• Adenoma, liver cell
• Allogeneic hematopoietic stem cell transplantation
• Aplastic anemia
• Myelodysplastic syndrome

• Humans
• Hematopoietic Stem Cell Transplantation/methods
• Retrospective Studies
• Adolescent
• Prognosis
• Middle Aged
• Adult
• Transplantation, Homologous
• Young Adult
• Liver Neoplasms/surgery
• Adenoma
• Male
• Female

• 81800116 National Natural Science Foundation of China

• Adult
• Female
• Humans
• Pregnancy
• alpha-Fetoproteins/genetics
• Carcinogenesis/genetics
• Carcinoma, Hepatocellular/diagnosis
• Carcinoma, Hepatocellular/genetics
• Hepatocytes
• Liver Neoplasms/diagnosis
• Liver Neoplasms/genetics

• R01 CA253651 NCI NIH HHS
• R01 CA277530 NCI NIH HHS
• R01 CA246304 NCI NIH HHS
• K08 CA259534 NCI NIH HHS
• R21 CA280444 NCI NIH HHS

Cancer development is a multistep process often starting with a single cell in which a number of epigenetic and genetic alterations have accumulated thus transforming it into a tumor cell. The progeny of such a single benign tumor cell expands in the tissue and can at some point progress to malignant tumor cells until a detectable tumor is formed. The dynamics from the early phase of a single cell to a detectable tumor with billions of tumor cells are complex and still not fully resolved, not even for the well-known prototype of multistage carcinogenesis, the adenoma-adenocarcinoma sequence of colorectal cancer. Mathematical models of such carcinogenesis are frequently tested and calibrated based on reported age-specific incidence rates of cancer, but they usually require calibration of four or more parameters due to the wide range of processes these models aim to reflect. We present a cell-based model, which focuses on the competition between wild-type and tumor cells in colonic crypts, with which we are able reproduce epidemiological incidence rates of colon cancer. Additionally, the fraction of cancerous tumors with precancerous lesions predicted by the model agree with clinical estimates. The correspondence between model and reported data suggests that the fate of tumor development is majorly determined by the early phase of tumor growth and progression long before a tumor becomes detectable. Due to the focus on the early phase of tumor development, the model has only a single fit parameter, the time scale set by an effective replacement rate of stem cells in the crypt. We find this effective rate to be considerable smaller than the actual replacement rate, which implies that the time scale is limited by the processes succeeding clonal conversion of crypts.

Cancer development is a multistep process often starting with a single cell turning into a tumor cell whose progeny growths via clonal expansion into a macroscopic tumor with billions of cells. While experimental insight exists on the cellular scale and cancer registries provide statistics on detectable tumors, the complex dynamics leading from the microscopic cellular scale to a macroscopic tumor is still not fully resolved. Models of cancer biology are commonly used to explain incidence rates but usually require the fit of several biological parameters due to the complexity of the incorporated processes. We employ a cell-based model based on the competition in colonic crypts, to reproduce epidemiological age-specific incidence rates of colon cancer. Due to the focus on the early stage of tumor development, only the time scale in the model has to be calibrated. The agreement between theoretical prediction and epidemiological observation suggests that the fate of tumor development is dominated by the early phase of tumor development long before a tumor becomes detectable.

• Age Factors
• Carcinogenesis
• Colon
• Colonic Neoplasms/epidemiology
• Colonic Neoplasms/genetics
• Humans
• Incidence

• ESF/SAB

• Hepatic adenoma
• Malignant transformation
• Molecular profiling

• Adenoma/complications
• Adenoma/diagnosis
• Adenoma/therapy
• Adenoma, Liver Cell/diagnosis
• Adenoma, Liver Cell/pathology
• Adenoma, Liver Cell/therapy
• Cell Transformation, Neoplastic/pathology
• Female
• Hemorrhage/etiology
• Humans
• Liver Neoplasms/diagnosis
• Liver Neoplasms/pathology
• Liver Neoplasms/therapy
• Male

Tuberous sclerosis complex (TSC) results in neurodevelopmental phenotypes, benign tumors, and cysts throughout the body. Recent studies show numerous rare findings in TSC. Guidelines suggest routine abdominal and chest imaging to monitor these thoracoabdominal findings, but imaging is not uniformly done across centers. Thus, the prevalence of many findings is unknown. To answer this, we categorized the clinical reads of 1398 thoracoabdominal scans from 649 patients of all ages in the Cincinnati Children’s Hospital TSC Repository Database.

Typical TSC findings were present in many patients: kidney cysts (72%), kidney fat-containing angiomyolipomas (51%), kidney lipid-poor angiomyolipomas (27%), liver angiomyolipomas (19%), and lung nodules thought to represent multifocal micronodular pneumocyte hyperplasia (MMPH) (18%). While many features were more common in TSC2 patients, TSC1 patients had a higher prevalence of MMPH than TSC2 patients (24% versus 13%, p = 0.05). Many rare findings (e.g., lymphatic malformations and liver masses) are more common in TSC than in the general population. Additionally, most thoracoabdominal imaging findings increased with age except kidney cysts which decreased, with the 0–10 years age group having the highest percentage (69% 0–10 years, 49% 10–21 years, 48% 21 + years, p < 0.001). Finally, in our population, no patients had renal cell carcinoma found on abdominal imaging.

These results show that regular thoracoabdominal scans in TSC may show several findings that should not be ignored or, conversely, over-reacted to when found in patients with TSC. Female sex, TSC2 mutation, and age are risk factors for many thoracoabdominal findings. The data suggest novel interactions of genetic mutation with pulmonary nodules and age with renal cysts. Finally, in agreement with other works, these findings indicate that several rare thoracoabdominal imaging findings occur at higher rates in the TSC population than in the general population. This work supports obtaining detailed thoracoabdominal imaging in patients with TSC.

The online version contains supplementary material available at 10.1186/s13023-022-02277-x.

• CT
• MRI
• Pulmonary nodules
• Renal angiomyolipomas
• Renal cysts
• TSC1
• TSC2
• Tuberous sclerosis

• Focal nodular hyperplasia
• contrast-enhanced ultrasound
• hepatobiliary contrast agents
• hepatocellular adenoma
• hepatocellular carcinoma

• Abdominal Pain/diagnosis
• Abdominal Pain/etiology
• Adenoma, Liver Cell/diagnosis
• Adult
• Carcinoma, Hepatocellular/diagnosis
• Conservative Treatment
• Constriction, Pathologic/diagnosis
• Contrast Media/administration & dosage
• Diagnosis, Differential
• Diagnostic Errors
• Focal Nodular Hyperplasia/diagnosis
• Focal Nodular Hyperplasia/pathology
• Focal Nodular Hyperplasia/surgery
• Hepatic Veins/pathology
• Humans
• Liver Diseases/etiology
• Liver Diseases/therapy
• Liver Neoplasms/pathology
• Liver Transplantation/methods
• Magnetic Resonance Imaging/methods
• Male
• Middle Aged
• Postoperative Complications
• Tomography, X-Ray Computed/methods
• Waiting Lists

• Hepatocellular carcinoma
• liver cirrhosis
• non-alcohol steatohepatitis
• non-alcoholic fatty liver disease

• Carcinoma, Hepatocellular/etiology
• Humans
• Liver Cirrhosis/complications
• Liver Neoplasms/etiology
• Non-alcoholic Fatty Liver Disease/complications

• Hepatic adenoma
• hemorrhage
• hepatocellular carcinoma
• inflammatory adenoma
• malignant transformation
• oral contraceptive pill

• beta-catenin activation
• inflammatory hepatocellular adenoma
• malignant transformation
• protein induced by vitamin K absence/antagonist-II

• Adenoma, Liver Cell/blood
• Adenoma, Liver Cell/pathology
• Adenoma, Liver Cell/surgery
• Adult
• Biomarkers/blood
• Biomarkers, Tumor
• Humans
• Liver Neoplasms/blood
• Liver Neoplasms/pathology
• Liver Neoplasms/surgery
• Male
• Protein Precursors/blood
• Prothrombin

• bioartificial liver
• cell isolation
• hepatic functions
• hepatocellular adenoma
• liver failure

Hepatocellular adenoma (HCA) is a rare benign liver tumor usually affecting young women with a history of prolonged use of hormonal contraception. Although the majority is asymptomatic, a low proportion may have significant complications such as bleeding or malignancy. Despite responding to the hormonal stimulus, the desire for pregnancy in patients with small HCA is not contraindicated. However, through this work we demonstrate that intensive hormonal therapies such as those used in the treatment of infertility can trigger serious complications

A 33-year-old female with a 10-year history of oral contraceptive use was diagnosed with a hepatic tumor as an incidental finding in an abdominal ultrasound. The patient showed no symptoms and physical examination was unremarkable. Laboratory functional tests were within normal limits and tests for serum tumor markers were negative. An abdominal magnetic resonance imaging (MRI) was performed, showing a 30 mm × 29 mm focal lesion in segment VI of the liver compatible with HCA or Focal Nodular Hyperplasia with atypical behavior. After a total of six years of follow-up, the patient underwent ovulation induction treatment for infertility. On a following MRI, a suspected malignancy was warned and hence, surgery was decided. The surgical specimen revealed malignant transformation of HCA towards trabecular hepatocarcinoma with dedifferentiated areas. There was non-evidence of tumor recurrence after three years of clinical and imaging follow-up.

HCAs can be malignant regardless its size and low-risk appearance on MRI when an ovultation induction therapy is indicated.

• Hepatocellular adenoma
• Malignant transformation
• Focal liver lesion
• Adenoma
• Ovulation induction
• Case report

The development of cancer is a multistep process in which cells increase in malignancy through progressive alterations. Such altered cells compete with wild-type cells and have to establish within a tissue in order to induce tumor formation. The range of this competition and the tumor-originating cell type which acquires the first alteration is unknown for most human tissues, mainly because the involved processes are hardly observable, aggravating an understanding of early tumor development. On the tissue scale, one observes different progression types, namely with and without detectable benign precursor stages. Human epidemiological data on the ratios of the two progression types exhibit large differences between cancers. The idea of this study is to utilize data of the ratios of progression types in human cancers to estimate the homeostatic range of competition in human tissues. This homeostatic competition range can be interpreted as necessary numbers of altered cells to induce tumor formation on the tissue scale. For this purpose, we develop a cell-based stochastic model which is calibrated with newly-interpreted human epidemiological data. We find that the number of tumor cells which inevitably leads to later tumor formation is surprisingly small compared to the overall tumor and largely depends on the human tissue type. This result points toward the existence of a tissue-specific tumor-originating niche in which the fate of tumor development is decided early and long before a tumor becomes detectable. Moreover, our results suggest that the fixation of tumor cells in the tumor-originating niche triggers new processes which accelerate tumor growth after normal tissue homeostasis is voided. Our estimate for the human colon agrees well with the size of the stem cell niche in colonic crypts. For other tissues, our results might aid to identify the tumor-originating cell type. For instance, data on primary and secondary glioblastoma suggest that the tumors originate from a cell type competing in a range of 300 – 1,900 cells.

• cancer development
• cell-based stochastic model
• spatial Moran model
• tumor formation and progression
• tumor origin

• Adenoma
• Adenomatosis
• HNF-1α
• Hepatic
• JAK-STAT pathway
• Liver
• β-Catenin

• Abscess
• FNH
• Hemangioma
• Hepatic adenoma
• MRI

Positron emission tomography computed tomography (PET-CT) using 18-Fluoro-deoxyglucose (¹⁸FDG) is an imaging modality that reflects cellular glucose metabolism. Most cancers show an uptake of ¹⁸FDG and benign tumors do not usually behave in such a way. The authors report herein the case of a 38-year-old female patient with a past medical history of cervical intraepithelial neoplasia and pheochromocytoma, in whom a liver lesion had been detected with PET-CT. The tumor was laparoscopically resected and the diagnosis of inflammatory hepatic adenoma was confirmed. This is the first description of an inflammatory hepatic adenoma with an ¹⁸FDG up-take.

• Liver surgery
• Liver tumor
• Liver cancer
• Benign tumor
• Laparoscopy
• Prognosis