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Medicina 2024Multiple Endocrine Neoplasia type 1 (MEN1) is an autosomal dominant inherited disease with an estimated prevalence of 2-10:100 000. The main locations of tumors are...
INTRODUCTION
Multiple Endocrine Neoplasia type 1 (MEN1) is an autosomal dominant inherited disease with an estimated prevalence of 2-10:100 000. The main locations of tumors are parathyroid glands (HPT), gastroenteropancreatic tract (GEPT), and anterior pituitary gland (PT). The aim of our investigation was to describe the phenotype and genotype of Argentinian patients with MEN1.
METHODS
A total of 68 index patients diagnosed with at least two of the three main tumors or one tumor and a relative with MEN1, and 84 first-degree relatives were studied. We sequenced the coding region (exons 2-10); the promoter, exon 1; and the flanking intronic regions of the MEN1 gene, following the Sanger method. We used MLPA in index patients without mutation.
RESULTS
Prevalence of tumors: HPT 87.5%, GEPT 49% (p< 0.001). No statistical differences in the prevalence of HPT vs. PT (68%). Prevalence of pathogenic variants: 90% in familial cases and 51% in sporadic cases. Of the different 36 pathogenic variants, 13 (36.2%) were frameshift micro-rearrangement, 8 (22.2%) were missense, 9 (25%) were nonsense, 3 (8.3%) were mutations in splicing sites, 2 (5.5%) were large deletions and, 1 in-frame micro-rearrangement. We found 7 novel pathogenic variants. Thirty-nine percent (n = 33) of first-degree relatives of 23 families were found to be mutation carriers.
CONCLUSION
The phenotype and genotype of Argentinian patients was similar to other MEN1 populations. A high frequency of PT and the identification of seven novel mutations are underscored.
Topics: Humans; Argentina; Male; Multiple Endocrine Neoplasia Type 1; Phenotype; Female; Adult; Genotype; Middle Aged; Adolescent; Young Adult; Child; Aged; Mutation; Child, Preschool; Parathyroid Neoplasms; Proto-Oncogene Proteins
PubMed: 38907957
DOI: No ID Found -
Cancer Epidemiology Jun 2024Serrated lesions and polyps (SP) are precursors of up to 30 % of colorectal cancers (CRC) through the serrated pathway. This often entails early BRAF mutations and...
BACKGROUND
Serrated lesions and polyps (SP) are precursors of up to 30 % of colorectal cancers (CRC) through the serrated pathway. This often entails early BRAF mutations and MLH1 hypermethylation leading to mismatch repair deficient (dMMR) CRC. We investigated predictors of dMMR CRC among patients with co-occurrence of CRC and SP to increase our knowledge on the serrated pathway.
METHODS
We used data from The Danish Pathology Registry and Danish Colorectal Cancer Groups Database from the period 2010-2021 to investigate risk factors for development of dMMR CRC. We used logistic regression models to identify difference in risk factors of developing dMMR CRC in comparison to CRC with proficient MMR (pMMR).
RESULTS
We included 3273 patients with a median age of 70.7 years [64.3,76.4] of which 1850 (56.5 %) were male. dMMR CRC was present in 592 patients (18.1 %), with loss of MLH1/PMS2 being most common. The risk of dMMR CRC was significantly higher in females OR 3.47 [2.87;4.20]. When adjusting for age, SP subtype, conventional adenomas (CA), anatomical location and lifestyle factors, female sex remained the strongest predictor OR 2.84 [2.27;3.56]. The presence of sessile serrated lesions with or without dysplasia was related to higher risk OR 1.60 [1.11;2.31] and OR 1.42 [1.11;1.82] respectively, while conventional adenomas constituted a lower risk OR 0.68 [0.55;0.84].
CONCLUSION
In conclusion we found several predictors of whom female sex had the strongest correlation with dMMR CRC in patients with SP.
PubMed: 38905781
DOI: 10.1016/j.canep.2024.102601 -
Endoscopy International Open Jun 2024Real-time visualization of red blood cell flow inside subepithelial microvessels is performed with magnifying endoscopy. However, microvascular blood flow velocity in...
Real-time visualization of red blood cell flow inside subepithelial microvessels is performed with magnifying endoscopy. However, microvascular blood flow velocity in the colorectum has not been investigated. Here, we aimed to evaluate the blood flow velocity of microvessels of colonic polyps and to compare it with that of surrounding mucosa. We examined 50 lesions, including 30 adenomas (ADs) and 20 hyperplastic polyps (HPs). Blood flow velocities of lesions and their surrounding mucosa were evaluated using magnifying blue laser imaging (BLI) prior to endoscopic resection. Calculation of mean blood flow velocities was based on mean movement distance of one tagged red blood cell using split video images of magnifying BLI. Mean microvascular blood flow velocity was significantly lower in ADs (1.65±0.66 mm/sec; range 0.46-2.90) than in HPs (2.83±1.10 mm/sec; 1.07-4.50) or the surrounding mucosa (3.73±1.11 mm/sec; 1.80-6.20; <0.001). The blood flow velocity rate compared with the surrounding mucosa was significantly lower in ADs (0.41±0.16; 0.10-0.82) than in HPs (0.89±0.25; 0.46-1.51; <0.001). We found that mean microvascular blood flow velocity was significantly lower in ADs than in HPs and the surrounding non-neoplastic mucosa. These findings indicate that a novel dynamic approach with microvascular blood flow velocity using magnifying endoscopy may be useful in assessing physiological differences between ADs and HPs.
PubMed: 38904061
DOI: 10.1055/a-2306-9218 -
Endoscopy International Open Jun 2024There is limited consensus on the optimal method for measuring disease severity in familial adenomatous polyposis (FAP). We aimed to systematically review the operating... (Review)
Review
There is limited consensus on the optimal method for measuring disease severity in familial adenomatous polyposis (FAP). We aimed to systematically review the operating properties of existing endoscopic severity indices for FAP. We searched MEDLINE, EMBASE, and the Cochrane Library from inception to February 2023 to identify randomized controlled trials (RCTs) that utilized endoscopic outcomes or studies that evaluated the operating properties of endoscopic disease severity indices in FAP. A total of 134 studies were included. We evaluated scoring indices and component items of scoring indices, such as polyp count, polyp size, and histology. Partial validation was observed for polyp count and size. The most commonly reported scoring index was the Spigelman classification system, which was used for assessing the severity of duodenal involvement. A single study reported almost perfect interobserver and intra-observer agreement for this system. The InSIGHT polyposis staging system, which was used for assessing colorectal polyp burden, has been partially validated. It showed substantial interobserver reliability; however, the intra-observer reliability was not assessed. Novel criteria for high-risk gastric polyps have been developed and assessed for interobserver reliability. However, these criteria showed a poor level of agreement. Other scoring indices assessing the anal transition zone, duodenal, and colorectal polyps have not undergone validation. There are no fully validated endoscopic disease severity indices for FAP. Development and validation of a reliable and responsive endoscopic disease severity instrument will be informative for clinical care and RCTs of pharmacological therapies for FAP.
PubMed: 38904059
DOI: 10.1055/a-2330-8037 -
Journal of Multidisciplinary Healthcare 2024This study aimed to develop and validate a nomogram for predicting positive colonoscopy results using the data from non-invasive screening strategies.
PURPOSE
This study aimed to develop and validate a nomogram for predicting positive colonoscopy results using the data from non-invasive screening strategies.
METHODS
The volunteers participated in primary colorectal cancer (CRC) screenings using Asia-Pacific colorectal screening (APCS) scoring, faecal immunochemical testing (FIT) and stool deoxyribonucleic acid (sDNA) testing and underwent a colonoscopy. The positive colonoscopy results included CRC, advanced adenoma (AA), high-grade intraepithelial neoplasia (HGIN), and low-grade intraepithelial neoplasia (LGIN). The enrolled participants were randomly selected for training and validation sets in a 7:3 ratio. A model for predicting positive colonoscopy results was virtualized by the nomogram using logistic regression analysis.
RESULTS
Among the 179 enrolled participants, 125 were assigned to training set, while 54 were assigned to validation set. After multivariable logistic regression was done, APCS score, FIT result, and sDNA result were all identified as the predictors for positive colonoscopy results. A model that incorporated the above independent predictors was developed and presented as a nomogram. The C-index of the nomogram in the validation set was 0.768 (95% CI, 0.644-0.891). The calibration curve demonstrated a good agreement between prediction and observation. The decision curve analysis (DCA) curve showed that the model achieved a net benefit across all threshold probabilities. The AUC of the prediction model for predicting positive colonoscopy results was much higher than that of the FIT + sDNA test scheme.
CONCLUSION
The nomogram for predicting positive colonoscopy results was successfully developed based on 3 non-invasive screening tools (APCS scoring, FIT and sDNA test).
PubMed: 38903878
DOI: 10.2147/JMDH.S465286 -
Frontiers in Oncology 2024Malignant melanoma of the parotid gland is an unusual tumor in the head and neck region, and most parotid melanoma is reported as a metastatic lesion of cutaneous...
Malignant melanoma of the parotid gland is an unusual tumor in the head and neck region, and most parotid melanoma is reported as a metastatic lesion of cutaneous malignant melanoma. We report a case of primary malignant melanoma arising in the parotid gland duct with diagnostic challenge. The patient was a 68-year-old man who complained of repeated right facial swelling that presented 3 months prior. Swelling was detected along the Stensen's duct of the cheek, and brown-colored saliva-like fluid was aspirated. On MR and CT images, a fluid-filled duct with small nodule and heterogeneously enhancing mass in the parotid parenchyma was detected. The nodular mass on the ductal wall grew rapidly, and the hyperintense T1 signal became significant on follow-up images. The final diagnosis via histopathologic examination using biopsy and parotidectomy specimen revealed the lesion as malignant melanoma of the duct and pleomorphic adenoma of the parenchyma. Even if the incidence of primary malignant melanoma is very low among tumors occurring in the parotid gland, efforts supporting an early diagnosis using imaging characteristics are important.
PubMed: 38903720
DOI: 10.3389/fonc.2024.1324214 -
Cureus May 2024Abernethy syndrome is a rare congenital anomaly characterized by an intrahepatic or extrahepatic portosystemic shunt. Most patients are asymptomatic; however, due to the...
Abernethy syndrome is a rare congenital anomaly characterized by an intrahepatic or extrahepatic portosystemic shunt. Most patients are asymptomatic; however, due to the alteration in, or lack of, a portovenous flow, patients with Abernethy syndrome are at high risk of developing sequelae of liver failure. Once these complications develop, the only definitive treatment is transplantation. Patients with Abernethy syndrome are also at a higher risk of developing benign and malignant liver lesions, including hepatic adenomas. Here, we describe the first case of deceased donor liver transplantation as a treatment for a patient with type 1 Abernethy syndrome complicated by large, unresectable hepatic adenoma, found to have focal hepatocellular carcinoma on pathologic examination. Our male patient was found to have elevated liver enzymes at age 33, during a routine outpatient medical appointment. Despite being asymptomatic, his history of prior liver resection prompted CT imaging, which revealed two large liver lesions concerning for hepatic adenomas. When surveillance imaging showed a significant growth of the liver lesions, biopsy was pursued, which confirmed a diagnosis of hepatic adenomas. However, given the size of these lesions, resection was not a viable option for the patient. Instead, the patient underwent liver transplantation at age 41, which he tolerated well. Our case demonstrates the utility of deceased donor liver transplantation as a treatment for patients with Abernethy syndrome complicated by unresectable adenomas.
PubMed: 38903310
DOI: 10.7759/cureus.60683 -
Clinical Endoscopy Jun 2024During endoscopy, white spots (WS) are sometimes observed around benign or malignant colorectal tumors; however, few reports have investigated WS, and their significance...
BACKGROUND/AIMS
During endoscopy, white spots (WS) are sometimes observed around benign or malignant colorectal tumors; however, few reports have investigated WS, and their significance remains unknown. Therefore, we investigated the significance of WS from clinical and pathological viewpoints and evaluated its usefulness in endoscopic diagnosis.
METHODS
Clinical data of patients with lesions diagnosed as epithelial tumors from January 1, 2019, to December 31, 2020, were analyzed (n=3,869). We also performed a clinicopathological analysis of adenomas or carcinomas treated with endoscopic resection (n=759). Subsequently, detailed pathological observations of the WS were performed.
RESULTS
The positivity rates for WS were 9.3% (3,869 lesions including advanced cancer and non-adenoma/carcinoma) and 25% (759 lesions limited to adenoma and early carcinoma). Analysis of 759 lesions showed that the WS-positive lesion group had a higher proportion of cancer cases and larger tumor diameters than the WS-negative group. Multiple logistic analysis revealed the following three statistically significant risk factors for carcinogenesis: positive WS, flat lesions, and tumor diameter ≥5 mm. Pathological analysis revealed that WS were macrophages that phagocytosed fat and mucus and were white primarily because of fat.
CONCLUSIONS
WS are cancer-related findings and can become a new criterion for endoscopic resection in the future.
PubMed: 38902852
DOI: 10.5946/ce.2024.027 -
Journal of Cardiothoracic Surgery Jun 2024Pulmonary papillary adenoma is an extremely rare benign tumor. It is derived from type II lung cells and club cells, suggesting that it may originate from stem cells... (Review)
Review
OBJECTIVE
Pulmonary papillary adenoma is an extremely rare benign tumor. It is derived from type II lung cells and club cells, suggesting that it may originate from stem cells with two-way differentiation. Only one case has been reported with FGFR2-IIIb overexpression.
METHODS
Two cases of pulmonary papillary adenoma with available data on clinical features, histological morphology, immunophenotype and molecular characteristics were analyzed.
RESULTS
Both tumors were well-circumscribed unencapsulated nodules composed of papillary structures with fibrovascular cores lined by a single layer of cuboidal or columnar epithelium without necrosis, nuclear atypia and mitoses, or invasion. But malignant transformation features include complex branching structures and significantly enlarged, irregular, and crowded malignant cells in one case. Immunohistochemistry showed that the tumor cells were strongly positive for TTF1, NapsinA, EMA and CK7 and negative for CEA and P63, with a low Ki-67 proliferation index. The EGFR somatic mutation exon19:c.2236_2256delinsATC (p.E746_S752delinsI) was found in one case by next-generation sequencing (NGS) technology.
CONCLUSION
Pulmonary papillary adenoma is very rare. Virtually all papillary adenomas are clinically silent and discovered incidentally. They are benign tumors, and resection is curative. An EGFR 19 exon deletion mutation in a patient with this tumor type was detected for the first time by NGS, and our results suggest that the malignant transformation of pulmonary papillary adenoma may be mediated by EGFR mutation.
Topics: Humans; Adenoma; ErbB Receptors; Immunohistochemistry; Lung Neoplasms; Mutation
PubMed: 38902753
DOI: 10.1186/s13019-024-02852-2 -
BMC Endocrine Disorders Jun 2024An increase of IGF-1 has been reported during therapy with dopamine agonists (DA) for prolactinomas; in such cases a correct diagnosis is pivotal to avoid an unnecessary...
PURPOSE
An increase of IGF-1 has been reported during therapy with dopamine agonists (DA) for prolactinomas; in such cases a correct diagnosis is pivotal to avoid an unnecessary reduction or withdrawal of DA, which are needed to maintain normal prolactin levels. This study was aimed to measure IGF-1 levels, at baseline and during follow-up, in a cohort of patients with prolactinoma, treated with cabergoline, stratified by body mass index.
METHODS
We retrospectively enrolled 35 patients (15 F/20 M; age m ± SD, years: 43.4 ± 13.7) with prolactinoma (21 microadenomas and 14 macroadenomas) who were followed-up at the Endocrinology Unit, in Siena, and with available pituitary hormone assessment at baseline and during follow-up (m ± SD, years: 2.74 ± 0.55).
RESULTS
IGF-1 increased in the whole cohort, but remaining within normal range, except two patients, in whom acromegaly was ruled out with oral glucose tolerance test. After dividing patients by weight, this trend was confirmed only in subjects with overweight and obesity (OV/OB) (p = 0.04). Interestingly, the reduction of prolactin levels was significantly greater in the OV/OB compared to normal-weight patients (median decrease of 97.5% versus 88.2%, p = 0.04).
CONCLUSIONS
Since DA and normalization of prolactin are known to improve insulin sensitivity, we speculated they have favored the increase of IGF-1 in OV/OB. Our results should be confirmed and the hypothesis proven by further studies.
Topics: Humans; Prolactinoma; Insulin-Like Growth Factor I; Female; Male; Adult; Retrospective Studies; Dopamine Agonists; Pituitary Neoplasms; Middle Aged; Cabergoline; Body Weight; Follow-Up Studies; Prolactin; Body Mass Index; Prognosis
PubMed: 38902646
DOI: 10.1186/s12902-024-01622-4