-
American Journal of Respiratory and... Nov 2019Lethal lung developmental disorders are a rare but important group of pediatric diffuse lung diseases presenting with neonatal respiratory failure. On the basis of... (Review)
Review
Lethal lung developmental disorders are a rare but important group of pediatric diffuse lung diseases presenting with neonatal respiratory failure. On the basis of histopathological appearance at lung biopsy or autopsy, they have been termed: alveolar capillary dysplasia with misalignment of the pulmonary veins, acinar dysplasia, congenital alveolar dysplasia, and other unspecified primary pulmonary hypoplasias. However, the histopathological continuum in these lethal developmental disorders has made accurate diagnosis challenging, which has implications for recurrence risk. Over the past decade, genetic studies in infants with alveolar capillary dysplasia with misalignment of the pulmonary veins have revealed the causative role of the dosage-sensitive gene and its noncoding regulatory variants in the distant lung-specific enhancer at chromosome 16q24.1. In contrast, the molecular bases of acinar dysplasia and congenital alveolar dysplasia have remained poorly understood. Most recently, disruption of the TBX4-FGF10-FGFR2 epithelial-mesenchymal signaling pathway has been reported in patients with these lethal pulmonary dysplasias. Application of next-generation sequencing techniques, including exome sequencing and whole-genome sequencing, has demonstrated their complex compound inheritance. These data indicate that noncoding regulatory elements play a critical role in lung development in humans. We propose that for more precise lethal lung developmental disorder diagnosis, a diagnostic pathway including whole-genome sequencing should be implemented.
Topics: Humans; Lung; Lung Diseases
PubMed: 31189067
DOI: 10.1164/rccm.201903-0495TR -
Indian Dermatology Online Journal 2024Ectodermal dysplasias are a heterogeneous group of disorders that are characterized by abnormal development of ectodermal structures like hair, teeth, nails, and sweat... (Review)
Review
Ectodermal dysplasias are a heterogeneous group of disorders that are characterized by abnormal development of ectodermal structures like hair, teeth, nails, and sweat glands. Alhough they were earlier classified according to the structures affected and hence the clinical manifestations, recent developments inch towards a genetic basis for classification. They are currently divided into four groups of disorders based on the pathway involved, which includes the ectodysplasin/nuclear factor-kappa B (NFKB) pathway, wingless-type MMTV integration site family, member 10 ([wingless related integration site] WNT10), tumor protein p63 (TP63), and the structural group. In spite of attempts at the segregation of the various disorders, there is a great degree of overlap in clinical features among the conditions, which makes a thorough history-taking and clinical examination important in helping us arrive at a diagnosis and judge the various systems involved. A multidisciplinary approach forms the crux of the management of patients with ectodermal dysplasias and their families, with a focus on education, counseling, prosthesis, and an overall rehabilitative outlook. Special attention must also be paid to screening family members for varying severities of the disorders, and an attempt must be made at a genetic diagnosis with genetic counseling.
PubMed: 38845644
DOI: 10.4103/idoj.idoj_599_23 -
Medicina Oral, Patologia Oral Y Cirugia... Jul 2022Actinic cheilitis is a potentially malignant lesion most commonly found in the lower lip of individuals with chronic exposure to ultraviolet radiation. The aim of this...
BACKGROUND
Actinic cheilitis is a potentially malignant lesion most commonly found in the lower lip of individuals with chronic exposure to ultraviolet radiation. The aim of this study was to develop and to test a clinical index that can be used to assess the severity of actinic cheilitis.
MATERIAL AND METHODS
The clinical index of actinic cheilitis was applied to 36 patients. An incisional biopsy was obtained to grade oral epithelial dysplasias following the World Health Organization (WHO) and binary systems, and to evaluate their association with clinical characteristics by Fisher's exact test (P<0.05). The accuracy of the index was evaluated based on sensitivity, specificity, positive and negative predictive values, and receiver operating curve.
RESULTS
The blurring between the border of the lip and the skin was significantly associated with cases without dysplasia/mild epithelial dysplasia (P=0.041) and with low risk of malignancy (P=0.005). Ulcers and crusts were significantly associated with moderate/severe epithelial dysplasia (P=0.002 and P=0.012, respectively) and high risk of malignancy (P=0.005 and P=0.045, respectively). Erosion showed a significant association only with high-risk cases of malignancy (P=0.024). The cut-off values of the diagnostic test showing the best performance were 10 for the WHO grading system and 11 for the binary system.
CONCLUSIONS
The index cut-offs with the highest accuracy were considered indicators for a biopsy. Erosion, ulceration and crusts were associated with more severe oral epithelial dysplasias.
Topics: Cheilitis; Humans; Hyperplasia; Lip; Lip Neoplasms; Ultraviolet Rays
PubMed: 35660729
DOI: 10.4317/medoral.25243 -
Current Reviews in Musculoskeletal... Feb 2020The purpose of this manuscript is to 1 define the features associated with borderline acetabular dysplasia and 2 review current status of diagnostic algorithms and... (Review)
Review
PURPOSE OF REVIEW
The purpose of this manuscript is to 1 define the features associated with borderline acetabular dysplasia and 2 review current status of diagnostic algorithms and treatment options for borderline dysplasia.
RECENT FINDINGS
Acetabular dysplasia is a common cause of hip pain secondary to insufficient coverage of the femoral head by the bony acetabulum. Historical classification of acetabular dysplasia has utilized the lateral center edge angle (LCEA); values above 25° are normal and below 20° are considered pathologic. Borderline dysplasia describes hips with LCEA between 20 and 25; treatment of these patients is controversial. While many studies utilize LCEA in classification of borderline dysplasia, isolated reliance on measurement of lateral femoral head coverage to define severity of undercoverage will continue to mislabel morphology. Thorough assessment of the characteristics of mild acetabular undercoverage is necessary for future studies, which will allow effective comparisons of results between hip arthroscopy and periacetabular osteotomy.
PubMed: 32030604
DOI: 10.1007/s12178-020-09599-y -
Cureus Oct 2023Ectodermal dysplasia (ED) is a rare genetic disorder that affects the developmental disturbance of ectoderm-derived tissues, organs, and accessory appendages, i.e. skin,...
Ectodermal dysplasia (ED) is a rare genetic disorder that affects the developmental disturbance of ectoderm-derived tissues, organs, and accessory appendages, i.e. skin, hair, tooth, nail, and sweat glands. ED has two types hypohidrotic or anhidrotic ectodermal dysplasia and hidrotic ectodermal dysplasia. We report this case of classical hypohidrotic ectodermal dysplasia (HED) with clubbing. The association of clubbing with HED is still rare. This case report aims to discuss the etiology, clinical manifestations, and management of ectodermal dysplasia. A multidisciplinary approach is required including dentists, nutritionists, dermatologists, and physicians to manage ectodermal dysplasia.
PubMed: 37927739
DOI: 10.7759/cureus.46530 -
Orthopaedic Journal of Sports Medicine Feb 2022Patients with borderline acetabular dysplasia are a controversial patient population in hip preservation, as some have primarily impingement-based symptoms and others... (Review)
Review
BACKGROUND
Patients with borderline acetabular dysplasia are a controversial patient population in hip preservation, as some have primarily impingement-based symptoms and others have instability-based symptoms. Borderline dysplasia is most commonly defined as a lateral center-edge angle (LCEA) of 20° to 25°. However, its prevalence has not been well established in the literature.
PURPOSE
To (1) define the prevalence of borderline hip dysplasia in the general population as well as in populations presenting with hip pain using a systematic review and meta-analysis of the literature and (2) describe differences between male and female patients as well as differences in prevalence from that of classic acetabular dysplasia.
STUDY DESIGN
Systematic review; Level of evidence, 3.
METHODS
A systematic review of the literature was performed using search terms to capture borderline dysplasia, or studies reporting prevalence by LCEA. The search yielded 1932 results, of which 11 articles met inclusion criteria and were included in the final systematic review. Studies were grouped by patient cohort as (1) asymptomatic general population, (2) asymptomatic targeted population (eg, athletes in a specific sport), and (3) symptomatic hip pain population. The reporting of prevalence rates by subject or by hip was recorded. In a study, the rates of borderline dysplasia were compared with those of classic acetabular dysplasia (LCEA, <20°).
RESULTS
The 11 studies included 19,648 hips (11,754 patients). In the asymptomatic general population, the pooled estimate of the prevalence of borderline dysplasia was 19.8% by subject and 23.3% by hip (range, 16.7%-46.0%). The targeted subpopulation group included 236 athletes with subgroups in ballet, football, hockey, volleyball, soccer, and track and field with prevalence ranging from 17.8% to 51.1%. The prevalence of borderline dysplasia in groups presenting with hip pain was 12.8% (range, 12.6%-16.0%). Borderline acetabular dysplasia was 3.5 times more common than classic acetabular dysplasia in the asymptomatic general population.
CONCLUSION
This study demonstrated a prevalence of borderline dysplasia of 19.8% to 23.3% in the asymptomatic general population. Additionally, an estimated prevalence of 12.8% of hips in symptomatic patients highlights the common decision-making challenges in this population.
PubMed: 35155698
DOI: 10.1177/23259671211040455 -
Clinics in Colon and Rectal Surgery Jan 2024Given the chronic nature of mucosal inflammation present in patients with inflammatory bowel disease (IBD), there is a high risk of dysplastic lesions progressing to... (Review)
Review
Given the chronic nature of mucosal inflammation present in patients with inflammatory bowel disease (IBD), there is a high risk of dysplastic lesions progressing to cancer, in addition to a high risk of synchronous and/or metachronous cancers developing in those diagnosed with dysplasia. Due to this, consensus guidelines recommend regular surveillance. When visible dysplasia is encountered, options include endoscopic or surgical resection depending on characteristics of the lesion. Advancements in endoscopic tools increasingly allow for endoscopic removal when appropriate. Invisible dysplasia discovered on random biopsy should prompt referral to physicians who specialize in IBD. While surgical resection with proctocolectomy significantly decreases the risk of colorectal cancer, the risk must be balanced against the morbidity of surgery and quality-of-life concerns. Management of dysplasia in IBD patients requires complex decision-making that requires balance of patient values and goals of care with cancer-related risk factors.
PubMed: 38188069
DOI: 10.1055/s-0043-1762559 -
The Korean Journal of Internal Medicine May 2023Some sessile serrated lesions (SSLs) progress into dysplasia and colorectal cancer, however, the clinical and endoscopic characteristics of SSLs with dysplasia remain to...
BACKGROUND/AIMS
Some sessile serrated lesions (SSLs) progress into dysplasia and colorectal cancer, however, the clinical and endoscopic characteristics of SSLs with dysplasia remain to be determined. In this study, we elucidated these characteristics in SSLs with dysplasia/carcinoma, compared with those of SSLs without dysplasia.
METHODS
We retrospectively collected the clinical, endoscopic, and pathological data of 254 SSLs from 216 patients endoscopically resected between January 2009 and December 2020.
RESULTS
All SSLs included 179 without dysplasia and 75 with dysplasia/carcinoma, including 55 with low-grade dysplasia, 10 with high-grade dysplasia, and 10 with submucosal cancer. In clinical characteristics, SSLs with dysplasia/carcinoma were significantly associated with advanced age, metabolic diseases, and high-risk adenomas. In endoscopic characteristics, SSLs with dysplasia/carcinoma were significantly associated with the distal colon, large size, polypoid morphology, surface-changes, no mucus cap, and narrow-band imaging international colorectal endoscopic classification (NICE) type 2/3. In the multivariate analysis, high-risk adenomas (odds ratio [OR], 2.98; p = 0.01), large size (OR, 1.18; p < 0.01), depression (OR, 11.74; p = 0.03), and NICE type 2/3 (OR, 14.97; p < 0.01) were significantly associated with SSLs with dysplasia/carcinoma.
CONCLUSION
SSLs had a higher risk of dysplasia in the distal colon than in the proximal colon. SSLs with large size, depression, and adenomatous surface-patterns, as well as those in patients with high-risk adenomas, increased the risk of dysplasia/ carcinoma. This suggests that the clinical and endoscopic characteristics can aid in the diagnosis and management of SSLs with dysplasia/carcinoma.
Topics: Humans; Colonic Polyps; Colonoscopy; Colorectal Neoplasms; Retrospective Studies; Adenoma; Carcinoma; Hyperplasia
PubMed: 36967594
DOI: 10.3904/kjim.2022.322 -
Annals of Coloproctology Feb 2022Ulcerative colitis (UC) is known to have an association with the increased risk of colorectal cancer (CRC), and UC-associated CRC does not follow the typical progress...
PURPOSE
Ulcerative colitis (UC) is known to have an association with the increased risk of colorectal cancer (CRC), and UC-associated CRC does not follow the typical progress pattern of adenoma-carcinoma. The aim of this study is to investigate molecular characteristics of UC-associated CRC and further our understanding of the association between UC and CRC.
METHODS
From 5 patients with UC-associated CRC, matched normal, dysplasia, and tumor specimens were obtained from formalin-fixed paraffin-embedded (FFPE) samples for analysis. Genomic DNA was extracted and whole exome sequencing was conducted to identify somatic variations in dysplasia and tumor samples. Statistical analysis was performed to identify somatic variations with significantly higher frequencies in dysplasia-initiated tumors, and their relevant functions were investigated.
RESULTS
Total of 104 tumor mutation genes were identified with higher mutation frequencies in dysplasia-initiated tumors. Four of the 5 dysplasia-initiated tumors (80.0%) have TP53 mutations with frequent stop-gain mutations that were originated from matched dysplasia. APC and KRAS are known to be frequently mutated in general CRC, while none of the 5 patients have APC or KRAS mutation in their dysplasia and tumor samples. Glycoproteins including mucins were also frequently mutated in dysplasia-initiated tumors.
CONCLUSION
UC-associated CRC tumors have distinct mutational characteristics compared to typical adenoma-carcinoma tumors and may have different cancer-driving molecular mechanisms that are initiated from earlier dysplasia status.
PubMed: 34788527
DOI: 10.3393/ac.2021.00290.0041