated at 11.44 and 0.49 (per 100,000), respectively, and case fatality rate was estimated at 4.35%. The patients' median age was 40 (interquartile range: 22-63), and 55.5% (n = 5073) were female. The hotspot and cluster analyses revealed high-risk areas in northern parts of Iran, especially in cold, humid, and densely populated areas. Moreover, influenza hotspots were more common during the colder months of the year, especially in high-elevated regions. Mortality was significantly associated with older age (adjusted odds ratio [aOR]: 1.01, 95% confidence interval [CI]: 1.01-1.02), infection with virus type-A (aOR: 1.64, 95% CI: 1.27-2.15), male sex (aOR: 1.77, 95% CI: 1.44-2.18), cardiovascular disease (aOR: 1.71, 95% CI: 1.33-2.20), chronic obstructive pulmonary disease (aOR: 1.82, 95% CI: 1.40-2.34), malignancy (aOR: 4.77, 95% CI: 2.87-7.62), and grade-II obesity (aOR: 2.11, 95% CI: 1.09-3.74). CONCLUSIONS: We characterized the spatial and epidemiological heterogeneities of severe hospitalized influenza cases confirmed by PCR in Iran. Detecting influenza hotspot clusters could inform prioritization and geographic specificity of influenza prevention, testing, and mitigation resource management, including vaccination planning in Iran.

Colorectal Cancer in North-Eastern Iran: a retrospective, comparative study of early-onset and late-onset cases based on data from the Iranian hereditary colorectal cancer registry.

BACKGROUND: The incidence rate of colorectal cancer (CRC) is increasing among patients below 50 years of age. The reason for this is unclear, but could have to do with the fact that indicative variables, such as tumour location, gender preference and genetic preponderance have not been followed up in a consistent mann er. The current study was primarily conducted to improve the hereditary CRC screening programme by assessing the demographic and clinicopathological characteristics of early-onset CRC compared to late-onset CRC in northeast Iran. METHODS: This retrospective study, carried out over a three-year follow-up period (2014-2017), included 562 consecutive CRCs diagnosed in three Mashhad city hospital laboratories in north-eastern Iran. We applied comparative analysis of pathological and hereditary features together with information on the presence of mismatch repair (MMR) gene deficiency with respect to recovery versus mortality. Patients with mutations resulting in absence of the MMR gene MLH1 protein product and normal BRAF status were considered to be at high risk of Lynch syndrome (LS). Analyses using R studio software were performed on early-onset CRC (n = 222) and late-onset CRC (n = 340), corresponding to patients ≤50 years of age and patients > 50 years. RESULTS: From an age-of-onset point of view, the distribution between the genders differed with females showing a higher proportion of early-onset CRC than men (56% vs. 44%), while the late-onset CRC disparity was less pronounced (48% vs. 52%). The mean age of all participants was 55.6 ± 14.8 years, with 40.3 ± 7.3 years for early-onset CRC and 65.1 ± 9.3 years for late-onset CRC. With respect to anatomical tumour location (distal, rectal and proximal), the frequencies were 61, 28 and 11%, respectively, but the variation did not reach statistical significance. However, there was a dramatic difference with regard to the history of CRC in second-degree relatives between two age categories, with much higher numbers of family-related CRCs in the early-onset group. Expression of the MLH1 and PMS2 genes were significantly different between recovered and deceased, while this finding was not observed with regard to the MSH6 and the MSH2 genes. Mortality was significantly higher in those at high risk of LS. CONCLUSION: The variation of demographic, pathological and genetic characteristics between early-onset and late-onset CRC emphasizes the need for a well-defined algorithm to identify high-risk patients.