Fat-Poor Hepatic Angiomyolipoma in Noncirrhotic Livers: Imaging Features, Pathology, and Differential Diagnosis.

OBJECTIVE: To investigate imaging features of fat-poor hepatic angiomyolipomas in noncirrhotic livers in order to enhance the diagnostic accuracy for this condition. METHODS: The clinical and imaging data of 19 patients with fat-poor hepatic angiomyolipoma (fpHAML) was retrospectively analyzed. RESULTS: Of the 19 patients without hepatitis, cirrhosis, or sarcoidosis, 16 had no clinical symptoms. There were 20 lesions in 19 patients. Macroscopic fat, calcification, hemorrhage, necrosis, and pseudocapsule were not observed in the 20 lesions. All lesions showed marked enhancement on the arterial phase, and the degree of enhancement was significantly higher than that in the adjacent hepatic parenchyma. In 8 cases, the enhancement of the portal phase was higher than that in the arterial phase. Multiple intratumor vessels were observed in the tumor, and lesions with diameters larger than 3.0 cm were more frequently observed. The degree of enhancement of 18 lesions on portal phase or delayed phase was slightly higher than or equal to that in the surrounding hepatic parenchyma. The lesions were hyperintense on diffusion-weighted imaging and showed homogeneous hypointensity on the hepatobiliary phase. Only 6 cases showed the presence of an early draining vein. CONCLUSIONS: These imaging features have some implications for the diagnosis of fpHAML. Therefore, an increased awareness of fpHAML is needed among radiologists.

Oncogenic Role of the NFATC2/NEDD4/FBP1 Axis in Cholangiocarcinoma.

Nuclear factor of activated T cells 2 (NFATC2) is reported to contribute to the initiation and progression of various cancers; however, its expression and function in cholangiocarcinoma (CCA) tissues remain elusive. Herein, we investigated the expression pattern, clinicopathologic characteristics, cell biological functions, and potential mechanisms of NFATC2 in CCA tissues. Real-time reverse-transcription PCR (RT-qPCR) and immunohistochemistry were performed to analyze the expression of NFATC2 in human CCA tissues. Cell counting kit 8, colony formation, flow cytometry, Western blotting, and Transwell assays, and in vivo xenograft and pulmonary metastasis models, were used to explore the effect of NFATC2 on the proliferation and metastasis of CCA. A dual-luciferase reporter system, oligonucleotide pull-down, chromatin immunoprecipitation, immunofluorescence, and coimmunoprecipitation were performed to reveal the potential mechanisms. We found that NFATC2 was upregulated in CCA tissues and cells, and its aberrantly high levels were associated with a poorer differentiation pattern. Functionally, NFATC2 overexpression promoted CCA cell proliferation and metastasis, whereas knockdown of NFATC2 led to opposite result. Mechanistically, NFATC2 could be enriched in the promoter region of neural precursor cell-expressed developmentally downregulated protein 4 (NEDD4) to facilitate its expression. Furthermore, NEDD4 targeted fructose-1, 6-bisphosphatase 1 (FBP1) and inhibited FBP1 expression via ubiquitination. In addition, silencing NEDD4 rescued the effects of NFATC2 overexpression on CCA cells. NEDD4 was upregulated in human CCA tissues, and its expression levels were positively correlated with those of NFATC2. We thus conclude that NFATC2 promotes the progression of CCA via the NEDD4/FBP1 axis, emphasizing the oncogenic role of NFATC2 in CCA progression.

Claudin18.2 as a potential therapeutic target for primary ovarian mucinous carcinomas and metastatic ovarian mucinous carcinomas from upper gastrointestinal primary tumours.

BACKGROUND: The vast majority of ovarian mucinous carcinomas are metastatic tumours derived from nonovarian primary cancers, typically gastrointestinal neoplasms. Therapy targeting claudin18.2 might be used in gastric, gastroesophageal junction and pancreatic cancers with high expression of claudin18.2. In this study, we aimed to profile the expression of claudin18.2 in primary ovarian mucinous carcinoma (POMC) and metastatic gastrointestinal mucinous carcinoma (MGMC). METHODS: Immunohistochemistry was used to detect claudin 18.2 expression in whole tissue sections of ovarian mucinous carcinomas, including 32 POMCs and 44 MGMCs, 23 of which were derived from upper gastrointestinal primary tumours and 21 of which were derived from lower gastrointestinal primary tumours. Immunohistochemical studies for claudin18.2, SATB2, PAX8, CK7 and CK20 were performed in all 76 cases. RESULTS: Among 76 primary and metastatic mucinous carcinomas, claudin18.2 was expressed in 56.6% (43/76) of cases. MGMCs from the upper gastrointestinal tract, including 22 derived from primary stomach tumours and one derived from a pancreas tumour, were positive for claudin 18.2 in 69.5% (16/23) of cases. MGMCs from the lower gastrointestinal tract, including 10 derived from primary appendiceal cancer and 11 derived from colorectal cancers, showed no claudin18.2 expression (0/21). The expression rate of claudin18.2 in primary ovarian mucinous neoplasms, including 22 primary ovarian mucinous carcinomas and 10 primary ovarian borderline mucinous tumours, was 84.4% (27/32). The common immunophenotypic characteristics of POMCs, upper gastrointestinal tract-derived MGMCs, and lower gastrointestinal tract-derived MGMCs were claudin18.2 + /PAX8 + /SATB2- (17/32), claudin18.2 + /PAX8-/SATB2- (16/23) and claudin18.2-/PAX8-/SATB2 + (19/21), respectively. CONCLUSION: Claudin18.2 is highly expressed in POMCs and MGMCs derived from upper gastrointestinal tract primary tumours; therefore, claudin18.2-targeted therapy might serve as a potential therapeutic strategy for POMCs and MGMCs from the upper gastrointestinal tract.

Yolk Sac Tumor Originating From Cervical Adenocarcinoma: A Case Predominated by Enteroblastic Differentiation.

The fetal gut-like phenotype can be found in yolk sac tumors and adenocarcinomas with enteroblastic differentiation (AEBDs). We report a cervical yolk sac tumor in a 44-yr-old woman. The tumor has similar morphology, immunophenotype, and molecular features to the AEBD of the digestive system. The tumor showed a glandular-predominant growth pattern, composed of columnar cells with clear glycogen-rich cytoplasm. The microcystic/reticular architecture or Schiller-Duval bodies were not found in the tumor. Immunohistochemically, the tumor cells were positive for p16, glypican-3 (GPC3), spalt-like transcription factor 4 (SALL4), CDX-2, and p53. TP53 mutation was identified by next-generation sequencing, and human papillomavirus (HPV) 35 was detected by HPV DNA polymerase chain reaction. In the present case, the adenocarcinoma cells in the superficial cervical glandular epithelium and the nonclear glandular components proved the existence of somatic components. The positivity of p16 and HPV also supports that the present case originates from an HPV-associated adenocarcinoma. The yolk sac tumor should be thought of as "germ cell differentiation" from a somatic carcinoma. This kind of yolk sac tumor arising from somatic-type adenocarcinoma in the female genital tract may be the counterpart of AEBD in the digestive tracts and adenocarcinomas with fetal gut-like morphology in other organs. The tumor might be more aggressive than conventional adenocarcinoma, pathologists should highlight the existence of the enteroblastic component in the pathologic report.

GmWRI1c Increases Palmitic Acid Content to Regulate Seed Oil Content and Nodulation in Soybean (Glycine max).

Soybean (Glycine max) is an important oil crop, but the regulatory mechanisms underlying seed oil accumulation remain unclear. We identified a member of the GmWRI1s transcription factor family, GmWRI1c, that is involved in regulating soybean oil content and nodulation. Overexpression of GmWRI1c in soybean hairy roots increased the expression of genes involved in glycolysis and de novo lipogenesis, the proportion of palmitic acid (16:0), and the number of root nodules. The effect of GmWRI1c in increasing the number of root nodules via regulating the proportion of palmitic acid was confirmed in a recombinant inbred line (RIL) population. GmWRI1c shows abundant sequence diversity and has likely undergone artificial selection during domestication. An association analysis revealed a correlation between seed oil content and five linked natural variations (Hap1/Hap2) in the GmWRI1c promoter region. Natural variations in the GmWRI1c promoter were strongly associated with the GmWRI1c transcript level, with higher GmWRI1c transcript levels in lines carrying GmWRI1cHap1 than in those carrying GmWRI1cHap2. The effects of GmWRI1c alleles on seed oil content were confirmed in natural and RIL populations. We identified a favourable GmWRI1c allele that can be used to breed new varieties with increased seed oil content and nodulation.

MED12 exon 2 and TERT promoter mutations in primary and recurrent breast fibroepithelial lesions.

The genetic alterations in the recurrent breast fibroepithelial tumors are poorly understood. In the present study, we aimed to investigate mediator protein complex subunit 12 (MED12) exon 2 and telomerase reverse transcriptase (TERT) promoter mutations in a series of primary and recurrent fibroepithelial tumors. Sanger sequencing for MED12 exon 2 and TERT promoter was performed in 26 pairs of primary and recurrent fibroepithelial tumors (19 pairs of phyllodes tumors and seven pairs of fibroadenomas). The relationship between the genotypes and clinicopathological variables was also analyzed. MED12 mutation was identified in 19 primary tumors (12 phyllodes tumors and 7 fibroadenomas) and 17 recurrences (14 phyllodes tumors and three fibroadenomas). Most recurrent phyllodes tumors retained the original MED12 variants (17/19). Six recurrent fibroadenomas showed different MED12 variants from their paired primary tumors (6/7). TERT promoter mutation was identified in 13 primary phyllodes tumors (13/19) and 15 recurrent phyllodes tumors (15/19). However, it was only identified in one primary fibroadenoma (1/7). Recurrent phyllodes tumors often retained the original MED12 and TERT promoter mutations, while recurrent fibroadenomas often acquired new MED12 mutations. Our findings suggest that recurrent phyllodes tumors may be "true recurrence," and TERT mutant "benign fibroepithelial tumors" should be treated as phyllodes tumors.

A case report of jejunum transplantation in the treatment of severe cervical esophageal stricture in patients with dystrophic epidermolysis bullosa.

Epidermolysis bullosa (EB) is a rare disorder caused by autosomal genetic variation. Its main clinical features include skin and mucous membrane blisters, erosion, repeated ulcers and scar formation. The lesions mostly involve the skin, oral cavity, digestive system and urinary system. Epidermolysis bullosa complicated with esophageal stenosis is a common gastrointestinal manifestation of this disorder. Currently, there is no cure for EB, and thus symptomatic treatment is usually applied. Here we describe the case of a patient with recessive dystrophic EB complicated with severe esophageal stenosis. The narrow segment of esophagus was removed and the free part of jejunum was transplanted into the esophageal defect to reconstruct the esophagus and restore the patient's normal swallowing. For patients with EB complicated with severe esophageal stenosis, surgical resection of the diseased esophagus and jejunal transplantation can be used to repair the esophageal and restore normal swallowing pathway, providing an effective treatment for this condition.

Membranous and nuclear staining of CLDN18 in HPV-independent and HPV-associated endocervical adenocarcinomas.

OBJECTIVES: A classification system for endocervical adenocarcinoma (ECA) based on high-risk human papillomavirus (HPV) status has been established; however, the immunohistochemical markers distinguishing HPV-independent and HPV-associated ECAs have not been fully described. Here, we aimed to characterize ECA immunopathological features. METHODS: We evaluated the immunohistochemical profile of CLDN18, CDX2, PAX8, p16, p53, and CEA in 60 ECAs comprising 10 HPV-independent ECAs and 50 HPV-associated ECAs. Both the membranous and nuclear expression levels of CLDN18 were analyzed. RESULTS: Membranous CLDN18 (CLDN18 [M]) was found to be expressed in the mucinous epithelium of all HPV-independent ECAs, including eight gastric-type ECAs (G-ECAs), one endometrioid ECA, and one clear cell ECA, but no nuclear CLDN18 (CLDN18 [N]) expression was detected in HPV-independent ECAs. Among HPV-associated ECAs, CLDN18 (M) expression levels in intestinal-type (I-ECAs) and usual-type ECAs (U-ECAs) were significantly different from those in invasive stratified mucin-producing (iSMILE) carcinomas (p = 0.036). Positive CLDN18 (M) staining was present in 55.6% (5/9) of intestinal-type and 39.4% (13/33) of usual-type ECAs and was not present in iSMILE ECAs. Silva pattern C cancers expressed higher levels of CLDN18 (M) than Silva pattern A and B cancers (p = 0.004), whereas the CLDN18 (N) expression levels in cancers showing Silva pattern A were significantly higher than those in cancers exhibiting Silva patterns B and C (p < 0.001). CONCLUSION: Membranous CLDN18 is expressed in ECAs and is particularly frequently expressed in HPV-independent ECAs, and membranous CLDN18 expression has potential as a therapeutic target. Nuclear staining of CLDN18 is a new immunohistochemical marker for diagnosing Silva pattern A HPV-associated ECAs and is associated with a good prognosis. Further studies should investigate the therapeutic and prognostic significance of membranous and nuclear CLDN18 expression and develop a related test that can be implemented in the clinical evaluation of ECAs.

Phosphate-solubilizing fungi enhances the growth of Brassica chinensis L. and reduces arsenic uptake by reshaping the rhizosphere microbial community.

High concentrations of arsenic in soil and plant systems are a threat to human health and ecosystems. The levels of phosphate ions in the soil strongly influence the soil efficacy and arsenic absorption by plants. This study investigated the effects of phosphate-solubilizing fungi (PSF) on environmental factors and structural changes in microbial community in soils contaminated with arsenic. Four experimental groups were created: control (CK), Penicillium GYAHH-CCT186 (W186), Aspergillus AHBB-CT196 (W196), and Penicillium GYAHH-CCT186 + Aspergillus AHBB-CT196 (W186 + W196), with Pakchoi (Brassica chinensis L.) as the test plant. Analysis of altered nutrient levels, enzyme activities and microbial community structure in the soil as well as the growth and physiological characteristics of Pakchoi, revealed a significant increase in the available phosphorus (AP), organic matter (OM), cation exchange capacity (CEC) and available arsenic (AAs) content of the soil following W186 + W196, W196 and W186 treatments. All experimental treatments enhanced the activity of soil ß-glucosidase (ß-GC) and soil catalase (S-CAT). W186 + W196 and W196 treatments significantly enhanced soil acid phosphatase (S-ACP) activity. Besides, W186 + W196 treatment significantly induced dehydrogenase (S-DHA) activity. Further, of the treatment with PSF increased the fresh weight, root length, plant height and chlorophyll levels while decreasing the arsenic accumulation in Pakchoi. Exposure to PSF also increased the activity of Ascomycota, Basidiomycota, Chytridiomycota, unclassified_Fungi, Mortierellomycota, Cryptomycota and Rozellomycota in the soil. The relative abundance of Ascomycota, Basidiomycota, and Mortierellomycota was positively correlated with the available nutrients (except iron) in the soil as well as enzyme activities. Consequently, the PSF improved the quality of soil and the safety of Pakchoi, suggesting that PSF can be utilized for the remediation of arsenic-contaminated soil.

Leiomyoma with Bizarre Nuclei: A Current Update.

Leiomyoma with bizarre nuclei (LBN), also known as symplastic leiomyoma, is a histological subtype of benign leiomyoma with bizarre cells and nuclear atypia. Differentiating LBN from other benign leiomyoma subtypes, uterine smooth muscle tumors of uncertain malignant potential (STUMP), or leiomyosarcoma (LMS) can be diagnostically challenging owing to overlapping features in clinical presentation and pathologic morphological analysis. The difficulty of distinguishing LBN from other lesions, especially from LMS, and the potential of LBN for subsequent malignant transformation make LBN an important topic of research. Herein, we review the definition, diagnosis, treatment, and prognosis of LBN. Histopathological examination is essential for distinguishing LBN from other diseases. Pathology sampling and morphological examination remain the key to diagnosis. The newly established ancillary immunohistochemical (IHC) and molecular genetic analysis can be useful tools for differential diagnosis. Furthermore, serum biomarkers and imaging examination may also be useful diagnostic tools. Attention should be paid to the differentiation between LBN and LMS because morphological diagnosis may still be challenging in some cases. Some IHC markers of LBN have been identified, which may be helpful for differential diagnosis. Furthermore, the use of IHC panels as diagnostic markers may be advocated. Molecular genetic studies suggest that some genes can aid with the differential diagnosis between LBN and LMS. However, increasing evidence support the idea that LBN and LMS are molecularly related, indicating that LBN may represent a potentially malignant stage of precancerous progression. At present, conservative treatment is recommended for primary LBN, especially for patients desiring to retain fertility, but close follow-up with imaging examinations is required.

The Clinical Diagnostic Values of SAA, PCT, CRP, and IL-6 in Children with Bacterial, Viral, or Co-Infections.

BACKGROUND: Bacterial, viral, and bacterial and viral co-infections generally lead to inflammatory-related diseases. The aim of this study is to assess the clinical diagnostic values of serum amyloid A (SAA), procalcitonin (PCT), C-reactive protein (CRP), and interleukin (IL)-6 in children with bacterial, viral, or co-infections. METHODS: A total of 181 children with infection symptoms (bacterial infection (Bac group), n = 46; viral infection (Vir group), n = 7; co-infections (Bac + Vir group), n = 128) were enrolled in our hospital from December 2019 to April 2020. Meanwhile, 42 healthy children without any infections were used as the controls. Venous blood samples were collected and the levels of serum SAA, PCT, CRP, and IL-6 were determined by immunoluminometric assay under an IMMAGE® analyzer. The diagnostic values of these biomarkers were assessed using the receiver operating characteristic (ROC) curves. RESULTS: The results indicated that IL-6 level was increased in three infection groups compared to the controls. Both SAA and CRP were significantly elevated in Vir and Bac + Vir groups. High level of PCT was observed in Bac and Bac + Vir goups. In addition, PCT (0.9281, 95% CI = 0.8645-0.9916) alone is an effective method for identifying bacterial infections. SAA in combination with CRP may distinguish co-infection from bacterial infection. Simultaneous positive of SAA, PCT, IL-6, and CRP can discriminate co-infection from the healthy controls. CONCLUSION: In a word, the levels of serum SAA, PCT, CRP, and IL-6 are increased to varying degrees in different infection situations. Our findings may provide early diagnosis for patients with different infections.

Clinicopathologic features and outcomes of primary cardiac tumors: a 16-year-experience with 212 patients at a Chinese medical center.

Primary cardiac tumors are uncommon, and the majority of them are benign which are curable but can cause significant morbidity if not diagnosed and treated in a timely fashion. The objective of this study was to review the clinicopathologic features and surgical outcomes of patients with primary cardiac tumors in a single medical center in China. We have retrospectively reviewed 212 consecutive adult patients who underwent surgical resection of primary cardiac tumors at our center from January of 2001 to June of 2017. All available clinicopathological features, imaging characteristics, and disease outcomes were summarized and presented. The present series enrolled 180 cardiac myxomas (84.9%) and 32 non-myxoma cases that included hemangioma, lipoma, papillary fibroelastoma, schwannoma, pericardial cyst, teratoma, paraganglioma, lymphoma, undifferentiated pleomorphic sarcoma, myxofibrosarcoma, angiosarcoma, and liposarcoma. All patients were diagnosed ante-mortem. The most frequent complaint was dyspnea. Benign tumors accounted for 93.9% of cases (199/212) and malignant tumors accounted for 5.7% (12/212), and the remaining one case was intermediate (paraganglioma). The outcome of benign tumors was favorable and only three recurrent cases were documented (1.5%) after surgical resection. All the seven patients with primary cardiac sarcomas (undifferentiated pleomorphic sarcoma, myxofibrosarcoma, angiosarcoma, and liposarcoma) suffered postoperative recurrence or disease related death. Cardiac myxoma represents the most frequent primary cardiac tumors. The clinical presentations, treatment strategies and outcomes of the primary cardiac tumors depend on the tumor location and histopathological type.

Pulmonary gangliocytic paraganglioma: a case report and review of the literature.

Gangliocytic paraganglioma (GP) is a rare histologic type of neuroendocrine tumors. We report a case of pulmonary GP in a 29-year-old male presenting with an asymptomatic endobronchial nodule. Grossly, the tumor showed a 4.0x3.8x3.5 cm well-defined nodule with yellowish cut surface. Microscopically, the tumor was composed of three distinct cellular types: epithelioid cells, ganglion-like cells and spindle cells. Meanwhile, transitional cells, having morphologic features between ganglion-like and epithelioid cells, were also presented. The epithelioid cells arranged in various morphologic architectures, including Zellballen, papillary, cystic and microcystic pattern. The epithelioid cells were positive for AE1/AE3, CAM 5.2, chromogranin A and synaptophysin. Ganglion-like cells showed immunoreactivity for chromogranin A and synaptophysin. A few ganglion-like cells were also positive for AE1/AE3 and/or CAM 5.2. The spindle cells were positive for S-100 protein and neurofilament. The transitional cells showed a similar immunohistochemical profile to the epithelioid cells. The authors believe stem cell theory is a reasonable explanation for the origin of GP. GP probably originate from some kind of mucosa associated stem cell which can differentiate into diverse cellular lineages.