-
International Journal of Surgery Case... Jul 2024Adrenocortical tumors (ACTs) are rare endocrine neoplasms in children, with functional ACTs being more prevalent than non-functional types. Clinical manifestations...
INTRODUCTION
Adrenocortical tumors (ACTs) are rare endocrine neoplasms in children, with functional ACTs being more prevalent than non-functional types. Clinical manifestations typically include virilization, Cushing's syndrome, and hyperaldosteronism. Surgical intervention is the primary treatment for ACTs, with a significant risk of recurrence in adrenocortical carcinoma even after complete resection.
PRESENTATION OF CASE
This case presentation describes a 3.5-year-old female with generalized hirsutism and clitoral hypertrophy, leading to the discovery of a left adrenal tumor. The child underwent adrenalectomy, revealing a benign adrenal cortical adenoma. Unfortunately, due to loss of follow-up, the child later presented with pulmonary metastases and passed away, preventing further investigation into the source of metastases.
DISCUSSION
Adrenocortical tumors are uncommon in children, with the classification of ACTs into adenomas and carcinomas. To our knowledge, this is the third case of an adrenocortical tumor in a child in Syria. We highlight the challenges in managing pediatric ACTs and emphasize the importance of timely intervention and close monitoring to improve outcomes. Regular follow-up is crucial to detect complications early and optimize treatment strategies, especially considering the unpredictable behavior of these tumors.
CONCLUSION
This case confirms that distinguishing between adrenocortical adenoma and carcinoma can be challenging even histologically. Therefore, it is necessary to follow up after treating each case of adenoma in a child to prevent major complications.
PubMed: 38852562
DOI: 10.1016/j.ijscr.2024.109878 -
Zhonghua Bing Li Xue Za Zhi = Chinese... Jun 2024To investigate the clinicopathological features of children with metachronous or synchronous primary tumors and to identify related genetic tumor syndromes. The...
To investigate the clinicopathological features of children with metachronous or synchronous primary tumors and to identify related genetic tumor syndromes. The clinicopathological data of 4 children with multiple primary tumors diagnosed in the Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China from 2011 to 2023 were collected. The histological, immunophenotypic and molecular characteristics were examined using H&E staining, immunohistochemical staining, PCR, Sanger sequencing and next-generation sequencing (NGS). The patients were followed up. Case 1 was an 8-year-old boy with the adrenal cortical carcinoma, and 5 years later a poorly differentiated gastric adenocarcinoma was detected. Case 2 was a 2-year-old boy, presented with a left ventricular choroid plexus carcinoma, and a hepatoblastoma was detected 8 months later. Case 3 was a 9-month-old girl, diagnosed with renal rhabdoid tumor first and intracranial atypical teratoid/rhabdoid tumor (AT/RT) 3 months later. Case 4 was a 7-year-old boy and had a sigmoid colon adenocarcinoma 3 years after the diagnosis of a glioblastoma. The morphology and immunohistochemical features of the metachronous or synchronous primary tumors in the 4 cases were similar to the corresponding symptom-presenting/first-diagnosed tumors. No characteristic germ line mutations were detected in cases 1 and 2 by relevant molecular detection, and the rhabdoid tumor predisposition syndrome was confirmed in case 3 using NGS. Case 4 was clearly related to constitutional mismatch repair deficiency as shown by the molecular testing and clinical features. Childhood multiple primary tumors are a rare disease with histological morphology and immunophenotype similar to the symptom-presenting tumors. They are either sporadic or associated with a genetic (tumor) syndrome. The development of both tumors can occur simultaneously (synchronously) or at different times (metachronously). Early identification of the children associated with genetic tumor syndromes can facilitate routine tumor screening and early treatment.
Topics: Humans; Male; Child; Female; Child, Preschool; Neoplasms, Multiple Primary; Liver Neoplasms; Kidney Neoplasms; Infant; Stomach Neoplasms; Rhabdoid Tumor; Hepatoblastoma; Adenocarcinoma; Choroid Plexus Neoplasms; Adrenocortical Carcinoma; Adrenal Cortex Neoplasms; Teratoma; Brain Neoplasms; SMARCB1 Protein; MutL Protein Homolog 1; Neoplasms, Second Primary; High-Throughput Nucleotide Sequencing; Neoplastic Syndromes, Hereditary
PubMed: 38825907
DOI: 10.3760/cma.j.cn112151-20231024-00299 -
Aging May 2024Pseudouridylation has demonstrated the potential to control the development of numerous malignancies. PUS7(Pseudouridine Synthase 7) is one of the pseudouridine...
AIM
Pseudouridylation has demonstrated the potential to control the development of numerous malignancies. PUS7(Pseudouridine Synthase 7) is one of the pseudouridine synthases, but the literature on this enzyme is limited to several cancer types. Currently, no investigation has been performed on the systematic pan-cancer analysis concerning PUS7 role in cancer diagnosis and prognosis.
METHODS
Employing public databases, including The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression Project (GTEx), Human Protein Atlas (HPA), UALCAN and Tumor Immune Single-cell Hub (TISCH), this work investigated the PUS7 carcinogenesis in pan-cancer. Differential expression analysis, prognostic survival analysis and biological function were systematically performed. Furthermore, PUS7 potential as an osteosarcoma biomarker for diagnosis and prognosis was assessed in this study.
RESULTS
The findings indicated that PUS7 was overexpressed in the majority of malignancies. High PUS7 expression contributed to the poor prognosis among 11 cancer types, including Adrenocortical Cancer (ACC), Bladder Cancer (BLCA), Liver Cancer (LIHC), Kidney Papillary Cell Carcinoma (KIRP), Mesothelioma (MESO), Lower Grade Glioma (LGG), Kidney Chromophobe (KICH), Sarcoma (SARC), osteosarcoma (OS), Pancreatic Cancer (PAAD), and Thyroid Cancer (THCA). In addition, elevated PUS7 expression was linked to advanced TNM across multiple malignancies, including ACC, BLCA, KIRP, LIHC and PAAD. The function enrichment analysis revealed that PUS7 participates in E2F targets, G2M checkpoint, ribosome biogenesis, and rRNA metabolic process. Moreover, PUS7 is also a reliable biomarker and a potential therapeutic target for osteosarcoma.
CONCLUSIONS
In summary, PUS7 is a putative pan-cancer biomarker that reliably forecasts cancer patients' prognosis. In addition, this enzyme regulates the cell cycle, ribosome biogenesis, and rRNA metabolism. Most importantly, PUS7 possibly regulates osteosarcoma initiation and progression.
Topics: Humans; Osteosarcoma; Biomarkers, Tumor; Prognosis; Gene Expression Regulation, Neoplastic; Bone Neoplasms; Neoplasms; Membrane Proteins; Adaptor Proteins, Signal Transducing
PubMed: 38819212
DOI: 10.18632/aging.205863 -
Scientific Reports May 2024Determination of body composition (the relative distribution of fat, muscle, and bone) has been used effectively to assess the risk of progression and overall clinical...
Determination of body composition (the relative distribution of fat, muscle, and bone) has been used effectively to assess the risk of progression and overall clinical outcomes in different malignancies. Sarcopenia (loss of muscle mass) is especially associated with poor clinical outcomes in cancer. However, estimation of muscle mass through CT scan has been a cumbersome, manually intensive process requiring accurate contouring through dedicated personnel hours. Recently, fully automated technologies that can determine body composition in minutes have been developed and shown to be highly accurate in determining muscle, bone, and fat mass. We employed a fully automated technology, and analyzed images from a publicly available cancer imaging archive dataset (TCIA) and a tertiary academic center. The results show that adrenocortical carcinomas (ACC) have relatively sarcopenia compared to benign adrenal lesions. In addition, functional ACCs have accelerated sarcopenia compared to non-functional ACCs. Further longitudinal research might shed further light on the relationship between body component distribution and ACC prognosis, which will help us incorporate more nutritional strategies in cancer therapy.
Topics: Humans; Sarcopenia; Body Composition; Adrenocortical Carcinoma; Male; Female; Adrenal Cortex Neoplasms; Tomography, X-Ray Computed; Middle Aged; Adult; Aged
PubMed: 38806535
DOI: 10.1038/s41598-024-62431-2 -
Diagnostic Pathology May 2024Current diagnostic criteria of adrenocortical neoplasms are mostly based on morphology. The utility of immunohistochemistry (IHC) and histochemistry is limited.
BACKGROUND
Current diagnostic criteria of adrenocortical neoplasms are mostly based on morphology. The utility of immunohistochemistry (IHC) and histochemistry is limited.
MATERIALS AND METHODS
To evaluate the diagnostic and prognostic utility of clinicopathological features, morphology, ancillary biomarkers, and reticular histochemistry in adrenocortical neoplasms. We examined 28 adrenocortical carcinomas (ACCs) and 50 adrenocortical adenomas (ACAs) obtained from pathology archives. Clinical data were retrieved from medical records. Two pathologists independently assessed hematoxylin and eosin-stained slides, employing modified Weiss criteria for all tumors and Lin-Weiss-Bisceglia criteria for oncocytic variants. Immunohistochemical markers (Calretinin, alpha-inhibin, MelanA, SF-1, Ki-67, PHH3, IGF-2, β-catenin, P53, CYP11B1, CYP11B2, MLH1, MSH2, MSH6, PMS2, EPCAM) and Gomori's Silver histochemistry were applied. Statistical analysis utilized SPSS Statistics 26.
RESULTS
ACCs exhibited larger tumor sizes (P<0.001) and symptomatic presentations (P = 0.031) compared to ACAs. Parameters of modified Weiss criteria and angioinvasion demonstrated diagnostic value for ACCs. Six immunohistochemical antibodies((MelanA, Ki-67, IGF-2, β-catenin, P53 and CYP11B1) and reticulin framework alterations showed diagnostic value. Notably, Ki-67 and reticulin staining were most recommended. Evident reticulin staining was frequently present in ACCs (P<0.001). Ki-67 was significantly higher in ACCs (P<0.001). Twenty-one conventional and seven oncocytic entities showed different necrosis frequencies. Symptoms and Ki-67 index ≥ 30% were prognostic for ACCs, correlating with shorter survival.
CONCLUSIONS
This study emphasizes the diagnostic value of reticulin framework alterations and a high Ki-67 index. Markers such as CYP11B1, IGF2, P53, β-catenin and MelanA also contribute to the diagnosis of ACCs. Symptoms and Ki-67 index ≥ 30% predict shorter survival. These findings encourges the use of ancillary markers such as reticulin histochemistry and Ki-67 in the workup of evaluations of adrenocortical neoplasms.
Topics: Humans; Adrenal Cortex Neoplasms; Adrenocortical Carcinoma; Male; Female; Biomarkers, Tumor; Middle Aged; Immunohistochemistry; Adult; Prognosis; Aged; Young Adult; Adolescent; Adrenocortical Adenoma; Child
PubMed: 38802933
DOI: 10.1186/s13000-024-01496-z -
Terapevticheskii Arkhiv Dec 2023Adrenocortical carcinoma (ACC) is a rare malignant tumor originating in the adrenal cortex and characterized by poor 5-year survival. It occurs with a frequency of 2-4...
Adrenocortical carcinoma (ACC) is a rare malignant tumor originating in the adrenal cortex and characterized by poor 5-year survival. It occurs with a frequency of 2-4 cases per 2 million in the population. Women are more frequently affected than men and it is mostly detected in the fourth and fifth decades. In the most of cases, the cancerogenesis occurs sporadically because of gene driver mutations in somatic adrenocortical cells, in other cases it can be found as part of a genetically determined syndrome such as Li-Fraumeni syndrome or Wermer's syndrome (multiple endocrine adenomatosis type I). ACC most frequently happens occurs without symptoms in the initial stages leading to poor diagnoses. Because of this lack of early detection, the tumor is not considered malignant reducing the benefits of further treatment. Sometimes the fact that the resected tumor is indeed adrenocortical carcinoma becomes clear only after recurrence, or after the appearance of metastases. We present a case of adrenocortical carcinoma in a 46-year-old woman who went to the doctor in 1.5 year after symptoms were manfested. This clinical case illustrates the consequences of late diagnosis of a malignant tumor. We would like to emphasize the importance of timely detection of a neoplasm, using all of the potential of laboratory-instrumental and genomic analysis. Due to low oncological awareness, our patient was slow to seek medical help, which in turn led not only to metastases, but also to complications in the cardiovascular system.
Topics: Humans; Female; Adrenal Cortex Neoplasms; Middle Aged; Delayed Diagnosis; Adrenocortical Carcinoma
PubMed: 38785058
DOI: 10.26442/00403660.2023.12.202430 -
Frontiers in Endocrinology 2024Adrenocortical carcinoma (ACC) is an aggressive endocrine malignancy with limited therapeutic options. Treating advanced ACC with mitotane, the cornerstone therapy,...
BACKGROUND
Adrenocortical carcinoma (ACC) is an aggressive endocrine malignancy with limited therapeutic options. Treating advanced ACC with mitotane, the cornerstone therapy, remains challenging, thus underscoring the significance to predict mitotane response prior to treatment and seek other effective therapeutic strategies.
OBJECTIVE
We aimed to determine the efficacy of mitotane via an assay using patient-derived ACC cells (PDCs), identify molecular biomarkers associated with mitotane response and preliminarily explore potential agents for ACC.
METHODS
mitotane sensitivity testing was performed in 17 PDCs and high-throughput screening against 40 compounds was conducted in 8 PDCs. Genetic features were evaluated in 9 samples using exomic and transcriptomic sequencing.
RESULTS
PDCs exhibited variable sensitivity to mitotane treatment. The median cell viability inhibition rate was 48.4% (IQR: 39.3-59.3%) and -1.2% (IQR: -26.4-22.1%) in responders (n=8) and non-responders (n=9), respectively. Median IC50 and AUC were remarkably lower in responders (IC50: 53.4 µM vs 74.7 µM, P<0.0001; AUC: 158.0 vs 213.5, P<0.0001). Genomic analysis revealed somatic alterations were only found in responders (3/5) while alterations only in non-responders (3/4). Transcriptomic profiling found pathways associated with lipid metabolism were upregulated in responder tumors whilst and expression were positively correlated to mitotane sensitivity. Furthermore, pharmacologic analysis identified that compounds including disulfiram, niclosamide and bortezomib exhibited efficacy against PDCs.
CONCLUSION
ACC PDCs could be useful for testing drug response, drug repurposing and guiding personalized therapies. Our results suggested response to mitotane might be associated with the dependency on lipid metabolism. and expression could be predictive markers for mitotane response, and disulfiram, niclosamide and bortezomib could be potential therapeutics, both warranting further investigation.
Topics: Humans; Mitotane; Adrenocortical Carcinoma; Adrenal Cortex Neoplasms; Female; Male; Antineoplastic Agents, Hormonal; Middle Aged; Adult; Pharmacogenomic Testing; Aged; Pharmacogenetics
PubMed: 38779454
DOI: 10.3389/fendo.2024.1365321 -
The Oncologist May 2024Venous thromboembolism (VTE) is a leading cause of death in patients with cancer. Limited data exist about VTE in patients with adrenocortical carcinoma (ACC). The...
BACKGROUND
Venous thromboembolism (VTE) is a leading cause of death in patients with cancer. Limited data exist about VTE in patients with adrenocortical carcinoma (ACC). The primary objective of this study was to identify the prevalence of VTE in a cohort of patients with ACC. Secondary objectives were to determine the impact of VTE events on overall survival (OS) and to describe the characteristics of VTE in patients with ACC.
PATIENTS AND METHODS
We retrospectively reviewed data from 289 patients with ACC cared for at a major referral center from February 2010 to June 2022.
RESULTS
VTE prevalence was 18.7% (54 events). Thirty patients (55.6%) had pulmonary embolism (PE); 12 patients (22.2%) had deep vein thrombosis (DVT); and 12 patients (22.2%) had both PE and DVT. VTE occurred after ACC diagnosis in 50 patients (92.6%) including 44 patients (88%) with stage 3 or 4 ACC. VTEs were CTCAE grade ≤2 in 32 cases (59.3%), grade 3 in 17 (31.5%), and grade 4 in 2 (3.7%). Thirteen patients (24%) died within 6 months after VTE diagnosis, although there was no statistically significant association between VTE and overall survival.
CONCLUSION
Despite the potential to underestimate the prevalence of VTEs, we found a high frequency of VTE events in patients with ACC. A majority of VTEs occurred in the context of advanced ACC and we observed high short-term mortality. Further studies are needed to validate our findings and investigate mechanisms associated with VTE in ACC.
PubMed: 38776552
DOI: 10.1093/oncolo/oyae099 -
Case Reports in Oncological Medicine 2024Li-Fraumeni syndrome (LFS) is a cancer predisposition syndrome associated with a high, lifetime risk of a broad spectrum of cancers caused by pathogenic germline TP53...
Li-Fraumeni syndrome (LFS) is a cancer predisposition syndrome associated with a high, lifetime risk of a broad spectrum of cancers caused by pathogenic germline TP53 mutations. Numerous different germline TP53 mutations have been associated with LFS, which has an exceptionally diverse clinical spectrum in terms of tumor type and age of onset. Our patient has developed six asynchronous tumors to date: a phyllode tumor of the breast, a pheochromocytoma, a rosette-forming glioneuronal tumor (RGNT), an adrenocortical carcinoma (ACC), a ductal carcinoma of the breast, and a thymoma. The occurrence of such a number of rare tumors is sporadic even among in the population of patients living with cancer predisposition syndromes. In this instance, the omission of pretest genetic counseling and thorough family tree analysis prior to selecting the test led to the oversight of an underlying TP53 likely pathogenic mutation (classified as Class 4). This emphasizes the necessity for such counseling to prevent overlooking crucial genetic information. Neglecting this step could have had profound implications on the patient's treatment, particularly considering the early onset and occurrence of multiple tumors, which typically raise suspicion of a hereditary component. The implications for family members must be considered.
PubMed: 38765733
DOI: 10.1155/2024/6699698 -
Molecular and Cellular Endocrinology Sep 2024Adrenocortical carcinoma (ACC) is a rare yet devastating tumour of the adrenal gland with a molecular pathology that remains incompletely understood. To gain novel...
Adrenocortical carcinoma (ACC) is a rare yet devastating tumour of the adrenal gland with a molecular pathology that remains incompletely understood. To gain novel insights into the cellular landscape of ACC, we generated single-nuclei RNA sequencing (snRNA-seq) data sets from twelve ACC tumour samples and analysed these alongside snRNA-seq data sets from normal adrenal glands (NAGs). We find the ACC tumour microenvironment to be relatively devoid of immune cells compared to NAG tissues, consistent with known high tumour purity values for ACC as an immunologically "cold" tumour. Our analysis identifies three separate groups of ACC samples that are characterised by different relative compositions of adrenocortical cell types. These include cell populations that are specifically enriched in the most clinically aggressive and hormonally active tumours, displaying hallmarks of reorganised cell mechanobiology and dysregulated steroidogenesis, respectively. We also identified and validated a population of mitotically active adrenocortical cells that strongly overexpress genes POLQ, DIAPH3 and EZH2 to support tumour expansion alongside an LGR4+ progenitor-like or cell-of-origin candidate for adrenocortical carcinogenesis. Trajectory inference suggests the fate adopted by malignant adrenocortical cells upon differentiation is associated with the copy number or allelic balance state of the imprinted DLK1/MEG3 genomic locus, which we verified by assessing bulk tumour DNA methylation status. In conclusion, our results therefore provide new insights into the clinical and cellular heterogeneity of ACC, revealing how genetic perturbations to healthy adrenocortical renewal and zonation provide a molecular basis for disease pathogenesis.
Topics: Humans; Adrenocortical Carcinoma; Adrenal Cortex Neoplasms; Tumor Microenvironment; Gene Expression Regulation, Neoplastic; Single-Cell Analysis; Intercellular Signaling Peptides and Proteins; Calcium-Binding Proteins; Membrane Proteins
PubMed: 38759836
DOI: 10.1016/j.mce.2024.112272