Association Of Dysplasia Research Articles

HRAS-related epidermal nevus syndromes: Expansion of the spectrum with first branchial arch defects.

Epidermal nevus syndrome (ENS) comprises a heterogeneous group of neurocutaneous syndromes associated with the presence of epidermal nevi and variable extracutaneous manifestations. Postzygotic activating HRAS pathogenic variants were previously identified in nevus sebaceous (NS), keratinocytic epidermal nevus (KEN), and different ENS, including Schimmelpenning-Feuerstein-Mims and cutaneous-skeletal-hypophosphatasia syndrome (CSHS). Skeletal involvement in HRAS-related ENS ranges from localized bone dysplasia in association with KEN to fractures and limb deformities in CSHS. We describe the first association of HRAS-related ENS and auricular atresia, thereby expanding the disease spectrum with first branchial arch defects if affected by the mosaic variant. In addition, this report illustrates the first concurrent presence of verrucous EN, NS, and nevus comedonicus (NC), indicating the possibility of mosaic HRAS variation as an underlying cause of NC. Overall, this report extends the pleiotropy of conditions associated with mosaic pathogenic variants in HRAS affecting ectodermal and mesodermal progenitor cells.

Characterizing the vaginal microbiome in patients with high grade cervical dysplasia (277)

Objectives: The influence of the vaginal microbiome on risk for cervical dysplasia and cancer is unknown. It is hypothesized that the microbiome can impact the infectivity of human papillomavirus, and some bacteria may even have pro-oncogenic effects. The impact of dysplasia and cancer treatment on the microbiome is also unknown. The objective of this study was to characterize the vaginal microbiome of patients with high-grade cervical dysplasia and determine whether microbiome phylotypes changed after the cervical loop electrosurgical excision procedure (LEEP). Methods: Pre-menopausal women undergoing LEEP for high-grade cervical dysplasia were recruited. Vaginal swabs were collected prior to the LEEP procedure and six weeks post-procedure. DNA was extracted, and the hypervariable V4 region of the bacterial and archaeal 16S rRNA gene was amplified and sequenced using Illumina next-generation sequencing. Sequenced reads were processed and quality-filtered using AdapterRemoval and clustered into operational taxonomic units (OTUs) using a closed-reference OTU-picking strategy implemented in QIIME. A 97% identity threshold was used, and taxonomy was assigned using the EZTaxon database. The resulting OTU table was rarefied to 10,000 sequences. Conclusions: Our findings are consistent with existing data demonstrating an association between an L. iners-dominant microbiome and severe cervical dysplasia. Additionally, a more diverse and less Lactobacillus-dominated vaginal microbiome has been shown to be more prevalent amongst HPV-positive women. In contrast to published data, our findings, while based on a small number of cases, did not demonstrate consistent alterations in vaginal microbiota after the LEEP procedure. We plan to collect more longitudinal data on the persistence and progression of dysplasia in association with vaginal microbiomes to better understand the relationship between these two entities. Objectives: The influence of the vaginal microbiome on risk for cervical dysplasia and cancer is unknown. It is hypothesized that the microbiome can impact the infectivity of human papillomavirus, and some bacteria may even have pro-oncogenic effects. The impact of dysplasia and cancer treatment on the microbiome is also unknown. The objective of this study was to characterize the vaginal microbiome of patients with high-grade cervical dysplasia and determine whether microbiome phylotypes changed after the cervical loop electrosurgical excision procedure (LEEP). Methods: Pre-menopausal women undergoing LEEP for high-grade cervical dysplasia were recruited. Vaginal swabs were collected prior to the LEEP procedure and six weeks post-procedure. DNA was extracted, and the hypervariable V4 region of the bacterial and archaeal 16S rRNA gene was amplified and sequenced using Illumina next-generation sequencing. Sequenced reads were processed and quality-filtered using AdapterRemoval and clustered into operational taxonomic units (OTUs) using a closed-reference OTU-picking strategy implemented in QIIME. A 97% identity threshold was used, and taxonomy was assigned using the EZTaxon database. The resulting OTU table was rarefied to 10,000 sequences. Conclusions: Our findings are consistent with existing data demonstrating an association between an L. iners-dominant microbiome and severe cervical dysplasia. Additionally, a more diverse and less Lactobacillus-dominated vaginal microbiome has been shown to be more prevalent amongst HPV-positive women. In contrast to published data, our findings, while based on a small number of cases, did not demonstrate consistent alterations in vaginal microbiota after the LEEP procedure. We plan to collect more longitudinal data on the persistence and progression of dysplasia in association with vaginal microbiomes to better understand the relationship between these two entities.

Obif, a Transmembrane Protein, Is Required for Bone Mineralization and Spermatogenesis in Mice.

BackgroundVarious kinds of transmembrane and secreted proteins play pivotal roles in development through cell-cell communication. We previously reported that Obif (Osteoblast induction factor, Tmem119), encoding a single transmembrane protein, is expressed in differentiating osteoblasts, and that Obif−/− mice exhibit significantly reduced bone volume in the femur. In the current study, we characterized the Obif protein and further investigated the biological phenotypes of a variety of tissues in Obif−/− mice.ResultsFirst, we found that O-glycosylation of the Obif protein occurs at serine residue 36 in the Obif extracellular domain. Next, we observed that Obif−/− mice exhibit bone dysplasia in association with significantly increased osteoid volume per osteoid surface (OV/OS) and osteoid maturation time (Omt), and significantly decreased mineral apposition rate (MAR) and bone formation rate per bone surface (BFR/BS). In addition, we observed that Obif−/− mice show a significant decrease in testis weight as well as in sperm number. By histological analysis, we found that Obif is expressed in spermatocytes and spermatids in the developing testis and that spermatogenesis is halted at the round spermatid stage in the Obif−/− testis that lacks sperm. However, the number of litters fathered by male mice was slightly reduced in Obif−/− mice compared with wild-type mice, although this was not statistically significant.ConclusionsOur results, taken together with previous observations, indicate that Obif is a type Ia transmembrane protein whose N-terminal region is O-glycosylated. In addition, we found that Obif is required for normal bone mineralization and late testicular differentiation in vivo. These findings suggest that Obif plays essential roles in the development of multiple tissues.

Congenital giant plexiform neurofibroma with occipital calvarial dysplasia in association with meningoencephalocele in neurofibromatosis Type 1 and segmental neurofibromatosis

Giant plexiform neurofibroma (GPNF) of the scalp is an extremely rare lesion reported in association with neurofibromatosis. Occipital location of GPNF is even more infrequent, especially in association with occipital dysplasia (OD). The authors report 2 pediatric cases of GPNF associated with OD. The first case had an associated meningoencephalocele, and the second had large vascular channels within the lesion and the dominant ipsilateral transverse sinus lying in the center of the calvarial defect. The authors present these 2 unusual cases with a review of literature and discuss the radiological findings, theories of etiopathogenesis of the OD, and management dilemmas.

Gigantism Treated by Pure Endoscopic Endonasal Approach in a Case of McCune-Albright Syndrome with Sphenoid Fibrous Dysplasia: A Case Report

McCune-Albright syndrome (MAS) is an uncommon polyostotic manifestation of fibrous dysplasia in association with at least one endocrinopathy that is mostly associated with precocious puberty and hyperpigmented skin macules named café-au-lait spots. We present an atypical manifestation of McCune-Albright syndrome in a 19-year-old man with the uncommon association of polyostotic fibrous dysplasia and gigantism in the absence of café-au-lait spots and precocious puberty. He presented with a height increase to 202 cm in the previous 3 years, which had become more progressive in the few months prior. Physical examination revealed only a mild facial asymmetry; however, a computed tomography (CT) scan discovered vast areas of voluminous bones with ground-glass density and thickening involving the craniofacial bones and skull base. Magnetic resonance imaging (MRI) found a right stalk shift of the pituitary with a 20 mm pituitary adenoma. We describe the diagnostic and endoscopic endonasal transsphenoidal approach for excision of the tumor.

Mondini Malformation Associated With Diastematomyelia and Presenting With Recurrent Meningitis

The authors report the case of 5-year-old girl who presented with 4 episodes of recurrent meningitis. Her initial workup revealed a lumbosacral dermoid sinus associated with diastematomyelia and a tethered cord. Therefore, a surgical repair to correct the anomaly was performed. However, another episode of meningitis occurred after surgery, and a subsequent temporal bone scan revealed the presence of left Mondini dysplasia. To the authors' knowledge, this is the first report of Mondini dysplasia in association with diastematomyelia.

Florid cemento osseous dysplasia in association with dentigerous cyst

We present a case of florid cemento-osseous dysplasia occurring in a 20-year-old Indian woman. The subject presented with three lesions involving the maxillary right quadrant, maxillary left quadrant and mandibular left quadrant. The mandibular left quadrant also demonstrated a cyst.The diagnosis was made by correlating the clinical presentation with that of the radiological and histopathological findings. This is a rare entity because of an unusual combination of Asian race along with the association of dentigerous cyst.

Diastrophic dysplasia in association with severe mental retardation and episodes of hyperglycemia

Soil saturated hydraulic conductivity (Ks) is a predominant input factor when forecasting the vertical transport of contaminants through the soil or when estimating the flood retention capacity of the soil. Displacement of contaminants in the soil over extended periods of time can be attributed mainly to matrix flow, whereas flow through macropores becomes significant under untypically wet conditions, e.g., during spills or rain storms. To obtain matrix conductivities for a soil, the effects of macropores should be excluded. However, the Ks values of a soil profile are unlikely to be reflected solely by pedotransfer tables based on soil texture and bulk density. In this study, we examined five different methods (pedotransfer table, soil core, borehole permeameter, particle-size distribution curve, and instantaneous profile) to determine Ks values for a mercury-contaminated riparian soil for subsequent simulation of long-term mercury displacement toward groundwater. We found that the determined Ks values increased in the following order: borehole permeameter < particle-size distribution curve < pedotransfer table < instantaneous profile < soil core. The instantaneous profile method yielded Ks values of matrix flow, which additionally reflected the structure-related features of Ks values as provided by the soil core method. Despite being labor intensive and requiring expensive field sensors, the instantaneous profile method may provide the best representative in-situ Ks values for the studied site.

Progressive noninfectious anterior vertebral fusion in a girl with axial mesodermal dysplasia spectrum

We report a 7-year-old-girl who presented with the clinical criteria of the axial mesodermal dysplasia spectrum. Her parents were first cousins. Her facial dysmorphism was compatible with Goldenhar syndrome and in addition, she had anterior noninfectious vertebral fusions of the cervical and the thoracolumbar vertebrae, a congenital dermal sinus and a hypoplastic sacrum. The urogenital and the anal-recto regions were normal. To the best of our knowledge, this is the first clinical report of a child with axial mesodermal dysplasia in association with progressive noninfectious anterior vertebral fusion.

Large mucinous cystic neoplasm of the pancreas associated with pregnancy

Mucinous cystic neoplasms (MCNs) of the pancreas occur mostly in females and are potentially sex hormone-sensitive. However, a MCN occurring during pregnancy is quite rare. A 30-year-old woman in the tenth week of pregnancy was referred to us because of a rapid increase in left hypochondrial distending pain. On ultrasound, the patient had a large intra-abdominal cystic lesion. She was thereafter diagnosed with missed abortion and a computed tomography scan showed that the lesion was a cystic tumor 18 cm in diameter originating from the pancreatic tail. The patient subsequently underwent tumor resection with distal pancreatectomy, sparing the spleen. Histopathological analysis of the specimen revealed a pancreatic MCN with moderate dysplasia. Immunohistochemically, the tumor was positive for both estrogen and progesterone receptors. To our knowledge, this is the first reported case of pancreatic MCN with moderate dysplasia in association with pregnancy. Our case strongly indicates that pancreatic MCN is female-hormone dependent.

Fibromuscular dysplasia in association with intrauterine cocaine exposure

Fibromuscular dysplasia (FMD) is an idiopathic disease of small- and medium-sized arteries, involving one or more vascular beds. Patients may present with a range of symptoms, which may not readily lead to a diagnosis of FMD. While maternal cocaine abuse during pregnancy has previously been associated with vascular alterations in the fetus, an association specifically with FMD has not previously been described. In this case report, a 21-month-old male presented with a 3-week history of daily vomiting, with temporary improvement of symptoms, then relapse followed by loss of consciousness. His medical history was significant only for maternal cocaine use. Clinical evaluation revealed dilated cardiomyopathy, and a presumptive diagnosis of myocarditis was rendered. Respiratory arrest and death occurred 2 days after admission. Postmortem examination demonstrated intimal-type multivessel FMD, which was determined to be the cause of the clinical presentation. Without a postmortem examination, it is unlikely that a diagnosis of intimal fibroplasia, a rare variant of FMD (5% of cases), would have been made. This case thus illustrates the continuing utility of the classic postmortem examination. More intriguingly, the case suggests a possible relationship between in utero cocaine exposure and the development of fibromuscular dysplasia in the child.

Septo-optic dysplasia with olfactory tract and bulb hypoplasia

Optic nerve hypoplasia can be associated with other central nervous system malformations. When associated with absence of the septum pellucidum or thinning of the corpus callosum, it is termed septo-optic dysplasia. Considered to be a first trimester event, the embryologic timing and etiology of this syndrome still is not clearly defined. This report represents the first documented case of septo-optic dysplasia with associated hypoplasia of the olfactory tract. Optic nerve hypoplasia is attributed to an abnormal developmental process during gestation. Generally accepted to be due to a first trimester insult, the timing of this abnormality has been debated given its association with other central nervous system abnormalities.1 These central nervous system abnormalities often include cerebral hemispheric and hypothalmic-pituitary axis abnormalities. Specifically, the presence of optic nerve hypoplasia with absence of the septum pellucidum and thinning of the corpus callosum has been termed septo-optic dysplasia or de Morsier's syndrome.1,2 Septo-optic dysplasia in association with olfactory tract and bulb hypoplasia has not been reported previously.J AAPOS 2001;5:398-9.

Ulcerative Colitis and Colon Cancer: More Controversy than Clarity

Although it is generally accepted that the risk of colorectal cancer in patients with ulcerative colitis is increased compared with the general population, the management of this increased risk remains controversial. Patients with pancolitis of > 8 years duration should consider periodic colonoscopic surveillance or prophylactic colectomy. For patients unwilling to undergo prophylactic colectomy, colonoscopic surveillance annually or biennially is recommended. High-grade dysplasia or low-grade dysplasia in association with a lesion or mass is an indication for colectomy when confirmed by 2 pathologists. Repeat colonoscopic surveillance (in 3–6 months) or colectomy is recommended for confirmed low-grade dysplasia.

Optic disc anomalies and frontonasal dysplasia

AIMSTo document the optic disc abnormalities in patients with frontonasal dysplasia in association with basal encephalocele.METHODSNames and hospital numbers of patients with midline clefts were obtained from the ophthalmology and...

Significance of Carcinoma in Situ and Dysplasia in Association with Bladder Cancer

Cystectomy specimens of 118 transitional cell carcinomas of the bladder were analyzed by stepsectioning. The carcinoma in situ and dysplasia adjacent to and remote from the visible bladder cancer were correlated with the tumor configuration on cystoscopy, and grade and stage of the disease. Results showed that a combination of papillary and nodular carcinomas in a single bladder was associated with a high incidence of mucosal involvement. Moreover, more than 50 per cent of all grade 3 carcinomas were associated with carcinoma in situ and dysplasia adjacent to and remote from the visible tumors. Carcinoma in situ and dysplasia were not related to the stage of disease. For management of bladder cancer, it appears important to assess the gross configuration of tumors by cystophotography and to determine the grade of tumors by biopsy, because mucosal involvement was found to be correlated closely with the tumor configuration and grade 3 disease.

A family study of renal dysplasia.

A family study was undertaken to investigate genetic involvement in renal dysplasia, which is defined as abnormal metanephric differentiation. Probands were ascertained through the retrospective examination of necropsy records and the reevaluation of available material, which included microscopic examinations of the kidneys, gross descriptions of organs, and gross photographs. We obtained family histories and performed physical examinations and renal ultrasonography on parents and sibs of the 21 probands. In only one family a sibling with renal dysplasia was discovered; both the proband and the previous stillborn sib had renal dysplasia in association with posterior urethral values. Renal dysplasia could have resulted from urinary tract obstruction secondary to the urethral valves, with inheritance of the valves as the primary abnormality. However, we cannot exclude primary inheritance of the renal abnormality, perhaps with multifactorial determination with a threshold. The empiric recurrence risk of 2.1%, calculated from this family study, was statistically not significantly different from zero. We can assume, therefore, that the multicystic and aplastic types of renal dysplasia, which predominated in this study, are sporadic or rarely familial, but certain other types of renal dysplasia, identified in the literature as familial, probably carry a higher recurrence risk.

Liver cell dysplasia in association with hepatocellular carcinoma, cirrhosis and hepatitis B surface antigen in Hong Kong.

Liver-cell dysplasia was identified in 60% of 558 cases of cirrhosis with and without hepatocellular carcinoma (HCC) in Chinese coming to necropsy in Hong Kong from 1963 to 1978. A significant correlation was found between liver-cell dysplasia and the identification of hepatitis B surface antigen (HBsAg) in the livers, suggesting that dysplasia may be casually related to hepatitis B virus (HBV). Applying Bayes' theorem to our series of male deaths, we calculated that for Chinese male non-cirrhotics showing liver-cell dysplasia at necropsy, compared with male non-cirrhotics showing no liver-cell dysplasia, the approximate risk factor for HCC is 13:1, whereas for male cirrhotics with liver-cell dysplasia, the risk factor for HCC is approximately 2:1. In the presence of dysplasia, the risk for HCC is increased two-fold in males who are also HBsAg-positive. Thus, the presence of liver-cell dysplasia in cirrhotic or non-cirrhotic livers accompanies a significantly higher risk of developing HCC, especially in the presence of HBsAg.

Ossifying Fibroma of Long Bone: Its Distinction from Fibrous Dysplasia and Its Association with Adamantinoma of Long Bone

Two cases of ossifying fibroma of long bones are presented. This tumor is confused with monostotic fibrous dysplasia, but can be distinguished by its intracortical location, as demonstrated radiographically, and by its histologic pattern. Distinction from fibrous dysplasia is important since ossifying fibroma of long bone is a more aggressive lesion with different therapeutic implications. It appears that ossifying fibroma and adamantinoma of long bones are somehow related, and that lesions resembling fibrous dysplasia in association with adamantinomas of long bones are actually ossifying fibromas.

Neuronal colonic dysplasia: An unusual association of Hirschsprung's disease

A case of neuronal colonic dysplasia in association with Hirschsprung's disease is described. It is suggested that this condition be borne in mind when investigating operated Hirschsprung's cases having residual symptoms.

The Plight of the Patient with Carcinoma in Situ of the Bladder

The Plight of the Patient with Carcinoma in Situ of the Bladder