Embryonic Rests Research Articles

Intracranial Dural Chondroma: Case Report and Review of Literature

Intracranial chondromas are slow-growing benign tumors originating from embryonic rests at the sphenoethmoidal region and sometimes can originate from the falx, convexity but rarely from the dura. We present the case of a 38-year-old patient with moderate to severe headaches, doing well after total removal of the lesion. Complete surgical removal of dural chondroma had shown to improve the patient's neurologic status.

The evolutionary cancer gene network theory versus embryogenic hypotheses.

The present paper compares the statements of the evolutionary cancer gene-network theory (cancer genome theory) with the statements of embryogenic hypotheses like the embryonic rest hypothesis, the very small embryonic-like stem cells hypothesis, (VSEL), the para-embryonic p-ESC hypothesis, and the PGCC-life cycle hypothesis, including the life code theory. In my opinion, the evolutionary gene network theory is the only theory that can satisfactorily explain the homologies between carcinogenesis, tumorigenesis, metastasis, gametogenesis, and early embryogenesis. From an evolutionary point of view, there is no reason to see the origin of cancer in cells of early embryonic life.

Skull Base Chordoma: The Thumb Sign

A 57 year old woman with no past medical history presented with headaches and progressive left vision loss. Subsequently, a contrast enhanced brain MRI was performed showing a large well defined skull base mass located laterally in the left petro clival fissure, exhibiting high T2 and FLAIR signal intensity (Figure A), with areas of low signal intensity on susceptibility weighted images consistent with calcifications and a heterogenous enhancement after injection. This tumor was responsible for mass effect on the orbital apex and optic nerve anteriorly and the mesio temporal lobe laterally. Most importantly, on the sagittal planes we can see the tumor projection indenting the pons which is displaced posteriorly. This finding is known as the thumb sign (Figure B and C) characteristic of chordomas. Given these MRI features and after a stereotactic biopsy the diagnosis of chordoma of the skull base was confirmed. Because of the major local extension, the patient underwent radiotherapy rather than surgical resection. Chordomas are rare skull base tumors arising from embryonal rest cells [1]. The major differential being chondrosarcomas with similar appearance but higher ADC values. The thumb sign is relatively specific of chordomas [2] although itcan be described in chondromas of the skull base and can also be seen in chondrosarcomas.

Abstract 6045: Methylation differences in cancer signaling pathways drive Beckwith-Wiedemann Syndrome Wilms Tumor oncogenesis

Abstract Wilms Tumor (WT), or nephroblastoma, is the most common pediatric renal cancer. This cancer is thought to arise from the expansion of embryonal nephrogenic rest cell population. The most common (epi)genetic alterations in WT occur on chromosome 11p15, accounting for about 75% of WT. These same changes on chromosome 11p15 also cause one of the most common WT predisposition syndromes, Beckwith-Wiedemann Syndrome (BWS). BWS is a pediatric overgrowth disorder affecting numerous tissues including the kidney and up to 28% of patients with BWS develop cancer. As patients with BWS have the same 11p15 epigenetic and structural changes that arise sporadically in non-syndromic WT, BWS WT provides a unique opportunity to investigate the specific molecular effect and mechanism by which 11p15 causes oncogenesis. Using clinical data and patient samples from the International BWS Registry and Biorepository, we used whole exome sequencing (WES) and methylation array technologies to examine the genomic and epigenomic landscape of BWS non-tumor kidney (NT) and WT tumors compared to control kidney samples. We found several large-scale recurrent copy number alterations (CNAs) in the BWS WT cohort across cancer-associated chr1p36, WT-associated chr16q, and novel chr15q. Two BWS WT presented with an above average number of genomic alterations compared to previous sporadic WT; one had mutations in telomerase-associated genes and the other had mutations in mismatch repair pathway genes. We investigated other known cancer-associated genes affected by CNAs and single nucleotide variants (SNVs) and found BCORL1 mutations in five BWS WT. Cancer-associated pathways, including targets of TP53, CTNNB1, and MYCN, were significantly differentially methylated between BWS WT and NT. Targets of TP53 and CTNNB1 were also differentially methylated between BWS NT and controls. In addition, FOXO-regulated gene promoters were significant when comparing both BWS WT to NT and BWS NT to control methylation. Overall, WES results indicate that BWS WT have similar genomic stability compared to pediatric cancers and sporadic WT, but we did identify two hyper-mutators including a rare mismatch repair defect WT within the cohort. Recurrent mutations in genes associated with sporadic WT, such as TP53, CTNNB1, and MYCN were not present in BWS samples; however, methylation differences were observed in TP53-, CTNNB1- and MYCN-related gene sets. These and other methylation changes in BWS NT and WT may influence the transcriptome in conjunction with 11p15 alterations to promote growth and oncogenesis without coding mutations. Data presented herein suggest one way in which 11p15-altered genomes predispose cells to oncogenic transitions. Further study of non-syndromic WT methylomes as well as BWS NT and WT tissue expression are required to fully understand these effects. Citation Format: Natali Sobel Naveh, Emily Traxler, Snehal Nirgude, Jennifer Kalish. Methylation differences in cancer signaling pathways drive Beckwith-Wiedemann Syndrome Wilms Tumor oncogenesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6045.

English

A dermoid cyst is a teratoma of a cystic nature which can occur wherever a teratoma can occur. Intra mesenteric dermoid cyst is rarest of rare case and even its incidence is not known. Here, we report a case of intra mesenteric dermoid cyst in 21 yr. old female patient who presented to us with complain of on & off mild pain in abdomen for last 2 years. Intra mesenteric dermoid cyst is a rare condition and when presented with symptoms, it should be operated upon for improving patient’s overall wellbeing. Dermoids belong to the group of congenital cystic tumours developing from an embryonic rest. Such tumours vary from those which contain only epidermal cells to those containing various dermal derivatives, such as glandular cells (sebaceous), and even hair and teeth. So, they vary from pure epidermoids to dermoids and then through the teratoid tumours to the teratomas. These tumours can arise wherever two ectodermal surfaces fuse together in the developing embryo when an ectodermal implant is retained deep in the surface.”1 Intra mesenteric dermoid is very rare and no previous case report regarding intra mesenteric dermoid was found.

SAT-201 Adrenal Myelolipoma in a Patient with Sickle Cell Disease

Background: Adrenal myelolipoma is a rare benign tumor of the adrenal gland, consisting of adipose tissue and hematopoetic elements. It has been reported to be associated with many chronic diseases such as haematological disorders. The majority of the adrenal myelolipomas are diagnosed in the fourth-sixth decades of life, usually as incidental findings. Despite its benign behavior, it may cause difficulties in the differential diagnosis. Clinical Case: A 33-year-old woman was found to have a right adrenal incidentaloma in a kidney ultrasonography, during work-up for suspected kidney pathology ultimately not confirmed. Her past medical history was significant for sickle cell disease. There was no history of hypertension nor personal or family history of endocrine diseases. The physical examination was unremarkable.The ultrasonography revealed a mass above the right kidney, measuring 5.5 cm in diameter, markedly heterogeneous and hypoechoic in the center. On CT imaging, one month later, this mass measured 6.2x4.3cm. The absolute contrast washout of 52% was indeterminate for adrenal adenoma. The MRI, twelve months later, showed a well-demarcated and heterogeneous tumor with 8x4.7x4cm, with fat areas, suggesting adrenal myelolipoma, but not excluding the possibility of a malignant lesion, such as liposarcoma. The mass was in contact with the liver although not invading it nor the kidney or inferior vena cava. There was no evidence of metastatic disease. Basal biochemical work-up did not disclose hormonal hypersecretion. The ACTH level was 19.6 pg/ml (N7.2-63.3); free urinary cortisol (24 hours) was 101 μg/24h (N36-137) and the overnight 1 mg dexamethasone suppression test was also normal (0.5 μg/dL). Serum metanephrines were within the normal range: metanephrine 7,8 pg/mL (N <65) and normetanephrine 52,3 pg/mL (N<196). Her remaining laboratory values were within normal values including potassium and sodium values.Due to the size, rate of growth and atypical features of the mass, right laparoscopic adrenalectomy was performed. The resected adrenal weighed 66.6g and within it there was an intraparenchymal nodule, measuring 7.5 x 3 x 3.5 cm, which on histologic examination proved to be an adrenal myelolipoma. Conclusion: Adrenal myelolipomas are usually clinically silent. However, their incidental diagnosis should warrant careful diagnostic study. Although the pathogenesis of these tumors remains unclear, theories include retention of embryonic rests, adrenocortical metaplasia and extramedullary hematopoiesis. In this patient with sickle cell disease, bone marrow elements within the myelolipoma may have grown as a result of the persistent anemia. Particular to this case is the patient’s young age, since most cases reported have occurred during the fourth-sixth decades of life. In addition, the association with sickle cell anemia has only been reported in a few cases.

The Importance of Dermoscopy In Umbilical Tumor

The pelvic endometriosis is considered a relatively common, benign, estrogen-dependent disease associated with complaints of pelvic pain and infertility, affecting 6% to 10% of women of reproductive age. The etiopathogenesis of the disease is based on some theories and hypotheses. Classical theories include the hypothesis of migratory pathogenesis by retrograde menstrual flow, the theory of celomic metaplasia, the theory of embryonic rest or even iatrogenic deposition during abdominal surgical procedures

Intracranial chondroma of the falx cerebri: A rare case report with review of literature

Intracranial chondromas are extremely rare, benign slow-growing cartilaginous tumors mostly originating from embryonic rests at sphenoethmoidal region and sometimes can originate from the falx, convexity dura, the tentorium, the choroid plexus, or the brain parenchyma. In this article, we present a 22-year-old woman with a chondroma of dural origin. The clinical, radiological, and histopathological findings along with the operative findings and postoperative course are described as well as the pertinent literature regarding intracranial chondromas is reviewed.

Embryonal Origin of Metanephric Adenoma and its Differential Diagnosis.

The association of Wilms' tumor (WT), papillary renal cell tumor (PRCT) and mucinous tubular and spindle cell carcinoma (MTSCC) with embryonal rests has already been documented, but the cellular origin of metanephric adenoma (MA) is not yet known. The aim of this study was to understand their developmental evolution and find diagnostic markers. CD57, KRT7, AMACR, SCEL, WT1 and CDH17 expression was analysed by immunohistochemistry in the four types of tumors and the associated pre-neoplastic lesions. Immunohistochemistry was able to differentiate WT, MA, MTSCC and PRCT. A phenotypic correlation between MA and perilobar nephrogenic rest associated with WT was identified. Perilobar nephrogenic rest and MA arise from differentiation arrested cells of the proximal domain of the S-shape body. We propose that WT1, MA, MTSCC and PRCT derive from different forms of maturation arrested embryonal rests.

Bronchogenic cyst of the tongue in an infant: a case report and review of literature

Bronchogenic cysts are rare congenital lesions and represent the most common primary cysts of the media stinum. However, extra thoracic bronchogenic cysts are uncommon occurrences and very few bronchogenic cysts in intraoral sites have been reported. Lingual bronchogenic cysts are rare and are considered by many authors to be choristomas. Although the aethiopathogenesis is not known with certainty, it has been suggested that the cysts may arise from undifferentiated embryonic rests of primitive foregut that are misplaced or entrapped between parts of the developing tongue. This case report discussed the case of a large lingual bronchogenic cyst of the tongue in 31 day old infant that enucleation of cyst done without recurrence 12 months after treatment.

Bronchogenic cyst of the tongue in an infant: a case report and review of literature

Bronchogenic cysts are rare congenital lesions and represent the most common primary cysts of the media stinum. However, extra thoracic bronchogenic cysts are uncommon occurrences and very few bronchogenic cysts in intraoral sites have been reported. Lingual bronchogenic cysts are rare and are considered by many authors to be choristomas. Although the aethiopathogenesis is not known with certainty, it has been suggested that the cysts may arise from undifferentiated embryonic rests of primitive foregut that are misplaced or entrapped between parts of the developing tongue. This case report discussed the case of a large lingual bronchogenic cyst of the tongue in 31 day old infant that enucleation of cyst done without recurrence 12 months after treatment.

Bronchogenic Cyst of the Tongue in an Infant

Bronchogenic cysts are rare congenital lesions and represent the most common primary cysts of the mediastinum. However, extra thoracic bronchogenic cysts are uncommon occurrences and very few bronchogenic cysts in intraoral sites have been reported. Lingual bronchogenic cysts are rare and are considered by many authors to be choristomas. Although the aethiopathogenesis is not known with certainty, it has been suggested that the cysts may arise from undifferentiated embryonic rests of primitive foregut that are misplaced or entrapped between parts of the developing tongue. This case report discussed the case of a large lingual bronchogenic cyst of the tongue in 31 day old infant that enucleation of cyst done without recurrence 12 months after treatment.

Case report: Diffuse hyperplastic perilobar nephroblastomatosis complicated by a unilateral Wilms tumour: diagnosis, treatment and follow-up

BackgroundNephroblastomatosis is an uncommon pathologic process characterized by the presence of persistent embryonic nephrogenic rests. Progression to Wilms tumour occurs in an estimated 35% of patients. Cure rates are based on histologic findings and disease stage and have improved from 10% in the 1920s to over 90% today.Case presentationWe report a case of a 9-month-old female presenting with a 2-month history of abdominal distension. Ultrasonographic and computed tomographic assessments demonstrated features consistent with bilateral, diffuse, hyperplastic perilobar nephroblastomatosis (DHPLNB) for which she underwent chemotherapy. Magnetic resonance imaging 6 weeks following commencement of chemotherapy revealed a mass concerning for unilateral Wilms tumor for which she underwent partial nephrectomy. Pathology confirmed DHPLNB with a unilateral Wilms tumor.Conclusion3.5 year radiographic follow up demonstrates complete recovery. To our knowledge, there are no similar cases with imaging depiction recently published. With potential for malignant transformation into Wilms tumour and low survival rate for late diagnosed Wilms tumors, it is important to recognize nephroblastomatosis early, both clinically and radiographically to improve overall patient prognosis.

Recalling Cohnheim's Theory: Papillary Renal Cell Tumor as a Model of Tumorigenesis from Impaired Embryonal Differentiation to Malignant Tumors in Adults.

We have suggested that papillary renal cell tumor (PRCT) of the kidney arises from nephrogenic rest-like lesions. To approve our hypothesis, we worked up 14 kidneys bearing papillary and 14 ones with conventional renal cell carcinoma (CRCC) histologically and found 42 papillary lesions in average per kidney bearing PRCT. PRCTs are characterized by loss of the Y chromosome and trisomy of chromosomes 7 and 17. The MET and HNF1B are localized to chromosome 7q31 and 17q21 and are frequently amplified in PRCT. We have analyzed the expression of the mutant MET in hereditary PRCTs and precursor lesions and found duplication and expression of the mutated allele. Because both genes are involved in early stage of nephron development, we have analyzed the expression of MET and HNF1B by immunohistochemistry in fetal kidneys, precursor lesions and PRCTs. We detected strong expression of MET and HNF1B in distal compartment of S-shaped body of fetal kidneys and in nephrogenic rest-like precursor lesions. Our finding suggests an association between expression of MET and HNF1B in precursor lesions and development of PRCT. We propose a model involving chromosomal clonal evolution and corresponding gene expression for development of PRCTs from embryonic rests due to impaired differentiation. Our model suggests that PRCT have a natural history distinct from that of most common CRCC.

Microscopic Heterotopic Extraovarian Sex Cord-Stromal Proliferations: Expanding the Histologic Spectrum.

Microscopic, heterotopic extraovarian sex cord-stromal proliferations have only recently been reported in the literature. We describe the largest series to date, of 30 cases of microscopic, incidentally detected, heterotopic extraovarian sex cord-stromal proliferation, in women aged 25-79 yr who had undergone surgery for a range of benign and malignant gynecologic conditions. In 14 patients the foci of proliferation comprised ovarian cortical stroma, in some cases with an ovarian fibroma-like appearance. Ten cases of adenofibroma and cystadenofibroma were also identified, including 1 Brenner adenofibroma; 2 cases comprised both ovarian cortical stroma and serous cystadenofibroma; 4 cases showed sex cord proliferation resembling microscopic adult granulosa cell tumors. Immunohistochemistry, where possible, confirmed the sex cord nature of the heterotopic proliferations. The foci of proliferation were <1-7 mm, and most were at the fimbrial end of the fallopian tube. These proliferations are likely to be encountered with increasing frequency as we sample the adnexa more extensively. Previous reports postulated that the proliferations probably represent embryonic rests caused by anomalous migration but we suggest that incorporation of exposed ovarian parenchymal tissue into the fimbrial stroma at the time of ovulation may be another possible cause.

Pluripotent Stem Cells in Adult Tissues: Struggling To Be Acknowledged Over Two Decades.

Stem cells have fascinated scientists for a long time and huge research efforts have been put into them as they have the potential to regenerate diseased organs. Besides embryonic stem cells (ES) and induced pluripotent stem cells (iPS), it has been postulated that pluripotent stem cells (PSCs) may also exist in various adult tissues. They are thought to be more primitive than the adult stem cells (ASCs), serve as a backup pool to give rise to ASCs and thus play a crucial role in maintaining life-long homeostasis. These PSCs could also be the embryonic stem cells in adult tissues that were proposed to initiate cancers according to the Embryonic Rest Hypothesis put forth in the nineteenth century. However, the very presence of PSCs in adult tissues is mired with controversies. This article is a sincere attempt to review research carried out by various investigators over the last two decades and various attempts to demonstrate their presence in adult tissues. Such adult PSCs could be the ideal stem cell candidates to bring about endogenous regeneration compared to ES/iPS cells grown in Petri dish and also score better over ASCs which in fact are tissue committed progenitors with limited regenerative potential that differentiate from the PSCs. PSCs in adult tissues have remained elusive until now as they possibly get unknowingly discarded due to their small size and inability to pellet at 1000-1200rpm (250 g). They will likely prove to be a game changer in the field of stem cells biology, for regenerative medicine and for our understanding of cancer initiation.

NaviSE: superenhancer navigator integrating epigenomics signal algebra

BackgroundSuperenhancers are crucial structural genomic elements determining cell fate, and they are also involved in the determination of several diseases, such as cancer or neurodegeneration. Although there are pipelines which use independent pieces of software to predict the presence of superenhancers from genome-wide chromatin marks or DNA-interaction protein binding sites, there is not yet an integrated software tool that processes automatically algebra combinations of raw data sequencing into a comprehensive final annotated report of predicted superenhancers.ResultsWe have developed NaviSE, a user-friendly streamlined tool which performs a fully-automated parallel processing of genome-wide epigenomics data from sequencing files into a final report, built with a comprehensive set of annotated files that are navigated through a graphic user interface dynamically generated by NaviSE. NaviSE also implements an ‘epigenomics signal algebra’ that allows the combination of multiple activation and repression epigenomics signals. NaviSE provides an interactive chromosomal landscaping of the locations of superenhancers, which can be navigated to obtain annotated information about superenhancer signal profile, associated genes, gene ontology enrichment analysis, motifs of transcription factor binding sites enriched in superenhancers, graphs of the metrics evaluating the superenhancers quality, protein-protein interaction networks and enriched metabolic pathways among other features. We have parallelised the most time-consuming tasks achieving a reduction up to 30% for a 15 CPUs machine. We have optimized the default parameters of NaviSE to facilitate its use. NaviSE allows different entry levels of data processing, from sra-fastq files to bed files; and unifies the processing of multiple replicates. NaviSE outperforms the more time-consuming processes required in a non-integrated pipeline. Alongside its high performance, NaviSE is able to provide biological insights, predicting cell type specific markers, such as SOX2 and ZIC3 in embryonic stem cells, CDK5R1 and REST in neurons and CD86 and TLR2 in monocytes.ConclusionsNaviSE is a user-friendly streamlined solution for superenhancer analysis, annotation and navigation, requiring only basic computer and next generation sequencing knowledge. NaviSE binaries and documentation are available at: https://sourceforge.net/projects/navise-superenhancer/.

Update on endometriosis pathogenesis.

Endometriosis is a chronic, inflammatory, condition of high incidence and serious reproductive and general health consequences. Understanding the pathogenesis of endometriosis is crucial for proper diagnostic and ordering the most effective treatment. Even though there is a large body of data regarding this pathology our understanding of the pathogenesis of this disease remains incomplete. The aim of this review is to summarize contemporary data regarding pathogenesis of endometriosis. Current data regarding endometrial origin, metaplastic and Mullerian embryonic rests theory will be reviewed here. Also genetic, epigenetic, environmental factors and immunological dysfunction role in endometriosis will be summarized. To conclude, a lot of effort must be put to integrate the abundant data from genetic, epigenetic and immunological studies to propose one coherent theory for the pathogenesis of endometriosis.

Adrenocortical Carcinoma Arising in an Adrenal Rest: a Case Report and Review of the Literature

Carcinomas arising from embryonic adrenal rests are rare with only a handful of reported cases. We report a case of an adrenocortical carcinoma arising from an adrenal rest located between the bladder and prostate in a 51 year-old man. The patient presented following a year of rectal pain and constipation. Computed tomography (CT) scan revealed a 9 cm pelvic mass that appeared to arise from the soft tissue between the bladder and prostate, with displacement of the organs and narrowing of the rectal lumen, suspected to be a sarcoma. The surgically resected specimen showed a well-circumscribed, partially encapsulated tumor measuring 10.0 cm in greatest dimension. Both adrenal glands were identified intraoperatively. Grossly, the lesion was heterogeneous tan-brown to yellow, hemorrhagic and necrotic. Histology revealed sheets and nests of high-grade pleomorphic tumor cells with abundant clear to vacuolated cytoplasm with areas of necrosis, a high mitotic index (>10 mitoses/10 HPF) and foci suspicious for lymphovascular invasion. Adjacent adrenal cortical-type tissue was identified. Immunohistochemical stains revealed the tumor cells were weakly and focally positive for MiTF, Melan-A, inhibin and synaptophysin, and negative for CKAE1/AE3, HMB-45, calretinin, EMA, SMA, chromogranin, PAX8, MDM2 and CDK4. Based upon the morphologic and immunohistochemical profile, this was diagnosed as an adrenocortical carcinoma, arising in an adrenal rest. To our knowledge, no such tumor has been previously described in this location.

Case report of extra -adrenal pheochromocytoma

The first reported case of pheochromocytoma is attributed to Frankel in 1886. Pheochromocytoma is a neuroendocrine tumour that usually develops ahead of the chromaffin cells of the adrenal medulla. Embryonic rests of chromaffin tissue arising from sympathetic plexus within bladder wall are believed to be the source of these tumors. Extra-adrenal pheochromocytomas usually are located within the abdomen in association with the celiac, superior mesenteric, inferior mesenteric ganglia and Organ of Zuckerkandl (chromaffin body derived from neural crest located at the bifurcation of the aorta or at the origin of the inferior mesenteric artery).